Long-Term Follow-Up
Guidelines
for Survivors of Childhood, Adolescent, and Young Adult Cancers

Version 6.0 - October 2023

Website: www.survivorshipguidelines.org
Copyright 2023 © Children’s Oncology GroupAll rights reserved worldwide

Long-Term Follow-Up Guidelines
for Survivors of Childhood, Adolescent, and Young Adult Cancers
Version 6.0 – October 2023

www.survivorshipguidelines.org
Copyright 2023 © Children’s Oncology GroupAll rights reserved worldwide
Generously supported byWith special appreciation to
Anna DeVine, RN, BSN, CPN, CPHON
Oncology-Survivorship
St. Jude Children’s Research Hospitalfor editing and typesetting

Contents
Introductory Materials

Page

Section #

Page

Sex

Therapeutic Agent

Potential Late Effect

x

13

14

Male

Alkylating Agents

Impaired spermatogenesis

Disclaimer and Notice of Proprietary Rights

xi

14

16

Female Alkylating Agents

Ovarian hormone deficiencies

Contributors - Panel of Experts

xii

15

18

Female Alkylating Agents

Diminished ovarian reserve (DOR)

Contributors - Task Force Membership 2019-2023

xv

16

20

Alkylating AgentsAcute myeloid leukemia; Myelodysplasia

Contributors - Guideline Development Task Force - Initial Versions

xx

17

21

Alkylating Agents

Pulmonary fibrosis

Preface

xxi

18

22

Alkylating Agents

Cataracts

Instructions for Use

xxvi

19

23

Alkylating Agents

Urinary tract toxicity

New to Version 6.0

xxviii

20

24

Alkylating Agents

Bladder malignancy

Abbreviations and parameters

xxxi

21

25

Alkylating Agents

Renal toxicity

22

26

Heavy Metals

Ototoxicity

23

28

Heavy Metals

Peripheral sensory neuropathy

24

29

Heavy Metals

Renal toxicity

25

30

Antimetabolites

Neurocognitive deficits

26

31

Antimetabolites

No known late effects (cytarabine [lowdose IV, IO, IT, SQ])

27

32

Antimetabolites

Hepatic dysfunction; Sinusoidal
obstruction syndrome (SOS)28

33

Antimetabolites

No known BMD late effects (methotrexate)

29

34

Antimetabolites

No known renal late effects (methotrexate)3035Antimetabolites

Hepatic dysfunction

3136

Antimetabolites

Neurocognitive deficits

32

37

Antimetabolites

Clinical leukoencephalopathy

33

38

Anthracycline Antibiotics

Acute myeloid leukemia

Abstract

Section #

Page

Sex

Therapeutic Agent

Potential Late Effect

Any Cancer Experience1

1

Any Cancer Experience

Adverse psychosocial/quality of life
effects

2

3

Any Cancer Experience

Mental health disorders

3

4

Any Cancer Experience

Risky behaviors

45

Any Cancer Experience

Psychosocial disability due to pain

5

6

Any Cancer Experience

Fatigue; Sleep problems

6

7

Any Cancer Experience

Limitations in healthcare and insurance
access7

8

Any Cancer Experience

Subsequent malignancy/Risk ofmalignancy in offspring

Blood/Serum Products
89Diagnosed prior to 1972

Chronic hepatitis B

34

39

Anthracycline Antibiotics

Cardiac toxicity

910

Diagnosed prior to 1993

Chronic hepatitis C

35

41

Anti-Tumor Antibiotics

Pulmonary toxicity

10

11

Diagnosed between 1977
and 1985

HIV infection

36

42

Anti-Tumor Antibiotics

No known late effects (dactinomycin)

37

43

Corticosteroids

Reduced bone mineral density (BMD)

Chemotherapy
11

12

12

13

Male

38

45

Corticosteroids

Osteonecrosis (avascular necrosis)

Any Chemotherapy

Dental abnormalities

39

46

Corticosteroids

Cataracts

Alkylating Agents

Testicular hormonal dysfunction

40

47

Enzymes

No known late effects (asparaginase)

COG LTFU Guidelines – Page v

Version 6.0 - October 2023

Table of Contents

Contents (cont)Section #

Page

41

48

Sex

Therapeutic Agent

Potential Late EffectSection #Page

Plant Alkaloids

Peripheral sensory or motor neuropathy

68

Sex

Therapeutic Agent

Potential Late Effect78

Neck/Thyroid

Thyroid cancer

79

Neck/Thyroid

Hypothyroidism

42

49

Plant Alkaloids

Vasospastic attacks (Raynaud's
phenomenon)

69
70

80

Neck/Thyroid

Hyperthyroidism

43

50

Epipodophyllotoxins

Acute myeloid leukemia

71

81

Neck/Thyroid

Carotid artery disease

72

82

Neck/Thyroid

Subclavian artery disease73

83

Female Breast

Breast cancer

74

84

Female Breast

Breast tissue hypoplasia

75

85

Lungs

Pulmonary toxicity

76

86

Lungs

Lung cancer

77

87

Heart

Cardiac toxicity

78

89

SpleenFunctional asplenia

79

90

GI/Hepatic System

Esophageal stricture

80

91

GI/Hepatic System

Impaired glucose metabolism/Diabetes
mellitus

Radiation
44

52

All Fields

Subsequent benign or malignant neoplasm
occurring in or near radiation field

45

53

All Fields

Dermatologic toxicity

46

54

Brain/Cranium

Brain tumor (benign or malignant)

47

55

Brain/Cranium

Neurocognitive deficits

48

57

Brain/Cranium

Clinical leukoencephalopathy

49

58

Brain/Cranium

Cerebrovascular complications

50

59

Brain/Cranium

Craniofacial abnormalities

51

60

Brain/Cranium

Chronic sinusitis

52

61

Neuroendocrine Axis

Overweight; Obesity

81

92

GI/Hepatic System

Dyslipidemia

53

63

Neuroendocrine Axis

Growth hormone deficiency

82

93

GI/Hepatic System

Hepatic toxicity

54

64

Male

Neuroendocrine Axis

Precocious puberty

83

94

GI/Hepatic System

Cholelithiasis

55

65

Female Neuroendocrine Axis

Precocious puberty

84

95

GI/Hepatic System

Bowel obstruction

56

66

Neuroendocrine Axis

Hyperprolactinemia

85

96

GI/Hepatic System

Chronic enterocolitis; Fistula; Strictures

57

67

Neuroendocrine Axis

Central hypothyroidism

86

97

GI/Hepatic System

Colorectal cancer

58

68

Male

Neuroendocrine Axis

Gonadotropin deficiency

87

98

Urinary Tract

Renal toxicity

59

69

Female Neuroendocrine Axis

Gonadotropin deficiency

88

99

Urinary Tract

Urinary tract toxicity

60

70

Neuroendocrine Axis

Central adrenal insufficiency

89

100

Urinary Tract

Bladder malignancy

61

71

Eye

Cataracts

90

101

Male

Male Reproductive System

Testicular hormonal dysfunction

62

72

Eye

Ocular toxicity

91

102

Male

Male Reproductive System

Impaired spermatogenesis

63

73

Ear

Ototoxicity

92

103

Ovarian hormone deficiencies

64

74

Oral Cavity

Xerostomia; Salivary gland dysfunction

Female Female Reproductive
System65

75

Oral Cavity

Dental abnormalities; Temporomandibular
joint dysfunction

93

104

Female Female Reproductive
SystemDiminished ovarian reserve

66

76

Oral Cavity

Osteoradionecrosis of the jaw

94

106

Uterine vascular insufficiency

67

77

Neck/Thyroid

Thyroid nodules

Female Female Reproductive
System

COG LTFU Guidelines – Page vi

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Table of Contents

Contents (cont)Section #

Page

Sex

Therapeutic Agent

95

107

Female Female Reproductive
System

96

108

97

109

98

110

Potential Late EffectSection #

Page

Sex

Vaginal fibrosis/stenosis

119

134

Female Hysterectomy

Musculoskeletal System

Musculoskeletal growth problems

120

135

Laparotomy

Adhesions; Bowel obstruction

Musculoskeletal System

Scoliosis/Kyphosis

121

136

Limb Sparing Procedure

Musculoskeletal System

Radiation-induced fracture

Complications related to limb sparing
procedure

Nephrectomy

Hydrocele; Renal toxicity

Hematopoietic Cell Transplant (HCT)

Therapeutic Agent

Potential Late EffectPelvic floor dysfunction; Urinary
incontinence; Sexual dysfunction

122

137

Male

Auto HCT

Acute myeloid leukemia; Myelodysplasia

123

138

Female Nephrectomy

HCT

Solid tumors

124

139

Neurosurgery-Brain

Neurocognitive deficits

Female HCT

Solid tumors

125

140

Neurosurgery-Brain

Motor and/or sensory deficits

HCT

Hepatic toxicity

126

141

Neurosurgery-Brain

Seizures

HCT

Osteonecrosis (avascular necrosis)

127

142

Neurosurgery-Brain

Hydrocephalus; Shunt malfunction

117

HCT

Reduced bone mineral density (BMD)

128

143

Neurosurgery-Brain

Overweight; Obesity

105

119

HCT

Renal toxicity

129

144

Neurosurgery-Brain

Diabetes insipidus

106

120

With Chronic GVHD

Dermatologic toxicity

130

145

Neurosurgery-Spinal Cord

Neurogenic bladder; Urinary incontinence

107

121

With Chronic GVHD

Xerophthalmia (keratoconjunctivitis sicca)

131

146

Neurosurgery-Spinal Cord

Neurogenic bowel; Fecal incontinence

108

122

With Chronic GVHD

Oral toxicity

132

147

Male

Neurosurgery-Spinal Cord

Psychosexual dysfunction

109

123

With Chronic GVHD

Pulmonary toxicity

133

148

Female Neurosurgery-Spinal Cord

Psychosexual dysfunction

110

124

With Chronic GVHD

Immunologic complications

134

149

111

125

With CURRENTLY ACTIVE
Chronic GVHD

Functional asplenia

135

150

Female Oophoropexy

Oophoropexy-related complications

136

151

Female Oophorectomy (Unilateral)

Ovarian hormone deficiencies

112

127

With Chronic GVHD

Esophageal stricture

137

152

Female Oophorectomy (Unilateral)

Diminished ovarian reserve

113

128

Female With Chronic GVHD

Vulvar scarring; Vaginal fibrosis/stenosis

138

153

Female Oophorectomy (Bilateral)

114

129

With Chronic GVHD

Ovarian hormone deficiencies; Loss ofovarian follicular pool

139

154

Male

Orchiectomy (Unilateral,
Partial)Testicular hormonal dysfunction

140

155

Male

Orchiectomy (Unilateral,
Partial)Impaired spermatogenesis

141

156

Male

Orchiectomy (Bilateral)

Testosterone deficiency; Azoospermia

142

157

Pelvic Surgery; Cystectomy

Urinary incontinence; Urinary tract
obstruction

99

112

100

113

Male

101

114

102

115

103

116

104

Neurosurgery-Spinal Cord

Joint contractures

Surgery
115

130

Amputation

Amputation-related complications

116

131

Central Venous Catheter

Thrombosis; Vascular insufficiency;
Infection of retained cuff or line tract;
Post-thrombotic syndrome

117

132

Cystectomy

Cystectomy-related complications

118

133

Enucleation

Impaired cosmesis; Poor prosthetic fit;
Orbital hypoplasia

COG LTFU Guidelines – Page vii

Renal toxicity

Scoliosis/Kyphosis

Version 6.0 - October 2023

Table of Contents

Contents (cont)Section #

Page

Sex

143

158

144

159

Male

145

160

Male

146

161

Female Pelvic Surgery; Cystectomy

147

162

Splenectomy

Asplenia

148

163

Thoracic Surgery

149

164

150
151

General Health Screening

Therapeutic Agent

Potential Late EffectPelvic Surgery; Cystectomy

Fecal incontinence

164

179

General Health Screening

Pelvic Surgery; Cystectomy

Psychosexual dysfunction

165

180

General Health Vaccinations

Pelvic Surgery; Cystectomy

Sexual dysfunction (anatomic); Infertility

Appendix I: Materials for Clinical Application of LTFU Guidelines

Sexual dysfunction

Reference Materials

2

Abbreviations

3

Pulmonary dysfunction

Chemotherapy Agents

5

Thoracic Surgery

Scoliosis/Kyphosis

Radiation Fields Defined

6

165

Thyroidectomy

Hypothyroidism

Radiation Dose Calculations

9

166

Partial Thyroidectomy

Hypothyroidism

Guideline Radiation Sections by Field

10

Guideline Radiation Sections by Potential Impact

11

Total Body Irradiation (TBI) Related Potential Late Effects

14

Other Therapeutic Models

Page

152

167

Systemic Radiation (I-131)

Lacrimal duct atrophy

153

168

Systemic Radiation (I-131)

Hypothyroidism

154

169

Systemic Radiation (I-131)

Xerostomia; Salivary gland dysfunction;
Chronic sialadenitis

155

170

Systemic Radiation (MIBG)

Hypothyroidism

156

171

Systemic Radiation (MIBG)

Thyroid nodules

157

172

Systemic Radiation (MIBG)

Thyroid cancer

Instructions

20

158

173

Bioimmunotherapy

Insufficient information available
regarding late effects

Template for Summary of Cancer Treatment (Abbreviated)

22

Template for Summary of Cancer Treatment (Comprehensive)

23

Key for Completing Summary of Cancer Treatment (Comprehensive)

25

159
160

174
175

BCR-ABL tyrosine kinase
inhibitors
BCR-ABL tyrosine kinase
inhibitors

Appeal Letter Following Denial of Insurance Claims for Survivorship Care

Hypothyroidism

161

176

Other targeted biologic
therapies

Insufficient information available
regarding late effects

162

177

B-cell directed antibodybased therapies

Immunologic complications

163

178

Other antibody-based
immune therapies(antibody drug
conjugates)

Insufficient information available
regarding late effects

16

Template for Letter from Patient, Parent, or Guardian17

Template for Letter from Long-Term Follow-Up Clinician

18

Summary of Cancer Treatment

Growth attenuation

15

Instructions

Patient-Specific Guideline Identification Tool

19

31

Instructions

32

Patient-Specific Guideline Identification Tool (Version 5.0)

33

Section Number Comparison - COG LTFU Guidelines Version 6.0 vs 5.0

39

Appendix II: Health Links (Patient Education Materials)

Page

Health Links

x

Health Links Index by Title

3

COG LTFU Guidelines – Page viii

Version 6.0 - October 2023

Table of Contents

Long-Term
Follow-Up
Guidelines
for Survivors of Childhood,
Adolescent, and Young Adult Cancers

Introductory
Materials
Version 6.0
October 2023

Abstract
Release date:

October 2023

Status:Updated from Version 5.0 incorporating modifications based on recommendations from the Children’s Oncology Group’s Long-Term Follow-Up Guideline Core Committee andits associated multidisciplinary Task Forces.

Overview:

These risk-based, exposure-related clinical practice guidelines provide recommendations for screening and management of late effects in survivors of pediatric malignancies.
(“Pediatric malignancies” are defined as those malignancies commonly associated with the pediatric population that may arise during childhood, adolescence or young
adulthood.) A complementary set of patient education materials, known as “Health Links” accompany the guidelines in order to enhance patient follow-up visits and broaden
the application of these guidelines. Additional accompanying materials include detailed instructions, templates for cancer treatment summary forms, a radiation reference
guide, and a tool to assist in identifying guideline applicability for individual survivors based on therapeutic exposures. The information provided in these guidelines isimportant for primary healthcare providers in the fields of pediatrics, oncology, internal medicine, family practice, and gynecology, as well as subspecialists in many fields.
Implementation of these guidelines is intended to increase awareness of potential late effects and to standardize and enhance follow-up care provided to survivors of pediatricmalignancies throughout their lifespan.

Source:Version 6.0 of the Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers, and related Health Links, canbe downloaded in their entirety from www.survivorshipguidelines.org.

Suggested Citations for COG Long-Term Follow-Up Guidelines
Guidelines
Children’s Oncology Group. Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers, Version 6.0. Monrovia, CA: Children’s Oncology Group; October
2023; Available on-line: www.survivorshipguidelines.org.
Guidelines Methodology
Landier W, Bhatia S, Eshelman DA, Forte KJ, Sweeney T, Hester AL, Darling J, Armstrong FD, Blatt J, Constine LS, Freeman CR, Friedman DL, Green DM, Marina N, Meadows AT, Neglia JP,
Oeffinger KC, Robison LL, Ruccione KS, Sklar CA, Hudson MM. Development of risk-based guidelines for pediatric cancer survivors: the Children’s Oncology Group long-term follow-up
guidelines from the Children’s Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol 2004; 22(24):4979-90.
Health Links Background and Application
Eshelman D, Landier W, Sweeney T, Hester AL, Forte K, Darling J & Hudson MM. Facilitating care for childhood cancer survivors: integrating Children’s Oncology Group long-term follow-up
guidelines and health links in clinical practice. J Pediatr Oncol Nurs 2004; 21(5): 271-280.

COG LTFU Guidelines – Page x

Version 6.0 - October 2023

Table of Contents

Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
For Informational Purposes Only: The information and contents of each document or series of documents made available by the Children’s Oncology Group relating to late effects of cancer
treatment and care or containing the title Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers or the title Health Link, whether available in print
or electronic format (including any digital format, e-mail transmission, or download from the website), shall be known hereinafter as “Informational Content”. All Informational Content is for
informational purposes only. The Informational Content is not intended to substitute for medical advice, medical care, diagnosis or treatment obtained from a physician or healthcare provider.
To cancer survivors (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified healthcare provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s
Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of
publication, no warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is
assumed by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following
terms of indemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of theChildren’s Oncology Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless
Indemnified Parties from any and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related
to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology
Group retains exclusive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help theChildren’s Oncology Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could
include signing consents and legal documents and limiting dissemination or reproduction of Informational Content.

COG LTFU Guidelines – Page xi

Version 6.0 - October 2023

Table of Contents

Contributors
Panel of Experts
The following members of the Children’s Oncology Group Long-Term Follow-Up (LTFU) Guidelines Core Committee participated in comprehensive review and scoring of Version 6.0 of the Children’s Oncology Group Long-Term
Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers:

CORE COMMITTEE
Smita Bhatia, MD, MPH
Co-Chair, COG LTFU Guidelines Core Committee
Professor and Vice Chair, Pediatrics
Director, Institute for Cancer Outcomes and SurvivorshipChildren’s Hospital of Alabama
University of Alabama at Birmingham
Birmingham, AL
Louis S. Constine, MD, FASTRO, FACR
The Philip Rubin Professor of Radiation Oncology and Pediatrics
Vice Chair, Department of Radiation Oncology
Director, The Judy DiMarzo Cancer Survivorship Program
James P. Wilmot Cancer institute
University of Rochester Medical Center
Rochester, NY

Saro Armenian, DO, MPH
Professor, Departments of Pediatrics and Population Sciences
Director, Center for Survivorship and Outcomes
City of Hope Comprehensive Cancer Center
Duarte, CA
Melissa A. Acquazzino, MD, MS
Associate Professor, Pediatrics
Medical Director Pediatric Cancer Survivorship Clinic
University of Nebraska Medical Center andChildren’s Hospital & Medical Center
Omaha, NE
Johnnie K. Bass, AuD, PhD
Research Audiologist, Rehabilitation Services
St. Jude Children’s Research Hospital
Memphis, TN

COG LTFU Guidelines – Page xii

Matthew J. Ehrhardt, MD, MS
Co-Chair, COG LTFU Guidelines Core Committee
Associate Member, Department of Oncology
St. Jude Children’s Research Hospital
Memphis, TN
Danielle N. Friedman, MD, MS
Co-Chair, COG LTFU Guidelines Core Committee
Associate Member, Department of Pediatrics
Director, Pediatric Survivorship Fellowship
Memorial Sloan Kettering Cancer Center
New York, NY

Alicia Kunin-Batson, PhD
Associate Professor, Pediatrics
Associate Director of Research
Clinical Behavioral Neuroscience
University of Minnesota Medical School
Minneapolis, MN
Daniel C. Bowers, MD
Professor, Pediatrics and Neurological Surgery
Director, After the Cancer Experience Program
UT Southwestern Medical School
Dallas, TX
Sharon Castellino, MD, MSc
Professor of Pediatrics
Emory University
Director, Leukemia/Lymphoma Program
Aflac Cancer and Blood Disorders Center
Children’s Healthcare of Atlanta
Atlanta, GA
Table of Contents

Melissa M. Hudson, MD
Co-Chair, COG LTFU Guidelines Core Committee
Member, Department of Oncology
Co-Leader, Cancer Control & Survivorship Program
Director, Cancer Survivorship Division and After Completion of
Therapy Program
St. Jude Children’s Research Hospital
Memphis, TN
Wendy Landier, PhD, CRNP
Co-Chair, COG LTFU Guidelines Core Committee
Professor, Pediatrics
Deputy Director, Institute for Cancer Outcomes and Survivorship
School of Medicine, University of Alabama at Birmingham
Birmingham, AL
Kay W. Chang, MD
Professor, Department of Otolaryngology
Stanford University School of Medicine
Palo Alto, CA
Wassim Chemaitilly, MD
Clinical Director, Division of Endocrinology and Diabetes
UPMC Children’s Hospital of Pittsburgh
Professor of Pediatrics
University of Pittsburgh School of Medicine
Pittsburgh, PA
Ming Hui Chen, MD, MMSc, FACC, FASE
Associate Professor of Pediatrics
Director, Cardiovascular Health for Cancer Survivors Program
Boston Children’s Hospital
Dana Farber Cancer Institute
Harvard Medical School
Boston, MA
Version 6.0 - October 2023

Contributors
Panel of Experts continued
The following members of the Children’s Oncology Group Long-Term Follow-Up (LTFU) Guidelines Core Committee participated in comprehensive review and scoring of Version 6.0 of the Children’s Oncology Group
Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers:

Eric J. Chow, MD, MPH
Associate Professor, Pediatrics
Director, Cancer Survivor Program
University of Washington School of Medicine
Seattle Children’s Hospital
Seattle, WA
Douglas Cipkala, MDChildren’s Center for Cancer and Blood Disorders
Peyton Manning Children’s Hospital at Ascension St. Vincent
Assistant Clinical Professor Marian University College of Osteopathic
Medicine
Indianapolis, IN
Laurie E. Cohen, MD
Professor of Pediatrics
Chief, Division of Pediatric Endocrinology and Diabetes
Associate Director, Reassessment and Evaluation After Cancer
Treatment (REACT) Clinic
The Children’s Hospital at Montefiore
Albert Einstein College of Medicine
Bronx, NY
Karen E. Effinger, MS, MD
Associate Professor Pediatrics
Medical Director, Cancer Survivor Program
Emory University
Children’s Healthcare of Atlanta
Atlanta, GA
Natia Esiashvili, MD
Professor, Chief Quality Officer, Department of Radiation Oncology
Emory University
Atlanta, GA

Paul G. Fisher, MD, MHS
Interim Chair, Department of Neurology and Neurological Sciences
Professor, Neurology and Pediatrics
Stanford University
Palo Alto, CA
Kayla L. Foster, MD, MPH
Assistant Professor, Pediatrics
Texas Children’s Cancer and Hematology Centers
Baylor College of Medicine
Houston, TX
M. Monica Gramatges, MD, PhD
Associate Professor, Pediatrics
Associate Chief, Oncology
Texas Children’s Cancer and Hematology Center
Baylor College of Medicine
Houston, TX
Daniel M. Green, MD
Member, Departments of Oncology and Epidemiology and Cancer
Control
St. Jude Children’s Research Hospital
Memphis, TN
Gregory M.T. Guilcher, MD, FRCPC, FAAP
Associate Professor of Oncology and Pediatrics
Pediatric Medical Director, Alberta Blood and Marrow Transplant
ProgramCumming School of Medicine, University of Calgary
Calgary, AB, Canada

COG LTFU Guidelines – Page xiii

Tara O. Henderson, MD, MPH
Arthur and Marian Edelstein Professor of Pediatrics
Chief, Cancer and Blood Diseases Service Line CCHA
Section Chief, Pediatric Hematology, Oncology and Stem Cell
Transplantation
The University of Chicago
Chicago, IL
David Hodgson, MD, MPH, FRCPC
Professor, Department of Radiation Oncology
Princess Margaret Cancer Centre, University of Toronto
Medical Director, Pediatric Oncology Group of Ontario
POGO Chair, Childhood Cancer Control, University of Toronto
Toronto, Canada
Lisa B. Kenney, MD, MPH
Senior Physician, David B. Perini Jr., Quality of Life Clinic
Dana-Farber Boston Children’s Cancer and Blood Disorders Center
Assistant Professor of Pediatrics, Harvard Medical School
Boston, MA
James Klosky, PhD, ABPP
Professor, Department of Pediatrics
Emory University School of Medicine &Director of Psychology and Neuropsychology
Aflac Cancer and Blood Disorders Center
Children’s Healthcare of Atlanta
Atlanta, GA
Kevin R. Krull, PhD, ABPP
Chair, Department of Psychology and Biobehavioral Sciences
St. Jude Children’s Research Hospital
Memphis, TN

Version 6.0 - October 2023

Table of Contents

Contributors
Panel of Experts continued
The following members of the Children’s Oncology Group Long-Term Follow-Up (LTFU) Guidelines Core Committee participated in comprehensive review and scoring of Version 6.0 of the Children’s Oncology Group
Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers:

Lillian R. Meacham, MD
Professor of Pediatrics
Emory University
Chair for Cancer Survivorship
Director of the Fertility Preservation andReproductive Health ProgramChildren’s Healthcare of Atlanta
Atlanta, GA
Cesar A. Migliorati, DDS, MS, PhD
Professor, Oral Medicine
Department of Oral and Maxillofacial Diagnostic Sciences
University of Florida College of Dentistry
Gainesville, Florida
Daniel A. Mulrooney, MD, MS
Associate Member, Department of Oncology
Deputy Director, After Completion of Therapy Clinic
St. Jude Children’s Research Hospital
Memphis, TN
Paul C. Nathan, MD, MSc, FRCPC
Professor, Paediatrics and Health Policy, Management & Evaluation
Director, Aftercare Program
The Hospital for Sick Children
University of Toronto
Toronto, Ontario, Canada

Kirsten K. Ness, PT, PhD
Member, Department of Epidemiology and Cancer Control
St. Jude Children’s Research Hospital
Memphis, TN
Kevin C. Oeffinger, MD
Professor, Medicine and Community and Family Medicine
Director, Center for Onco-Primary Care and Supportive Care andSurvivorship Center
Duke University Medical Center
Durham, NC
Linda Rivard, RN, BSN, CPON
Survivorship Coordinator/P.O.S.T. Clinic
Patient Advocate
Pediatric Hematology/Oncology
Advocate Children’s Hospital
Oak Lawn, IL
Fiona Schulte, PhD
Associate Professor, Department of Oncology, Division of
Psychosocial Oncology
Cumming School of Medicine, University of Calgary
Hematology, Oncology and Transplant Program
Alberta Children’s Hospital
Calgary, Canada

COG LTFU Guidelines – Page xiv

Ami J. Shah, MD
Clinical Professor of Pediatrics
Division of Hematology/Oncology/Stem Cell Transplantation andRegenerative Medicine
Stanford School of Medicine
Lucile Packard Children’s Hospital
Palo Alto, CA
Sheri L. Spunt, MD, MBA
Endowed Professor of Pediatric Cancer
Department of Pediatrics
Stanford University School of Medicine
Stanford, CA
Stephanie Smith, MD, MPH
Instructor, Pediatric Oncology
Lucile Packard Children’s Hospital Stanford
Stanford University School of Medicine
Palo Alto, CA
Nicole Ullrich, MD, PhD, MMSci
Professor, Neurology
Director of Neurologic NeuroOncology
Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
Harvard Medical School
Boston, MA

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Contributors
Task Force Membership 2019-2023
Task Force

Task Force Members

COG Institution

Expertise

Auditory

Douglas A. Cipkala, MD, Chair
Pinki Prasad, MD, MPH, Silo Leader
Tambra R. Dahlheimer, RN, CPNP, CNP
Kristin Knight, MS, CCC-A, FAAA
Etan Orgel, MD
Catherine Woodman, MD
Torunn I. Yock, MD

Saint Vincent Hospital and Health Care Center
Children’s Hospital New Orleans
University of Minnesota, Masonic Cancer Center
Oregon Health and Science University
Keck School of Medicine, University of Southern California
Massachusetts General Hospital Cancer Center
University of Iowa College of Medicine

Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Audiology
Pediatric Hematology Oncology
Radiation Oncology
Family Medicine

Endocrine:
Bone Mineral Density

Wassim Chemaitilly, MD, Chair
Jill H. Simmons, MD, Silo Leader
Nathalie Alos, MD
Sue Kaste, DO
Sogol Mostoufi-Moab, MD, MSCE
Susan V. Shannon, RN, MSN, CPNP, CPON
Linda M. Vrooman, MD, MSc

Children’s Hospital of Philadelphia UMPC
Vanderbilt University Medical Center
Université de Montréal
St. Jude Children’s Research HospitalChildren’s Hospital of Philadelphia UMPC
Miller Children’s and Women’s Hospital Long BeachDana-Farber/Harvard Cancer Center

Pediatric Endocrinology
Pediatric Endocrinology
Pediatric Endocrinology
Pediatric Radiology
Pediatric Oncology & Endocrinology
Pediatric Hematology Oncology
Pediatric Hematology Oncology

CardiovascularMatthew J. Ehrhardt, MD, MS, Chair
Joy M. Fulbright, MD, Silo Leader
Anne Blaes, MD
Rachel Conyers, MD
Kasey J. Leger, MD
Hari Narayan, MD
Thomas Walwyn, MBBS

St. Jude Children’s Research HospitalChildren’s Mercy Hospitals and Clinics
University of Minnesota/Masonic Cancer Center
Royal Children’s Hospital, Melbourne
Seattle Children’s Hospital
University of California San Diego
Perth Children’s Hospital

Pediatric Hematology Oncology
Pediatric Hematology Oncology
Oncology
Hematopoietic Cell Transplantation and Pediatric Oncology
Pediatric Hematology Oncology
Pediatric Cardiology
Pediatric Hematology Oncology

Clinical Care Translation

Melissa Acquazzino, MD, MS, Co-Chair
Kayla Foster, MD, MPH, Co-Chair
Shekinah Andrews, FNP
Roma Bhuta, DO, MPH
Ashlee Blumhoff, APRN-CNP
Leeann Carmichael, DNP, APN, FNP-BC, CPHON
Casey DeBais, MSN, APRN, FNP-BC, CPHON
Amelia Derosa, RN, BSN, CPON
Deirdre Fischer, MEd
Beth Fisher, DNP, APRN, CPNP, CPON, CHPPN
Sarah Ford, MS, PA-C
Julie Nichols, RN, BSN
Linda S. Rivard, RN, BSN, CPON
Daniel Smith, RN, DNP, FNP
S. Ashley Speckhart, MD
Katheryn Tomlinson, RN, BSN
Angela Yarbrough, DNP, APRN, FNP-BC, CPHON
Christine S Yun, MSN, PNP, CPON

Children’s Hospital and Medical Center of Omaha
Baylor College of Medicine, Texas Children’s Hospital
St. Jude Children’s Research Hospital
Rhode Island Hospital, Hasbro Children’s Hospital
Sanford USD Medical Center - Sioux Falls
St. Jude Children’s Research Hospital
University of Chicago Medicine, Comer Children’s Hospital
Memorial Sloan Kettering Cancer Center
Advocate Children’s HospitalChildren’s Hospital of Georgia
St. Jude Children’s Research HospitalChildren’s Hospital of Wisconsin
Advocate Children’s Hospital-Oak Lawn
St. Jude Children’s Research Hospital
Maine Medical Center, Maine Children’s Cancer ProgramChildren’s Hospital of Wisconsin
MD Anderson Cancer Center
Children’s Hospital of Orange County

Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology

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Contributors
Task Force Membership 2019-2023 (cont)
Task Force

Task Force Members

COG Institution

Expertise

Endocrine:
ObesityInsulin Resistance

Wassim Chemaitilly, MD, Chair
Emily S. Tonorezos, MD, MPH, Silo Leader
Rusha Bhandari, MD, MS
Smita Dandekar, MD
Stephanie Dixon, MD
Adam J. Esbenshade, MD, MSci
Heather D. Escoto, MD
Cheng-Chia Fred Wu, MD, PhD

Children’s Hospital of Philadelphia UPMC
National Cancer Institute
City of HopePenn State Children’s
St. Jude Children’s Research Hospital
Vanderbilt University/Ingram Cancer Center
Saint Vincent Hospital and Health Care Center
Columbia University Medical Center

Pediatric Endocrinology
Internal Medicine
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Radiation Oncology

Endocrine:
Ovarian

Wassim Chemaitilly, MD, Chair
Ksenya Shliakhtsitsava, MD, Silo Leader
Leslie Appiah, MD
Kari Bjornard, MD
Serena Chan, MD, FACOG
Brooke Cherven, PhD, MPH, RN, CPON
Sobenna George, MD
Stacey Marjerrison, MD
Sripriya Raman, MD
Christine Yu, MDChildren’s Hospital of Philadelphia UPMCUT Southwestern/Simmons Cancer Center-Dallas
Colorado Children’s
Indiana University
Children’s Hospital of Pittsburgh-UPMC
Children’s Healthcare of Atlanta
Children’s Healthcare of Atlanta - Egleston
McMaster Children’s Hamilton, OntarioChildren’s Hospital of Pittsburgh of UPMC
St. Jude Children’s Research Hospital

Pediatric Endocrinology
Pediatric Hematology Oncology
Pediatric and Adolescent Gynecology
Pediatric Hematology Oncology
Gynecology
Nursing Research
Pediatric Endocrinology
Pediatric Hematology Oncology
Pediatric Endocrinology
Endocrinology

Endocrine:
Pituitary
AdrenalThyroid

Wassim Chemaitilly, MD, Chair
Angela Delaney, MD
Nursen Gurtunca, MD
Maya Lodish, MD, MHSc
Alfonso Hoyos-Martinez, MD, FAAP
Joel Thompson, MD
Jonathan Wasserman, MD, PhD
Gregory C. Wheeler, MBBS, FRANZCRAngela Yarbrough, DNP, APRN, FNP-BC, CPHONKevin Yuen, MD

Children’s Hospital of Philadelphia UPMC
St. Jude Children’s Research HospitalChildren’s Hospital of Pittsburgh
UCSF
Baylor College of Medicine, Texas Children’s Hospital
Mercy-Kansas City
Sick Kids, Toronto
Royal Children’s Hospital and Monash Medical Center
MD Anderson
Oregon Health and Science University

Pediatric Endocrinology
Pediatric Endocrinology
Pediatric Endocrinology
Pediatric Endocrinology
Pediatric Endocrinology
Pediatric Hematology Oncology
Pediatric Endocrinology
Radiation Oncology
Pediatric Hematology Oncology
Endocrinology

Endocrine:
Testicular

Wassim Chemaitilly, MD, Chair
Zoltan Antal, MD, Silo Leader
Laurie E. Cohen, MD
Sarah Hensley, MD
Vincent Horne, MD
Lisa B. Kenney, MD, MPH
Lillian R. Meacham, MD
Leena Nahata, MD
Megan Pruett, MSN, CPNP

Children’s Hospital of Philadelphia UPMC
Memorial Sloan Kettering Cancer Center
Dana-Farber/Harvard Cancer Center
Children’s Hospital of Richmond at VCU
Baylor College of Medicine, Texas Children’s HospitalDana-Farber/Harvard Cancer Center
Children’s Healthcare of Atlanta - Egleston
Nationwide Children’s HospitalChildren’s Healthcare of Atlanta

Pediatric Endocrinology
Pediatric Endocrinology
Pediatric Endocrinology
Pediatric Endocrinology
Pediatric Endocrinology
Pediatric Hematology Oncology
Pediatric Endocrinology
Pediatric Endocrinology
Pediatric Endocrinology

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Table of Contents

Contributors
Task Force Membership 2019-2023 (cont)
Task Force

Task Force Members

COG Institution

Expertise

Endocrine:
Testicular continued

Denise Rokitka, MD, MPH
Seth Rotz, MD
Jenna Sopfe, MD

Roswell Park Comprehensive Care Center
Cleveland Clinic
Children’s Hospital Colorado

Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology

Gastrointestinal
Hepatic

Karen E. Effinger, MD, MS, Chair
Kathy J. Ruble, RN, CRNP, PhD, AOCN, Silo Leader
Sahaja Acharya, MD
Jennifer Burgis, MD
Sharon M. Castellino, MD, MSc
Cathleen M. Cook, MD
John K. Petty, MD
Julia O’Malley Stepenske, RN, BSN, CPON

Children’s Healthcare of Atlanta - Egleston
Johns Hopkins University
Johns Hopkins University
Lucile Packard Children’s Hospital Stanford University
Children’s Healthcare of Atlanta - Egleston
East Carolina University
Wake Forest University Health Sciences
Advocate Children’s Hospital-Park Ridge

Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Radiation Oncology
Pediatric Gastroenterology/ Hepatology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Surgery
Pediatric Hematology Oncology

Hematopoietic Cell Transplantation
ImmuneDermatologic

Greg Guilcher, MD, FRCPC, FAAP, Chair
Hesham Eissa, MD, Silo Leader
Lesleigh Abbott, MD, FRCPC
Lynnette Anderson, RN, MSN, CPNP
Eric J. Chow, MD, MPH
Tal Schechter-Finkelstein, MD
Lisa Hackney, MD
Jennifer T. Huang, MD
Wendy G. Pelletier, MSW, RSW
Shanti Ramachandran, MBBS, FRACP, MPaeds
Linda S. Rivard, RN, BSN, CPON
Ami J. Shah, MD
Lena Winestone, MD, MS
Kenneth Wong, MD

University of Calgary, Alberta Children’s HospitalChildren’s Hospital Colorado
University of Ottawa
Children’s Hospital of Wisconsin
Seattle Children’s Hospital
University of Toronto
Case Western
Dana-Farber/Harvard Cancer Center
Alberta Children’s Hospital
Perth Children’s Hospital
Advocate Children’s Hospital-Oak Lawn
Lucile Packard Children’s Hospital Stanford University
UCSF
University of Southern California

Pediatric Oncology
Hematopoietic Cell Transplantation and Pediatric Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Hematopoietic Cell Transplantation
Pediatric Hematology Oncology
Pediatric Dermatology
Social Work
Hematopoietic Cell Transplantation
Pediatric Hematology Oncology
Hematopoietic Cell Transplantation
Pediatric Hematology Oncology
Radiation Oncology

Musculoskeletal

Douglas A. Cipkala, MD, Chair
Rozalyn Rodwin, MD, Silo Leader
LaVette S. Bowles, MN, NPc
Jill Cannoy, PT, DPT
Colleen Coulter, PT, DPT, PhD, PCS
Madhu Gowda, MD
Winston W. Huh, MD
Jill L. Lee, MSN, CPNP-AC, CPON
Valerae O. Lewis, MD
Anita Mahajan, MD
Lor Randall, MD, FACS
Carmen Wilson, PhD
Lauren Zeitlinger, DO

Ascension Hospital System Indianapolis
Yale School of Medicine
Mattel Children’s Hospital UC
Children’s Healthcare of Atlanta
Children’s Healthcare of Atlanta - Egleston
Children’s Hospital of Richmond at VCU
MD Anderson Cancer Center
University of Minnesota/Masonic Cancer Center
MD Anderson Cancer Center
Mayo Clinic
UC Davis
St. Jude Children’s Research Hospital
Orthopedic Specialties of Central PA - UPMC

Pediatric Hematology Oncology
Pediatric Hematology Oncology
Family Medicine
Physical Therapy
Physical Therapy
Pediatric Hematology Oncology
Pediatric Oncology
Pediatric Hematology Oncology
Orthopedic Oncology
Radiation Oncology
Orthopedic Oncology
Epidemiology
Orthopedic Surgery

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Table of Contents

Contributors
Task Force Membership 2019-2023 (cont)
Task Force

Task Force Members

COG Institution

Expertise

Neurocognitive

Alicia Kunin-Batson, PhD, Chair
Ellen van der Plas, PhD, Silo Leader
Yin Ting Cheung, PhD
Lisa Jacola, PhD, ABPP-CN
Katharine Rae Lange, MD
Kim Raghubar, PhD

University of Minnesota/Masonic Cancer Center
University of Arkansas, Arkansas Children’s Hospital
Chinese University of Hong Kong
St. Jude Children’s Research Hospital
Hackensack Meridian Children’s Health
Texas Children’s Hospital/Baylor College of Medicine

Neuropsychology
Cognitive Neuroscience
Pharmacoepidemiology
Pediatric Neuropsychology
Pediatric Hematology Oncology
Neuropsychology

Neurologic

Douglas A. Cipkala, MD, Chair
Zsila S. Sadighi, MD, Silo Leader
Eugenia Chang, MD
Jessica Goodman, MD
Fatema Malbari, MD
Susan McGovern, MD, PhD
Neha Patel, MD
Suzanne M. Russo, MD

Ascension Hospital System Indianapolis
University of Texas, MD Anderson
St. Luke’s Children’s Cancer Institute
Peyton Manning Children’s Hospital
Texas Children’s Hospital/Baylor College of Medicine
University of Texas, MD Anderson
Cleveland Clinic
UH Seidman Cancer Center

Pediatric Hematology Oncology
Pediatric Neuro-Oncology/Neurology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Neuro-Oncology/Neurology
Radiation Oncology
Pediatric Neuro-Oncology
Radiation Oncology

New Agents

Stephanie Smith, MD, MPH, Chair
Maya Lodish, MD, MHSc, Silo Leader
Neel S. Bhatt, MD, MBBS, MPH
Sharon M. Castellino, MD, MSc
Matthew J. Ehrhardt, MD, MS
Michael Gleason, MD, MSPH
Brinda Mehta, MBBS
Esther Adebayo-Olojo, PhD, MS, RPh
Serina Patel, MD
Robert Raphael, MD
Jessica Sun, MD

Lucile Packard Children’s Hospital Stanford University
UCSF
Seattle Children’s HospitalChildren’s Healthcare of Atlanta - Egleston
St. Jude Children’s Research Hospital
Texas Children’s Hospital/Baylor College of Medicine
Children’s Hospital of Illinois
New York (NYU/LIU)
Children’s Hospital/London Health Sciences Center
UCSF
Duke University

Medicine and Pediatrics
Pediatric Endocrinology
Pediatric Hematology Oncology
Pediatric Gastroenterology/Hepatology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pharmacy
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology

OcularDouglas A. Cipkala, MD, Chair
Pinki K. Prasad, MD, MPH, Silo Leader
Charline Boente, MD

Saint Vincent Hospital and Health Care Center
Children’s Hospital New Orleans
Indiana University, Riley Hospital for Children

Pediatric Oncology
Pediatric Oncology
Pediatric Opthalmology

Oral/Dental

Karen E. Effinger, MD, MS, Chair
Kathy J. Ruble, RN, CPNP, PhD, Silo Leader
Zachary Abramson, MD, DMD
Sahaja Acharya, MD
Cathleen M. Cook, MD
Julia O’Malley Stepenske, RN, BSN, CPON
Nathaniel Treister, DMD, DMSc
Rebecca Williams, DMD

Children’s Healthcare of Atlanta - Egleston
Johns Hopkins University/Sidney Kimmel Cancer Center
St. Jude Children’s Research Hospital
Johns Hopkins University
East Carolina University
Advocate Children’s Hospital-Park Ridge
Dana-Farber/Harvard Cancer Center
Perth Children’s Hospital

Pediatric Hematology Oncology
Pediatric Hematology Oncology
Maxillofacial Imaging
Radiation Oncology
Pediatric Hematology Oncology
Family Medicine
Oral/Dental Medicine
Pediatric Oral/Dental Medicine

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Table of Contents

Contributors
Task Force Membership 2019-2023 (cont)
Task Force

Task Force Members

COG Institution

Expertise

Psychosocial

Fiona Schulte, PhD, Chair
Rebecca Foster, PhD, Silo Leader
Tara M. Brinkman, PhD
Katie Devine, PhD, MPH
Kristin Foster, DNP, C-PNP, C-PMHNP
Cynthia Karlson, PhD
Jordan Gilleland Marchak, PhD, ABPP
Sunnye Mayes, PhD, ABPP
Sapna Oberoi, MBBS, MD, DM
Wendy G. Pelletier, MSW, RSW
Karen Long-Traynor, PhD
Victoria W. Willard, PhD

University of Calgary, Alberta Children’s Hospital
Washington University, St. Louis Children’s Hospital
St. Jude Children’s Research Hospital
Rutgers Cancer Institute of New Jersey
University of Iowa Hospitals and Clinics
University of Mississippi Medical Center
Children’s Healthcare of Atlanta
University of Louisville, Norton Children’s Cancer Institute
Max Rady School of Medicine, University of Manitoba
Alberta Children’s Hospital
Rutgers Cancer Institute of New Jersey
St. Jude Children’s Research Hospital

Psychology
Pediatric Psychology
Pediatric Psychology
Pediatric Hematology Oncology
Pediatric Psychology
Pediatric Psychology
Pediatric Psychology
Pediatric Psychology
Pediatric Hematology Oncology
Social Work
Clinical Psychology
Pediatric Psychology

Pulmonary

Matthew J. Ehrhardt, MD, MS, Chair
Neel S. Bhatt, MD, MBBS, MPH, Silo Leader
Jennifer E. Agrusa, MD, MS
Aarati Didwania, MD
Mary Frances McAleer, MD, PhD
Daniel Weiner, MD

St. Jude Children’s Research Hospital
Seattle Children’s Hospital
University of Michigan, C. S. Mott Children’s HospitalNorthwestern University Feinberg School of Medicine
MD Anderson
Children’s Hospital of Pittsburgh, UPMC

Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Internal Medicine
Radiation Oncology
Pediatric Pulmonology

Subsequent Malignant Neoplasms

Danielle N. Friedman, MD, MS, Co-Chair
Monica M. Gramatges, MD, PhD, Co-Chair
Dana Barnea, MD
Taumoha Ghosh, MD
Tara O. Henderson, MD, MPH
David Hodgson, MD, MPH, FRCPC
Lenat Joffe, MD
Katharine Rae Lange, MD
Chaya Moskowitz, PhD
Paul C. Nathan, MD, MSc, FRCPCKevin C. Oeffinger, MD
Kenneth Roberts, MD
Omar Shakeel, MD
Stephanie Smith, MD, MPH
Eugene Suh, MD
Tara Suntum, MD
Lucie M. Turcotte, MD, Silo Leader
Tung Wynn, MD
Alia Zaidi, MD

Memorial Sloan Kettering Cancer Center
Texas Children’s Hospital/Baylor College of Medicine
Memorial Sloan Kettering Cancer Center
University of Miami
University of Chicago Comprehensive Cancer Center
University of Toronto
Columbia University
Hackensack Meridian Children’s Health
Memorial Sloan Kettering Cancer Center
Hospital for Sick Children
Duke University Medical Center
Yale University School of Medicine/Smillow Cancer Hospital
Texas Children’s Hospital/Baylor College of Medicine
Lucile Packard Children’s Hospital Stanford University
Loyola University Medical Center
Medstar Georgetown University Hospital
University of Minnesota/Masonic Cancer Center
University of Florida
St. Jude Children’s Research Hospital

Pediatric Hematology Oncology
Pediatric Hematology Oncology
Internal Medicine
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Radiation Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Biostatistics, Survivorship
Pediatric Hematology Oncology
Family Medicine
Radiation Oncology
Pediatric Hematology Oncology
Medicine and Pediatrics
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology

COG LTFU Guidelines – Page xix

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Contributors
Task Force Membership 2019-2023 (cont)
Task Force

Task Force Members

COG Institution

Expertise

Urinary Tract

Karen E. Effinger, MD, MS, Chair
Kathleen Kieran, MD, MS, Silo Leader
Kala Kamdar, MD
Anne Crowley Mauck, RN, MSN, CPNP
Kerry M. Moss, MD
Daniel A. Mulrooney, MD, MS
Jonathan C. Routh, MD, MPH
Sheri L. Spunt, MD

Children’s Healthcare of Atlanta - Egleston
Seattle Children’s Hospital
Texas Children’s Hospital/Baylor College of Medicine
Virginia Commonwealth University/Massey Cancer Center
Connecticut Children’s Medical Center
St. Jude Children’s Research Hospital
Duke University Medical Center
Lucile Packard Children’s Hospital Stanford University

Pediatric Hematology Oncology
Pediatric Urology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Hematology Oncology
Pediatric Urology
Pediatric Hematology Oncology

Contributors
Guideline Development Task Force - Initial Versions
The Children’s Oncology Group Nursing Discipline and Late Effects Committee collaboratively developed the initial versions (1.0, 1.1, and 1.2) of the Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors ofChildhood, Adolescent, and Young Adult Cancers. The following individuals comprised the original Guideline Development Task Force:
Development Task Force
Melissa M. Hudson, MD, Task Force Co-Chair, St. Jude Children’s Research Hospital, Memphis, TN
Wendy Landier, PhD, CPNP, Task Force Co-Chair, Children’s Hospital of Alabama, Birmingham, AL
Joan Darling, PhD, COG Patient Advocate Committee, Lincoln, NE
Kathy Forte, RN, MS, CPNP, Children’s Healthcare of Atlanta - Egleston, Atlanta, GA
Allison Hester, RN, MSN, CPNP, Arkansas Children’s Hospital, Little Rock, AR
Debra A. Kent, RN, MSN, CPNP, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
Teresa Sweeney, RN, MSN, CPNP, St. Jude Children’s Research Hospital, Memphis, TN

Special Acknowledgment:
Smita Bhatia, MD, MPH, Children’s Hospital of Alabama, Birmingham, AL for her leadership in overseeing
the initial development of the COG LTFU Guidelines as Chair of the COG Late Effects Committee, and for her
continued oversight of all content in all versions of the COG LTFU Guidelines
Louis S. “Sandy” Constine, MD, University of Rochester, Rochester, NY for his in-depth expert review andextensive contributions to all radiation-related sections in all versions of the COG LTFU Guidelines

COG LTFU Guidelines – Page xx

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Table of ContentsPreface
Overview

Goal

The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood,
Adolescent, and Young Adult Cancers (COG LTFU Guidelines) are risk-based, exposurerelated clinical practice guidelines for screening and management of late effects resulting
from therapeutic exposures used during treatment for pediatric malignancies. “Late effects”
are defined as therapy-related complications or adverse effects that persist or arise after
completion of treatment for a pediatric malignancy. “Pediatric malignancies” are defined as
those malignancies commonly associated with the pediatric population that may arise duringchildhood, adolescence, or young adulthood.

Implementation of these guidelines is intended to increase quality of life and decrease
complication-related healthcare costs for pediatric cancer survivors by providing standardized
and enhanced follow-up care throughout the lifespan that:

These guidelines represent a statement of consensus from a panel of experts in the lateeffects of pediatric cancer treatment. The guidelines are both evidence-based (utilizing
established associations between therapeutic exposures and late effects to identify highrisk categories) and grounded in the collective clinical experience of experts (matching themagnitude of the risk with the intensity of the screening recommendations).

Focus

Since therapeutic interventions for a specific pediatric malignancy may vary considerably
based on the patient’s age, presenting features, and treatment era, a therapy-based design
was chosen to permit modular formatting of the guidelines by therapeutic exposure.
Importantly, the recommended periodic screening underscores the use of a thorough history
and physical examination (H&P) as the primary assessment for cancer-related treatment
effects. In regard to the screening recommendations outlined for the 165 therapeutic
exposures in the COG LTFU Guidelines:•

113 (68%) are derived primarily from the H&P, of which 91 (55%) rely solely on the H&P
and 22 (13%) rely on the H&P plus a baseline diagnostic study (e.g., lab, imaging)•

44 (27%) include periodic laboratory, diagnostic imaging, or other testing•

8 (5%) recommend no screening (agents with no known late effects)

Interventions exceeding minimal screening are provided for consideration in individuals withpositive screening tests. Medical citations supporting the association of each late effect witha specific therapeutic exposure are included. Patient education materials complementing theguidelines have been organized into Health Links that feature health protective counselingon 45 topics, enhancing patient follow-up visits and broadening application of the guidelines.
Additional accompanying materials include detailed instructions, templates for cancer
treatment summary forms, a radiation reference guide, a tool to assist in identifying guideline
applicability for individual survivors based on therapeutic exposures, and templates for letters
appealing denied insurance claims.

a.

Promotes healthy lifestylesb.

Provides for ongoing monitoring of health statusc.

Facilitates early identification of late effectsd.

Provides timely intervention for late effects

These guidelines are intended for use beginning two or more years following thecompletion of cancer therapy, and provide a framework for ongoing late effects monitoringin childhood cancer survivors; however, these guidelines are not intended to provide
guidance for follow-up of the pediatric cancer survivor’s primary disease.
Target Population
The recommendations for periodic screening evaluations provided in the COG LTFU Guidelines
are appropriate for asymptomatic survivors of childhood, adolescent, or young adult cancers
who present for routine exposure-related medical follow-up. More extensive evaluations
are presumed, as clinically indicated, for survivors presenting with signs and symptoms
suggesting illness or organ dysfunction.
Intended Users
The COG LTFU Guidelines were developed as a resource for clinicians who provide ongoinghealthcare to survivors of pediatric malignancies. The information within these guidelines isimportant for clinicians (e.g., physicians, nurse practitioners, physician assistants, nurses) in
the fields of pediatrics, oncology, internal medicine, family practice, and gynecology, as well as
subspecialists in many fields (e.g., endocrinology, cardiology, pulmonology). A basic knowledgeof ongoing issues related to the long-term follow-up needs of this patient population isassumed. Healthcare professionals who do not regularly care for survivors of pediatricmalignancies are encouraged to consult with a pediatric oncology long-term follow-up center
if any questions or concerns arise when reviewing or using these guidelines.
Although the information within the guidelines will certainly prove valuable to the survivors
themselves, at this time the only version available is targeted to healthcare professionals.
Therefore, survivors who choose to review these guidelines are strongly encouraged to do so

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Table of ContentsPreface (cont)with the assistance of a healthcare professional knowledgeable about long-term follow-up
care for survivors of childhood, adolescent, and young adult cancers. This is important in orderto put the recommendations in perspective, avoid over-testing, address potential anxieties, andprovide a comprehensive evaluation of the survivor’s health status. The Children’s Oncology
Group itself does not provide individualized treatment advice to survivors or their families, andstrongly recommends discussing this information with a qualified medical professional.

the draft, including focused review of selected guideline sections. Revisions were made basedon these recommendations. The revised draft was then sent out to additional multidisciplinary
experts for further review. A total of 62 individuals participated in the review process. The
guidelines subsequently underwent comprehensive review and scoring by a panel of experts inthe late effects of pediatric malignancies, comprised of multidisciplinary representatives fromthe COG Late Effects Committee.

Developer

In a parallel effort led by the Nursing Clinical Practice Subcommittee, complementary patient
education materials (Health Links) were developed. Each Health Link underwent two levels ofreview; first by the Nursing Clinical Practice Subcommittee to verify accuracy of content andrecommendations, and then by members of the Late Effects Committee (to provide expert
medical review) and Patient Advocacy Committee (to provide feedback regarding presentationof content to the lay public).

The COG LTFU Guidelines were developed as a collaborative effort of the Children’s Oncology
Group Nursing Discipline and Late Effects Committee and are maintained and updated by
the Children’s Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its
associated Task Forces. All Children’s Oncology Group members have complied with the
COG conflict of interest policy, which requires disclosure of any potential financial or otherconflicting interests.
Evidence Collection
Pertinent information from the published medical literature over the past 20 years (updated asof October 2023) was retrieved and reviewed during the development and updating of theseguidelines. For each therapeutic exposure, a complete search was performed via MEDLINE(National Library of Medicine, Bethesda, MD). Keywords included “childhood cancer therapy,”“complications,” and “late effects,” combined with keywords for each therapeutic exposure.
References from the bibliographies of selected articles were used to broaden the search.
Methods
In 2002, the leadership of the Children’s Oncology Group Late Effects Committee and Nursing
Discipline appointed a 7-member task force, with representation from the Late Effects
Committee, Nursing Discipline, and Patient Advocacy Committee. The task force was convened
to review and summarize the medical literature and develop a draft of clinical practiceguidelines to direct long-term follow-up care for pediatric cancer survivors. The task force
followed a modified version of the guideline development process established by the National
Comprehensive Cancer Network (NCCN), integrating available literature with expert opinion
using reiterative feedback loops.
The original draft went through several iterations within the task force prior to initial review.
Multidisciplinary experts in the field, including nurses, physicians (pediatric oncologists
and other subspecialists), patient advocates, behavioral specialists, and other healthcare
professionals, were then recruited by the task force to provide an extensive, targeted review of

Pre-Release Review
The initial version of the guidelines (Version 1.0 – Children’s Oncology Group Late Effects
Screening Guidelines) was released to the Children’s Oncology Group membership in March
2003 for a six-month trial period. This allowed for initial feedback from the COG membership,
resulting in additional review and revision of the guidelines by the Late Effects Committee prior
to public release.
Revisions
The guidelines were initially released to the public (Version 1.1 – Childhood Cancer Survivor
Long-Term Follow-Up Guidelines ) on the Children’s Oncology Group Website in September
2003. Following this release, clarification regarding the applicability of the guidelines to theadolescent and young adult populations of cancer survivors was requested. In response,
additional minor modifications were made and the title of the guidelines was changed. A
revised version (Version 1.2 – Long-Term Follow-Up Guidelines for Survivors of Childhood,
Adolescent, and Young Adult Cancers ) was released to the public on the Children’s Oncology
Group Website in March 2004.
In order to keep the guidelines current and clinically meaningful, the COG Late Effects
Committee organized multidisciplinary task forces in March 2004. These task forces arecharged with the responsibility for monitoring the medical literature in regard to specificsystem-related clinical topics relevant to the guidelines (e.g., cardiovascular, neurocognitive,
fertility/reproductive), providing periodic reports to the COG Outcomes and Survivorship
Committee, and recommending revisions to the guidelines and their associated healtheducation materials and references (including the addition of therapeutic exposures) as new

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Table of ContentsPreface (cont)information becomes available. Task force members are assigned according to their respective
areas of expertise and clinical interest and membership is updated every 5 years. A list ofthese task forces and their membership is included in the “Contributors” section of thisdocument, reflecting contributions and recommendations relevant to the current release of
these guidelines (Version 6.0 – October 2023).
All revisions proposed by the task forces were evaluated by a panel of experts, and if
accepted, assigned a score (see “Scoring Explanation” section of Preface). Proposed revisions
that were rejected by the expert panel were returned with explanation to the relevant task
force chair. If desired, task force chairs were given an opportunity to respond by providing
additional justification and resubmitting the rejected task force recommendation(s) for further
consideration by the expert panel.

were assigned according to a modified version of the National Comprehensive Cancer Network“Categories of Consensus,” as follows:
Category Statement of Consensus
1

There is uniform consensus of the panel that:
1. There is high-level evidence linking the late effect with the therapeutic
exposure
2. The screening recommendation is appropriate based on the collective
clinical experience of panel members

2A

There is uniform consensus of the panel that:
1. There is lower-level evidence linking the late effect with the therapeutic
exposure
2. The screening recommendation is appropriate based on the collective
clinical experience of panel members

2B

There is non-uniform consensus of the panel that:
1. There is lower-level evidence linking the late effect with the therapeutic
exposure
2. The screening recommendation is appropriate based on the collective
clinical experience of panel members

3

There is major disagreement that the recommendation is appropriate.

Plan for Updates
The multidisciplinary task forces described above will continue to monitor the literature andreport to the COG Long-Term Follow-Up Guideline Core Committee during each guideline
review/update cycle. Periodic revisions to these guidelines are planned as new information
becomes available, and at least every 5 years. Clinicians are advised to check the Children’s
Oncology Group website periodically for the latest updates and revisions to the guidelines,
which will be posted at www.survivorshipguidelines.org.
Scoring Explanation
These guidelines represent a statement of consensus from a multidisciplinary panel ofexperts in the late effects of pediatric cancer treatment. The guidelines outline minimum
recommendations for specific health screening evaluations in order to detect potential lateeffects arising as a result of therapeutic exposures received during treatment of childhood,adolescent, and young adult cancers.
Each score relates to the strength of the association of the identified late effect withthe specific therapeutic exposure based on current literature, and is coupled with arecommendation for periodic health screening based on the collective clinical experience ofthe panel of experts. This is due to the fact that there are no randomized clinical trials (andnone forthcoming in the foreseeable future) on which to base recommendations for periodic
screening evaluations in this population; therefore, the guidelines should not be misconstrued
as representing conventional “evidence-based clinical practice guidelines” or “standards ofcare”.
Each item was scored based on the level of evidence currently available to support it. Scores

Uniform consensus: Near-unanimous agreement of the panel with some possible neutral positions.
Non-uniform consensus: The majority of panel members agree with the recommendation; however, there
is recognition among panel members that, given the quality of evidence, clinicians may choose to adopt
different approaches.
High-level evidence: Evidence derived from high quality case control or cohort studies.
Lower-level evidence: Evidence derived from non-analytic studies, case reports, case series, and clinicalexperience.

All “Category 1” recommendations reflect uniform consensus among the reviewers.
“Category 2” recommendations are designated as “2A” (there is uniformity of consensus
among the reviewers regarding strength of evidence and appropriateness of the screening
recommendation) or “2B” (there is non-uniform consensus among the reviewers regarding
strength of evidence and appropriateness of the screening recommendation).
Rather than submitting recommendations representing major disagreements, items scoredas “Category 3” were either deleted or revised by the panel of experts to provide at least a“Category 2B” score for all recommendations included in the guidelines.

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Table of ContentsPreface (cont)
Recommendations and Rationale
Screening and follow-up recommendations are organized by therapeutic exposure andincluded throughout the guidelines. Pediatric cancer survivors represent a relatively small but
growing population at high risk for various therapy-related complications. Although several
well-conducted studies on large populations of childhood cancer survivors have demonstrated
associations between specific exposures and late effects, the size of the survivor populationand the rate of occurrence of late effects does not allow for clinical studies that would assess
the impact of screening recommendations on the morbidity and mortality associated with thelate effect. Therefore, scoring of each exposure reflects the expert panel’s assessment of thelevel of literature support linking the therapeutic exposure with the late effect coupled with anassessment of the appropriateness of the recommended screening modality in identifying thepotential late effect based on the panel’s collective clinical experience.
Potential Benefits and Harms
Potential benefits of implementing these guidelines into clinical practice include earlier
identification of and intervention for late onset therapy-related complications in this at-risk
population, potentially reducing or ameliorating the impact of late complications on the healthstatus of survivors. In addition, ongoing healthcare that promotes healthy lifestyle choices andprovides ongoing monitoring of health status is important for all cancer survivors.
Potential harms of guideline implementation include increased patient anxiety related toenhanced awareness of possible complications, as well as the potential for false-positive
screening evaluations, leading to unnecessary further workup. In addition, costs of longterm follow-up care may be prohibitive for some survivors, particularly those lacking
health insurance, or those with insurance that does not cover the recommended screening
evaluations.
Patient Preferences
Ultimately, as with all clinical guidelines, decisions regarding screening and clinicalmanagement for any specific patient should be individually tailored, taking into consideration
the patient’s treatment history, risk factors, co-morbidities, and lifestyle. These guidelines are
therefore not intended to replace clinical judgment or to exclude other reasonable alternative
follow-up procedures. The Children’s Oncology Group recognizes that specific patient caredecisions are the prerogative of the patient, family, and healthcare provider.

provided to survivors of pediatric malignancies throughout the lifespan. Considerations in thisregard include the practicality and efficiency of applying these broad guidelines in individual
clinical situations. Studies to address guideline implementation and refinement are a toppriority of the COG Long-Term Follow-Up Guideline Core Committee; studies of feasibility ofguideline use have been reported in limited institutions and others are currently underway.
Issues being addressed include description of anticipated barriers to application of therecommendations in the guidelines and development of review criteria for measuring changes
in care when the guidelines are implemented. Additional concerns surround the lack of current
evidence establishing the efficacy of screening for late complications in pediatric cancer
survivors. While most clinicians believe that ongoing surveillance for these late complications
is important in order to allow for early detection and intervention for complications that may
arise, development of studies addressing the efficacy of this approach is imperative in order todetermine which screening modalities are optimal for asymptomatic survivors.
In addition, the clinical utility of this lengthy document has also been a top concern of the
COG Long-Term Follow-Up Guideline Core Committee. While recognizing that the length anddepth of these guidelines is important in order to provide clinically-relevant, evidence-based
recommendations and supporting health education materials, clinician time limitations andthe effort required to identify the specific recommendations relevant to individual survivors
have been identified as barriers to their clinical application. Therefore, the COG Long-Term
Follow-Up Guideline Core Committee has partnered with the Baylor School of Medicine todevelop a web-based interface, known as “Passport for Care,” that generates individualized
exposure-based recommendations from these guidelines in a clinician-focused format for easeof patient-specific application of the guidelines in the clinical setting. The Passport for Care®
application is available to Children’s Oncology member institutions at no cost. For additional
information, please contact Monica Gramatges, MD, PhD (gramatge@bcm.edu) or Susan
Krause (skrause@texaschildrens.org ).
Funding SourceThis work was supported by the Children’s Oncology Group Chair’s Grant (U10 CA098543) andthe National Clinical Trials Network Group Operations Center Grant (U10 CA180886) from the
National Cancer Institute. The Version 6.0 update, including typesetting, was supported by the
St. Baldrick’s Foundation.

Implementation Considerations
Implementation of these guidelines is intended to standardize and enhance follow-up care
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Instructions for Use
Guideline Organization

System/Score

The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood,
Adolescent, and Young Adult Cancers are organized according to therapeutic exposures,arranged by column as follows:
Section Number

Unique identifier for each guideline section.

Therapeutic Agent

Therapeutic intervention for malignancy, including chemotherapy,
radiation, surgery, blood/serum products, hematopoietic celltransplant, and other therapeutic modalities.

Potential Late
Effects

Most common late treatment complications associated with specified
therapeutic intervention.

Periodic
Evaluations

Recommended screening evaluations, including health history,
physical examination, laboratory evaluation, imaging, andpsychosocial assessment. Recommendation for minimum frequency
of periodic evaluations is based on risk factors and magnitude of risk,
as supported by the medical literature and/or the combined clinicalexperience of the reviewers and panel of experts.

Health Counseling/
Further
Considerations

Health Links: Health education materials developed specifically toaccompany these guidelines. Title(s) of Health Link(s) relevant toeach guideline section are referenced in this column. Health Link
documents are included in Appendix II, and are also available on the
COG website at www.survivorshipguidelines.org.

Body system (e.g., auditory, musculoskeletal) most relevant to eachguideline section.
Score assigned by expert panel representing the strength of datafrom the literature linking a specific late effect with a therapeutic
exposure coupled with an assessment of the appropriateness of thescreening recommendation based on collective clinical experience.
See “Scoring Explanation” in the Preface for more information.

Additional
Information

Patient and cancer/treatment factors, pre-morbid/co-morbid
health conditions, and health behaviors that may increase risk fordeveloping the complication and additional information pertinent to
the late effects or its evaluation (previously known as “Info Links”)

References

References are listed immediately following each guideline
section. Included are medical citations that provide evidence forthe association of the therapeutic intervention with the specifictreatment complication and/or evaluation of predisposing risk factors.
In addition, some general review articles have been included in the
Reference section for clinician convenience.

Resources: Books and websites that may provide the clinician withadditional relevant information.
Counseling: Suggested patient counseling regarding measures
to prevent/reduce risk or promote early detection of the potential
treatment complication.
Potential Considerations for Further Testing and Intervention:
Recommendations for further diagnostic evaluations beyond
minimum screening for individuals with positive history and/or physical examination findings or positive screening tests,
recommendations for consultation and/or referral, andrecommendations for management of exacerbating or predisposing
conditions.
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Instructions for Use (cont)
Using the COG LTFU Guidelines to Develop Individualized Screening Recommendations
In order to accurately derive individualized screening recommendations for a specific childhood
cancer survivor using the Children’s Oncology Group Long-Term Follow-Up Guidelines for
Survivors of Childhood, Adolescent, and Young Adult Cancers, the following procedure should
be followed. (Note: For ease of use, a Patient-Specific Guideline Identification Tool has beendeveloped to streamline the following process and is included in Appendix I).
1.

Obtain the survivor’s Cancer Treatment Summary (see templates for comprehensive
and abbreviated summaries in Appendix 1). Note: In order to generate accurate exposure-based follow-up recommendations from these guidelines, the following information
regarding the survivor’s diagnosis and treatment is required, at minimum:

Cancer Treatment: Radiation• Names of all radiation field(s) treated– For list of radiation fields addressed by these guidelines (Sections 44-98), see “Radiation” portionof the Patient-Specific Guideline Identification Tool in Appendix I– For definition of radiation fields, see “Radiation Fields Defined" in Appendix I• For head/brain, neck, chest, abdomen, spine (whole, cervical, thoracic) radiation and TBI, total dose(in Gy):– Total radiation dose to each field (should include boost dose, if given)– To convert cGy or rads to Gy, divide dose by 100 (example: 2400 cGy = 2400 rads = 24 Gy)

Demographics

Cancer Treatment: Hematopoietic Cell Transplant(s)• Name• Sex• Date of birth• Whether or not the survivor underwent a HCT, and if so:– Transplant type (autologous vs allogeneic)– Chronic graft-versus-host disease (cGVHD) status (no history of cGVHD, history of cGVHD,
currently active cGVHD)

Cancer Diagnosis

Cancer Treatment: Surgery• Diagnosis• Date of diagnosis• Date cancer therapy was completed• Names of all surgical procedures.
– For list of surgical procedures addressed by these guidelines (Sections 115–151), see “Surgery”
portion of the Patient-Specific Guideline Identification Tool in Appendix I

Cancer Treatment: Chemotherapy• Names of all chemotherapy agents received– For a list of chemotherapy agents addressed by these guidelines (Sections 11-43), see the“Chemotherapy” portion of the Patient-Specific Guideline Identification Tool in Appendix I.
– For generic and brand names of chemotherapy agents, see Chemotherapy Agents in Appendix I.
• Cumulative dose of all anthracycline chemotherapy received (i.e., doxorubicin, daunorubicin,
idarubicin, mitoxantrone and epirubicin)– See Section 34 of Guidelines for anthracycline isotoxic dose-equivalent conversion.
– For doses in mg/kg, multiply by 30 to obtain equivalent dosing in mg/m2 (example: 2 mg/kg = 60
mg/m2).
• For carboplatin, whether any dose was myeloablative (i.e., given as conditioning for HCT)• For cytarabine and methotrexate:– Route of administration (i.e., IV, IM, SQ, PO, IT, IO)– If IV, designation of “high dose” (any single dose ≥ 1000 mg/m2) versus “standard dose” (allsingle doses < 1000 mg/m2)

Cancer Treatment: Other Therapeutic Modalities• Whether or not the survivor received radioiodine therapy (I-131 thyroid ablation), systemic MIBG (intherapeutic doses), or other novel agents (Sections 152-163)

2.

COG LTFU Guidelines – Page xxvi

Compile a list of guideline sections relevant to the survivor based off the list generated instep 1.
•

Sections 1 - 7: Applicable to all survivors•

Section 8: Survivors diagnosed before 1972•

Section 9: Survivors diagnosed before 1993•

Section 10: Survivors diagnosed between 1977 and 1985•

Section 11: All survivors who received chemotherapy•

Sections 12-43: For survivors who received chemotherapy, include relevant sections•

Sections 44, 45, 96: All survivors who received radiation
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Instructions for Use (cont)1.

•

Sections 46 - 95, 97- 98: For survivors who received radiation, include relevant
sections

information, please contact Monica Gramatges, MD, PhD (gramatge@bcm.edu) or Susan
Krause (skrause@texaschildrens.org ).

•Sections 100 - 105: All survivors who underwent HCT

We are hopeful that this revised version of the Children’s Oncology Group Long-Term FollowUp Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers will enhance
the follow-up care provided to this unique group of cancer survivors. If you have questions,suggestions, or concerns regarding use of these guidelines, please contact:–

Section 100 is for males only–

Section 101 is for females only•

Section 99: For survivors who underwent autologous HCT•

Sections 106 - 114: For survivors who underwent allogeneic HCT, include relevant
sections•

Sections 115 - 151: For survivors who underwent surgery, include relevant sections•

Sections 152 - 163: For survivors who received other therapeutic modalities, include
relevant sections•

Section 164-165: Applicable to all survivors

Review all guideline sections generated in the list above, and develop a plan for screening the individual survivor, taking into consideration the survivor’s relevant risk factors,
current health, co-morbidities, health-related behaviors and preferences.

Note: The above procedure is applicable to generation of follow-up guidelines from the current
version of this document; however, the COG Long-Term Follow-Up Guidelines Core Committee
recognizes that as new evidence becomes available and these guidelines are updated,additional details regarding the childhood cancer survivor’s therapeutic exposures may berequired in order to generate comprehensive recommendations. Therefore, we strongly advisethat a comprehensive treatment summary be prepared for each childhood cancer survivor,
including a record of all therapeutic exposures with applicable dates, details of administration,and cumulative doses of all agents, including those not currently addressed by theseguidelines.

Co-Chairs, COG Long-Term Follow-Up Guidelines Core Committee:
Matthew J. Ehrhardt, MD, MS
St. Jude Children’s Research Hospital
Memphis, TN(901) 595-5913
matt.ehrhardt@stjude.org

Danielle N. Friedman, MD, MS
Memorial Sloan Kettering Cancer Center
New York, NY(212) 639-7376
friedmad@mskcc.org

Melissa M. Hudson, MD
St. Jude Children’s Research Hospital
Memphis, Tennessee(901) 595-4781
melissa.hudson@stjude.org

Louis S. “Sandy” Constine, MD
University of Rochester Medical Center
Rochester, NY(585) 275-5622
louis_constine@urmc.rochester.edu

Wendy Landier, PhD, CPNP
Children’s Hospital of Alabama
University of Alabama at Birmingham
Birmingham, Alabama(205) 638-2120
wlandier@peds.uab.edu

Smita Bhatia, MD, MPH
Children’s Hospital of Alabama
University of Alabama at Birmingham
Birmingham, Alabama(205) 638-2120
sbhatia@peds.uab.edu

The COG Long-Term Follow-Up Guidelines Core Committee recognizes that the time required
to identify patient-specific recommendations from these guidelines is significant, and has been
identified as a barrier to clinical use. Therefore, COG has partnered with the Baylor School of
Medicine to develop a web-based interface, known as “Passport for Care,” that generates
individualized exposure-based recommendations from these guidelines in a clinician-focusedformat for ease of patient-specific application in the clinical setting. The Passport for Care®
application is available to Children’s Oncology member institutions at no cost. For additional
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New to Version 6.0
All guideline sections have been reviewed by the Long-Term Follow-Up Guidelines Task Forces
and modifications have been made per their recommendations and with the approval of theExpert Panel. The most significant modifications are detailed below.
Simplification
A continued overall goal of Version 6.0 of the COG Long-Term Follow-Up Guidelines is tosimplify the format and content of the guidelines in order to focus on clinically relevant
content, reduce the burden of medical record data abstraction necessary to determine tailored
recommendations for survivors, reduce the complexity of guideline application to individual
survivors, and better align COG’s screening recommendations with those of the International
Guideline Harmonization Group. Version 6.0 therefore features the following modifications:•

Guideline navigation has been simplified through the use of hyperlinks. Hyperlinks aredenoted with blue text and assist in moving more easily through the guideline contents.
Additionally, there is often a hyperlink at the bottom of most pages to direct the user backto a section or the guideline table of contents.

•

Simplification of design/format with a focus on clinical information that drives screening•

Continuation of defined and simplified radiation fields–

All radiation fields from Version 5.0 are still mapped to body parts–

In most cases, knowing the general area of the body that received radiation is now
all that is necessary in order to generate tailored radiation-related recommendations
for survivors–••

It is not necessary to know or record specific radiation doses (with a few exceptions)Radiation dose cut-offs largely eliminated–Emerging evidence indicates that some late effects (e.g., breast and colorectal
cancers) are occurring below the previously determined minimum dose thresholds–

The dose cut-offs that remain are for late effects that require screening beyond thehistory and physical examination and for which evidence indicates that there is a low
risk of developing the late effect below the radiation threshold

Revisions have been made to Counseling and Potential Considerations in most sections•

References have been updated in all applicable sections•

Secondary malignancy has been renamed Subsequent throughout the guidelines•

References to veno-occlusive disease (VOD) has been removed throughout the guidelines
and replaced with the current sinusoidal obstruction syndrome (SOS) term•

Templates remain in Appendix I to assist with drafting appeal letters for denied insurance
claimsNew Sections/Late Effects
The following new sections/late effects have been added:•

Subsequent malignancy and/or Risk of malignancy in offspring related to any cancer
experience (section 7)•

Hypothyroidism related to (partial) Thyroidectomy (section 151)•

Xerostomia and/or Salivary gland dysfunction and/or Chronic sialadenitis related toradioiodine therapy (I-131 thyroid ablation) (section 154)•

Growth attenuation related to BCR-ABL tyrosine kinase inhibitors (section 159)•

Hypothyroidism related to BCR-ABL tyrosine kinase inhibitors (section 160)•

Insufficient information regarding late effects from Other targeted biologic therapies(section 161)•

Immunologic complications related to B-cell directed antibody-based therapies (section
162)•

Insufficient information regarding late effects from Other antibody-based immune
therapies (section 163)•

General health screening regarding vaccinations (section 165)

Sections/Late Effects Removed

All Risk Factors and Highest Risk Factors have been moved to Additional Information

The following sections or late effects have been removed from Version 6.0 of the COG LTFU
Guidelines:

General Updates••

Some History and Physical Exam elements have been reworded for consistency between
sections•

Clinical leukoencephalopathy related to high dose cytarabine (section 24 of Version 4.0)•

Lymphoma related to HCT (section 106 of Version 4.0)

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New to Version 6.0 (cont)•

Renal toxicity related to methotrexate (section 28 changed to “No Known Renal Late
Effects” in Version 5.0)•

Reduced bone mineral density related to methotrexate (section 27 changed to “No Known
BMD Late Effects” in Version 6.0)•

The Cancer Screening Guidelines Sections (156-164 in Version 5.0) for average risk
individuals have been removed due to inconsistencies across cooperative groups andpractice standards, as well as timing alignment with suggested changes and publication.
Your health care providers will offer guidance based on current recommendations andguidelines.

•

Reduced ovarian follicular pool renamed as Diminished ovarian reserve (DOR) (15, 93, 137)•

Secondary benign or malignant neoplasm occurring in or near radiation field renamed as
Subsequent benign or malignant neoplasm occurring in or near radiation field (44)

Newly Combined Sections
These sections from Version 5.0 have been combined into one section (164) in Version 6.0:
Breast cancer screening guidelines standard risk (previous section 156)•

Cervical cancer screening guidelines standard risk (previous section 157)•

Colorectal cancer screening guidelines standard risk (previous section 158)•

Endometrial cancer screening guidelines standard risk (previous section 159)•

Lung cancer screening guidelines standard risk (previous section 160)•

Oral cancer screening guidelines standard risk (previous section 161)•

Prostate cancer screening guidelines standard risk (previous section 162)•

Skin cancer screening guidelines standard risk (previous section 163)•

Testicular cancer screening guidelines standard risk (previous section 164)

New Potential Late Effects Subcategories Added•

Subsequent malignancy (section 7)•

Risk of malignancy in offspring (section 7)•

Altered skin pigmentation (section 106)

Guidelines for Genetic Risk Assessment for Cancer Predisposition (Section 7)
There is risk for subsequent malignancy and/or malignancy in offspring based on genetic
predisposition which warrants further assessment based on the determined risk factors.
Screening for Decreased Bone Mineral Density after Methotrexate (Section 28)

Late Effects Renamed•

Major Screening Changes
Guidelines for Genetic Risk Assessment for Cancer Predisposition (7)Screening for Decreased Bone Mineral Density after Methotrexate (28)
Cardiomyopathy Screening (34, 77)
Cancer Screening for Average Risk Individuals (previously 156-164)

No association has been found concerning decreased BMD and methotrexate; screening is nolonger recommended, but the section remains for reference
Cardiomyopathy Screening (Sections 34, 77)• Echocardiogram screening is not recommended for individuals with both <15Gy radiationdose (with potential impact to heart) and a cumulative doxorubicin equivalent anthracycline
dose <100 mg/m2• Anthracycline dose conversion of mitoxantrone changed to “multiply total dose x 10”
versus the previous recommendation to multiply the total dose x 4
Cancer Screening for Average Risk Individuals
The Average Risk Cancer screening guidelines (Version 5.0 sections 156-164) have been
removed and replaced with a combined screening guideline section (164) for average risk
individuals. Patients with high risk needs related to their cancer treatment are meticulously
addressed in their specific sections. Standard risk patients should consult with their healthcare
provider for general health maintenance based on age and gender. High risk patients are thosewith a history of the following exposure(s):• Breast cancer: radiation (TBI, chest, axilla) review section 73• Cervical cancer: HCT review section 100• Colorectal cancer: radiation (TBI, abdominal, pelvic, spinal [lumbar, sacral, whole]) review
section 85• Lung cancer: radiation (TBI, chest, axilla) review section 75• Oral cancer: radiation (TBI, head/brain, neck) review section 43 and/or GVHD should review
section 107• Skin cancer: radiation review section 44, with a history of HCT review section 100/101,
and/or with a history of cGVHD review section 106

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New to Version 6.0 (cont)
Additional Screening Change Highlights••

Testicular hormonal dysfunction related to alkylating agents and/or testicular radiation:
Screening with AM testosterone in high-risk patients starting at age 18 years is
recommended (12, 90)
Cyclophosphamide equivalent dose calculator (CED) has been added to assist in
determining high risk status (12, 13, 14, 15, 92, 93)•

Cataracts related to corticosteroids, alkylating agents, and/or radiation recommends a
yearly evaluation by an ophthalmologist or optometrist (18, 39, 61)•

Reduced bone mineral density related to steroids and HCT: Adjustments for gender andmenopause status regarding z-score, as well as the age metric changing from 20 to
50 years old. Guidelines for follow up are indicated with a specific algorithm for ease of
implementation. Vitamin D recommendations updated to reflect AAP guidelines with age
specific parameters (37, 104)•

Monthly breast “self-exam” is no longer recommended (73)General Recommendations Regarding Use of the Simplified COG LTFU Guidelines, V 6.0•

The COG Long-Term Follow-Up Guidelines are designed to offer general guidance and are
not meant to provide or replace the medical advice or judgment of clinicians caring forindividual survivors.

•

The recommendations in Version 6.0 of these Guidelines rely more extensively on history
and physical examination and less on screening evaluations, when compared to prior
Guideline versions.

•

We recognize that recommendations for over-screening may occur (primarily due toelimination of radiation dose-cutoffs and simplification of radiation fields); however,additional screening will generally result in recommendations for components of thehistory and physical examination only.

•

It is important for clinicians to recognize that not all survivors may be at-risk for all lateeffects that are associated with the broader exposure categories in Version 6.0; forexample, survivors with radiation fields that are known to be limited to a specific targetedarea within a broader field. Thus, if clinicians have more detailed information that supports
refraining from a specific screening for a particular patient, clinical judgment should be
used to guide the individual evaluation.

•

Since a number of previously recommended screening evaluations are now to beconsidered based on findings from the history and physical examination, cliniciansneed to carefully discern which history and physical examination findings should trigger
further evaluations. Additional, more intensive screening and/or diagnostic workup arerecommended for any survivors for whom the clinician believes there is reason to suspect
the presence of a late effect.

•

If clinicians have more detailed information that supports additional screening (orrefraining from screening), clinicians are encouraged to modify their recommendations
for individual survivors based on their knowledge of that survivor’s specific therapeutic
exposures during treatment and their current clinical status.

Health Links•

The Health Links have been modified to reflect all Version 6.0 Guideline changes.

•

Five Health Links have been renamed:
Diet and Physical Activity is now Staying Healthy through Nutrition and Physical Activity
Educational Issues is now School After Cancer Treatment
Emotional Issues is now Mental Health After Cancer Treatment
Female Health Issues after Cancer Treatment is now Ovarian and Reproductive Health afterCancer Treatment
Male Health Issues after Cancer Treatment is now Testicular and Reproductive Health afterCancer Treatment•

Two new Health Links for Version 6.0:
Vaccines after Treatment for Cancer Survivors Treated with Hematopoietic Cell Transplant(HCT)
Vaccines after Treatment for Cancer Survivors Treated with Chemotherapy and/or Radiation(Non-HCT)

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Abbreviations & Parameters
Abbreviation

Definition

Abbreviation

Definition

Abbreviation

Definition

AAP

American Academy of Pediatrics

COG

Children’s Oncology GroupHCV

Hepatitis C virus

ABR

Auditory brainstem response

CRT

Cranial radiation therapy

HDL

High-density lipoproteins

ACIP

Advisory Committee on Immunization
PracticesCT

Computed tomography

HIB

Haemophilus influenzae type B

CVRF

Cardiovascular risk factors

ACS

American Cancer Society

HIV

Human immunodeficiency virusdB

DecibelAHA

American Heart Association

HLA

Human leukocyte antigen

DES

Diethylstilbestrol

ALL

Acute lymphoblastic leukemia

HNPCC

Hereditary nonpolyposis colorectal cancer

DI

Diabetes Insipidus

ALT

Alanine aminotransferase

HPF

High power field

DLCO

Diffusion capacity of carbon monoxide

AMH

Anti-Mullerian hormone

HPV

Human papillomavirus

DOR

Diminished ovarian reserve

AML

Acute myeloid leukemia

htHeightDTI

Diffusion-tensor imaging

AST

Aspartate aminotransferase

Hz

Hertz

DWI

Diffusion-weighted imaging

ATG

Anti-thymocyte globulin

IBD

Inflammatory bowel disease

DXA

Dual energy x-ray absorptiometryATM

Ataxia telangiectasia cancer susceptibility
gene (located on chromosome 11)

K

Potassium

ECHO

Echocardiogram

I-131

Iodine 131 radioisotope

AVN

Avascular necrosis

EKG

Electrocardiogram

IgA

Immunoglobulin A

BMD

Bone mineral density

EIA

Enzyme immunoassay

IL-2

Interleukin-2

BMI

Body mass index

FAP

Familial adenomatous polyposis

IM

Intramuscular

BRCA1

Breast cancer susceptibility gene 1 (locatedon chromosome 17)

FM

Frequency modulated

IMRTIntensity-modulated radiation therapy

FNA

Fine needle aspiration

IO

Intra-Ommaya

FNH

Focal nodular hyperplasia

IQIntelligence quotient

FSH

Follicle stimulating hormone

IT

Intrathecal

Granulocyte colony stimulating factor

IU

International unit

BRCA2

Breast cancer susceptibility gene 2 (locatedon chromosome 13)

BUN

Blood urea nitrogen

G-CSF

Ca

CalciumGH

Growth hormone

IV

Intravenous

CAD

Coronary artery disease

GI

Gastrointestinal

IVIG

Intravenous immunoglobulin

Complete blood count

gm

Gram

kg

Kilogram

CCG

Children’s Cancer GroupGVHD

Graft versus host disease

KUB

Kidneys, ureters, bladder radiograph

CDC

Centers for Disease Control

Gy

Gray

LH

Luteinizing hormone

cGVHD

Chronic graft versus host disease

HbA1c

Hemoglobin A1c

LV

Left ventricular

Chloride

HBcAb

Hepatitis B core antibodym

Square meter

Central nervous system

HBsAg

Hepatitis B surface antigen

MDS

Myelodysplastic syndrome

Carbon dioxide

HCT

Hematopoietic cell transplant

MIBG

Iodine-131-meta-iodobenzylguanidine

CBC

Cl
CNS
CO2

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Abbreviations & Parameters (cont.)
Abbreviation

Definition

Abbreviation

Definitionmg

Milligram

SCUBA

Mg

Magnesium

Self-contained underwater breathingapparatus

MMF

Mycophenolate mofetil

SD

Standard deviation

MOPP

Mechlorethamine, Oncovin, Procarbazine,
Prednisone

SOS

Sinusoidal obstruction syndrome

SQ

SubcutaneousMR

Magnetic resonance

STLI

Subtotal lymphoid irradiation

MRA

Magnetic resonance angiography

T4

Thyroxine

MRI

Magnetic resonance imaging

TBI

Total body irradiation

Na

SodiumTLI

Total lymphoid irradiation

NF1

Neurofibromin 1 (neurofibromatosis)
cancer susceptibility gene (located on
chromosome 17)

TPN

Total parenteral nutrition

TSH

Thyroid stimulating hormone

U

Units

USPSTF

United States Preventive Services Task
Force

V-A

Ventriculoatrial

VOD

Veno-occlusive disease

V-P

Ventriculoperitoneal

V-V

Ventriculovenus

VZIG

Varicella zoster immunoglobulin

WAGR

Wilms tumor, aniridia, genitourinary
anomalies, range of developmental delays

wt

WeightNHL

Non-Hodgkin lymphoma

NSAIDs

Non-steroidal anti-inflammatory drugs

p53

Cancer susceptibility gene associated withfamilial cancers (located on chromosome
17)

PAP

Papanicolaou

PCR

Polymerase chain reaction

PFTs

Pulmonary function tests

PNET

Primitive neuroectodermal tumor

PNS

Peripheral nervous systemPOBy mouth

PO4

Phosphate

PSA

Prostate specific antigen

PUVA

Psoralen plus ultraviolet-A radiation

QTc

Corrected QT interval

RB1

Retinoblastoma cancer susceptibility gene(located on chromosome 13)

RBC

Red blood cell

RUQ

Right upper quadrant

Parameters commonly referenced in the guidelines≥1000 mg/m2

High dose methotrexate<1000mg/m

Standard dose methotrexate22≥1000 mg/m

High dose cytarabine

2<1000mg/m

Standard dose cytarabine

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Long-Term
Follow-Up
Guidelines
for Survivors of Childhood,
Adolescent, and Young Adult Cancers

Guidelines
Version 6.0
October 2023

ANY CANCER EXPERIENCESec #Therapeutic
Exposure

Potential
Late Effects

1

Any Cancer Experience

Adverse psychosocial/qualityof life effects
Social withdrawal
Educational problems
Relationship problems
Under-employment/
Unemployment
Dependent living

Periodic Evaluation

Health Counseling/
Further Considerations

HISTORYHEALTH LINKS
Psychosocial assessment with attention to: Introduction to Long-Term Follow-Up• Educational and/or vocational progress Mental Health• Social withdrawal
School After Treatment
YearlyRESOURCES‘Childhood Cancer Survivors: A Practical Guide to Your Future,’ by Nancy Keene,
Wendy Hobbie & Kathy Ruccione, Childhood Cancer Guides, 2012
‘Educating the Child with Cancer: A Guide for Parents and Teachers,’ edited by
Ruth Hoffman, American Childhood Cancer Organization, 2013
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Preference should be given to self vs. proxy report.
Psychological consultation in patients with emotional difficulties related tocancer experience, including physical deformities or chronic disabilities.
Social work consultation.
Refer as indicated to school liaison in community or cancer center (psychologist,social worker, school counselor) to facilitate acquisition of educational or
vocational resources.
Refer as indicated for neuropsychological evaluation.
Assess social determinants of health including economic stability, education
access and quality, health care access and quality, neighborhood andbuilt environment, and social and community context (https://health.gov/
healthypeople/objectives-and-data/social-determinants-health).
SYSTEM = Psychosocial
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at diagnosis, family history of depression, anxiety, or mental illness, lower household income, lower educational attainment, school withdrawal, race/ethnicity- Cancer/Treatment factors: Bone tumor, CNS tumor, CNS-directed therapy, history of HCT- Pre-morbid/Co-morbid medical conditions: Premorbid learning or emotional difficulties, chronic conditions after cancer treatment (e.g., obesity, endocrine, pulmonary, cardiac conditions) are associated with increased risk forneurocognitive difficulties, and/or increased symptom burden (e.g., pain, fatigue) including neurocognitive problems

References
Barrera M, Shaw AK, Speechley KN, et al: Educational and social late effects of childhood cancer and related clinical, personal, and familial characteristics. Cancer 104:1751-60, 2005
Bernard F, Auquier P, Herrmann I, et al: Health status of childhood leukemia survivors who received hematopoietic cell transplantation after BU or TBI: an LEA study. Bone Marrow Transplant 49:709-16, 2014
Boman KK, Lindblad F, Hjern A: Long-term outcomes of childhood cancer survivors in Sweden: a population-based study of education, employment, and income. Cancer 116:1385-91, 2010
Brinkman TM, Bass JK, Li Z, et al: Treatment-induced hearing loss and adult social outcomes in survivors of childhood CNS and non-CNS solid tumors: Results from the St. Jude Lifetime Cohort Study. Cancer 121:4053-61, 2015
Brinkman TM, Krasin MJ, Liu W, et al: Long-term neurocognitive functioning and social attainment in adult survivors of pediatric CNS tumors: results from the St Jude Lifetime Cohort Study. J Clin Oncol 34:1358-67, 2016
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ANY CANCER EXPERIENCE (CONT)
Section 1 References (cont)
Brinkman TM, Ullrich NJ, Zhang N, et al: Prevalence and predictors of prescription psychoactive medication use in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Cancer Surviv 7:104-14,
2013
de Blank PM, Fisher MJ, Lu L, et al: Impact of vision loss among survivors of childhood central nervous system astroglial tumors. Cancer 122:730-9, 2016
Devine KA, Christen S, Mulder RL, et al: Recommendations for the surveillance of education and employment outcomes in survivors of childhood, adolescent, and young adult cancer: a report from the International Late Effects ofChildhood Cancer Guideline Harmonization Group. Cancer 1;128(13):2405-2419, 2022
Edelmann MN, Daryani VM, Bishop MW, et al: Neurocognitive and patient-reported outcomes in adult survivors of childhood osteosarcoma. JAMA Oncol 2(2):201-8, 2016
Font-Gonzalez A, Feijen EL, Sieswerda E, et al: Social outcomes in adult survivors of childhood cancer compared to the general population: linkage of a cohort with population registers. Psycho-Oncol 25:933-41, 2016
Hornquist L, Rickardsson J, Lannering B, et al: Altered self-perception in adult survivors treated for a CNS tumor in childhood or adolescence: population-based outcomes compared with the general population. Neuro Oncol 17:73340, 2015
Iijima M, Liu W, Panetta JC, et al. Association between obesity and neurocognitive function in survivors of childhood acute lymphoblastic leukemia treated only with chemotherapy. Cancer 127(17):3202-3213, 2021
Janson C, Leisenring W, Cox C, et al: Predictors of marriage and divorce in adult survivors of childhood cancers: a report from the Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 18:2626-35, 2009
Kinahan KE, Sharp LK, Seidel K, et al: Scarring, disfigurement, and quality of life in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 30:2466-74, 2012
Kirchhoff AC, Krull KR, Ness KK, et al: Occupational outcomes of adult childhood cancer survivors: A report from the Childhood Cancer Survivor Study. Cancer 117:3033-44, 2011
Kirchhoff AC, Leisenring W, Krull KR, et al: Unemployment among adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Med Care 48:1015-25, 2010
Kunin-Batson A, Kadan-Lottick N, Zhu L, et al: Predictors of independent living status in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 57:1197-203, 2011
Lancashire ER, Frobisher C, Reulen RC, et al: Educational attainment among adult survivors of childhood cancer in Great Britain: a population-based cohort study. J Natl Cancer Inst 102:254-70, 2010
Lown EA, Phillips F, Schwartz LA, et al: Psychosocial follow-up in survivorship as a standard of care in pediatric oncology. Pediatr Blood Cancer 62 Suppl 5:S514-84, 2015
Lund LW, Schmiegelow K, Rechnitzer C, et al: A systematic review of studies on psychosocial late effects of childhood cancer: structures of society and methodological pitfalls may challenge the conclusions. Pediatr Blood Cancer
56:532-43, 2011
Mitby PA, Robison LL, Whitton JA, et al: Utilization of special education services and educational attainment among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 97:1115-26,
2003
Rueegg CS, Gianinazzi ME, Rischewski J, et al: Health-related quality of life in survivors of childhood cancer: the role of chronic health problems. J Cancer Surviv 7:511-22, 2013
Schulte F, Kunin-Batson AS, Olson-Bullis BA, et al: Social attainment in survivors of pediatric central nervous system tumors: a systematic review and meta-analysis from the Children’s Oncology Group. J Cancer Surviv 13(6):921931, 2019
Stokke J, Sung L, Gupta A, et al: Systematic review and meta-analysis of objective and subjective quality of life among pediatric, adolescent, and young adult bone tumor survivors. Pediatr Blood Cancer 62:1616-29, 2015
Wengenroth L, Rueegg CS, Michel G, et al: Life partnerships in childhood cancer survivors, their siblings, and the general population. Pediatr Blood Cancer 61:538-45, 2014

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ANY CANCER EXPERIENCE (CONT)Sec #2Therapeutic
Exposure
Any Cancer Experience

Potential
Late Effects
Mental health disorders
Depression
Anxiety
Post-traumatic stressSuicidal behavior

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Psychosocial assessment with attention to:• Depression• Anxiety• Post-traumatic stress• Suicidal ideation
YearlyHEALTH LINKS
Mental HealthRESOURCES‘Childhood Cancer Survivors: A Practical Guide to Your Future,’ by Nancy Keene, Wendy
Hobbie & Kathy Ruccione, Childhood Cancer Guides, 2012
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Preference should be given to self vs. proxy report.
Psychological consultation in patients with emotional difficulties related to cancer
experience, including physical deformities or chronic disabilities.
Appropriate psychotropic medications, as clinically indicated.
Evaluation of parent for posttraumatic stress.
Assess social determinants of health including economic stability, education access andquality, health care access and quality, neighborhood and built environment, and socialand community context (https://health.gov/healthypeople/objectives-and-data/social-determinants-health).
SYSTEM = Psychosocial
SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Female sex, family history of depression, anxiety, or mental illness, lower household income, lower educational attainment, especially school withdrawal, unemployment, not in a relationship, poor social support, perceived poor physical health, no health insurance or public health insurance- Cancer/Treatment factors: CNS tumor, CNS-directed therapy, history of HCT- Pre-morbid/Co-morbid medical conditions: Chronic pain, scarring or physical disfigurement, permanent hair loss, premorbid learning or emotional difficulties, sleep/fatigue issues, substance misuse

References
Allen J, Willard VW, Klosky JL, et al: Posttraumatic stress-related psychological functioning in adult survivors of childhood cancer. J Cancer Survivorship 12(2),216–223, 2018
Brinkman TM, Li C, Vannatta K, et al: Behavioral, social, and emotional symptom comorbidities and profiles in adolescent survivors of childhood cancer: a report From the Childhood Cancer Survivor Study. J Clin Oncol 1;34(28):3417-25, 2016
Brinkman TM, Zhu L, Zeltzer LK, et al: Longitudinal patterns of psychological distress in adult survivors of childhood cancer. Br J Cancer 109:1373-81, 2013
Cunningham SJ, Patton M, Schulte F, et al: Worry about somatic symptoms as a sign of cancer recurrence: prevalence and associations with fear of recurrence and quality of life in survivors of childhood cancer. Psycho-onc 30(7),1077–1085, 2021
Kinahan KE, Sharp LK, Seidel K, et al: Scarring, disfigurement, and quality of life in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 30:2466-74, 2012
Klosky JL, Krull KR, Kawashima T, et al: Relations between posttraumatic stress and posttraumatic growth in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Health Psychol 33:878-82, 2014
Korhonen LM, Taskinen M, Rantanen M, et al: Suicides and deaths linked to risky health behavior in childhood cancer patients: a Nordic population-based register study. Cancer 125(20):3631-8, 2019
Lown EA, Phillips F, Schwartz LA, et al: Psychosocial follow-up in survivorship as a standard of care in pediatric oncology. Pediatr Blood Cancer 62 Suppl 5:S514-84, 2015
Michel G, Rebholz CE, von der Weid NX, et al: Psychological distress in adult survivors of childhood cancer: the Swiss Childhood Cancer Survivor Study. J Clin Oncol 28:1740-8, 2010
Oancea SC, Brinkman TM, Ness KK, et al: Emotional distress among adult survivors of childhood cancer. J Cancer Surviv 8:293-303, 2014
Prasad PK, Hardy KK, Zhang N, et al: Psychosocial and neurocognitive outcomes in adult survivors of adolescent and early young adult cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 33:2545-52, 2015
Recklitis CJ, Diller LR, Li X, et al: Suicide ideation in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 28:655-61, 2010
Shah SS, Dellarole A, Peterson EC, et al: Long-term psychiatric outcomes in pediatric brain tumor survivors. Childs Nerv Syst 31:653-63, 2015
Stuber ML, Meeske KA, Krull KR, et al: Prevalence and predictors of posttraumatic stress disorder in adult survivors of childhood cancer. Pediatrics 125:e1124-34, 2010
Zebrack BJ, Landier W: The perceived impact of cancer on quality of life for post-treatment survivors of childhood cancer. Qual Life Res 20:1595-608, 2011
Zebrack BJ, Stuber ML, Meeske KA, et al: Perceived positive impact of cancer among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Psycho-Oncol 21:630-9, 2012

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ANY CANCER EXPERIENCE (CONT)Sec #Therapeutic
Exposure

Potential
Late Effects

3

Any Cancer Experience

Risky behaviors
Behaviors known to increase
the likelihood of subsequentillness or injury

Periodic Evaluation
HISTORY
Psychosocial assessment
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Mental HealthRESOURCES‘Childhood Cancer Survivors: A Practical Guide to Your Future,’ by Nancy Keene,
Wendy Hobbie & Kathy Ruccione, Childhood Cancer Guides, 2012www.smokefree.gov
www.cancer.org/healthy/stay-away-from-tobacco
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Psychological consultation in patients with emotional difficulties related tocancer experience.
Assess social determinants of health including economic stability, education
access and quality, health care access and quality, neighborhood andbuilt environment, and social and community context (https://health.gov/
healthypeople/objectives-and-data/social-determinants-health).
SYSTEM = Psychosocial
SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Adolescent/Young adult at diagnosis or follow-up, male sex, lower household income, lower educational attainment, rural neighborhood, psychological distress

References
Buchanan N, Leisenring W, Mitby PA, et al: Behaviors associated with ultraviolet radiation exposure in a cohort of adult survivors of childhood and adolescent cancer: a report from the Childhood Cancer Survivor Study. Cancer 115:4374-84, 2009
Frobisher C, Lancashire ER, Reulen RC, et al: Extent of alcohol consumption among adult survivors of childhood cancer: the British Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 19:1174-84, 2010
Gibson TM, Liu W, Armstrong GT, et al: Longitudinal smoking patterns in survivors of childhood cancer: an update from the Childhood Cancer Survivor Study. Cancer 121:4035-43, 2015
Howell CR, Wilson CL, Yasui Y, et al: Neighborhood effect and obesity in adult survivors of pediatric cancer: a report from the St. Jude lifetime cohort study. Int J Cancer 147(2),338–349, 2020
Ji X, Cummings JR, Mertens AC, et al: Substance use, substance use disorders, and treatment in adolescent and young adult cancer survivors-results from a national survey. Cancer 127(17),3223–3231, 2021
Klosky JL, Howell CR, Li Z, et al: Risky health behavior among adolescents in the Childhood Cancer Survivor Study cohort. J Pediatr Psychol 37:634-46, 2012
Milam J, Slaughter R, Meeske K, et al: Substance use among adolescent and young adult cancer survivors. Psycho-Oncol 25:1357-1362, 2016
Oancea SC, Gurney JG, Ness KK, et al: Cigarette smoking and pulmonary function in adult survivors of childhood cancer exposed to pulmonary-toxic therapy: results from the St. Jude Lifetime Cohort Study. Cancer Epidemiol Biomarkers Prev
23:1938-43, 2014
Pinto S, Fresneau B, Hounsossou HC, et al: Identifying clusters of health risk behaviors and their predictors in adult survivors of childhood cancer: a report from the French Childhood Cancer Survivor Study. Psychooncology, 29(10),1595-1603,
2020
Sundberg KK, Lampic C, Arvidson J, et al: Sexual function and experience among long-term survivors of childhood cancer. Eur J Cancer 47:397-403, 2011

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ANY CANCER EXPERIENCE (CONT)Sec #Therapeutic
Exposure

Potential
Late Effects

4

Any Cancer Experience

Psychosocial disability due
to painHealth Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Psychosocial assessment
YearlyHEALTH LINKS
Chronic Pain after Childhood Cancer
RESOURCES‘Childhood Cancer Survivors: A Practical Guide to Your Future,’ by Nancy Keene,
Wendy Hobbie & Kathy Ruccione, Childhood Cancer Guides, 2012
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Psychological consultation in patients with chronic pain.
Appropriate psychotropic medications, as clinically indicated.
Referral to pain rehabilitation clinic.
SYSTEM = Psychosocial
SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Female sex- Cancer/Treatment factors: CNS tumor, Hodgkin lymphoma, sarcoma/bone diagnosis, radiation to bone/joint, vincristine exposure- Pre-morbid/Co-morbid medical conditions: History of osteonecrosis, depression, anxiety, sleep/fatigue issues, severe/life threatening chronic medical conditions

References
Karlson CW, Alberts NM, Liu W, et al: Longitudinal pain and pain interference in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 15;126(12):2915-2923, 2020
Lu Q, Krull KR, Leisenring W, et al: Pain in long-term adult survivors of childhood cancers and their siblings: a report from the Childhood Cancer Survivor Study. Pain 152:2616-24, 2011
Ness KK, Hudson MM, Jones KE, et al: Effect of temporal changes in therapeutic exposure on self-reported health status in childhood cancer survivors. Ann Intern Med 166:89-98, 2017
Schulte FSM, Patton M, Alberts NM, et al: Pain in long-term survivors of childhood cancer: A systematic review of the current state of knowledge and a call to action from the Children’s Oncology Group. Cancer 1;127(1):35-44, 2021
Tonning Olsson I, Alberts NM, Li C, et al: Pain and functional outcomes in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort study. Cancer 15;127(10):1679-1689, 2021

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ANY CANCER EXPERIENCE (CONT)Sec #Therapeutic
Exposure5

Any Cancer Experience

Potential
Late Effects
FatigueSleep problems

Periodic Evaluation
HISTORY
Psychosocial assessment
YearlyHealth Counseling/
Further Considerations
RESOURCES‘Childhood Cancer Survivors: A Practical Guide to Your Future,’ by Nancy Keene,
Wendy Hobbie & Kathy Ruccione, Childhood Cancer Guides, 2012
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Screen for physical sources of fatigue, such as anemia, sleep disturbances,
nutritional deficiencies, cardiomyopathy, pulmonary fibrosis, hypothyroidism, orother endocrinopathies.
Referral to specialties such as endocrinology, sleep lab/study, or nutrition as
indicated.
Referral to psychology for behavioral intervention for emotional difficulties
contributing to sleep/fatigue issues.
Refer as indicated for cognitive-behavior therapy for insomnia.
Assess social determinants of health including economic stability, education
access and quality, health care access and quality, neighborhood andbuilt environment, and social and community context (https://health.gov/
healthypeople/objectives-and-data/social-determinants-health).
SYSTEM = Psychosocial
SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Female sex- Cancer/Treatment factors: CNS tumor (e.g., craniopharyngioma), pulmonary radiation- Pre-morbid/Co-morbid medical conditions: Depression, anxiety, obesity, sleep/fatigue issues, pain

References
Christen S, Roser K, Mulder RL, et al: Recommendations for the surveillance of cancer-related fatigue in childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. J Cancer Surviv 14(6):923-938, 2020
Jacobsen PB: Assessment of fatigue in cancer patients. J Natl Cancer Inst Monogr:93-7, 2004
Lawrence DP, Kupelnick B, Miller K, et al: Evidence report on the occurrence, assessment, and treatment of fatigue in cancer patients. J Natl Cancer Inst Monogr:40-50, 2004
Mulrooney DA, Ness KK, Neglia JP, et al: Fatigue and sleep disturbance in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study (CCSS). Sleep 31:271-81, 2008
Rosen G, Brand SR: Sleep in children with cancer: case review of 70 children evaluated in a comprehensive pediatric sleep center. Support Care Cancer 19:985-94, 2011
Verberne LM, Maurice-Stam H, Grootenhuis MA, et al: Sleep disorders in children after treatment for a CNS tumour. J Sleep Res 21:461-9, 2012
Zeller B, Loge JH, Kanellopoulos A, et al: Chronic fatigue in long-term survivors of childhood lymphomas and leukemia: persistence and associated clinical factors. J Pediatr Hematol Oncol 36:438-44, 2014
Zhou ES, Vrooman LM, Manley PE, et al: Adapted delivery of cognitive-behavioral treatment for insomnia in adolescent and young adult cancer survivors: a pilot study. Behav Sleep Med 15:288-301, 2017

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ANY CANCER EXPERIENCE (CONT)Sec #Therapeutic
Exposure

Potential
Late Effects

6

Any Cancer Experience

Limitations in healthcare andinsurance access

Periodic Evaluation
HISTORY
Psychosocial assessment with attention to
healthcare and insurance accessYearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Finding and Paying for Healthcare
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Social work consultation.
Healthcare and insurance access may differ by country and/or state.
Assess social determinants of health including economic stability, education
access and quality, health care access and quality, neighborhood andbuilt environment, and social and community context (https://health.gov/
healthypeople/objectives-and-data/social-determinants-health).
SYSTEM = Psychosocial
SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Lower household income, lower educational attainment, unemployment

References
Caplin DA, Smith KR, Ness KK, et al: Effect of population socioeconomic and health system factors on medical care of childhood cancer survivors: a report from the Childhood Cancer Survivor Study. J Adolesc Young Adult Oncol 6:7482, 2017
Fiala MA. Disparities in health care affordability among childhood cancer survivors persist following the Affordable Care Act. Pediatr Blood Cancer 68(12):e29370, 2021
Huang IC, Bhakta N, Brinkman TM, et al: Determinants and consequences of financial hardship among adult survivors of childhood cancer: a report from the St. Jude Lifetime Cohort Study. J Natl Cancer Inst 111(2):189-200, 2019
Nathan PC, Greenberg ML, Ness KK, et al: Medical care in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 26:4401-9, 2008
Park ER, Kirchhoff AC, Nipp RD, et al: Assessing health insurance coverage characteristics and impact on health care cost, worry, and access: a report from the Childhood Cancer Survivor Study. JAMA Intern Med 177(12):1855-1858,2017
Park ER, Kirchhoff AC, Zallen JP, et al: Childhood Cancer Survivor Study participants’ perceptions and knowledge of health insurance coverage: implications for the Affordable Care Act. J Cancer Surviv 6:251-9, 2012

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ANY CANCER EXPERIENCE (CONT)Sec #Therapeutic
Exposure

7

Any Cancer Experience

Potential
Late Effects
Subsequent malignancy
Risk of malignancy inoffspring

Table 1

Solid Tumor
Adrenocortical carcinoma
Desmoid tumor
Endolymphatic sac tumor
Gastrointestinal stromal tumor
Malignant peripheral nerve sheath tumor
Medullary thyroid cancer
Osteosarcoma
Ovarian Sertoli cell or Sertoli-Leydig cell tumor
Paraganglioma
Pheochromocytomaw

Periodic Evaluation
HISTORY
Strongly consider assessment for cancer
predisposition in the following settings:• Any tumor listed in Table 1• Any bilateral cancer• >1 primary cancer• ≥1 first degree relative(s) with cancer• Other concerning family history including consanguinity• Diagnosis of adult-type cancer in a child(basal cell carcinoma, breast, colon,
gastrointestinal, ovarian, etc.)• Diagnosis of cancer predisposition syndrome in a relative

Solid Tumor (cont)Pleuropulmonary blastoma
Renal cell carcinoma
Rhabdoid tumor
Schwannoma
CNS Tumor
Atypical teratoid rhabdoid tumor
Choroid plexus carcinoma
Ciliary body medullo-ephithelioma
Hemangioblastoma
Optic pathway glioma

Health Counseling/
Further Considerations
RESOURCES
McGill Interactive Pediatric OncoGenetic Guidelines: www.mipogg.com
National Society of Genetic Counselors: www.nsgc.org
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
For patients who may be at risk for cancer predisposition by history, or with ahistory of one of the cancer types listed in Table 1, consider:• Referral to genetic counseling or clinical genetics• Referral for preconception/prenatal counseling
SYSTEM = SMNSCORE = 1

CNS Tumor (cont)Pineoblastoma
Pituitary blastoma
Retinoblastoma
Sub-ependymomal giant cell astrocytoma
Non-Malignant/Other
Cystic nephroma
Juvenile myelomonocytic leukemia
Meningioma
Myelodysplastic syndrome

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
Common cancers for which there is increased risk for underlying predisposition under specific clinical scenarios include:- AML with personal or family history of cytopenias or chronic infections, monosomy 7, short stature, microcephaly, other congenital anomalies, or 3 or more café au lait macules- B-cell ALL with low hypodiploid cytogenetics (32-39 chromosomes)- Embryonal rhabdomyosarcoma diagnosed <4 years old, diffuse anaplasia or botryoid subtype, or in genitourinary location- Medulloblastoma of SHH or WNT subtypes, or diagnosed <3 years old if subtype unknown- Hepatoblastoma with family history of GI cancer/polyps, or with features of hemihyperplasia/overgrowth syndrome- Wilms tumor diagnosed <2 years old with GU anomalies (including history of undescended testicle or hypospadias), hemihyperplasia/overgrowth, or other syndromic features

References
Goudie C, Witkowski L, Cullinan N, et al: Performance of the McGill Interactive Pediatric OncoGenetic Guidelines for Identifying Cancer Predisposition Syndromes. JAMA Oncol 1;7(12):1806-1814, 2021
Jongmans MC, Loeffen JL, Waanders E, et al: Recognition of genetic predisposition in pediatric cancer patients: an easy-to-use selection tool. Eur J Med Genet 59(3):116-25, 2016
Ripperger T, Bielack SS, Borkhardt A, et al: Childhood cancer predisposition syndromes-a concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology. Am J
Med Genet A173(4):1017-1037, 2017
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BLOOD/SERUM PRODUCTS
Sec #Therapeutic
Exposure

8

Diagnosed prior to 1972

Potential
Late Effects
Chronic hepatitis B

Periodic Evaluation

Health Counseling/
Further Considerations

SCREENING
Hepatitis B surface antigen (HBsAg)
Hepatitis B core antibody (anti-HBc or
HBcAb)
Once in patients who received treatment forcancer prior to 1972
Note: Date may vary for international patientsHEALTH LINKS
Hepatitis
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Screen for viral hepatitis in patients with persistently abnormal liver function
regardless of transfusion history.
Gastroenterology or hepatology consultation for patients with chronic hepatitis.
Hepatitis A and B immunization in at-risk patients lacking immunity.
SYSTEM = Immune
SCORE = 1w

Additional Information

Exposure to blood/serum products prior to initiation of hepatitis B screening of blood supply (1972 in the United States - dates may differ in other countries) is associated with risk of chronic hepatitis B.
Since the vast majority of patients received some type of blood product during childhood cancer treatment, screening based on date of diagnosis/treatment is recommended unless there is absolute certainty that the patient did notreceive any blood or blood products.
Relevant exposures include packed red cells, whole blood, granulocytes, platelets, fresh frozen plasma, cryoprecipitate, IVIG, VZIG, factor concentrate, and allogeneic marrow, cord blood, or stem cells.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Living in hyperendemic areas- Cancer/Treatment factors: Chronic immunosuppression- Health behaviors: History of IV drug use, unprotected sex, multiple partners, high-risk sexual behavior, sexually transmitted infections, tattoos, body piercing

References
Castellino S, Muir A, Shah A, et al: Hepato-biliary late effects in survivors of childhood and adolescent cancer: a report from the Children’s Oncology Group. Pediatr Blood Cancer 54:663-9, 2010
Locasciulli A, Alberti A, Rossetti F, et al: Acute and chronic hepatitis in childhood leukemia: a multicentric study from the Italian Pediatric Cooperative Group for Therapy of Acute Leukemia (AIL-AIEOP). Med Pediatr Oncol 13:203-6,
1985
Willers E, Webber L, Delport R, et al: Hepatitis B--a major threat to childhood survivors of leukaemia/lymphoma. J Trop Pediatr 47:220-5, 2001
Zou S, Stramer SL, Dodd RY: Donor testing and risk: current prevalence, incidence, and residual risk of transfusion-transmissible agents in US allogeneic donations. Transfus Med Rev 26:119-28, 2012

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BLOOD/SERUM PRODUCTS (CONT)Sec #Therapeutic
Exposure

9

Diagnosed prior to 1993

Potential
Late Effects
Chronic hepatitis C

Periodic Evaluation
SCREENING
Hepatitis C antibody
Once in patients who received treatment forcancer prior to 1993
Note: Date may vary for international patients
Hepatitis C PCR (to establish chronic
infection)
Once in patients with positive Hepatitis C
antibody

Health Counseling/
Further Considerations
HEALTH LINKS
Hepatitis
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Screen for viral hepatitis in patients with persistently abnormal liver function
regardless of transfusion history.
PCR testing for HCV in immunosuppressed patients who are negative for
antibody.
Gastroenterology or hepatology consultation for management of patients withchronic hepatitis.
Hepatitis A and B immunization in at-risk patients lacking immunity.
SYSTEM = Immune
SCORE = 1w

Additional Information

Exposure to blood/serum products prior to initiation of hepatitis C screening of blood supply (1993 in the United States [considering the more reliable EIA-2 screening was released in the U.S. in 1992] - dates may differ in othercountries) is associated with risk of chronic hepatitis C.
Since the vast majority of patients received some type of blood product during childhood cancer treatment, screening based on date of diagnosis/treatment is recommended unless there is absolute certainty that the patient did notreceive any blood or blood products.
Relevant exposures include packed red cells, whole blood, granulocytes, platelets, fresh frozen plasma, cryoprecipitate, IVIG, VZIG, factor concentrates, and allogeneic marrow, cord blood, or stem cells.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Living in hyperendemic areas- Cancer/Treatment factors: Chronic immunosuppression, exposure to blood/serum products prior to 1986 (when surrogate screening of blood donors with ALT was initiated and donors with self-reported high-risk behaviors
were deferred)- Health behaviors: History of IV drug use, unprotected sex, multiple partners, high-risk sexual behavior, sexually transmitted infections, tattoos, body piercing

References
Bardi E, Mulder RL, van Dalen EC, et al. Late hepatic toxicity surveillance for survivors of childhood, adolescent and young adult cancer: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.
Cancer Treat Rev 100:102296, 2021
Castellino S, Lensing S, Riely C, et al: The epidemiology of chronic hepatitis C infection in survivors of childhood cancer: an update of the St Jude Children’s Research Hospital hepatitis C seropositive cohort. Blood 103:2460-6, 2004
Castellino S, Muir A, Shah A, et al: Hepato-biliary late effects in survivors of childhood and adolescent cancer: a report from the Children’s Oncology Group. Pediatr Blood Cancer 54:663-9, 2010
Cesaro S, Bortolotti F, Petris MG, et al: An updated follow-up of chronic hepatitis C after three decades of observation in pediatric patients cured of malignancy. Pediatr Blood Cancer 55:108-12, 2010
Green DM, Wang M, Krasin MJ, et al. Serum alanine aminotransferase elevations in survivors of childhood cancer: a report from the St. Jude Lifetime Cohort Study. Hepatol 69(1):94-106, 2019
Lansdale M, Castellino S, Marina N, et al: Knowledge of hepatitis C virus screening in long-term pediatric cancer survivors: a report from the Childhood Cancer Survivor Study. Cancer 116:974-82, 2010
Locasciulli A, Testa M, Pontisso P, et al: Prevalence and natural history of hepatitis C infection in patients cured of childhood leukemia. Blood 90:4628-33, 1997
Peffault de Latour R, Levy V, Asselah T, et al: Long-term outcome of hepatitis C infection after bone marrow transplantation. Blood 103:1618-24, 2004
Psaros Einberg A, Ekman AT, Söderhäll S, et al. Prevalence of chronic hepatitis C virus infection among childhood cancer survivors in Stockholm, Sweden. Acta Oncol, 58(7):997-1002, 2019

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BLOOD/SERUM PRODUCTS (CONT)
Sec #
10

Therapeutic
Exposure

Potential
Late Effects

Diagnosed between 1977 HIV infection
and 1985

Periodic Evaluation

Health Counseling/
Further Considerations

SCREENING
HIV testingOnce in patients who received treatment forcancer between 1977 and 1985
Note: Date may vary for international patients

COUNSELING
Standard counseling regarding safer sex, universal precautions and high-risk
behaviors that exacerbate risk.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
HIV/Infectious diseases specialist consultation for patients with chronic infection.
SYSTEM = Immune
SCORE = 1w

Additional Information

Exposure to blood/serum products prior to initiation of HIV screening of blood supply (between 1977 and 1985 in the United States - dates may differ in other countries) is associated with risk of HIV infection.
Since the vast majority of patients received some type of blood product during childhood cancer treatment, screening based on date of diagnosis/treatment is recommended unless there is absolute certainty that the patient did notreceive any blood or blood products.
Relevant exposures include packed red cells, whole blood, granulocytes, platelets, fresh frozen plasma, cryoprecipitate, IVIG, VZIG, factor concentrates, and allogeneic marrow, cord blood, or stem cells.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Health behaviors: History of IV drug use, unprotected sex, multiple partners, high-risk sexual behavior, sexually transmitted infections, tattoos, body piercing

References
Zou S, Stramer SL, Dodd RY: Donor testing and risk: current prevalence, incidence, and residual risk of transfusion-transmissible agents in US allogeneic donations. Transfus Med Rev 26:119-28, 2012

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CHEMOTHERAPY
Sec #
11

w

Therapeutic
Exposure
Any Chemotherapy

ANY CHEMOTHERAPY
Potential
Late Effects

Dental abnormalities
Tooth/Root agenesis
Root thinning/shortening
Enamel dysplasia
Microdontia
Ectopic molar eruption
Dental caries

Health Counseling/
Further Considerations

Periodic Evaluation
PHYSICAL
Oral exam
YearlySCREENING
Dental exam and cleaning
Every 6 months

HEALTH LINKS
Dental Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Regular dental care including fluoride applications.
Baseline panorex prior to dental procedures to evaluate root development.
SYSTEM = Dental
SCORE
Ectopic Molar Eruption = 2A
All Else = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Any patient who had not developed permanent dentition at time of cancer therapy, younger age at treatment, especially age <5 years- Cancer/Treatment factors: Any radiation treatment involving the oral cavity or salivary glands

References
Busenhart DM, Erb J, Rigakos G, et al: Adverse effects of chemotherapy on the teeth and surrounding tissues of children with cancer: a systematic review with meta-analysis. Oral Oncol 83:64-72, 2018
Effinger KE, Migliorati CA, Hudson MM, et al: Oral and dental late effects in survivors of childhood cancer: a Children’s Oncology Group report. Support Care Cancer 22:2009-19, 2014
Goho C: Chemoradiation therapy: effect on dental development. Pediatr Dent 15:6-12, 1993
Hsieh SG, Hibbert S, Shaw P, et al: Association of cyclophosphamide use with dental developmental defects and salivary gland dysfunction in recipients of childhood antineoplastic therapy. Cancer 117:2219-27, 2011
Immonen E, Nikkilä A, Peltomäki T, et al: Late adverse effects of childhood acute lymphoblastic leukemia treatment on developing dentition. Pediatr Blood Cancer 68(9), 2021
Kaste SC, Goodman P, Leisenring W, et al: Impact of radiation and chemotherapy on risk of dental abnormalities: a report from the Childhood Cancer Survivor Study. Cancer 115:5817-27, 2009
Ko Y, Park K, Kim JY: Effect of anticancer therapy on ectopic eruption of permanent first molars. Pediatr Dent 35:530-3, 2013
Proc P, Szczepanska J, Skiba A, et al: Dental anomalies as late adverse effect among young children treated for cancer. Cancer Res Treat 48:658-67, 2016
Shum M, Mahoney E, Naysmith K, et al. Associations between childhood cancer treatment and tooth agenesis. N Z Med J 133(1523):41-54, 2020
Sonis AL, Tarbell N, Valachovic RW, et al: Dentofacial development in long-term survivors of acute lymphoblastic leukemia. A comparison of three treatment modalities. Cancer 66:2645-52, 1990

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CHEMOTHERAPYSec #12(male)

ALKYLATING AGENTS

Therapeutic
Exposure

Potential
Late Effects

Classical Alkylating AgentsBusulfan
Carmustine (BCNU)
Chlorambucil
Cyclophosphamide
Ifosfamide
Lomustine (CCNU)
Mechlorethamine
Melphalan
Procarbazine
Thiotepa
Heavy Metals
Carboplatin
Cisplatin
Non-Classical Alkylators
Dacarbazine (DTIC)
Temozolomide

Testicular hormonal dysfunction
Testosterone deficiency/
insufficiency
Delayed/Arrested puberty

HISTORY
Onset and tempo of puberty
Sexual function (erections, nocturnal emissions,libido)Medication use
YearlyPHYSICAL
Tanner staging until sexually mature
Testicular volume by Prader orchidometer
YearlyMonitor growth until mature
YearlySCREENING
AM testosterone in high risk patients startingat 18 years

Commonly used alkylators can be converted to a cyclophosphamide equivalent dose by using: CED (mg/m2)=
1.0 (cumulative cyclophosphamide dose (mg/m2)) + 0.244 (cumulative ifosfamide dose (mg/m2)) +0.857 (cumulative procarbazine dose (mg/m2)) + 14.286 (cumulative chlorambucil dose (mg/m2)) +15 (cumulative BCNU dose (mg/m2)) + 16 (cumulative CCNU dose (mg/m2)) + 40 (cumulative melphalan dose (mg/m2)) +50 (cumulative thiotepa dose (mg/m2)) + 100 (cumulative nitrogen mustard dose (mg/m2)) +8.823 (cumulative busulfan dose (mg/m2))w

Health Counseling/
Further Considerations

Periodic Evaluation
HEALTH LINKS

Testicular and Reproductive Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Testosterone insufficiency or deficiency requiring hormone replacement after alkylating
agents only is rare.
Endocrine referral for the following:• No signs of puberty by age 14 years• Failure of pubertal progression• Adults with low AM testosterone levels
Periodic re-evaluation of testosterone in males with low normal testosterone as they age
or if they become symptomatic.
Bone density evaluation in androgen deficient patients.
Consider assessment of fertility status prior to initiation of testosterone replacement
therapy.
SYSTEM = Reproductive (Male)SCOREClassical Alkylating Agents = 1
Heavy Metals = 2A
Non-Classical Alkylators = 2A

Additional Information

Testicular volume is not a reliable indicator of pubertal onset/stage in boys treated with alkylating agents and/or direct testicular radiotherapy.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Testicular cancer, higher cumulative doses of alkylators (especially cyclophosphamide dose ≥20 gm/m2 or ifosfamide ≥60 gm/m2), combinations of alkylators, combination with MOPP, cyclophosphamide as conditioning for HCT, in combination with radiation (to abdomen/pelvis, testes [especially dose ≥20 Gy], brain/cranium [neuroendocrine axis], or TBI), and unilateral orchiectomy- Health behaviors: Tobacco/Marijuana use

References
Brignardello E, Felicetti F, Castiglione A, et al: Gonadal status in long-term male survivors of childhood cancer. J Cancer Res Clin Oncol 142:1127-32, 2016
Chemaitily W, Liu Q, van Iersel L, et al: Leydig cell function in male survivors of childhood cancer: a report from the St Jude Lifetime cohort study. J Clin Oncol 37:3018-31, 2019
Hamre H, Kiserud CE, Ruud E, et al: Gonadal function and parenthood 20 years after treatment for childhood lymphoma: a cross-sectional study. Pediatr Blood Cancer 59:271-7, 2012
Kenney LB, Antal Z, Ginsberg JP, et al: Improving male reproductive health after childhood, adolescent, and young adult cancer: progress and future directions for survivorship research. J Clin Oncol 36:2160-68, 2018
Kenney LB, Laufer MR, Grant FD, et al: High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer 91:613-21, 2001
Lopez R, Plat G, Bertrand Y, et al: Testosterone deficiency in men surviving childhood acute leukemia after treatment with hematopoietic stem cell transplantation or testicular radiation: an L.E.A. study. Bone Marrow Transplant 56(6):1422-1425, 2021
Mostafi-Moab S, Seidel K, Leisenring WM, et al: Endocrine abnormalities in aging survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. J Clin Oncol 34:3240-47, 2016
Practice Committee of American Society for Reproductive Medicine: Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril 98:294-301, 2012
Skinner R, Mulder RL, Kremer LC, et al: Recommendations for gonadotoxiity surveillance in male childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guidelines Harmonization Group in collaboration with the PanCareSurFup Consortium, Lancet Oncol 18:e75-90, 2017
Sprauten M, Brydoy M, Haugnes HS, et al: Longitudinal serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels in a population-based sample of long-term testicular cancer survivors. J Clin Oncol 32:571-8, 2014
Williams D, Crofton PM, Levitt G: Does ifosfamide affect gonadal function? Pediatr Blood Cancer 50:347-51, 2008

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CHEMOTHERAPYSec #13(male)

ALKYLATING AGENTS (CONT)

Therapeutic
Exposure

Potential
Late Effects

Classical Alkylating
AgentsBusulfan
Carmustine (BCNU)
Chlorambucil
Cyclophosphamide
Ifosfamide
Lomustine (CCNU)
Mechlorethamine
Melphalan
Procarbazine
Thiotepa
Heavy Metals
Carboplatin
Cisplatin
Non-Classical Alkylators
Dacarbazine (DTIC)
Temozolomide

Impaired spermatogenesis
Reduced fertility
Oligospermia
Azoospermia
Infertility

Periodic Evaluation
HISTORY
Onset and tempo of puberty
Sexual function (erections, nocturnal
emissions, libido)
Medication use
YearlyPHYSICAL
Tanner staging until sexually mature
Testicular volume by Prader orchidometer
YearlyCommonly used alkylators can be converted to a cyclophosphamide equivalent dose by using: CED (mg/m2)=
1.0 (cumulative cyclophosphamide dose (mg/m2)) + 0.244 (cumulative ifosfamide dose (mg/m2)) +0.857 (cumulative procarbazine dose (mg/m2)) + 14.286 (cumulative chlorambucil dose (mg/m2)) +15 (cumulative BCNU dose (mg/m2)) + 16 (cumulative CCNU dose (mg/m2)) + 40 (cumulative melphalan dose (mg/m2)) +50 (cumulative thiotepa dose (mg/m2)) + 100 (cumulative nitrogen mustard dose (mg/m2)) +8.823 (cumulative busulfan dose (mg/m2))w

Health Counseling/
Further Considerations
HEALTH LINKS
Testicular and Reproductive HealthRESOURCES
American Society for Reproductive Medicine: www.asrm.org
Alliance for Fertility Preservation: www.allianceforfertilitypreservation.org
COUNSELING
Need for contraception.
Fertility recovery can be seen in the early years after completion of therapy andoccasionally thereafter.
Review previous fertility preservation counseling/interventions.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
For sexually mature patients who desire information about potential future
fertility: semen analysis (optimal) and/or FSH and inhibin B (alternative if
unable or unwilling to provide semen sample).
Reproductive endocrinology/urology referral for infertility evaluation andconsultation regarding assisted reproductive technologies.
Alkylating agent doses that cause gonadal dysfunction show individual variation.
Germ cell function (spermatogenesis) is impaired at lower doses compared to
Leydig cell (testosterone production) function.
Prepubertal status at treatment does not protect from gonadal injury in males.
SYSTEM = Reproductive (Male)SCOREClassical Alkylating Agents = 1
Heavy Metals = 2A
Non-Classical Alkylators = 2A

Additional Information

Testicular volume is not a reliable indicator of pubertal onset/stage in boys treated with alkylating agents and/or direct testicular radiotherapy.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Medications (anabolic steroids, testosterone), occupational exposures (pesticides, heavy metals, solvents)- Cancer/Treatment factors: Testicular cancer, higher cumulative doses of alkylators (especially busulfan ≥600 mg/m2, cyclophosphamide ≥4 gm/m2, CED >4 gm/m2, ifosfamide ≥50 gm/m2), and cisplatin >488 mg/m2, combinations ofalkylators, MOPP ≥3 cycles, cyclophosphamide as conditioning for HCT, in combination with radiation to abdomen/pelvis, testes, brain/cranium (neuroendocrine axis), or TBI, genitourinary surgery- Pre-morbid/Co-morbid medical conditions: Obesity, ejaculatory dysfunction, history of sexually transmitted infections, cGVHD- Health behaviors: Tobacco/Marijuana use

References
Chow EJ, Stratton KL, Leisenring WM, et al: Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 17:567-76,
2016
da Cunha MF, Meistrich ML, Fuller LM, et al: Recovery of spermatogenesis after treatment for Hodgkin’s disease: limiting dose of MOPP chemotherapy. J Clin Oncol 2:571-7, 1984
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CHEMOTHERAPY

ALKYLATING AGENTS (CONT)

Section 13 References (cont)Eskenazi B, Wyrobek AJ, Sloter E, et al: The association of age and semen quality in healthy men. Hum Reprod 18:447-454, 2003
Green DM, Kawashima T, Stovall M, et al: Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 28:332-9, 2010
Green DM, Liu W, Kutteh WH, et al: Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study. Lancet Oncol 15:1215-23, 2014
Green DM, Zhu L, Zhang N, et al: Lack of specificity of plasma concentrations of inhibin B and follicle-stimulating hormone for identification of azoospermic survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study. J Clin
Oncol 31:1324-8, 2013
Kenney LB, Antal Z, Ginsberg JP, et al: Improving male reproductive health after childhood, adolescent, and young adult cancer: progress and future directions for survivorship research. J Clin Oncol 36:2160-68, 2018
Loren AW, Mangu PB, Beck LN, et al: Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 31:2500-10, 2013
Meistrich ML, Chawla SP, Da Cunha MF, et al: Recovery of sperm production after chemotherapy for osteosarcoma. Cancer 63:2115-23, 1989
Nudell DM, Monoski MM, Lipshultz LI: Common medications and drugs: how they affect male fertility. Urol Clin N Am 29:965-+, 2002
Practice Committee of American Society for Reproductive Medicine: Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril 98:294-301, 2012
Romerius P, Stahl O, Moell C, et al: High risk of azoospermia in men treated for childhood cancer. Int J Androl 34:69-76, 2011
Sprauten M, Brydoy M, Haugnes HS, et al: Longitudinal serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels in a population-based sample of long-term testicular cancer survivors. J Clin Oncol 32:571-8, 2014

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CHEMOTHERAPYSec #14(female)ALKYLATING AGENTS (CONT)

Therapeutic
Exposure

Potential
Late Effects

Classical Alkylating
AgentsBusulfan
Carmustine (BCNU)
Chlorambucil
Cyclophosphamide
Ifosfamide
Lomustine (CCNU)
Mechlorethamine
Melphalan
Procarbazine
Thiotepa
Heavy Metals
Carboplatin
Cisplatin
Non-Classical Alkylators
Dacarbazine (DTIC)
Temozolomide

Ovarian hormone deficiencies
Delayed puberty
Arrested pubertyPremature ovarian
insufficiency/Prematuremenopause

Periodic Evaluation
HISTORY
Onset and tempo of puberty
Menstrual history
Sexual function (vaginal dryness, libido)
Menopausal symptoms
Medication use
YearlyPHYSICAL
Tanner staging until sexually mature
YearlyMonitor growth until mature
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Ovarian and Reproductive Health
COUNSELING
Higher cumulative doses of alkylating agents with or without radiation may
increase risk. Dose can be estimated using CED dose calculation.
Adverse impact of ovarian hormone deficiencies on growth, bone mineralization,
cardiovascular disease and sexual dysfunction.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
FSH and estradiol and/or endocrine/gynecology referral for patients with:• No signs of puberty by age 13 years• Failure of pubertal progression• Abnormal menstrual patterns or menopausal symptoms• Ovarian hormone deficiency/insufficiency to weigh risks and benefits of hormonal replacement therapy
Bone density evaluation in patients with ovarian hormone deficiencies.

Commonly used alkylators can be converted to a cyclophosphamide equivalent dose by using: CED (mg/m2)=
1.0 (cumulative cyclophosphamide dose (mg/m2)) + 0.244 (cumulative ifosfamide dose (mg/m2)) +0.857 (cumulative procarbazine dose (mg/m2)) + 14.286 (cumulative chlorambucil dose (mg/m2)) +15 (cumulative BCNU dose (mg/m2)) + 16 (cumulative CCNU dose (mg/m2)) + 40 (cumulative melphalan dose (mg/m2)) +50 (cumulative thiotepa dose (mg/m2)) + 100 (cumulative nitrogen mustard dose (mg/m2)) +8.823 (cumulative busulfan dose (mg/m2))w

SYSTEM = Reproductive (Female)
SCORE
Classical Alkylating Agents = 1
Heavy Metals = 2B
Non-Classical Alkylators = 2A

Additional Information

Alkylating agent doses that cause gonadal dysfunction show individual variation. Females can typically maintain gonadal function at higher cumulative doses than males.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Older age at treatment- Cancer/Treatment factors: Higher cumulative doses of alkylators or combinations of alkylators, combination with radiation to abdomen/pelvis, lumbar or sacral spine (from ovarian scatter), or brain/cranium (neuroendocrineaxis), any alkylators combined with pelvic radiation or TBI- Health behaviors: Smoking

References
Afify Z, Shaw PJ, Clavano-Harding A, et al: Growth and endocrine function in children with acute myeloid leukaemia after bone marrow transplantation using busulfan/cyclophosphamide. Bone Marrow Transplant 25:1087-92, 2000
Armstrong GT, Whitton JA, Gajjar A, et al: Abnormal timing of menarche in survivors of central nervous system tumors: a report from the Childhood Cancer Survivor Study. Cancer 115:2562-70, 2009
Chemaitilly W, Li Z, Krasin MJ, et al: Premature ovarian insufficiency in childhood cancer survivors: a report from the St. Jude Lifetime Cohort. J Clin Endocrinol Metab 102(7):2242-50, 2017
Chemaitilly W, Mertens AC, Mitby P, et al: Acute ovarian failure in the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 91:1723-8, 2006
Levine JM, Whitton JA, Ginsberg JP, et al: Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 124(5):1044-52, 2018
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Section 14 References (cont)Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol 31:1239-47, 2013
Molinari S, Parissone F, Evasi V, et al: Serum anti-Mullerian hormone as a marker of ovarian reserve after cancer treatment and/or hematopoietic stem cell transplantation in childhood: proposal for a systematic approach to gonadal assessment.
Eur J Endocrinol 185:717-728, 2021
Overbeek A, van den Berg M, van Leeuwen F, et al: Chemotherapy-related late adverse effects on ovarian function in female survivors of childhood and young adult cancer: a systematic review. Cancer Treatment Reviews 53:10-24, 2017
Sklar CA, Mertens AC, Mitby P, et al: Premature menopause in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 98:890-6, 2006
Wallace WH, Shalet SM, Crowne EC, et al: Gonadal dysfunction due to cis-platinum. Med Pediatr Oncol 17:409-13, 1989

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Sec #15(female)Therapeutic
ExposureClassical Alkylating AgentsBusulfan
Carmustine (BCNU)
Chlorambucil
Cyclophosphamide
Ifosfamide
Lomustine (CCNU)
Mechlorethamine
Melphalan
Procarbazine
Thiotepa
Heavy Metals
Carboplatin
Cisplatin
Non-Classical Alkylators
Dacarbazine (DTIC)
Temozolomide

ALKYLATING AGENTS (CONT)
Potential
Late Effects

Diminished Ovarian Reserve(DOR)
Infertility

HISTORY
Menstrual and pregnancy history
Hormonal therapy
YearlyPHYSICAL
Tanner staging until sexually mature
YearlyCommonly used alkylators can be converted to a cyclophosphamide equivalent dose by using: CED (mg/m2)=
1.0 (cumulative cyclophosphamide dose (mg/m2)) + 0.244 (cumulative ifosfamide dose (mg/m2)) +0.857 (cumulative procarbazine dose (mg/m2)) + 14.286 (cumulative chlorambucil dose (mg/m2)) +15 (cumulative BCNU dose (mg/m2)) + 16 (cumulative CCNU dose (mg/m2)) + 40 (cumulative melphalan dose (mg/m2)) +50 (cumulative thiotepa dose (mg/m2)) + 100 (cumulative nitrogen mustard dose (mg/m2)) +8.823 (cumulative busulfan dose (mg/m2))w

Health Counseling/
Further Considerations

Periodic Evaluation
HEALTH LINKS

Ovarian and Reproductive HealthRESOURCES
American Society for Reproductive Medicine: www.asrm.org
Alliance for Fertility Preservation: www.allianceforfertilitypreservation.org
Livestrong Foundation: www.livestrong.org/what-we-do/program/fertility
Oncofertility Consortium: https://oncofertility.msu.edu
COUNSELING
Need for contraception.
Review previous fertility preservation counseling/interventions.
Fertility recovery can be seen in the early years after the completion of therapy andoccasionally thereafter.
Potential for shorter period of fertility in family planning. Those with DOR should consider
discussing reproductive health options with a reproductive endocrinologist or fertility
specialist.
Higher cumulative doses of alkylating agents with or without radiation may increase risk.
Dose can be estimated using CED dose calculation.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
FSH and estradiol for patients with menstrual cycle dysfunction suggestive of premature
ovarian insufficiency or those who desire information about potential for future fertility.
AMH to assess for diminished ovarian reserve.
Reproductive endocrinology referral for antral follicle count, ovarian reserve evaluationand consultation regarding assisted reproductive technologies in at-risk patients who
desire information about potential fertility and interventions to preserve future fertility.
Alkylating agent doses that cause gonadal dysfunction show individual variation. Females
can typically maintain gonadal function at higher cumulative doses than males.
SYSTEM = Reproductive (Female)
SCORE
Classical Alkylating Agents = 1
Heavy Metals = 2B
Non-Classical Alkylators = 2A

Additional Information

AMH may be low in the presence of normal FSH. AMH should be interpreted relative to age-specific reference ranges. FSH is lowered and AMH may be lowered by concurrent hormonal contraceptive use.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Older age at treatment- Cancer/Treatment factors: Higher cumulative doses of alkylators or combinations of alkylators, combination with radiation to abdomen/pelvis, lumbar or sacral spine (from ovarian scatter), or brain, cranium (neuroendocrineaxis), any alkylators combined with pelvic radiation or TBI- Health behaviors: Smoking
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Section 15 References (cont)Chemaitilly W, Li Z, Krasin MJ, et al. Premature ovarian insufficiency in childhood cancer survivors: a report from the St. Jude Lifetime Cohort. J Clin Endocrinol Metab 102(7):2242-50, 2017
Gracia CR, Sammel MD, Freeman E, et al: Impact of cancer therapies on ovarian reserve. Fertil Steril 97:134-40 e1, 2012
Green DM, Kawashima T, Stovall M, et al: Fertility of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 27:2677-2685, 2009
Hamre H, Kiserud CE, Ruud E, et al: Gonadal function and parenthood 20 years after treatment for childhood lymphoma: a cross-sectional study. Pediatr Blood Cancer 59:271-7, 2012
Krawczuk-Rybak M, Leszczynska E, Poznanska M, et al: Anti-Mullerian hormone as a sensitive marker of ovarian function in young cancer survivors. Int J Endocrinol 2013:125080, 2013
Levine JM, Kelvin JF, Quinn GP, et al: Infertility in reproductive-age female cancer survivors. Cancer 121:1532-9, 2015
Levine JM, Whitton JA, Ginsberg JP, et al. Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 124(5):1044-52, 2018
Lunsford AJ, Whelan K, McCormick K, et al: Anti-Mullerian hormone as a measure of reproductive function in female childhood cancer survivors. Fertil Steril 101:227-31, 2014
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Nyström A, Mörse H, Nordlöf H, et al. Anti-müllerian hormone compared with other ovarian markers after childhood cancer treatment. Acta Oncol 58(2):218-24, 2019
Overbeek A, van den Berg M, van Leeuwen F, et al. Chemotherapy-related late adverse effects on ovarian function in female survivors of childhood and young adult cancer: a systematic review. Cancer Treatment Reviews 53:10-24,
2017
Thomas-Teinturier C, Allodji RS, Svetlova E, et al: Ovarian reserve after treatment with alkylating agents during childhood. Hum Reprod 30:1437-46, 2015

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CHEMOTHERAPY
Sec #
16

w

Therapeutic
ExposureClassical Alkylating
AgentsBusulfan
Carmustine (BCNU)
Chlorambucil
Cyclophosphamide
Ifosfamide
Lomustine (CCNU)
Mechlorethamine
Melphalan
Procarbazine
Thiotepa
Heavy Metals
Carboplatin
Cisplatin
Non-Classical Alkylators
Dacarbazine (DTIC)
Temozolomide

ALKYLATING AGENTS (CONT)
Potential
Late Effects

Acute myeloid leukemia(AML)
Myelodysplasia (MDS)

Periodic Evaluation
HISTORY
Fatigue
Bleeding
Easy bruising
Yearly, up to 10 years after exposure to agent
PHYSICAL
Dermatologic exam (pallor, petechiae,
purpura)Yearly, up to 10 years after exposure to agent

Health Counseling/
Further Considerations
HEALTH LINKS
Reducing the Risk of Subsequent Cancers
COUNSELING
Promptly seek medical attention for fatigue, pallor, petechiae or bone pain.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
CBC and bone marrow exam as clinically indicated.
SYSTEM = SMN
SCOREClassical Alkylating Agents = 1
Heavy Metals = 2A
Non-Classical Alkylators = 2A

Additional Information

There is negligible benefit to obtaining a screening CBC in the absence of clinical signs and symptoms for AML/MDS.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Less than 10 years since exposure to agent, higher cumulative alkylator dose or combination of alkylators, autologous HCT. Note melphalan and mechlorethamine are more potent leukemogens thancyclophosphamide.
- Pre-morbid/Co-morbid medical conditions: Evidence is conflicting that splenectomy modifies risk for AML/MDS

References
Allodji RS, Schwartz B, Veres C, et al: Risk of subsequent leukemia after a solid tumor in childhood: impact of bone marrow radiation therapy and chemotherapy. Int J Radiat Oncol Biol Phys 93:658-67, 2015
Bhatia S: Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol 40:666-75, 2013
Bhatia S, Krailo MD, Chen Z, et al: Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: a report from the Children’s Oncology Group. Blood 109:46-51, 2007
Eichenauer DA, Thielen I, Haverkamp H, et al: Therapy-related acute myeloid leukemia and myelodysplastic syndromes in patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood 123:1658-64, 2014
Greene MH, Harris EL, Gershenson DM, et al: Melphalan may be a more potent leukemogen than cyclophosphamide. Ann Intern Med 105:360-7, 1986
Hijiya N, Ness KK, Ribeiro RC, et al: Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues. Cancer 115:23-35, 2009
Koontz MZ, Horning SJ, Balise R, et al: Risk of therapy-related secondary leukemia in Hodgkin lymphoma: the Stanford University experience over three generations of clinical trials. J Clin Oncol 31:592-8, 2013
Landier W, Armenian SH, Lee J, et al: Yield of screening for long-term complications using the Children’s Oncology Group long-term follow-up guidelines. J Clin Oncol 30:4401-8, 2012
Nottage K, Lanctot J, Li Z, et al: Long-term risk for subsequent leukemia after treatment for childhood cancer: a report from the Childhood Cancer Survivor Study. Blood 117:6315-8, 2011
Rihani R, Bazzeh F, Faqih N, et al: Secondary hematopoietic malignancies in survivors of childhood cancer: an analysis of 111 cases from the Surveillance, Epidemiology, and End Result-9 registry. Cancer 116:4385-94, 2010

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Sec #
17

w

Therapeutic
ExposureClassical Alkylating
AgentsBusulfan
Carmustine (BCNU)
Lomustine (CCNU)

ALKYLATING AGENTS (CONT)
Potential
Late Effects

Pulmonary fibrosis

Periodic Evaluation
HISTORY
Cough
Wheezing
Shortness of breath
Dyspnea on exertion
YearlyPHYSICAL
Pulmonary exam
YearlySCREENING
PFTs (including DLCO and spirometry)
Baseline at entry into long-term follow-up,
repeat as clinically indicated in patients withabnormal results or progressive pulmonary
dysfunction

Health Counseling/
Further Considerations
HEALTH LINKS
Pulmonary HealthRESOURCES
www.smokefree.gov
COUNSELING
Tobacco avoidance/Smoking cessation/Environmental tobacco smoke.
Influenza and Pneumococcal vaccinations.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Repeat PFTs prior to general anesthesia.
Pulmonary consultation for patients with symptomatic pulmonary dysfunction.
Pulmonary consultation for survivors who desire to SCUBA dive (due to potential
undiagnosed pulmonary toxicities, and limited data to guide safe diving
recommendations for individuals treated with pulmonary toxic therapy).
SYSTEM = Pulmonary
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher cumulative doses, especially BCNU ≥600 mg/m2 and busulfan ≥500 mg (transplant doses), combination with bleomycin, combination with chest radiation or TBI- Pre-morbid/Co-morbid medical conditions: Atopic history- Health behaviors: Smoking, inhaled illicit drug use

References
Dietz AC, Chen Y, Yasui Y, et al: Risk and impact of pulmonary complications in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 122:3687-3696, 2016
Green DM, Zhu L, Wang M, et al: Pulmonary function after treatment for childhood cancer. A report from the St. Jude Lifetime Cohort Study (SJLIFE). Ann Am Thorac Soc 13:1575-85, 2016
Huang TT, Hudson MM, Stokes DC, et al: Pulmonary outcomes in survivors of childhood cancer: a systematic review. Chest 140:881-901, 2011
Lohani S, O’Driscoll BR, Woodcock AA: 25-year study of lung fibrosis following carmustine therapy for brain tumor in childhood. Chest 126:1007, 2004
Tetrault JM, Crothers K, Moore BA, et al: Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch Intern Med 167:221-8, 2007
van Hulst RA, Rietbroek RC, Gaastra MT, et al: To dive or not to dive with bleomycin: a practical algorithm. Aviat Space Environ Med 82:814-8, 2011
Wolff AJ, O’Donnell AE: Pulmonary effects of illicit drug use. Clin Chest Med 25:203-16, 2004

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18

w

Therapeutic
ExposureClassical Alkylating
AgentsBusulfan

ALKYLATING AGENTS (CONT)
Potential
Late Effects

Cataracts

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Visual changes (decreased acuity, halos,
diplopia)
YearlyPHYSICAL
Visual acuity
Funduscopic exam
YearlySCREENING
Evaluation by ophthalmologist or
optometrist
YearlyHEALTH LINKS
Cataracts
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Ophthalmology consultation as clinically indicated.
Refer patients with visual deficits to school liaison in community or cancer
center (psychologist, social worker, school counselor) to facilitate acquisition of
educational resources.
SYSTEM = Ocular
SCORE = 2B

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Combination with corticosteroids, combination with TBI, cranial, orbital, or eye radiation, longer interval since treatment

References
Horwitz M, Auquier P, Barlogis V, et al: Incidence and risk factors for cataract after haematopoietic stem cell transplantation for childhood leukaemia: an LEA study. Br J Haematol 168:518-25, 2015
Saglio F, Zecca M, Pagliara D, et al: Occurrence of long-term effects after hematopoietic stem cell transplantation in children affected by acute leukemia receiving either busulfan or total body irradiation: results of an AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) retrospective study. Bone Marrow Transplant 55,1918–1927, 2020Socie G, Salooja N, Cohen A, et al: Nonmalignant late effects after allogeneic stem cell transplantation. Blood 101:3373-85, 2003

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Sec #
19

Therapeutic
ExposureClassical Alkylating
AgentsCyclophosphamide
Ifosfamide

ALKYLATING AGENTS (CONT)
Potential
Late Effects

Urinary tract toxicity
Hemorrhagic cystitis
Bladder fibrosis
Dysfunctional voiding
Vesicoureteral reflux
Hydronephrosis

Periodic Evaluation
HISTORY
Hematuria
Urinary urgency/frequency
Urinary incontinence/retention
Dysuria
Nocturia
Abnormal urinary stream
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Bladder Health
COUNSELING
Promptly report dysuria or gross hematuria.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Urinalysis, urine culture, spot urine calcium/creatinine ratio for patients withpositive history.
Ultrasound of kidneys and bladder for patients with microscopic hematuria(defined as >5 RBC/HPF on at least 2 occasions).
Nephrology or urology referral for patients with culture-negative microscopic
hematuria AND abnormal ultrasound and/or abnormal calcium/creatinine ratio.
Urology referral for patients with culture-negative macroscopic hematuria,
incontinence, or dysfunctional voiding.
SYSTEM = Urinary
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher cumulative doses (decreased incidence with Mesna), especially cyclophosphamide dose ≥3 gm/m2, combination with pelvic radiation, especially pelvic radiation dose ≥30 Gy- Health behaviors: Alcohol use, smoking

References
Dieffenbach BV, Liu Q, Murphy AJ, et al: Late-onset kidney failure in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Eur J Cancer 155:216-226, 2021
Green DM, Wang M, Krasin M, et al: Kidney function after treatment for childhood cancer: a report from the St. Jude Lifetime Cohort Study. J Am Soc Nephrol 32(4):983-993, 2021
Hale GA, Marina NM, Jones-Wallace D, et al: Late effects of treatment for germ cell tumors during childhood and adolescence. J Pediatr Hematol Oncol 21:115-22, 1999
Heyn R, Raney RB, Jr., Hays DM, et al: Late effects of therapy in patients with paratesticular rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee. J Clin Oncol 10:614-23, 1992
Jerkins GR, Noe HN, Hill D: Treatment of complications of cyclophosphamide cystitis. J Urol 139:923-5, 1988
Kooijmans EC, Bökenkamp A, Tjahjadi NS, et al: Early and late adverse renal effects after potentially nephrotoxic treatment for childhood cancer. Cochrane Database Syst Rev 11;3(3), 2019
Lima MV, Ferreira FV, Macedo FY, et al: Histological changes in bladders of patients submitted to ifosfamide chemotherapy even with mesna prophylaxis. Cancer Chemother Pharmacol 59:643-50, 2007
Stillwell TJ, Benson RC, Jr.: Cyclophosphamide-induced hemorrhagic cystitis. A review of 100 patients. Cancer 61:451-7, 1988
Stillwell TJ, Benson RC, Jr., Burgert EO, Jr.: Cyclophosphamide-induced hemorrhagic cystitis in Ewing’s sarcoma. J Clin Oncol 6:76-82, 1988

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Sec #
20

Therapeutic
ExposureClassical Alkylating
AgentsCyclophosphamide

ALKYLATING AGENTS (CONT)
Potential
Late Effects

Bladder malignancy

Periodic Evaluation
HISTORY
Hematuria
Urinary urgency/frequency
Urinary incontinence/retention
Dysuria
Nocturia
Abnormal urinary stream
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Bladder Health
COUNSELING
Promptly seek medical attention for dysuria or gross hematuria.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Urinalysis, urine culture, spot urine calcium/creatinine ratio for patients withpositive history.
Ultrasound of kidneys and bladder for patients with microscopic hematuria(defined as >5 RBC/HPF on at least 2 occasions).
Nephrology or urology referral for patients with culture-negative microscopic
hematuria AND abnormal ultrasound.
Urology referral for patients with culture-negative macroscopic hematuria.
SYSTEM = SMNSCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Combination with pelvic radiation- Health behaviors: Alcohol use, smoking

References
Chou R, Dana T: Screening adults for bladder cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 153:461-8, 2010
Chou WH, McGregor B, Schmidt A, et al: Cyclophosphamide-associated bladder cancers and considerations for survivorship care: A systematic review. Urol Oncol 39(10):678-685, 2021
Kersun LS, Wimmer RS, Hoot AC, et al: Secondary malignant neoplasms of the bladder after cyclophosphamide treatment for childhood acute lymphocytic leukemia. Pediatr Blood Cancer 42:289-91, 2004
Pedersen-Bjergaard J, Ersboll J, Hansen VL, et al: Carcinoma of the urinary bladder after treatment with cyclophosphamide for non-Hodgkin’s lymphoma. N Engl J Med 318:1028-32, 1988
Ritchey M, Ferrer F, Shearer P, et al: Late effects on the urinary bladder in patients treated for cancer in childhood: a report from the Children’s Oncology Group. Pediatr Blood Cancer 52:439-46, 2009
Travis LB, Curtis RE, Glimelius B, et al: Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin’s lymphoma. J Natl Cancer Inst 87:524-30, 1995

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Sec #
21

Therapeutic
ExposureClassical Alkylating
AgentsIfosfamide

ALKYLATING AGENTS (CONT)
Potential
Late Effects

Renal toxicity
Glomerular injury
Renal insufficiency
Hypertension
Tubular injury (renal tubularacidosis, Fanconi syndrome,
hypophosphatemic rickets)

Periodic Evaluation
PHYSICAL
Blood pressure
YearlySCREENING
BUN
Creatinine
Na, K, Cl, CO2, Ca, Mg, PO4
Baseline at entry into long-term follow-up,
repeat as clinically indicatedHealth Counseling/
Further Considerations
HEALTH LINKS
Kidney Health
Cardiovascular Risk Factors
COUNSELINGIn patients with salt-wasting tubular dysfunction, educate that low magnesium
levels potentiate coronary atherosclerosis.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTIONElectrolyte supplements for patients with persistent electrolyte wasting.
Nephrology consultation for patients with hypertension or progressive renal
insufficiency.
SYSTEM = Urinary
SCORE = 1w

Additional Information

Ifosfamide-related renal toxicity typically occurs during the acute treatment phase and improves or progresses over time.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, especially age <4 years- Cancer/Treatment factors: Tumor infiltration of kidney(s), nephrectomy, higher cumulative dose, especially ifosfamide dose ≥60 grams/m2, combination with other nephrotoxic agents (e.g., cisplatin, carboplatin, aminoglycosides, amphotericin, immunosuppressants, methotrexate, radiation impacting the kidney), renal radiation dose ≥15 Gy- Pre-morbid/Co-morbid medical conditions: Pre-existing renal impairment, congenital absence of kidney

References
Arndt C, Morgenstern B, Hawkins D, et al: Renal function following combination chemotherapy with ifosfamide and cisplatin in patients with osteogenic sarcoma. Med Pediatr Oncol 32:93-6, 1999
Ceremuzynski L, Gebalska J, Wolk R, et al: Hypomagnesemia in heart failure with ventricular arrhythmias. Beneficial effects of magnesium supplementation. J Intern Med 247:78-86, 2000
Dekkers IA, Blijdorp K, Cransberg K, et al: Long-term nephrotoxicity in adult survivors of childhood cancer. Clin J Am Soc Nephrol 8:922-9, 2013
Ho PT, Zimmerman K, Wexler LH, et al: A prospective evaluation of ifosfamide-related nephrotoxicity in children and young adults. Cancer 76:2557-64, 1995
Langer T, Stohr W, Bielack S, et al: Late effects surveillance system for sarcoma patients. Pediatr Blood Cancer 42:373-9, 2004
Loebstein R, Atanackovic G, Bishai R, et al: Risk factors for long-term outcome of ifosfamide-induced nephrotoxicity in children. J Clin Pharmacol 39:454-61, 1999
Skinner R, Cotterill SJ, Stevens MC: Risk factors for nephrotoxicity after ifosfamide treatment in children: a UKCCSG Late Effects Group study. United Kingdom Children’s Cancer Study Group. Br J Cancer 82:1636-45, 2000
Skinner R, Sharkey IM, Pearson AD, et al: Ifosfamide, mesna, and nephrotoxicity in children. J Clin Oncol 11:173-90, 1993
Stohr W, Paulides M, Bielack S, et al: Ifosfamide-induced nephrotoxicity in 593 sarcoma patients: a report from the Late Effects Surveillance System. Pediatr Blood Cancer 48:447-52, 2007

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Sec #
22

Therapeutic
Exposure
Heavy Metals
Carboplatin (myeloablative
doses)
Cisplatin

HEAVY METALS
Potential
Late Effects

Ototoxicity
Sensorineural hearing loss
Tinnitus
Vertigo

Periodic Evaluation

Health Counseling/
Further Considerations

HISTORY
Hearing difficulties (with/withoutbackground noise)
Tinnitus
VertigoYearlyPHYSICAL
Otoscopic exam
YearlySCREENING
Complete audiological evaluation byaudiologist
Yearly, for patients ages ≤5 years

HEALTH LINKS
Hearing Loss
School After Treatment
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Additional testing with high frequency audiometry at >8000 Hz is recommended
if equipment is available.
Audiology consultation for any survivor who has symptoms suggestive of
hearing loss, tinnitus, or abnormal pure tone audiometry results showing a lossof more than 15 dB absolute threshold level (1000-8000 Hz).
Ongoing follow-up with audiology for patients with hearing loss.
Otolaryngology consultation in patients with chronic infection, cerumen
impaction, or other anatomical problems exacerbating or contributing tohearing loss.
Speech and language therapy for patients with hearing loss.
Pure tone audiometry testing at 1000-8000 Refer patients with auditory deficits to school liaison in community or cancer
center (psychologist, social worker, school counselor) to facilitate acquisition ofHz
educational resources.
Every 2 years, for patients ages 6-12 years,
Specialized
evaluation for specific needs and/or preferential classroom seating,then every 5 years beginning at age 13 years
FM amplification system, and other educational assistance as indicated.
SYSTEM = Auditory
SCORE = 1w

Additional Information

Myeloablative doses of carboplatin are given as conditioning for HCT and are typically ≥1500 mg/m2.
A “complete audiological evaluation” includes pure tone air and bone conduction, speech audiometry, and tympanometry for both ears.
Frequency-specific auditory brainstem response can be performed if the above is inconclusive.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Age <4 years at treatment- Cancer/Treatment factors: CNS neoplasm, cumulative cisplatin dose ≥360 mg/m2, high dose cisplatin (i.e., 40 mg/m2 per day x 5 days per course), carboplatin conditioning for HCT, combination with cranial/ear radiation or
ototoxic drugs (e.g., aminoglycosides, loop diuretics), cisplatin administered AFTER cranial/ear radiation, combination with radiation involving ear ≥30 Gy- Pre-morbid/Co-morbid medical conditions: Chronic otitis, cerumen impaction, renal dysfunction, cerebrospinal fluid shunt

References
Bass JK, Knight KR, Yock TI, et al: Evaluation and management of hearing loss in survivors of childhood and adolescent cancers: a report from the Children’s Oncology Group. Pediatr Blood Cancer 63:1152-62, 2016
Bertolini P, Lassalle M, Mercier G, et al: Platinum compound-related ototoxicity in children: long-term follow-up reveals continuous worsening of hearing loss. J Pediatr Hematol Oncol 26:649-55, 2004
Clemens E, de Vries AC, Pluijm SF, et al: Determinants of ototoxicity in 451 platinum-treated Dutch survivors of childhood cancer: A DCOG late-effects study. Eur J Cancer 69:77-85, 2016
Clemens E, van den Heuvel-Eibrink MM, Mulder RL, et al: Recommendations for ototoxicity surveillance for childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer
Guideline Harmonization Group in collaboration with the PanCare Consortium. The Lancet Onc 20(1):e29-e41, 2019
Gurney JG, Tersak JM, Ness KK, et al: Hearing loss, quality of life, and academic problems in long-term neuroblastoma survivors: a report from the Children’s Oncology Group. Pediatrics 120:e1229-36, 2007
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Section 22 References (cont)
Heitzer AM, Villagran AM, Raghubar K, et al: Effect of sensorineural hearing loss on neurocognitive and adaptive functioning in survivors of pediatric embryonal brain tumor. J Neuro-Onc 146(1):147-56, 2020
Knight KR, Chen L, Freyer D, et al: Group-wide, prospective study of ototoxicity assessment in children receiving cisplatin chemotherapy (ACCL05C1): a report from the Children’s Oncology Group. J Clin Oncol 35:440-445, 2017
Knight KR, Kraemer DF, Neuwelt EA: Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development. J Clin Oncol 23:8588-96, 2005
Knight KR, Kraemer DF, Winter C, et al: Early changes in auditory function as a result of platinum chemotherapy: use of extended high-frequency audiometry and evoked distortion product otoacoustic emissions. J Clin Oncol
25:1190-5, 2007
Kushner BH, Budnick A, Kramer K, et al: Ototoxicity from high-dose use of platinum compounds in patients with neuroblastoma. Cancer 107:417-22, 2006
Weiss A, Sommer G, Kasteler R, et al: Long-term auditory complications after childhood cancer: a report from the Swiss Childhood Cancer Survivor Study. Pediatr Blood Cancer 64(2):364-73, 2017
Weiss A, Sommer G, Schindera C, et al: Hearing loss and quality of life in survivors of paediatric CNS tumours and other cancers. Qual Life Res 28(2):515-521, 2019

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Therapeutic
Exposure
Heavy Metals
Carboplatin
Cisplatin

HEAVY METALS (CONT)
Potential
Late Effects

Peripheral sensory
neuropathy
Paresthesias
Dysesthesias

Periodic Evaluation
HISTORY
Paresthesias
Dysesthesias
Yearly, until 2 to 3 years after therapy, monitor
yearly if symptoms persist
PHYSICAL
Neurologic exam
Yearly, until 2 to 3 years after therapy, monitor
yearly if symptoms persist

Health Counseling/
Further Considerations
HEALTH LINKS
Peripheral Neuropathy
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Physical therapy referral for patients with symptomatic neuropathy.
Physical and occupational therapy assessment of hand function.
Treat with effective agent for neuropathic pain (e.g., gabapentin or amitriptyline).
SYSTEM = PNSSCORE = 2A

Additional Information

Acute toxicities most commonly occur and usually improve or resolve prior to patients entry to long-term follow-up.
Neuropathy can persist after treatment and is typically not late in onset.
Studies of adults treated during childhood support higher prevalence of deficits than previously appreciated.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Cumulative cisplatin dose ≥300 mg/m2, combination with vincristine, taxanes, gemcitabine

References
Ness KK, Jones KE, Smith WA, et al: Chemotherapy-related neuropathic symptoms and functional impairment in adult survivors of extracranial solid tumors of childhood: results from the St. Jude Lifetime Cohort Study. Arch Phys Med
Rehabil 94:1451-7, 2013

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Therapeutic
Exposure
Heavy Metals
Carboplatin
Cisplatin

HEAVY METALS (CONT)
Potential
Late Effects

Renal toxicity
Glomerular injury
Renal insufficiency
Hypertension
Tubular injury (renal tubularacidosis, Fanconi syndrome,
hypophosphatemic rickets)

Periodic Evaluation
PHYSICAL
Blood pressure
YearlySCREENING
BUN
Creatinine
Na, K, Cl, CO2, Ca, Mg, PO4
Baseline at entry into long-term follow-up,
repeat as clinically indicatedHealth Counseling/
Further Considerations
HEALTH LINKS
Kidney Health
Cardiovascular Risk Factors
COUNSELINGIn patients with salt-wasting tubular dysfunction, educate that low magnesium
levels potentiate coronary atherosclerosis.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTIONElectrolyte supplements for patients with persistent electrolyte wasting.
Nephrology consultation for patients with hypertension or progressive renal
insufficiency.
SYSTEM = Urinary
SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Nephrectomy, combination with other nephrotoxic agents (e.g., aminoglycosides, amphotericin, immunosuppressants, methotrexate, radiation impacting the kidney), cisplatin dose ≥200 mg/m2,
renal radiation dose ≥15 Gy- Pre-morbid/Co-morbid medical conditions: Diabetes mellitus, hypertension, congenital absence of kidney

References
Arndt C, Morgenstern B, Hawkins D, et al: Renal function following combination chemotherapy with ifosfamide and cisplatin in patients with osteogenic sarcoma. Med Pediatr Oncol 32:93-6, 1999
Bianchetti MG, Kanaka C, Ridolfi-Luthy A, et al: Persisting renotubular sequelae after cisplatin in children and adolescents. Am J Nephrol 11:127-30, 1991
Ceremuzynski L, Gebalska J, Wolk R, et al: Hypomagnesemia in heart failure with ventricular arrhythmias. Beneficial effects of magnesium supplementation. J Intern Med 247:78-86, 2000
Hutchison FN, Perez EA, Gandara DR, et al: Renal salt wasting in patients treated with cisplatin. Ann Intern Med 108:21-5, 1988
Jimenez-Triana CA, Castelan-Martinez OD, Rivas-Ruiz R, et al: Cisplatin nephrotoxicity and longitudinal growth in children with solid tumors: a retrospective cohort study. Medicine (Baltimore) 94:e1413, 2015
Liao F, Folsom AR, Brancati FL: Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 136:480-90, 1998
Stohr W, Paulides M, Bielack S, et al: Nephrotoxicity of cisplatin and carboplatin in sarcoma patients: a report from the late effects surveillance system. Pediatr Blood Cancer 48:140-7, 2007von der Weid NX, Erni BM, Mamie C, et al: Cisplatin therapy in childhood: renal follow up 3 years or more after treatment. Swiss Pediatric Oncology Group. Nephrol Dial Transplant 14:1441-4, 1999

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ANTIMETABOLITESTherapeutic
Exposure

Potential
Late Effects

Antimetabolites
Cytarabine (high dose IV)

Neurocognitive deficits
Functional deficits in:• Executive function (planningand organization)• Sustained attention• Memory (particularly visual,sequencing, temporal
memory)• Processing speed• Visual-motor integration• Fine motor dexterity
Learning deficits in math andreading (particularly reading
comprehension)
Diminished IQ
Behavioral change

Periodic Evaluation
HISTORY
Educational and/or vocational progress
YearlySCREENING
Referral for formal neuropsychologicalevaluation
Baseline at entry into long-term follow-up,
then periodically as clinically indicatedfor patients with evidence of impaired
educational or vocational progress

Health Counseling/
Further Considerations
HEALTH LINKS
School After Treatment
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Referral to school liaison in community or cancer center (psychologist, social
worker, school counselor) to facilitate acquisition of educational resources and/or social skills training.
Psychotropic medication (e.g., stimulants) or evidence-based rehabilitation
training. Caution—lower starting dose and assessment of increased sensitivity
when initiating therapy is recommended.
Referral to community services for vocational rehabilitation or for services fordevelopmentally disabled.
SYSTEM = CNSSCORE = 2A

Additional Information

Formal neuropsychological evaluation includes tests of processing speed, computer-based attention, visual motor integration, memory, comprehension of verbal instructions, verbal fluency, executive function and planning.
Neurocognitive deficits in survivors of leukemia and lymphoma are more frequently related to information processing (e.g., slow processing speed, attention problems). Extent of deficit depends on age at treatment, intensity of treatment, and time since treatment. New and progressive deficits may emerge over time.
Acute toxicity predominates if cytarabine is administered systemically as a single agent. Cytarabine may contribute to late neurotoxicity if combined with high dose or intrathecal methotrexate and/or cranial radiation.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, especially age <3 years, female sex, family history of learning or attention problems- Cancer/Treatment factors: CNS leukemia/lymphoma, relapsed leukemia/lymphoma treated with CNS-directed therapy, longer elapsed time since therapy, combination with corticosteroids, methotrexate (IT, IO, high dose IV),
radiation dose ≥24 Gy, TBI, especially single fraction TBI (10 Gy), cranial radiation- Pre-morbid/Co-morbid medical conditions: Pre-morbid learning or attention problems

References
Ehrhardt MJ, Mulrooney DA, Li C, et al: Neurocognitive, psychosocial, and quality-of-life outcomes in adult survivors of childhood non-Hodgkin lymphoma. Cancer 124(2):417-25, 2018
Hardy KK, Embry L, Kairalla JA, et al: Neurocognitive functioning of children treated for high-risk b-acute lymphoblastic leukemia randomly assigned to different methotrexate and corticosteroid treatment strategies: a report from thechildren’s oncology group. J Clin Oncol 35(23):2700-7 2017
Kadan-Lottick NS, Zeltzer LK, Liu Q, et al: Neurocognitive functioning in adult survivors of childhood non-central nervous system cancers. J Natl Cancer Inst 102:881-93, 2010

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ANTIMETABOLITES (CONT)

Therapeutic
Exposure

Potential
Late Effects

Antimetabolites
Cytarabine (low dose IV)
Cytarabine IO
Cytarabine IT
Cytarabine SQ

No known late effects

Periodic Evaluation

Health Counseling/
Further Considerations
SYSTEM = No Known Late Effects
SCORE = 1

Additional Information

Acute toxicities predominate, from which the majority of patients recover without sequelae.

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ANTIMETABOLITES (CONT)

Therapeutic
Exposure

Potential
Late Effects

Antimetabolites
Mercaptopurine (6MP)
Thioguanine (6TG)

Hepatic dysfunction
Sinusoidal obstruction
syndrome (SOS)

Periodic Evaluation
PHYSICAL
Scleral icterus
Jaundice
Ascites
Hepatomegaly
Splenomegaly
YearlySCREENING
ALT
AST
Bilirubin
Baseline at entry into long-term follow-up,
repeat as clinically indicated.

Health Counseling/
Further Considerations
HEALTH LINKS
Liver Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Platelet count for evaluation of hypersplenism and prothrombin time for
evaluation of hepatic synthetic function in patients with abnormal liver
screening tests.
Screen for viral hepatitis in patients with persistently abnormal liver function or
any patient transfused prior to 1993.
Gastroenterology/Hepatology consultation in patients with persistent liver
dysfunction.
Hepatitis A and B immunization in at-risk patients lacking immunity.
SYSTEM = GI/Hepatic
SCORE = 2A

Additional Information

Acute toxicities predominate from which the majority of patients recover without sequelae.
Delayed hepatic dysfunction may occur after a history of acute SOS, presenting as portal hypertension with liver biopsy indicating nodular regenerative hyperplasia, fibrosis, or siderosis.
Patients treated on CCG-1952, Regimens B1 and B2, received 6TG in place of 6MP during maintenance therapy.
Acute hepatotoxicity (manifesting as SOS) occurred in about 25% of patients.
Portal hypertension was identified as a late complication of 6TG in a small subset of patients (see Broxson et al., 2005).
Outcomes are detailed in Stork et al., 2010.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Pre-morbid/Co-morbid medical conditions: Viral hepatitis (especially chronic viral hepatitis), previous SOS, siderosis

References
Bardi E, Mulder RL, van Dalen EC, et al. Late hepatic toxicity surveillance for survivors of childhood, adolescent and young adult cancer: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Cancer Treat Rev 100:102296, 2021
Broxson EH, Dole M, Wong R, et al: Portal hypertension develops in a subset of children with standard risk acute lymphoblastic leukemia treated with oral 6-thioguanine during maintenance therapy. Pediatr Blood Cancer 44:226-31,
2005
Castellino S, Muir A, Shah A, et al: Hepato-biliary late effects in survivors of childhood and adolescent cancer: a report from the Children’s Oncology Group. Pediatr Blood Cancer 54:663-9, 2010
Green DM, Wang M, Krasin MJ, et al. Serum alanine aminotransferase elevations in survivors of childhood cancer: a report from the St. Jude Lifetime Cohort Study. Hepatol 69(1):94-106, 2019
Piel B, Vaidya S, Lancaster D, et al: Chronic hepatotoxicity following 6-thioguanine therapy for childhood acute lymphoblastic leukaemia. Br J Haematol 125:410-1; author reply 412, 2004
Rawat D, Gillett PM, Devadason D, et al: Long-term follow-up of children with 6-thioguanine-related chronic hepatoxicity following treatment for acute lymphoblastic leukaemia. J Pediatr Gastroenterol Nutr 53:478-9, 2011
Stork LC, Matloub Y, Broxson E, et al: Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children’s Oncology Group CCG-1952
clinical trial. Blood 115:2740-8, 2010

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Therapeutic
Exposure
Antimetabolites
Methotrexate (high dose IV)
Methotrexate (low dose IV)
Methotrexate IM
Methotrexate POw

ANTIMETABOLITES (CONT)
Potential
Late Effects

Periodic Evaluation

No known bone mineraldensity (BMD) late effects

Health Counseling/
Further Considerations
SYSTEM = No Known BMD Late Effects
SCORE = 2B

References

Siegel DA, Claridy M, Mertens A, et al: Risk factors and surveillance for reduced bone mineral density in pediatric cancer survivors. Pediatr Blood Cancer 64(9), 2017
van Atteveld JE, Mulder RL, van den Heuvel-Eibrink MM, et al. Bone mineral density surveillance for childhood, adolescent, and young adult cancer survivors: evidence-based recommendations from the International Late Effects ofChildhood Cancer Guideline Harmonization Group. Lancet Diabetes Endocrinol 9(9):622-637, 2021
van Atteveld JE, Pluijm SMF, Ness KK, et al: Prediction of low and very low bone mineral density among adult survivors of childhood cancer. J Clin Oncol 37(25):2217-25, 2019

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Therapeutic
Exposure
Antimetabolites

ANTIMETABOLITES (CONT)
Potential
Late Effects

Periodic Evaluation

No known renal late effects

SYSTEM = No Known Renal Late Effects
SCORE = 2A

Methotrexate (high dose IV)
Methotrexate (low dose IV)
Methotrexate IM
Methotrexate POw

Health Counseling/
Further Considerations

Additional Information

Acute toxicities predominate, from which the majority of patients recover without sequelae.
Renal injury from other events (aminoglycoside exposure, tumor lysis) may make patients more vulnerable.

References
Dekkers IA, Blijdorp K, Cransberg K, et al: Long-term nephrotoxicity in adult survivors of childhood cancer. Clin J Am Soc Nephrol 8:922-9, 2013
Mulder RL, Knijnenburg SL, Geskus RB, et al: Glomerular function time trends in long-term survivors of childhood cancer: a longitudinal study. Cancer Epidemiol Biomarkers Prev 22:1736-46, 2013
Yetgin S, Olgar S, Aras T, et al: Evaluation of kidney damage in patients with acute lymphoblastic leukemia in long-term follow-up: value of renal scan. Am J Hematol 77:132-9, 2004

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Therapeutic
Exposure
Antimetabolites

Potential
Late Effects
Hepatic dysfunction

Methotrexate (high dose IV)
Methotrexate (low dose IV)
Methotrexate IM
Methotrexate POw

ANTIMETABOLITES (CONT)Periodic Evaluation
PHYSICAL
Scleral icterus
Jaundice
Ascites
Hepatomegaly
Splenomegaly
YearlySCREENING
ALT
AST
Bilirubin
Baseline at entry into long-term follow-up,
repeat as clinically indicated.

Health Counseling/
Further Considerations
HEALTH LINKS
Liver Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Platelet count for evaluation of hypersplenism and prothrombin time for
evaluation of hepatic synthetic function in patients with abnormal liver
screening tests.
Screen for viral hepatitis in patients with persistently abnormal liver function or
any patient transfused prior to 1993.
Gastroenterology/hepatology consultation in patients with persistent liver
dysfunction.
Hepatitis A and B immunization in at-risk patients lacking immunity.
SYSTEM = GI/Hepatic
SCORE = 2A

Additional Information

Acute toxicities predominate from which the majority of patients recover without sequelae.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Abdominal radiation, treatment before 1970
- Pre-morbid/Co-morbid medical conditions: Viral hepatitis (especially chronic viral hepatitis)

References
Bardi E, Mulder RL, van Dalen EC, et al. Late hepatic toxicity surveillance for survivors of childhood, adolescent and young adult cancer: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Cancer Treat Rev 100:102296, 2021
Castellino S, Muir A, Shah A, et al: Hepato-biliary late effects in survivors of childhood and adolescent cancer: a report from the Children’s Oncology Group. Pediatr Blood Cancer 54:663-9, 2010
Dietz AC, Seidel K, Leisenring WM, et al: Solid organ transplantation after treatment for childhood cancer: a retrospective cohort analysis from the Childhood Cancer Survivor Study. Lancet Oncol 20(10):1420-1431, 2019
Green DM, Wang M, Krasin MJ, et al. Serum alanine aminotransferase elevations in survivors of childhood cancer: a report from the St. Jude Lifetime Cohort Study. Hepatol 69(1):94-106, 2019
McIntosh S, Davidson DL, O’Brien RT, et al: Methotrexate hepatotoxicity in children with leukemia. J Pediatr 90:1019-21, 1977

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Therapeutic
Exposure
Antimetabolites
Methotrexate (high dose IV)
Methotrexate IO
Methotrexate ITw

ANTIMETABOLITES (CONT)
Potential
Late Effects

Neurocognitive deficits
Functional deficits in:• Executive function (planningand organization)• Sustained attention• Memory (particularly visual,sequencing, temporal
memory)• Processing speed• Visual-motor integration• Fine motor dexterity
Learning deficits in math andreading (particularly reading
comprehension)
Diminished IQ
Behavioral change

Periodic Evaluation
HISTORY
Educational and/or vocational progress
YearlySCREENING
Referral for formal neuropsychologicalevaluation
Baseline at entry into long-term follow-up,
then periodically as clinically indicatedfor patients with evidence of impaired
educational or vocational progress

Health Counseling/
Further Considerations
HEALTH LINKS
School After Treatment
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Referral to school liaison in community or cancer center (psychologist, social
worker, school counselor) to facilitate acquisition of educational resources and/or social skills training.
Psychotropic medication (e.g., stimulants) or evidence-based rehabilitation
training. Caution—lower starting dose and assessment of increased sensitivity
when initiating therapy is recommended.
Referral to community for vocational rehabilitation or for services fordevelopmentally disabled.
SYSTEM = CNSSCORE = 1

Additional Information

Formal neuropsychological evaluation includes tests of processing speed, computer-based attention, visual motor integration, memory, comprehension of verbal instructions, verbal fluency, executive function and planning.
Neurocognitive deficits in survivors of leukemia and lymphoma are more frequently related to information processing (e.g., slow processing speed, attention problems). Extent of deficit depends on age at treatment, intensity of treatment, and time since treatment. New and progressive deficits may emerge over time.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, especially age <3 years, female sex, family history of learning or attention problems- Cancer/Treatment factors: CNS leukemia/lymphoma, relapsed leukemia/lymphoma treated with CNS-directed therapy, longer elapsed time since therapy, combination with corticosteroids, cytarabine (high dose IV), TBI, especially single fraction TBI (10 Gy), or CRT especially ≥24 Gy- Pre-morbid/Co-morbid medical conditions: Pre-morbid learning or attention problems

References
Cheung YT, Sabin ND, Reddick WE, et al: Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal
analysis. Lancet Haematol 3(10):e456-e66, 2016
Ehrhardt MJ, Mulrooney DA, Li C, et al: Neurocognitive, psychosocial, and quality-of-life outcomes in adult survivors of childhood non-Hodgkin lymphoma. Cancer 124(2):417-25, 2018
Hardy KK, Embry L, Kairalla JA, et al: Neurocognitive functioning of children treated for high-risk B-acute lymphoblastic leukemia randomly assigned to different methotrexate and corticosteroid treatment strategies: a report from the children’s
oncology group. J Clin Oncol 35(23):2700-7, 2017
Iuvone L, Mariotti P, Colosimo C, et al: Long-term cognitive outcome, brain computed tomography scan, and magnetic resonance imaging in children cured for acute lymphoblastic leukemia. Cancer 95:2562-70, 2002
Jacola LM, Edelstein K, Liu W, et al: Cognitive, behaviour, and academic functioning in adolescent and young adult survivors of childhood acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study. Lancet Psychiatry3(10):965-72, 2016
Jacola LM, Krull KR, Pui CH, et al: Longitudinal assessment of neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia treated on a contemporary chemotherapy protocol. J Clin Oncol 34:1239-47, 2016
Kadan-Lottick NS, Brouwers P, Breiger D, et al: A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia. Blood 114:1746-52, 2009
Krull KR, Cheung YT, Liu W, et al: Chemotherapy pharmacodynamics and neuroimaging and neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia. J Clin Oncol 34(22):2644-53, 2016
Riva D, Giorgi C, Nichelli F, et al: Intrathecal methotrexate affects cognitive function in children with medulloblastoma. Neurology 59:48-53, 2002
van der Plas E, Qiu W, Nieman BJ, et al: Sex-specific associations between chemotherapy, chronic conditions and neurocognitive impairment in ALL survivors: A report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 4;113(5):588-596,
2021
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Exposure
Antimetabolites
Methotrexate (high dose IV)
Methotrexate IO
Methotrexate ITw

ANTIMETABOLITES (CONT)
Potential
Late Effects

Clinical leukoencephalopathy
Spasticity
AtaxiaDysarthria
Dysphagia
Hemiparesis
Seizures

Periodic Evaluation
HISTORY
Cognitive, motor and/or sensory deficits
Seizures
Other neurologic symptoms
YearlyPHYSICAL
Neurologic exam
YearlyHealth Counseling/
Further Considerations
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Brain CT or Brain MRI with MRA as clinically indicated with preferred study
based on intracranial lesion to be evaluated:• Calcifications: CT• White matter: MRI with DTI• Microvascular injury: Gadolinium-enhanced MRI with DWI
Neurology consultation and follow-up as clinically indicated.
SYSTEM = CNSSCORE = 1

Additional Information

Clinical leukoencephalopathy may present with or without imaging abnormalities (e.g., leukoencephalopathy, cerebral lacunes, cerebral atrophy, dystrophic calcifications, mineralizing microangiopathy).
Transient white matter anomalies may follow radiotherapy and high dose chemotherapy for medulloblastoma/PNET, may mimic tumor recurrence, and signify risk of persistent neurologic sequelae.
Neuroimaging changes do not always correlate with degree of cognitive dysfunction.
Prospective studies are needed to define the dose/effect relationship of neurotoxic agents.
New deficits may emerge over time.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment- Cancer/Treatment factors: CNS leukemia/lymphoma, relapsed leukemia/lymphoma treated with CNS-directed therapy, combination with cytarabine (high dose IV), dexamethasone, CRT especially ≥24 Gy

References
Hertzberg H, Huk WJ, Ueberall MA, et al: CNS late effects after ALL therapy in childhood. Part I: Neuroradiological findings in long-term survivors of childhood ALL--an evaluation of the interferences between morphology andneuropsychological performance. The German Late Effects Working Group. Med Pediatr Oncol 28:387-400, 1997
Matsumoto K, Takahashi S, Sato A, et al: Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy--an MR analysis. Int J Radiat Oncol Biol Phys
32:913-8, 1995
Ness KK, Hudson MM, Pui CH, et al: Neuromuscular impairments in adult survivors of childhood acute lymphoblastic leukemia: associations with physical performance and chemotherapy doses. Cancer 118:828-38, 2012

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Therapeutic
Exposure

ANTHRACYCLINE ANTIBIOTICS
Potential
Late Effects

Anthracycline Antibiotics Acute myeloid leukemia
Daunorubicin
Doxorubicin
Epirubicin
Idarubicin
Mitoxantrone

Periodic Evaluation
HISTORY
Fatigue
Bleeding
Easy bruising
Yearly, up to 10 years after exposure to agent
PHYSICAL
Dermatologic exam (pallor, petechiae,
purpura)Yearly, up to 10 years after exposure to agent

Health Counseling/
Further Considerations
HEALTH LINKS
Reducing the Risk of Subsequent Cancers
COUNSELING
Promptly seek medical attention for fatigue, pallor, petechiae or bone pain.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
CBC and bone marrow exam as clinically indicated.
SYSTEM = SMNSCORE = 1

Additional Information

Although mitoxantrone technically belongs to the anthraquinone class of anti-tumor antibiotics, it is related to the anthracycline family.
There is negligible benefit to obtaining a screening CBC in the absence of clinical signs and symptoms of AML.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Less than 5 years since exposure to agent, autologous HCT- Pre-morbid/Co-morbid medical conditions: Evidence is conflicting that splenectomy modifies risk for AML

References
Bhatia S: Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol 40:666-75, 2013
Bhatia S, Krailo MD, Chen Z, et al: Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: a report from the Children’s Oncology Group. Blood 109:46-51, 2007
Eichenauer DA, Thielen I, Haverkamp H, et al: Therapy-related acute myeloid leukemia and myelodysplastic syndromes in patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood 123:1658-64, 2014
Felix CA: Leukemias related to treatment with DNA topoisomerase II inhibitors. Med Pediatr Oncol 36:525-35, 2001
Hijiya N, Ness KK, Ribeiro RC, et al: Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues. Cancer 115:23-35, 2009
Koontz MZ, Horning SJ, Balise R, et al: Risk of therapy-related secondary leukemia in Hodgkin lymphoma: the Stanford University experience over three generations of clinical trials. J Clin Oncol 31:592-8, 2013
Landier W, Armenian SH, Lee J, et al: Yield of screening for long-term complications using the Children’s Oncology Group long-term follow-up guidelines. J Clin Oncol 30:4401-8, 2012
Le Deley MC, Leblanc T, Shamsaldin A, et al: Risk of secondary leukemia after a solid tumor in childhood according to the dose of epipodophyllotoxins and anthracyclines: a case-control study by the Societe Francaise d’Oncologie
Pediatrique. J Clin Oncol 21:1074-81, 2003
Nottage K, Lanctot J, Li Z, et al: Long-term risk for subsequent leukemia after treatment for childhood cancer: a report from the Childhood Cancer Survivor Study. Blood 117:6315-8, 2011
Rihani R, Bazzeh F, Faqih N, et al: Secondary hematopoietic malignancies in survivors of childhood cancer: an analysis of 111 cases from the Surveillance, Epidemiology, and End Result-9 registry. Cancer 116:4385-94, 2010

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ANTHRACYCLINE ANTIBIOTICS (CONT)

Therapeutic
Exposure

Potential
Late Effects

Anthracycline Antibiotics
Daunorubicin
Doxorubicin
Epirubicin
Idarubicin
Mitoxantrone

Cardiac toxicity
Cardiomyopathy
Subclinical left ventricular
dysfunction
Congestive heart failure
Arrhythmia

Dose Conversion
Use the following formulas
to convert to doxorubicin
isotoxic equivalents prior to
calculating total cumulative
anthracycline dose.
To estimate cumulative
anthracycline dose in doxorubicin
isotoxic equivalents
1.0 x (doxorubicin total dose) +0.5 x (daunorubicin total dose) +0.67 x (epirubicin total dose) +5.0 x (idarubicin total dose) +10.0 x (mitoxantrone total dose)

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Shortness of breath
Dyspnea on exertion
Orthopnea
Chest pain
Palpitations
If under 25 yrs: nausea, vomiting
YearlyPHYSICAL
Blood pressure
Cardiac exam
YearlySCREENING
Echo (or comparable imaging to evaluate
cardiac function)
RECOMMENDED FREQUENCY OF ECHOCARDIOGRAM
Anthracycline
Dose*
None to <100mg/m2

Radiation
Dose**

Recommended
Frequency

None to <15Gy

No screening

15Gy to <30Gy
None to <100mg/m2
Every 5 years≥100 to <250mg/m²
None to <15Gy≥100 to <250mg/m²≥15Gy
None to Any≥30Gy
Every 2 years≥ 250mg/m²
None to Any*Based on doxorubicin isotonic equivalent dose.
**Based on radiation dose with potential impact to heart(radiation to chest, abdomen, spine [thoracic, whole], TBI).
See section 77.

EKG (include evaluation of QTc interval)
Baseline at entry into long-term follow-up, repeat
as clinically indicated

HEALTH LINKS

Heart Health
Cardiovascular Risk Factors
Nutrition and Physical Activity
COUNSELING
Traditional CVRFs significantly increase survivors’ risk of cardiomyopathy. Counsel
regarding the importance of maintaining blood pressure, BMI, lipids, and glucose levels
within goal ranges per general population guidelines.
Regarding exercise:• Exercise is generally safe and encouraged for patients with normal LV systolic function• Consult cardiology for survivors with asymptomatic cardiomyopathy to define physicalactivity limits and precautions.
• Consider cardiology consultation to define physical activity limits and precautions forhigh risk survivors (i.e., those requiring an echo every 2 years) who plan to participate
in intensive exercise.
If QTc interval is prolonged: Caution use of QTc prolonging medications (e.g., tricyclic
anti-depressants, antifungals, macrolide antibiotics, metronidazole).
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Cardiac MRI as an adjunct imaging modality when echo images are suboptimal.
Cardiology consultation in patients with subclinical abnormalities on screening
evaluations, LV dysfunction, dysrhythmia, or prolonged QTc interval.
For patients who are pregnant or planning to become pregnant, additional cardiology
evaluation is indicated in patients who received:• ≥250 mg/m2 anthracyclines• ≥30 Gy chest radiation, or• Anthracycline (any dose) combined with chest radiation (≥15 Gy)• Evaluation should include a baseline echo (pre- or early-pregnancy). For those without
prior abnormalities and with normal pre- or early-pregnancy baseline echos, follow-up
echos may be obtained at the provider’s discretion. Those with a history of systolic
dysfunction or with pre- or early-pregnancy systolic dysfunction are at highest risk for
pregnancy-associated cardiomyopathy, and should be monitored periodically during
pregnancy, labor and delivery due to increased risk for heart failure.
SYSTEM = Cardiovascular
SCORE = 1w

Additional Information

Although mitoxantrone is an anthraquinone, it is related to the anthracycline family and is included in this section because of its cardiotoxic potential.
Childhood cancer survivors exhibit clinical and subclinical toxicity at lower levels than adults. In patients with abnormal LV systolic function, certain conditions (such as isometric exercise and viral infections) have been anecdotally
reported to precipitate cardiac decompensation. Prospective studies are needed to better define the contribution of these factors to cardiac disease risk.
Abdominal symptoms (nausea, emesis) may be seen more frequently than exertional dyspnea or chest pain in younger patients.
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Exertional intolerance is an uncommon presentation of left ventricular dysfunction in patients <25 years old.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Age <5 years at time of treatment, genetic variants associated with increased anthracycline-induced cardiotoxicity- Cancer/Treatment factors: Combined with radiation involving the heart, higher cumulative anthracycline doses (≥550 mg/m2 in patients ≥18 years at time of treatment, ≥250 mg/m2 in patients <18 years at time of treatment), chest radiation ≥15 Gy chest radiation combined with ≥100 mg/m2 anthracycline, longer time since treatment- Pre-morbid/Co-morbid medical conditions: Obesity, congenital heart disease, hypertension, diabetes mellitus, dyslipidemia. For female patients, pregnancy if systolic function is abnormal pre-pregnancy- Health behaviors: Smoking, drug use (e.g., cocaine, diet pills, ephedra, mahuang)

References
Armstrong GT, Oeffinger KC, Chen Y, et al: Modifiable risk factors and major cardiac events among adult survivors of childhood cancer. J Clin Oncol 31:3673-80, 2013
Armstrong GT, Plana JC, Zhang N, et al: Screening adult survivors of childhood cancer for cardiomyopathy: comparison of echocardiography and cardiac magnetic resonance imaging. J Clin Oncol 30:2876-84, 2012
Blanco JG, Sun CL, Landier W, et al: Anthracycline-related cardiomyopathy after childhood cancer: role of polymorphisms in carbonyl reductase genes-a report from the Children’s Oncology Group. J Clin Oncol 30:1415-21, 2012
Chen Y, Chow EJ, Oeffinger KC, et al: Traditional cardiovascular risk factors and individual prediction of cardiovascular events in childhood cancer survivors. J Natl Cancer Inst 112:3,256-265, 2020
Chow EJ, Chen Y, Kremer LC, et al: Individual prediction of heart failure among childhood cancer survivors. J Clin Oncol 33:394-402, 2015
Ehrhardt MJ, Leerink JM, Mulder RL, et al: Systematic review and updated recommendations for cardiomyopathy surveillance for survivors of childhood, adolescent, and young adult cancer from the International Late Effects ofChildhood Cancer Guideline Harmonization Group. Lancet Oncol 24(3):e108-e120, 2023
Ehrhardt MJ, Ward ZJ, Liu Q, et al: Cost-effectiveness of the International Late Effects of Childhood Cancer Guideline Harmonization Group screening guidelines to prevent heart failure in survivors of childhood cancer. J Clin Oncol
38(33):3851-3862, 2020
Feijen EA, Leisenring WM, Stratton KL, et al: Derivation of anthracycline and anthraquinone equivalence ratios to doxorubicin for late-onset cardiotoxicity. JAMA Oncol Jun 5(6):864-871, 2019
Feijen EA, Leisenring WM, Stratton KL, et al: Equivalence ratio for daunorubicin to doxorubicin in relation to late heart failure in survivors of childhood cancer. J Clin Oncol 33:3774-80, 2015
Haddy N, Diallo S, El-Fayech C, et al: Cardiac diseases following childhood cancer treatment: cohort study. Circulation 133:31-8, 2016
Hines MR, Mulrooney DA, Hudson MM, et al: Pregnancy-associated cardiomyopathy in survivors of childhood cancer. J Cancer Surviv 10:113-21, 2016
Leger KJ, Cushing-Haugen K, Hansen JA, et al: Clinical and genetic determinants of cardiomyopathy risk among hematopoietic cell transplantation survivors. Biol Blood Marrow Transplant 22(6):1094-1101, 2016
Lipshultz SE, Adams MJ, Colan SD, et al: Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association. Circulation 128:1927-95, 2013
Mulrooney DA, Armstrong GT, Huang S, et al: Cardiac outcomes in adult survivors of childhood cancer exposed to cardiotoxic therapy: a cross-sectional study. Ann Intern Med 164:93-101, 2016
Mulrooney DA, Hyun G, Ness KK, et al: Major cardiac events for adult survivors of childhood cancer diagnosed between 1970 and 1999: report from the Childhood Cancer Survivor Study cohort. BMJ 368:l6794, 2020
Spewak MB, Williamson RS, Mertens AC, et al: Yield of screening echocardiograms during pediatric follow-up in survivors treated with anthracyclines and cardiotoxic radiation. Pediatr Blood Cancer 64(6), 2017van Dalen EC, van der Pal HJ, Kok WE, et al: Clinical heart failure in a cohort of children treated with anthracyclines: a long-term follow-up study. Eur J Cancer 42:3191-8, 2006
van Dalen EC, van der Pal HJ, van den Bos C, et al: Clinical heart failure during pregnancy and delivery in a cohort of female childhood cancer survivors treated with anthracyclines. Eur J Cancer 42:2549-53, 2006
van der Pal HJ, van Dalen EC, van Delden E, et al: High risk of symptomatic cardiac events in childhood cancer survivors. J Clin Oncol 30:1429-37, 2012

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Therapeutic
Exposure
Anti-Tumor Antibiotics
Bleomycin

ANTI-TUMOR ANTIBIOTICS
Potential
Late Effects

Pulmonary toxicity
Pulmonary fibrosis
Interstitial pneumonitis
Acute respiratory distresssyndrome (very rare)

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Cough
Wheezing
Shortness of breath
Dyspnea on exertion
YearlyPHYSICAL
Pulmonary exam
YearlySCREENING
PFTs (including DLCO and spirometry)
Baseline at entry into long-term follow-up, repeat
as clinically indicated in patients with abnormal
results or progressive pulmonary dysfunction

HEALTH LINKS
Pulmonary HealthBleomycin AlertRESOURCES
www.smokefree.gov
COUNSELING
Notify healthcare providers of history of bleomycin therapy and risk of worsening fibrosis
with high oxygen exposure such as during general anesthesia.
Administration of high concentrations of oxygen may result in chronic progressive
pulmonary fibrosis.
Tobacco avoidance/smoking cessation/environmental tobacco smoke.
Influenza and Pneumococcal vaccinations.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Repeat PFTs prior to general anesthesia.
Pulmonary consultation for patients with symptomatic pulmonary dysfunction.
Pulmonary consultation for survivors who desire to SCUBA dive (due to potential
undiagnosed pulmonary toxicities, and limited data to guide safe diving
recommendations for individuals treated with pulmonary toxic therapy).
SYSTEM = Pulmonary
SCORE
ARDS = 2B
All Else = 1wAdditional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Pulmonary toxicity- Cancer/Treatment factors: Higher cumulative dose, especially bleomycin dose ≥400 U/m2 (pulmonary function deficits observed at doses as low as 60-100 U/m2 in children on formal pulmonary function testing), combination with busulfan,
carmustine (BCNU), or lomustine (CCNU), combination with chest radiation, or TBI- Pre-morbid/Co-morbid medical conditions: Renal dysfunction, high dose oxygen support such as during general anesthesia- Health behaviors: Smoking, inhaled illicit drug use

References
Armenian SH, Landier W, Francisco L, et al: Long-term pulmonary function in survivors of childhood cancer. J Clin Oncol 33:1592-600, 2015
De A, Kamath S, Wong K, et al: Correlation of pulmonary function abnormalities with dose volume histograms in children treated with lung irradiation. Pediatr Pulmonol 50:596-603, 2015
Dietz AC, Chen Y, Yasui Y, et al: Risk and impact of pulmonary complications in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 122:3687-3696, 2016
Green DM, Zhu L, Wang M, et al: Pulmonary function after treatment for childhood cancer. A report from the St. Jude Lifetime Cohort Study (SJLIFE). Ann Am Thorac Soc 13:1575-85, 2016
Huang TT, Hudson MM, Stokes DC, et al: Pulmonary outcomes in survivors of childhood cancer: a systematic review. Chest 140:881-901, 2011
Hudson MM, Ness KK, Gurney JG, et al: Clinical ascertainment of health outcomes among adults treated for childhood cancer. JAMA 309:2371-2381, 2013
Mulder RL, Thonissen NM, van der Pal HJ, et al: Pulmonary function impairment measured by pulmonary function tests in long-term survivors of childhood cancer. Thorax 66:1065-71, 2011
Tetrault JM, Crothers K, Moore BA, et al: Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch Intern Med 167:221-8, 2007
van Hulst RA, Rietbroek RC, Gaastra MT, et al: To dive or not to dive with bleomycin: a practical algorithm. Aviat Space Environ Med 82:814-8, 2011
Wolff AJ, O’Donnell AE: Pulmonary effects of illicit drug use. Clin Chest Med 25:203-16, 2004
Zorzi AP, Yang CL, Dell S, et al: Bleomycin-associated lung toxicity in childhood cancer survivors. J Pediatr Hematol Oncol 37:e447-52, 2015

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ANTI-TUMOR ANTIBIOTICS (CONT)

Therapeutic
Exposure

Potential
Late Effects

Anti-Tumor Antibiotics
Dactinomycin

No known late effects

Periodic Evaluation

Health Counseling/
Further Considerations
SYSTEM = No Known Late Effects
SCORE = 1

Additional Information

Dactinomycin has been associated with acute SOS, from which the majority of patients recover without sequelae.

References
Green DM, Norkool P, Breslow NE, et al: Severe hepatic toxicity after treatment with vincristine and dactinomycin using single-dose or divided-dose schedules: a report from the National Wilms’ Tumor Study. J Clin Oncol 8:1525-30,
1990

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Therapeutic
Exposure
Corticosteroids
Dexamethasone
Prednisone

CORTICOSTEROIDS
Potential
Late Effects

Reduced bone mineral density(BMD)
Defined as Z-score >2 SD below
the mean in male survivors <50
years old and premenopausal
women or T-score >1 SD below
the mean in male survivors >50
years old and postmenopausal
women

Health Counseling/
Further Considerations

Periodic Evaluation
SCREENING
Bone density evaluation (DXA)
Adjust for height-age Z-score in survivors <age
20 years*Baseline BMD at entry into long-term follow-up (2to 5 years after completion of therapy) with thefollowing recommended actions:• If Z-score >1 SD above the mean (normal),repeat at 25 years of age when peak bone mass
should be achieved• Between these two measurements and thereafter, screen as clinically indicated based on BMD
and ongoing risk assessment• If Z-score >2 SD below the mean, referral to (orconsultation of) a bone health specialist• If Z-score >1 and <2 SD below the mean,evaluation for endocrine defects (e.g., hypogonadism or GH deficiency) and consultation with abone health specialist for further evaluation andinterpretation of findings as clinically indicated.
Repeat DXA after 2 years and thereafter as clinically indicated based on BMD change (i.e., BMD
decline is greater than the DXA least significant
change) and ongoing risk assessment

HEALTH LINKS

Bone HealthRESOURCES
National Osteoporosis Foundation: www.nof.org
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Ensure the AAP recommended minimum daily intake of vitamin D (400 IU/day) for infants<12 months, 600 IU/day for those age 12 months through age 70 years, 800 IU/day for
those >70 years
Ensure adequate dietary calcium (see table in the “Bone Health” Health Link for ageappropriate recommendations). Supplements may be necessary if there are dietary
restrictions.
Use caution regarding calcium supplementation in patients with history of renal lithiasis.
Advocate for regular weight-bearing exercises such as running and jumping.
Treat exacerbating or predisposing conditions (e.g., hormonal replacement therapy
for hypogonadism, GH deficiency, correction of chronic metabolic acidosis that could
accelerate bone loss).
Endocrine consultation for patients with osteoporosis or history of multiple fractures
for pharmacologic interventions (e.g., bisphosphonates, calcitonin, selective estrogen
receptor modulators).
SYSTEM = Musculoskeletal
SCORE = 2B

*Pediatric Z-score calculator adjusted forheight age: https://zscore.research.chop.edu/
calcpedbonedens.phpw

Additional Information

The World Health Organization definition of osteoporosis in adults is based on comparison of a measured BMD of young adults at peak bone age and defined as a T-score.
A T-score is the number of standard deviations the BMD measurement is above or below the mean.
Current definitions of osteopenia (T-scores between 1.0 and 2.5 SD below the mean) and osteoporosis (T-scores >2.5 SD below the mean) were developed primarily in the context of postmenopausal women. In this population,T-scores have a well-validated correlation with fracture risk that increases with age.
The fracture risk associated with T-scores in younger populations, including cancer survivors with treatment-related hypogonadism, has not been established.
T-scores are not appropriate to assess skeletal health in pediatric patients who have not achieved peak adult bone mass.
Pediatric BMD reference data sets calculate Z-scores based on age and gender.
A Z-score is the number of standard deviations the measurement is above or below the age-matched mean BMD.
The fracture risk in pediatric patients with low BMD for chronologic age based on Z-scores has not been established.
There are no defined standards for referral or treatment of low BMD in children.

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Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Caucasian race, lower weight/BMI. Both genders are at risk.
- Cancer/Treatment factors: Corticosteroids (especially prolonged therapy, e.g., for cGVHD), higher cumulative corticosteroid dose (especially ≥9 gm/m2), cranial/craniospinal radiation, HCT, or TBI.
- Pre-morbid/Co-morbid medical conditions: GH deficiency, hypogonadism/delayed puberty, hyperthyroidism- Health behaviors: Intake of calcium and vitamin D, intake of alcohol and carbonated beverages, weight bearing exercise, smoking

References
Bischoff-Ferrari HA: Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol 624:55-71, 2008
Chaiban J, Muwakkit S, Arabi A, et al: Modeling pathways for low bone mass in children with malignancies. J Clin Densitom 12:441-9, 2009
Esbenshade AJ, Sopfe J, Zhao Z, et al: Screening for vitamin D insufficiency in pediatric cancer survivors. Pediatr Blood Cancer 61:723-8, 2014
Kaste SC, Qi A, Smith K, et al: Calcium and cholecalciferol supplementation provides no added benefit to nutritional counseling to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL). Pediatr
Blood Cancer 61:885-93, 2014
Landier W, Armenian SH, Lee J, et al: Yield of screening for long-term complications using the Children’s Oncology Group long-term follow-up guidelines. J Clin Oncol 30:4401-8, 2012
Leonard MB: Assessment of bone health in children and adolescents with cancer: promises and pitfalls of current techniques. Med Pediatr Oncol 41:198-207, 2003
Mostoufi-Moab S, Brodsky J, Isaacoff EJ, et al: Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation. J Clin Endocrinol Metab 97:3584-92, 2012
NIH Office of Dietary Supplements: Vitamin D health professionals fact sheet. Accessed March 16, 2023: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional
Polgreen LE, Petryk A, Dietz AC, et al: Modifiable risk factors associated with bone deficits in childhood cancer survivors. BMC Pediatr 12:40, 2012
The International Society for Clinical Densitometry. 2019 ISCD official positions. Accessed March 2023: https://iscd.org/learn/official-positions
van Leeuwen BL, Kamps WA, Jansen HW, et al: The effect of chemotherapy on the growing skeleton. Cancer Treat Rev 26:363-76, 2000
Wasilewski-Masker K, Kaste SC, Hudson MM, et al: Bone mineral density deficits in survivors of childhood cancer: long-term follow-up guidelines and review of the literature. Pediatrics 121:e705-13, 2008
Wilson CL, Dilley K, Ness KK, et al: Fractures among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 118:5920-8, 2012
Zemel BS, Leonard MB, Kelly A, et al: Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children. J Clin Endocrinol Metab 95:1265-73, 2010

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Therapeutic
Exposure
Corticosteroids
Dexamethasone
Prednisone

CORTICOSTEROIDS (CONT)
Potential
Late Effects

Osteonecrosis (avascularnecrosis)

Periodic Evaluation
HISTORY
Joint pain
Swelling
Immobility
Limited range of motion
YearlyPHYSICAL
Musculoskeletal exam
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Osteonecrosis
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
MRI as clinically indicated.
Orthopedic consultation in patients with positive imaging and/or symptoms ofosteonecrosis.
Physical therapy evaluation (for non-pharmacologic pain management, range of
motion, strengthening, stretching, functional mobility).
SYSTEM = Musculoskeletal
SCORE = 1

Additional Information

Osteonecrosis typically occurs during the acute treatment phase; may progress over time or resolve.
Multifocal osteonecrosis is significantly more common (3:1) than unifocal.
Symptomatic lesions confer the greatest risk for collapse.
Dexamethasone is associated with a greater risk than prednisone, especially for patients with ALL ≥10 years of age at time of exposure.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Being pubertal or post-pubertal at time of treatment, genetic polymorphisms- Cancer/Treatment factors: High dose radiation to any bone, orthovoltage radiation (commonly used before 1970) due to delivery of greater dose to skin and bones, TBI, prolonged immunosuppression (e.g., for cGVHD)- Pre-morbid/Co-morbid medical conditions: Sickle cell disease, cGVHD

References
Elmantaser M, Stewart G, Young D, et al: Skeletal morbidity in children receiving chemotherapy for acute lymphoblastic leukaemia. Arch Dis Child 95:805-9, 2010
Kadan-Lottick NS, Dinu I, Wasilewski-Masker K, et al: Osteonecrosis in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 26:3038-45, 2008
Karimova EJ, Rai SN, Ingle D, et al: MRI of knee osteonecrosis in children with leukemia and lymphoma: Part 2, clinical and imaging patterns. AJR Am J Roentgenol 186:477-82, 2006
Karol SE, Yang W, Van Driest SL, et al: Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. Blood 126:1770-6, 2015
Kawedia JD, Kaste SC, Pei D, et al: Pharmacokinetic, pharmacodynamic, and pharmacogenetic determinants of osteonecrosis in children with acute lymphoblastic leukemia. Blood 117:2340-7; quiz 2556, 2011
Mattano LA, Jr., Devidas M, Nachman JB, et al: Effect of alternate-week versus continuous dexamethasone scheduling on the risk of osteonecrosis in paediatric patients with acute lymphoblastic leukaemia: results from the CCG-1961
randomised cohort trial. Lancet Oncol 13:906-15, 2012
Mattano LA, Jr., Sather HN, Trigg ME, et al: Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children’s Cancer Group. J Clin Oncol 18:3262-72, 2000
Ojala AE, Paakko E, Lanning FP, et al: Osteonecrosis during the treatment of childhood acute lymphoblastic leukemia: a prospective MRI study. Med Pediatr Oncol 32:11-7, 1999
Plesa M, Gagné V, Glisovic S, et al: Influence of BCL2L11 polymorphism on osteonecrosis during treatment of childhood acute lymphoblastic leukemia. Pharmacogenomics J 19(1):33-41, 2019
Relling MV, Yang W, Das S, et al: Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia. J Clin Oncol 22:3930-6, 2004
te Winkel ML, Pieters R, Hop WC, et al: Prospective study on incidence, risk factors, and long-term outcome of osteonecrosis in pediatric acute lymphoblastic leukemia. J Clin Oncol 29:4143-50, 2011

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Therapeutic
Exposure
Corticosteroids
Dexamethasone
Prednisone

CORTICOSTEROIDS (CONT)
Potential
Late Effects

Cataracts

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Visual changes (decreased acuity, halos,
diplopia)
YearlyPHYSICAL
Visual acuity
Funduscopic exam
YearlySCREENING
Evaluation by ophthalmologist or
optometrist
YearlyHEALTH LINKS
Cataracts
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Ophthalmology consultation as clinically indicated.
Refer patients with visual deficits to school liaison in community or cancer
center (psychologist, social worker, school counselor) to facilitate acquisition of
educational resources.
SYSTEM = Ocular
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Combination with busulfan, combination with TBI, cranial, orbital or eye radiation, longer interval since treatment

References
Alloin AL, Barlogis V, Auquier P, et al: Prevalence and risk factors of cataract after chemotherapy with or without central nervous system irradiation for childhood acute lymphoblastic leukaemia: an LEA study. Br J Haematol 164:94100, 2014
Benyunes MC, Sullivan KM, Deeg HJ, et al: Cataracts after bone marrow transplantation: long-term follow-up of adults treated with fractionated total body irradiation. Int J Radiat Oncol Biol Phys 32:661-70, 1995

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Therapeutic
Exposure
Enzymes
Asparaginase

ENZYMES
Potential
Late Effects

Periodic Evaluation

No known late effects

Health Counseling/
Further Considerations
SYSTEM = No Known Late Effects
SCORE = 1

Additional Information

Acute toxicities predominate, from which the majority of patients recover without sequelae.

References
Duval M, Suciu S, Ferster A, et al: Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children’s Leukemia Group phase 3 trial. Blood 99:2734-9, 2002
Parsons SK, Skapek SX, Neufeld EJ, et al: Asparaginase-associated lipid abnormalities in children with acute lymphoblastic leukemia. Blood 89:1886-95, 1997

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Therapeutic
Exposure
Plant Alkaloids
Vinblastine
Vincristine

PLANT ALKALOIDS
Potential
Late Effects

Peripheral sensory or motor
neuropathy
Areflexia
Weakness
Foot drop
Paresthesias
Dysesthesias

Periodic Evaluation
HISTORY
Areflexia
Weakness
Foot drop
Paresthesias
Dysesthesias
Yearly, until 2 to 3 years after therapy, monitor
yearly if symptoms persist
PHYSICAL
Neurologic exam
Yearly, until 2 to 3 years after therapy, monitor
yearly if symptoms persist

Health Counseling/
Further Considerations
HEALTH LINKS
Peripheral Neuropathy
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Physical therapy referral for patients with symptomatic neuropathy.
Physical and occupational therapy assessment of hand function.
Treat with effective agent for neuropathic pain (e.g., gabapentin or amitriptyline).
SYSTEM = PNSSCORE = 2A

Additional Information

Acute toxicities most commonly occur and usually improve or resolve prior to patients entering long-term follow-up.
Neuropathy can persist after treatment and is typically not late in onset.
Studies of adults treated during childhood support higher prevalence of deficits than previously appreciated.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Combination with platinum chemotherapy, gemcitabine, taxanes- Pre-morbid/Co-morbid medical conditions: Anorexia, severe weight loss, Charcot-Marie-Tooth disease

References
Chauvenet AR, Shashi V, Selsky C, et al: Vincristine-induced neuropathy as the initial presentation of Charcot-Marie-Tooth disease in acute lymphoblastic leukemia: a Pediatric Oncology Group study. J Pediatr Hematol Oncol 25:31620, 2003
Lehtinen SS, Huuskonen UE, Harila-Saari AH, et al: Motor nervous system impairment persists in long-term survivors of childhood acute lymphoblastic leukemia. Cancer 94:2466-73, 2002
Ness KK, Jones KE, Smith WA, et al: Chemotherapy-related neuropathic symptoms and functional impairment in adult survivors of extracranial solid tumors of childhood: results from the St. Jude Lifetime Cohort Study. Arch Phys Med
Rehabil 94:1451-7, 2013

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CHEMOTHERAPY
Sec #
42

Therapeutic
Exposure
Plant Alkaloids
Vinblastine
Vincristine

PLANT ALKALOIDS (CONT)
Potential
Late Effects

Vasospastic attacks(Raynaud’s phenomenon)

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Vasospasms of hands, feet, nose, lips,
cheeks, or earlobes related to stress orcold temperatures
YearlyPHYSICAL
Physical exam of affected area
As clinically indicated

HEALTH LINKS
Raynaud’s Phenomenon
COUNSELING
Wear appropriate protective clothing in cold environments.
Symptoms may be exacerbated by medications/chemicals that cause
vasoconstriction (e.g., pseudoephedrine, stimulants), illicit drugs (e.g., cocaine),and nicotine.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Vasodilating medications (calcium-channel blockers, alpha blockers) for
patients with frequent, severe vasospastic attacks unresponsive to behavioral
management.
SYSTEM = PNSSCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Pre-morbid/Co-morbid medical conditions: Smoking, illicit drug use, use of vasoconstricting medications/substances, exposure to repetitive vibration

References
Bokemeyer C, Berger CC, Kuczyk MA, et al: Evaluation of long-term toxicity after chemotherapy for testicular cancer. J Clin Oncol 14:2923-32, 1996
Doll DC, Ringenberg QS, Yarbro JW: Vascular toxicity associated with antineoplastic agents. J Clin Oncol 4:1405-17, 1986
Vogelzang NJ, Bosl GJ, Johnson K, et al: Raynaud’s phenomenon: a common toxicity after combination chemotherapy for testicular cancer. Ann Intern Med 95:288-92, 1981

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w

Therapeutic
Exposure
Epipodophyllotoxins
Etoposide (VP16)
Teniposide (VM26)

EPIPODOPHYLLOTOXINS
Potential
Late Effects

Acute myeloid leukemia (AML)

Periodic Evaluation
HISTORY
Fatigue
Bleeding
Easy bruising
Yearly, up to 10 years after exposure to agent
PHYSICAL
Dermatologic exam (pallor, petechiae,
purpura)Yearly, up to 10 years after exposure to agent

Health Counseling/
Further Considerations
HEALTH LINKS
Reducing the Risk of Subsequent Cancers
COUNSELING
Promptly seek medical attention for fatigue, pallor, petechiae or bone pain.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
CBC and bone marrow exam as clinically indicated.
SYSTEM = SMNSCORE = 1

Additional Information

Epipodophyllotoxin administration schedules have been modified since approximately 1990 to reduce the risk of AML.
There is negligible benefit to obtaining a screening CBC in the absence of clinical signs and symptoms for AML.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Weekly or twice weekly administration, <5 years since exposure to agent, autologous HCT- Pre-morbid/Co-morbid medical conditions: Evidence is conflicting that splenectomy modifies risk for AML

References
Eichenauer DA, Thielen I, Haverkamp H, et al: Therapy-related acute myeloid leukemia and myelodysplastic syndromes in patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood 123:1658-64, 2014
Hijiya N, Ness KK, Ribeiro RC, et al: Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues. Cancer 115:23-35, 2009
Koontz MZ, Horning SJ, Balise R, et al: Risk of therapy-related secondary leukemia in Hodgkin lymphoma: the Stanford University experience over three generations of clinical trials. J Clin Oncol 31:592-8, 2013
Krishnan A, Bhatia S, Slovak ML, et al: Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors. Blood 95:1588-93, 2000
Landier W, Armenian SH, Lee J, et al: Yield of screening for long-term complications using the Children’s Oncology Group long-term follow-up guidelines. J Clin Oncol 30:4401-8, 2012
Le Deley MC, Leblanc T, Shamsaldin A, et al: Risk of secondary leukemia after a solid tumor in childhood according to the dose of epipodophyllotoxins and anthracyclines: a case-control study by the Societe Francaise d’Oncologie
Pediatrique. J Clin Oncol 21:1074-81, 2003
Nottage K, Lanctot J, Li Z, et al: Long-term risk for subsequent leukemia after treatment for childhood cancer: a report from the Childhood Cancer Survivor Study. Blood 117:6315-8, 2011
Pui CH, Relling MV, Rivera GK, et al: Epipodophyllotoxin-related acute myeloid leukemia: a study of 35 cases. Leukemia 9:1990-6, 1995
Rihani R, Bazzeh F, Faqih N, et al: Secondary hematopoietic malignancies in survivors of childhood cancer: an analysis of 111 cases from the Surveillance, Epidemiology, and End Result-9 registry. Cancer 116:4385-94, 2010
Sanford NN, Miao R, Wang H, et al: Characteristics and predictors for secondary leukemia and myelodysplastic syndrome in Ewing and osteosarcoma survivors. Int J Radiat Oncol Biol Phys 103(1):52-61, 2019
Smith MA, Rubinstein L, Anderson JR, et al: Secondary leukemia or myelodysplastic syndrome after treatment with epipodophyllotoxins. J Clin Oncol 17:569-77, 1999

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RADIATIONINSTRUCTIONS

Determining Applicability of Radiation Sections for Specific Patients Based on
Exposure

Guideline Radiation Sections by Field
Applicable guideline sections indicated in bold/dark blue; M=Male; F=Female

The radiation sections of the COG Long-Term Follow-Up Guidelines (Sections 44-98) areorganized by anatomic region from the head downward. In this current version of the
COG LTFU Guidelines, the radiation fields are still simplified and categorized by anatomic
region, as follows:-

Head/Brain
Neck
Chest
AxillaAbdomenPelvisTesticularSpine (cervical, thoracic, lumbar, sacral, whole)
Skin/soft tissues/bones/extremities
TBI

64, 65, 66*, 67,
68, 69, 70, 71, 79
44, 45, 46,
47, 48, 53,
58M, 59F,
61, 64, 65,
67, 68, 69,
73F, 74F,
75, 76, 80,
81, 86, 87,
91M, 92F,
93F, 94F, 96

The Guideline sections applicable to each radiation field are listed on the accompanying
diagram.
Traditional and combined radiation fields (e.g., mantle, mediastinal, para-aortic, etc.) aredefined in Appendix I and mapped to the anatomic fields specified above, as follows:-

46, 47, 48, 49, 50, 51, 52,
53, 54M, 55F, 56, 57, 58M,
59F, 60*, 61, 62, 63*, 63,
65, 66*, 67, 68, 69, 70, 71

72, 77*, 79, 97
44,
44,
45,
45,
96,
96,
98
97

Whole Spine

Radiation Fields Defined, Table: Appendix I, pages 6-7
Radiation Fields Defined, Diagram: Appendix I, page 8

Radiation Dose Calculations: Appendix I, page 9

Guideline Radiation Sections by Potential Impact, Table: Appendix I, pages 11-12
Guideline Radiation Sections by Potential Impact, Diagram: Appendix I, page 13
Total Body Irradiation (TBI) Related Potential Late Effects: Appendix I, page 14

Use the “Patient-Specific Guideline Identification Tool” in Appendix I (pages 32-37) todetermine specific screening guidelines by section number for individual patients.
COG LTFU Guidelines – Page 51

73F, 74F,
75, 76

77*, 78*, 79,
80, 81, 82,
83, 84, 85,
86, 87, 97

84, 85, 86, 97

Further details regarding radiation impact by organ systems, with associated potential lateeffects, are also available in Appendix I, as follows:-

72, 73F,
74F, 75, 76,
77*, 79, 97

64, 65, 66*, 67,
68, 69, 70, 71, 72,
77*, 79, 84, 85,
86, 88, 89, 92F,
93F, 94F, 97,

Five sections of these Guidelines (Sections 60, 63, 66, 77, 78) include minimum dose
specifications. These five Guideline sections are applicable only to patients who received
radiation to any of the relevant fields at a total dose higher than the specified minimum
dose. Instructions regarding calculating combined radiation doses are available asfollows:-

64, 65, 66*,
67, 68, 69, 70,
71, 72, 79

84, 85, 86, 88,
89, 92F, 93F,
94F, 95F

84, 85, 86, 88, 89
92F, 93F, 94F

90M, 91M*Minimum dose
specifications apply.
For instructions andexamples regarding
radiation dose
calculations, refer to“Radiation Dose
Calculations” in COG
Long-Term Follow-Up
Guidelines Appendix I
Reference Materials.
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RADIATION
Sec #
44

ALL FIELDS

Therapeutic
Exposure

Potential
Late Effects

Any Radiation (Including
TBI)

Subsequent benign ormalignant neoplasm
occurring in or nearradiation field
Such as dysplastic nevi, skincancer (basal cell carcinoma,squamous cell carcinoma),bone malignancies, oral
cancerPeriodic Evaluation
HISTORY
Skin lesions
Changing moles (asymmetry, bleeding,increasing size, indistinct borders)
Bone pain (especially in irradiated field)
Persistent thickening or lump of soft tissue
or boneYearlyPHYSICAL
Skin self exam
Monthly
Inspection and palpation of skin and soft
tissues in irradiated field(s)Dermatologic exam of irradiated fields
Palpation of bones in irradiated field
Yearlyw

Health Counseling/
Further Considerations
HEALTH LINKS
Reducing the Risk of Subsequent Cancers
Skin Health
COUNSELING
Promptly seek medical attention for symptoms (e.g., bone pain, bone mass,
persistent fevers).
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
See relevant guideline sections to determine screening for specific radiation
fields.
Dermatology consultation for evaluation and monitoring of atypical nevi.
Diagnostic imaging in patients as clinically indicated.
Surgical and/or oncology consultation as clinically indicated.
SYSTEM = SMNSCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, adolescent at treatment [bone malignancies]- Cancer/Treatment factors: Higher radiation dose, especially ≥30 Gy (bone malignancies), large radiation treatment volumes, alkylating agent exposure, orthovoltage radiation (commonly used before 1970) due to delivery ofgreater dose to skin and bones- Pre-morbid/Co-morbid medical conditions: Predisposing mutation (e.g., p53, NF1), bilateral or familial retinoblastoma (implying RB1 likely pathogenic variant), Gorlin syndrome (nevoid basal cell carcinoma syndrome)- Health behaviors: Sun exposure, tanning booths

References
Armstrong GT, Liu W, Leisenring W, et al: Occurrence of multiple subsequent neoplasms in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 29:3056-64, 2011
Baker KS, Leisenring WM, Goodman PJ, et al: Total body irradiation dose and risk of subsequent neoplasms following allogeneic hematopoietic cell transplantation. Blood 133(26):2790-2799, 2019
Bhatia S, Louie AD, Bhatia R, et al: Solid cancers after bone marrow transplantation. J Clin Oncol 19:464-71, 2001
Bright CJ, Hawkins MM, Winter DL, et al: Risk of Soft-Tissue Sarcoma Among 69 460 Five-Year Survivors of Childhood Cancer in Europe. J Natl Cancer Inst 110(6):649-660, 2018
Henderson TO, Rajaraman P, Stovall M, et al: Risk factors associated with secondary sarcomas in childhood cancer survivors: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys 84:224-30, 2012
Inskip PD, Sigurdson AJ, Veiga L, et al: Radiation-related new primary solid cancers in the Childhood Cancer Survivor Study: comparative radiation dose response and modification of treatment effects. Int J Radiat Oncol Biol Phys
94:800-7, 2016
Reulen RC, Frobisher C, Winter DL, et al: Long-term risks of subsequent primary neoplasms among survivors of childhood cancer. JAMA 305:2311-9, 2011
Schaapveld M, Aleman BM, van Eggermond AM, et al: Second cancer risk up to 40 years after treatment for Hodgkin’s lymphoma. N Engl J Med 373:2499-511, 2015
Schwartz B, Benadjaoud MA, Clero E, et al: Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment. Radiat Environ Biophys 53:381-90, 2014
Teepen JC, Kok JL, Kremer LC, et al: Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study. J Natl Cancer Inst 111(8):845-853, 2019
Turcotte LM, Liu Q, Yasui Y, et al: Temporal trends in treatment and subsequent neoplasm risk among 5-year survivors of childhood cancer, 1970-2015. JAMA 317(8):814-824, 2017
Turcotte LM, Whitton JA, Friedman DL, et al: Risk of subsequent neoplasms during the fifth and sixth decades of life in the Childhood Cancer Survivor Study cohort. J Clin Oncol 33:3568-75, 2015
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RADIATION
Sec #
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w

ALL FIELDS (CONT)

Therapeutic
Exposure

Potential
Late Effects

Any Radiation (Including
TBI)

Dermatologic toxicity otherthan neoplasms
Permanent alopecia
Altered skin pigmentation
Telangiectasias
Fibrosis

Health Counseling/
Further Considerations

Periodic Evaluation
PHYSICAL
Dermatologic exam of irradiated fields
YearlyHEALTH LINKS
Skin Health
SYSTEM = Dermatologic
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment- Cancer/Treatment factors: Total radiation dose ≥40 Gy, especially ≥50 Gy, large dose fractions (e.g., ≥2 Gy per fraction), orthovoltage radiation (commonly used before 1970) due to delivery of greater dose to skin and bones

References
Alsner J, Andreassen CN, Overgaard J: Genetic markers for prediction of normal tissue toxicity after radiotherapy. Semin Radiat Oncol 18:126-35, 2008
Kinahan KE, Sharp LK, Seidel K, et al: Scarring, disfigurement, and quality of life in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 30:2466-74, 2012
Lawenda BD, Gagne HM, Gierga DP, et al: Permanent alopecia after cranial irradiation: dose-response relationship. Int J Radiat Oncol Biol Phys 60:879-87, 2004
Marcus RB, Esiashivilli N: Musculoskeletal, integument, in Schwartz CL, Hobbie WL, Constine LS, et al (eds): Survivors of Childhood and Adolescent Cancer: A Multidisciplinary Approach (ed 3). Switzerland, Springer International
Publishing, 2015, pp 297-324
Rannan-Eliya YF, Rannan-Eliya S, Graham K, et al: Surgical interventions for the treatment of radiation-induced alopecia in pediatric practice. Pediatr Blood Cancer 49:731-6, 2007
Rogers S, Donachie P, Sugden E, et al: Comparison of permanent hair loss in children with standard risk PNETS of the posterior fossa following radiotherapy alone or chemotherapy and radiotherapy after surgical resection. Pediatr
Blood Cancer 57:1074-6, 2011

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POTENTIAL IMPACT TO
BRAIN/CRANIUM

RADIATION
Sec #
46

w

Therapeutic
Exposure
Head/Brain
TBI

Potential
Late Effects
Brain tumor (benign ormalignant)Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Headaches
Vomiting
Cognitive, motor or sensory deficits
Seizures and other neurologic symptoms
YearlyPHYSICAL
Neurologic exam
YearlyPOTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Brain MRI as clinically indicated for symptomatic patients.
Brain MRI every other year for patients with neurofibromatosis beginning 2 years
after radiation therapy.
Neurosurgical consultation for tissue diagnosis and/or resection.
Neuro-oncology consultation for medical management.
SYSTEM = SMNSCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, especially age <6 years- Cancer/Treatment factors: Higher radiation dose (risk of subsequent CNS tumor after cranial radiation increases in a dose-dependent fashion)- Pre-morbid/Co-morbid medical conditions: Neurofibromatosis, ataxia telangiectasia

References
Bowers DC, Moskowitz CS, Chou JF, et al: Morbidity and Mortality Associated With Meningioma After Cranial Radiotherapy: A Report From the Childhood Cancer Survivor Study. J Clin Oncol 35(14):1570-1576, 2017
Bowers DC, Verbruggen LC, Kremer LCM, et al: Surveillance for subsequent neoplasms of the CNS for childhood, adolescent, and young adult cancer survivors: a systematic review and recommendations from the International Late
Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol 22(5):e196-e206, 2021
Friedman DL, Whitton J, Leisenring W, et al: Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 102:1083-95, 2010
Kok JL, Teepen JC, van Leeuwen FE, et al: Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort: contributions of radiation dose, exposed cranial volume, and age. Neuro Oncol 21(3):392-403, 2019
Neglia JP, Robison LL, Stovall M, et al: New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 98:1528-37, 2006
Sharif S, Ferner R, Birch JM, et al: Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy. J Clin Oncol 24:2570-5, 2006
Taylor AJ, Little MP, Winter DL, et al: Population-based risks of CNS tumors in survivors of childhood cancer: the British Childhood Cancer Survivor Study. J Clin Oncol 28:5287-93, 2010
Walter AW, Hancock ML, Pui CH, et al: Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children’s Research Hospital. J Clin Oncol 16:3761-7, 1998

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Sec #
47

w

Therapeutic
Exposure
Head/Brain
TBI

Potential
Late Effects
Neurocognitive deficits
Functional deficits in:• Executive function (planningand organization)• Sustained attention• Memory (particularly visual,sequencing, temporal
memory)• Processing speed• Visual-motor integration• Fine motor dexterity• Language• Academic fluency
Learning deficits in math andreading (particularly reading
comprehension)
Diminished IQ
Behavioral change

Periodic Evaluation
HISTORY
Educational and/or vocational progress
YearlySCREENING
Referral for formal neuropsychologicalevaluation
Baseline at entry into long-term follow-up,
then periodically as clinically indicatedfor patients with evidence of impaired
educational or vocational progress

Health Counseling/
Further Considerations
HEALTH LINKS
School After Treatment
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Referral to school liaison in community or cancer center (psychologist, social
worker, school counselor) to facilitate acquisition of educational resources and/or social skills training.
Psychotropic medication (e.g., stimulants) or evidence-based rehabilitation
training. Caution—lower starting dose and assessment of increased sensitivity
when initiating therapy is recommended.
Referral to community services for vocational rehabilitation or for services fordevelopmentally disabled.
SYSTEM = CNSSCORE = 1

Additional Information

Formal neuropsychological evaluation includes tests of processing speed, computer-based attention, visual motor integration, memory, comprehension of verbal instructions, verbal fluency, executive function and planning.
Neurocognitive deficits in survivors of leukemia and lymphoma are more frequently related to information processing (e.g., slow processing speed, attention problems). Neurocognitive deficits in brain tumor survivors treated withhigher doses of cranial radiation are more global (significant decline in IQ). Extent of deficit depends on age at treatment, intensity of treatment, and time since treatment. New or progressive deficits may emerge over time.
Note: academic fluency is defined as the ability to correctly complete multiple simple academic problems (e.g., reading words, simple math equations) within a limited amount of time.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, especially age <3 years, female sex, family history of learning or attention problems- Cancer/Treatment factors: Primary CNS tumor, CNS leukemia/lymphoma, relapsed leukemia/lymphoma treated with CNS-directed therapy, head/neck tumors with brain in radiation field, temporal lobe field including hippocampus (without hippocampal sparing), higher radiation dose, larger radiation field, greater cortical volumes, cranial radiation in combination with TBI, lack of volume-sparing radiation techniques (e.g., proton beam therapy),
combination with corticosteroids, methotrexate (IT, IO, high dose IV), cytarabine (high dose IV), longer elapsed time since therapy- Pre-morbid/Co-morbid medical conditions: Pre-morbid learning or attention problems, sleep disturbance, seizures, hydrocephalus, CRT-induced ototoxicity, chronic conditions (e.g., endocrine, cardiopulmonary, frailty)

References
Acharya S, Wu S, Ashford JM, et al: Association between hippocampal dose and memory in survivors of childhood or adolescent low-grade glioma: a 10-year neurocognitive longitudinal study. Neurooncol 21(9),1175-1183, 2019
Ali JS, Ashford JM, Swain MA, et al: Predictors of cognitive performance among infants treated for brain tumors: findings from a multisite, prospective, longitudinal trial. J Clin Oncol 39(21),2350-2358, 2021
Bass JK, Liu W, Banerjee P, et al: Association of hearing impairment with neurocognition in survivors of childhood cancer. JAMA Oncol 6(9),1363-1371, 2020
Brinkman TM, Krasin MJ, Liu W, et al: Long-term neurocognitive functioning and social attainment in adult survivors of pediatric CNS tumors: results from the St Jude Lifetime Cohort Study. J Clin Oncol 34:1358-67, 2016
Cheung YT, Brinkman TM, Li C, et al: Chronic health conditions and neurocognitive function in aging survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst 110(4),411-419, 2018Child AE, Warren EA, Grosshans DR, et al: Long-term cognitive and academic outcomes among pediatric brain tumor survivors treated with proton versus photon radiotherapy. Pediatr Blood Cancer 68(9),e29125, 2021
Dixon SB, Chen Y, Yasui Y, et al: Reduced morbidity and mortality in survivors of childhood acute lymphoblastic leukemia: a report from the childhood cancer survivor study. J Clin Oncol 38(29),3418-3429, 2020
Eaton BR, Fong GW, Ingerski LM, et al: Intellectual functioning among case-matched cohorts of children treated with proton or photon radiation for standard-risk medulloblastoma. Cancer 127(20),3840-3846, 2021
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BRAIN/CRANIUM (CONT)RADIATION
Section 47 References (cont)Goda JS, Dutta D, Krishna U, et al: Hippocampal radiotherapy dose constraints for predicting long-term neurocognitive outcomes: mature data from a prospective trial in young patients with brain tumors. Neurooncol 22(11),16771685, 2020
Heitzer AM, Villagran AM, Raghubar K, et al: Effect of sensorineural hearing loss on neurocognitive and adaptive functioning in survivors of pediatric embryonal brain tumor. Journal of Neurooncol 146(1),147-156, 2020
Kahalley LS, Conklin HM, Tyc VL, et al: Slower processing speed after treatment for pediatric brain tumor and acute lymphoblastic leukemia. Psycho-Oncol 22:1979-86, 2013
Kahalley LS, Peterson R, Ris MD, et al: Superior intellectual outcomes after proton radiotherapy compared with photon radiotherapy for pediatric medulloblastoma. J Clin Oncol 38(5),454-461, 2020
Kahalley LS, Ris MD, Grosshans DR, et al: Comparing intelligence quotient change after treatment with proton versus photon radiation therapy for pediatric brain tumors. J Clin Oncol 34(10),1043-1049, 2016
Krull KR, Brinkman TM, Li C, et al: Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: a report from the St Jude Lifetime Cohort Study. J Clin Oncol 31:4407-15, 2013
Krull KR, Li C, Phillips NS, et al: Growth hormone deficiency and neurocognitive function in adult survivors of childhood acute lymphoblastic leukemia. Cancer 125(10),1748-1755, 2019
Michalski JM, Janss AJ, Vezina LG, et al: Children’s oncology group phase III trial of reduced-dose and reduced-volume radiotherapy with chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol 39(24),26852697, 2021
Mulrooney DA, Hyun G, Ness KK, et al: The changing burden of long-term health outcomes in survivors of childhood acute lymphoblastic leukaemia: a retrospective analysis of the St Jude Lifetime Cohort Study. Lancet Haematol
6(6),e306-e316, 2019
Olivier TW, Bass JK, Ashford JM, et al: Cognitive implications of ototoxicity in pediatric patients with embryonal brain tumors. J Clin Oncol 37(18),1566-1575, 2019
Orgel E, O’Neil SH, Kayser K, et al: Effect of sensorineural hearing loss on neurocognitive functioning in pediatric brain tumor survivors. Pediatr Blood Cancer 63(3),527-534, 2016
Tsang DS, Kim L, Liu ZA, et al: Intellectual changes after radiation for children with brain tumors: which brain structures are most important? Neurooncol 23(3),487-497, 2021
van Iersel L, van Santen HM, Potter B, et al: Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma. Pediatr Blood Cancer 67(12),e28723, 2020
Weusthof K, Luttich P, Regnery S, et al: Neurocognitive outcomes in pediatric patients following brain irradiation. Cancers 13(14), 2021
Williams AM, Krull KR, Howell CR, et al: Physiologic frailty and neurocognitive decline among young-adult childhood cancer survivors: a prospective study from the st jude lifetime cohort. J Clin Oncol 39(31),3485-3495, 2021
Zureick AH, Evans CL, Niemierko A, et al: Left hippocampal dosimetry correlates with visual and verbal memory outcomes in survivors of pediatric brain tumors. Cancer 124(10),2238-2245, 2018

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POTENTIAL IMPACT TO
BRAIN/CRANIUM (CONT)RADIATION
Sec #
48

w

Therapeutic
Exposure
Head/Brain
TBI

Potential
Late Effects
Clinical leukoencephalopathy
Spasticity
AtaxiaDysarthria
Dysphagia
Hemiparesis
Seizures

Periodic Evaluation
HISTORY
Cognitive, motor and/or sensory deficits
Seizures
Other neurologic symptoms
YearlyPHYSICAL
Neurologic exam
YearlyHealth Counseling/
Further Considerations
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Brain CT or Brain MRI with MRA as clinically indicated with preferred study
based on intracranial lesion to be evaluated:• Calcifications: CT• White matter: MRI with DTI• Microvascular injury: Gadolinium-enhanced MRI with DWI
Neurology consultation and follow-up as clinically indicated.
SYSTEM = CNSSCORE = 1

Additional Information

Clinical leukoencephalopathy may present with or without imaging abnormalities (e.g., leukoencephalopathy, cerebral lacunes, cerebral atrophy, dystrophic calcifications, mineralizing microangiopathy).
Transient white matter anomalies may follow radiotherapy and high dose chemotherapy for medulloblastoma/PNET, may mimic tumor recurrence, and signify risk of persistent neurologic sequelae.
Neuroimaging changes do not always correlate with degree of cognitive dysfunction.
Prospective studies are needed to define the dose/effect relationship of neurotoxic agents.
New deficits may emerge over time.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment- Cancer/Treatment factors: CNS leukemia/lymphoma, relapsed leukemia/lymphoma treated with CNS-directed therapy, longer elapsed time since therapy, higher radiation dose, especially ≥24 Gy or fraction dose ≥3 Gy, larger
radiation field, greater cortical volumes, combination with dexamethasone, methotrexate (IT, IO, high dose IV), cytarabine (high dose IV)

References
Faraci M, Lanino E, Dini G, et al: Severe neurologic complications after hematopoietic stem cell transplantation in children. Neurology 59:1895-904, 2002
Faraci M, Morana G, Bagnasco F, et al: Magnetic resonance imaging in childhood leukemia survivors treated with cranial radiotherapy: a cross sectional, single center study. Pediatr Blood Cancer 57:240-6, 2011
Hertzberg H, Huk WJ, Ueberall MA, et al: CNS late effects after ALL therapy in childhood. Part I: Neuroradiological findings in long-term survivors of childhood ALL--an evaluation of the interferences between morphology andneuropsychological performance. The German Late Effects Working Group. Med Pediatr Oncol 28:387-400, 1997
King TZ, Wang L, Mao H: Disruption of white matter integrity in adult survivors of childhood brain tumors: correlates with long-term intellectual outcomes. PLoS One 10:e0131744, 2015
Kingma A, Mooyaart EL, Kamps WA, et al: Magnetic resonance imaging of the brain and neuropsychological evaluation in children treated for acute lymphoblastic leukemia at a young age. Am J Pediatr Hematol Oncol 15:231-8, 1993
Matsumoto K, Takahashi S, Sato A, et al: Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy--an MR analysis. Int J Radiat Oncol Biol Phys
32:913-8, 1995
Reddick WE, Taghipour DJ, Glass JO, et al: Prognostic factors that increase the risk for reduced white matter volumes and deficits in attention and learning for survivors of childhood cancers. Pediatr Blood Cancer 61:1074-9, 2014

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Sec #
49

w

Therapeutic
Exposure
Head/Brain

Potential
Late Effects
Cerebrovascularcomplications
StrokeMoyamoyaOcclusive cerebral
vasculopathy
Cavernomas

Periodic Evaluation
HISTORY
Hemiparesis
Hemiplegia
Weakness
Aphasia
YearlyPHYSICAL
Neurologic exam
YearlyHealth Counseling/
Further Considerations
COUNSELING
Importance of controlling health conditions known to increase cardiovascularand stroke risk (e.g., hypertension, diabetes, dyslipidemia).
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Brain MRI with DWI with MRA as clinically indicated.
Neurology/Neurosurgery consultation and follow-up.
Physical and occupational therapy as clinically indicated.
Revascularization procedures as indicated for moyamoya.
SYSTEM = CNSSCORE = 1

Additional Information

Moyamoya syndrome is the complete occlusion of ≥1 of the three major cerebral vessels with the development of small, immature collateral vessels, and reflects an attempt to revascularize the ischemic portion of the brain.
Cavernomas are a common late effect of cranial radiation, but the majority of patients with cavernomas are asymptomatic.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Parasellar tumor, radiation dose ≥18 Gy, especially ≥50 Gy, supra-sellar radiation, circle of Willis in radiation field- Pre-morbid/Co-morbid medical conditions: Down syndrome, sickle cell disease, neurofibromatosis

References
Bowers DC, Liu Y, Leisenring W, et al: Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. J Clin Oncol 24:5277-82, 2006
Burn S, Gunny R, Phipps K, et al: Incidence of cavernoma development in children after radiotherapy for brain tumors. J Neurosurg 106:379-83, 2007
Campen CJ, Kranick SM, Kasner SE, et al: Cranial irradiation increases risk of stroke in pediatric brain tumor survivors. Stroke 43:3035-40, 2012
Faraci M, Morana G, Bagnasco F, et al: Magnetic resonance imaging in childhood leukemia survivors treated with cranial radiotherapy: a cross sectional, single center study. Pediatr Blood Cancer 57:240-6, 2011
Haddy N, Mousannif A, Tukenova M, et al: Relationship between the brain radiation dose for the treatment of childhood cancer and the risk of long-term cerebrovascular mortality. Brain 134:1362-72, 2011
Hall MD, Bradley JA, Rotondo RL, et al: Risk of radiation vasculopathy and stroke in pediatric patients treated with proton therapy for brain and skull base tumors. Int J Radiat Oncol Biol Phys 101(4):854-859, 2018
Morris B, Partap S, Yeom K, et al: Cerebrovascular disease in childhood cancer survivors: a Children’s Oncology Group report. Neurology 73:1906-13, 2009
Mueller S, Fullerton HJ, Stratton K, et al: Radiation, atherosclerotic risk factors, and stroke risk in survivors of pediatric cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys 86:649-55, 2013
Passos J, Nzwalo H, Marques J, et al: Late cerebrovascular complications after radiotherapy for childhood primary central nervous system tumors. Pediatr Neurol 53:211-5, 2015
Ullrich NJ, Robertson R, Kinnamon DD, et al: Moyamoya following cranial irradiation for primary brain tumors in children. Neurology 68:932-8, 2007
Wu YH, Chang FC, Liang ML, et al: Incidence and long-term outcome of postradiotherapy moyamoya syndrome in pediatric patients with primary brain tumors: a single institute experience in Taiwan. Cancer Med 5:2155-60, 2016
Yeom KW, Lober RM, Partap S, et al: Increased focal hemosiderin deposition in pediatric medulloblastoma patients receiving radiotherapy at a later age. J Neurosurg Pediatr 12:444-51, 2013

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Sec #
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w

Therapeutic
Exposure
Head/Brain

Potential
Late Effects
Craniofacial abnormalities

Periodic Evaluation

Health Counseling/
Further Considerations

HISTORYRESOURCES
Psychosocial assessment with attention to: FACES—The National Craniofacial Association: www.faces-cranio.org• Educational and/or vocational progress
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION• Depression
Reconstructive craniofacial surgical consultation.
• Anxiety
Consultation with psychologist in patients with adjustment disorders related to• Post-traumatic stressfacial asymmetry/deformity.
• Social withdrawal
YearlySYSTEM = Musculoskeletal
SCORE = 1
PHYSICAL
Craniofacial abnormalities
YearlyAdditional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, especially age <5 years- Cancer/Treatment factors: Higher radiation dose, especially dose ≥30 Gy

References
Frascino AV, Fava M, Collassanti MDS, Odone-Filho V. Impact of Pediatric Hematopoietic Stem-Cell Transplantation on Craniofacial Growth. Clinics 75, 2020
Kaste SC, Chen G, Fontanesi J, et al: Orbital development in long-term survivors of retinoblastoma. J Clin Oncol 15:1183-9, 1997
Kinahan KE, Sharp LK, Seidel K, et al: Scarring, disfigurement, and quality of life in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 30:2466-74, 2012
Mattos VD, Ferman S, Araújo Magalhães DM, et al: Dental and craniofacial alterations in long-term survivors of childhood head and neck rhabdomyosarcoma. Oral Surg Oral Med Oral Pathol Oral Radiol 127(4),272-281, 2019
Schoot RA, Slater O, Ronckers CM, et al: Adverse events of local treatment in long-term head and neck rhabdomyosarcoma survivors after external beam radiotherapy or AMORE treatment. Eur J Cancer 51:1424-34, 2015
Shildkrot Y, Kirzhner M, Haik BG, et al: The effect of cancer therapies on pediatric anophthalmic sockets. Ophthalmology 118:2480-6, 2011

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Sec #
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w

Therapeutic
Exposure
Head/Brain

Potential
Late Effects
Chronic sinusitis

Periodic Evaluation
HISTORY
Rhinorrhea, postnasal discharge
History of URIs
YearlyPHYSICAL
Nasal and sinus exam
YearlyHealth Counseling/
Further Considerations
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
CT scan of sinuses as clinically indicated.
Otolaryngology consultation as clinically indicated.
SYSTEM = Immune
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Radiation dose to sinuses ≥30 Gy, radiomimetic chemotherapy (e.g., doxorubicin, dactinomycin)- Pre-morbid/Co-morbid medical conditions: Atopic history, hypogammaglobulinemia, underlying immunodeficiency

References
Chang CC, Chen MK, Wen YS, et al: Effects of radiotherapy for nasopharyngeal carcinoma on the paranasal sinuses: study based on computed tomography scanning. J Otolaryngol 29:23-7, 2000
Huang WH, Liu CM, Chao TK, et al: Middle meatus bacteriology of acute rhinosinusitis in patients after irradiation of nasopharynx. Am J Rhinol 21:286-8, 2007
Indelicato DJ, Rotondo RL, Mailhot Vega RB, et al: 45 GyRBE for group III orbital embryonal rhabdomyosarcoma. Acta Oncol 58(10):1404-1409, 2019
Lockney NA, Friedman DN, Wexler LH, et al: Late toxicities of intensity-modulated radiation therapy for head and neck rhabdomyosarcoma. Pediatr Blood Cancer 63(9):1608-14, 2016

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POTENTIAL IMPACT TO
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Sec #52

Therapeutic
Exposure
Head/Brain

Potential
Late Effects
Overweight
Obesity

Periodic Evaluation
PHYSICAL
HeightWeight
BMI
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Nutrition and Physical Activity
Cardiovascular Risk Factors
COUNSELING
Obesity-related health risks.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Evaluate for other co-morbid conditions, including dyslipidemia, hypertension,and impaired glucose metabolism.
Refer to dietitian for nutrition education and weight management.
SYSTEM = Endocrine/Metabolic
SCORE = 1w

Additional Information

Definition of Overweight: Age 2-20 years BMI for age ≥85th to <95th percentile. Age ≥21 years BMI ≥25-29.9.
Definition of Obesity: Age 2-20 years BMI for age ≥95th percentile. Age ≥21 years BMI ≥30.
BMI=wt(kg)/ht(m2). BMI calculator available on-line at: www.nhlbi.nih.gov/guidelines/obesity/BMI/bmicalc.htm. Growth charts for patients <21 years of age available on-line at: www.cdc.gov/growthcharts.
Overweight/Obesity may occur in a constellation of conditions known as metabolic syndrome.
Definitions of metabolic syndrome generally include a combination of central (abdominal) obesity with at least 2 or more of the following: elevated blood pressure, atherogenic dyslipidemia (elevated triglycerides, reduced HDLcholesterol), and abnormal glucose metabolism.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, especially age <4 years, female sex- Cancer/Treatment factors: Higher cranial radiation dose (especially ≥18 Gy), surgery in supra-sellar region, corticosteroids (especially prolonged therapy, e.g., for cGVHD)- Pre-morbid/Co-morbid medical conditions: GH deficiency, hypothyroidism, hypogonadism, inability to exercise

References
Alberti KG, Eckel RH, Grundy SM, et al: Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute;
American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640-5, 2009
Brennan BM, Rahim A, Blum WF, et al: Hyperleptinaemia in young adults following cranial irradiation in childhood: growth hormone deficiency or leptin insensitivity? Clin Endocrinol (Oxf) 50:163-9, 1999
Constine LS, Woolf PD, Cann D, et al: Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med 328:87-94, 1993
Cooksey R, Wu SY, Klesse L, et al: Metabolic syndrome is a sequela of radiation exposure in hypothalamic obesity among survivors of childhood brain tumors. J Investig Med 67(2):295-302, 2019
Dalton VK, Rue M, Silverman LB, et al: Height and weight in children treated for acute lymphoblastic leukemia: relationship to CNS treatment. J Clin Oncol 21:2953-60, 2003
Faienza MF, Delvecchio M, Giordano P, et al: Metabolic syndrome in childhood leukemia survivors: a meta-analysis. Endocrine 49:353-60, 2015
Garmey EG, Liu Q, Sklar CA, et al: Longitudinal changes in obesity and body mass index among adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol 26:4639-45,
2008
Howell CR, Wilson CL, Yasui Y,et al: Neighborhood effect and obesity in adult survivors of pediatric cancer: a report from the St. Jude Lifetime Cohort Study. Int J Cancer 147(2):338-49, 2020
Lustig RH, Rose SR, Burghen GA, et al: Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist. J Pediatr 135:162-8, 1999
Meacham LR, Chow EJ, Ness KK, et al: Cardiovascular risk factors in adult survivors of pediatric cancer--a report from the Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 19:170-81, 2010
Nathan PC, Jovcevska V, Ness KK, et al: The prevalence of overweight and obesity in pediatric survivors of cancer. J Pediatr 149:518-25, 2006
Nottage KA, Ness KK, Li C, et al: Metabolic syndrome and cardiovascular risk among long-term survivors of acute lymphoblastic leukaemia - From the St. Jude Lifetime Cohort. Br J Haematol 165:364-74, 2014
Oeffinger KC, Adams-Huet B, Victor RG, et al: Insulin resistance and risk factors for cardiovascular disease in young adult survivors of childhood acute lymphoblastic leukemia. J Clin Oncol 27:3698-704, 2009
Oudin C, Simeoni MC, Sirvent N, et al: Prevalence and risk factors of the metabolic syndrome in adult survivors of childhood leukemia. Blood 117:4442-8, 2011
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Section 52 References (cont)

Razzouk BI, Rose SR, Hongeng S, et al: Obesity in survivors of childhood acute lymphoblastic leukemia and lymphoma. J Clin Oncol 25:1183-9, 2007
Reilly JJ, Ventham JC, Newell J, et al: Risk factors for excess weight gain in children treated for acute lymphoblastic leukaemia. Int J Obes Relat Metab Disord 24:1537-41, 2000
Steffens M, Beauloye V, Brichard B, et al: Endocrine and metabolic disorders in young adult survivors of childhood acute lymphoblastic leukaemia (ALL) or non-Hodgkin lymphoma (NHL). Clin Endocrinol (Oxf) 69:819-27, 2008
Steinberger J, Daniels SR, Eckel RH, et al: Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in the
Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism. Circulation 119:628-47, 2009
Talvensaari KK, Lanning M, Tapanainen P, et al: Long-term survivors of childhood cancer have an increased risk of manifesting the metabolic syndrome. J Clin Endocrinol Metab 81:3051-5, 1996
Warner JT, Evans WD, Webb DK, et al: Body composition of long-term survivors of acute lymphoblastic leukaemia. Med Pediatr Oncol 38:165-72, 2002
Weiss R, Dziura J, Burgert TS, et al: Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 350:2362-74, 2004
Wilson CL, Liu W, Yang JJ, et al: Genetic and clinical factors associated with obesity among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort. Cancer 121:2262-70, 2015
Withycombe JS, Post-White JE, Meza JL, et al: Weight patterns in children with higher risk ALL: A report from the Children’s Oncology Group (COG) for CCG 1961. Pediatr Blood Cancer 53:1249-54, 2009

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POTENTIAL IMPACT TO
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Sec #53

Therapeutic
Exposure
Head/Brain
TBI

Potential
Late Effects
Growth hormone deficiency

Periodic Evaluation
HISTORY
Assessment of nutritional status
Every 6 months until growth is completed,then yearly
PHYSICAL
Tanner staging
Every 6 months until sexually mature
HeightWeightBMI
Every 6 months until growth is completed,then yearly

Health Counseling/
Further Considerations
HEALTH LINKS
Growth Hormone Deficiency
Hypopituitarism
RESOURCES
Magic Foundation for Children’s Growth: www.magicfoundation.org
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Growth velocity can be assessed using dedicated charts or electronic medical
record tools if available.
Consider bone density testing in patients who are GH deficient.
Evaluate thyroid function in any poorly growing child.
Endocrine consultation for:• Dose ≥30 Gy• Poor growth for age or stage of puberty as evidenced by persistent decline
in growth velocity and change in percentile rankings on growth chart, weight<3rd percentile on growth chart• Discuss risks/benefits of adult GH replacement
SYSTEM = Endocrine/Metabolic
SCORE = 1w

Additional Information

Growth charts available on-line at www.cdc.gov/growthcharts/ and www.who.int/tools/child-growth-standards/standards
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment- Cancer/Treatment factors: Surgery in supra-sellar region, higher radiation dose (especially ≥18 Gy), pretransplant radiation (especially CRT), ≥12 Gy fractionated, TBI given in single fraction (especially ≥ 10Gy)

References
Brownstein CM, Mertens AC, Mitby PA, et al: Factors that affect final height and change in height standard deviation scores in survivors of childhood cancer treated with growth hormone: a report from the Childhood Cancer Survivor Study. J Clin
Endocrinol Metab 89:4422-7, 2004
Cattoni A, Clarke E, Albanese A. The predictive value of insulin-like growth factor 1 in irradiation-dependent growth hormone deficiency in childhood cancer survivors. Horm Res Paediatr 90(5):314-325, 2018
Clement SC, Schouten-van Meeteren AY, Boot AM, et al: Prevalence and risk factors of early endocrine disorders in childhood brain tumor survivors: a nationwide, multicenter study. J Clin Oncol 34(36):4362-70, 2016
Frisk P, Arvidson J, Gustafsson J, et al: Pubertal development and final height after autologous bone marrow transplantation for acute lymphoblastic leukemia. Bone Marrow Transplant 33:205-10, 2004
Indelicato DJ, Ioakeim-Ioannidou M, Bradley JA, et al: Proton therapy for pediatric ependymoma: mature results from a bicentric study. Int J Radiat Oncol Biol Phys 1;110(3):815-820, 2021
Merchant TE, Rose SR, Bosley C, et al: Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors. J Clin Oncol 29:4776-80, 2011
Mostoufi-Moab S, Seidel K, Leisenring WM, et al: Endocrine abnormalities in aging survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 20;34(27):3240-7, 2016
Raman S, Grimberg A, Waguespack SG, et al: Risk of neoplasia in pediatric patients receiving growth hormone therapy--a report from the pediatric endocrine society drug and therapeutics committee. J Clin Endocrinol Metab 100:2192-203, 2015
Shalitin S, Gal M, Goshen Y, et al: Endocrine outcome in long-term survivors of childhood brain tumors. Horm Res Paediatr 76:113-22, 2011
Sklar CA, Antal Z, Chemaitilly W, et al: Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 1;103(8):2761-2784, 2018
van Iersel L, Li Z, Srivastava DK, et al: Hypothalamic-pituitary disorders in childhood cancer survivors: prevalence, risk factors and long-term health outcomes. J Clin Endocrinol Metab 1;104(12):6101-6115, 2019van Iersel L, van Santen HM, Potter B, et al: Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma. Pediatr Blood Cancer 67(12):e28723, 2020

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POTENTIAL IMPACT TO
NEUROENDOCRINE AXIS (CONT)RADIATIONSec #54

Therapeutic
Exposure
Head/Brain

Potential
Late Effects
Precocious puberty(male)

Periodic Evaluation
PHYSICAL
HeightWeightTanner staging
Testicular volume by Prader orchidometer
Yearly until sexually mature

Health Counseling/
Further Considerations
HEALTH LINKS
Precocious Puberty
RESOURCES
Magic Foundation for Children’s Growth: www.magicfoundation.org
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
FSH, LH, testosterone, as clinically indicated in patients with signs of accelerated
pubertal progression and growth.
X-ray for bone age in rapidly growing children.
Growth velocity can be assessed using dedicated charts or electronic medical
record tools if available.
Endocrine consultation for suspected precocious puberty (males <9 years).
SYSTEM = Endocrine/Metabolic
SCORE = 1w

Additional Information

Testicular volume is not a reliable indicator of pubertal onset/stage in boys treated with alkylating agents and/or direct testicular radiotherapy.
Affected children may present with accelerated linear growth but this could mask co-existing GH deficiency.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment- Cancer/Treatment factors: Tumor near hypothalamus and/or optic pathways, radiation doses ≥18 Gy- Pre-morbid/Co-morbid medical conditions: History of hydrocephalus

References
Chemaitilly W, Merchant TE, Li Z, et al: Central precocious puberty following the diagnosis and treatment of paediatric cancer and central nervous system tumours: presentation and long-term outcomes. Clin Endocrinol (Oxf) 84:36171, 2016
Clement SC, Schouten-van Meeteren AY, Boot AM, et al: Prevalence and risk factors of early endocrine disorders in childhood brain tumor survivors: a nationwide, multicenter study. J Clin Oncol 34(36):4362-70, 2016
Darzy KH: Radiation-induced hypopituitarism after cancer therapy: who, how and when to test. Nat Clin Pract Endocrinol Metab 5:88-99, 2009
Gan HW, Phipps K, Aquilina K, et al: Neuroendocrine morbidity after pediatric optic gliomas: a longitudinal analysis of 166 children over 30 years. J Clin Endocrinol Metab 100:3787-99, 2015
Oberfield SE, Soranno D, Nirenberg A, et al: Age at onset of puberty following high dose central nervous system radiation therapy. Arch Pediatr Adolesc Med 150:589-92, 1996
Ogilvy-Stuart AL, Clayton PE, Shalet SM: Cranial irradiation and early puberty. J Clin Endocrinol Metab 78:1282-6, 1994
Quigley C, Cowell C, Jimenez M, et al: Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia. N Engl J Med 321:143-51, 1989
Sklar CA, Antal Z, Chemaitilly W, et al: Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 1;103(8):2761-2784, 2018
Sklar CA, Constine LS: Chronic neuroendocrinological sequelae of radiation therapy. Int J Radiat Oncol Biol Phys 31:1113-21, 1995
van Iersel L, Li Z, Srivastava DK, et al: Hypothalamic-pituitary disorders in childhood cancer survivors: prevalence, risk factors and long-term health outcomes. J Clin Endocrinol Metab 1;104(12):6101-6115, 2019van Iersel L, van Santen HM, Potter B, et al: Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma. Pediatr Blood Cancer 67(12):e28723, 2020

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POTENTIAL IMPACT TO
NEUROENDOCRINE AXIS (CONT)RADIATION
Sec #55

Therapeutic
Exposure
Head/Brain

Potential
Late Effects
Precocious puberty(female)Periodic Evaluation
PHYSICAL
HeightWeightTanner staging
Yearly until sexually mature

Health Counseling/
Further Considerations
HEALTH LINKS
Precocious Puberty
RESOURCES
Magic Foundation for Children’s Growth: www.magicfoundation.org
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
FSH, LH, estradiol, as clinically indicated in patients with signs of accelerated
pubertal progression and growth.
X-ray for bone age in rapidly growing children.
Growth velocity can be assessed using dedicated charts or electronic medical
record tools if available.
Endocrine consultation for suspected precocious puberty (females <8 years).
SYSTEM = Endocrine/Metabolic
SCORE = 1w

Additional Information

Affected children may present with accelerated linear growth but this could mask co-existing GH deficiency.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment- Cancer/Treatment factors: Tumor near hypothalamus and/or optic pathways, radiation doses ≥18 Gy- Pre-morbid/Co-morbid medical conditions: History of hydrocephalus

References
Armstrong GT, Whitton JA, Gajjar A, et al: Abnormal timing of menarche in survivors of central nervous system tumors: a report from the Childhood Cancer Survivor Study. Cancer 115:2562-70, 2009
Chemaitilly W, Merchant TE, Li Z, et al: Central precocious puberty following the diagnosis and treatment of paediatric cancer and central nervous system tumours: presentation and long-term outcomes. Clin Endocrinol (Oxf) 84:36171, 2016
Clement SC, Schouten-van Meeteren AY, Boot AM, et al: Prevalence and risk factors of early endocrine disorders in childhood brain tumor survivors: a nationwide, multicenter study. J Clin Oncol 34(36):4362-70, 2016
Darzy KH: Radiation-induced hypopituitarism after cancer therapy: who, how and when to test. Nat Clin Pract Endocrinol Metab 5:88-99, 2009
Gan HW, Phipps K, Aquilina K, et al: Neuroendocrine morbidity after pediatric optic gliomas: a longitudinal analysis of 166 children over 30 years. J Clin Endocrinol Metab 100:3787-99, 2015
Oberfield SE, Soranno D, Nirenberg A, et al: Age at onset of puberty following high dose central nervous system radiation therapy. Arch Pediatr Adolesc Med 150:589-92, 1996
Ogilvy-Stuart AL, Clayton PE, Shalet SM: Cranial irradiation and early puberty. J Clin Endocrinol Metab 78:1282-6, 1994
Quigley C, Cowell C, Jimenez M, et al: Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia. N Engl J Med 321:143-51, 1989
Sklar CA, Antal Z, Chemaitilly W, et al: Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 1;103(8):2761-2784, 2018
Sklar CA, Constine LS: Chronic neuroendocrinological sequelae of radiation therapy. Int J Radiat Oncol Biol Phys 31:1113-21, 1995
van Iersel L, Li Z, Srivastava DK, et al: Hypothalamic-pituitary disorders in childhood cancer survivors: prevalence, risk factors and long-term health outcomes. J Clin Endocrinol Metab 1;104(12):6101-6115, 2019van Iersel L, van Santen HM, Potter B, et al: Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma. Pediatr Blood Cancer 67(12):e28723, 2020

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POTENTIAL IMPACT TO
NEUROENDOCRINE AXIS (CONT)RADIATION
Sec #56

Therapeutic
Exposure
Head/Brain

Potential
Late Effects
Hyperprolactinemia

Periodic Evaluation
HISTORY
Decreased libido
Galactorrhea
Menstrual history
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Hyperprolactinemia
RESOURCES
Magic Foundation for Children’s Growth: www.magicfoundation.org
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Prolactin level in patients with galactorrhea or decreased libido, or in femaleswith amenorrhea.
CT evaluation of sella turcica for pituitary adenoma in patients withhyperprolactinemia.
Endocrine consultation for patients with hyperprolactinemia or galactorrhea.
SYSTEM = Endocrine/Metabolic
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher radiation dose (≥40 Gy, especially ≥50 Gy), surgery or tumor in hypothalamic area

References
Constine LS, Woolf PD, Cann D, et al: Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med 328:87-94, 1993
Sklar CA, Constine LS: Chronic neuroendocrinological sequelae of radiation therapy. Int J Radiat Oncol Biol Phys 31:1113-21, 1995

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Sec #
57

w

Therapeutic
Exposure
Head/Brain

Potential
Late Effects
Central hypothyroidism

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Fatigue
Weight gain
Cold intolerance
Constipation
Dry skinBrittle hair
Depressed moodYearly, consider more frequent screening
during periods of rapid growth
PHYSICAL
HeightWeightHair
Skin
Thyroid exam
Yearly, consider more frequent screening
during periods of rapid growth
SCREENING
TSHFree T4
Yearly, consider more frequent screening
during periods of rapid growth

HEALTH LINKS
Thyroid Problems
Hypopituitarism
COUNSELINGFor females, thyroid levels prior to attempting pregnancy and periodicallythroughout pregnancy.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
If dose ≥30 Gy refer to endocrinologist for ongoing management, given risk ofmultiple hormone deficiencies. If endocrinology care is not readily available,
screen as indicated, and refer to endocrinologist for thyroid hormone
replacement.
SYSTEM = Endocrine/Metabolic
SCORE = 1

Additional Information

Central hypothyroidism includes thyroid-releasing and TSH deficiency.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher radiation dose, especially ≥30 Gy, may occur at lower doses with longer follow-up, surgery or tumor in supra-sellar area.

References
Aldrich KD, Horne VE, Bielamowicz K, et al: Comparison of hypothyroidism, growth hormone deficiency, and adrenal insufficiency following proton and photon radiotherapy in children with medulloblastoma. J Neurooncol 155(1):93100, 2021
Huang S, Wang X, Hu C, et al: Hypothalamic-pituitary-thyroid dysfunction induced by intensity-modulated radiotherapy (IMRT) for adult patients with nasopharyngeal carcinoma. Med Oncol 30:710, 2013
Inskip PD, Veiga LHS, Brenner AV, et al: Hypothyroidism after radiation therapy for childhood cancer: a report from the Childhood Cancer Survivor Study. Radiat Res 190(2):117-132, 2018
Lando A, Holm K, Nysom K, et al: Thyroid function in survivors of childhood acute lymphoblastic leukaemia: the significance of prophylactic cranial irradiation. Clin Endocrinol (Oxf) 55:21-5, 2001
Sklar CA, Antal Z, Chemaitilly W, et al: Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 1;103(8):2761-2784, 2018
Sklar CA, Constine LS: Chronic neuroendocrinological sequelae of radiation therapy. Int J Radiat Oncol Biol Phys 31:1113-21, 1995
van Iersel L, Li Z, Srivastava DK, et al: Hypothalamic-pituitary disorders in childhood cancer survivors: prevalence, risk factors and long-term health outcomes. J Clin Endocrinol Metab 1;104(12):6101-6115, 2019van Iersel L, van Santen HM, Potter B, et al: Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma. Pediatr Blood Cancer 67(12):e28723, 2020
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POTENTIAL IMPACT TO
NEUROENDOCRINE AXIS (CONT)RADIATION
Sec #58(male)

Therapeutic
Exposure
Head/Brain
TBI

Potential
Late Effects
Gonadotropin deficiency
LH and FSH deficiency

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Onset and tempo of puberty
Sexual function (erections, nocturnal
emissions, libido)
Medication use
YearlyPHYSICAL
Tanner staging until sexually mature
Testicular volume by Prader orchidometer
YearlyMonitor growth until mature
YearlyHEALTH LINKS
Testicular and Reproductive HealthHypopituitarism
RESOURCES
American Society for Reproductive Medicine: www.asrm.org
Alliance for Fertility Preservation: www.allianceforfertilitypreservation.org
COUNSELING
Need for contraception.
Spermatogenesis can be induced with gonadotropins in men withhypogonadotropic hypogonadism.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
FSH, LH, testosterone as clinically indicated in patients with delayed/arrested
puberty and/or clinical signs and symptoms of testosterone deficiency.
If dose ≥30 Gy refer to endocrinologist for ongoing management, given risk ofmultiple hormone deficiencies. If endocrinology care is not readily available,
screen as indicated, and refer to endocrinologist for thyroid hormone
replacement.
Hormonal replacement therapy for hypogonadal patients.
Refer to reproductive endocrinology as clinically indicated for infertility
evaluation and consultation regarding assisted reproductive technologies.
BMD testing in patients who are gonadotropin deficient.
SYSTEM = Reproductive (Male)SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher radiation dose, especially ≥30 Gy, may occur at lower doses with longer follow-up, surgery or tumor in supra-sellar area

References
Darzy KH: Radiation-induced hypopituitarism after cancer therapy: who, how and when to test. Nat Clin Pract Endocrinol Metab 5:88-99, 2009
Gleeson HK, Shalet SM: The impact of cancer therapy on the endocrine system in survivors of childhood brain tumours. Endocr Relat Cancer 11:589-602, 2004
Kenney LB, Cohen LE, Shnorhavorian M, et al: Male reproductive health after childhood, adolescent, and young adult cancers: a report from the Children’s Oncology Group. J Clin Oncol 30:3408-16, 2012
Schmiegelow M, Lassen S, Poulsen HS, et al: Gonadal status in male survivors following childhood brain tumors. J Clin Endocrinol Metab 86:2446-52, 2001
Sklar CA, Antal Z, Chemaitilly W, et al: Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 1;103(8):2761-2784, 2018
van Iersel L, Li Z, Srivastava DK, et al: Hypothalamic-pituitary disorders in childhood cancer survivors: prevalence, risk factors and long-term health outcomes. J Clin Endocrinol Metab 1;104(12):6101-6115, 2019van Iersel L, van Santen HM, Potter B, et al: Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma. Pediatr Blood Cancer 67(12):e28723, 2020

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POTENTIAL IMPACT TO
NEUROENDOCRINE AXIS (CONT)RADIATION
Sec #59(female)Therapeutic
Exposure
Head/Brain
TBI

Potential
Late Effects
Gonadotropin deficiency
LH and FSH deficiency

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Onset and tempo of puberty
Menstrual history
Sexual function (vaginal dryness, libido)
Medication use
YearlyPHYSICAL
Tanner staging until sexually mature
YearlyMonitor growth until mature
YearlyHEALTH LINKS
Ovarian and Reproductive HealthHypopituitarism
RESOURCES
American Society for Reproductive Medicine: www.asrm.org
Alliance for Fertility Preservation: www.allianceforfertilitypreservation.org
COUNSELING
Need for contraception.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
FSH, LH, estradiol as clinically indicated in patients with delayed or arrested
puberty, irregular menses, primary or secondary amenorrhea, or clinical signs
and symptoms of estrogen deficiency.
If dose ≥30 Gy refer to endocrinologist for ongoing management, given risk ofmultiple hormone deficiencies. If endocrinology care is not readily available,
screen as indicated, and refer to endocrinologist for thyroid hormone
replacement.
Hormonal replacement therapy for hypogonadal patients.
Refer to reproductive endocrinology as clinically indicated for infertility
evaluation and consultation regarding assisted reproductive technologies.
BMD testing in patients who are gonadotropin deficient.
SYSTEM = Reproductive (Female)
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher radiation dose, especially ≥30 Gy, may occur at lower doses with longer follow-up, surgery or tumor in supra-sellar area

References
Chemaitilly W, Li Z, Huang S, et al: Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude Lifetime Cohort Study. J Clin Oncol 33:492-500, 2015
Chow EJ, Friedman DL, Yasui Y, et al: Timing of menarche among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 50:854-8, 2008
Darzy KH: Radiation-induced hypopituitarism after cancer therapy: who, how and when to test. Nat Clin Pract Endocrinol Metab 5:88-99, 2009
Gleeson HK, Shalet SM: The impact of cancer therapy on the endocrine system in survivors of childhood brain tumours. Endocr Relat Cancer 11:589-602, 2004
Green DM, Kawashima T, Stovall M, et al: Fertility of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 27:2677-2685, 2009
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol 31:1239-47, 2013
Mills JL, Fears TR, Robison LL, et al: Menarche in a cohort of 188 long-term survivors of acute lymphoblastic leukemia. J Pediatr 131:598-602, 1997
Sklar CA, Antal Z, Chemaitilly W, et al: Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 1;103(8):2761-2784, 2018
van Iersel L, Li Z, Srivastava DK, et al: Hypothalamic-pituitary disorders in childhood cancer survivors: prevalence, risk factors and long-term health outcomes. J Clin Endocrinol Metab 1;104(12):6101-6115, 2019van Iersel L, van Santen HM, Potter B, et al: Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma. Pediatr Blood Cancer 67(12):e28723, 2020
Wo JY, Viswanathan AN: Impact of radiotherapy on fertility, pregnancy, and neonatal outcomes in female cancer patients. Int J Radiat Oncol Biol Phys 73:1304-12, 2009
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POTENTIAL IMPACT TO
NEUROENDOCRINE AXIS (CONT)RADIATION
Sec #60

Therapeutic
Exposure

Potential
Late Effects

Head/Brain
TBI(TBI is included for
cumulative dose
calculation purposes
only; this section is notapplicable to patients
who received TBI alone.)

Central adrenal insufficiency

Periodic Evaluation

Health Counseling/
Further Considerations

HISTORY
If dose ≥30 Gy:
Failure to thrive
Anorexia
Dehydration
Hypoglycemia
Lethargy
Unexplained hypotension
YearlySCREENING
If dose ≥30 Gy:
8 AM cortisol
Yearly, refer to endocrinology for further
testing if level <13 mcg/dL or <365 nmol/L

HEALTH LINKS
Central Adrenal Insufficiency
Hypopituitarism
RESOURCES
Magic Foundation for Children’s Growth: www.magicfoundation.org
COUNSELING
Need for corticosteroid replacement therapy and stress dosing.
Obtain medical alert bracelet or card.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
If dose ≥30 Gy refer to endocrinologist for ongoing management, given risk ofmultiple hormone deficiencies. If endocrinology care is not readily available,
screen as indicated, and refer to endocrinologist for thyroid hormone
replacement.
SYSTEM = Endocrine/Metabolic
SCORE = 1w

Additional Information

Cortisol secretion follows a circadian rhythm. Levels should be drawn as close as possible to 8AM and before 9 AM.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher radiation dose, especially ≥30 Gy, may occur at lower doses with longer follow-up, surgery or tumor in supra-sellar area
- Pre-morbid/Co-morbid medical conditions: History of another hypothalamic-pituitary endocrinopathy

References
Aldrich KD, Horne VE, Bielamowicz K, et al: Comparison of hypothyroidism, growth hormone deficiency, and adrenal insufficiency following proton and photon radiotherapy in children with medulloblastoma. J Neurooncol 155(1):93100, 2021
Clement SC, Schouten-van Meeteren AY, Boot AM, et al: Prevalence and risk factors of early endocrine disorders in childhood brain tumor survivors: a nationwide, multicenter study. J Clin Oncol 34(36):4362-70, 2016
Darzy KH: Radiation-induced hypopituitarism after cancer therapy: who, how and when to test. Nat Clin Pract Endocrinol Metab 5:88-99, 2009
Follin C, Wiebe T, Moell C, et al: Moderate dose cranial radiotherapy causes central adrenal insufficiency in long-term survivors of childhood leukaemia. Pituitary 17:7-12, 2014
Gleeson HK, Shalet SM: The impact of cancer therapy on the endocrine system in survivors of childhood brain tumours. Endocr Relat Cancer 11:589-602, 2004
Kazlauskaite R, Evans AT, Villabona CV, et al: Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 93:4245-53, 2008
Patterson BC, Truxillo L, Wasilewski-Masker K, et al: Adrenal function testing in pediatric cancer survivors. Pediatr Blood Cancer 53:1302-7, 2009
Sklar CA, Antal Z, Chemaitilly W, et al: Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 1;103(8):2761-2784, 2018
Sklar CA, Constine LS: Chronic neuroendocrinological sequelae of radiation therapy. Int J Radiat Oncol Biol Phys 31:1113-21, 1995
van Iersel L, van Santen HM, Potter B, et al: Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma. Pediatr Blood Cancer 67(12):e28723, 2020

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POTENTIAL IMPACT TO
EYE

RADIATION
Sec #
61

w

Therapeutic
Exposure
Head/Brain
TBI

Potential
Late Effects
Cataracts

Periodic Evaluation
HISTORY
Visual changes (decreased acuity, halos,
diplopia)
YearlyPHYSICAL
Visual acuity
Funduscopic exam
YearlySCREENING
Evaluation by ophthalmologist or
optometrist
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Cataracts
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Refer patients with visual deficits to school liaison in community or cancer
center (psychologist, social worker, school counselor) to facilitate acquisition of
educational resources.
SYSTEM = Ocular
SCORE = 1

Additional Information

Radiation-related ocular complications other than cataracts are generally associated only with orbital/eye radiation or higher dose CRT.
Patients with a history of an ocular tumor (e.g., retinoblastoma) are at higher risk for late-onset ocular complications and should receive ongoing follow-up by an ophthalmologist at least annually, and more frequently if clinicallyindicated.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Radiation dose ≥10 Gy, especially ≥15 Gy, radiation fraction dose ≥2 Gy, TBI dose ≥2 Gy in single fraction, TBI dose ≥5 Gy fractionated, especially ≥10 Gy, cranial/orbital/eye radiation combined with
TBI, radiation combined with corticosteroids or busulfan, longer interval since treatment

References
Allodji RS, Diallo I, El-Fayech C, et al: Association of radiation dose to the eyes with the risk for cataract after nonretinoblastoma solid cancers in childhood. JAMA Ophthalmol 134(4):390-7, 2016
Chodick G, Sigurdson AJ, Kleinerman RA, et al: The risk of cataract among survivors of childhood and adolescent cancer: a report from the Childhood Cancer Survivor Study. Radiat Res 185:366-74, 2016
Fahnehjelm KT, Tornquist AL, Olsson M, et al: Visual outcome and cataract development after allogeneic stem-cell transplantation in children. Acta Ophthalmol Scand 85:724-33, 2007
Ferry C, Gemayel G, Rocha V, et al: Long-term outcomes after allogeneic stem cell transplantation for children with hematological malignancies. Bone Marrow Transplant 40:219-24, 2007
Gurney JG, Ness KK, Rosenthal J, et al: Visual, auditory, sensory, and motor impairments in long-term survivors of hematopoietic stem cell transplantation performed in childhood: results from the Bone Marrow Transplant Survivor
study. Cancer 106:1402-8, 2006
Horwitz M, Auquier P, Barlogis V, et al: Incidence and risk factors for cataract after haematopoietic stem cell transplantation for childhood leukaemia: an LEA study. Br J Haematol 168:518-25, 2015
Socie G, Salooja N, Cohen A, et al: Nonmalignant late effects after allogeneic stem cell transplantation. Blood 101:3373-85, 2003
van Kempen-Harteveld ML, Belkacemi Y, Kal HB, et al: Dose-effect relationship for cataract induction after single-dose total body irradiation and bone marrow transplantation for acute leukemia. Int J Radiat Oncol Biol Phys 52:136774, 2002
van Kempen-Harteveld ML, Struikmans H, Kal HB, et al: Cataract after total body irradiation and bone marrow transplantation: degree of visual impairment. Int J Radiat Oncol Biol Phys 52:1375-80, 2002
Zierhut D, Lohr F, Schraube P, et al: Cataract incidence after total-body irradiation. Int J Radiat Oncol Biol Phys 46:131-5, 2000

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POTENTIAL IMPACT TO
EYE (CONT)RADIATION
Sec #
62

w

Therapeutic
Exposure
Head/Brain

Potential
Late Effects
Ocular toxicity
Orbital hypoplasia
Lacrimal duct atrophy
Xerophthalmia(keratoconjunctivitis sicca)
Keratitis
Telangiectasias
Retinopathy
Optic chiasm neuropathy
Enophthalmos
Chronic painful eye
Maculopathy
Papillopathy
Glaucoma

Periodic Evaluation
HISTORY
Visual changes (decreased acuity, halos,
diplopia)
Dry eye
Persistent eye irritation
Excessive tearing
Light sensitivity
Poor night vision
Painful eye
YearlyPHYSICAL
Visual acuity
Funduscopic exam
YearlySCREENING
Evaluation by ophthalmologist or
optometrist
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Eye HealthRESOURCESFACES—The National Craniofacial Association: www.faces-cranio.org
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Refer patients with visual deficits to school liaison in community or cancer
center (psychologist, social worker, school counselor) to facilitate acquisition of
educational resources.
SYSTEM = Ocular
SCORE = 1

Additional Information

Radiation-related ocular complications other than cataracts are generally associated only with orbital/eye radiation or higher dose CRT.
Patients with a history of an ocular tumor (e.g., retinoblastoma) are at higher risk for late-onset ocular complications and should receive ongoing opthalmology follow-up at least annually, and more frequently if clinically indicated.
Reduced visual acuity may be associated with cataracts, retinal damage, and optic nerve damage.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher radiation dose, especially ≥30 Gy, higher daily fraction dose, especially fraction dose ≥2 Gy, radiomimetic chemotherapy (e.g., doxorubicin, dactinomycin), problems related to tearing- Pre-morbid/Co-morbid medical conditions: cGVHD (xerophthalmia only)

References
Albrecht F, Wolters H, Ziert Y, et al: Evaluation of treatment-associated eye toxicity after irradiation in childhood and adolescence-results from the Registry of the Evaluation of Side Effects after Radiotherapy in Childhood and Adolescence (RiSK). Strahlenther Onkol 197(8):700-710, 2021
Jeganathan VS, Wirth A, MacManus MP: Ocular risks from orbital and periorbital radiation therapy: a critical review. Int J Radiat Oncol Biol Phys 79:650-9, 2011
Mayo C, Martel MK, Marks LB, et al: Radiation dose-volume effects of optic nerves and chiasm. Int J Radiat Oncol Biol Phys 76:S28-35, 2010
Oberlin O, Rey A, Anderson J, et al: Treatment of orbital rhabdomyosarcoma: survival and late effects of treatment--results of an international workshop. J Clin Oncol 19:197-204, 2001
Shields CL, Shields JA, Cater J, et al: Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors. Ophthalmology 108:2116-21, 2001
Tinkle CL, Pappo A, Wu J, et al: Efficacy and safety of limited-margin conformal radiation therapy for pediatric rhabdomyosarcoma: long-term results of a phase 2 study. Int J Radiat Oncol Biol Phys 107(1):172-180, 2020
Whelan KF, Stratton K, Kawashima T, et al: Ocular late effects in childhood and adolescent cancer survivors: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 54:103-9, 2010

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POTENTIAL IMPACT TO
EARRADIATION
Sec #63

Therapeutic
Exposure

Potential
Late Effects

Head/Brain
TBI(TBI is included for
cumulative dose
calculation purposes
only; this section is notapplicable to patients
who received TBI alone.)

Ototoxicity
Tympanosclerosis
Otosclerosis
Eustachian tube dysfunction
Conductive hearing loss
Sensorineural hearing loss
Tinnitus
Vertigo

Periodic Evaluation
HISTORY
If dose ≥30 Gy:
Hearing difficulties (with/withoutbackground noise)
Tinnitus
VertigoYearlyPHYSICAL
If dose ≥30 Gy:
Otoscopic exam
YearlySCREENING
If dose ≥30 Gy:
Complete audiological evaluation byaudiologist
Yearly, for patients ages ≤5 years
Pure tone audiometry testing at 1000-8000
Hz
Every 2 years, for patients ages 6-12, thenevery 5 years beginning at age 13 years

w

Health Counseling/
Further Considerations
HEALTH LINKS
Hearing Loss
School After Treatment
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Additional testing with high frequency audiometry at >8000 Hz is recommended
if equipment is available.
Audiology consultation for any survivor who has symptoms suggestive of
hearing loss, tinnitus, or abnormal pure tone audiometry results showing a lossof more than 15 dB absolute threshold level (1000-8000 Hz).
Ongoing follow-up with audiology for patients with hearing loss.
Otolaryngology consultation in patients with chronic infection, cerumen
impaction, or other anatomical problems exacerbating or contributing tohearing loss.
Speech and language therapy for patients with hearing loss.
Refer patients with auditory deficits to school liaison in community or cancer
center (psychologist, social worker, school counselor) to facilitate acquisition of
educational resources.
Specialized evaluation for specific needs and/or preferential classroom seating,
FM amplification system, and other educational assistance as indicated.
SYSTEM = Auditory
SCORE = 1

Additional Information

A “complete audiological evaluation” includes pure tone air and bone conduction, speech audiometry, and tympanometry for both ears.
Frequency-specific auditory brainstem response can be performed if the above is inconclusive.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment- Cancer/Treatment factors: All hearing loss types: higher radiation dose; sensorineural hearing loss/tinnitus: CNS neoplasm, conventional (non-conformal) radiation, combination with other ototoxic agents (cisplatin, carboplatin, aminoglycosides, loop diuretics), radiation administered prior to platinum chemotherapy- Pre-morbid/Co-morbid medical conditions: All hearing loss types: chronic otitis, chronic cerumen impaction; sensorineural hearing loss/tinnitus: cerebrospinal fluid shunt

References
Bass JK, Hua CH, Huang J, et al: Hearing loss in patients who received cranial radiation therapy for childhood cancer. J Clin Oncol 34:1248-55, 2016
Bass JK, Knight KR, Yock TI, et al: Evaluation and management of hearing loss in survivors of childhood and adolescent cancers: a report from the Children’s Oncology Group. Pediatr Blood Cancer 63:1152-62, 2016
Hua C, Bass JK, Khan R, et al: Hearing loss after radiotherapy for pediatric brain tumors: effect of cochlear dose. Int J Radiat Oncol Biol Phys 72:892-9, 2008
Huang E, Teh BS, Strother DR, et al: Intensity-modulated radiation therapy for pediatric medulloblastoma: early report on the reduction of ototoxicity. Int J Radiat Oncol Biol Phys 52:599-605, 2002
Khan A, Budnick A, Barnea D, et al: Hearing loss in adult survivors of childhood cancer treated with radiotherapy. Children 5(5):59, 2018
Low WK, Toh ST, Wee J, et al: Sensorineural hearing loss after radiotherapy and chemoradiotherapy: a single, blinded, randomized study. J Clin Oncol 24:1904-9, 2006
Meijer AJM, Clemens E, Hoetink AE, et al: Tinnitus during and after childhood cancer: a systematic review. Crit Rev Oncol Hematol 135:1-7, 2019
Merchant TE, Gould CJ, Xiong X, et al: Early neuro-otologic effects of three-dimensional irradiation in children with primary brain tumors. Int J Radiat Oncol Biol Phys 58:1194-207, 2004
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POTENTIAL IMPACT TO
ORAL CAVITY

RADIATION
Sec #
64

w

Therapeutic
Exposure

Potential
Late Effects

Head/Brain
Neck
Spine (cervical, whole)
TBI

Xerostomia
Salivary gland dysfunction

Periodic Evaluation
HISTORY
Xerostomia (dry mouth)YearlyPHYSICAL
Oral exam
YearlySCREENING
Dental exam and cleaning
Every 6 months

Health Counseling/
Further Considerations
HEALTH LINKS
Dental Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Supportive care with saliva substitutes, moistening agents, and sialagogues(e.g., pilocarpine).
Regular dental care including fluoride applications.
SYSTEM = Dental
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Head and neck radiation involving the parotid gland, higher proportion of one gland or both salivary glands in the radiation field, higher radiation doses, radiomimetic chemotherapy (e.g.,doxorubicin, dactinomycin)- Pre-morbid/Co-morbid medical conditions: cGVHD

References
Bolling T, Weege J, Eich HT, et al: Acute and late side effects to salivary glands and oral mucosa after head and neck radiotherapy in children and adolescents. Results of the “Registry for the evaluation of side effects after radiotherapy in childhood and adolescence.” Head Neck 37:1137-41, 2015
Dahllof G, Bagesund M, Remberger M, et al: Risk factors for salivary dysfunction in children 1 year after bone marrow transplantation. Oral Oncol 33:327-31, 1997
Dahllof G, Bagesund M, Ringden O: Impact of conditioning regimens on salivary function, caries-associated microorganisms and dental caries in children after bone marrow transplantation. A 4-year longitudinal study. Bone Marrow
Transplant 20:479-83, 1997
Effinger KE, Migliorati CA, Hudson MM, et al: Oral and dental late effects in survivors of childhood cancer: a Children’s Oncology Group report. Support Care Cancer 22:2009-19, 2014
Jensen SB, Pedersen AM, Vissink A, et al: A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact. Support Care Cancer 18:1061-79, 2010
Jensen SB, Pedersen AM, Vissink A, et al: A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life. Support Care Cancer 18:1039-60, 2010
Kaste SC, Goodman P, Leisenring W, et al: Impact of radiation and chemotherapy on risk of dental abnormalities: a report from the Childhood Cancer Survivor Study. Cancer 115:5817-27, 2009
Milgrom SA, van Luijk P, Pino R, et al: Salivary and dental complications in childhood cancer survivors treated with radiation therapy to the head and neck: a Pediatric Normal Tissue Effects in the Clinic (PENTEC) comprehensive
review. Int J Radiat Oncol Biol Phys S0360-3016(21)00443, 2021
Qiu WZ, Peng XS, Xia HQ, et al: A retrospective study comparing the outcomes and toxicities of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy for the treatment of children and adolescentnasopharyngeal carcinoma, J Cancer Res Clin Oncol 143(8):1563-1572, 2017

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POTENTIAL IMPACT TO
ORAL CAVITY (CONT)RADIATION
Sec #
65

w

Therapeutic
Exposure
Head/Brain
Neck
Spine (cervical, whole)
TBI

Potential
Late Effects
Dental abnormalities
Tooth/root agenesis
Root thinning/shortening
Enamel dysplasia
Microdontia
Ectopic molar eruption
Dental caries
Periodontal disease
Malocclusion
Temporomandibular joint
dysfunction

Periodic Evaluation
PHYSICAL
Oral exam
YearlySCREENING
Dental exam and cleaning
Every 6 months

Health Counseling/
Further Considerations
HEALTH LINKS
Dental Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Regular dental care including fluoride applications.
Baseline panorex prior to dental procedures to evaluate root development.
Consultation with orthodontist experienced in management of irradiatedchildhood cancer survivors.
SYSTEM = Dental
SCORE
Ectopic Molar Eruption = 2A
All Else = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, especially age <5 years, Gorlin syndrome (nevoid basal cell carcinoma syndrome)- Cancer/Treatment factors: Higher radiation dose (especially ≥10 Gy)

References
Dahllof G, Jonsson A, Ulmner M, et al: Orthodontic treatment in long-term survivors after pediatric bone marrow transplantation. Am J Orthod Dentofacial Orthop 120:459-65, 2001
Effinger KE, Migliorati CA, Hudson MM, et al: Oral and dental late effects in survivors of childhood cancer: a Children’s Oncology Group report. Support Care Cancer 22:2009-19, 2014
Goho C: Chemoradiation therapy: effect on dental development. Pediatr Dent 15:6-12, 1993
Kaste SC, Goodman P, Leisenring W, et al: Impact of radiation and chemotherapy on risk of dental abnormalities: a report from the Childhood Cancer Survivor Study. Cancer 115:5817-27, 2009
Ko Y, Park K, Kim JY: Effect of anticancer therapy on ectopic eruption of permanent first molars. Pediatr Dent 35:530-3, 2013
Krasin MJ, Wiese KM, Spunt SL, et al: Jaw dysfunction related to pterygoid and masseter muscle dosimetry after radiation therapy in children and young adults with head-and-neck sarcomas. Int J Radiat Oncol Biol Phys 82:355-60,
2012
Milgrom SA, van Luijk P, Pino R, et al: Salivary and dental complications in childhood cancer survivors treated with radiation therapy to the head and neck: a Pediatric Normal Tissue Effects in the Clinic (PENTEC) comprehensive
review. Int J Radiat Oncol Biol Phys S0360-3016(21)00443, 2021
Qiu WZ, Peng XS, Xia HQ, et al: A retrospective study comparing the outcomes and toxicities of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy for the treatment of children and adolescentnasopharyngeal carcinoma, J Cancer Res Clin Oncol 143(8):1563-1572, 2017
Sonis AL, Tarbell N, Valachovic RW, et al: Dentofacial development in long-term survivors of acute lymphoblastic leukemia. A comparison of three treatment modalities. Cancer 66:2645-52, 1990

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POTENTIAL IMPACT TO
ORAL CAVITY (CONT)RADIATION
Sec #
66

w

Therapeutic
Exposure
Head/Brain
Neck
Spine (cervical, whole)
TBI(TBI is included for
cumulative dose
calculation purposes
only; this section is notapplicable to patients
who received TBI alone.)

Potential
Late Effects
Osteoradionecrosis of thejaw

Periodic Evaluation
HISTORY
If dose ≥40 Gy:
Impaired or delayed healing following
dental work
Persistent jaw pain or swelling
TrismusYearlyPHYSICAL
If dose ≥40 Gy:
Impaired wound healing
Jaw swelling
TrismusAs clinically indicatedHealth Counseling/
Further Considerations
HEALTH LINKS
Osteoradionecrosis
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Imaging studies (x-ray, CT scan and/or MRI) may assist in making diagnosis.
Biopsy may be needed to confirm diagnosis.
Hyperbaric oxygen treatments pre- or post-mandibular surgery to facilitate
healing.
SYSTEM = Dental
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Radiation dose ≥40 Gy (especially ≥50 Gy)

References
Ashamalla HL, Ames JW, Uri A, et al: Hyperbaric oxygen in the management of osteoradionecrosis. Med Pediatr Oncol 27:48-53, 1996
Effinger KE, Migliorati CA, Hudson MM, et al: Oral and dental late effects in survivors of childhood cancer: a Children’s Oncology Group report. Support Care Cancer 22:2009-19, 2014
Mercado CE, Little SB, Mazewski C, et al: Mandibular condyle erosion and sclerosis in pediatric patients treated with radiotherapy to the head and neck region. Pediatr Blood Cancer 61:1479-80, 2014

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POTENTIAL IMPACT TO
NECK/THYROIDRADIATION
Sec #67

Therapeutic
Exposure
Head/Brain
Neck
Spine (cervical, whole)
TBI

Potential
Late Effects
Thyroid nodules

Periodic Evaluation
PHYSICAL
Thyroid exam
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Thyroid Problems
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Ultrasound for evaluation of palpable nodule(s).
FNA as clinically indicated.
Endocrine and/or surgical consultation for further management.
SYSTEM = SMNSCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, female sex- Cancer/Treatment factors: Thyroid gland directly in radiation field, TBI

References
Bhatti P, Veiga LH, Ronckers CM, et al: Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the Childhood Cancer Survivor Study. Radiat Res 174:741-52, 2010
Clement SC, Kremer LCM, Verburg FA, et al: Balancing the benefits and harms of thyroid cancer surveillance in survivors of childhood, adolescent and young adult cancer: Recommendations from the International Late Effects ofChildhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium. Cancer Treat Rev 63:28-39, 2018
Clement SC, Lebbink CA, Klein Hesselink MS, et al: Presentation and outcome of subsequent thyroid cancer among childhood cancer survivors compared to sporadic thyroid cancer: a matched national study. Eur J Endocrinol183(2):169-180, 2020
Lubin JH, Adams MJ, Shore R, et al: Thyroid cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts. J Clin Endocrinol Metab 1;102(7):2575-2583, 2017
Metzger ML, Howard SC, Hudson MM, et al: Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma. Pediatr Blood Cancer 46:314-9, 2006
Sklar C, Whitton J, Mertens A, et al: Abnormalities of the thyroid in survivors of Hodgkin’s disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 85:3227-32, 2000
Vivanco M, Dalle JH, Alberti C, et al: Malignant and benign thyroid nodules after total body irradiation preceding hematopoietic cell transplantation during childhood. Eur J Endocrinol 167:225-33, 2012

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POTENTIAL IMPACT TO
NECK/THYROID (CONT)RADIATION
Sec #68

Therapeutic
Exposure
Head/Brain
Neck
Spine (cervical, whole)
TBI

Potential
Late Effects
Thyroid cancer

Health Counseling/
Further Considerations

Periodic Evaluation
PHYSICAL
Thyroid exam
YearlyHEALTH LINKS
Thyroid Problems
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Ultrasound for evaluation of palpable nodule(s).
FNA as clinically indicated.
Endocrine and/or surgical consultation for further management.
SYSTEM = SMNSCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment- Cancer/Treatment factors: >5 years after irradiation, highest risk is between 10-30 Gy, thyroid gland directly in radiation field, TBI, alkylating agents

References
Bhatti P, Veiga LH, Ronckers CM, et al: Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the Childhood Cancer Survivor Study. Radiat Res 174:741-52, 2010
Cohen A, Rovelli A, Merlo DF, et al: Risk for secondary thyroid carcinoma after hematopoietic stem-cell transplantation: an EBMT Late Effects Working Party Study. J Clin Oncol 25:2449-54, 2007
Clement SC, Kremer LCM, Verburg FA, et al: Balancing the benefi ts and harms of thyroid cancer surveillance in survivors of childhood, adolescent and young adult cancer: Recommendations from the International Late Effects ofChildhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium. Cancer Treat Rev 63:28-39, 2018
Clement SC, Lebbink CA, Klein Hesselink MS, et al: Presentation and outcome of subsequent thyroid cancer among childhood cancer survivors compared to sporadic thyroid cancer: a matched national study. Eur J Endocrinol183(2):169-180, 2020
de Vathaire F, Haddy N, Allodji RS, et al: Thyroid radiation dose and other risk factors of thyroid carcinoma following childhood cancer. J Clin Endocrinol Metab 100:4282-90, 2015
Inskip PD: Thyroid cancer after radiotherapy for childhood cancer. Med Pediatr Oncol 36:568-73, 2001
Lubin JH, Adams MJ, Shore R, et al: Thyroid cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts. J Clin Endocrinol Metab 1;102(7):2575-2583, 2017
Veiga LH, Bhatti P, Ronckers CM, et al: Chemotherapy and thyroid cancer risk: a report from the Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 21:92-101, 2012
Veiga LH, Holmberg E, Anderson H, et al: Thyroid Cancer after Childhood Exposure to External Radiation: An Updated Pooled Analysis of 12 Studies. Radiat Res 185:473-84, 2016

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POTENTIAL IMPACT TO
NECK/THYROID (CONT)RADIATION
Sec #
69

w

Therapeutic
Exposure
Head/Brain
Neck
Spine (cervical, whole)
TBI

Potential
Late Effects
Hypothyroidism

Periodic Evaluation
HISTORY
Fatigue
Weight gain
Cold intolerance
Constipation
Dry skinBrittle hair
Depressed mood
Menstrual Irregularity
Yearly, consider more frequent screening during
periods of rapid growth
PHYSICAL
HeightWeightHair
Skin
Thyroid exam
Yearly, consider more frequent screening during
periods of rapid growth
SCREENING
TSHFree T4
Yearly, consider more frequent screening during
periods of rapid growth

Health Counseling/
Further Considerations
HEALTH LINKS
Thyroid Problems
COUNSELINGFor females, thyroid levels prior to attempting pregnancy and periodically throughout
pregnancy.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Endocrine consultation for thyroid hormone replacement.
SYSTEM = Endocrine/Metabolic
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Female sex- Cancer/Treatment factors: Radiation dose ≥10 Gy (especially radiation dose ≥20 Gy), thyroid gland directly in radiation field, TBI

References
Aldrich KD, Horne VE, Bielamowicz K, et al: Comparison of hypothyroidism, growth hormone deficiency, and adrenal insufficiency following proton and photon radiotherapy in children with medulloblastoma. J Neurooncol 155(1):93-100, 2021
Chemaitilly W, Li Z, Brinkman TM, et al: Primary hypothyroidism in childhood cancer survivors: prevalence, risk factors, and long-term consequences. Cancer 1;128(3):606-614, 2022
Cheuk DK, Billups CA, Martin MG, et al: Prognostic factors and long-term outcomes of childhood nasopharyngeal carcinoma. Cancer 117:197-206, 2011
Clement SC, Schouten-van Meeteren AY, Boot AM, et al: Prevalence and risk factors of early endocrine disorders in childhood brain tumor survivors: a nationwide, multicenter study. J Clin Oncol 34(36):4362-70, 2016
Katsanis E, Shapiro RS, Robison LL, et al: Thyroid dysfunction following bone marrow transplantation: long-term follow-up of 80 pediatric patients. Bone Marrow Transplant 5:335-40, 1990
Massimino M, Gandola L, Pignoli E, et al: TSH suppression as a possible means of protection against hypothyroidism after irradiation for childhood Hodgkins lymphoma. Pediatr Blood Cancer 57:166-8, 2011
Mostoufi-Moab S, Seidel K, Leisenring WM, et al: Endocrine abnormalities in aging survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 20;34(27):3240-7, 2016
Sanders JE: Endocrine complications of high dose therapy with stem cell transplantation. Pediatr Transplant 8 Suppl 5:39-50, 2004
Sklar C, Boulad F, Small T, et al: Endocrine complications of pediatric stem cell transplantation. Front Biosci 6:G17-22, 2001
Sklar CA, Kim TH, Ramsay NK: Thyroid dysfunction among long-term survivors of bone marrow transplantation. Am J Med 73:688-94, 1982
Vatner RE, Niemierko A, Misra M, et al: Endocrine deficiency as a function of radiation dose to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. J Clin Oncol 36(28):2854-62, 2018
Vogelius IR, Bentzen SM, Maraldo MV, et al: Risk factors for radiation-induced hypothyroidism: a literature-based meta-analysis. Cancer 117:5250-60, 2011

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POTENTIAL IMPACT TO
NECK/THYROID (CONT)RADIATION
Sec #
70

w

Therapeutic
Exposure
Head/Brain
Neck
Spine (cervical, whole)

Potential
Late Effects
Hyperthyroidism

Periodic Evaluation
HISTORY
Heat intolerance
Tachycardia
Palpitations
Weight loss
Emotional lability
Muscular weakness
Hyperphagia
YearlyPHYSICAL
Eyes
Skin
Thyroid
Cardiac
Neurologic
YearlySCREENING
TSHFree T4
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Thyroid Problems
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Endocrine consultation for medical management.
SYSTEM = Endocrine/Metabolic
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher radiation dose, especially ≥30 Gy

References
Constine LS, Donaldson SS, McDougall IR, et al: Thyroid dysfunction after radiotherapy in children with Hodgkin’s disease. Cancer 53:878-83, 1984
DeGroot LJ: Effects of irradiation on the thyroid gland. Endocrinol Metab Clin North Am 22:607-15, 1993
Mostoufi-Moab S, Seidel K, Leisenring WM, et al: Endocrine abnormalities in aging survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 20;34(27):3240-7, 2016
Perz JB, Marin D, Szydlo RM, et al: Incidence of hyperthyroidism after unrelated donor allogeneic stem cell transplantation. Leuk Res 31:1433-6, 2007
Sklar C, Boulad F, Small T, et al: Endocrine complications of pediatric stem cell transplantation. Front Biosci 6:G17-22, 2001
Sklar C, Whitton J, Mertens A, et al: Abnormalities of the thyroid in survivors of Hodgkin’s disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 85:3227-32, 2000

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POTENTIAL IMPACT TO
NECK/THYROID (CONT)RADIATION
Sec #71

Therapeutic
Exposure

Potential
Late Effects

Head/Brain
Neck
Spine (cervical, whole)

Carotid artery disease

Periodic Evaluation
HISTORY
Memory impairment
YearlyPHYSICAL
Blood pressure
Diminished carotid pulses
Carotid bruits
Abnormal neurologic exam (compromise ofblood flow to brain)
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Cardiovascular Risk Factors
Nutrition and Physical Activity
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Optimize CVRFs, including blood pressure, lipid profile, and blood glucose.
Doppler ultrasound of carotid vessels as clinically indicated. Refer to cardiology
if abnormal.
MRI with DWI with MRA and cardiovascular surgery consultation as clinicallyindicated.
For survivors who received ≥40 Gy radiation to the neck: Color Doppler
ultrasound 10 years after completion of radiation therapy as a baseline. Referto cardiologist if abnormal.
SYSTEM = Cardiovascular
SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: ≥40 Gy radiation dose
- Pre-morbid/Co-morbid medical conditions: Hypertension, diabetes mellitus, hypercholesterolemia, smoking

References
Bowers DC, McNeil DE, Liu Y, et al: Stroke as a late treatment effect of Hodgkin’s disease: a report from the Childhood Cancer Survivor Study. J Clin Oncol 23:6508-15, 2005
De Bruin ML, Dorresteijn LD, van’t Veer MB, et al: Increased risk of stroke and transient ischemic attack in 5-year survivors of Hodgkin lymphoma. J Natl Cancer Inst 101:928-37, 2009
Hull MC, Morris CG, Pepine CJ, et al: Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of Hodgkin lymphoma treated with radiation therapy. JAMA 290:2831-7, 2003
Jonas DE, Feltner C, Amick HR, et al: Screening for asymptomatic carotid artery stenosis: a systematic review and meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med 161(5):336-46, 2014
Meeske KA, Siegel SE, Gilsanz V, et al: Premature carotid artery disease in pediatric cancer survivors treated with neck irradiation. Pediatr Blood Cancer 53:615-21, 2009
Morris B, Partap S, Yeom K, et al: Cerebrovascular disease in childhood cancer survivors: a Children’s Oncology Group report. Neurology 73:1906-13, 2009
Qureshi AI, Alexandrov AV, Tegeler CH, et al: Guidelines for screening of extracranial carotid artery disease: a statement for healthcare professionals from the multidisciplinary Practice Guidelines Committee of the American Society of
Neuroimaging; cosponsored by the Society of Vascular and Interventional Neurology. J Neuroimaging 17:19-47, 2007
van Leeuwen-Segarceanu EM, Bos WJ, Dorresteijn LD, et al: Screening Hodgkin lymphoma survivors for radiotherapy induced cardiovascular disease. Cancer Treat Rev 37:391-403, 2011
van Leeuwen-Segarceanu EM, Dorresteijn LD, Vogels OJ, et al: Arterial stiffness is increased in Hodgkin lymphoma survivors treated with radiotherapy. Leuk Lymphoma 54:1734-41, 2013
Zaletel LZ, Popit M, Zaletel M: Is carotid stiffness a possible surrogate for stroke in long-term survivors of childhood cancer after neck radiotherapy? Radiol Oncol 52(2):136-142, 2018

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POTENTIAL IMPACT TO
NECK/THYROID (CONT)RADIATION
Sec #72

Therapeutic
Exposure
Neck
Chest
Spine (thoracic, whole)

Potential
Late Effects
Subclavian artery disease

Periodic Evaluation
PHYSICAL
Blood pressure in both arms (checking for
wide blood pressure variation)
Diminished brachial and radial pulses
Pallor of upper extremities
Coolness of skin
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Cardiovascular Risk Factors
Nutrition and Physical Activity
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Optimize CVRFs, including blood pressure, lipid profile, and blood glucose.
Doppler ultrasound of carotid vessels as clinically indicated. Refer to cardiology
if abnormal.
MRI with DWI with MRA and cardiovascular surgery consultation as clinicallyindicated.
For survivors who received ≥40 Gy radiation to the neck: Color Doppler
ultrasound 10 years after completion of radiation therapy as a baseline. Referto cardiologist if abnormal.
SYSTEM = Cardiovascular
SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: ≥40 Gy radiation dose
- Pre-morbid/Co-morbid medical conditions: Hypertension, diabetes mellitus, hypercholesterolemia

References
Bowers DC, McNeil DE, Liu Y, et al: Stroke as a late treatment effect of Hodgkin’s disease: a report from the Childhood Cancer Survivor Study. J Clin Oncol 23:6508-15, 2005
Hull MC, Morris CG, Pepine CJ, et al: Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of Hodgkin lymphoma treated with radiation therapy. JAMA 290:2831-7, 2003
van Leeuwen-Segarceanu EM, Bos WJ, Dorresteijn LD, et al: Screening Hodgkin lymphoma survivors for radiotherapy induced cardiovascular disease. Cancer Treat Rev 37:391-403, 2011
van Leeuwen-Segarceanu EM, Dorresteijn LD, Vogels OJ, et al: Arterial stiffness is increased in Hodgkin lymphoma survivors treated with radiotherapy. Leuk Lymphoma 54:1734-41, 2013

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POTENTIAL IMPACT TO
BREAST

RADIATION
Sec #73(female)Therapeutic
Exposure
Chest
AxillaTBI

Potential
Late Effects
Breast cancer

Periodic Evaluation
PHYSICAL
Clinical breast exam
Yearly, beginning at puberty until age 25, thenevery 6 months
SCREENING
Mammogram
Yearly, beginning 8 years after radiation or atage 25, whichever occurs lastHealth Counseling/
Further Considerations
HEALTH LINKS
Breast Cancer
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Surgery and/or oncology consultation as clinically indicated.
SYSTEM = SMNSCORE = 1

Breast MRI
Yearly, as an adjunct to mammography
beginning 8 years after radiation or at age
25, whichever occurs lastw

Additional Information

Mammography is limited in its ability to evaluate the premenopausal breast.
MRI is now recommended as an adjunct to mammography in women treated with chest radiation for childhood cancer, similar to screening of other populations at high risk for breast cancer (e.g., premenopausal known or likely
carriers of pathogenic or likely pathogenic variant of known penetrance).
The upper age limit at which mammography and breast MRI should be used for breast cancer surveillance has not been established.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Family history of breast cancer- Cancer/Treatment factors: Higher radiation dose, especially ≥10 Gy, longer time since radiation (>5 years). Note decreased risk in women treated with alkylating agents of sufficient dose to ablate ovarian function, althoughannual surveillance is still recommended.
- Pre-morbid/Co-morbid medical conditions: Personal history of BRCA1, BRCA2, ATM or p53 mutation or in absence of personal genetic testing, known BRCA mutation in first degree relative

References
Bhatia S, Robison LL, Oberlin O, et al: Breast cancer and other second neoplasms after childhood Hodgkin’s disease. N Engl J Med 334:745-51, 1996
Ehrhardt MJ, Howell CR, Hale K, et al: Subsequent Breast Cancer in Female Childhood Cancer Survivors in the St Jude Lifetime Cohort Study (SJLIFE). J Clin Oncol 37(19):1647-1656, 2019Friedman DL, Rovo A, Leisenring W, et al: Increased risk of breast cancer among survivors of allogeneic hematopoietic cell transplantation: a report from the FHCRC and the EBMT-Late Effect Working Party. Blood 111:939-44, 2008
Henderson TO, Amsterdam A, Bhatia S, et al: Systematic review: surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer. Ann Intern Med 152:444-55; W144-54, 2010
Henderson TO, Moskowitz CS, Chou JF, et al: Breast cancer risk in childhood cancer survivors without a history of chest radiotherapy: a report from the Childhood Cancer Survivor Study. J Clin Oncol 34:910-8, 2016
Lange JM, Takashima JR, Peterson SM, et al: Breast cancer in female survivors of Wilms tumor: a report from the National Wilms Tumor Late Effects Study. Cancer 120:3722-30, 2014
Moskowitz CS, Chou JF, Wolden SL, et al: Breast cancer after chest radiation therapy for childhood cancer. J Clin Oncol 32:2217-23, 2014
Moskowitz CS, Ronckers CM, Chou JF, et al: Development and Validation of a Breast Cancer Risk Prediction Model for Childhood Cancer Survivors Treated With Chest Radiation: A Report From the Childhood Cancer Survivor Study and the Dutch
Hodgkin Late Effects and LATER Cohorts. J Clin Oncol 39(27):3012-3021, 2021
Mulder RL, Hudson MM, Bhatia S, et al: Updated Breast Cancer Surveillance Recommendations for Female Survivors of Childhood, Adolescent, and Young Adult Cancer From the International Guideline Harmonization Group. J Clin Oncol
38(35):4194-4207, 2020
Ng AK, Garber JE, Diller LR, et al: Prospective study of the efficacy of breast magnetic resonance imaging and mammographic screening in survivors of Hodgkin lymphoma. J Clin Oncol 31:2282-8, 2013
Schaapveld M, Aleman BM, van Eggermond AM, et al: Second cancer risk up to 40 years after treatment for Hodgkin’s lymphoma. N Engl J Med 373:2499-511, 2015
Travis LB, Hill DA, Dores GM, et al: Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease. JAMA 290:465-75, 2003
Yeh JM, Lowry KP, Schechter CB, et al: Benefits, Harms, and Cost-Effectiveness of Breast Cancer Screening for Survivors of Childhood Cancer Treated With Chest Radiation: A Comparative Modeling Study. Ann Intern Med 173(5):331-341, 2020

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POTENTIAL IMPACT TO
BREAST (CONT)RADIATION
Sec #74(female)w

Therapeutic
Exposure
Chest
AxillaTBI

Potential
Late Effects
Breast tissue hypoplasia

Periodic Evaluation
PHYSICAL
Clinical breast exam
YearlyHealth Counseling/
Further Considerations
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Surgical consultation for breast reconstruction after completion of growth.
SYSTEM = Reproductive (Female)
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Prepubertal at time of treatment- Cancer/Treatment factors: Radiation dose ≥10 Gy to prepubertal breast bud (especially dose ≥20 Gy)

References
Furst CJ, Lundell M, Ahlback SO, et al: Breast hypoplasia following irradiation of the female breast in infancy and early childhood. Acta Oncol 28:519-23, 1989
Johnston K, Vowels M, Carroll S, et al: Failure to lactate: a possible late effect of cranial radiation. Pediatr Blood Cancer 50:721-2, 2008
Lo AC, Ronckers C, Aznar MC, et al: Breast hypoplasia and decreased lactation from radiation therapy in survivors of pediatric malignancy: a PENTEC comprehensive review. Int J Radiat Oncol Biol Phys 6:S0360-3016(21)02725-5,
2021
Macklis RM, Oltikar A, Sallan SE: Wilms’ tumor patients with pulmonary metastases. Int J Radiat Oncol Biol Phys 21:1187-93, 1991

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POTENTIAL IMPACT TOLUNGSRADIATION
Sec #
75

w

Therapeutic
Exposure
Chest
AxillaTBI

Potential
Late Effects
Pulmonary toxicity
Pulmonary fibrosis
Interstitial pneumonitis
Restrictive lung disease
Obstructive lung disease

Periodic Evaluation
HISTORY
Cough
Wheezing
Shortness of breath
Dyspnea on exertion
YearlyPHYSICAL
Pulmonary exam
YearlySCREENING
PFTs (including DLCO and spirometry)
Baseline at entry into long-term follow-up,
repeat as clinically indicated in patients withabnormal results or progressive pulmonary
dysfunction

Health Counseling/
Further Considerations
HEALTH LINKS
Pulmonary HealthRESOURCES
www.smokefree.gov
COUNSELING
Tobacco and environmental tobacco smoke avoidance/Smoking cessation.
Influenza and Pneumococcal vaccinations.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Repeat PFTs prior to general anesthesia.
Pulmonary consultation for patients with symptomatic pulmonary dysfunction.
Pulmonary consultation for survivors who desire to SCUBA dive (due to potential
undiagnosed pulmonary toxicities, and limited data to guide safe diving
recommendations for individuals treated with pulmonary toxic therapy).
SYSTEM = Pulmonary
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at irradiation- Cancer/Treatment factors: Radiation dose >10 Gy, especially ≥15 Gy, TBI ≥6 Gy in single fraction, TBI ≥12 Gy fractionated, chest radiation combined with TBI, radiation combined with bleomycin, busulfan, carmustine (BCNU),
or lomustine (CCNU), radiomimetic chemotherapy (e.g., doxorubicin, dactinomycin)- Pre-morbid/Co-morbid medical conditions: Atopic history- Health behaviors: Smoking, inhaled illicit drug use

References
Armenian SH, Landier W, Francisco L, et al: Long-term pulmonary function in survivors of childhood cancer. J Clin Oncol 33:1592-600, 2015
Dietz AC, Chen Y, Yasui Y, et al: Risk and impact of pulmonary complications in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 122:3687-3696, 2016
Green DM, Zhu L, Wang M, et al: Pulmonary function after treatment for childhood cancer. A report from the St. Jude Lifetime Cohort Study (SJLIFE). Ann Am Thorac Soc 13:1575-85, 2016
Huang TT, Hudson MM, Stokes DC, et al: Pulmonary outcomes in survivors of childhood cancer: a systematic review. Chest 140:881-901, 2011
Hudson MM, Ness KK, Gurney JG, et al: Clinical ascertainment of health outcomes among adults treated for childhood cancer. JAMA 309:2371-2381, 2013
Mulder RL, Thonissen NM, van der Pal HJ, et al: Pulmonary function impairment measured by pulmonary function tests in long-term survivors of childhood cancer. Thorax 66:1065-71, 2011
Tetrault JM, Crothers K, Moore BA, et al: Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch Intern Med 167:221-8, 2007
van Hulst RA, Rietbroek RC, Gaastra MT, et al: To dive or not to dive with bleomycin: a practical algorithm. Aviat Space Environ Med 82:814-8, 2011
Venkatramani R, Kamath S, Wong K, et al: Correlation of clinical and dosimetric factors with adverse pulmonary outcomes in children after lung irradiation. Int J Radiat Oncol Biol Phys 86:942-8, 2013
Wolff AJ, O’Donnell AE: Pulmonary effects of illicit drug use. Clin Chest Med 25:203-16, 2004

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POTENTIAL IMPACT TO
LUNGS (CONT)RADIATION
Sec #
76

w

Therapeutic
Exposure
Chest
AxillaTBI

Potential
Late Effects
Lung cancer

Periodic Evaluation
HISTORY
Cough
Wheezing
Shortness of breath
Dyspnea on exertion
YearlyPHYSICAL
Pulmonary Exam
YearlySCREENING
Spiral CT Scan
Discuss the benefits and risks/harms of spiral
CT scanning for patients at highest risk (i.e.,smokers)

Health Counseling/
Further Considerations
HEALTH LINKS
Reducing the Risk of Subsequent Cancers
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Imaging and surgery and/or oncology consultation as clinically indicated.
SYSTEM = SMNSCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Workplace exposure to asbestos, arsenic, radiation, second hand smoke (in non-smokers)- Health behaviors: Smoking, especially 30 pack-years or more

References
Ghosh T, Chen Y, Dietz AC, et al: Lung Cancer as a Subsequent Malignant Neoplasm in Survivors of Childhood Cancer. Cancer Epidemiol Biomarkers Prev 30(12):2235-2243, 2021
Holmqvist AS, Chen Y, Berano Teh J, et al: Risk of solid subsequent malignant neoplasms after childhood Hodgkin lymphoma-Identification of high-risk populations to guide surveillance: A report from the Late Effects Study Group.
Cancer 125(8):1373-1383, 2019
Moyer VA, U. S. Preventive Services Task Force: Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 160:330-8, 2014
National Lung Screening Trial Research Team, Church TR, Black WC, et al: Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med 368:1980-91, 2013
Schaapveld M, Aleman BM, van Eggermond AM, et al: Second cancer risk up to 40 years after treatment for Hodgkin’s lymphoma. N Engl J Med 373:2499-511, 2015
Smith RA, Andrews KS, Brooks D, et al: Cancer screening in the United States, 2017: A review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin 67:100-121, 2017
Swerdlow AJ, Higgins CD, Smith P, et al: Second cancer risk after chemotherapy for Hodgkin’s lymphoma: a collaborative British cohort study. J Clin Oncol 29:4096-104, 2011
Wattson DA, Hunink MG, DiPiro PJ, et al: Low-dose chest computed tomography for lung cancer screening among Hodgkin lymphoma survivors: a cost-effectiveness analysis. Int J Radiat Oncol Biol Phys 90:344-53, 2014

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POTENTIAL IMPACT TO
HEARTRADIATION
Sec #77

Therapeutic
Exposure
Chest
AbdomenSpine (thoracic, whole)
TBI(TBI is included for
cumulative dose calculation
purposes only; this section
is not applicable to patients
who received TBI <15 Gy
alone.)

Potential
Late Effects
Cardiac toxicity
Cardiomyopathy
Subclinical left ventricular
dysfunction
Congestive heart failure
Pericarditis
Pericardial fibrosis
Valvular disease
Atherosclerotic heart disease
Myocardial infarction
Arrhythmia

Periodic Evaluation
HISTORY
If dose ≥15 Gy:
Shortness of breath
Dyspnea on exertion
Orthopnea
Chest pain
Palpitations
If under 25 yrs: abdominal symptoms (nausea,
vomiting)
YearlyPHYSICAL
If dose ≥15 Gy:
Blood pressure
Cardiac exam
YearlySCREENING
Echo (or comparable imaging to evaluate
cardiac anatomy and function)
RECOMMENDED FREQUENCY OF ECHOCARDIOGRAM
Anthracycline
Dose*
None to <100mg/m2

Radiation
Dose**

Recommended
Frequency

None to <15Gy

No screening

None to <100mg/m2
15Gy to <30Gy
Every 5 years≥100 to <250mg/m²
None to <15Gy≥100 to <250mg/m²≥15Gy
None to Any≥30Gy
Every 2 years≥ 250mg/m²
None to Any*Based on doxorubicin isotonic equivalent dose. See doseconversion instructions in section 34.
**Based on radiation dose with potential impact to heart (radiation to chest, abdomen, spine [thoracic, whole], TBI).

If dose ≥15 Gy:
EKG (include evaluation of QTc interval)
Baseline at entry into long-term follow-up, repeat
as clinically indicatedHealth Counseling/
Further Considerations
HEALTH LINKS
Heart Health
Cardiovascular Risk Factors
Nutrition and Physical Activity
Dental Health
COUNSELING
Traditional CVRFs significantly increase survivors’ risk of cardiomyopathy. Counsel
regarding the importance of maintaining blood pressure, BMI, lipids, and glucose levels
within goal ranges per general population guidelines.
Regarding exercise:• Exercise is generally safe and encouraged for patients with normal LV systolic function• Consult cardiology for survivors with asymptomatic cardiomyopathy to define physicalactivity limits and precautions.
• Consider cardiology consultation to define physical activity limits and precautions forhigh risk survivors (i.e., those requiring an echo every 2 years) who plan to participate
in intensive exercise.
If QTc interval is prolonged: Caution use of QTc prolonging medications (e.g., tricyclic
anti-depressants, antifungals, macrolide antibiotics, metronidazole).
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Cardiac MRI as an adjunct imaging modality when echo images are suboptimal.
Cardiology consultation in patients with subclinical abnormalities on screening
evaluations, LV dysfunction, dysrhythmia, or prolonged QTc interval.
Cardiology consultation (5 to 10 years after radiation) may be reasonable to evaluate risk
for coronary artery disease in survivors who received ≥30 Gy chest radiation alone or≥15 Gy chest radiation plus anthracycline.
In survivors with valvular disorders: Consult cardiologist to advise regarding need for
endocarditis prophylaxis.
Female patients only: For patients who are pregnant or planning to become pregnant,additional cardiology evaluation is indicated in patients who received:• ≥250 mg/m2 anthracyclines• ≥30 Gy chest radiation, or• Anthracycline (any dose) combined with chest radiation (≥15 Gy)• Evaluation should include a baseline echo (pre- or early-pregnancy). For those without
prior abnormalities and with normal pre- or early-pregnancy baseline echos, follow-up
echos may be obtained at the provider’s discretion. Those with a history of systolic
dysfunction or with pre- or early-pregnancy systolic dysfunction are at highest risk for
pregnancy-associated cardiomyopathy, and should be monitored periodically during
pregnancy and during labor and delivery due to increased risk for heart failure.
SYSTEM = Cardiovascular
SCORE = 1

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POTENTIAL IMPACT TO
HEART (CONT)RADIATION
Additional Information

Exertional intolerance is an uncommon presentation of LV dysfunction in patients <25 years old.
Abdominal symptoms (nausea, emesis) may be observed more frequently than exertional dyspnea or chest pain in younger patients.
The AHA now limits their recommendation regarding endocarditis prophylaxis only to patients whose cardiac conditions are associated with the highest risk of adverse outcome, which includes, but is not limited to the following four
categories: (1) prosthetic heart valves, (2) previous history of infective endocarditis, (3) certain patients with congenital heart disease, and (4) valvulopathy following cardiac transplantation.
Survivors diagnosed with heart valve disorders should discuss the need for endocarditis prophylaxis with their cardiologist. See Wilson et al. (2007) for specifics.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at irradiation, especially age <5 years, family history of dyslipidemia, CAD- Cancer/Treatment factors: Radiation dose ≥20 Gy to chest, TBI, anteriorly-weighted radiation fields, lack of subcarinal shielding, combined with radiomimetic chemotherapy (e.g., doxorubicin, dactinomycin), doses ≥15 Gy inpatients who have received ≥100 mg/m2 of anthracyclines, doses ≥30 Gy in patients who have not received anthracyclines, longer time since treatment- Pre-morbid/Co-morbid medical conditions: Obesity, congenital heart disease, hypertension, diabetes mellitus, dyslipidemia. For female patients, premature ovarian failure (untreated), pregnancy if systolic function is abnormal pre-pregnancy- Health behaviors: Smoking, drug use (e.g., cocaine, diet pills, ephedra, mahuang)

References
Armstrong GT, Joshi VM, Ness KK, et al: Comprehensive echocardiographic detection of treatment-related cardiac dysfunction in adult survivors of childhood cancer: results from the St. Jude Lifetime Cohort Study. J Am Coll Cardiol
65:2511-22, 2015
Armstrong GT, Oeffinger KC, Chen Y, et al: Modifiable risk factors and major cardiac events among adult survivors of childhood cancer. J Clin Oncol 31:3673-80, 2013
Blanco JG, Sun CL, Landier W, et al: Anthracycline-related cardiomyopathy after childhood cancer: role of polymorphisms in carbonyl reductase genes--a report from the Children’s Oncology Group. J Clin Oncol 30:1415-21, 2012
Chow EJ, Chen Y, Hudson MM, et al: Prediction of ischemic heart disease and stroke in survivors of childhood cancer. J Clin Oncol 36:44-52, 2018
Chow EJ, Chen Y, Kremer LC, et al: Individual prediction of heart failure among childhood cancer survivors. J Clin Oncol 33:394-402, 2015
Christiansen JR, Hamre H, Massey R, et al: Left ventricular function in long-term survivors of childhood lymphoma. Am J Cardiol 114:483-90, 2014
Ehrhardt MJ, Leerink JM, Mulder RL, et al: Systematic review and updated recommendations for cardiomyopathy surveillance for survivors of childhood, adolescent, and young adult cancer from the International Late Effects ofChildhood Cancer Guideline Harmonization Group. Lancet Oncol 24(3):e108-e120, 2023
Ehrhardt MJ, Ward ZJ, Liu Q, et al: Cost-effectiveness of the International Late Effects of Childhood Cancer Guideline Harmonization Group screening guidelines to prevent heart failure in survivors of childhood cancer. J Clin Oncol
38(33):3851-3862, 2020
Haddy N, Diallo S, El-Fayech C, et al: Cardiac diseases following childhood cancer treatment: cohort study. Circulation 133:31-8, 2016
Hines MR, Mulrooney DA, Hudson MM, et al: Pregnancy-associated cardiomyopathy in survivors of childhood cancer. J Cancer Surviv 10:113-21, 2016
Mulrooney DA, Armstrong GT, Huang S, et al: Cardiac outcomes in adult survivors of childhood cancer exposed to cardiotoxic therapy: a cross-sectional study. Ann Intern Med 164:93-101, 2016
Mulrooney DA, Hyun G, Ness KK, et al: Major cardiac events for adult survivors of childhood cancer diagnosed between 1970 and 1999: report from the Childhood Cancer Survivor Study cohort. BMJ 368:l6794, 2020
Schellong G, Riepenhausen M, Bruch C, et al: Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for Hodgkin disease in children and adolescents: report from the longitudinal GPOH follow-up
project of the German-Austrian DAL-HD studies. Pediatr Blood Cancer 55:1145-52, 2010
Swerdlow AJ, Higgins CD, Smith P, et al: Myocardial infarction mortality risk after treatment for Hodgkin disease: a collaborative British cohort study. J Natl Cancer Inst 99:206-14, 2007
van Dalen EC, van der Pal HJ, van den Bos C, et al: Clinical heart failure during pregnancy and delivery in a cohort of female childhood cancer survivors treated with anthracyclines. Eur J Cancer 42:2549-53, 2006
van der Pal HJ, van Dalen EC, van Delden E, et al: High risk of symptomatic cardiac events in childhood cancer survivors. J Clin Oncol 30:1429-37, 2012
van Nimwegen FA, Schaapveld M, Janus CP, et al: Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk. JAMA Intern Med 175:1007-17, 2015
Wilson W, Taubert KA, Gewitz M, et al: Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group.
Circulation 116:1736-54, 2007

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POTENTIAL IMPACT TO
SPLEENRADIATION
Sec #78

Therapeutic
Exposure

Potential
Late Effects

AbdomenTBI(TBI is included for
cumulative dose calculation
purposes only; this section
is not applicable to patients
who received TBI alone.)

Functional asplenia
At risk for life-threatening infection
with encapsulated organisms(e.g., Haemophilus influenzae,
Streptococcus pneumoniae,
meningococcus)

Periodic Evaluation
PHYSICAL
If radiation dose ≥40 Gy:
Physical exam at time of febrile illness toevaluate degree of illness and potential
source of infection
When febrile T ≥101°F (38.3°C)
SCREENING
If dose ≥40 Gy:
Blood culture
When febrile T ≥101°F (38.3°C)

Health Counseling/
Further Considerations
HEALTH LINKS
Splenic Precautions
COUNSELING
Risk of life-threatening infections with encapsulated organisms.
Risk of malaria and tick-borne diseases if living in or visiting endemic areas.
Obtain medical alert bracelet/card noting functional asplenia.
Discuss importance of immunization with Pneumococcal, Meningococcal (including
serotype B), Influenza and HIB vaccines according to current ACIP recommendations.
For further details regarding antibiotic prophylaxis and immunizations, see current editionof AAP Red Book.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Administer a long-acting, broad-spectrum parenteral antibiotic (e.g., ceftriaxone) inpatients with T ≥101°F (38.3°C) or other signs of serious illness and continue close
medical monitoring while awaiting blood culture results.
Hospitalize and broaden antimicrobial coverage (e.g., addition of vancomycin) undercertain circumstances, such as the presence of marked leukocytosis, neutropenia, or
significant change from baseline CBC, toxic clinical appearance, fever ≥104°F (40°C),
meningitis, pneumonia, or other serious focus of infection, signs of septic shock, orprevious history of serious infection.
Discuss with dental provider potential need for antibiotic prophylaxis based on planned
procedure.
SYSTEM = Immune
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher radiation dose, larger volume of spleen in treatment field, include documentation of splenic radiation dose exposure in the survivor’s treatment summary.

References
Castagnola E, Fioredda F: Prevention of life-threatening infections due to encapsulated bacteria in children with hyposplenia or asplenia: a brief review of current recommendations for practical purposes. Eur J Haematol 71:319-26, 2003
Centers for Disease Control and Prevention: Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR Morb Mortal Wkly Rep 61:816-9, 2012
Centers for Disease Control and Prevention: Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 62:521-4, 2013
Committee on Infectious Disease, American Academy of Pediatrics: Immunization in special clinical circumstances, in Kimberlin DW, Barnett ED, Lynfield R, et al (eds): Red Book: 2021 Report of the Committee on Infectious Diseases (ed 32). Itasca, IL, American
Academy of Pediatrics, 2021, pp 67-105
Guilcher GMT, Rivard L, Huang JT, et al: Immune function in childhood cancer survivors: a Children’s Oncology Group review. Lancet Child Adolesc Health 5(4):284-294, 2021
Mbaeyi SA, Bozio CH, Duffy J, et al: Meningococcal vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 69(9);1-41, 2020
Mourtzoukou EG, Pappas G, Peppas G, et al: Vaccination of asplenic or hyposplenic adults. Br J Surg 95:273-80, 2008
Price VE, Blanchette VS, Ford-Jones EL: The prevention and management of infections in children with asplenia or hyposplenia. Infect Dis Clin North Am 21:697-710, viii-ix, 2007
Smets F, Bourgois A, Vermylen C, et al: Randomised revaccination with pneumococcal polysaccharide or conjugate vaccine in asplenic children previously vaccinated with polysaccharide vaccine. Vaccine 25:5278-82, 2007
Spelman D, Buttery J, Daley A, et al: Guidelines for the prevention of sepsis in asplenic and hyposplenic patients. Intern Med J 38:349-56, 2008

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POTENTIAL IMPACT TO
GI/HEPATIC SYSTEMRADIATION
Sec #79

Therapeutic
Exposure

Potential
Late Effects

Neck
Esophageal stricture
Chest
AbdomenSpine (cervical, thoracic,
whole)

Periodic Evaluation
HISTORY
Dysphagia
HeartburnYearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Gastrointestinal Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Surgery and/or gastroenterology consultation for symptomatic patients.
SYSTEM = GI/Hepatic
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Radiation dose ≥30 Gy (increased risk with higher radiation dose, especially ≥40 Gy)- Pre-morbid/Co-morbid medical conditions: Gastroesophageal reflux, history of Candida esophagitis, gut GVHD

References
Asdahl PH, Oeffinger KC, Albieri V, et al. Esophageal disease among childhood cancer survivors - a report from the Childhood Cancer Survivors Study. Pediatr Blood Cancer 68(8):e29043, 2021
Lal DR, Foroutan HR, Su WT, et al: The management of treatment-related esophageal complications in children and adolescents with cancer. J Pediatr Surg 41:495-9, 2006
Mahboubi S, Silber JH: Radiation-induced esophageal strictures in children with cancer. Eur Radiol 7:119-22, 1997
Rodriguez ML, Martin MM, Padellano LC, et al: Gastrointestinal toxicity associated to radiation therapy. Clin Transl Oncol 12:554-61, 2010

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POTENTIAL IMPACT TO
GI/HEPATIC SYSTEM (CONT)RADIATION
Sec #80

Therapeutic
Exposure
Abdomen
TBI

Potential
Late Effects
Impaired glucose
metabolism/Diabetes
mellitus

Periodic Evaluation
SCREENING
Fasting blood glucose OR HbA1c
Every 2 years

Health Counseling/
Further Considerations
HEALTH LINKS
Nutrition and Physical Activity
Cardiovascular Risk Factors
COUNSELING
Obesity-related health risks.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Endocrine consultation
Evaluate for other co-morbid conditions, including dyslipidemia, hypertension,and overweight/obesity.
Refer to dietitian for blood sugar management.
SYSTEM = Endocrine/Metabolic
SCORE = 1w

Additional Information

Impaired glucose metabolism may occur as a part of a constellation of conditions known as metabolic syndrome.
Definitions of metabolic syndrome generally include a combination of central (abdominal) obesity and ≥2 of the following: elevated blood pressure, atherogenic dyslipidemia (elevated triglycerides, reduced HDL cholesterol), abnormal
glucose metabolism.
Note: Patients who received TBI may develop features of metabolic syndrome without associated obesity.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Family history of diabetes mellitus, pregnancy- Cancer/Treatment factors: Prolonged corticosteroid therapy (e.g., for cGVHD)- Pre-morbid/Co-morbid medical conditions: Obesity

References
Baker KS, Ness KK, Steinberger J, et al: Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the Bone Marrow Transplantation Survivor Study. Blood 109:1765-72, 2007
Chow EJ, Simmons JH, Roth CL, et al: Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic leukemia treated with total body irradiation. Biol Blood Marrow Transplant 16:1674-81, 2010de Vathaire F, El-Fayech C, Ben Ayed FF, et al: Radiation dose to the pancreas and risk of diabetes mellitus in childhood cancer survivors: a retrospective cohort study. Lancet Oncol 13:1002-10, 2012Friedman DN, Moskowitz CS, Hilden P, et al: Radiation dose and volume to the pancreas and subsequent risk of diabetes mellitus: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 112(5):525-32, 2020
Hoffmeister PA, Storer BE, Sanders JE: Diabetes mellitus in long-term survivors of pediatric hematopoietic cell transplantation. J Pediatr Hematol Oncol 26:81-90, 2004
Lorini R, Cortona L, Scaramuzza A, et al: Hyperinsulinemia in children and adolescents after bone marrow transplantation. Bone Marrow Transplant 15:873-7, 1995
Meacham LR, Chow EJ, Ness KK, et al: Cardiovascular risk factors in adult survivors of pediatric cancer--a report from the Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 19:170-81, 2010
Meacham LR, Sklar CA, Li S, et al: Diabetes mellitus in long-term survivors of childhood cancer. Increased risk associated with radiation therapy: a report for the Childhood Cancer Survivor Study. Arch Intern Med 169:1381-8, 2009
Mostoufi-Moab S, Seidel K, Leisenring WM, et al: Endocrine abnormalities in aging survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 34(27):3240-7, 2016
Shalitin S, Phillip M, Stein J, et al: Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence. Bone Marrow Transplant 37:1109-17, 2006
Taskinen M, Saarinen-Pihkala UM, Hovi L, et al: Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood. Lancet 356:993-7, 2000

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POTENTIAL IMPACT TO
GI/HEPATIC SYSTEM (CONT)RADIATION
Sec #81

Therapeutic
Exposure
Abdomen
TBI

Potential
Late Effects
Dyslipidemia

Periodic Evaluation
SCREENING
Fasting lipid profile
Every 2 years

Health Counseling/
Further Considerations
HEALTH LINKS
Nutrition and Physical Activity
Cardiovascular Risk Factors
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Evaluate for other co-morbid conditions, including hypertension, impaired
glucose metabolism, and overweight/obesity.
Refer to dietitian.
SYSTEM = Endocrine/Metabolic
SCORE
Abdominal Radiation = 2A
TBI = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Family history of dyslipidemia- Cancer/Treatment factors: Prolonged corticosteroid therapy (e.g., for cGVHD)

References
Bajwa R, Skeens M, Garee A, et al: Metabolic syndrome and endocrine dysfunctions after HSCT in children. Pediatr Transplant 16:872-8, 2012
Baker KS, Ness KK, Steinberger J, et al: Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the Bone Marrow Transplantation Survivor Study. Blood 109:1765-72, 2007
Chow EJ, Simmons JH, Roth CL, et al: Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic leukemia treated with total body irradiation. Biol Blood Marrow Transplant 16:1674-81, 2010
Daniels SR, Greer FR, Committee on Nutrition: Lipid screening and cardiovascular health in childhood. Pediatrics 122:198-208, 2008
Felicetti F, D’Ascenzo F, Moretti C, et al: Prevalence of cardiovascular risk factors in long-term survivors of childhood cancer: 16 years follow up from a prospective registry. Eur J Prev Cardiol 22:762-70, 2015
Meacham LR, Sklar CA, Li S, et al: Diabetes mellitus in long-term survivors of childhood cancer. Increased risk associated with radiation therapy: a report for the Childhood Cancer Survivor Study. Arch Intern Med 169:1381-8, 2009
Oudin C, Simeoni MC, Sirvent N, et al: Prevalence and risk factors of the metabolic syndrome in adult survivors of childhood leukemia. Blood 117:4442-8, 2011
Shalitin S, Phillip M, Stein J, et al: Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence. Bone Marrow Transplant 37:1109-17, 2006
Taskinen M, Saarinen-Pihkala UM, Hovi L, et al: Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood. Lancet 356:993-7, 2000
van Waas M, Neggers SJ, Uitterlinden AG, et al: Treatment factors rather than genetic variation determine metabolic syndrome in childhood cancer survivors. Eur J Cancer 49:668-75, 2013

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POTENTIAL IMPACT TO
GI/HEPATIC SYSTEM (CONT)RADIATION
Sec #
82

w

Therapeutic
Exposure
AbdomenPotential
Late Effects
Hepatic toxicity
Hepatic fibrosis
Cirrhosis
FNH

Periodic Evaluation
PHYSICAL
Scleral icterus
Jaundice
Ascites
Hepatomegaly
Splenomegaly
YearlySCREENING
ALT
AST
Bilirubin
Baseline at entry into long-term follow-up,
repeat as clinically indicatedHealth Counseling/
Further Considerations
HEALTH LINKS
Liver Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Platelet count for evaluation of hypersplenism and prothrombin time for
evaluation of hepatic synthetic function in patients with abnormal liver
screening tests.
Screen for viral hepatitis in patients with persistently abnormal liver function or
any patient transfused prior to 1993.
Gastroenterology/Hepatology consultation in patients with persistent liver
dysfunction.
Hepatitis A and B immunization in at-risk patients lacking immunity.
SYSTEM = GI/Hepatic
SCORE = 1

Additional Information

FNH is a benign change that represents a scar in the liver.
FNH is usually an asymptomatic finding noted on MRI or ultrasound of the liver.
Continued observation or biopsy may be indicated depending on individual patient factors and imaging features.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher radiation dose to liver, especially ≥30 Gy, or to larger volume- Pre-morbid/Co-morbid medical conditions: Chronic hepatitis, history of SOS- Health behaviors: Alcohol use (in relation to hepatic fibrosis and cirrhosis)

References
Bardi E, Mulder RL, van Dalen EC, et al: Late hepatic toxicity surveillance for survivors of childhood, adolescent and young adult cancer: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Cancer Treat Rev 100:102296, 2021
Castellino S, Muir A, Shah A, et al: Hepato-biliary late effects in survivors of childhood and adolescent cancer: a report from the Children’s Oncology Group. Pediatr Blood Cancer 54:663-9, 2010
Green DM, Wang M, Krasin MJ, et al: Serum alanine aminotransferase elevations in survivors of childhood cancer: a report from the St. Jude Lifetime Cohort Study. Hepatol 69(1):94-106, 2019
Mulder RL, van Dalen EC, Van den Hof M, et al: Hepatic late adverse effects after antineoplastic treatment for childhood cancer. Cochrane Database Syst Rev:CD008205, 2011
Pan CC, Kavanagh BD, Dawson LA, et al: Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 76:S94-100, 2010
Pillon M, Carucci NS, Mainardi C, et al: Focal nodular hyperplasia of the liver: an emerging complication of hematopoietic SCT in children. Bone Marrow Transplant 50:414-9, 2015
Smith EA, Salisbury S, Martin R, et al: Incidence and etiology of new liver lesions in pediatric patients previously treated for malignancy. AJR Am J Roentgenol 199:186-91, 2012

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GI/HEPATIC SYSTEM (CONT)RADIATION
Sec #
83

w

Therapeutic
Exposure
AbdomenPotential
Late Effects
Cholelithiasis

Periodic Evaluation
HISTORY
Colicky abdominal pain related to fatty
food intake
Excessive flatulence
YearlyPHYSICAL
Epigastric or RUQ tenderness
Positive Murphy’s sign
As clinically indicatedHealth Counseling/
Further Considerations
HEALTH LINKS
Gastrointestinal Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Gallbladder ultrasound in patients with chronic abdominal pain.
SYSTEM = GI/Hepatic
SCORE = 2B

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Family history of cholelithiasis- Cancer/Treatment factors: Radiation dose ≥30 Gy, abdominal surgery, abdominal radiation, TPN, HCT- Pre-morbid/Co-morbid medical conditions: Ileal conduit, obesity, pregnancy

References
Castellino S, Muir A, Shah A, et al: Hepato-biliary late effects in survivors of childhood and adolescent cancer: a report from the Children’s Oncology Group. Pediatr Blood Cancer 54:663-9, 2010
Dieffenbach BV, Li N, Madenci AL, et al: Incidence of and risk factors for late cholecystectomy in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Eur J Cancer 133:4-13, 2020
Hoffmeister PA, Storer BE, McDonald GB, et al: Gallstones in pediatric hematopoietic cell transplant survivors with up to 40 years of follow-up. J Pediatr Hematol Oncol 36:484-90, 2014
Mahmoud H, Schell M, Pui CH: Cholelithiasis after treatment for childhood cancer. Cancer 67:1439-42, 1991

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POTENTIAL IMPACT TO
GI/HEPATIC SYSTEM (CONT)RADIATION
Sec #
84

w

Therapeutic
Exposure
AbdomenPelvisSpine (lumbar, sacral,whole)

Potential
Late Effects
Bowel obstruction

Periodic Evaluation
HISTORY
Abdominal pain
Distension
Vomiting
Constipation
YearlyPHYSICAL
Tenderness
Abdominal guarding
Distension
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Gastrointestinal Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Imaging as clinically indicated for suspected obstruction.
Surgical consultation in patients unresponsive to medical management.
SYSTEM = GI/Hepatic
SCORE = 1

Additional Information

Bowel obstruction is rarely seen in individuals treated with abdominal radiation who have not had abdominal surgery.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Abdominal surgery, radiation dose ≥20 Gy (especially ≥45 Gy). Obstruction may occur in people who received lower doses of abdominal radiation during childhood.

References
Emami B, Lyman J, Brown A, et al: Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21:109-22, 1991
Madenci AL, Fisher S, Diller LR, et al: Intestinal obstruction in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 33:2893-900, 2015
Paulino AC, Wen BC, Brown CK, et al: Late effects in children treated with radiation therapy for Wilms’ tumor. Int J Radiat Oncol Biol Phys 46:1239-46, 2000

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POTENTIAL IMPACT TO
GI/HEPATIC SYSTEM (CONT)RADIATION
Sec #85

Therapeutic
Exposure
AbdomenPelvisSpine (lumbar, sacral,whole)

Potential
Late Effects
Chronic enterocolitis
FistulaStrictures

Periodic Evaluation
HISTORY
NauseaVomiting
Abdominal pain
Diarrhea
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Gastrointestinal Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Serum protein and albumin in patients with chronic diarrhea or fistula.
Surgical and/or gastroenterology consultation.
SYSTEM = GI/Hepatic
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Abdominal surgery, radiation dose ≥30 Gy (particularly radiation dose ≥45 Gy), higher radiation dose to bowel

References
Donaldson SS, Jundt S, Ricour C, et al: Radiation enteritis in children. A retrospective review, clinicopathologic correlation, and dietary management. Cancer 35:1167-78, 1975
Heyn R, Raney RB, Jr., Hays DM, et al: Late effects of therapy in patients with paratesticular rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee. J Clin Oncol 10:614-23, 1992
Madenci AL, Dieffenbach BV, Liu Q, et al. Late-onset anorectal disease and psychosocial impact in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 125(21):3873-3881, 2019
Raney B, Jr., Heyn R, Hays DM, et al: Sequelae of treatment in 109 patients followed for 5 to 15 years after diagnosis of sarcoma of the bladder and prostate. A report from the Intergroup Rhabdomyosarcoma Study Committee. Cancer
71:2387-94, 1993
Rodriguez ML, Martin MM, Padellano LC, et al: Gastrointestinal toxicity associated to radiation therapy. Clin Transl Oncol 12:554-61, 2010

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POTENTIAL IMPACT TO
GI/HEPATIC SYSTEM (CONT)RADIATION
Sec #86

Therapeutic
Exposure
AbdomenPelvisSpine (lumbar, sacral,whole)
TBI

Potential
Late Effects
Colorectal cancer

Periodic Evaluation

Health Counseling/
Further Considerations

SCREENING
HEALTH LINKS
Regular screening selected from the options
Colorectal Cancer
below based on informed decision-making
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
between patient and provider
Gastroenterology, surgery and/or oncology consultation as clinically indicated.
Beginning 5 years after radiation or at age 30 years(whichever occurs last)
SYSTEM = SMN
Radiation-Related Colorectal Cancer
SCORE = 2A
Screening Options
Test

Frequency

Multitarget stool DNA test*

Every 3 years

Colonoscopy

Every 5 years*Positive result should be followed up with timely
colonoscopy.
Note: Colonoscopy is considered the gold standard forcolorectal cancer screening in high-risk populations;however, recognizing that not all survivors are willing or able
to undergo colonoscopy, multitarget stool DNA testing isdeemed a reasonable alternative. Alternative stool-based
testing (i.e., annual fecal immunochemical testing (FIT) or
high-sensitivity guaiac-based fecal occult blood testing) oralternative structural examination (i.e., every 5 year CT
colonography or flexible sigmoidoscopy) may also be
considered if colonoscopy or multitarget stool DNA testing
are not feasible or acceptable to the survivor. All positive
results from these alternative testing methods should be
followed up with timely colonoscopy.
w

Additional Information

Participation in screening remains poor in the cancer survivor population, with >70% of at-risk survivors unscreened (see Daniel et al. 2015); thus it is important for clinicians to engage survivors in informed decision-making, weighing risks andbenefits of the available options, and selecting an option that is acceptable to the survivor and likely to result in successful completion of timely periodic screening.
For patients at high risk due to personal or family history or hereditary syndromes predisposing to colorectal cancer, more intensive and earlier screening is recommended (see Giardiello et al. 2014, Kahl et al. 2016, Lieberman et al. 2012, andSyngal et al. 2015).
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Current age ≥45 years, family history of colorectal cancer or polyps in first degree relative- Cancer/Treatment factors: Hepatoblastoma, gastrointestinal malignancy, higher radiation dose, especially ≥20 Gy, combination with chemotherapy (especially alkylators)- Pre-morbid/Co-morbid medical conditions: Obesity, ulcerative colitis, adenomatous polyps, familial polyposis- Health behaviors: High fat/low fiber diet

References
Daniel CL, Kohler CL, Stratton KL, et al: Predictors of colorectal cancer surveillance among survivors of childhood cancer treated with radiation: a report from the Childhood Cancer Survivor Study. Cancer 121:1856-63, 2015
Henderson TO, Oeffinger KC, Whitton J, et al: Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study. Ann Intern Med 156:757-66, W-260, 2012
Hodgson DC, Koh ES, Tran TH, et al: Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma. Cancer 110:2576-86, 2007
Nottage K, McFarlane J, Krasin MJ, et al: Secondary colorectal carcinoma after childhood cancer. J Clin Oncol 30:2552-8, 2012
Teepen JC, de Vroom SL, van Leeuwen FE, et al: Risk of subsequent gastrointestinal cancer among childhood cancer survivors: A systematic review. Cancer Treat Rev 43:92-103, 2016

Teepen JC, Kok JL, van Leeuwen FE, et al: Colorectal adenomas and cancers after childhood cancer treatment: A DCOG-LATER Record Linkage Study. J Natl Cancer Inst 110(7):758-767, 2018
Tukenova M, Diallo I, Anderson H, et al: Second malignant neoplasms in digestive organs after childhood cancer: a cohort-nested case-control study. Int J Radiat Oncol Biol Phys 82:e383-90, 2012
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POTENTIAL IMPACT TO
URINARY TRACTRADIATION
Sec #
87

w

Therapeutic
Exposure
Abdomen
TBI

Potential
Late Effects
Renal toxicity
Glomerular injury
Renal insufficiency
Hypertension

Periodic Evaluation
PHYSICAL
Blood pressure
YearlySCREENING
BUN
Creatinine
Na, K, Cl, CO2, Ca, Mg, PO4
Baseline at entry into long-term follow-up,
repeat as clinically indicatedHealth Counseling/
Further Considerations
HEALTH LINKS
Kidney Health
Cardiovascular Risk Factors
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Nephrology consultation for patients with hypertension or progressive renal
insufficiency.
SYSTEM = Urinary
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Bilateral Wilms tumor, nephrectomy, radiomimetic chemotherapy (e.g., doxorubicin, dactinomycin), combination with other nephrotoxic agents (e.g., cisplatin, carboplatin, ifosfamide, aminoglycosides, amphotericin, immunosuppressants), radiation dose ≥10 Gy, especially dose ≥15 Gy, TBI ≥6 Gy in single fraction, TBI ≥12 Gy fractionated, TBI combined with radiation to the kidney- Pre-morbid/Co-morbid medical conditions: Diabetes mellitus, hypertension, congenital absence of kidney

References
Dekkers IA, Blijdorp K, Cransberg K, et al: Long-term nephrotoxicity in adult survivors of childhood cancer. Clin J Am Soc Nephrol 8:922-9, 2013
Delgado J, Cooper N, Thomson K, et al: The importance of age, fludarabine, and total body irradiation in the incidence and severity of chronic renal failure after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 12:75-83, 2006
Dieffenbach BV, Liu Q, Murphy AJ, et al: Late-onset kidney failure in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Eur J Cancer 155:216-226, 2021
Fels LM, Bokemeyer C, van Rhee J, et al: Evaluation of late nephrotoxicity in long-term survivors of Hodgkin’s disease. Oncology 53:73-8, 1996
Frisk P, Bratteby LE, Carlson K, et al: Renal function after autologous bone marrow transplantation in children: a long-term prospective study. Bone Marrow Transplant 29:129-36, 2002
Green DM, Wang M, Krasin M, et al: Kidney function after treatment for childhood cancer: a report from the St. Jude Lifetime Cohort Study. J Am Soc Nephrol 32(4):983-993, 2021
Gronroos MH, Bolme P, Winiarski J, et al: Long-term renal function following bone marrow transplantation. Bone Marrow Transplant 39:717-23, 2007
Knijnenburg SL, Jaspers MW, van der Pal HJ, et al: Renal dysfunction and elevated blood pressure in long-term childhood cancer survivors. Clin J Am Soc Nephrol 7:1416-27, 2012
Lawton CA, Cohen EP, Murray KJ, et al: Long-term results of selective renal shielding in patients undergoing total body irradiation in preparation for bone marrow transplantation. Bone Marrow Transplant 20:1069-74, 1997
Miralbell R, Bieri S, Mermillod B, et al: Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease. J Clin Oncol 14:579-85, 1996
Ritchey ML, Green DM, Thomas PR, et al: Renal failure in Wilms’ tumor patients: a report from the National Wilms’ Tumor Study Group. Med Pediatr Oncol 26:75-80, 1996
Tarbell NJ, Guinan EC, Niemeyer C, et al: Late onset of renal dysfunction in survivors of bone marrow transplantation. Int J Radiat Oncol Biol Phys 15:99-104, 1988

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POTENTIAL IMPACT TO
URINARY TRACT (CONT)RADIATION
Sec #88

Therapeutic
Exposure
PelvisSpine (sacral, whole)

Potential
Late Effects
Urinary tract toxicity
Hemorrhagic cystitis
Bladder fibrosis
Dysfunctional voiding
Vesicoureteral reflux
Hydronephrosis

Periodic Evaluation
HISTORY
Hematuria
Urinary urgency/frequency
Urinary incontinence/retention
Dysuria
Nocturia
Abnormal urinary stream
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Bladder Health
COUNSELING
Promptly report dysuria or gross hematuria.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Urinalysis, urine culture, spot urine calcium/creatinine ratio for patients withpositive history.
Ultrasound of kidneys and bladder for patients with microscopic hematuria(defined as >5 RBC/HPF on at least 2 occasions).
Nephrology or urology referral for patients with culture-negative microscopic
hematuria AND abnormal ultrasound and/or abnormal calcium/creatinine ratio.
Urology referral for patients with culture-negative macroscopic hematuria,
incontinence, or dysfunctional voiding.
SYSTEM = Urinary
SCORE
Hemorrhagic cystitis = 2A
All Else = 1wAdditional Information

The bladder is included in the left and right flank/hemiabdomen treatment fields only if the fields extended below the iliac crest.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Higher radiation dose, especially ≥30 Gy to entire bladder, ≥45 Gy to portion of bladder, combination with cyclophosphamide, ifosfamide or vincristine

References
Hale GA, Marina NM, Jones-Wallace D, et al: Late effects of treatment for germ cell tumors during childhood and adolescence. J Pediatr Hematol Oncol 21:115-22, 1999
Levy A, Martelli H, Fayech C, et al: Late toxicity of brachytherapy after female genital tract tumors treated during childhood: Prospective evaluation with a long-term follow-up. Radiother Oncol 117:206-12, 2015
Marks LB, Carroll PR, Dugan TC, et al: The response of the urinary bladder, urethra, and ureter to radiation and chemotherapy. Int J Radiat Oncol Biol Phys 31:1257-80, 1995
Piver MS, Rose PG: Long-term follow-up and complications of infants with vulvovaginal embryonal rhabdomyosarcoma treated with surgery, radiation therapy, and chemotherapy. Obstet Gynecol 71:435-7, 1988
Raney B, Jr., Heyn R, Hays DM, et al: Sequelae of treatment in 109 patients followed for 5 to 15 years after diagnosis of sarcoma of the bladder and prostate. A report from the Intergroup Rhabdomyosarcoma Study Committee. Cancer
71:2387-94, 1993
Soler R, Macedo A, Jr., Bruschini H, et al: Does the less aggressive multimodal approach of treating bladder-prostate rhabdomyosarcoma preserve bladder function? J Urol 174:2343-6, 2005
Stillwell TJ, Benson RC, Jr.: Cyclophosphamide-induced hemorrhagic cystitis. A review of 100 patients. Cancer 61:451-7, 1988
Stillwell TJ, Benson RC, Jr., Burgert EO, Jr.: Cyclophosphamide-induced hemorrhagic cystitis in Ewing’s sarcoma. J Clin Oncol 6:76-82, 1988
Yeung CK, Ward HC, Ransley PG, et al: Bladder and kidney function after cure of pelvic rhabdomyosarcoma in childhood. Br J Cancer 70:1000-3, 1994

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POTENTIAL IMPACT TO
URINARY TRACT (CONT)RADIATION
Sec #89

Therapeutic
Exposure
PelvisSpine (sacral, whole)

Potential
Late Effects
Bladder malignancy

Periodic Evaluation
HISTORY
Hematuria
Urinary urgency/frequency
Urinary incontinence/retention
Dysuria
Nocturia
Abnormal urinary stream
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Bladder Health
COUNSELING
Promptly seek medical attention for dysuria or gross hematuria.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Urinalysis, urine culture, spot urine calcium/creatinine ratio for patients withpositive history.
Ultrasound of kidneys and bladder for patients with microscopic hematuria(defined as >5 RBC/HPF on at least 2 occasions).
Nephrology or urology referral for patients with culture-negative microscopic
hematuria AND abnormal ultrasound.
Urology referral for patients with culture-negative macroscopic hematuria.
SYSTEM = SMNSCORE = 2Aw

Additional Information

The bladder is included in the left and right flank/hemiabdomen treatment fields only if the fields extended below iliac crest.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Combination with cyclophosphamide or ifosfamide- Health behaviors: Alcohol use, smoking

References
Chou R, Dana T: Screening adults for bladder cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 153:461-8, 2010
Kersun LS, Wimmer RS, Hoot AC, et al: Secondary malignant neoplasms of the bladder after cyclophosphamide treatment for childhood acute lymphocytic leukemia. Pediatr Blood Cancer 42:289-91, 2004
Pedersen-Bjergaard J, Ersboll J, Hansen VL, et al: Carcinoma of the urinary bladder after treatment with cyclophosphamide for non-Hodgkin’s lymphoma. N Engl J Med 318:1028-32, 1988
Ritchey M, Ferrer F, Shearer P, et al: Late effects on the urinary bladder in patients treated for cancer in childhood: a report from the Children’s Oncology Group. Pediatr Blood Cancer 52:439-46, 2009
Travis LB, Curtis RE, Glimelius B, et al: Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin’s lymphoma. J Natl Cancer Inst 87:524-30, 1995

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POTENTIAL IMPACT TO
MALE REPRODUCTIVE SYSTEMRADIATION
Sec #90

Therapeutic
Exposure
Testes(male)

Potential
Late Effects
Testicular hormonal
dysfunction
Testosterone deficiency/
insufficiency
Delayed/Arrested puberty

Periodic Evaluation
HISTORY
Onset and tempo of puberty
Sexual function (erections, nocturnal
emissions, libido)
Medication use
YearlyPHYSICAL
Tanner staging until sexually mature
Testicular volume by Prader orchidometer
YearlyMonitor growth until mature
YearlySCREENING
AM testosterone in high risk patients
starting at 18 years

w

Health Counseling/
Further Considerations
HEALTH LINKS
Testicular and Reproductive Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Testosterone insufficiency or deficiency requiring hormone replacement after
alkylating agents only is rare.
Endocrine referral for the following:• No signs of puberty by age 14 years• Failure of pubertal progression• Adults with low AM testosterone levels
Periodic re-evaluation of testosterone in males with low normal testosterone asthey age or if they become symptomatic.
Bone density evaluation in androgen deficient patients.
Consider assessment of fertility status prior to initiation of testosterone
replacement therapy.
SYSTEM = Reproductive (Male)SCORE = 1

Additional Information

Testicular volume is not a reliable indicator of pubertal onset/stage in boys treated with alkylating agents and/or direct testicular radiotherapy.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Testicular cancer, testicular irradiation combined with head/brain irradiation, testicular dose ≥12 Gy, combination with alkylating agents, combination with cyclophosphamide conditioning for HCT,
combination with unilateral orchiectomy

References
Chemaitily W, Liu Q, van Iersel L, et al: Leydig cell function in male survivors of childhood cancer: a report from the St Jude Lifetime cohort study. J Clin Oncol 37:3018-31, 2019
Greenfield DM, Walters SJ, Coleman RE, et al: Prevalence and consequences of androgen deficiency in young male cancer survivors in a controlled cross-sectional study. J Clin Endocrinol Metab 92:3476-82, 2007
Kenney LB, Antal Z, Ginsberg JP, et al: Improving male reproductive health after childhood, adolescent, and young adult cancer: progress and future directions for survivorship research. J Clin Oncol 36:2160-68, 2018
Leung W, Hudson MM, Strickland DK, et al: Late effects of treatment in survivors of childhood acute myeloid leukemia. J Clin Oncol 18:3273-9, 2000
Lopez R, Plat G, Bertrand Y, et al: Testosterone deficiency in men surviving childhood acute leukemia after treatment with hematopoietic stem cell transplantation or testicular radiation: an L.E.A. study. Bone Marrow Transplant56(6):1422-1425, 2021
Mostafi-Moab S, Seidel K, Leisenring WM, et al: Endocrine abnormalities in aging survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. J Clin Oncol 34:3240-47, 2016
Petersen PM, Giwercman A, Daugaard G, et al: Effect of graded testicular doses of radiotherapy in patients treated for carcinoma-in-situ in the testis. J Clin Oncol 20:1537-43, 2002
Skinner R, Mulder RL, Kremer LC, et al: Recommendations for gonadotoxiity surveillance in male childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guidelines
Harmonization Group in collaboration with the PanCareSurFup Consortium, Lancet Oncol 18:e75-90, 2017
Sklar CA, Robison LL, Nesbit ME, et al: Effects of radiation on testicular function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Children Cancer Study Group. J Clin Oncol 8:1981-7, 1990
Sprauten M, Brydoy M, Haugnes HS, et al: Longitudinal serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels in a population-based sample of long-term testicular cancer survivors. J Clin Oncol 32:571-8,
2014
Wilhelmsson M, Vatanen A, Borgstrom B, et al: Adult testicular volume predicts spermatogenetic recovery after allogeneic HSCT in childhood and adolescence. Pediatr Blood Cancer 61:1094-100, 2014

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POTENTIAL IMPACT TO
MALE REPRODUCTIVE SYSTEM (CONT)RADIATION
Sec #91(male)

Therapeutic
Exposure
TestesTBI

Potential
Late Effects
Impaired spermatogenesis
Reduced fertility
Oligospermia
Azoospermia
Infertility

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Onset and tempo of puberty
Sexual function (erections, nocturnal
emissions, libido)
Medication use
YearlyPHYSICAL
Tanner staging until sexually mature
Testicular volume by Prader orchidometer
YearlyHEALTH LINKS

Testicular and Reproductive HealthRESOURCES
American Society for Reproductive Medicine: www.asrm.org
Alliance for Fertility Preservation: www.allianceforfertilitypreservation.org
COUNSELING
Need for contraception.
Review previous fertility preservation counseling/interventions.
Fertility recovery can be seen in the early years after completion of therapy andoccasionally thereafter.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
For sexually mature patients who desire information about potential future fertility:
semen analysis (optimal) and/or FSH and inhibin B (alternative if unable orunwilling to provide semen sample).
Reproductive endocrinology/urology referral for infertility evaluation and consultation
regarding assisted reproductive technologies.
SYSTEM = Reproductive (Male)SCORE = 1w

Additional Information

Testicular volume is not a reliable indicator of pubertal onset/stage in boys treated with alkylating agents and/or direct testicular radiotherapy.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Medications (anabolic steroids, testosterone), occupational exposures (pesticides, heavy metals, solvents)- Cancer/Treatment factors: Testicular cancer, fractionated small doses greater risk than single large doses, radiation dose to testes (up to 6 Gy azoospermia may be transient, ≥6 Gy azoospermia likely permanent and especially testiculardose ≥20 Gy), combination with alkylating agents, genitourinary surgery- Pre-morbid/Co-morbid medical conditions: Obesity, ejaculatory dysfunction, history of sexually transmitted infections, cGVHD- Health behaviors: Tobacco/Marijuana use

References
Anserini P, Chiodi S, Spinelli S, et al: Semen analysis following allogeneic bone marrow transplantation. Additional data for evidence-based counselling. Bone Marrow Transplant 30:447-51, 2002
Couto-Silva AC, Trivin C, Thibaud E, et al: Factors affecting gonadal function after bone marrow transplantation during childhood. Bone Marrow Transplant 28:67-75, 2001
Green DM, Kawashima T, Stovall M, et al: Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 28:332-9, 2010
Grigg AP, McLachlan R, Zaja J, et al: Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg). Bone Marrow Transplant 26:1089-95, 2000
Howell SJ, Shalet SM: Spermatogenesis after cancer treatment: damage and recovery. J Natl Cancer Inst Monogr:12-7, 2005
Jacob A, Barker H, Goodman A, et al: Recovery of spermatogenesis following bone marrow transplantation. Bone Marrow Transplant 22:277-9, 1998
Kenney LB, Antal Z, Ginsberg JP, et al: Improving male reproductive health after childhood, adolescent, and young adult cancer: progress and future directions for survivorship research. J Clin Oncol 36:2160-68, 2018
Rovo A, Tichelli A, Passweg JR, et al: Spermatogenesis in long-term survivors after allogeneic hematopoietic stem cell transplantation is associated with age, time interval since transplantation, and apparently absence of chronic GvHD. Blood
108:1100-5, 2006
Sklar CA, Robison LL, Nesbit ME, et al: Effects of radiation on testicular function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Children Cancer Study Group. J Clin Oncol 8:1981-7, 1990
Sprauten M, Brydoy M, Haugnes HS, et al: Longitudinal serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels in a population-based sample of long-term testicular cancer survivors. J Clin Oncol 32:571-8, 2014

Wasilewski-Masker K, Seidel KD, Leisenring W, et al: Male infertility in long-term survivors of pediatric cancer: a report from the Childhood Cancer Survivor Study. J Cancer Surviv 8:437-47, 2014
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POTENTIAL IMPACT TO
FEMALE REPRODUCTIVE SYSTEMRADIATION
Sec #92(female)Therapeutic
Exposure
PelvisSpine (sacral, whole)
TBI

Potential
Late Effects
Ovarian hormone deficiencies
Delayed puberty
Arrested pubertyPremature ovarian
insufficiency/Prematuremenopause

Periodic Evaluation
HISTORY
Onset and tempo of puberty
Menstrual history
Sexual function (vaginal dryness, libido)
Menopausal symptoms
Medication use
YearlyPHYSICAL
Tanner staging until sexually mature
YearlyMonitor growth until mature
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Ovarian and Reproductive Health
COUNSELING
Review previous fertility preservation counseling/interventions.
Higher cumulative doses of alkylating agents with or without radiation may
increase risk. Dose can be estimated using CED dose calculation located in
section 14.
Adverse impact of ovarian hormone deficiencies on growth, bone mineralization,
cardiovascular disease and sexual dysfunction.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
FSH and estradiol and/or endocrine/gynecology referral for patients with:• No signs of puberty by age 13 years• Failure of pubertal progression• Abnormal menstrual patterns or menopausal symptoms• Ovarian hormone deficiency/insufficiency to weigh risks and benefits of hormonal replacement therapy
Bone density evaluation in patients with ovarian hormone deficiencies.
SYSTEM = Reproductive (Female)
SCORE = 1w

Additional Information

The ovaries are included in the left and right flank/hemiabdomen treatment fields only if the fields extended below the iliac crest.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Older age at irradiation- Cancer/Treatment factors: Radiation dose ≥5 Gy if pubertal (especially ≥10 Gy), dose ≥10 Gy if prepubertal (especially ≥15 Gy), combination with alkylating agent chemotherapy, longer time since treatment, combination withcyclophosphamide conditioning for HCT- Health behaviors: Smoking

References
Chemaitilly W, Li Z, Krasin MJ, et al: Premature ovarian insufficiency in childhood cancer survivors: a report from the St. Jude Lifetime Cohort. J Clin Endocrinol Metab 102(7):2242-50, 2017
Chemaitilly W, Mertens AC, Mitby P, et al: Acute ovarian failure in the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 91:1723-8, 2006
Couto-Silva AC, Trivin C, Thibaud E, et al: Factors affecting gonadal function after bone marrow transplantation during childhood. Bone Marrow Transplant 28:67-75, 2001
Green DM, Sklar CA, Boice JD, Jr., et al: Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol 27:2374-81, 2009
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Molinari S, Parissone F, Evasi V, et al: Serum anti-Mullerian hormone as a marker of ovarian reserve after cancer treatment and/or hematopoietic stem cell transplantation in childhood: proposal for a systematic approach to gonadal
assessment. Eur J Endocrinol 185:717-728, 2021
Roshandel R, van Dijk M, Overbeek A, et al: LATER-VEVO Study Group. Female reproductive function after treatment of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 68(4):e28894, 2021
Sklar CA, Mertens AC, Mitby P, et al: Premature menopause in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 98:890-6, 2006
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POTENTIAL IMPACT TO
FEMALE REPRODUCTIVE SYSTEM (CONT)RADIATION
Sec #93(female)Therapeutic
Exposure
PelvisSpine (sacral, whole)
TBI

Potential
Late Effects
Diminished Ovarian Reserve(DOR)
Infertility

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Menstrual and pregnancy history
Hormonal Therapy
YearlyPHYSICAL
Tanner staging until sexually mature
YearlyHEALTH LINKS

Ovarian and Reproductive HealthRESOURCES
American Society for Reproductive Medicine: www.asrm.org
Alliance for Fertility Preservation: www.allianceforfertilitypreservation.org
Livestrong Foundation: www.livestrong.org/what-we-do/program/fertility
Oncofertility Consortium: https://oncofertility.msu.edu
COUNSELING
Need for contraception.
Review previous fertility preservation counseling/interventions.
Fertility recovery can be seen in the early years after the completion of therapy andoccasionally thereafter.
Potential for shorter period of fertility in family planning. Those with DOR should consider
discussing reproductive health options with a reproductive endocrinologist or fertility
specialist.
Higher cumulative doses of alkylating agents with or without radiation may increase risk.
Dose can be estimated using CED dose calculation located in section 15.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
FSH and estradiol for patients with menstrual cycle dysfunction suggestive of premature
ovarian insufficiency or those who desire information about potential for future fertility.
AMH to assess for diminished ovarian reserve.
Reproductive endocrinology referral for antral follicle count, ovarian reserve evaluationand consultation regarding assisted reproductive technologies in at-risk patients who
desire information about potential fertility and interventions to preserve future fertility.
SYSTEM = Reproductive (Female)
SCORE = 1w

Additional Information

The ovaries are included in the left and right flank/hemiabdomen treatment fields only if the fields extended below the iliac crest.
AMH may be low in the presence of normal FSH. AMH should be interpreted relative to age-specific reference ranges. FSH is lowered and AMH may be lowered by concurrent hormonal contraceptive use.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Older age at irradiation- Cancer/Treatment factors: Radiation dose ≥5 Gy if pubertal (especially ≥10 Gy), radiation dose ≥10 Gy if prepubertal (especially ≥15 Gy), combination with alkylating agent chemotherapy, longer time since treatment, combination with cyclophosphamide conditioning for HCT- Health behaviors: Smoking

References
Chemaitilly W, Li Z, Krasin MJ, et al: Premature ovarian insufficiency in childhood cancer survivors: a report from the St. Jude Lifetime Cohort. J Clin Endocrinol Metab 102(7):2242-50, 2017
Couto-Silva AC, Trivin C, Thibaud E, et al: Factors affecting gonadal function after bone marrow transplantation during childhood. Bone Marrow Transplant 28:67-75, 2001
Gao W, Liang JX, Yan Q: Exposure to radiation therapy is associated with female reproductive health among childhood cancer survivors: a meta-analysis study. J Assist Reprod Genet 32:1179-86, 2015
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POTENTIAL IMPACT TO
FEMALE REPRODUCTIVE SYSTEM (CONT)RADIATION
Section 93 References (cont)Green DM, Kawashima T, Stovall M, et al: Fertility of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 27:2677-2685, 2009
Green DM, Sklar CA, Boice JD, Jr., et al: Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol 27:2374-81, 2009
Levine JM, Kelvin JF, Quinn GP, et al: Infertility in reproductive-age female cancer survivors. Cancer 121:1532-9, 2015
Lie Fong S, Laven JS, Hakvoort-Cammel FG, et al: Assessment of ovarian reserve in adult childhood cancer survivors using anti-Mullerian hormone. Hum Reprod 24:982-90, 2009
Lunsford AJ, Whelan K, McCormick K, et al: Anti-Mullerian hormone as a measure of reproductive function in female childhood cancer survivors. Fertil Steril 101:227-31, 2014
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Sudour H, Chastagner P, Claude L, et al: Fertility and pregnancy outcome after abdominal irradiation that included or excluded the pelvis in childhood tumor survivors. Int J Radiat Oncol Biol Phys 76:867-73, 2010

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POTENTIAL IMPACT TO
FEMALE REPRODUCTIVE SYSTEM (CONT)RADIATION
Sec #94(female)Therapeutic
Exposure
PelvisSpine (sacral, whole)
TBI

Potential
Late Effects

Periodic Evaluation

Uterine vascular insufficiency HISTORY
Resulting in adverse pregnancy Pregnancy
outcomes such as:Childbirth history• Spontaneous abortion
Yearly for women of reproductive age• Neonatal death• Low-birth weight infant• Fetal malposition• Premature labor

Health Counseling/
Further Considerations
HEALTH LINKS
Ovarian and Reproductive HealthRESOURCES
American Society for Reproductive Medicine: www.asrm.org
Alliance for Fertility Preservation: www.allianceforfertilitypreservation.org
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
High-level ultrasound evaluation of genitourinary tract after pubertal
development as clinically indicated in patients contemplating pregnancy.
High-risk obstetrical care during pregnancy.
SYSTEM = Reproductive (Female)
SCORE = 2Bw

Additional Information

The uterus is included in the left and right flank/hemiabdomen treatment fields only if the fields extended below iliac crest.
10% of girls with Wilms tumor have congenital uterine anomalies.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Wilms tumor and associated Mullerian anomalies (i.e., agenesis, hypoplasia), prepubertal at time of treatment- Cancer/Treatment factors: TBI, higher radiation dose to pelvis, radiation dose ≥30 Gy

References
Gao W, Liang JX, Yan Q: Exposure to radiation therapy is associated with female reproductive health among childhood cancer survivors: a meta-analysis study. J Assist Reprod Genet 32:1179-86, 2015
Green DM, Lange JM, Peabody EM, et al: Pregnancy outcome after treatment for Wilms tumor: a report from the national Wilms tumor long-term follow-up study. J Clin Oncol 28:2824-30, 2010
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Rozen G, Rogers P, Chander S, et al: Clinical summary guide: reproduction in women with previous abdominopelvic radiotherapy or total body irradiation. Hum Reprod Open 25(4):hoaa045, 2020
Signorello LB, Cohen SS, Bosetti C, et al: Female survivors of childhood cancer: preterm birth and low birth weight among their children. J Natl Cancer Inst 98:1453-61, 2006
Signorello LB, Mulvihill JJ, Green DM, et al: Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study. Lancet 376:624-30, 2010
van de Loo LEXM, van den Berg MH, Overbeek A, et al: Uterine function, pregnancy complications, and pregnancy outcomes among female childhood cancer survivors. Fertil Steril 111(2):372-380, 2019
Winther JF, Boice JD, Jr., Svendsen AL, et al: Spontaneous abortion in a Danish population-based cohort of childhood cancer survivors. J Clin Oncol 26:4340-6, 2008

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POTENTIAL IMPACT TO
FEMALE REPRODUCTIVE SYSTEM (CONT)RADIATION
Sec #95

Therapeutic
Exposure
PelvisPotential
Late Effects
Vaginal fibrosis/stenosis(female)w

Periodic Evaluation
HISTORY
Psychosocial assessment
Dyspareunia
Post-coital bleeding
Difficulty with tampon insertion
Vaginal dryness
Vulvar pain/tenderness
Vulvovaginal burning or pruritus
Dysuria
YearlyPHYSICAL
Exam of external genitalia
YearlyHealth Counseling/
Further Considerations
COUNSELING
Avoid frequent contact with irritants (e.g., bubble bath, wet wipes and soaps).
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Gynecologic consultation for management.
Psychological consultation in patients with emotional difficulties.
SYSTEM = Reproductive (Female)
SCORE = 2A

Additional Information

The vagina is included in the left and right flank/hemiabdomen treatment fields only if the fields extended below iliac crest.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Vaginal tumor or pelvic tumor adjacent to vagina, radiation dose ≥50 Gy if postpubertal (especially dose ≥55 Gy), radiation dose ≥25 Gy if prepubertal (especially dose ≥35 Gy)- Pre-morbid/Co-morbid medical conditions: cGVHD

References
Flamant F, Gerbaulet A, Nihoul-Fekete C, et al: Long-term sequelae of conservative treatment by surgery, brachytherapy, and chemotherapy for vulval and vaginal rhabdomyosarcoma in children. J Clin Oncol 8:1847-53, 1990
Gaillard P, Krasin MJ, Laningham FH, et al: Hematometrocolpos in an adolescent female treated for pelvic Ewing sarcoma. Pediatr Blood Cancer 50:157-60, 2008
Levy A, Martelli H, Fayech C, et al: Late toxicity of brachytherapy after female genital tract tumors treated during childhood: Prospective evaluation with a long-term follow-up. Radiother Oncol 117:206-12, 2015
Magne N, Oberlin O, Martelli H, et al: Vulval and vaginal rhabdomyosarcoma in children: update and reappraisal of Institut Gustave Roussy brachytherapy experience. Int J Radiat Oncol Biol Phys 72:878-83, 2008
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Schover LR: Sexuality and fertility after cancer. Hematology Am Soc Hematol Educ Program:523-7, 2005
Spunt SL, Sweeney TA, Hudson MM, et al: Late effects of pelvic rhabdomyosarcoma and its treatment in female survivors. J Clin Oncol 23:7143-51, 2005

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POTENTIAL IMPACT TO
MUSCULOSKELETAL SYSTEMRADIATION
Sec #
96

w

Therapeutic
Exposure

Potential
Late Effects

Any Radiation (Including
TBI)

Musculoskeletal growth
problems
Hypoplasia
Fibrosis
Reduced or uneven growth
Shortened trunk height (trunkradiation)
Limb length discrepancy(extremity radiation)

Periodic Evaluation
PHYSICAL
HeightWeightYearlySitting height
Yearly for patients who had trunk radiation

Health Counseling/
Further Considerations
COUNSELING
Increased risk of fractures in weight-bearing irradiated bones.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Orthopedic consultation for any deficit noted in growing child.
Plastic surgery consult for reconstruction.
SYSTEM = Musculoskeletal
SCORE = 1

Limb lengths
Yearly for patients who had extremity radiation

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, especially prepubertal at treatment- Cancer/Treatment factors: Higher cumulative radiation dose, especially dose ≥20 Gy, larger radiation treatment field, higher radiation dose per fraction, orthovoltage radiation (commonly used before 1970) due to delivery ofgreater dose to skin and bones, epiphysis in treatment field

References
Chow EJ, Friedman DL, Yasui Y, et al: Decreased adult height in survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Pediatr 150:370-5, 375 e1, 2007
Chow EJ, Liu W, Srivastava K, et al: Differential effects of radiotherapy on growth and endocrine function among acute leukemia survivors: a Childhood Cancer Survivor Study report. Pediatr Blood Cancer 60:110-5, 2013
Fletcher BD: Effects of pediatric cancer therapy on the musculoskeletal system. Pediatr Radiol 27:623-36, 1997
Gawade PL, Hudson MM, Kaste SC, et al: A systematic review of selected musculoskeletal late effects in survivors of childhood cancer. Curr Pediatr Rev 10:249-62, 2014
Hogeboom CJ, Grosser SC, Guthrie KA, et al: Stature loss following treatment for Wilms tumor. Med Pediatr Oncol 36:295-304, 2001
Linsenmeier C, Thoennessen D, Negretti L, et al: Total body irradiation (TBI) in pediatric patients. A single-center experience after 30 years of low-dose rate irradiation. Strahlenther Onkol 186:614-20, 2010
Merchant TE, Nguyen L, Nguyen D, et al: Differential attenuation of clavicle growth after asymmetric mantle radiotherapy. Int J Radiat Oncol Biol Phys 59:556-61, 2004
Noorda EM, Somers R, van Leeuwen FE, et al: Adult height and age at menarche in childhood cancer survivors. Eur J Cancer 37:605-12, 2001
Probert JC, Parker BR: The effects of radiation therapy on bone growth. Radiology 114:155-62, 1975
Rohde RS, Puhaindran ME, Morris CD, et al: Complications of radiation therapy to the hand after soft tissue sarcoma surgery. J Hand Surg Am 35:1858-63, 2010

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POTENTIAL IMPACT TO
MUSCULOSKELETAL SYSTEM (CONT)RADIATION
Sec #97

Therapeutic
Exposure
Chest
AbdomenSpine (thoracic, lumbar,
whole)

Potential
Late Effects
Scoliosis/Kyphosis

Periodic Evaluation

Health Counseling/
Further Considerations

PHYSICALHEALTH LINKS
Exam of back/spine
Scoliosis and Kyphosis
Yearly until growth completed, may need more POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
frequent assessment during puberty or if
Spine films in patients with clinically apparent curve.
curve detected
Orthopedic consultation as indicated based on physical and/or radiographic
exam.
SYSTEM = Musculoskeletal
SCORE = 1w

Additional Information

With contemporary treatment approaches, scoliosis is infrequently seen as a consequence of radiation unless the patient has also undergone surgery to the hemithorax, abdomen or spine.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at irradiation- Cancer/Treatment factors: Paraspinal malignancies, hemithoracic, abdominal or spinal surgery, hemithoracic or abdominal radiation, radiation of only a portion of (rather than whole) vertebral body, radiation doses ≥20 Gy(lower doses for infants), orthovoltage radiation (commonly used before 1970)- Pre-morbid/Co-morbid medical conditions: Neurofibromatosis

Referencesde Jonge T, Slullitel H, Dubousset J, et al: Late-onset spinal deformities in children treated by laminectomy and radiation therapy for malignant tumours. Eur Spine J 14:765-71, 2005
Gawade PL, Hudson MM, Kaste SC, et al: A systematic review of selected musculoskeletal late effects in survivors of childhood cancer. Curr Pediatr Rev 10:249-62, 2014
Interiano RB, Kaste SC, Li C, et al: Associations between treatment, scoliosis, pulmonary function, and physical performance in long-term survivors of sarcoma. J Cancer Surviv 11(5),553–561, 2017Laverdiere C, Liu Q, Yasui Y, et al: Long-term outcomes in survivors of neuroblastoma: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 101:1131-40, 2009
Marcus RB, Esiashivilli N: Musculoskeletal, Integument, in Schwartz CL, Hobbie WL, Constine LS, et al (eds): Survivors of Childhood and Adolescent Cancer: A Multidisciplinary Approach. Switzerland, Springer International Publishing,
2015, pp pp. 297-324
Oshiro Y, Mizumoto M, Pan H, et al: Spinal changes after craniospinal irradiation in pediatric patients. Pediatr Blood Cancer 67(12):e28728, 2020
Paulino AC, Mayr NA, Simon JH, et al: Locoregional control in infants with neuroblastoma: role of radiation therapy and late toxicity. Int J Radiat Oncol Biol Phys 52:1025-31, 2002
Paulino AC, Wen BC, Brown CK, et al: Late effects in children treated with radiation therapy for Wilms’ tumor. Int J Radiat Oncol Biol Phys 46:1239-46, 2000

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POTENTIAL IMPACT TO
MUSCULOSKELETAL SYSTEM (CONT)RADIATION
Sec #98

Therapeutic
Exposure
Any Radiation (notincluding TBI)

Potential
Late Effects
Radiation-induced fracture

Periodic Evaluation
PHYSICAL
Pain, swelling, deformity of bone
As clinically indicatedHealth Counseling/
Further Considerations
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTIONRadiograph of affected bone as clinically indicated.
Orthopedic evaluation as clinically indicated.
SYSTEM = Musculoskeletal
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: History of surgery to cortex of bone, radiation dose ≥40 Gy, radiation dose ≥50 Gy to bone

References
Blaes AH, Lindgren B, Mulrooney DA, et al: Pathologic femur fractures after limb-sparing treatment of soft-tissue sarcomas. J Cancer Surviv 4:399-404, 2010
Cannon CP, Lin PP, Lewis VO, et al: Management of radiation-associated fractures. J Am Acad Orthop Surg 16:541-9, 2008
Im C, Li N, Moon W, et al: Genome-wide association studies reveal novel locus with sex-/therapy-specific fracture risk effects in childhood cancer survivors. J Bone Miner Res 36(4):685-695, 2021
Paulino AC: Late effects of radiotherapy for pediatric extremity sarcomas. Int J Radiat Oncol Biol Phys 60:265-74, 2004

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HEMATOPOIETIC CELL TRANSPLANT

INSTRUCTIONS

Hematopoietic Cell Transplant Introductory Information•

Complications after HCT have multifactorial etiologies, including prior therapy forprimary malignancy, intensity of transplant conditioning, stem cell product (e.g.,marrow, cord blood, peripheral stem cells), donor (e.g., autologous, allogeneic,
unrelated), quality of donor to recipient match, complications of the transplant
process (immunosuppression and GVHD), complications in the post-transplant period,
underlying disease, host genetic factors, and lifestyle behaviors.

Total Body Irradiation (TBI) Related Potential Late Effects
SectionNumberSex

Potential Late Effect

44

Both

Subsequent benign or malignant neoplasm occurring in ornear radiation field

45

Both

Dermatologic toxicity

46

Both

Brain tumor (benign or malignant)

47

Both

Neurocognitive deficits•

This section includes late treatment complications that may be observed inhematopoietic cell transplant recipients not covered elsewhere in these guidelines.

•

Refer to other sections of these guidelines for specific details related to latecomplications of radiation and of specific chemotherapeutic agents.

48

Both

Clinical leukoencephalopathy

53

Both

Growth hormone deficiency•

For HCT follow-up recommendations from the European Group for Blood and Marrow
Transplantation, Center for International Blood and Marrow Transplant Research, and
the American Society for Blood and Marrow Transplantation (EBMT/CIBMTR/ASBMT),
see: Majhail NS, Rizzo JD, Lee SJ, et al: Recommended screening and preventive
practices for long-term survivors after hematopoietic cell transplantation. Bone
Marrow Transplant 47:337-41, 2012.

58

Male

Gonadotropin deficiency

59

FemaleGonadotropin deficiency

61

Both

Cataracts

64

Both

Xerostomia; Salivary gland dysfunction

65

Both

Dental abnormalities; Temporomandibular joint dysfunction

For the Children’s Oncology Group Report regarding late effects surveillance
recommendations among survivors of childhood hematopoietic cell transplantation,see: Chow EJ, Anderson L, Baker KS, et al: Late Effects Surveillance
Recommendations among Survivors of Childhood Hematopoietic Cell Transplantation:
A Children’s Oncology Group Report. Biol Blood Marrow Transplant 22:782-95, 2016.

67

Both

Thyroid nodules

68

Both

Thyroid cancer

69

Both

Hypothyroidism

73

FemaleBreast cancer

74

FemaleBreast tissue hypoplasia

75

Both

Pulmonary toxicity

76

Both

Lung cancer

80

Both

Impaired glucose metabolism/diabetes mellitus

81

Both

Dyslipidemia

86

Both

Colorectal cancer

87

Both

Renal toxicity

91

Male

Impaired spermatogenesis

92

FemaleOvarian hormone deficiencies

93

FemaleDiminished ovarian reserve

94

FemaleUterine vascular insufficiency

96

Both

Musculoskeletal growth problems•

Total Body Irradiation (TBI) Related Potential Late Effects•

The complete list of potential late effects and associated Guideline section numbers
are included on the accompanying table for clinician convenience when evaluating
patients who received TBI. For details regarding each potential late effect andindicated screening, please refer to the relevant section within the Guidelines.

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HEMATOPOIETIC CELL TRANSPLANT
Sec #
99

w

Therapeutic
Exposure

Potential
Late Effects

Autologous
Hematopoietic Cell
Transplant (HCT)Acute myeloid leukemia(AML)
Myelodysplasia (MDS)

Periodic Evaluation
HISTORY
Fatigue
Bleeding
Easy bruising
Yearly, up to 10 years after transplant
PHYSICAL
Dermatologic exam (pallor, petechiae,
purpura)Yearly, up to 10 years after transplant

Health Counseling/
Further Considerations
HEALTH LINKS
Reducing the Risk of Subsequent Cancers
COUNSELING
Promptly seek medical attention for fatigue, pallor, petechiae or bone pain.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
CBC and bone marrow exam as clinically indicated.
SYSTEM = SMNSCORE = 1

Additional Information

There is negligible benefit to obtaining a screening CBC in the absence of clinical signs and symptoms for AML/MDS.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Older age at transplant- Cancer/Treatment factors: Radiation therapy, alkylating agent chemotherapy, epipodophyllotoxins, anthracyclines, history of non-Hodgkin and Hodgkin lymphoma, peripheral blood stem cells as the stem cell source- Pre-morbid/Co-morbid medical conditions: Evidence is conflicting that splenectomy modifies risk for AML/MDS

References
Allodji RS, Schwartz B, Veres C, et al: Risk of subsequent leukemia after a solid tumor in childhood: impact of bone marrow radiation therapy and chemotherapy. Int J Radiat Oncol Biol Phys 93:658-67, 2015
Baker KS, DeFor TE, Burns LJ, et al: New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol 21:1352-8, 2003
Bhatia S: Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol 40:666-75, 2013
Bhatia S, Ramsay NK, Steinbuch M, et al: Malignant neoplasms following bone marrow transplantation. Blood 87:3633-9, 1996
Danner-Koptik KE, Majhail NS, Brazauskas R, et al: Second malignancies after autologous hematopoietic cell transplantation in children. Bone Marrow Transplant 48:363-8, 2013
Kalaycio M, Rybicki L, Pohlman B, et al: Risk factors before autologous stem-cell transplantation for lymphoma predict for secondary myelodysplasia and acute myelogenous leukemia. J Clin Oncol 24:3604-10, 2006
Krishnan A, Bhatia S, Slovak ML, et al: Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors. Blood 95:1588-93, 2000
Landier W, Armenian SH, Lee J, et al: Yield of screening for long-term complications using the Children’s Oncology Group long-term follow-up guidelines. J Clin Oncol 30:4401-8, 2012
Pole JD, Darmawikarta D, Gassas A, et al: Subsequent malignant neoplasms in pediatric cancer patients treated with and without hematopoietic SCT. Bone Marrow Transplant 50:721-6, 2015
Rihani R, Bazzeh F, Faqih N, et al: Secondary hematopoietic malignancies in survivors of childhood cancer: an analysis of 111 cases from the Surveillance, Epidemiology, and End Result-9 registry. Cancer 116:4385-94, 2010

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HEMATOPOIETIC CELL TRANSPLANT (CONT)
Sec #
100
(male)

Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT)

Potential
Late Effects
Solid tumors
Such as basal cell carcinoma,
melanoma, liver cancer

Periodic Evaluation
PHYSICAL
Skin self exam
Monthly
Dermatologic exam
Abdominal exam
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Reducing the Risk of Subsequent Cancers
COUNSELING
Importance of sun protection measures.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Dermatology and/or oncology consultation as clinically indicated.
SYSTEM = SMNSCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at transplant- Cancer/Treatment factors: Radiation therapy (especially TBI), second HCT, umbilical cord blood HCT, haploidentical HCT, unrelated donor transplant, HLA mismatch, T-cell depletion, ATG- Pre-morbid/Co-morbid medical conditions: Hepatitis C infection, cGVHD, Fanconi anemia, primary immune deficiency

References
Baker KS, DeFor TE, Burns LJ, et al: New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol 21:1352-8, 2003
Bhatia S, Louie AD, Bhatia R, et al: Solid cancers after bone marrow transplantation. J Clin Oncol 19:464-71, 2001
Bhatia S, Ramsay NK, Steinbuch M, et al: Malignant neoplasms following bone marrow transplantation. Blood 87:3633-9, 1996
Curtis RE, Metayer C, Rizzo JD, et al: Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood 105:3802-11, 2005
Curtis RE, Rowlings PA, Deeg HJ, et al: Solid cancers after bone marrow transplantation. N Engl J Med 336:897-904, 1997
Leisenring W, Friedman DL, Flowers ME, et al: Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation. J Clin Oncol 24:1119-26, 2006
Majhail NS, Brazauskas R, Rizzo JD, et al: Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning. Blood 117:316-22, 2011
Pole JD, Darmawikarta D, Gassas A, et al: Subsequent malignant neoplasms in pediatric cancer patients treated with and without hematopoietic SCT. Bone Marrow Transplant 50:721-6, 2015
Rizzo JD, Curtis RE, Socie G, et al: Solid cancers after allogeneic hematopoietic cell transplantation. Blood 113:1175-83, 2009
Schwartz JL, Kopecky KJ, Mathes RW, et al: Basal cell skin cancer after total-body irradiation and hematopoietic cell transplantation. Radiat Res 171:155-63, 2009
Socie G, Curtis RE, Deeg HJ, et al: New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia. J Clin Oncol 18:348-57, 2000
Witherspoon RP, Fisher LD, Schoch G, et al: Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia. N Engl J Med 321:784-9, 1989

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HEMATOPOIETIC CELL TRANSPLANT (CONT)
Sec #
101
(female)Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT)

Potential
Late Effects
Solid tumors
Such as basal cell carcinoma,
melanoma, liver cancer, cervicalcancerPeriodic Evaluation
PHYSICAL
Skin self exam
Monthly
Dermatologic exam
Abdominal exam
YearlyPelvic exam
Every 3-5 years beginning at age 21 years (see“Screening” below for specific recommendations)
SCREENING
Cervical PAP smear
Cervical cancer screening should begin at age 21
years
Women: 21 to 29 years: PAP test every 3 years.
Women: 30 to 65 years: HPV and PAP test every 5
years (optimal), or PAP test alone every 3 years(alternative).
Women: >65 years: No testing for cervical cancer ifnormal screening results in past 10 years.

w

Health Counseling/
Further Considerations
HEALTH LINKS
Reducing the Risk of Subsequent Cancers
COUNSELING
Importance of sun protection measures.
Safer sexual practices to reduce HPV transmission.
Importance of HPV vaccination.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Dermatology, gynecology and/or oncology consultation as clinically indicated.
HPV vaccination per current recommendations.
SYSTEM = SMNSCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at transplant- Cancer/Treatment factors: Radiation therapy (especially TBI), second HCT, umbilical cord blood HCT, haploidentical HCT, unrelated donor transplant, HLA mismatch, T-cell depletion, ATG- Pre-morbid/Co-morbid medical conditions: Hepatitis C infection, HPV infection, cGVHD, Fanconi anemia, primary immune deficiency

References
Baker KS, DeFor TE, Burns LJ, et al: New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol 21:1352-8, 2003
Bhatia S, Louie AD, Bhatia R, et al: Solid cancers after bone marrow transplantation. J Clin Oncol 19:464-71, 2001
Bhatia S, Ramsay NK, Steinbuch M, et al: Malignant neoplasms following bone marrow transplantation. Blood 87:3633-9, 1996
Curtis RE, Metayer C, Rizzo JD, et al: Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood 105:3802-11, 2005
Curtis RE, Rowlings PA, Deeg HJ, et al: Solid cancers after bone marrow transplantation. N Engl J Med 336:897-904, 1997Friedman DL, Rovo A, Leisenring W, et al: Increased risk of breast cancer among survivors of allogeneic hematopoietic cell transplantation: a report from the FHCRC and the EBMT-Late Effect Working Party. Blood 111:939-44, 2008
Leisenring W, Friedman DL, Flowers ME, et al: Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation. J Clin Oncol 24:1119-26, 2006
Majhail NS, Brazauskas R, Rizzo JD, et al: Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning. Blood 117:316-22, 2011
Ojha RP, Tota JE, Offutt-Powell TN, et al: Human papillomavirus-associated subsequent malignancies among long-term survivors of pediatric and young adult cancers. PLoS One 8:e70349, 2013
Pole JD, Darmawikarta D, Gassas A, et al: Subsequent malignant neoplasms in pediatric cancer patients treated with and without hematopoietic SCT. Bone Marrow Transplant 50:721-6, 2015
Rizzo JD, Curtis RE, Socie G, et al: Solid cancers after allogeneic hematopoietic cell transplantation. Blood 113:1175-83, 2009
Schwartz JL, Kopecky KJ, Mathes RW, et al: Basal cell skin cancer after total-body irradiation and hematopoietic cell transplantation. Radiat Res 171:155-63, 2009
Socie G, Curtis RE, Deeg HJ, et al: New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia. J Clin Oncol 18:348-57, 2000
Witherspoon RP, Fisher LD, Schoch G, et al: Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia. N Engl J Med 321:784-9, 1989
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Sec #
102

Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT)

Potential
Late Effects
Hepatic toxicity
Chronic hepatitis
Cirrhosis
Iron overload
Cholelithiasis
FNH

Health Counseling/
Further Considerations

Periodic Evaluation
PHYSICAL
Scleral icterus
Jaundice
Ascites
Hepatomegaly
Splenomegaly
YearlySCREENING
ALT
AST
Bilirubin
Ferritin
Baseline at entry into long-term follow-up,
repeat as clinically indicated

HEALTH LINKS
Liver Health
Gastrointestinal Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Platelet count to evaluate hypersplenism and prothrombin time fto evaluate
hepatic synthetic function in patients with abnormal liver screening tests.
Screen for viral hepatitis in patients with persistently abnormal liver function or
any patient transfused prior to 1993.
PCR testing for HCV in immunosuppressed patients negative for antibody.
Gastroenterology/Hepatology consultation in patients with persistent liver
dysfunction or known hepatitis.
Hepatitis A and B immunization in at-risk patients lacking immunity.
T2* MRI for evaluation of liver iron content.
Liver biopsy in patients with evidence of excessive liver iron content (based onclinical context and magnitude of elevation).
Phlebotomy or chelation therapy for treatment of iron overload.
SYSTEM = GI/Hepatic
SCORE = 1w

Additional Information

FNH is a benign change that represents a scar in the liver.
FNH is usually an asymptomatic finding noted on MRI or ultrasound of the liver.
Continued observation or biopsy may be indicated depending on individual patient factors and imaging features.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: History of multiple transfusions, radiation to the liver, antimetabolite therapy- Pre-morbid/Co-morbid medical conditions: cGVHD, viral hepatitis, history of SOS, chronic hepatitis C with siderosis, steatosis, cholelithiasis- Health behaviors: Alcohol use (in relation to hepatic fibrosis and cirrhosis)

References
Castellino S, Muir A, Shah A, et al: Hepato-biliary late effects in survivors of childhood and adolescent cancer: a report from the Children’s Oncology Group. Pediatr Blood Cancer 54:663-9, 2010
Hoffmeister PA, Storer BE, McDonald GB, et al: Gallstones in pediatric hematopoietic cell transplant survivors with up to 40 years of follow-up. J Pediatr Hematol Oncol 36:484-90, 2014
Masetti R, Colecchia A, Rondelli R, et al: Benign hepatic nodular lesions after treatment for childhood cancer. J Pediatr Gastroenterol Nutr 56:151-5, 2013
McDonald GB: Hepatobiliary complications of hematopoietic cell transplantation, 40 years on. Hepatology 51:1450-60, 2010
McKay PJ, Murphy JA, Cameron S, et al: Iron overload and liver dysfunction after allogeneic or autologous bone marrow transplantation. Bone Marrow Transplant 17:63-6, 1996
Mulder RL, van Dalen EC, Van den Hof M, et al: Hepatic late adverse effects after antineoplastic treatment for childhood cancer. Cochrane Database Syst Rev:CD008205, 2011
Peffault de Latour R, Levy V, Asselah T, et al: Long-term outcome of hepatitis C infection after bone marrow transplantation. Blood 103:1618-24, 2004
Pillon M, Carucci NS, Mainardi C, et al: Focal nodular hyperplasia of the liver: an emerging complication of hematopoietic SCT in children. Bone Marrow Transplant 50:414-9, 2015
Schempp A, Lee J, Kearney S, et al: Iron overload in survivors of childhood cancer. J Pediatr Hematol Oncol 38(1):27-31, 2016

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w

Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT)

Potential
Late Effects
Osteonecrosis (avascularnecrosis)

Periodic Evaluation
HISTORY
Joint pain
Swelling
Immobility
Limited range of motion
YearlyPHYSICAL
Musculoskeletal exam
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Osteonecrosis
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
MRI as clinically indicated.
Orthopedic consultation in patients with positive imaging and/or symptoms ofosteonecrosis.
Physical therapy evaluation (for non-pharmacologic pain management, range of
motion, strengthening, stretching, functional mobility).
SYSTEM = Musculoskeletal
SCORE = 1

Additional Information

Osteonecrosis typically occurs during the acute treatment phase, may progress over time or resolve.
Multifocal osteonecrosis is significantly more common (3:1) than unifocal.
Symptomatic lesions confer the greatest risk for collapse.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Being pubertal or post-pubertal at time of transplant- Cancer/Treatment factors: Corticosteroids (dexamethasone effect is more potent than prednisone), other immunosuppressants, prolonged immunosuppressive therapy (e.g., for cGVHD), TBI, high dose radiation to any bone,allogeneic HCT > autologous HCT- Pre-morbid/Co-morbid medical conditions: Sickle cell disease, cGVHD, pre-transplant osteonecrosis

References
Campbell S, Sun CL, Kurian S, et al: Predictors of avascular necrosis of bone in long-term survivors of hematopoietic cell transplantation. Cancer 115:4127-35, 2009
Faraci M, Calevo MG, Lanino E, et al: Osteonecrosis after allogeneic stem cell transplantation in childhood. A case-control study in Italy. Haematologica 91:1096-9, 2006
Kadan-Lottick NS, Dinu I, Wasilewski-Masker K, et al: Osteonecrosis in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 26:3038-45, 2008
Karimova EJ, Wozniak A, Wu J, et al: How does osteonecrosis about the knee progress in young patients with leukemia?: a 2- to 7-year study. Clin Orthop Relat Res 468:2454-9, 2010
Kuhlen M, Bader P, Sauer M, et al: Low incidence of symptomatic osteonecrosis after allogeneic HSCT in children with high-risk or relapsed ALL - results of the ALL-SCT 2003 trial. Br J Haematol 183(1):104-109, 2018
Leung W, Ahn H, Rose SR, et al: A prospective cohort study of late sequelae of pediatric allogeneic hematopoietic stem cell transplantation. Medicine (Baltimore) 86:215-24, 2007
Mattano LA, Jr., Sather HN, Trigg ME, et al: Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children’s Cancer Group. J Clin Oncol 18:3262-72, 2000
Schulte CM, Beelen DW: Avascular osteonecrosis after allogeneic hematopoietic stem-cell transplantation: diagnosis and gender matter. Transplantation 78:1055-63, 2004
Sun CL, Francisco L, Kawashima T, et al: Prevalence and predictors of chronic health conditions after hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study. Blood 116:3129-39; quiz 3377, 2010

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HEMATOPOIETIC CELL TRANSPLANT (CONT)
Sec #
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Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT)

Potential
Late Effects
Reduced bone mineral density(BMD)
Defined as Z-score >2 SD below
the mean in male survivors <50
years old and premenopausal
women or T-score >1 SD below
the mean in male survivors >50
years old and postmenopausal
women

Periodic Evaluation
SCREENING
Bone density evaluation (DXA)
Adjust for height-age Z-score in survivors <age
20 years*Baseline BMD at entry into long-term follow-up (2to 5 years after completion of therapy) with thefollowing recommended actions:• If Z-score >1 SD above the mean (normal),repeat at 25 years of age when peak bone mass
should be achieved• Between these two measurements and thereafter, screen as clinically indicated based on BMD
and ongoing risk assessment• If Z-score >2 SD below the mean, referral to (orconsultation of) a bone health specialist• If Z-score >1 and <2 SD below the mean,evaluation for endocrine defects (e.g., hypogonadism or GH deficiency) and consultation with abone health specialist for further evaluation andinterpretation of findings as clinically indicated.
Repeat DXA after 2 years and thereafter as clinically indicated based on BMD change (i.e., BMD
decline is greater than the DXA least significant
change) and ongoing risk assessment

Health Counseling/
Further Considerations
HEALTH LINKS
Bone HealthRESOURCES
National Osteoporosis Foundation: www.nof.org
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Ensure the AAP recommended minimum daily intake of vitamin D (400 IU/day) for infants<12 months, 600 IU/day for those aged 12 months through aged 70 years, 800 IU/day
for those >70 years
Ensure adequate dietary calcium (see table in the “Bone Health” Health Link for ageappropriate recommendations). Supplements may be necessary if there are dietary
restrictions.
Use caution regarding calcium supplementation in patients with history of renal lithiasis.
Advocate for regular weight-bearing exercises such as running and jumping.
Treat exacerbating or predisposing conditions (e.g., hormonal replacement therapy
for hypogonadism, GH deficiency, correction of chronic metabolic acidosis that could
accelerate bone loss).
Endocrine consultation for patients with osteoporosis or history of multiple fractures
for pharmacologic interventions (e.g., bisphosphonates, calcitonin, selective estrogen
receptor modulators).
SYSTEM = Musculoskeletal
SCORE = 2B

*Pediatric Z-score calculator adjusted forheight age: https://zscore.research.chop.edu/
calcpedbonedens.phpw

Additional Information

The World Health Organization definition of osteoporosis in adults is based on comparison of a measured BMD of young adults at peak bone age and defined as a T-score.
A T-score is the number of standard deviations the BMD measurement is above or below the mean.
Current definitions of osteopenia (T-scores between 1.0 and 2.5 SD below the mean) and osteoporosis (T-scores >2.5 SD below the mean) were developed primarily in the context of postmenopausal women. In this population, T-scores have awell-validated correlation with fracture risk that increases with age.
The fracture risk associated with T-scores in younger populations, including cancer survivors with treatment-related hypogonadism, has not been established.
T-scores are not appropriate to assess skeletal health in pediatric patients who have not achieved peak adult bone mass.
Pediatric BMD reference data sets calculate Z-scores based on age and gender.
A Z-score is the number of standard deviations the measurement is above or below the age-matched mean BMD.
The fracture risk in pediatric patients with low bone density for chronologic age based on Z-scores has not been established.
There are no defined standards for referral or treatment of low BMD in children.

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HEMATOPOIETIC CELL TRANSPLANT (CONT)
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Caucasian race, lower weight/BMI.
- Cancer/Treatment factors: Corticosteroids (especially prolonged therapy, e.g., for cGVHD), CRT, craniospinal radiation, HCT/TBI- Pre-morbid/Co-morbid medical conditions: GH deficiency, hypogonadism/delayed puberty, hyperthyroidism, central and primary hypogonadism- Health behaviors: Intake of calcium and vitamin D, intake of alcohol and carbonated beverages, lack of weight bearing exercise, smoking

References
Bischoff-Ferrari HA: Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol 624:55-71, 2008
Buxbaum NP, Robinson C, Sinaii N, et al: Impaired bone mineral density in pediatric patients with chronic graft-versus-host disease. Biol Blood Marrow Transplant 24(7):1415-23, 2018
Chemaitilly W, Li Z, Krasin MJ, et al: Premature ovarian insufficiency in childhood cancer survivors: a report from the St. Jude Lifetime Cohort. J Clin Endocrinol Metab 102(7):2242-50, 2017
Chemaitilly W, Sklar CA: Endocrine complications of hematopoietic stem cell transplantation. Endocrinol Metab Clin North Am 36:983-98; ix, 2007
Cho WK, Ahn MB, Lee JW, et al: Low bone mineral density in adolescents with leukemia after hematopoietic stem cell transplantation: prolonged steroid therapy for GvHD and endocrinopathy after hematopoietic stem cell transplantation might bemajor concerns? Bone Marrow Transplant 52(1):144-6, 2017
Kaste SC, Shidler TJ, Tong X, et al: Bone mineral density and osteonecrosis in survivors of childhood allogeneic bone marrow transplantation. Bone Marrow Transplant 33:435-41, 2004
Klopfenstein KJ, Clayton J, Rosselet R, et al: Prevalence of abnormal bone density of pediatric patients prior to blood or marrow transplant. Pediatr Blood Cancer 53:675-7, 2009
Landier W, Armenian SH, Lee J, et al: Yield of screening for long-term complications using the Children’s Oncology Group long-term follow-up guidelines. J Clin Oncol 30:4401-8, 2012
Le Meignen M, Auquier P, Barlogis V, et al: Bone mineral density in adult survivors of childhood acute leukemia: impact of hematopoietic stem cell transplantation and other treatment modalities. Blood 118:1481-9, 2011
McDonald L, Luke J, Jude V, et al: Development of an evidence-based clinical guideline for age-appropriate screening, prevention, and management of bone abnormalities in children post-hematopoietic stem cell transplant. J Pediatr Oncol Nurs
30:78-89, 2013
NIH Office of Dietary Supplements: Vitamin D health professionals fact sheet. Accessed March 16, 2023: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional
Polgreen LE, Petryk A, Dietz AC, et al: Modifiable risk factors associated with bone deficits in childhood cancer survivors. BMC Pediatr 12:40, 2012
Ruble K: Skeletal complications after bone marrow transplant in childhood. J Pediatr Oncol Nurs 25:79-85, 2008
The International Society for Clinical Densitometry. 2019 ISCD official positions. Accessed March 2023: https://iscd.org/learn/official-positions
Tylavsky FA, Smith K, Surprise H, et al: Nutritional intake of long-term survivors of childhood acute lymphoblastic leukemia: evidence for bone health interventional opportunities. Pediatr Blood Cancer 55:1362-9, 2010
van Atteveld JE, Mulder RL, van den Heuvel-Eibrink MM, et al. Bone mineral density surveillance for childhood, adolescent, and young adult cancer survivors: evidence-based recommendations from the International Late Effects of Childhood
Cancer Guideline Harmonization Group. Lancet Diabetes Endocrinol 9(9):622-637, 2021
Zemel BS, Leonard MB, Kelly A, et al: Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children. J Clin Endocrinol Metab 95:1265-73, 2010

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HEMATOPOIETIC CELL TRANSPLANT (CONT)
Sec #
105

Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT)

Potential
Late Effects
Renal toxicity
Glomerular injury
Renal insufficiency
Hypertension
Tubular injury (renal tubularacidosis, Fanconi syndrome,
hypophosphatemic rickets)

Periodic Evaluation
PHYSICAL
Blood pressure
YearlySCREENING
BUN
Creatinine
Na, K, Cl, CO2, Ca, Mg, PO4
Baseline at entry into long-term follow-up,
repeat as clinically indicatedHealth Counseling/
Further Considerations
HEALTH LINKS
Kidney Health
Cardiovascular Risk Factors
COUNSELINGIn patients with salt-wasting tubular dysfunction, educate that low magnesium
levels potentiate coronary atherosclerosis.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTIONElectrolyte supplements for patients with persistent electrolyte wasting.
Nephrology consultation for patients with hypertension or progressive renal
insufficiency.
SYSTEM = Urinary
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Older age- Cancer/Treatment factors: Chronic cyclosporine use, TBI- Pre-morbid/Co-morbid medical conditions: Acute kidney injury within 6 months of HCT, history of cGVHD

References
Abboud I, Porcher R, Robin M, et al: Chronic kidney dysfunction in patients alive without relapse 2 years after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 15:1251-7, 2009
Al-Hazzouri A, Cao Q, Burns LJ, et al: Similar risks for chronic kidney disease in long-term survivors of myeloablative and reduced-intensity allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 14:658-63, 2008
Ando M, Ohashi K, Akiyama H, et al: Chronic kidney disease in long-term survivors of myeloablative allogeneic haematopoietic cell transplantation: prevalence and risk factors. Nephrol Dial Transplant 25:278-82, 2010
Ceremuzynski L, Gebalska J, Wolk R, et al: Hypomagnesemia in heart failure with ventricular arrhythmias. Beneficial effects of magnesium supplementation. J Intern Med 247:78-86, 2000
Choi M, Sun CL, Kurian S, et al: Incidence and predictors of delayed chronic kidney disease in long-term survivors of hematopoietic cell transplantation. Cancer 113:1580-7, 2008
Ellis MJ, Parikh CR, Inrig JK, et al: Chronic kidney disease after hematopoietic cell transplantation: a systematic review. Am J Transplant 8:2378-90, 2008
Esiashvili N, Chiang KY, Hasselle MD, et al: Renal toxicity in children undergoing total body irradiation for bone marrow transplant. Radiother Oncol 90:242-6, 2009
Gerstein J, Meyer A, Sykora KW, et al: Long-term renal toxicity in children following fractionated total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT). Strahlenther Onkol 185:751-5, 2009
Hoffmeister PA, Hingorani SR, Storer BE, et al: Hypertension in long-term survivors of pediatric hematopoietic cell transplantation. Biol Blood Marrow Transplant 16:515-24, 2010
Majhail NS, Challa TR, Mulrooney DA, et al: Hypertension and diabetes mellitus in adult and pediatric survivors of allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 15:1100-7, 2009
Nieder ML, McDonald GB, Kida A, et al: National Cancer Institute-National Heart, Lung and Blood Institute/Pediatric Blood and Marrow Transplant Consortium First International Consensus Conference on late effects after pediatrichematopoietic cell transplantation: long-term organ damage and dysfunction. Biol Blood Marrow Transplant 17:1573-84, 2011

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Therapeutic
Exposure

Potential
Late Effects

Hematopoietic Cell
Transplant (HCT) withany history of cGVHD

Dermatologic toxicity
Permanent alopecia
Nail dystrophy
Vitiligo
Sclerodermatous changes
Squamous cell carcinoma of
the skin
Melanoma
Altered skin pigmentation

Periodic Evaluation
PHYSICAL
Skin self exam
Every 3 months
Hair (alopecia)
Nails (dystrophy)
Skin (vitiligo, atypical and changing skinlesions, sclerodermatous changes)
YearlyWITH CHRONIC GVHD
Health Counseling/
Further Considerations
HEALTH LINKS
Skin Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Surgery, dermatology, and/or oncology consultation as clinically indicated.
SYSTEM = Dermatologic
SCORE = 1

Additional Information

Dermatologic toxicity is more common in presence of active cGVHD; effects may persist after cGVHD resolves.

References
Antin JH: Clinical practice. Long-term care after hematopoietic-cell transplantation in adults. N Engl J Med 347:36-42, 2002
Curtis RE, Metayer C, Rizzo JD, et al: Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood 105:3802-11, 2005
Huang JT, Duncan CN, Boyer D, et al: Nail dystrophy, edema, and eosinophilia: harbingers of severe chronic GVHD of the skin in children. Bone Marrow Transplant 49:1521-7, 2014
Kinahan KE, Sharp LK, Seidel K, et al: Scarring, disfigurement, and quality of life in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 30:2466-74, 2012
Leisenring W, Friedman DL, Flowers ME, et al: Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation. J Clin Oncol 24:1119-26, 2006
Sanli H, Akay BN, Arat M, et al: Vitiligo after hematopoietic cell transplantation: six cases and review of the literature. Dermatology 216:349-54, 2008
Skert C, Patriarca F, Sperotto A, et al: Sclerodermatous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: incidence, predictors and outcome. Haematologica 91:258-61, 2006
Vajdic CM, Mayson E, Dodds AJ, et al: Second cancer risk and late mortality in adult Australians receiving allogeneic hematopoietic stem cell transplantation: a population-based cohort study. Biol Blood Marrow Transplant 22:949-56,
2016
Zuo RC, Naik HB, Steinberg SM, et al: Risk factors and characterization of vitiligo and alopecia areata in patients with chronic graft-vs-host disease. JAMA Dermatol 151:23-32, 2015

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Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT) withany history of cGVHD

Potential
Late Effects

Periodic Evaluation

Xerophthalmia
HISTORY(keratoconjunctivitis sicca) Dry eyes (burning, itching, foreign bodysensation, inflammation)
YearlyPHYSICAL
Eye exam
YearlySCREENING
Evaluation by ophthalmologist or
optometrist
YearlyWITH CHRONIC GVHD (CONT)
Health Counseling/
Further Considerations
HEALTH LINKS
Eye Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Supportive care with artificial tears.
SYSTEM = Ocular
SCORE = 1

Additional Information

Xerophthalmia is more common in presence of active cGVHD; effects may persist after cGVHD resolves.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Cranial radiation, higher radiation dose, especially ≥30 Gy, radiation fraction ≥2 Gy, radiomimetic chemotherapy (e.g., doxorubicin, dactinomycin)

References
Espana EM, Shah S, Santhiago MR, et al: Graft versus host disease: clinical evaluation, diagnosis and management. Graefes Arch Clin Exp Ophthalmol 251:1257-66, 2013
Ng JS, Lam DS, Li CK, et al: Ocular complications of pediatric bone marrow transplantation. Ophthalmology 106:160-4, 1999
Riemens A, te Boome L, Imhof S, et al: Current insights into ocular graft-versus-host disease. Curr Opin Ophthalmol 21:485-94, 2010
Shikari H, Antin JH, Dana R: Ocular graft-versus-host disease: a review. Surv Ophthalmol 58:233-51, 2013
Socie G, Salooja N, Cohen A, et al: Nonmalignant late effects after allogeneic stem cell transplantation. Blood 101:3373-85, 2003
Suh DW, Ruttum MS, Stuckenschneider BJ, et al: Ocular findings after bone marrow transplantation in a pediatric population. Ophthalmology 106:1564-70, 1999
Townley JR, Dana R, Jacobs DS: Keratoconjunctivitis sicca manifestations in ocular graft versus host disease: pathogenesis, presentation, prevention, and treatment. Semin Ophthalmol 26:251-60, 2011
Westeneng AC, Hettinga Y, Lokhorst H, et al: Ocular graft-versus-host disease after allogeneic stem cell transplantation. Cornea 29:758-63, 2010

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Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT) withany history of cGVHD

Potential
Late Effects
Oral toxicity
Xerostomia
Salivary gland dysfunction
Dental caries
Periodontal disease
Oral cancer (squamous cell
carcinoma)

Periodic Evaluation
HISTORY
Xerostomia
YearlyPHYSICAL
Oral exam
YearlySCREENING
Dental exam and cleaning
Every 6 months

WITH CHRONIC GVHD (CONT)
Health Counseling/
Further Considerations
HEALTH LINKS
Dental Health
COUNSELING
Safer sexual practices to reduce HPV transmission.
Importance of HPV vaccination.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Supportive care with saliva substitutes, moistening agents, and sialagogues(pilocarpine).
Regular dental care including fluoride applications and intraoral malignancy
screening.
Head and neck/otolaryngology consultation as indicated.
HPV vaccination per current recommendations.
SYSTEM = Dental
SCORE = 1w

Additional Information

Oral-dental late effects are more common in presence of active cGVHD; effects may persist after cGVHD resolves.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Use of azathioprine for cGVHD management, head and neck radiation involving the parotid gland, higher radiation dose, especially ≥30 Gy, radiomimetic chemotherapy (e.g., doxorubicin,
dactinomycin)- Pre-morbid/Co-morbid medical conditions: High grade of cGVHD, Fanconi anemia, dyskeratosis congenita, HPV infection

References
Alter BP, Giri N, Savage SA, et al: Cancer in dyskeratosis congenita. Blood 113:6549-57, 2009
American Academy of Pediatric Dentistry: Guideline on dental management of pediatric patients receiving chemotherapy, hematopoietic cell transplantation, and/or radiation. Pediatr Dent 35:E185-93, 2013
Bhatia S, Louie AD, Bhatia R, et al: Solid cancers after bone marrow transplantation. J Clin Oncol 19:464-71, 2001
Brocklehurst P, Kujan O, O’Malley LA, et al: Screening programmes for the early detection and prevention of oral cancer. Cochrane Database Syst Rev:CD004150, 2013
Chaturvedi AK, Graubard BI, Broutian T, et al: Effect of prophylactic human papillomavirus (HPV) vaccination on oral HPV infections among young adults in the United States. J Clin Oncol 36:262-267, 2018
Curtis RE, Metayer C, Rizzo JD, et al: Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood 105:3802-11, 2005
Dahllof G, Bagesund M, Remberger M, et al: Risk factors for salivary dysfunction in children 1 year after bone marrow transplantation. Oral Oncol 33:327-31, 1997
Effinger KE, Migliorati CA, Hudson MM, et al: Oral and dental late effects in survivors of childhood cancer: a Children’s Oncology Group report. Support Care Cancer 22:2009-19, 2014
Elad S, Raber-Durlacher JE, Brennan MT, et al: Basic oral care for hematology-oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of
Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT). Support Care Cancer 23:223-36, 2015
Gawade PL, Hudson MM, Kaste SC, et al: A systematic review of dental late effects in survivors of childhood cancer. Pediatr Blood Cancer 61:407-16, 2014
Guchelaar HJ, Vermes A, Meerwaldt JH: Radiation-induced xerostomia: pathophysiology, clinical course and supportive treatment. Support Care Cancer 5:281-8, 1997
Masserot C, Peffault de Latour R, Rocha V, et al: Head and neck squamous cell carcinoma in 13 patients with Fanconi anemia after hematopoietic stem cell transplantation. Cancer 113:3315-22, 2008
Meier JK, Wolff D, Pavletic S, et al: Oral chronic graft-versus-host disease: report from the International Consensus Conference on clinical practice in cGVHD. Clin Oral Investig 15:127-39, 2011
Ojha RP, Tota JE, Offutt-Powell TN, et al: Human papillomavirus-associated subsequent malignancies among long-term survivors of pediatric and young adult cancers. PLoS One 8:e70349, 2013
Treister NS, Woo SB, O’Holleran EW, et al: Oral chronic graft-versus-host disease in pediatric patients after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 11:721-31, 2005
van der Pas-van Voskuilen IG, Veerkamp JS, Raber-Durlacher JE, et al: Long-term adverse effects of hematopoietic stem cell transplantation on dental development in children. Support Care Cancer 17:1169-75, 2009
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Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT) withany history of cGVHD

Potential
Late Effects
Pulmonary toxicity
Bronchiolitis obliterans
Chronic bronchitis
Bronchiectasis

Periodic Evaluation
HISTORY
Cough
Wheezing
Shortness of breath
Dyspnea on exertion
YearlyPHYSICAL
Pulmonary exam
YearlySCREENING
PFTs (including DLCO and spirometry)
Baseline at entry into long-term follow-up,
repeat as clinically indicated in patients withabnormal results or progressive pulmonary
dysfunction

WITH CHRONIC GVHD (CONT)
Health Counseling/
Further Considerations
HEALTH LINKS
Pulmonary HealthRESOURCES
www.smokefree.gov
COUNSELING
Tobacco and Environmental tobacco smoke avoidance/Smoking cessation.
Influenza and Pneumococcal vaccinations.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Repeat PFTs prior to general anesthesia.
Pulmonary consultation for patients with symptomatic pulmonary dysfunction.
Pulmonary consultation for survivors who desire to SCUBA dive (due to potential
undiagnosed pulmonary toxicities, and limited data to guide safe diving
recommendations for individuals treated with pulmonary toxic therapy).
SYSTEM = Pulmonary
SCORE = 1

Additional Information

Pulmonary late effects are more common in presence of active cGVHD; effects may persist after cGVHD resolves.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Prolonged immunosuppression related to cGVHD, chest radiation, TBI, pulmonary toxic chemotherapy (e.g., busulfan, bleomycin, carmustine [BCNU], lomustine [CCNU])- Health behaviors: Smoking, inhaled illicit drug use

References
Dietz AC, Chen Y, Yasui Y, et al: Risk and impact of pulmonary complications in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 122:3687-3696, 2016
Gower WA, Collaco JM, Mogayzel PJ, Jr.: Lung function and late pulmonary complications among survivors of hematopoietic stem cell transplantation during childhood. Paediatr Respir Rev 11:115-22, 2010
Huang TT, Hudson MM, Stokes DC, et al: Pulmonary outcomes in survivors of childhood cancer: a systematic review. Chest 140:881-901, 2011
Inaba H, Yang J, Pan J, et al: Pulmonary dysfunction in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem cell transplantation. Cancer 116:2020-30, 2010
Madanat-Harjuoja LM, Valjento S, Vettenranta K, et al: Pulmonary function following allogeneic stem cell transplantation in childhood: a retrospective cohort study of 51 patients. Pediatr Transplant 18:617-24, 2014
Nakasone H, Onizuka M, Suzuki N, et al: Pre-transplant risk factors for cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia after hematopoietic cell transplantation. Bone Marrow Transplant 48:1317-23,
2013
Nishio N, Yagasaki H, Takahashi Y, et al: Late-onset non-infectious pulmonary complications following allogeneic hematopoietic stem cell transplantation in children. Bone Marrow Transplant 44:303-8, 2009
Uhlving HH, Bang CL, Christensen IJ, et al: Lung function after allogeneic hematopoietic stem cell transplantation in children: a longitudinal study in a population-based cohort. Biol Blood Marrow Transplant 19:1348-54, 2013
van Hulst RA, Rietbroek RC, Gaastra MT, et al: To dive or not to dive with bleomycin: a practical algorithm. Aviat Space Environ Med 82:814-8, 2011
Yoshihara S, Yanik G, Cooke KR, et al: Bronchiolitis obliterans syndrome (BOS), bronchiolitis obliterans organizing pneumonia (BOOP), and other late-onset noninfectious pulmonary complications following allogeneic hematopoietic
stem cell transplantation. Biol Blood Marrow Transplant 13:749-59, 2007

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Therapeutic
Exposure

Potential
Late Effects

Hematopoietic Cell
Transplant (HCT) withany history of cGVHD

Immunologic complications
Secretory IgA deficiency
Hypogammaglobulinemia
Decreased B cells
T cell dysfunction
Chronic infections (e.g.,
conjunctivitis, sinusitis, andbronchitis)

WITH CHRONIC GVHD (CONT)
Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Chronic conjunctivitis
Chronic sinusitis
Chronic bronchitis
Recurrent or unusual infections
SepsisYearlyPHYSICAL
Eye exam
Nasal exam
Pulmonary exam
YearlyPOTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Administer pneumocystis jirovecii pneumonia prophylaxis, consider antibiotic
prophylaxis for encapsulated organisms, and anti-viral and anti-fungal
prophylaxis in patients with active cGVHD for duration of immunosuppressive
therapy.
Immunize with inactivated vaccines for all patients according to publishedguidelines; postponing vaccination in patients with GVHD is not recommended
with the exception of live vaccines.
Immunology or infectious diseases consultation for assistance with managementof infections.
Some patients with hypogammaglobulinemia require lifelong IgG replacement.
SYSTEM = Immune
SCORE = 1

Additional Information

Immunologic complications related to cGVHD may persist or resolve over time. Immunologic abnormalities may persist for up to 20 years post transplant.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Pre-morbid/Co-morbid medical conditions: Active cGVHD, prolonged immunosuppression related to cGVHD and its treatment

References
Centers for Disease Control and Prevention: Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 61:816-9, 2012
Centers for Disease Control and Prevention: Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 62:521-4, 2013
Engelhard D, Cordonnier C, Shaw PJ, et al: Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey. Br J Haematol 117:444-50, 2002
Guilcher GMT, Rivard L, Huang JT, et al: Immune function in childhood cancer survivors: a Children’s Oncology Group review. Lancet Child Adolesc Health 5(4):284-294, 2021
Majhail NS, Rizzo JD, Lee SJ, et al: Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Bone Marrow Transplant 47:337-41, 2012
Maury S, Mary JY, Rabian C, et al: Prolonged immune deficiency following allogeneic stem cell transplantation: risk factors and complications in adult patients. Br J Haematol 115:630-41, 2001
Mbaeyi SA, Bozio CH, Duffy J, et al: Meningococcal vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 69(9);1-41, 2020
Nordoy T, Kolstad A, Endresen P, et al: Persistent changes in the immune system 4-10 years after ABMT. Bone Marrow Transplant 24:873-8, 1999
Perkins JL, Chen Y, Harris A, et al: Infections among long-term survivors of childhood and adolescent cancer: a report from the Childhood Cancer Survivor Study. Cancer 120:2514-21, 2014
Robin M, Porcher R, De Castro Araujo R, et al: Risk factors for late infections after allogeneic hematopoietic stem cell transplantation from a matched related donor. Biol Blood Marrow Transplant 13:1304-12, 2007
Storek J, Gooley T, Witherspoon RP, et al: Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts. Am J Hematol 54:131-8, 1997
Tomblyn M, Chiller T, Einsele H, et al: Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 15:1143-238, 2009

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Sec #
111

Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT) with
CURRENTLY ACTIVE
cGVHD

Potential
Late Effects
Functional asplenia
At risk for life-threatening infection
with encapsulated organisms(e.g., Haemophilus influenzae,
Streptococcus pneumoniae,
meningococcus)

Periodic Evaluation
PHYSICAL
Physical exam at time of febrile illness toevaluate degree of illness and potential
source of infection
When febrile T ≥101°F (38.3°C) as indicated forpatients with active cGVHD
SCREENING
Blood culture
When febrile T ≥101°F (38.3°C) as indicated forpatients with active cGVHD

WITH CHRONIC GVHD (CONT)
Health Counseling/
Further Considerations
HEALTH LINKS
Splenic Precautions
COUNSELING
Risk of life-threatening infections with encapsulated organisms.
Risk associated with malaria and tick-borne diseases if living in or visiting endemicareas.
Obtain medical alert bracelet/card noting functional asplenia.
Discuss importance of immunization with Pneumococcal, Meningococcal (including
serotype B), Influenza and HIB vaccines according to current ACIP recommendations.
For further details regarding antibiotic prophylaxis and immunizations, see current editionof AAP Red Book.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Antibiotic prophylaxis for encapsulated organisms and bacteremia/endocarditis
prophylaxis for duration of immunosuppressive therapy for cGVHD (see: American
Academy of Pediatric Dentistry, Guideline on Antibiotic Prophylaxis for Dental Patients at
Risk for Infection).
Administer a long-acting, broad-spectrum parenteral antibiotic (e.g., ceftriaxone) inpatients with T ≥101°F (38.3°C) or other signs of serious illness and continue close
medical monitoring while awaiting blood culture results.
Hospitalize and broaden antimicrobial coverage (e.g., addition of vancomycin) undercertain circumstances, such as the presence of marked leukocytosis, neutropenia, or
significant change from baseline CBC, toxic clinical appearance, fever ≥104°F (40°C),
meningitis, pneumonia, or other serious focus of infection, signs of septic shock, orprevious history of serious infection.
SYSTEM = Immune
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Splenic radiation, ongoing immunosuppression- Pre-morbid/Co-morbid medical conditions: Hypogammaglobulinemia

References
American Academy of Pediatric Dentistry Clinical Affairs Committee, American Academy of Pediatric Dentistry Council on Clinical Affairs: Guideline on antibiotic prophylaxis for dental patients at risk for infection. Chicago, IL, American
Academy of Pediatric Dentistry, 2011
Castagnola E, Fioredda F: Prevention of life-threatening infections due to encapsulated bacteria in children with hyposplenia or asplenia: a brief review of current recommendations for practical purposes. Eur J Haematol 71:319-26,
2003
Centers for Disease Control and Prevention: Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 61:816-9, 2012
Centers for Disease Control and Prevention: Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 62:521-4, 2013
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HEMATOPOIETIC CELL TRANSPLANT

WITH CHRONIC GVHD (CONT)

Section 111 References (cont)Committee on Infectious Disease, American Academy of Pediatrics: Immunization in special clinical circumstances, in Kimberlin DW, Barnett ED, Lynfield R, et al (eds): Red Book: 2021 Report of the Committee on Infectious Diseases(ed 32). Itasca, IL, American Academy of Pediatrics, 2021, pp 67-105
Engelhard D, Cordonnier C, Shaw PJ, et al: Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey. Br J Haematol 117:444-50, 2002
Guilcher GMT, Rivard L, Huang JT, et al: Immune function in childhood cancer survivors: a Children’s Oncology Group review. Lancet Child Adolesc Health 5(4):284-294, 2021
Mbaeyi SA, Bozio CH, Duffy J, et al: Meningococcal vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 69(9);1-41, 2020
Mourtzoukou EG, Pappas G, Peppas G, et al: Vaccination of asplenic or hyposplenic adults. Br J Surg 95:273-80, 2008
Price VE, Blanchette VS, Ford-Jones EL: The prevention and management of infections in children with asplenia or hyposplenia. Infect Dis Clin North Am 21:697-710, viii-ix, 2007
Smets F, Bourgois A, Vermylen C, et al: Randomised revaccination with pneumococcal polysaccharide or conjugate vaccine in asplenic children previously vaccinated with polysaccharide vaccine. Vaccine 25:5278-82, 2007
Spelman D, Buttery J, Daley A, et al: Guidelines for the prevention of sepsis in asplenic and hyposplenic patients. Intern Med J 38:349-56, 2008

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Sec #
112

Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT) withany history of cGVHD

Potential
Late Effects
Esophageal stricture

WITH CHRONIC GVHD (CONT)
Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Dysphagia
HeartburnYearlyHEALTH LINKS
Gastrointestinal Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Surgery and/or gastroenterology consultation for symptomatic patients.
SYSTEM = GI/Hepatic
SCORE = 1w

Additional Information

Esophageal stricture related to cGVHD is generally not reversible over time.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Radiation involving the esophagus, radiation dose ≥30 Gy (increased risk with higher radiation dose, particularly dose ≥40 Gy)- Pre-morbid/Co-morbid medical conditions: Gastroesophageal reflux, candida esophagitis, gut GVHD

References
Lal DR, Foroutan HR, Su WT, et al: The management of treatment-related esophageal complications in children and adolescents with cancer. J Pediatr Surg 41:495-9, 2006
Stemmelin GR, Pest P, Peters RA, et al: Severe esophageal stricture after autologous bone marrow transplant. Bone Marrow Transplant 15:1001-2, 1995
Williams M: Gastrointestinal manifestations of graft-versus-host disease: diagnosis and management. AACN Clin Issues 10:500-6, 1999

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(female)w

Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT) withany history of cGVHD

Potential
Late Effects
Vulvar scarring
Vaginal fibrosis/stenosis

Periodic Evaluation
HISTORY
Psychosocial assessment
Dyspareunia
Post-coital bleeding
Difficulty with tampon insertion
Vaginal dryness
Vulvar pain/tenderness
Vulvovaginal burning or pruritus
Dysuria
YearlyPHYSICAL
Exam of genitalia for lichen planus-likefeatures, erosions, fissures, ulcers
YearlyWITH CHRONIC GVHD (CONT)
Health Counseling/
Further Considerations
COUNSELING
Avoid frequent contact with irritants (bubble bath, wet wipes and soaps).
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Gynecologic consultation for management.
Psychological consultation in patients with emotional difficulties.
SYSTEM = Reproductive (Female)
SCORE = 1

Additional Information

Vulvovaginal cGVHD is rare before the onset of puberty, but should be considered beyond thelarche.
Estrogen deficiency and infection (HPV/HSV, yeast, bacteria and other recognized gynecological pathogens) should be ruled out before a diagnosis of genital cGVHD is made.
Vaginal fibrosis/stenosis related to cGVHD is generally not reversible over time.
Physical examination should be done with each assessment for cGVHD to detect vulvar lesions before vaginal stenosis develops.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Pelvic radiation

References
Carpenter PA, Kitko CL, Elad S, et al: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. The 2014 Ancillary Therapy and Supportive Care Working Group
Report. Biol Blood Marrow Transplant 21:1167-87, 2015
Costantini S, Di Capua E, Bosi S, et al: The management of severe vaginal obstruction from genital chronic graft-versus-host disease: diagnosis, surgical technique and follow-up. Minerva Ginecol 58:11-6, 2006
Duncan CN, Majhail NS, Brazauskas R, et al: Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes. Biol
Blood Marrow Transplant 21:151-8, 2015
Frey Tirri B, Hausermann P, Bertz H, et al: Clinical guidelines for gynecologic care after hematopoietic SCT. Report from the international consensus project on clinical practice in chronic GVHD. Bone Marrow Transplant 50:3-9, 2015
Gifford G, Sim J, Horne A, et al: Health status, late effects and long-term survivorship of allogeneic bone marrow transplantation: a retrospective study. Intern Med J 44:139-47, 2014
Hirsch P, Leclerc M, Rybojad M, et al: Female genital chronic graft-versus-host disease: importance of early diagnosis to avoid severe complications. Transplantation 93:1265-9, 2012
Jagasia MH, Greinix HT, Arora M, et al: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol
Blood Marrow Transplant 21:389-401 e1, 2015
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Smith Knutsson E, Bjork Y, Broman AK, et al: Genital chronic graft-versus-host disease in females: a cross-sectional study. Biol Blood Marrow Transplant 20:806-11, 2014
Tauchmanova L, Selleri C, Di Carlo C, et al: Estrogen-progestogen induced hematocolpometra following allogeneic stem cell transplant. Gynecol Oncol 93:112-5, 2004
Zantomio D, Grigg AP, MacGregor L, et al: Female genital tract graft-versus-host disease: incidence, risk factors and recommendations for management. Bone Marrow Transplant 38:567-72, 2006

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w

Therapeutic
Exposure
Hematopoietic Cell
Transplant (HCT) withany history of cGVHD

Potential
Late Effects
Joint contractures

Periodic Evaluation
PHYSICAL
Musculoskeletal exam
YearlyWITH CHRONIC GVHD (CONT)
Health Counseling/
Further Considerations
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Consultation with physical therapy, rehabilitation medicine/physiatrist.
SYSTEM = Musculoskeletal
SCORE = 1

Additional Information

Joint contractures related to cGVHD are generally not reversible over time.

References
Antin JH: Clinical practice. Long-term care after hematopoietic-cell transplantation in adults. N Engl J Med 347:36-42, 2002
Beredjiklian PK, Drummond DS, Dormans JP, et al: Orthopaedic manifestations of chronic graft-versus-host disease. J Pediatr Orthop 18:572-5, 1998
Carpenter PA: Late effects of chronic graft-versus-host disease. Best Pract Res Clin Haematol 21:309-31, 2008
Flowers ME, Parker PM, Johnston LJ, et al: Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial.
Blood 100:415-9, 2002

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SURGERYSec #115

AMPUTATION

Therapeutic
Exposure
Amputation

Potential
Late Effects
Amputation-related
complications
Impaired cosmesis
Functional and activity limitations
Residual limb integrity problems
Pain
Increased energy expenditure
Impaired quality of life
Psychological maladjustment

Periodic Evaluation
HISTORY
Phantom pain
Functional, activity, and fitness limitations
YearlyPHYSICAL
Residual limb integrity
YearlySCREENING
Prosthetic evaluation
Every 6 months until skeletally mature, then yearly

Health Counseling/
Further Considerations
HEALTH LINKS
Amputation
COUNSELING
Skin checks
Signs of poor prosthetic fit
Residual limb and prosthetic hygiene
Physical fitness
Importance of maintaining a healthy weight and lifestyle.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Physical therapy consultation as needed per changing physical status such as weightgain or gait training with a new prosthesis, and for non-pharmacological pain
management.
Occupational therapy consultation as needed to assist with activities of daily living.
Psychological/social work consultation to assist with emotional difficulties related to body
image, marriage, pregnancy, parenting, employment, insurance, depression, sexual
health, or high-risk behaviors (e.g., alcohol or tobacco use).
Vocational counseling/training to identify vocations that will not produce/exacerbate
functional limitations.
SYSTEM = Musculoskeletal
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Skeletally immature/growing children- Cancer/Treatment factors: Hemipelvectomy site of amputation (trans-femur amputation, trans-tibia amputation)- Pre-morbid/Co-morbid medical conditions: Obesity, diabetes, poor residual limb healing

References
Aulivola B, Hile CN, Hamdan AD, et al: Major lower extremity amputation: outcome of a modern series. Arch Surg 139:395-9; discussion 399, 2004
Bekkering WP, Vliet Vlieland TP, Koopman HM, et al: Functional ability and physical activity in children and young adults after limb-salvage or ablative surgery for lower extremity bone tumors. J Surg Oncol 103:276-82, 2011
Eiser C, Darlington AS, Stride CB, et al: Quality of life implications as a consequence of surgery: limb salvage, primary and secondary amputation. Sarcoma 5:189-95, 2001
Eiser C, Grimer RJ: Quality of life in survivors of a primary bone tumour: a systematic review. Sarcoma 3:183-90, 1999
Fernandez-Pineda I, Hudson MM, Pappo AS, et al: Long-term functional outcomes and quality of life in adult survivors of childhood extremity sarcomas: a report from the St. Jude Lifetime Cohort Study. J Cancer Surviv 11(1):1-12, 2017
Griesser MJ, Gillette B, Crist M, et al: Internal and external hemipelvectomy or flail hip in patients with sarcomas: quality-of-life and functional outcomes. Am J Phys Med Rehabil 91:24-32, 2012
Lown EA, Hijiya N, Zhang N, et al: Patterns and predictors of clustered risky health behaviors among adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Cancer 122(17):2747-2756, 2016
Nagarajan R, Mogil R, Neglia JP, et al: Self-reported global function among adult survivors of childhood lower-extremity bone tumors: a report from the Childhood Cancer Survivor Study (CCSS). J Cancer Surviv 3:59-65, 2009
Nagarajan R, Neglia JP, Clohisy DR, et al: Education, employment, insurance, and marital status among 694 survivors of pediatric lower extremity bone tumors: a report from the Childhood Cancer Survivor Study. Cancer 97:2554-64, 2003
Ottaviani G, Robert RS, Huh WW, et al: Sociooccupational and physical outcomes more than 20 years after the diagnosis of osteosarcoma in children and adolescents: limb salvage versus amputation. Cancer 119:3727-36, 2013
Renard AJ, Veth RP, Schreuder HW, et al: Function and complications after ablative and limb-salvage therapy in lower extremity sarcoma of bone. J Surg Oncol 73:198-205, 2000
Stokke J, Sung L, Gupta A, et al: Systematic review and meta-analysis of objective and subjective quality of life among pediatric, adolescent, and young adult bone tumor survivors. Pediatr Blood Cancer 62:1616-29, 2015

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SURGERYCENTRAL VENOUS CATHETERSec #Therapeutic
Exposure

Potential
Late Effects

116

Central venous catheter

Thrombosis
Vascular insufficiency
Infection of retained cuff orline tract
Post-thrombotic syndromew

Periodic Evaluation
HISTORY
Tenderness or swelling at previous
catheter site
YearlyPHYSICAL
Venous stasis
Swelling
Tenderness at previous catheter site
YearlyHealth Counseling/
Further Considerations
SYSTEM = Cardiovascular
SCORE = 2A

References

Kuhle S, Spavor M, Massicotte P, et al: Prevalence of post-thrombotic syndrome following asymptomatic thrombosis in survivors of acute lymphoblastic leukemia. J Thromb Haemost 6:589-94, 2008
Polen E, Weintraub M, Stoffer C, et al: Post-thrombotic syndrome after central venous catheter removal in childhood cancer survivors: A prospective cohort study. Pediatr Blood Cancer 62:285-290, 2015
Revel-Vilk S, Menahem M, Stoffer C, et al: Post-thrombotic syndrome after central venous catheter removal in childhood cancer survivors is associated with a history of obstruction. Pediatr Blood Cancer 55:153-6, 2010
Wilimas JA, Hudson M, Rao B, et al: Late vascular occlusion of central lines in pediatric malignancies. Pediatrics 101:E7, 1998

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Sec #
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w

CYSTECTOMY

Therapeutic
Exposure
Cystectomy

Potential
Late Effects
Cystectomy-related
complications
Asymptomatic bacteriuria
Chronic urinary tract infection
Renal dysfunction
Vesicoureteral reflux
Hydronephrosis
Reservoir calculi
Spontaneous neobladderperforation
Vitamin B12/Folate/Carotene
deficiency (patients with ileal
enterocystoplasty only)

Health Counseling/
Further Considerations

Periodic Evaluation
SCREENING
Vitamin B12 level
Yearly, starting 5 years after cystectomy(patients with ileal enterocystoplasty only)
Evaluation by urologist
YearlyHEALTH LINKS
Cystectomy
Kidney Health
SYSTEM = Urinary
SCORE
Reservoir calculi = 2A
Vitamin B12/folate/carotene deficiency = 2B
All Else = 1

Additional Information

All potential late effects for pelvic surgery apply to cystectomy (see also sections 141-145).
Reservoir calculi are stones in the neobladder (a reservoir for urine usually constructed of ileum/colon).

References
Castagnetti M, Angelini L, Alaggio R, et al: Oncologic outcome and urinary function after radical cystectomy for rhabdomyosarcoma in children: role of the orthotopic ileal neobladder based on 15-year experience at a single center. J
Urol 191:1850-5, 2014
DeFoor W, Tackett L, Minevich E, et al: Risk factors for spontaneous bladder perforation after augmentation cystoplasty. Urology 62:737-41, 2003
Hautmann RE, de Petriconi R, Gottfried HW, et al: The ileal neobladder: complications and functional results in 363 patients after 11 years of followup. J Urol 161:422-7; discussion 427-8, 1999
Hensle TW, Bingham J, Lam J, et al: Preventing reservoir calculi after augmentation cystoplasty and continent urinary diversion: the influence of an irrigation protocol. BJU Int 93:585-7, 2004
Inouye BM, Shah BB, Massanyi EZ, et al: Urologic complications of major genitourinary reconstruction in the exstrophy-epispadias complex. J Pediatr Urol 10:680-7, 2014
Jahnson S, Pedersen J: Cystectomy and urinary diversion during twenty years--complications and metabolic implications. Eur Urol 24:343-9, 1993
Kalloo NB, Jeffs RD, Gearhart JP: Long-term nutritional consequences of bowel segment use for lower urinary tract reconstruction in pediatric patients. Urology 50:967-71, 1997
Metcalfe PD, Casale AJ, Kaefer MA, et al: Spontaneous bladder perforations: a report of 500 augmentations in children and analysis of risk. J Urol 175:1466-70; discussion 1470-1, 2006
Raney B, Jr., Heyn R, Hays DM, et al: Sequelae of treatment in 109 patients followed for 5 to 15 years after diagnosis of sarcoma of the bladder and prostate. A report from the Intergroup Rhabdomyosarcoma Study Committee. Cancer
71:2387-94, 1993
Rosenbaum DH, Cain MP, Kaefer M, et al: Ileal enterocystoplasty and B12 deficiency in pediatric patients. J Urol 179:1544-7; discussion 1547-8, 2008
Sim HG, Lau WK, Cheng CW: A twelve-year review of radical cystectomies in Singapore General Hospital. Ann Acad Med Singapore 31:645-50, 2002
Stewart D, Inouye BM, Goldstein SD, et al: Pediatric surgical complications of major genitourinary reconstruction in the exstrophy-epispadias complex. J Pediatr Surg 50:167-70, 2015

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ENUCLEATION

Therapeutic
Exposure
Enucleation

Potential
Late Effects
Impaired cosmesis
Poor prosthetic fit
Orbital hypoplasia

Periodic Evaluation
SCREENING
Evaluation by ocularist
YearlyEvaluation by ophthalmologist
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Eye Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Psychological consultation in patients with emotional difficulties related tocosmetic and visual impairment.
Vocational rehabilitation referral as clinically indicated.
SYSTEM = Ocular
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at enucleation- Cancer/Treatment factors: Combination with radiation

References
Chojniak MM, Chojniak R, Testa ML, et al: Abnormal orbital growth in children submitted to enucleation for retinoblastoma treatment. J Pediatr Hematol Oncol 34:e102-5, 2012
Kaste SC, Chen G, Fontanesi J, et al: Orbital development in long-term survivors of retinoblastoma. J Clin Oncol 15:1183-9, 1997
Shildkrot Y, Kirzhner M, Haik BG, et al: The effect of cancer therapies on pediatric anophthalmic sockets. Ophthalmology 118:2480-6, 2011

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HYSTERECTOMY

Therapeutic
Exposure
Hysterectomy(female)Potential
Late Effects
Pelvic floor dysfunction
Urinary incontinence
Sexual dysfunction

Periodic Evaluation
HISTORY
Psychosocial assessment
Urinary leakage
Abdominal pain
Dyspareunia
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Ovarian and Reproductive Health
COUNSELING
Potential for biologic parenthood using gestational surrogate.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Reproductive endocrinology consultation for patients wishing to pursue
pregnancy via gestational surrogate.
Female pelvic medicine and reconstructive surgery consultation for patients withurinary complaints after hysterectomy.
SYSTEM = Reproductive (Female)
SCORE = 2Aw

Additional Information

For patients who also underwent oophorectomy, see also: sections 136-137 (unilateral oophorectomy) or section 138 (bilateral oophorectomy).
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Pelvic radiation

References
Benedetti-Panici P, Zullo MA, Plotti F, et al: Long-term bladder function in patients with locally advanced cervical carcinoma treated with neoadjuvant chemotherapy and type 3-4 radical hysterectomy. Cancer 100:2110-7, 2004
Jensen PT, Groenvold M, Klee MC, et al: Early-stage cervical carcinoma, radical hysterectomy, and sexual function. A longitudinal study. Cancer 100:97-106, 2004
Laterza RM, Sievert KD, de Ridder D, et al: Bladder function after radical hysterectomy for cervical cancer. Neurourol Urodyn 34:309-15, 2015
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Skjeldestad FE, Hagen B: Long-term consequences of gynecological cancer treatment on urinary incontinence: a population-based cross-sectional study. Acta Obstet Gynecol Scand 87:469-75, 2008

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w

LAPAROTOMY

Therapeutic
Exposure
Laparotomy

Potential
Late Effects
Adhesions
Bowel obstruction

Periodic Evaluation
HISTORY
Abdominal pain
Distension
Vomiting
Constipation
YearlyPHYSICAL
Tenderness
Abdominal guarding
Distension
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Gastrointestinal Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Imaging as clinically indicated for suspected obstruction.
Surgical consultation for patients unresponsive to medical management.
SYSTEM = GI/Hepatic
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Combined with radiation

References
Cooke-Barber J, Scorletti F, Rymeski B, et al. Long-term follow-up of surgical outcomes for patients with Wilms tumor and neuroblastoma. Cancer 127(17):3232-3238, 2021
Jockovich M, Mendenhall NP, Sombeck MD, et al: Long-term complications of laparotomy in Hodgkin’s disease. Ann Surg 219:615-21; discussion 621-4, 1994
Madenci AL, Fisher S, Diller LR, et al: Intestinal obstruction in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 33:2893-900, 2015
Paulino AC, Wen BC, Brown CK, et al: Late effects in children treated with radiation therapy for Wilms’ tumor. Int J Radiat Oncol Biol Phys 46:1239-46, 2000
Ritchey ML, Shamberger RC, Haase G, et al: Surgical complications after primary nephrectomy for Wilms’ tumor: report from the National Wilms’ Tumor Study Group. J Am Coll Surg 192:63-8; quiz 146, 2001

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LIMB SPARING PROCEDURE

Sec #Therapeutic
Exposure

Potential
Late Effects

121

Limb sparing procedure

Conditions related to limb
sparing procedure
Functional and activity
limitations
Contractures
Chronic infection
Chronic pain
Limb length discrepancy
Increased energy expenditure
Fibrosis
Prosthetic malfunction(loosening, non-union,
fracture) requiring revision,
replacement or amputation
Impaired quality of life
Complications with pregnancy/
delivery (in female patientswith internal hemipelvectomy)w

Periodic Evaluation
HISTORY
Functional and activity limitations
YearlyPHYSICAL
Residual limb integrity
YearlySCREENING
Radiograph of affected limb
YearlyEvaluation by orthopedic surgeon (ideallyby an orthopedic oncologist)
Every 6 months until skeletally mature, thenyearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Limb Sparing Procedures
COUNSELING
Potential need to discuss antibiotic prophylaxis prior to dental and invasive
procedures with their treating dentist/orthopedic surgeon.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Physical therapy consultation as needed per changes in functional status (suchas post-lengthening, revisions, life changes such as pregnancy), and for nonpharmacological pain management.
Psychological consultation as needed to assist with emotional difficulties related
to body image, marriage, pregnancy, parenting, employment, insurance,
depression or sexual health.
Vocational counseling/training to identify vocations that will not produce/
exacerbate functional limitations.
SYSTEM = Musculoskeletal
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at surgery, being skeletally immature, rapid growth spurt- Cancer/Treatment factors: Tibial endoprosthesis, use of biologic material (allograft or autograft) for reconstruction, radiation to extremity- Pre-morbid/Co-morbid medical conditions: Obesity, endoprosthetic infection, history of poor healing, infection of reconstruction- Health behaviors: High level of physical activity (associated with higher risk loosening), low level of physical activity (associated with higher risk of contractures or functional limitations)

References
American Academy of Orthopedic Surgeons, American Dental Association: Prevention of orthopaedic implant infection in patients undergoing dental procedures. Rosemont, IL, American Academy of Orthopedic Surgeons, 2012
Eiser C, Darlington AS, Stride CB, et al: Quality of life implications as a consequence of surgery: limb salvage, primary and secondary amputation. Sarcoma 5:189-95, 2001
Groundland JS, Ambler SB, Houskamp LDJ, et al: Surgical and functional outcomes after limb-preservation surgery for tumor in pediatric patients: a systematic review. J Bone J Surg 4(2):1-13, 2016
Nagarajan R, Mogil R, Neglia JP, et al: Self-reported global function among adult survivors of childhood lower-extremity bone tumors: a report from the Childhood Cancer Survivor Study (CCSS). J Cancer Surviv 3:59-65, 2009
Nagarajan R, Neglia JP, Clohisy DR, et al: Limb salvage and amputation in survivors of pediatric lower-extremity bone tumors: what are the long-term implications? J Clin Oncol 20:4493-501, 2002
Ottaviani G, Robert RS, Huh WW, et al: Sociooccupational and physical outcomes more than 20 years after the diagnosis of osteosarcoma in children and adolescents: limb salvage versus amputation. Cancer 119:3727-36, 2013
Portney DA, Bi AS, Christian RA, et al: Outcomes of expandable prostheses for primary bone malignancies in skeletally immature patients: a systematic review and pooled data analysis. J Pediatr Orthop 40(6):e487-e497, 2020
Stokke J, Sung L, Gupta A, et al: Systematic review and meta-analysis of objective and subjective quality of life among pediatric, adolescent, and young adult bone tumor survivors. Pediatr Blood Cancer 62:1616-29, 2015
Tsuda Y, Tsoi K, Stevenson JD, et al: Extendable endoprostheses in skeletally immature patients: a study of 124 children surviving more than 10 years after resection of bone sarcomas. J Bone Joint Surg Am 15;102(2):151-162, 2020
Wright EH, Gwilym S, Gibbons CL, et al: Functional and oncological outcomes after limb-salvage surgery for primary sarcomas of the upper limb. J Plast Reconstr Aesthet Surg 61:382-7, 2008

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NEPHRECTOMY

Therapeutic
Exposure
Nephrectomy(male)

Potential
Late Effects
Hydrocele
Renal toxicity
Proteinuria
Hyperfiltration
Renal insufficiency
Hypertension

Periodic Evaluation
PHYSICAL
HeightWeightBMI
Blood pressure
YearlyTesticular exam to evaluate for hydrocele
YearlySCREENING
BUN
Na, K, Cl, CO2, Ca, Mg, PO4
Baseline at entry into long-term follow-up,
repeat as clinically indicated
Urine dipstick for protein
Creatinine with calculated eGFR*
Yearlyw

Health Counseling/
Further Considerations
HEALTH LINKS
Single Kidney Health
Kidney Health
Cardiovascular Risk Factors
COUNSELING
Counsel mononephric survivors regarding sports and activity safety, stressing
the importance of physical fitness, and proper use of seatbelts (i.e., wearing
lap belts around hips, not waist). Consideration should be given to survivor
health status, current kidney health (position, size, function), and acceptabilityof unlikely risk of sports-related renal injury to the survivor and/or family.
Use NSAIDs with caution.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Nephrology consultation for patients with hypertension, proteinuria, or
progressive renal insufficiency.
SYSTEM = Urinary
SCORE = 1

Additional Information

Surgery-induced renal atrophy (vanishing kidney) is a rare complication reported in survivors who have undergone retroperitoneal tumor resections. Once this diagnosis is established, annual screening should include evaluations
recommended for children treated with nephrectomy.
*eGFR Calculator available at: https://www.niddk.nih.gov/health-information/professionals/clinical-tools-patient-management/kidney-disease/laboratory-evaluation/glomerular-filtration-rate-calculators/recommended
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Bilateral Wilms tumor, other nephrotoxic therapy (e.g., cisplatin, carboplatin, ifosfamide, aminoglycosides, amphotericin, immunosuppressants, methotrexate, radiation impacting the kidneys)- Pre-morbid/Co-morbid medical conditions: Denys-Drash syndrome, WAGR syndrome, hypospadias, cryptorchidism

References
Bailey S, Roberts A, Brock C, et al: Nephrotoxicity in survivors of Wilms’ tumours in the North of England. Br J Cancer 87:1092-8, 2002
Breslow NE, Collins AJ, Ritchey ML, et al: End stage renal disease in patients with Wilms tumor: results from the National Wilms Tumor Study Group and the United States Renal Data System. J Urol 174:1972-5, 2005
Cozzi DA, Ceccanti S, Frediani S, et al: Renal function adaptation up to the fifth decade after treatment of children with unilateral renal tumor: a cross-sectional and longitudinal study. Pediatr Blood Cancer 60:1534-8, 2013
Dieffenbach BV, Liu Q, Murphy AJ, et al: Late-onset kidney failure in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Eur J Cancer 155:216-226, 2021
Ginsberg JP, Hobbie WL, Ogle SK, et al: Prevalence of and risk factors for hydrocele in survivors of Wilms tumor. Pediatr Blood Cancer 42:361-3, 2004
Green DM, Wang M, Krasin M, et al: Kidney function after treatment for childhood cancer: a report from the St. Jude Lifetime Cohort Study. J Am Soc Nephrol 32(4):983-993, 2021
Grinsell MM, Showalter S, Gordon KA, et al: Single kidney and sports participation: perception versus reality. Pediatrics 118:1019-27, 2006
Hubertus J, Gunther B, Becker K, et al: Development of hypertension is less frequent after bilateral nephron sparing surgery for bilateral Wilms tumor in a long-term survey. J Urol 193:262-6, 2015
Johnson B, Christensen C, Dirusso S, et al: A need for reevaluation of sports participation recommendations for children with a solitary kidney. J Urol 174:686-9; discussion 689, 2005
Paulino AC, Wen BC, Brown CK, et al: Late effects in children treated with radiation therapy for Wilms’ tumor. Int J Radiat Oncol Biol Phys 46:1239-46, 2000
Ritchey ML, Green DM, Thomas PR, et al: Renal failure in Wilms’ tumor patients: a report from the National Wilms’ Tumor Study Group. Med Pediatr Oncol 26:75-80, 1996
Sharp DS, Ross JH, Kay R: Attitudes of pediatric urologists regarding sports participation by children with a solitary kidney. J Urol 168:1811-4; discussion 1815, 2002
Srinivas M, Agarwala S, Padhy AK, et al: Somatic growth and renal function after unilateral nephrectomy for Wilms’ tumor. Pediatr Surg Int 14:185-8, 1998
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NEPHRECTOMY (CONT)

Therapeutic
Exposure
Nephrectomy(female)Potential
Late Effects
Renal toxicity
Proteinuria
Hyperfiltration
Renal insufficiency
Hypertension

Periodic Evaluation
PHYSICAL
HeightWeightBMI
Blood pressure
YearlySCREENING
BUN
Na, K, Cl, CO2, Ca, Mg, PO4
Baseline at entry into long-term follow-up,
repeat as clinically indicated
Urine dipstick for protein
Creatinine with calculated eGFR*
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Single Kidney Health
Kidney Health
Cardiovascular Risk Factors
COUNSELING
Counsel mononephric survivors regarding sports and activity safety, stressing
the importance of physical fitness, and proper use of seatbelts (i.e., wearing
lap belts around hips, not waist). Consideration should be given to survivor
health status, current kidney health (position, size, function), and acceptabilityof unlikely risk of sports-related renal injury to the survivor and/or family.
Use NSAIDs with caution.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Nephrology consultation for patients with hypertension, proteinuria, or
progressive renal insufficiency.
SYSTEM = Urinary
SCORE = 1w

Additional Information

Surgery-induced renal atrophy (vanishing kidney) is a rare complication reported in survivors who have undergone retroperitoneal tumor resections. Once this diagnosis is established, annual screening should include evaluations
recommended for children treated with nephrectomy.
*eGFR Calculator available at: https://www.niddk.nih.gov/health-information/professionals/clinical-tools-patient-management/kidney-disease/laboratory-evaluation/glomerular-filtration-rate-calculators/recommended
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Bilateral Wilms tumor, other nephrotoxic therapy (e.g., cisplatin, carboplatin, ifosfamide, aminoglycosides, amphotericin, immunosuppressants, methotrexate, radiation impacting the kidneys)- Pre-morbid/Co-morbid medical conditions: Denys-Drash syndrome, WAGR syndrome

References
Bailey S, Roberts A, Brock C, et al: Nephrotoxicity in survivors of Wilms’ tumours in the North of England. Br J Cancer 87:1092-8, 2002
Breslow NE, Collins AJ, Ritchey ML, et al: End stage renal disease in patients with Wilms tumor: results from the National Wilms Tumor Study Group and the United States Renal Data System. J Urol 174:1972-5, 2005
Cozzi DA, Ceccanti S, Frediani S, et al: Renal function adaptation up to the fifth decade after treatment of children with unilateral renal tumor: a cross-sectional and longitudinal study. Pediatr Blood Cancer 60:1534-8, 2013
Dieffenbach BV, Liu Q, Murphy AJ, et al: Late-onset kidney failure in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Eur J Cancer 155:216-226, 2021
Green DM, Wang M, Krasin M, et al: Kidney function after treatment for childhood cancer: a report from the St. Jude Lifetime Cohort Study. J Am Soc Nephrol 32(4):983-993, 2021
Grinsell MM, Showalter S, Gordon KA, et al: Single kidney and sports participation: perception versus reality. Pediatrics 118:1019-27, 2006
Hubertus J, Gunther B, Becker K, et al: Development of hypertension is less frequent after bilateral nephron sparing surgery for bilateral Wilms tumor in a long-term survey. J Urol 193:262-6, 2015
Johnson B, Christensen C, Dirusso S, et al: A need for reevaluation of sports participation recommendations for children with a solitary kidney. J Urol 174:686-9; discussion 689, 2005
Paulino AC, Wen BC, Brown CK, et al: Late effects in children treated with radiation therapy for Wilms’ tumor. Int J Radiat Oncol Biol Phys 46:1239-46, 2000
Ritchey ML, Green DM, Thomas PR, et al: Renal failure in Wilms’ tumor patients: a report from the National Wilms’ Tumor Study Group. Med Pediatr Oncol 26:75-80, 1996
Sharp DS, Ross JH, Kay R: Attitudes of pediatric urologists regarding sports participation by children with a solitary kidney. J Urol 168:1811-4; discussion 1815, 2002
Srinivas M, Agarwala S, Padhy AK, et al: Somatic growth and renal function after unilateral nephrectomy for Wilms’ tumor. Pediatr Surg Int 14:185-8, 1998

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Neurosurgery-Brainw

NEUROSURGERY—BRAIN
Potential
Late Effects
Neurocognitive deficits
Functional deficits in:• Executive function (planningand organization)• Sustained attention• Memory (particularly visual,sequencing, temporal
memory)• Processing speed• Visual-motor integration
Learning deficits in math andreading (particularly reading
comprehension)
Diminished IQ
Behavioral change

Periodic Evaluation
HISTORY
Educational and/or vocational progress
YearlySCREENING
Referral for formal neuropsychologicalevaluation
Baseline at entry into long-term follow-up,
then periodically as clinically indicatedfor patients with evidence of impaired
educational or vocational progress

Health Counseling/
Further Considerations
HEALTH LINKS
School After Treatment
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Referral to school liaison in community or cancer center (psychologist, social
worker, school counselor) to facilitate acquisition of educational resources and/or social skills training.
Psychotropic medication (e.g., stimulants) or evidence-based rehabilitation
training. Caution—lower starting dose and assessment of increased sensitivity
when initiating therapy is recommended.
Referral to community services for vocational rehabilitation or for services fordevelopmentally disabled.
SYSTEM = CNSSCORE = 1

Additional Information

Formal neuropsychological evaluation includes tests of processing speed, computer-based attention, visual motor integration, memory, comprehension of verbal instructions, verbal fluency, executive function and planning.
Neurocognitive deficits vary with extent of surgery, postoperative complications and location. Neurosensory deficits (i.e., vision, hearing) due to tumor or its therapy may complicate neurocognitive outcomes. Extent of deficit depends
on age at treatment, intensity of treatment, and time since treatment. New and progressive deficits may emerge over time.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Younger age at treatment, especially age <3 years, family history of learning or attention problems- Cancer/Treatment factors: Primary CNS tumor, extent and location of resection, longer elapsed time since therapy, combination with methotrexate (IT, IO, high dose IV), cytarabine (high dose IV), radiation dose ≥24 Gy to wholebrain, radiation dose ≥40 Gy to local fields, TBI, CRT- Pre-morbid/Co-morbid medical conditions: Pre-morbid learning or attention problems, hydrocephalus/history of shunt placement, seizures, posterior fossa syndrome, CNS infection, neurologic and pulmonary conditions

References
Aarsen FK, Paquier PF, Arts WF, et al: Cognitive deficits and predictors 3 years after diagnosis of a pilocytic astrocytoma in childhood. J Clin Oncol 27:3526-32, 2009
Armstrong GT, Conklin HM, Huang S, et al: Survival and long-term health and cognitive outcomes after low-grade glioma. Neuro Oncol 13:223-34, 2011
Carpentieri SC, Waber DP, Pomeroy SL, et al: Neuropsychological functioning after surgery in children treated for brain tumor. Neurosurgery 52:1348-56; discussion 1356-7, 2003
Catsman-Berrevoets CE, Aarsen FK: The spectrum of neurobehavioural deficits in the posterior fossa syndrome in children after cerebellar tumour surgery. Cortex 46:933-46, 2010
Mulhern RK, Merchant TE, Gajjar A, et al: Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet Oncol 5:399-408, 2004
Reimers TS, Ehrenfels S, Mortensen EL, et al: Cognitive deficits in long-term survivors of childhood brain tumors: Identification of predictive factors. Med Pediatr Oncol 40:26-34, 2003
Williams AM, Cheung YT, Hyun G, et al. Childhood neurotoxicity and brain resilience to adverse events during adulthood. Ann Neurol 89(3):534-545, 2021

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Neurosurgery-Brainw

NEUROSURGERY—BRAIN (CONT)
Potential
Late Effects
Motor and/or sensory deficits
Paralysis
Movement disorders
AtaxiaEye problems (ocularnerve palsy, gaze paresis,
nystagmus, papilledema, optic
atrophy)

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Paralysis
Movement problems
AtaxiaEye problems
YearlyPHYSICAL
Neurologic exam
YearlyPOTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Evaluation by neurologist for persistent neurologic symptoms.
Speech, physical, and occupational therapy in patients with persistent deficits.
Evaluation by physiatrist/rehabilitation medicine specialist in patients with motor
dysfunction.
Ophthalmology evaluation as clinically indicated.
SYSTEM = CNSSCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Primary CNS tumor, skull base tumors, optic pathway tumor, hypothalamic tumor, supra-sellar tumor (eye problems)- Pre-morbid/Co-morbid medical conditions: Hydrocephalus

References
Elliott RE, Hsieh K, Hochm T, et al: Efficacy and safety of radical resection of primary and recurrent craniopharyngiomas in 86 children. J Neurosurg Pediatr 5:30-48, 2010
Jane JA, Jr., Prevedello DM, Alden TD, et al: The transsphenoidal resection of pediatric craniopharyngiomas: a case series. J Neurosurg Pediatr 5:49-60, 2010
Kotecha RS, Jacoby P, Cole CH, et al: Morbidity in survivors of child and adolescent meningioma. Cancer 119:4350-7, 2013
Lo AC, Howard AF, Nichol A, et al: Long-term outcomes and complications in patients with craniopharyngioma: the British Columbia Cancer Agency experience. Int J Radiat Oncol Biol Phys 88:1011-8, 2014
Pietila S, Korpela R, Lenko HL, et al: Neurological outcome of childhood brain tumor survivors. J Neurooncol 108:153-61, 2012
Robertson PL, Muraszko KM, Holmes EJ, et al: Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children’s Oncology Group. J Neurosurg 105:444-51,
2006
Sonderkaer S, Schmiegelow M, Carstensen H, et al: Long-term neurological outcome of childhood brain tumors treated by surgery only. J Clin Oncol 21:1347-51, 2003
Ullrich NJ, Pomeroy SL, Kapur K, et al: Incidence, risk factors, and longitudinal outcome of seizures in long-term survivors of pediatric brain tumors. Epilepsia 56:1599-604, 2015
Wibroe M, Cappelen J, Castor C, et al: Cerebellar mutism syndrome in children with brain tumours of the posterior fossa. BMC Cancer 17:439, 2017
Yano S, Kudo M, Hide T, et al: Quality of life and clinical features of long-term survivors surgically treated for pediatric craniopharyngioma. World Neurosurg 85:153-62, 2016

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Neurosurgery-Brainw

NEUROSURGERY—BRAIN (CONT)
Potential
Late Effects
Seizures

Periodic Evaluation
HISTORY
SeizuresYearlyPHYSICAL
Neurologic exam
YearlyHealth Counseling/
Further Considerations
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Evaluation by neurologist as clinically indicated.
SYSTEM = CNSSCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Primary CNS tumor, methotrexate (IV, IT, IO)

References
Kotecha RS, Jacoby P, Cole CH, et al: Morbidity in survivors of child and adolescent meningioma. Cancer 119:4350-7, 2013
Lo AC, Howard AF, Nichol A, et al: Long-term outcomes and complications in patients with craniopharyngioma: the British Columbia Cancer Agency experience. Int J Radiat Oncol Biol Phys 88:1011-8, 2014
Pietila S, Korpela R, Lenko HL, et al: Neurological outcome of childhood brain tumor survivors. J Neurooncol 108:153-61, 2012
Sonderkaer S, Schmiegelow M, Carstensen H, et al: Long-term neurological outcome of childhood brain tumors treated by surgery only. J Clin Oncol 21:1347-51, 2003
Ullrich NJ, Pomeroy SL, Kapur K, et al: Incidence, risk factors, and longitudinal outcome of seizures in long-term survivors of pediatric brain tumors. Epilepsia 56:1599-604, 2015
Yano S, Kudo M, Hide T, et al: Quality of life and clinical features of long-term survivors surgically treated for pediatric craniopharyngioma. World Neurosurg 85:153-62, 2016

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Neurosurgery-Brainw

NEUROSURGERY—BRAIN (CONT)
Potential
Late Effects
Hydrocephalus
Shunt malfunction

Periodic Evaluation
HISTORY
Headaches
Nausea/Vomiting
AtaxiaIrritability
Drowsiness
YearlyPHYSICAL
Neurologic exam
YearlySCREENING
Abdominal x-ray
After pubertal growth spurt for patients withshunts to assure distal shunt tubing inperitoneum

Health Counseling/
Further Considerations
COUNSELING
Educate patient/family regarding potential symptoms of shunt malfunction.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Evaluation by neurosurgeon for patients with shunts.
Per the American Academy of Pediatric Dentistry endocarditis prophylaxis
guidelines, antibiotic prophylaxis prior to dental work is indicated for survivors
with V-A and V-V shunts, but not for survivors with V-P shunts.
SYSTEM = CNSSCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Primary CNS tumor

References
American Academy of Pediatric Dentistry Clinical Affairs Committee, American Academy of Pediatric Dentistry Council on Clinical Affairs: Guideline on antibiotic prophylaxis for dental patients at risk for infection. Chicago, IL, American
Academy of Pediatric Dentistry, 2011
Kotecha RS, Jacoby P, Cole CH, et al: Morbidity in survivors of child and adolescent meningioma. Cancer 119:4350-7, 2013
Lo AC, Howard AF, Nichol A, et al: Long-term outcomes and complications in patients with craniopharyngioma: the British Columbia Cancer Agency experience. Int J Radiat Oncol Biol Phys 88:1011-8, 2014
Pietila S, Korpela R, Lenko HL, et al: Neurological outcome of childhood brain tumor survivors. J Neurooncol 108:153-61, 2012
Ullrich NJ, Pomeroy SL, Kapur K, et al: Incidence, risk factors, and longitudinal outcome of seizures in long-term survivors of pediatric brain tumors. Epilepsia 56:1599-604, 2015
Yano S, Kudo M, Hide T, et al: Quality of life and clinical features of long-term survivors surgically treated for pediatric craniopharyngioma. World Neurosurg 85:153-62, 2016

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SURGERYSec #128

NEUROSURGERY—BRAIN (CONT)

Therapeutic
Exposure
Neurosurgery-Brain(applies only toneurosurgery withpotential to affect the
hypothalamic-pituitaryaxis)

Potential
Late Effects
Overweight
Obesity

Periodic Evaluation
PHYSICAL
HeightWeight
BMI
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Nutrition and Physical Activity
Cardiovascular Risk Factors
COUNSELING
Obesity-related health risks.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Evaluate for central endocrinopathies, including GH deficiency, central
hypothyroidism, central adrenal insufficiency, precocious puberty, andgonadotropin deficiency.
Refer to endocrine for management of hormonal dysfunction.
Evaluate for other co-morbid conditions, including dyslipidemia, hypertension,and impaired glucose metabolism.
Refer to dietitian for weight management.
SYSTEM = Endocrine/Metabolic
SCORE = 2Aw

Additional Information

Definition of Overweight: Age 2-20 years BMI for age ≥85th to <95th percentile. Age ≥21 years BMI ≥25-29.9.
Definition of Obesity: Age 2-20 years BMI for age ≥95th percentile. Age ≥21 years BMI ≥30.
BMI=wt(kg)/ht(m2). BMI calculator available on-line at: www.nhlbi.nih.gov/guidelines/obesity/BMI/bmicalc.htm. Growth charts for patients <21 years of age available on-line at: www.cdc.gov/growthcharts.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Craniopharyngioma, tumor extension to hypothalamus, surgery in supra-sellar region- Pre-morbid/Co-morbid medical conditions: Pre-treatment obesity

References
De Vile CJ, Grant DB, Kendall BE, et al: Management of childhood craniopharyngioma: can the morbidity of radical surgery be predicted? J Neurosurg 85:73-81, 1996
Elliott RE, Hsieh K, Hochm T, et al: Efficacy and safety of radical resection of primary and recurrent craniopharyngiomas in 86 children. J Neurosurg Pediatr 5:30-48, 2010
Elliott RE, Wisoff JH: Surgical management of giant pediatric craniopharyngiomas. J Neurosurg Pediatr 6:403-16, 2010
Jane JA, Jr., Prevedello DM, Alden TD, et al: The transsphenoidal resection of pediatric craniopharyngiomas: a case series. J Neurosurg Pediatr 5:49-60, 2010
Lustig RH, Post SR, Srivannaboon K, et al: Risk factors for the development of obesity in children surviving brain tumors. J Clin Endocrinol Metab 88:611-6, 2003
Muller HL, Emser A, Faldum A, et al: Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma. J Clin Endocrinol Metab 89:3298-305, 2004
Muller HL, Gebhardt U, Faldum A, et al: Functional capacity and body mass index in patients with sellar masses--cross-sectional study on 403 patients diagnosed during childhood and adolescence. Childs Nerv Syst 21:539-45, 2005
Puget S, Garnett M, Wray A, et al: Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement. J Neurosurg 106:3-12, 2007
Sainte-Rose C, Puget S, Wray A, et al: Craniopharyngioma: the pendulum of surgical management. Childs Nerv Syst 21:691-5, 2005

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SURGERYSec #129

NEUROSURGERY—BRAIN (CONT)

Therapeutic
Exposure
Neurosurgery-Brain(applies only toneurosurgery withpotential to affect the
hypothalamic-pituitaryaxis)

Potential
Late Effects
Diabetes insipidus

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Assessment of excessive thirst/polyuria
YearlyHEALTH LINKS
Hypopituitarism
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Na, K, Cl, CO2, serum osmolality, and urine osmolality as clinically indicated if
history consistent with excessive thirst and/or polyuria.
Evaluation for other central endocrinopathies, including GH deficiency, central
hypothyroidism, central adrenal insufficiency, precocious puberty, andgonadotropin deficiency.
Refer to endocrine to manage hormonal dysfunction.
Diabetes insipidus is unlikely to occur as a late effect past two years fromtherapeutic exposure, other causes should be considered in the presence ofsymptoms.
SYSTEM = Endocrine/Metabolic
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Craniopharyngioma, extension of tumor into hypothalamus, surgery in supra-sellar region, reoperation for recurrent tumor

References
Elliott RE, Hsieh K, Hochm T, et al: Efficacy and safety of radical resection of primary and recurrent craniopharyngiomas in 86 children. J Neurosurg Pediatr 5:30-48, 2010
Jane JA, Jr., Prevedello DM, Alden TD, et al: The transsphenoidal resection of pediatric craniopharyngiomas: a case series. J Neurosurg Pediatr 5:49-60, 2010
Lawson SA, Horne VE, Golekoh MC, et al: Hypothalamic-pituitary function following childhood brain tumors: analysis of prospective annual endocrine screening. Pediatric Blood Cancer 66(5):e27631, 2019
Lo AC, Howard AF, Nichol A, et al: Long-term outcomes and complications in patients with craniopharyngioma: the British Columbia Cancer Agency experience. Int J Radiat Oncol Biol Phys 88:1011-8, 2014
Olsson DS, Andersson E, Bryngelsson IL, et al: Excess mortality and morbidity in patients with craniopharyngioma, especially in patients with childhood onset: a population-based study in Sweden. J Clin Endocrinol Metab 100:467-74,
2015
Puget S, Garnett M, Wray A, et al: Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement. J Neurosurg 106:3-12, 2007
Sainte-Rose C, Puget S, Wray A, et al: Craniopharyngioma: the pendulum of surgical management. Childs Nerv Syst 21:691-5, 2005
Vinchon M, Baroncini M, Leblond P, et al: Morbidity and tumor-related mortality among adult survivors of pediatric brain tumors: a review. Childs Nerv Syst 27:697-704, 2011
Yano S, Kudo M, Hide T, et al: Quality of life and clinical features of long-term survivors surgically treated for pediatric craniopharyngioma. World Neurosurg 85:153-62, 2016

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SURGERYSec #130

NEUROSURGERY—SPINAL CORD

Therapeutic
Exposure
Neurosurgery-Spinal
cord

Potential
Late Effects
Neurogenic bladder
Urinary incontinence

Periodic Evaluation
HISTORY
Urinary urgency/frequency
Urinary incontinence/retention
Dysuria
Nocturia
Abnormal urinary stream
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Neurogenic Bladder
COUNSELING
Importance of adequate fluid intake, regular voiding, and seeking medical
attention for symptoms of voiding dysfunction or urinary tract infection.
Importance of compliance with recommended bladder catheterization regimen.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Urologic consultation for patients with dysfunctional voiding or recurrent urinary
tract infections.
SYSTEM = CNSSCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Tumor adjacent to or compressing spinal cord or cauda equina, injury above the level of the sacrum, radiation dose ≥45 Gy to lumbar and/or sacral spine and/or cauda equina, especially radiationdose ≥50 Gy

References
Fowler CJ, Sakakibara R, Frohman EM, et al: Neurologic bladder, bowel and sexual dysfunction, in Munsat TL (ed): World Federation of Neurology Seminars in Clinical Neurology. The Netherlands, Elsevier Science B.V., 2001
Hoover M, Bowman LC, Crawford SE, et al: Long-term outcome of patients with intraspinal neuroblastoma. Med Pediatr Oncol 32:353-9, 1999
McGirt MJ, Chaichana KL, Atiba A, et al: Resection of intramedullary spinal cord tumors in children: assessment of long-term motor and sensory deficits. J Neurosurg Pediatr 1:63-7, 2008
Poretti A, Zehnder D, Boltshauser E, et al: Long-term complications and quality of life in children with intraspinal tumors. Pediatr Blood Cancer 50:844-8, 2008

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SURGERY
Sec #
131

w

NEUROSURGERY—SPINAL CORD (CONT)

Therapeutic
Exposure
Neurosurgery-Spinal
cord

Potential
Late Effects
Neurogenic bowel
Fecal incontinence

Periodic Evaluation
HISTORY
Chronic constipation
Fecal soiling
YearlyPHYSICAL
Rectal exam
As clinically indicatedHealth Counseling/
Further Considerations
COUNSELING
Benefits of adherence to bowel regimen, including adequate hydration, fiber,
laxatives/enemas as clinically indicated.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
GI consultation to establish bowel regimen for patients with chronic impaction or
fecal soiling.
SYSTEM = CNSSCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Tumor adjacent to or compressing spinal cord or cauda equina, injury above the level of the sacrum, radiation dose ≥50 Gy to bladder, pelvis, or spine

References
Fowler CJ, Sakakibara R, Frohman EM, et al: Neurologic bladder, bowel and sexual dysfunction, in Munsat TL (ed): World Federation of Neurology Seminars in Clinical Neurology. The Netherlands, Elsevier Science B.V., 2001
Hoover M, Bowman LC, Crawford SE, et al: Long-term outcome of patients with intraspinal neuroblastoma. Med Pediatr Oncol 32:353-9, 1999

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SURGERYSec #132(male)NEUROSURGERY—SPINAL CORD (CONT)

Therapeutic
Exposure
Neurosurgery-Spinal
cord

Potential
Late Effects
Psychosexual dysfunction
Erectile dysfunction
Ejaculatory dysfunction

Periodic Evaluation
HISTORY
Sexual function (erections, nocturnal
emissions, libido)
Medication use
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Testicular and Reproductive Health
COUNSELING
Use of assisted reproductive technology for sperm retrieval.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Urologic consultation in patients with positive history.
SYSTEM = Reproductive (Male)SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Tumor adjacent to or compressing spinal cord or cauda equina, radiation to bladder, pelvis, or spine, radiation dose ≥55 Gy to penile bulb in adult, ≥45 Gy in prepubertal child- Pre-morbid/Co-morbid medical conditions: Testosterone deficiency/insufficiency, injury above the level of the sacrum

References
Albright TH, Grabel Z, DePasse JM, et al: Sexual and reproductive function in spinal cord injury and spinal surgery patients. Orthop Rev (Pavia) 7:5842, 2015
Fowler CJ, Sakakibara R, Frohman EM, et al: Neurologic bladder, bowel and sexual dysfunction, in Munsat TL (ed): World Federation of Neurology Seminars in Clinical Neurology. The Netherlands, Elsevier Science B.V., 2001
Kenney LB, Cohen LE, Shnorhavorian M, et al: Male reproductive health after childhood, adolescent, and young adult cancers: a report from the Children’s Oncology Group. J Clin Oncol 30:3408-16, 2012
Kubota M, Yagi M, Kanada S, et al: Long-term follow-up status of patients with neuroblastoma after undergoing either aggressive surgery or chemotherapy--a single institutional study. J Pediatr Surg 39:1328-32, 2004
Ritenour CW, Seidel KD, Leisenring W, et al: Erectile dysfunction in male survivors of childhood cancer-a report from the Childhood Cancer Survivor Study. J Sex Med 13:945-54, 2016

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SURGERYSec #133(female)w

NEUROSURGERY—SPINAL CORD (CONT)

Therapeutic
Exposure
Neurosurgery-Spinal
cord

Potential
Late Effects
Psychosexual dysfunction

Periodic Evaluation
HISTORY
Altered or diminished sensation, loss of
sensation
Dyspareunia
Medication use
YearlyHealth Counseling/
Further Considerations
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Gynecologic consultation in patients with positive history.
SYSTEM = Reproductive (Female)
SCORE = 2A

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Tumor adjacent to or compressing spinal cord or cauda equina, radiation to bladder, pelvis, or spine- Pre-morbid/Co-morbid medical conditions: Hypogonadism, vaginal fibrosis/stenosis, cGVHD, injury above the level of the sacrum

References
Bjornard KL, Howell CR, Klosky JL, et al: Psychosexual functioning of female childhood cancer survivors: a report from the St. Jude Lifetime Cohort Study. J Sex Med 17(10):1981-1994, 2020
Fowler CJ, Sakakibara R, Frohman EM, et al: Neurologic bladder, bowel and sexual dysfunction, in Munsat TL (ed): World Federation of Neurology Seminars in Clinical Neurology. The Netherlands, Elsevier Science B.V., 2001
Korse NS, Nicolai MP, Both S, et al: Discussing sexual health in spinal care. Eur Spine J 25:766-73, 2016
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Piotrowski K, Snell L: Health needs of women with disabilities across the lifespan. J Obstet Gynecol Neonatal Nurs 36:79-87, 2007

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SURGERYSec #134

NEUROSURGERY—SPINAL CORD (CONT)

Therapeutic
Exposure
Neurosurgery-Spinal
cordLaminectomy
Laminoplasty

Potential
Late Effects
Scoliosis/Kyphosis

Periodic Evaluation

Health Counseling/
Further Considerations

PHYSICALHEALTH LINKS
Exam of back/spine
Scoliosis and Kyphosis
Yearly until growth completed, may need more POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
frequent assessment during puberty or if
Spine films in patients with clinically apparent curve.
curve detected
Orthopedic consultation as indicated based on physical and/or radiographic
exam.
SYSTEM = Musculoskeletal
SCORE = 1w

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Young age (deformity can still develop even if skeletally mature at time of surgery)- Cancer/Treatment factors: Radiation to the spine, increasing number of laminae removed, especially >3 laminae removed, facetectomy, laminectomy (versus laminotomy), laminectomy without fusion, increasing number ofresections, surgery of thoracolumbar junction- Pre-morbid/Co-morbid medical conditions: Preoperative deformity

References
Anakwenze OA, Auerbach JD, Buck DW, et al: The role of concurrent fusion to prevent spinal deformity after intramedullary spinal cord tumor excision in children. J Pediatr Orthop 31:475-9, 2011de Jonge T, Slullitel H, Dubousset J, et al: Late-onset spinal deformities in children treated by laminectomy and radiation therapy for malignant tumours. Eur Spine J 14:765-71, 2005
Gawade PL, Hudson MM, Kaste SC, et al: A systematic review of selected musculoskeletal late effects in survivors of childhood cancer. Curr Pediatr Rev 10:249-62, 2014
Laverdiere C, Liu Q, Yasui Y, et al: Long-term outcomes in survivors of neuroblastoma: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 101:1131-40, 2009
McGirt MJ, Chaichana KL, Atiba A, et al: Incidence of spinal deformity after resection of intramedullary spinal cord tumors in children who underwent laminectomy compared with laminoplasty. J Neurosurg Pediatr 1:57-62, 2008
Papagelopoulos PJ, Peterson HA, Ebersold MJ, et al: Spinal column deformity and instability after lumbar or thoracolumbar laminectomy for intraspinal tumors in children and young adults. Spine 22:442-451, 1997
Paulino AC, Fowler BZ: Risk factors for scoliosis in children with neuroblastoma. Int J Radiat Oncol Biol Phys 61:865-869, 2005
Yao KC, Mcgirt MJ, Chaichana KL, et al: Risk factors for progressive spinal deformity following resection of intramedullary spinal cord tumors in children: an analysis of 161 consecutive cases. J Neurosurg 107:463-468, 2007

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SURGERYSec #135

Therapeutic
Exposure
Oophoropexy(female)w

OOPHOROPEXY
Potential
Late Effects
Oophoropexy-related
complications
Inability to conceive despite
normal ovarian function
Dyspareunia
Symptomatic ovarian cysts
Bowel obstruction
Pelvic adhesions

Periodic Evaluation
HISTORY
Inability to conceive
Dyspareunia
Abdominal pain
Pelvic pain
YearlyHealth Counseling/
Further Considerations
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Gynecologic consultation for patients with positive history.
SYSTEM = Reproductive (Female)
SCORE = 2A

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Ovarian radiation, tubo-ovarian dislocation (especially with lateral ovarian transposition)

References
Chambers SK, Chambers JT, Kier R, et al: Sequelae of lateral ovarian transposition in irradiated cervical cancer patients. Int J Radiat Oncol Biol Phys 20:1305-8, 1991
Damewood MD, Hesla HS, Lowen M, et al: Induction of ovulation and pregnancy following lateral oophoropexy for Hodgkin’s disease. Int J Gynaecol Obstet 33:369-71, 1990
Hadar H, Loven D, Herskovitz P, et al: An evaluation of lateral and medial transposition of the ovaries out of radiation fields. Cancer 74:774-9, 1994
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Terenziani M, Piva L, Meazza C, et al: Oophoropexy: a relevant role in preservation of ovarian function after pelvic irradiation. Fertil Steril 91:935 e15-6, 2009
Thibaud E, Ramirez M, Brauner R, et al: Preservation of ovarian function by ovarian transposition performed before pelvic irradiation during childhood. J Pediatr 121:880-4, 1992

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SURGERYSec #136(female)OOPHORECTOMY (UNILATERAL)

Therapeutic
Exposure
Oophorectomy
unilateral

Potential
Late Effects
Ovarian hormone deficiencies
Delayed puberty
Arrested pubertyPremature ovarian
insufficiency/Prematuremenopause

Periodic Evaluation
HISTORY
Onset and tempo of puberty
Menstrual history
Sexual function (vaginal dryness, libido)
Menopausal symptoms
Medication use
YearlyPHYSICAL
Tanner staging until sexually mature
YearlyMonitor growth until mature
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Ovarian and Reproductive Health
COUNSELING
Adverse impact of ovarian hormone deficiencies on growth, bone mineralization,
cardiovascular disease and sexual dysfunction.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
FSH and estradiol and/or endocrine/gynecology referral for patients with:• No signs of puberty by age 13 years• Failure of pubertal progression• Abnormal menstrual patterns or menopausal symptoms• Ovarian hormone deficiency/insufficiency to weigh risks and benefits of hormonal replacement therapy
Bone density evaluation in patients with ovarian hormone deficiencies.
SYSTEM = Reproductive (Female)
SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Combination with pelvic radiation, TBI, or alkylating agents- Health behaviors: Smoking

References
Bercow A, Nitecki R, Brady PC, et al: Outcomes after fertility-sparing surgery for women with ovarian cancer: a systematic review of the literature. J Minim Invasive Gynecol 28(3):527-536.e1, 2021
Chen J, Wang FF, Zhang Y, et al: Oncological and reproductive outcomes of fertility-sparing surgery in women with early-stage epithelial ovarian carcinoma: a multicenter retrospective study. Curr Med Sci 40(4):745-752, 2020
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Thomas-Teinturier C, El Fayech C, Oberlin O, et al: Age at menopause and its influencing factors in a cohort of survivors of childhood cancer: earlier but rarely premature. Hum Reprod 28:488-95, 2013

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SURGERYSec #137(female)OOPHORECTOMY (UNILATERAL) (CONT)

Therapeutic
Exposure
Oophorectomy
unilateral

Potential
Late Effects
Diminished Ovarian Reserve(DOR)
Infertility

Periodic Evaluation
HISTORY
Menstrual and pregnancy history
Hormonal therapy
YearlyPHYSICAL
Tanner staging until sexually mature
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Ovarian and Reproductive HealthRESOURCES
American Society for Reproductive Medicine: www.asrm.org
Alliance for Fertility Preservation: www.allianceforfertilitypreservation.org
Livestrong Foundation: www.livestrong.org/what-we-do/program/fertility
Oncofertility Consortium: https://oncofertility.msu.edu
COUNSELING
Potential for shorter period of fertility in family planning. Those with DOR
should consider discussing reproductive health options with a reproductive
endocrinologist or fertility specialist.
Review previous fertility preservation counseling/interventions.
Need for contraception.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
FSH and estradiol for patients with menstrual cycle dysfunction suggestiveof premature ovarian insufficiency or those who desire information about
potential for future fertility.
AMH to assess for DOR.
Reproductive endocrinology referral for antral follicle count, ovarian reserve
evaluation and consultation regarding assisted reproductive technologies in atrisk patients who desire information about potential fertility and interventions
to preserve future fertility.
SYSTEM = Reproductive (Female)
SCORE = 2Aw

Additional Information

AMH may be low in the presence of normal FSH. AMH should be interpreted relative to age-specific reference ranges. FSH is lowered and AMH may be lowered by concurrent hormonal contraceptive use.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Combination with pelvic radiation, TBI, or alkylating agents- Health behaviors: Smoking

References
Chemaitilly W, Li Z, Krasin MJ, et al. Premature ovarian insufficiency in childhood cancer survivors: a report from the St. Jude Lifetime Cohort. J Clin Endocrinol Metab 102(7):2242-50, 2017
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Thomas-Teinturier C, El Fayech C, Oberlin O, et al: Age at menopause and its influencing factors in a cohort of survivors of childhood cancer: earlier but rarely premature. Hum Reprod 28:488-95, 2013

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SURGERYSec #138(female)Therapeutic
Exposure
Oophorectomy
bilateral

OOPHORECTOMY (BILATERAL)
Potential
Late Effects

Periodic Evaluation

Ovarian hormone deficiencies SCREENING
Absence of puberty
Endocrinologic or gynecologic consultation
Loss of ovarian follicular poolfor initiation of hormonal replacement
Infertility
therapy
At age 11 years or immediately for postpubertal patients

Health Counseling/
Further Considerations
HEALTH LINKS
Ovarian and Reproductive HealthRESOURCES
American Society for Reproductive Medicine: www.asrm.org
Alliance for Fertility Preservation: www.allianceforfertilitypreservation.org
Livestrong Foundation www.livestrong.org/what-we-do/program/fertility
Oncofertility Consortium https://oncofertility.msu.edu
COUNSELING
Benefits of hormone replacement therapy in promoting pubertal progression,bone and cardiovascular health.
Counsel women regarding pregnancy potential with donor eggs (if intact uterus).
Review previous fertility preservation counseling/interventions.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Reproductive endocrinology referral regarding assisted reproductive
technologies.
BMD evaluation.
SYSTEM = Reproductive (Female)
SCORE = 1w

References

Candy B, Jones L, Vickerstaff V, et al: Interventions for sexual dysfunction following treatments for cancer in women. Cochrane Database of Systematic Reviews, 2016
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Rivera CM, Grossardt BR, Rhodes DJ, et al: Increased cardiovascular mortality after early bilateral oophorectomy. Menopause 16:15-23, 2009
Schover LR: Sexuality and fertility after cancer. Hematology Am Soc Hematol Educ Program:523-7, 2005

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SURGERYSec #139(male)ORCHIECTOMY (UNILATERAL, PARTIAL)

Therapeutic
Exposure
Orchiectomy
unilateralpartialPotential
Late Effects
Testicular hormonal
dysfunction
Testosterone deficiency/
insufficiency
Delayed/Arrested puberty

Periodic Evaluation
HISTORY
Onset and tempo of puberty
Sexual function (erections, nocturnal
emissions, libido)
Medication use
YearlyPHYSICAL
Tanner staging until sexually mature
Testicular volume by Prader orchidometer
YearlyMonitor growth until mature
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Testicular and Reproductive Health
COUNSELING
Wear athletic supporter with protective cup during athletic activities.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Testosterone insufficiency or deficiency requiring hormone replacement after
alkylating agents only is rare.
Endocrine referral for the following:• No signs of puberty by age 14 years• Failure of pubertal progression• Adults with low AM testosterone levels
Periodic re-evaluation of testosterone in males with low-normal testosterone asthey age or if they become symptomatic.
Bone density evaluation in androgen deficient patients.
Surgical placement of testicular prosthesis and ongoing monitoring for surgicalcomplications after prosthesis placement.
Psychology referral (because orchiectomy can be associated with psychologicaldistress related to altered body image).
SYSTEM = Reproductive (Male)SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Medications (anabolic steroids, testosterone), occupational exposures (pesticides, heavy metals, solvents)- Cancer/Treatment factors: Testicular cancer, unilateral orchiectomy combined with pelvic or testicular radiation and/or alkylating agents, higher cumulative dose platinum chemotherapy, infradiaphragmatic radiation- Pre-morbid/Co-morbid medical conditions: Obesity, ejaculatory dysfunction, history of sexually transmitted infections- Health behaviors: Tobacco/Marijuana use

References
Bandak M, Aksglaede L, Juul A, et al: The pituitary-Leydig cell axis before and after orchiectomy in patients with stage I testicular cancer. Eur J Cancer 47:2585-2591, 2011
Eberhard J, Stahl O, Cwikiel M, et al: Risk factors for post-treatment hypogonadism in testicular cancer patients. Eur J Endocrinol 158:561-570, 2008
Huddart RA, Norman A, Moynihan C, et al: Fertility, gonadal and sexual function in survivors of testicular cancer. Br J Cancer 93:200-207, 2005
Jacobsen KD, Fossa SD, Bjoro TP, et al: Gonadal function and fertility in patients with bilateral testicular germ cell malignancy. Eur Urol 42:229-237, 2002
Sprauten M, Brydoy M, Haugnes HS, et al: Longitudinal serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels in a population-based sample of long-term testicular cancer survivors. J Clin Oncol 32:571-8,
2014
Woo LL, Ross JH: The role of testis-sparing surgery in children and adolescents with testicular tumors. Urol Oncol 34:76-83, 2016
Yossepowitch O, Aviv D, Wainchwaig L, et al: Testicular prostheses for testis cancer survivors: patient perspectives and predictors of long-term satisfaction. J Urol 186:2249-2252, 2011

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SURGERYSec #140(male)ORCHIECTOMY (UNILATERAL, PARTIAL) (CONT)

Therapeutic
Exposure
Orchiectomy
unilateralpartialPotential
Late Effects
Impaired spermatogenesis
Reduced fertility
Oligospermia
Azoospermia
Infertility

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Onset and tempo of puberty
Sexual function (erections, nocturnal
emissions, libido)
Medication use
YearlyPHYSICAL
Tanner staging until sexually mature
Testicular volume by Prader orchidometer
YearlyHEALTH LINKS

Testicular and Reproductive HealthRESOURCES
American Society for Reproductive Medicine: www.asrm.org
Alliance for Fertility Preservation: www.allianceforfertilitypreservation.org
COUNSELING
Need for contraception.
Review previous fertility preservation counseling/interventions.
Wear athletic supporter with protective cup during athletic activities.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
For sexually mature patients who desire information about potential future fertility:
semen analysis (optimal) and/or FSH and inhibin B (alternative if unable orunwilling to provide semen sample).
Reproductive endocrinology/urology referral for infertility evaluation and consultation
regarding assisted reproductive technologies.
Surgical placement of testicular prosthesis and ongoing monitoring for surgicalcomplications after prosthesis placement.
Psychology referral (because orchiectomy can be associated with psychologicaldistress related to altered body image).
SYSTEM = Reproductive (Male)SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Medications (anabolic steroids, testosterone), occupational exposures (pesticides, heavy metals, solvents)- Cancer/Treatment factors: Testicular cancer, unilateral orchiectomy combined with pelvic or testicular radiation and/or alkylating agents, higher cumulative dose platinum chemotherapy, infradiaphragmatic radiation- Pre-morbid/Co-morbid medical conditions: Obesity, ejaculatory dysfunction, history of sexually transmitted infections- Health behaviors: Tobacco/Marijuana use

References
Eskenazi B, Wyrobek AJ, Sloter E, et al: The association of age and semen quality in healthy men. Hum Reprod 18:447-454, 2003
Green DM, Zhu L, Zhang N, et al: Lack of specificity of plasma concentrations of inhibin B and follicle-stimulating hormone for identification of azoospermic survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study. J Clin Oncol
31:1324-8, 2013
Huddart RA, Norman A, Moynihan C, et al: Fertility, gonadal and sexual function in survivors of testicular cancer. Br J Cancer 93:200-207, 2005
Jacobsen KD, Fossa SD, Bjoro TP, et al: Gonadal function and fertility in patients with bilateral testicular germ cell malignancy. Eur Urol 42:229-237, 2002
Nudell DM, Monoski MM, Lipshultz LI: Common medications and drugs: how they affect male fertility. Urol Clin N Am 29:965-73, 2002
Romerius P, Stahl O, Moell C, et al: High risk of azoospermia in men treated for childhood cancer. Int J Androl 34:69-76, 2011
Sprauten M, Brydoy M, Haugnes HS, et al: Longitudinal serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels in a population-based sample of long-term testicular cancer survivors. J Clin Oncol 32:571-8, 2014
Woo LL, Ross JH: The role of testis-sparing surgery in children and adolescents with testicular tumors. Urol Oncol 34:76-83, 2016
Yossepowitch O, Aviv D, Wainchwaig L, et al: Testicular prostheses for testis cancer survivors: patient perspectives and predictors of long-term satisfaction. J Urol 186:2249-2252, 2011
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SURGERYSec #141(male)

Therapeutic
Exposure
Orchiectomy
bilateral

ORCHIECTOMY (BILATERAL)
Potential
Late Effects
Testosterone deficiency
Absence of puberty
Azoospermia
Infertility

Periodic Evaluation
PHYSICAL
Exam of testicular prostheses
YearlySCREENING
Endocrinologic consultation for initiation of
hormonal replacement therapy
At age 11 years or immediately for postpubertal patients

Health Counseling/
Further Considerations
HEALTH LINKS
Testicular and Reproductive Health
COUNSELING
Review previous fertility preservation counseling/interventions.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Surgical placement of testicular prostheses and ongoing monitoring for surgicalcomplications after prostheses placement.
Psychology referral (because orchiectomy can be associated with psychologicaldistress related to altered body image).
Bone density evaluation.
SYSTEM = Reproductive (Male)SCORE = 1w

References

Herman-Giddens ME, Steffes J, Harris D, et al: Secondary sexual characteristics in boys: data from the pediatric research in office settings network. Pediatrics 130:E1058-E1068, 2012
Jacobsen KD, Fossa SD, Bjoro TP, et al: Gonadal function and fertility in patients with bilateral testicular germ cell malignancy. Eur Urol 42:229-237, 2002
Modh RA, Mulhall JP, Gilbert SM: Sexual dysfunction after cystectomy and urinary diversion. Nat Rev Urol 11:445-53, 2014
Yossepowitch O, Aviv D, Wainchwaig L, et al: Testicular prostheses for testis cancer survivors: patient perspectives and predictors of long-term satisfaction. J Urol 186:2249-2252, 2011

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SURGERYSec #142

PELVIC SURGERY

Therapeutic
Exposure
Pelvic surgery
Cystectomy

Potential
Late Effects
Urinary incontinence
Urinary tract obstruction

Periodic Evaluation
HISTORY
Urinary urgency/frequency
Urinary incontinence/retention
Dysuria
Nocturia
Abnormal urinary stream
YearlyHealth Counseling/
Further Considerations
COUNSELING
Importance of adequate fluid intake, regular voiding, and seeking medical
attention for symptoms of voiding dysfunction or urinary tract infection.
Importance of compliance with recommended bladder catheterization regimen.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Urologic consultation for patients with dysfunctional voiding or recurrent urinary
tract infections.
SYSTEM = Urinary
SCORE = 1w

Additional Information

For patients with cystectomy, see also section 117.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Pre-morbid/Co-morbid medical conditions: Tumor adjacent to or compressing spinal cord or cauda equina, retroperitoneal node dissection, extensive pelvic dissection (e.g., bilateral ureteral re-implantation, retroperitoneal
tumor resection), radiation to the bladder, pelvis, and/or lumbar-sacral spine

References
Derikx JPM, De Backer A, van de Schoot L, et al: Long-term functional sequelae of sacrococcygeal teratoma: a national study in the Netherlands. J Pediatr Surg 42:1122-1126, 2007
Hale GA, Marina NM, Jones-Wallace D, et al: Late effects of treatment for germ cell tumors during childhood and adolescence. J Pediatr Hematol Oncol 21:115-22, 1999
Heyn R, Raney RB, Jr., Hays DM, et al: Late effects of therapy in patients with paratesticular rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee. J Clin Oncol 10:614-23, 1992
Koyle MA, Hatch DA, Furness PD, et al: Long-term urological complications in survivors younger than 15 months of advanced stage abdominal neuroblastoma. J Urol 166:1455-1458, 2001
Kremer ME, Derikx JP, van Baren R, et al: Patient-reported defecation and micturition problems among adults treated for sacrococcygeal teratoma during childhood--the need for new surveillance strategies. Pediatr Blood Cancer
63:690-4, 2016
Ozkan KU, Bauer SB, Khoshbin S, et al: Neurogenic bladder dysfunction after sacrococcygeal teratoma resection. J Urol 175:292-296, 2006
Raney B, Anderson J, Jenney M, et al: Late effects in 164 patients with rhabdomyosarcoma of the bladder/prostate region: A report from the international workshop. J Urol 176:2190-2194, 2006

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PELVIC SURGERY (CONT)

Therapeutic
Exposure
Pelvic surgery
Cystectomy

Potential
Late Effects
Fecal incontinence

Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Chronic constipation
Fecal soiling
YearlyPHYSICAL
Rectal exam
As clinically indicated

COUNSELING
Benefits of adherence to bowel regimen, including adequate hydration, fiber,
laxatives/enemas as clinically indicated.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
GI consultation to establish bowel regimen for patients with chronic impaction or
fecal soiling.
SYSTEM = GI/Hepatic
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Tumor adjacent to or compressing spinal cord or cauda equina, radiation to bladder, pelvis, or spine

References
Hale GA, Marina NM, Jones-Wallace D, et al: Late effects of treatment for germ cell tumors during childhood and adolescence. J Pediatr Hematol Oncol 21:115-22, 1999
Hoover M, Bowman LC, Crawford SE, et al: Long-term outcome of patients with intraspinal neuroblastoma. Med Pediatr Oncol 32:353-9, 1999
Moore SW, Kaschula ROC, Albertyn R, et al: The outcome of solid tumors occurring in the neonatal-period. Pediatr Surg Int 10:366-370, 1995
Rao S, Azmy A, Carachi R: Neonatal tumours: a single-centre experience. Pediatr Surg Int 18:306-309, 2002

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SURGERYSec #144(male)PELVIC SURGERY (CONT)

Therapeutic
Exposure
Pelvic surgery
Cystectomy

Potential
Late Effects
Psychosexual dysfunction
Erectile dysfunction

Periodic Evaluation
HISTORY
Sexual function (erections, nocturnal
emissions, libido)
Medication use
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Testicular and Reproductive Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Urologic consultation in patients with positive history.
SYSTEM = Reproductive (Male)SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Tumor adjacent to spine, retroperitoneal node dissection, retroperitoneal tumor resection, extensive presacral tumor resection, cystectomy, radical prostatectomy, radiation to bladder, pelvis, or spine,or dissection, radiation dose ≥55 Gy to penile bulb in adult, ≥45 Gy in prepubertal child- Pre-morbid/Co-morbid medical conditions: Hypogonadism

References
Brydoy M, Fossa SD, Klepp O, et al: Paternity following treatment for testicular cancer. J Natl Cancer Inst 97:1580-1588, 2005
Jacobsen KD, Ous S, Waehre H, et al: Ejaculation in testicular cancer patients after post-chemotherapy retroperitoneal lymph node dissection. Br J Cancer 80:249-55, 1999
Macedo A, Jr., Ferreira PV, Barroso U, Jr., et al: Sexual function in teenagers after multimodal treatment of pelvic rhabdomyosarcoma: A preliminary report. J Pediatr Urol 6:605-8, 2010
Modh RA, Mulhall JP, Gilbert SM: Sexual dysfunction after cystectomy and urinary diversion. Nat Rev Urol 11:445-53, 2014
Ritenour CW, Seidel KD, Leisenring W, et al: Erectile dysfunction in male survivors of childhood cancer-a report from the Childhood Cancer Survivor Study. J Sex Med 13:945-54, 2016
Zippe C, Nandipati K, Agarwal A, et al: Sexual dysfunction after pelvic surgery. Int J Impot Res 18:1-18, 2006

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SURGERYSec #145(male)PELVIC SURGERY (CONT)

Therapeutic
Exposure
Pelvic surgery
Cystectomy

Potential
Late Effects
Sexual dysfunction(anatomic)
Retrograde ejaculation
Anejaculation
Obstructive azoospermia
Infertility

Periodic Evaluation

Health Counseling/
Further Considerations

HISTORYHEALTH LINKS
Quality of ejaculate (frothy white urine
Testicular and Reproductive Healthwith first void after intercourse suggests COUNSELING
retrograde ejaculation)
Use of assisted reproductive technology for sperm retrieval.
YearlyPOTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Urologic consultation in patients with positive history.
SYSTEM = Reproductive (Male)SCORE = 2Aw

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Tumor adjacent to spine, retroperitoneal node dissection, retroperitoneal tumor resection, extensive presacral tumor resection, cystectomy, radical prostatectomy, radiation to bladder, pelvis, or spine,or dissection, radiation dose ≥55 Gy to penile bulb in adult, ≥45 Gy in prepubertal child- Pre-morbid/Co-morbid medical conditions: Hypogonadism

References
Brydoy M, Fossa SD, Klepp O, et al: Paternity following treatment for testicular cancer. J Natl Cancer Inst 97:1580-1588, 2005
Jacobsen KD, Ous S, Waehre H, et al: Ejaculation in testicular cancer patients after post-chemotherapy retroperitoneal lymph node dissection. Br J Cancer 80:249-55, 1999
Macedo A, Jr., Ferreira PV, Barroso U, Jr., et al: Sexual function in teenagers after multimodal treatment of pelvic rhabdomyosarcoma: A preliminary report. J Pediatr Urol 6:605-8, 2010
Modh RA, Mulhall JP, Gilbert SM: Sexual dysfunction after cystectomy and urinary diversion. Nat Rev Urol 11:445-53, 2014
Ritenour CW, Seidel KD, Leisenring W, et al: Erectile dysfunction in male survivors of childhood cancer-a report from the Childhood Cancer Survivor Study. J Sex Med 13:945-54, 2016
Zippe C, Nandipati K, Agarwal A, et al: Sexual dysfunction after pelvic surgery. Int J Impot Res 18:1-18, 2006

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SURGERYSec #146(female)w

PELVIC SURGERY (CONT)

Therapeutic
Exposure
Pelvic surgery
Cystectomy

Potential
Late Effects
Sexual dysfunction

Periodic Evaluation
HISTORY
Altered or diminished sensation, loss of
sensation
Dyspareunia
Medication use
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Ovarian and Reproductive Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Gynecologic consultation for patients with positive history.
SYSTEM = Reproductive (Female)
SCORE = 2A

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Tumor adjacent to spine, radiation to bladder, pelvis or spine- Pre-morbid/Co-morbid medical conditions: cGVHD, hypogonadism

References
Aerts L, Enzlin P, Verhaeghe J, et al: Sexual and psychological functioning in women after pelvic surgery for gynaecological cancer. Eur J Gynaecol Oncol 30:652-6, 2009
Bjornard KL, Howell CR, Klosky JL, et al: Psychosexual functioning of female childhood cancer survivors: a report from the St. Jude Lifetime Cohort Study. J Sex Med 17(10):1981-1994, 2020
Metzger ML, Meacham LR, Patterson B, et al: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol
31:1239-47, 2013
Schover LR: Sexuality and fertility after cancer. Hematology Am Soc Hematol Educ Program:523-7, 2005
Spunt SL, Sweeney TA, Hudson MM, et al: Late effects of pelvic rhabdomyosarcoma and its treatment in female survivors. J Clin Oncol 23:7143-51, 2005

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SURGERYSec #147

Therapeutic
Exposure
Splenectomy

SPLENECTOMY
Potential
Late Effects
Asplenia
At risk for life-threatening infection
with encapsulated organisms(e.g., Haemophilus influenzae,
Streptococcus pneumoniae,
meningococcus)

Periodic Evaluation
PHYSICAL
Physical exam at time of febrile illness toevaluate degree of illness and potential
source of infection
When febrile T ≥101°F (38.3°C)
SCREENING
Blood culture
When febrile T ≥101°F (38.3°C)

Health Counseling/
Further Considerations
HEALTH LINKS
Splenic Precautions
COUNSELING
Risk of life-threatening infections with encapsulated organisms.
Risk of malaria and tick-borne diseases if living in or visiting endemic areas.
Obtain medical alert bracelet/card noting asplenia.
Discuss importance of immunization with Pneumococcal, Meningococcal (including
serotype B), Influenza and HIB vaccines according to current ACIP recommendations.
For further details regarding antibiotic prophylaxis and immunizations, see current editionof AAP Red Book.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Administer a long-acting, broad-spectrum parenteral antibiotic (e.g., ceftriaxone) inpatients with T ≥101°F (38.3°C) or other signs of serious illness and continue close
medical monitoring while awaiting blood culture results.
Hospitalize and broaden antimicrobial coverage (e.g., addition of vancomycin) undercertain circumstances, such as the presence of marked leukocytosis, neutropenia, or
significant change from baseline CBC, toxic clinical appearance, fever ≥104°F (40°C),
meningitis, pneumonia, or other serious focus of infection, signs of septic shock, orprevious history of serious infection.
Discuss with dental provider potential need for antibiotic prophylaxis based on planned
procedure.
SYSTEM = Immune
SCORE = 2Aw

References

Castagnola E, Fioredda F: Prevention of life-threatening infections due to encapsulated bacteria in children with hyposplenia or asplenia: a brief review of current recommendations for practical purposes. Eur J Haematol 71:319-26, 2003
Centers for Disease Control and Prevention: Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 61:816-9, 2012
Centers for Disease Control and Prevention: Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of theAdvisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 62:521-4, 2013
Committee on Infectious Disease, American Academy of Pediatrics: Immunization in special clinical circumstances, in Kimberlin DW, Barnett ED, Lynfield R, et al (eds): Red Book: 2021 Report of the Committee on Infectious Diseases (ed 32). Itasca,
IL, American Academy of Pediatrics, 2021, pp 67-105
Guilcher GMT, Rivard L, Huang JT, et al: Immune function in childhood cancer survivors: a Children’s Oncology Group review. Lancet Child Adolesc Health 5(4):284-294, 2021
Jockovich M, Mendenhall NP, Sombeck MD, et al: Long-term complications of laparotomy in Hodgkin’s disease. Ann Surg 219:615-21; discussion 621-4, 1994

Mbaeyi SA, Bozio CH, Duffy J, et al: Meningococcal vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 69(9);1-41, 2020
Mourtzoukou EG, Pappas G, Peppas G, et al: Vaccination of asplenic or hyposplenic adults. Br J Surg 95:273-80, 2008
Newland A, Provan D, Myint S: Preventing severe infection after splenectomy - Patients should know the risks, be immunised, and take prophylactic antibiotics. BMJ 331:417-418, 2005
Omlin AG, Muhlemann K, Fey MF, et al: Pneumococcal vaccination in splenectomised cancer patients. Eur J Cancer 41:1731-1734, 2005
Price VE, Blanchette VS, Ford-Jones EL: The prevention and management of infections in children with asplenia or hyposplenia. Infect Dis Clin North Am 21:697-710, viii-ix, 2007
Smets F, Bourgois A, Vermylen C, et al: Randomised revaccination with pneumococcal polysaccharide or conjugate vaccine in asplenic children previously vaccinated with polysaccharide vaccine. Vaccine 25:5278-82, 2007
Spelman D, Buttery J, Daley A, et al: Guidelines for the prevention of sepsis in asplenic and hyposplenic patients. Intern Med J 38:349-56, 2008
Taylor MD, Genuit T, Napolitano LM: Overwhelming postsplenectomy sepsis and trauma: Time to consider revaccination? J Trauma 59:1482-1485, 2005
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THORACIC SURGERY

Therapeutic
ExposureThoracic surgery

Potential
Late Effects
Pulmonary dysfunction

Periodic Evaluation
HISTORY
Cough
Wheezing
Shortness of breath
Dyspnea on exertion
YearlyPHYSICAL
Pulmonary exam
YearlySCREENING
PFTs (including DLCO and spirometry)
Baseline at entry into long-term follow-up,
repeat as clinically indicated in patients withabnormal results or progressive pulmonary
dysfunction

Health Counseling/
Further Considerations
HEALTH LINKS
Pulmonary HealthRESOURCES
www.smokefree.gov
COUNSELING
Tobacco and Environmental tobacco smoke avoidance/Smoking cessation.
Influenza and Pneumococcal vaccinations.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Repeat PFTs prior to general anesthesia.
Pulmonary consultation for patients with symptomatic pulmonary dysfunction.
Pulmonary consultation for survivors who desire to SCUBA dive (due to potential
undiagnosed pulmonary toxicities, and limited data to guide safe diving
recommendations for individuals treated with pulmonary toxic therapy).
SYSTEM = Pulmonary
SCORE = 2A

Additional Information

Thoracic surgery includes thoractomy, chest wall surgery, rib resection, pulmonary lobectomy, pulmonary metastasectomy and pulmonary wedge resection.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Combination with pulmonary toxic therapy (e.g., bleomycin, busulfan, carmustine [BCNU], lomustine [CCNU]), combination with chest radiation and TBI- Pre-morbid/Co-morbid medical conditions: Atopic history- Health behaviors: Smoking, inhaled illicit drug use

References
Dietz AC, Chen Y, Yasui Y, et al: Risk and impact of pulmonary complications in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 122:3687-3696, 2016
Green DM, Zhu L, Wang M, et al: Pulmonary function after treatment for childhood cancer. A report from the St. Jude Lifetime Cohort Study (SJLIFE). Ann Am Thorac Soc 13:1575-85, 2016
Hudson MM, Ness KK, Gurney JG, et al: Clinical ascertainment of health outcomes among adults treated for childhood cancer. JAMA 309:2371-2381, 2013
Mulder RL, Thonissen NM, van der Pal HJ, et al: Pulmonary function impairment measured by pulmonary function tests in long-term survivors of childhood cancer. Thorax 66:1065-71, 2011
Tetrault JM, Crothers K, Moore BA, et al: Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch Intern Med 167:221-8, 2007
van Hulst RA, Rietbroek RC, Gaastra MT, et al: To dive or not to dive with bleomycin: a practical algorithm. Aviat Space Environ Med 82:814-8, 2011
Wolff AJ, O’Donnell AE: Pulmonary effects of illicit drug use. Clin Chest Med 25:203-16, 2004

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THORACIC SURGERY (CONT)

Therapeutic
ExposureThoracic surgery

Potential
Late Effects
Scoliosis/Kyphosis

Periodic Evaluation

Health Counseling/
Further Considerations

PHYSICALHEALTH LINKS
Exam of back/spine
Scoliosis and Kyphosis
Yearly until growth completed, may need more POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
frequent assessment during puberty or if
Spine films in patients with clinically apparent curve.
curve detected
Orthopedic consultation as indicated based on physical and/or radiographic
exam.
SYSTEM = Musculoskeletal
SCORE = 2Aw

Additional Information

Thoracic surgery includes thoractomy, chest wall surgery, rib resection, pulmonary lobectomy, pulmonary metastasectomy and pulmonary wedge resection.
Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Patient factors: Young age (deformity can still develop even if skeletally mature at time of surgery)- Cancer/Treatment factors: Radiation to the spine, greater number of ribs resected- Pre-morbid/Co-morbid medical conditions: Preoperative deformity

References
Deschamps C, Tirnaksiz BM, Darbandi R, et al: Early and long-term results of prosthetic chest wall reconstruction. J Thorac Cardiovasc Surg 117:588-91; discussion 591-2, 1999
Dingemann C, Linderkamp C, Weidemann J, et al: Thoracic wall reconstruction for primary malignancies in children: short- and long-term results. Eur J Pediatr Surg 22:34-9, 2012
Gawade PL, Hudson MM, Kaste SC, et al: A systematic review of selected musculoskeletal late effects in survivors of childhood cancer. Curr Pediatr Rev 10:249-62, 2014
Interiano RB, Kaste SC, Li C, et al: Associations between treatment, scoliosis, pulmonary function, and physical performance in long-term survivors of sarcoma. J Cancer Surviv 11(5),553–561, 2017
Kawakami N, Winter RB, Lonstein JE, et al: Scoliosis secondary to rib resection. J Spinal Disord 7:522-7, 1994
Laverdiere C, Liu Q, Yasui Y, et al: Long-term outcomes in survivors of neuroblastoma: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 101:1131-40, 2009
Scalabre A, Parot R, Hameury F, et al: Prognostic risk factors for the development of scoliosis after chest wall resection for malignant tumors in children. J Bone Joint Surg Am 96:e10, 2014
Soyer T, Karnak I, Ciftci AO, et al: The results of surgical treatment of chest wall tumors in childhood. Pediatr Surg Int 22:135-139, 2006

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SURGERYSec #150

THYROIDECTOMY

Therapeutic
Exposure
Thyroidectomy

Potential
Late Effects
Hypothyroidism

Health Counseling/
Further Considerations

Periodic Evaluation
SCREENING
Endocrine consultation for initiation of
thyroid hormone replacement
Immediately

HEALTH LINKS
Thyroid Problems
COUNSELINGFor females, thyroid levels prior to attempting pregnancy and periodicallythroughout pregnancy.
SYSTEM = Endocrine/Metabolic
SCORE = 1w

Additional Information

Total thyroidectomy is associated with the risk of hypoparathyroidism. This complication generally occurs in the early postoperative period and may persist.
Patients with a history of total thyroidectomy should be monitored for signs and symptoms of hypoparathyroidism (e.g., paresthesias, muscle cramping, altered mental status, hyperreflexia, tetany, hypocalcemia, and hyperphosphatemia).

References
Diesen DL, Skinner MA: Pediatric thyroid cancer. Semin Pediatr Surg 21:44-50, 2012
La Quaglia MP, Telander RL: Differentiated and medullary thyroid cancer in childhood and adolescence. Semin Pediatr Surg 6:42-9, 1997
Lallier M, St-Vil D, Giroux M, et al: Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome. J Pediatr Surg 33:846-8, 1998

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THYROIDECTOMY (PARTIAL)

Therapeutic
Exposure
Thyroidectomy
partialPotential
Late Effects
Hypothyroidism

Periodic Evaluation
HISTORY
Fatigue
Weight gain
Cold intolerance
Constipation
Dry skinBrittle hair
Depressed moodYearly, consider more frequent screening
during periods of rapid growth
PHYSICAL
HeightWeightHair
Skin
Thyroid exam
Yearly, consider more frequent screening
during periods of rapid growth
SCREENING
TSHFree T4
Yearly, consider more frequent screening
during periods of rapid growth

Health Counseling/
Further Considerations
HEALTH LINKS
Thyroid Problems
COUNSELINGFor females, thyroid levels prior to attempting pregnancy and periodicallythroughout pregnancy.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Endocrine consultation for thyroid hormone replacement.
SYSTEM = Endocrine/Metabolic
SCORE = 1

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Thyroid gland in radiation field

References
Chemaitilly W, Li Z, Brinkman TM, et al: Primary hypothyroidism in childhood cancer survivors: prevalence, risk factors, and long-term consequences. Cancer 1;128(3):606-614, 2022
Lallier M, St-Vil D, Giroux M, et al: Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome. J Pediatr Surg 33:846-8, 1998
Verloop H, Louwerens M, Schoones JW, et al: Risk of hypothyroidism following hemithyroidectomy: systematic review and meta-analysis of prognostic studies. J Clin Endocrinol Metab 97(7):2243-55, 2012
Zatelli MC, Lamartina L, Meringolo D, et al: Thyroid nodule recurrence following lobo-isthmectomy: incidence, patient’s characteristics, adn risk factors. J Endocrinol Invest 41(12):1469-1475, 2018

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Therapeutic
Exposure

Potential
Late Effects

Radioiodine therapy (I-131 Lacrimal duct atrophy
thyroid ablation)

SYSTEMIC RADIATION

Periodic Evaluation
HISTORY
Excessive tearing

Yearlyw

Health Counseling/
Further Considerations
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Ophthalmology consultation as clinically indicated.
SYSTEM = Ocular
SCORE = 2A

References

Burns JA, Morgenstern KE, Cahill KV, et al: Nasolacrimal obstruction secondary to I-131 therapy. Ophthal Plast Recons 20:126-129, 2004
Morgenstern KE, Vadysirisack DD, Zhang ZX, et al: Expression of sodium iodide symporter in the lacrimal drainage system: Implication for the mechanism underlying nasolacrimal duct obstruction in I-131-treated patients. Ophthal
Plast Recons 21:337-344, 2005
Zettinig G, Hanselmayer G, Fueger BJ, et al: Long-term impairment of the lacrimal glands after radioiodine therapy: a cross-sectional study. Eur J Nucl Med Mol Imaging 29:1428-32, 2002

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w

Therapeutic
Exposure

Potential
Late Effects

Radioiodine therapy (I-131 Hypothyroidism
thyroid ablation)

SYSTEMIC RADIATION (CONT)
Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Fatigue
Weight gain
Cold intolerance
Constipation
Dry skinBrittle hair
Depressed moodYearly, consider more frequent screening during
periods of rapid growth
PHYSICAL
HeightWeightHair
Skin
Thyroid exam
Yearly, consider more frequent screening during
periods of rapid growth
SCREENING
TSHFree T4
Yearly, consider more frequent screening during
periods of rapid growth

HEALTH LINKS

Thyroid Problems
COUNSELINGFor females, thyroid levels prior to attempting pregnancy and periodically throughout
pregnancy.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Endocrine consultation for thyroid hormone replacement.
SYSTEM = Endocrine/Metabolic
SCORE = 2A

References

Safa AM, Schumacher OP, Rodriguez-Antunez A: Long-term follow-up results in children and adolescents treated with radioactive iodine (131I) for hyperthyroidism. N Engl J Med 292:167-71, 1975
Safa AM, Skillern PG: Treatment of hyperthyroidism with a large initial dose of sodium iodide I 131. Arch Intern Med 135:673-5, 1975

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w

Therapeutic
Exposure

Potential
Late Effects

Radioiodine therapy (I-131 Xerostomia
thyroid ablation)
Salivary gland dysfunction
Chronic sialadenitis

SYSTEMIC RADIATION (CONT)
Health Counseling/
Further Considerations

Periodic Evaluation
HISTORY
Xerostomia
YearlyPHYSICAL
Oral Exam
YearlySCREENING
Dental Exam and Cleaning
Every 6 months

HEALTH LINKS

Dental Health
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Supportive care with saliva substitutes, moistening agents, and sialagogues(pilocarpine).
Regular dental care including fluoride applications.
SYSTEM = Oral/Dental
SCORE

References

Albano D, Bertagna F, Panarotto MB, et al: Early and late adverse effects of radioiodine for pediatric differentiated thyroid cancer. Pediatr Blood Cancer 64(11), 2017
Clement SC, Peeters RP, Ronckers CM, et al: Intermediate and long-term adverse effects of radioiodine therapy for differentiated thyroid carcinoma--a systematic review. Cancer Treat Rev 41(10):925-34, 2015
Horvath E, Skoknic V, Majlis S, et al: Radioiodine-Induced salivary gland damage detected by ultrasonography in patients treated for papillary thyroid cancer: radioactive iodine activity and risk. Thyroid (11):1646-1655, 2020
Selvakumar T, Nies M, Klein Hesselink MS, et al: Long-term effects of radioiodine treatment on salivary gland function in adult survivors of pediatric differentiated thyroid carcinoma. J Nucl Med Nov, 2018

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w

Therapeutic
Exposure
Systemic MIBG (intherapeutic doses)

Potential
Late Effects
Hypothyroidism

SYSTEMIC RADIATION (CONT)Periodic Evaluation
HISTORY
Fatigue
Weight gain
Cold intolerance
Constipation
Dry skinBrittle hair
Depressed moodYearly, consider more frequent screening
during periods of rapid growth
PHYSICAL
HeightWeightHair
Skin
Thyroid exam
Yearly, consider more frequent screening
during periods of rapid growth
SCREENING
TSHFree T4
Yearly, consider more frequent screening
during periods of rapid growth

Health Counseling/
Further Considerations
HEALTH LINKS
Thyroid Problems
COUNSELINGFor females, thyroid levels prior to attempting pregnancy and periodicallythroughout pregnancy.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Endocrine consultation for thyroid hormone replacement.
SYSTEM = Endocrine/Metabolic
SCORE = 1

Additional Information

MIBG used for diagnostic purposes (i.e., MIBG scanning) does NOT put patients at risk for hypothyroidism.

References
Bhandari S, Cheung NK, Kushner BH, et al: Hypothyroidism after 131I-monoclonal antibody treatment of neuroblastoma. Pediatr Blood Cancer 55:76-80, 2010
Brans B, Monsieurs M, Laureys G, et al: Thyroidal uptake and radiation dose after repetitive I-131-MIBG treatments: influence of potassium iodide for thyroid blocking. Med Pediatr Oncol 38:41-6, 2002
Picco P, Garaventa A, Claudiani F, et al: Primary hypothyroidism as a consequence of 131-I-metaiodobenzylguanidine treatment for children with neuroblastoma. Cancer 76:1662-4, 1995
van Santen HM, de Kraker J, van Eck BL, et al: High incidence of thyroid dysfunction despite prophylaxis with potassium iodide during (131)I-meta-iodobenzylguanidine treatment in children with neuroblastoma. Cancer 94:2081-9,
2002
van Santen HM, de Kraker J, van Eck BLF, et al: Improved radiation protection of the thyroid gland with thyroxine, methimazole, and potassium iodide during diagnostic and therapeutic use of radiolabeled metaiodobenzylguanidine inchildren with neuroblastoma. Cancer 98:389-396, 2003

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156

Therapeutic
Exposure
Systemic MIBG (intherapeutic doses)

Potential
Late Effects
Thyroid nodules

SYSTEMIC RADIATION (CONT)Periodic Evaluation
PHYSICAL
Thyroid exam
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Thyroid Problems
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Ultrasound for evaluation of palpable nodule(s).
FNA as clinically indicated.
Endocrine and/or surgical consultation for further management.
SYSTEM = SMNSCORE = 2Aw

References

Clement SC, Kremer LCM, Verburg FA, et al: Balancing the benefits and harms of thyroid cancer surveillance in survivors of childhood, adolescent and young adult cancer: Recommendations from the International Late Effects ofChildhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium. Cancer Treat Rev 63:28-39, 2018
Clement SC, van Rijn RR, van Eck-Smit BL, et al: Long-term efficacy of current thyroid prophylaxis and future perspectives on thyroid protection during 131I-metaiodobenzylguanidine treatment in children with neuroblastoma. Eur J
Nucl Med Mol Imaging 42:706-15, 2015

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Therapeutic
Exposure
Systemic MIBG (intherapeutic doses)

Potential
Late Effects
Thyroid cancer

SYSTEMIC RADIATION (CONT)Periodic Evaluation
PHYSICAL
Thyroid exam
YearlyHealth Counseling/
Further Considerations
HEALTH LINKS
Thyroid Problems
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Ultrasound for evaluation of palpable nodule(s).
FNA as clinically indicated.
Endocrine and/or surgical consultation for further management.
SYSTEM = SMNSCORE = 2Aw

References

Clement SC, Kremer LCM, Verburg FA, et al: Balancing the benefits and harms of thyroid cancer surveillance in survivors of childhood, adolescent and young adult cancer: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium. Cancer Treat Rev 63:28-39, 2018
Clement SC, van Eck-Smit BL, van Trotsenburg AS, et al: Long-term follow-up of the thyroid gland after treatment with 131I-Metaiodobenzylguanidine in children with neuroblastoma: importance of continuous surveillance. Pediatr
Blood Cancer 60:1833-8, 2013
Clement SC, van Rijn RR, van Eck-Smit BL, et al: Long-term efficacy of current thyroid prophylaxis and future perspectives on thyroid protection during 131I-metaiodobenzylguanidine treatment in children with neuroblastoma. Eur J
Nucl Med Mol Imaging 42:706-15, 2015

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Therapeutic
Exposure

Potential
Late Effects

Bioimmunotherapy(e.g., G-CSF, IL-2,
erythropoietin)

Insufficient information
currently available
regarding late effects

BIOIMMUNOTHERAPY

Periodic Evaluation

Health Counseling/
Further Considerations
SYSTEM = No Known Late Effects
SCORE = N/Aw

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w

Therapeutic
Exposure
BCR-ABL tyrosine
kinase inhibitors (e.g.,
imatinib, dasatinib,
nilotinib)

Potential
Late Effects
Growth attenuation

TARGETED BIOLOGIC THERAPIES

Periodic Evaluation

Health Counseling/
Further Considerations

HISTORY
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Parental heights at baseline
Endocrine consultation for poor growth for age or stage of puberty as evidenced
Growth rateby decline in growth velocity and change in percentile rankings on growth
Signs of puberty
chart.
YearlyNeed for systematic study of the use of GH in children on chronic TKI therapy.
PHYSICALSYSTEM = Endocrine/Metabolic
Tanner staging every 6 months until
SCORE = 2A
sexually mature
Height and weight measured at every visit,
at least every 6 months
Plot growth velocity
SCREENING
None recommended aside from History andPhysical items listed above

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Cranial/CRT, HCT, chronic steroid treatment

References
Hijiya N, Maschan A, Rizzari C, et al. A phase 2 study of nilotinib in pediatric patients with CML: long-term update on growth retardation and safety. Blood Advances 5(14):2925-2934, 2021
Lodish MB. Kinase inhibitors: adverse effects related to the endocrine system. J Clin Endocrinol Metab 98(4):1333-1342, 2013
Millot F, Guilhot J, Baruchel A, et al. Growth deceleration in children treated with imatinib for chronic myeloid leukaemia. Eur J Cancer 50(18):3206-11, 2014
Narayanan KR, Bansal D, Walia R, et al. Growth failure in children with chronic myeloid leukemia receiving imatinib is due to disruption of GH/IGF-1 axis. Pediatr Blood Cancer 60(7):1148-53, 2013
Samis J, Lee P, Zimmerman D, et al. Recognizing endocrinopathies associated with tyrosine kinase inhibitor therapy in children with chronic myelogenous leukemia. Pediatr Blood Cancer (8):1332-1338, 2016
Shima H, Tokuyama M, Tanizawa A, et al. Distinct impact of imatinib on growth at prepubertal and pubertal ages of children with chronic myeloid leukemia. J Pediatr 159(4):676-81, 2011
Walia R, Aggarwal A, Bhansali A, et al. Acquired neuro-secretory defect in growth hormone secretion due to Imatinib mesylate and the efficacy of growth hormone therapy in children with chronic myeloid leukemia. Pediatr Hematol
Oncol, 37(2):99-108, 2020

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w

Therapeutic
Exposure
BCR-ABL tyrosine
kinase inhibitors (e.g.,
imatinib, dasatinib,
nilotinib)

Potential
Late Effects
Hypothyroidism

TARGETED BIOLOGIC THERAPIES (CONT)Periodic Evaluation
HISTORY
Fatigue
Weight gain
Cold intolerance
Constipation
Dry skinBrittle hair
Depressed moodYearly, consider more frequent screening
during periods of rapid growth
PHYSICAL
HeightWeightHair
Skin
Thyroid exam
Yearly, consider more frequent screening
during periods of rapid growth
SCREENING
TSHFree T4
Yearly, consider more frequent screening
during periods of rapid growth

Health Counseling/
Further Considerations
HEALTH LINKS
Thyroid Problems
COUNSELINGFor females, thyroid levels prior to attempting pregnancy and periodicallythroughout pregnancy.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Other forms of thyroid dysfunction (hyperthyroidism) may occur.
Endocrine consultation for thyroid hormone replacement.
SYSTEM = Endocrine/Metabolic
SCORE = 2B

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Thyroid gland in radiation field

References
Lodish MB. Kinase Inhibitors: Adverse Effects Related to the Endocrine System. J Clin Endocrinol Metab 98(4):1333-1342, 2013
Patel S, Nayernama A, Jones SC, et al: BCR-ABL1 tyrosine kinase inhibitor-associated thyroid dysfunction: a review of cases reported to the FDA Adverse Event Reporting System and published in the literature. Am J Hematol95(12):E332-35, 2020
Samis J, Lee P, Zimmerman D, et al: Recognizing endocrinopathies associated with tyrosine kinase inhibitor therapy in children with chronic myelogenous leukemia. Pediatr Blood Cancer 63(8):1332-1338, 2016

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161

Therapeutic
Exposure
Other targeted biologic
therapies

Potential
Late Effects

TARGETED BIOLOGIC THERAPIES (CONT)Periodic Evaluation

Insufficient information
currently available
regarding late effects

Health Counseling/
Further Considerations
SYSTEM = No Known Late Effects
SCORE = N/Aw

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162

Therapeutic
Exposure

Potential
Late Effects

B-cell directed antibody- Immunologic complications
based therapies
Hypogammaglobulinemia(rituximab)

ANTIBODY-BASED IMMUNE THERAPIES

Periodic Evaluation
HISTORY
Recurrent unusual infections
SCREENING
Serum quantitative immunoglobulins
Baseline at entry into long-term follow-up,
repeat as clinically indicated in patients withabnormal resultsw

Health Counseling/
Further Considerations
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
Immunology or infectious diseases consultation for assistance with managementof infections.
Some patients with hypogammaglobulinemia require lifelong IgG replacement.
SYSTEM = Immune
SCORE = 2A

Additional Information

Consider patient and cancer/treatment factors, pre-morbid/co-morbid health conditions, and health behaviors that may increase risk.
- Cancer/Treatment factors: Prior HCT- Pre-morbid/Co-morbid medical conditions: Underlying primary immunodeficiency

References
Labrosse R, Barmettler S, Derfalvi B, et al. Rituximab-induced hypogammaglobulinemia and infection risk in pediatric patients. J Allergy Clin Immunol 148(2):523-532, 2021
Minard-Colin V, Aupérin A, Pillon M, et al. Rituximab for high-risk, mature B-Cell Non-Hodgkin’s Lymphoma in children. N Engl J Med 382(23):2207-19, 2020

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163

Therapeutic
Exposure
Other antibody-based
immune therapies,
including antibody
drug conjugates(e.g., blinatumomab,
brentuximab
vedotin, inotuzumab,
gemtuzumab
ozogamicin,
dinutuximab,
naxitamab,
pembrolizumab,
ipilimumab,
nivolumab,
atezolizumab)

Potential
Late Effects

ANTIBODY-BASED IMMUNE THERAPIES (CONT)Periodic Evaluation

Insufficient information
currently available
regarding late effects

Health Counseling/
Further Considerations
SYSTEM = No Known Late Effects
SCORE = N/Aw

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Sec #
164

GENERAL HEALTH
Health Counseling/
Further Considerations

Screening
SCREENING
Refer to the Centers for Disease Control andPrevention recommendations for screening,
vaccines, and healthy choices:www.cdc.gov/cancer/dcpc/prevention

COUNSELING
Importance of general health maintenance based on age and gender, including all recommended immunizations and cancer
screening.
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
General health maintenance and screening per standard recommendations for age.
Screening for hypertension, obesity, depression, tobacco use, alcohol misuse.
Certain subpopulations require screening for lipid disorders, sexually transmitted infections, and diabetes mellitus. Others require
counseling regarding the prevention of cardiovascular disease, osteoporosis, and other disorders.
See www.ahrq.gov/clinic/uspstfix.htm for specific recommendations.
Follow preventive screening recommendations for common adult-onset cancers for average risk individuals.

References
Agency for Healthcare Research and Quality: Clinical Guidelines and Recommendations: U.S. Preventive Services Task Force. www.ahrq.gov/clinic/uspstfi.htm
Committee on Infectious Disease, American Academy of Pediatrics: Immunization in special clinical circumstances, in Kimberlin DW, Barnett ED, Lynfield R, et al (eds): Red Book: 2021 Report of the Committee on Infectious Diseases (ed32). Itasca, IL, American Academy of Pediatrics, 2021, pp 67-105

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VACCINATIONS
Health Counseling/
Further Considerations

Screening
SCREENING
Review age-appropriate vaccination history yearly

HEALTH LINKS
Vaccines after Treatment for Cancer Survivors Treated with HCT
Vaccines after Treatment for Cancer Survivors Treated with Chemotherapy and/or Radiation (Non-HCT)
COUNSELING
For survivors who have NOT received HCT:• At entry into long-term follow-up, confirm survivors have been offered catch-up vaccinations for any that were missed during
therapy according to national or regional guidelines
For survivors who have received HCT:
• Revaccinate allogeneic and autologous HCT survivors per international guidelines and after discussing with primary HCT team
POTENTIAL CONSIDERATIONS FOR FURTHER TESTING AND INTERVENTION
All cancer survivors: screen for HPV vaccination - all cancer survivors should receive the 3-dose series regardless of age at first
HPV vaccine dose.
Regarding all other immunizations, reimmunize as indicated below:
HCT patients consider current recommendations (Tomblyn et al, 2009: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3103296)
Non-HCT patients, some survivors treated with conventional therapy may lose vaccine-related immunity. Shared decision-making
regarding revaccinations/boosters for previously received vaccines may include any of the following approaches:• Give boosters for all routine vaccinations• Measure antibody titres (serology check) to assess for seroprotection and boosting as needed• Observe and manage as needed. See https://www.cdc.gov/vaccines/schedules/index.html for current immunization
schedules

Additional Information
Testing of immune function and referral to immunology in survivors (other than allogeneic HCT survivors) should be considered only if there is clinical suspicion of immune dysfunction.
Allogeneic HCT recipients undergo testing of immune reconstitution at some centers, but there are no universal standards.
New therapies (eg immunotherapy such as chimeric antigen receptor T-cell therapy) may impact immunologic function in both the short and long term; challenges exist in recommending standard testing or re-vaccination in survivors
due to paucity of long-term data.

References
Guilcher, GMT, Rivard L, Huang JT, et al: Immune function in childhood cancer survivors: a Children’s Oncology Group review. Lancet Child Adolesc Health 5:284-94, 2021
Mikulska M, Cesaro S, de Lavallade H, et al: Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European Conference on Infections in Leukaemia (ECIL7). Lancet Infect
Dis 19:e188-199, 2019
Rubin LG, Levin MJ, Ljungman P, et al: 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 58:e44-100, 2014
Tomblyn M, Chiller T, Einsele H, et al: Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 15:1143-238, 2009

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Long-Term
Follow-Up
Guidelines
for Survivors of Childhood, Adolescent,and Young Adult Cancers

Appendix I

Materials forClinicalApplication

Version 6.0
October 2023

Copyright 2023 © Children’s Oncology GroupAll rights reserved worldwide

Contents
Appendix I: Materials for Clinical Application of LTFU Guidelines

Page

Reference Materials

2

Abbreviations

3

Chemotherapy Agents

5

Radiation Fields Defined6

Radiation Dose Calculations

9

Guideline Radiation Sections by Field

10

Guideline Radiation Sections by Potential Impact

11

Total Body Irradiation (TBI) Related Potential Late Effects

14

Appeal Letter Following Denial of Insurance Claims for Survivorship Care

15

Instructions

16

Template for Letter from Patient, Parent, or Guardian17

Template for Letter from Long-Term Follow-Up Clinician

18

Summary of Cancer Treatment

19

Instructions

20

Template for Summary of Cancer Treatment (Abbreviated)

22

Template for Summary of Cancer Treatment (Comprehensive)

23

Key for Completing Summary of Cancer Treatment (Comprehensive)

25

Patient-Specific Guideline Identification Tool

31

Instructions

32

Patient-Specific Guideline Identification Tool (Version 6.0)

33

Section Number Comparison - COG LTFU Guidelines Version 6.0 vs 5.0

COG LTFU Guidelines Appendix I – Page 1

Table of Contents

39

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Long-Term
Follow-Up
Guidelines
for Survivors of Childhood, Adolescent,and Young Adult Cancers

Reference
Materials

Version 6.0
October 2023

Copyright 2023 © Children’s Oncology GroupAll rights reserved worldwideAbbreviations
Abbreviation

Definition

Abbreviation

Definition

AAP

American Academy of Pediatrics

DOR

Diminished ovarian reserve

ABR

Auditory brainstem response

DTI

Diffusion-tensor imaging

ACIP

Advisory Committee on Immunization Practices

DWI

Diffusion-weighted imaging

ACS

American Cancer Society

DXA

Dual energy x-ray absorptiometry

AHA

American Heart Association

ECHO

Echocardiogram

ALL

Acute lymphoblastic leukemia

EKG

Electrocardiogram

ALT

Alanine aminotransferase

EIA

Enzyme immunoassay

AMH

Anti-Mullerian hormone

FAP

Familial adenomatous polyposis

AML

Acute myeloid leukemia

FM

Frequency modulated

AST

Aspartate aminotransferase

FNA

Fine needle aspirate

ATG

Anti-thymocyte globulin

FNH

Focal nodular hyperplasia

ATM

Ataxia telangiectasia cancer susceptibility gene(located on chromosome 11)

FSH

Follicle stimulating hormone

G-CSF

Granulocyte colony stimulating factor

AVN

Avascular necrosis

GH

Growth hormone

BMD

Bone mineral density

GI

Gastrointestinal

BMI

Body mass index

gm

Gram

BRCA1

Breast cancer susceptibility gene 1 (located on
chromosome 17)

GVHD

Graft versus host disease

Gy

Gray

Breast cancer susceptibility gene 2 (located on
chromosome 13)

HbA1c

Hemoglobin A1c

HBcAb

Hepatitis B core antibody

BUN

Blood urea nitrogen

HBsAg

Hepatitis B surface antigen

Ca

Calcium

HCT

Hematopoietic cell transplant

CAD

Coronary artery disease

HCV

Hepatitis C virus

CBC

Complete blood count

HDL

High-density lipoproteins

CCG

Children’s Cancer GroupHIB

Haemophilus influenzae type B

CDC

Centers for Disease Control

HIV

Human immunodeficiency virus

cGVHD

Chronic graft versus host disease

HLA

Human leukocyte antigen

Cl

Chloride

HNPCC

Hereditary nonpolyposis colorectal cancer

CNS

Central nervous system

HPF

High power field

CO2

Carbon dioxide

HPV

Human papillomavirus

COG

Children’s Oncology Groupht

HeightCRT

Cranial radiation

Hz

Hertz

CT

Computed tomography

IBD

Inflammatory bowel disease

CVRF

Cardiovascular risk factors

K

PotassiumdB

DecibelI-131

Iodine 131 radioisotope

DES

Diethylstilbestrol

IgA

Immunoglobulin A

DI

Diabetes Insipidus

IL-2Interleukin-2

DLCO

Diffusion capacity of carbon monoxide

IM

Intramuscular

BRCA2

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App I Contents

Abbreviations (cont)Abbreviation

Definition

Abbreviation

Definition

IMRTIntensity-modulated radiation therapy

PUVA

Psoralen plus ultraviolet-A radiation

IO

Intra-Ommaya

QTc

Corrected QT interval

IQIntelligence quotient

RB1

IT

Intrathecal

Retinoblastoma cancer susceptibility gene (locatedon chromosome 13)

IU

International unit

RBC

Red blood cellIV

Intravenous

RUQ

Right upper quadrant

IVIG

Intravenous immunoglobulin

SCUBA

Self-contained underwater breathing apparatus

kg

Kilogram

SDStandard deviation

KUB

Kidneys, ureters, bladder radiograph

SOS

Sinusoidal obstruction syndrome

LH

Luteinizing hormone

SQ

Subcutaneous

LV

Left ventricular

STLI

Subtotal lymphoid irradiationm

Square meter

T4

Thyroxine

MDS

Myelodysplastic syndrome

TBI

Total body irradiation

MIBG

Iodine-131-meta-iodobenzylguanidine

TLI

Total lymphoid irradiation

mg

Milligram

TPN

Total parenteral nutrition

Mg

Magnesium

TSH

Thyroid stimulating hormone

MMF

Mycophenolate mofetil

U

Units

MOPP

Mechlorethamine, Oncovin, Procarbazine,
Prednisone

USPSTF

United States Preventive Services Task Force

V-A

Ventriculoatrial

MR

Magnetic resonance

V-P

Ventriculoperitoneal

MRA

Magnetic resonance angiography

V-V

Ventriculovenus

MRI

Magnetic resonance imaging

VZIG

Varicella zoster immunoglobulin

Na

SodiumWAGR

NF1

Neurofibromin 1 (neurofibromatosis) cancer
susceptibility gene (located on chromosome 17)

Wilms' tumor, aniridia, genitourinary anomalies,
range of developmental delays

wt

Weight2

NHL

Non-Hodgkin lymphoma

NSAIDs

Non-steroidal anti-inflammatory drugs

p53

Cancer susceptibility gene associated with familial
cancers (located on chromosome 17)

PAP

Papanicolaou

PCR

Polymerase chain reaction

PFTs

Pulmonary function tests

PNET

Primitive neuroectodermal tumor

PNS

Peripheral nervous systemPOBy mouth

PO4

Phosphate

PSA

Prostate specific antigen

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App I Contents

Chemotherapy Agents
Generic Name

Additional Name(s)Classification

Asparaginase

EnzymeElsparErwinia asparaginase
Kidrolase®
L-asparaginase
Oncaspar®
PEG-asparaginase®

Generic Name

Additional Name(s)Classification

Ifosfamide

Ifex

Alkylating agent

Lomustine

CeeNU
CCNU

Alkylating agent

Mechlorethamine

Mustargen®
Nitrogen Mustard

Alkylating agent®
®

Bleomycin

Blenoxane®

Anti-tumor antibiotic

Melphalan

Alkeran®

Alkylating agent

BusulfanBusulfex
Busulphan
Myleran®

Alkylating agent

Mercaptopurine

6-Mercaptopurine
6MP
Purinethol®

Antimetabolite

Carboplatin

CBDCA
Paraplatin®

Heavy metal

Methotextrate

Antimetabolite

CarmustineBCNU
BiCNU®

Alkylating agent

Amethopterin
Folex®
Mexate®
Trexall®

Chlorambucil

Leukeran®

Alkylating agent

Mitoxantrone

Novantrone®

Anthracycline
antibiotic

Cisplatin

CDDP
Cisplatinum
Platinol®

Heavy metal

Prednisone

Corticosteroid

Cyclophosphamide

CPM
Cytoxan®
Neosar®
Procytox®

Alkylating agent

Deltasone®
Methylprednisolone
Prednisolone

Procarbazine

Matulane®
Natulan®

Alkylating agent

Temozolomide

Ara-C
Cytosar®
Cytosar-U®
Cytosine arabinoside

Antimetabolite

Temodal®
Temodar®

Non-classicalalkylator

Teniposide

VM26
Vumon®

Epipodophyllotoxin

Dacarbazine

DTIC
DTIC-Dome®

Non-classicalalkylator

Thioguanine

Antimetabolite

Dactinomycin

Actinomycin-D
Cosmegen®

Anti-tumor antibiotic

Lanvis®
Tabloid®
6-Thioguanine
6TG

Thiotepa

Thioplex®

Alkylating agent

Daunorubicin

Cerubidine
Daunomycin
DaunoXome®

Anthracycline
antibiotic

Vinblastine

VBL
Velban®
Velbe®

Plant alkaloid

Dexamethasone

Decadron®

Corticosteroid

Vincristine

Plant alkaloid

Doxorubicin

Adriamycin®
Doxil®
Rubex®

Anthracycline
antibiotic

Oncovin®
VCR
Vincasar®
Vincrex®

Epirubicin

Ellence®
Pharmorubicin PFS®

Anthracycline
antibiotic

Etoposide

VePesid®
VP16

Epipodophyllotoxin

Idarubicin

Idamycin®

Anthracycline
antibiotic

Cytarabine®

®

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Radiation Fields Defined
Traditional Radiation
Field

Definition

Corresponding
Version 5.0 Fields

Total body irradiation (TBI)

Entire body; encompassing all radiation fields

TBI

CranialAny field involving the cranium, head, brain and/or face

Head/brain

Waldeyer’s ring

Nasopharyngeal and oropharyngeal (tonsils and adenoids)

Head/brain

Spine-cervical

Including some or all of the cervical spine (C1–C7)

Spine (cervical)

Spine -thoracic

Including some or all of the thoracic spine (T1–T12)

Spine (thoracic)

Spine-lumbar

Including some or all of the lumbar spine (L1–L5)Spine (lumbar)

Spine-sacral

Including some or all of the sacral spine (S1–S5)Spine (sacral)

Spine-whole

Including the cervical, thoracic, lumbar and sacral spine

Spine (whole)Mini-mantle

Bilateral cervical (neck), supraclavicular and axillary fields (excludes mediastinal and lung) Neck
AxillaMantleBilateral cervical (neck), supraclavicular, mediastinal, hilar, and axillary fields

Neck
AxillaChest

Extended mantle

Mantle and paraaortic fields

Neck
AxillaChest
AbdomenSubtotal lymphoid
irradiation (STLI)

Mantle + paraaortic + splenic

Neck
AxillaChest
AbdomenInverted Y

Paraaortic + pelvic ± splenic

AbdomenPelvisTotal lymphoid irradiation(TLI)

Mantle + inverted Y (paraaortic/pelvic) + splenic

Neck
AxillaChest
AbdomenPelvisChest (thorax)

May include any of the following: Mediastinal, hilar, whole lung, chest wall

Chest

Mediastinal

Mediastinum and bilateral hilar fields

Chest

Abdomen(also commonly referred
to as “upper abdomen”)

Top of diaphragm to iliac crests (bilaterally), including the following fields:• Hepatic• Upper quadrant (right, left)• Renal/Renal bed• Paraaortic• Spleen (partial, entire)• Flank/Hemiabdomen (right, left)

AbdomenParaaortic

Paraaortic lymph nodes (generally from T10 to L4 cephalad-caudad, and the transverse
processes laterally) ± splenic

Abdomen

Renal

Renal bed

Abdomen

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Radiation Fields Defined (cont)Traditional Radiation
Field
Flank/Hemiabdomen

Definition

Corresponding
Version 5.0 Fields

Top of diaphragm to iliac crest (unilateral; medial border along contralateral vertebral
bodies)Abdomen± Pelvis

Note: Most hemiabdominal fields do not extend beyond the iliac crest; however, in somecases, depending on tumor location, the hemiabdominal field may have extended into
the pelvis. If the hemiabdominal field extended below the iliac crest, exposure to pelvic
fields should be considered in assessing risk for late sequelae.
Whole abdomen

Includes all abdominal and pelvic fields

AbdomenPelvisPelvisIliac crest to 3 cm below ischium, including the following fields:• Pelvic• Iliac• Vaginal• Inguinal• Prostate• Femoral• Bladder

PelvisExtremities

Including some or all of the arm(s), leg(s), feet or hand(s)Extremities

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Radiation Fields Defined (cont)Version 6.0 fields shown in black boxes

COG LTFU Guidelines Appendix I – Page 8

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Radiation Dose Calculations
Instructions for Radiation Dose Calculation:
Five sections of the COG Long-Term Follow-Up Guidelines (sections 60, 63, 66, 77, 78) include radiation dose specifications. These specifications
indicate the minimum dose of radiation that is believed (based on available evidence and the recommendations of the expert panel) to placepatients sufficiently at risk of the referenced late effect to recommend screening. For guideline sections that have a minimum specified dose, thefollowing considerations apply in determining the applicability of the section for a patient based on his/her radiation exposure.
Sections with minimum dose specifications are applicable to a patient only if:
1. Patient received radiation to any field(s) relevant to the particular guideline section at ≥ the specified minimum dose†OR
2. Patient received a combination of radiation to any relevant field(s)† plus relevant spinal radiation‡ and/or TBI, the sum of which is ≥ thespecified minimum dose
†Total dose to each field should include boost dose, if given. If patient received radiation to more than one field relevant to a particular guideline section during asingle planned course of radiation treatment (excluding spinal radiation and TBI), the field that received the largest radiation dose should be used in making
the determination as to the applicability of the indicated guideline section(s). Exception: If patient received radiation to the same field at different times (e.g., attime of diagnosis AND at relapse), these doses should be added together when considering the applicability of the indicated guideline section.
‡Use the largest dose of radiation delivered to the spinal field(s) specified in the guideline section.

Examples of Radiation Dose Calculations:
Step 1: If radiation was given to more than one field relevant to the guideline (not including spine, TBI), select the largest dose received
Step 2: If patient received radiation to the same field at different times (e.g., at time of diagnosis AND at relapse), add these doses together
Step 3: If patient received relevant spinal field radiation, add the largest relevant spinal dose
Step 4: If patient received TBI, add TBI dose
Example #1
Guideline Information

Patient Information

Guideline section

Minimum dose
specification
for screening

Relevant
Patient's relevant
radiation fields radiation fields

Step 1

Step 2

Section 66,
osteoradionecrosisof the jaw≥40 GyHead/Brain
Neck
Spine (cervical)
Spine (whole)
TBI

Radiation at diagnosis: 24 Gy• Head/Brain: 24 Gy• Neck: 18 Gy
Radiation at relapse:• Head/Brain: 12 Gy• TBI: 12 Gy

24 Gy

Step 3

Step 4N/A

36 Gy

Conclusion

48 Gy+ 12 Gy+ 12 Gy

36 Gy

48 Gy

Guideline
65 isapplicable

Example #2
Guideline Information

Patient Information

Guideline section

Minimum dose
specification
for screening

Relevant
Patient's relevant
radiation fields radiation fields

Section 77, cardiac
toxicity≥15 GyChest
AbdomenSpine (thoracic)
Spine (whole)
TBI

Radiation at diagnosis:• Chest: 6 Gy
Radiation at relapse:• Spine (whole):
12 Gy

Step 1

Step 2

Step 3

Step 4

Conclusion

6 Gy

N/A

6 Gy

N/A

18 Gy

+ 12 Gy
18 Gy

COG LTFU Guidelines Appendix I – Page 9

Guideline
76 isapplicable

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Guideline Radiation Sections by Field
Applicable guideline sections indicated in bold/dark blue; M=Male; F=Female*46, 47, 48, 49, 50, 51, 52,
53, 54M, 55F, 56, 57, 58M,
59F, 60*, 61, 62, 63*,
65, 66*, 67, 68, 69, 70, 71
64, 65, 66*, 67,
68, 69, 70, 71, 79
44, 45, 46,
47, 48, 53,
58M, 59F,
61, 64, 65,
67, 68, 69,
73F, 74F,
75, 76, 80,
81, 86, 87,
91M, 92F,
93F, 94F, 96

64, 65, 66*,
67, 68, 69, 70,
71, 72, 79

72, 77*, 79, 97
44,
45,
96,
97

72, 73F,
74F, 75, 76,
77*, 79, 97

Whole Spine64, 65, 66*, 67,
68, 69, 70, 71, 72,
77*, 79, 84, 85,
86, 88, 89, 92F,
93F, 94F, 97

84, 85, 86, 97

77*, 78*, 79,
80, 81, 82,
83, 84, 85,
86, 87, 97

84, 85, 86, 88, 89,
92F, 93F, , 94F

84, 85, 86, 88,
89, 92F, 93F,
94F, 95F

73F, 74F,
75, 76,

90M, 91M*Minimum dose
specifications apply.
For instructions andexamples regarding
radiation dose
calculations, refer to”Radiation Dose
Calculations” in COG
Long-Term Follow-Up
Guidelines Appendix I
Reference Materials.

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Guideline Radiation Sections by Potential Impact
Applicable guideline sections indicated in bold/dark blue; M=Male; F=Female

Potential Impact

Fields

Dose

SectionNumbers

Potential Late Effects

All Fields

Any radiation

Any

44*

Subsequent benign or malignant neoplasm

45*

Dermatologic toxicity

46*

Brain tumor (benign or malignant)47*

Neurocognitive deficits

48*

Clinical leukoencephalopathy

49

Cerebrovascular complications

50

Craniofacial abnormalities

51

Chronic sinusitis

52

Overweight; Obesity

53*

Growth hormone deficiency

54M

Precocious puberty (male)

55F

Precocious puberty (female)

56

Hyperprolactinemia

57

Central hypothyroidism

58M*

Gonadotropin deficiency (male)

59F*

Gonadotropin deficiency (female)≥30Gy**

60

Central adrenal insufficiency

Any

61*

Cataracts

62

Ocular toxicity

Brain/Cranium

Neuroendocrine
Axis

Eye

Head/Brain

Any

Head/Brain

Any

Head/Brain

Ear

Head/Brain≥30Gy**

63

Ototoxicity

Oral Cavity

Head/Brain
Neck
Spine (cervical, whole)

Any

64*

Xerostomia; Salivary gland dysfunction

65*

Dental abnormalities; Temporomandibular joint
dysfunction≥40 Gy**66

Osteoradionecrosis of the jaw

Any

67*

Thyroid nodules

68*

Thyroid cancer

69*

Hypothyroidism

70

Hyperthyroidism

71

Carotid artery disease72

Subclavian artery disease

Neck/Thyroid

Head/Brain
Neck
Spine (cervical, whole)

Neck
Chest
Spine (thoracic, whole)

Any* Patients who received TBI are at risk for this late effect. For a full list of TBI related sections, refer to "Total Body Irradiation Related Potential
Late Effects" in COG Long-Term Follow-Up Guidelines Appendix I Reference Materials.
**TBI should be included for dose calculation purposes only

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Guideline Radiation Sections by Potential Impact (cont)
Applicable guideline sections indicated in bold/dark blue; M=Male; F=Female

Potential Impact
BreastSectionNumbers
73F*

Potential Late Effects
Breast cancer

74F*

Breast tissue hypoplasia

75*

Pulmonary toxicity

76*

Lung cancer≥15 Gy**77

Cardiac toxicity

Abdomen≥40 Gy**78

Functional asplenia

Neck
Chest
AbdomenSpine (cervical, thoracic, whole)

Any

79

Esophageal stricture

AbdomenAny

80*

Impaired glucose metabolism/Diabetes mellitus

81*

Dyslipidemia

82

Hepatic toxicity

83

Cholelithiasis

84

Bowel obstruction

85

Chronic enterocolitis; Fistula; Strictures

86*

Colorectal cancer

Fields
Chest
Axilla

Dose
Any

Chest
Axilla

Any

Heart

Chest
AbdomenSpine (thoracic, whole)

SpleenGI/Hepatic
SystemLungs

AbdomenPelvisSpine (lumbar, sacral, whole)
Urinary Tract

Any

AbdomenAny

87

Renal toxicity

PelvisSpine (sacral, whole)

Any

88

Urinary tract toxicity

89

Bladder malignancy

Male
Reproductive
SystemTestesAny

90M

Testicular hormonal dysfunction

91M*

Impaired spermatogenesis

FemaleReproductive
SystemPelvisSpine (sacral, whole)

92F*

Ovarian hormone deficiencies

93F*

Diminished ovarian reserve (DOR)

94F*

Uterine vascular insufficiency

Musculoskeletal
SystemAny

PelvisAny

95F

Vaginal fibrosis/stenosis

Any radiation

Any

96*

Musculoskeletal growth problems

Chest
AbdomenSpine (thoracic, lumbar, whole)

Any

97

Scoliosis/Kyphosis

Any radiation

Any

98

Radiation-induced fracture* Patients who received TBI are at risk for this late effect. For a full list of TBI related sections, refer to "Total Body Irradiation Related Potential
Late Effects" in COG Long-Term Follow-Up Guidelines Appendix I Reference Materials.
**TBI should be included for dose calculation purposes only

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Guideline Radiation Sections by Potential Impact (cont)
Applicable guideline sections indicated in bold/dark blue; M=Male; F=Female

Brain/Cranium/Sensory
4646 4747 4848
4949 5050 5151
5252 5353 54M
54M
55F
55F5656 5757
58M
58M
59F
59F60*
60*
6161 6262 63*
63*

Oral Cavity
6464656566*
66*

Neck/Thyroid

676768686969
707071717272

4444
4545
4646
4747
4848
5353
58M
58M
59F
59F
6161
6464
6565
6767
6868
6969
73F
73F
74F
74F
7575
7676
8080
8181
8686
8787
91M
91M
92F
92F
93F
93F
94F
94F
9696

BreastEsophagus
7979

73F
73F74F
74F

Lungs

Heart

75757676

77*
77*

Liver/Pancreas
8080818182828383

4444
4545

Kidneys Spleen
8787

78*
78*

Bowel
8484
8585
Female Reproductive 8686
92F
92F93F
93F94F
94F95F
95F

Bladder/Urinary Tract
88888989

9696
9797
9898

Male
Reproductive*Minimum dose
specifications apply.
For instructions andexamples regarding
radiation dose
calculations, refer to”Radiation Dose
Calculations” in COG
Long-Term Follow-Up
Guidelines Appendix I
Reference Materials.

90M
90M91M
91M

Note: Oral cavity,
neck/thyroid, heart,esophagus, and bowel
are affected bymultiple anatomic
regions.

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Total Body Irradiation (TBI) Related Potential Late Effects
The complete list of potential late effects and associated Guideline section numbers are included here for clinician convenience when evaluating
patients who received TBI. For details regarding each potential late effect and indicated screening, please refer to the relevant section within the
Guidelines.
SectionNumberSex

Potential Late Effect

44

Both

Subsequent benign or malignant neoplasm occurring in or near radiation field

45

Both

Dermatologic toxicity

46

Both

Brain tumor (benign or malignant)

47

Both

Neurocognitive deficits

48

Both

Clinical leukoencephalopathy

53

Both

Growth hormone deficiency

58

Male

Gonadotropin deficiency

59

FemaleGonadotropin deficiency

61

Both

Cataracts

64

Both

Xerostomia; Salivary gland dysfunction

65

Both

Dental abnormalities; Temporomandibular joint dysfunction

67

Both

Thyroid nodules

68

Both

Thyroid cancer

69

Both

Hypothyroidism

73

FemaleBreast cancer

74

FemaleBreast tissue hypoplasia

75

Both

Pulmonary toxicity

76

Both

Lung cancer

80

Both

Impaired glucose metabolism/Diabetes mellitus

81

Both

Dyslipidemia

86

Both

Colorectal cancer

87

Both

Renal toxicity

91

Male

Impaired spermatogenesis

92

FemaleOvarian hormone deficiencies

93

FemaleDiminished ovarian reserve

94

FemaleUterine vascular insufficiency

96

Both

Musculoskeletal growth problems

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Long-Term
Follow-Up
Guidelines
for Survivors of Childhood, Adolescent,and Young Adult Cancers

Appeal Letter
Following Denialof Insurance
ClaimsVersion 6.0
October 2023

Copyright 2023 © Children’s Oncology GroupAll rights reserved worldwide

Instructions:Appeal Letter Following Denial of Insurance Claims for Survivorship Care
Not all insurance companies recognize the need for ongoing long-term follow-up care for survivors of childhood, adolescent, and young adultcancers. As with any medical care, it is prudent for the survivor to determine coverage for anticipated screening tests that may be recommended
as part of their long-term follow-up care, and to work with the survivorship provider to obtain any pre-authorizations that may be necessary.
Nevertheless, we recognize that some essential services may be denied from time to time. The letters on the following pages are designed foruse as templates to appeal denial letters from insurance companies, should the need arise. One letter is designed to be completed and submitted
to the insurance company by the patient (or his/her parent). The other letter is designed to be completed and submitted to the insurance company
by the patient’s survivorship care provider. Although neither letter can guarantee insurance coverage, we are hopeful that these letters may be
helpful in securing the indicated coverage for tests recommended as part of routine long-term follow-up care after the completion of cancerdirected therapy.
These templates were developed by Kristy Sharif and Alison Olig, COG Patient Advocacy Committee, 2018.

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Appeal Letter Following Denial of Insurance Claims for Survivorship Care:
Template for Letter from Patient, Parent or Guardian(Date)(Name)(Insurance Company Name)(Address)(City, State ZIP)Re:

(Patient's Name)(Type of Coverage)(Group number/Policy number)

Dear (name of contact person at insurance company),
Please accept this letter as (patient's name)’s appeal to (insurance company name)’s decision to deny coverage for (name of test). It is myunderstanding based on your letter of denial dated (date) that (name of test) has been denied because:(Quote the specific reason for the denial stated in denial letter)
It is possible that you did not have all the necessary information at the time of your initial review. (Patient's name) was diagnosed with (disease)on (date). Currently (name of long-term follow-up clinician) from (name of treating facility), a specialist in long-term follow-up after therapy
for cancer during childhood, adolescence, and young adulthood, has indicated that (patient's name) requires (name of test) in order to monitor
for long-term complications related to (patient’s name) cancer treatment. Please see the enclosed letter from (name of long-term follow-up
clinician) that discusses (patient's name)’s medical history and provides justification for this testing in more detail. Also included are medical
records and support documentation explaining the evidence-based recommendations for this required monitoring.
Based on this information, (patient's name) is asking that you reconsider your previous decision and allow coverage for the procedure Dr. (name)outlines in the enclosed letter. (Name of test) is recommended to be completed by (date). Should you require additional information, please do
not hesitate to contact me at (phone number). I look forward to hearing from you in the near future.
Sincerely,(Patient, parent or guardian name)

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Appeal Letter Following Denial of Insurance Claims for Survivorship Care:
Template for Letter from Long-Term Follow-Up Clinician(Date)(Name)(Insurance Company Name)(Address)(City, State ZIP)Re:

(Patient's Name)(Type of Coverage)(Group number/Policy number)

Dear (name of contact person at insurance company),
This letter is written in support of (patient's name)’s appeal to (insurance company name)’s decision to deny coverage for (name of test).
I am the clinician who is currently providing long-term follow-up care for this patient. Based on your letter of denial dated (date), it is myunderstanding that (name of test) has been denied because:(Quote the specific reason for the denial stated in denial letter)(Patient's name) is a (age) year old (male/female) who was diagnosed with (disease) on (date) and began treatment on (date). Treatment wascompleted on (date).
The treatments that (patient's name) received for (disease) were lifesaving, however, this treatment has the potential to cause significant
long-term complications (late effects) that can negatively impact (patient’s name)’s health. Ongoing monitoring is required so that any long-term
complications of cancer therapy can be identified and treated in a timely fashion in order to optimize (patient’s name)’s health and prevent a
decline in health status.
Because (patient's name) received (name of relevant therapeutic exposures/doses) as part of (his/her) cancer therapy, (he/she) is at risk for(relevant late effect(s)). The Children’s Oncology Group (COG) Long-Term Follow-Up Guidelines, which set the standard of care for the ongoing
follow-up of survivors of childhood, adolescent, and young adult cancers, provide specific follow-up recommendations related to (patient’sname)’s treatment, including (name of test denied). These evidence-based guidelines are based on the known long-term risks associatedwith cancer therapy delivered during childhood, adolescence, and young adulthood. The recommendations within the COG Long-Term Follow-Up
Guidelines represent the consensus of experts in the late effects of pediatric cancer treatment.
I have attached documentation that supports the recommended testing in more detail [attach relevant sections from COG LTFU Guidelines andany additional supportive materials such as journal articles], along with (patient’s name)’s relevant medical records. Additional information
is available from the Children’s Oncology Group at www.survivorshipguidelines.org.
Based on this information, as the clinician providing (patient's name)’s long-term follow-up care, I am asking that you reconsider your previous
decision and allow coverage for (name of test). (Name of test) is recommended to be completed by (date). Should you require additional
information, please do not hesitate to contact me at (phone number). I look forward to hearing from you
Sincerely,(Name of long-term follow-up clinician)

COG LTFU Guidelines Appendix I – Page 18

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Long-Term
Follow-Up
Guidelines
for Survivors of Childhood, Adolescent,and Young Adult Cancers

Summaryof Cancer
Treatment

Version 6.0
October 2023

Copyright 2023 © Children’s Oncology GroupAll rights reserved worldwide

Instructions:
Summary of Cancer Treatment
Importance of a Comprehensive Cancer Treatment Summary
The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers are based ontherapeutic exposures received during cancer treatment. Availability of a comprehensive treatment summary, including all therapeutic agentsreceived by the survivor, is presumed. Patients who do not have a comprehensive treatment summary should be instructed to obtain one from theinstitution(s) where they received their treatment.
The following table outlines:
1. The minimum information necessary to generate patient-specific guidelines (i.e., an abbreviated treatment summary).
2. The ideal information included in the comprehensive treatment summary. We strongly advise that a comprehensive treatment summary
be prepared for each childhood cancer survivor when feasible.

At Minimum

Additional Information- Strongly Advised if Feasible

Demographics

Demographics• Name• Sex• Date of birth• Race/Ethnicity• Social security number, if available• COG registration number, if available• Contact information

Cancer Diagnosis

Cancer Diagnosis• Diagnosis• Date of diagnosis• Date cancer therapy was completed• Diagnosis, including date, site/stage, laterality, and relapse(s) if any• Pertinent hereditary conditions, past medical history and subsequent
neoplasms• Treating institution and teamCancer Treatment: Protocols

Cancer Treatment: Protocols

N/A• Treatment protocol information, if applicable

Cancer Treatment: Chemotherapy

Cancer Treatment: Chemotherapy• Names of all chemotherapy agents received– For a list of chemotherapy agents addressed by these guidelines(Sections 11-43), see the “Chemotherapy” portion of the Patient-Specific
Guideline Identification Tool in Appendix I.
– For generic and brand names of chemotherapy agents, see
Chemotherapy Agents in Appendix I.
• Cumulative dose of all anthracycline chemotherapy received (i.e.,
doxorubicin, daunorubicin, idarubicin, mitoxantrone and epirubicin)– See Section 34 of Guidelines for anthracycline isotoxic dose-equivalent
conversion.
– For doses in mg/kg, multiply by 30 to obtain equivalent dosing in mg/m2(example: 2 mg/kg = 60 mg/m2).
• For carboplatin, whether any dose was myeloablative (i.e., given as
conditioning for HCT)• For cytarabine and methotrexate:– Route of administration (i.e., IV, IM, SQ, PO, IT, IO)– If IV, designation of “high dose” (any single dose ≥ 1000 mg/m2) versus“standard dose” (all single doses < 1000 mg/m2)• Cumulative doses for all other agents should be provided if available,
particularly for alkylators and bleomycin.
– For doses in mg/kg, multiply by 30 to obtain equivalent dosing in mg/m2(example: 2 mg/kg = 60 mg/m2).
• Route of administration for all other agents

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Instructions:
Summary of Cancer Treatment (cont)At Minimum

Additional Information- Strongly Advised if Feasible

Cancer Treatment: Radiation

Cancer Treatment: Radiation• Laterality (if applicable), start/stop dates, radiation type, number of• Names of all radiation field(s) treatedfractions, dose per fraction, boost dose/location (if applicable)– For list of radiation fields addressed by these guidelines (Sections 44-98),• Total dose (in Gy) for all other fields
see “Radiation” portion of the Patient-Specific Guideline Identification
Tool in Appendix I– Should include boost dose if given– For definition of radiation fields, see "Radiation Fields Defined" in– To convert cGy or rads to Gy, divide dose by 100 (example: 2400 cGy =Appendix I
2400 rads = 24 Gy)• For head/brain, neck, chest, abdomen, spine (whole, cervical, thoracic)• Treating institution and radiation oncologist
radiation and TBI, total dose (in Gy):
– Total radiation dose to each field (should include boost dose, if given)– To convert cGy or rads to Gy, divide dose by 100 (example: 2400 cGy =2400 rads = 24 Gy)
Cancer Treatment: Hematopoietic Cell Transplant(s)Cancer Treatment: Hematopoietic Cell Transplant(s)• Whether or not the survivor underwent a hematopoietic cell transplant(HCT), and if so:– Transplant type (autologous vs allogeneic)– Chronic graft-versus-host disease (cGVHD) status (no history of chronic
GVHD, history of chronic GVHD, currently active chronic GVHD)• Type(s), source(s), date(s), conditioning regimen(s), GVHD prophylaxis and/or treatment• Treating institution and transplant physician

Cancer Treatment: Surgery

Cancer Treatment: Surgery• Names of all surgical procedures.
– For list of surgical procedures addressed by these guidelines (Sections
115–151), see “Surgery” portion of the Patient-Specific Guideline
Identification Tool in Appendix I• Dates, site (if applicable), laterality (if applicable)• Treating institution and surgeon

Cancer Treatment: Other Therapeutic Modalities

Cancer Treatment: Other Therapeutic Modalities• Whether or not the survivor received radioiodine therapy (I-131 thyroid
ablation), systemic MIBG (in therapeutic doses), or a novel therapy• Names, routes and cumulative doses of all other therapeutic modalities
received

Additional Clinical Information

Additional Clinical Information

N/A• Significant complications/late effects with dates of onset/resolution• Adverse drug reactions/allergies• Additional information/comments

Templates for Summary of Cancer Treatment
Two templates for summarizing cancer treatment are included in Appendix I (also available in electronic format atwww.survivorshipguidelines.org). These templates were originally developed by the COG Nursing Clinical Practice Subcommittee under theleadership of Lisa Bashore, MS, RN, CPNP, CPON® and Lori Boucher, RN, CRA. The templates were subsequently pilot tested and revised, thenfurther refined based on feedback from the Late Effects Committee and a working group from the National Cancer Institute.
The abbreviated form contains all data elements currently necessary for generation of patient-specific recommendations from the COG LTFU
Guidelines, and meets the minimum data requirements for initial use of the “Passport for Care” web-based guideline interface. However, theCOG Long-Term Follow-Up Guidelines Core Committee recognizes that as new evidence becomes available and these guidelines are updated,additional details regarding the childhood cancer survivor’s therapeutic exposures may be required in order to generate comprehensive
recommendations. Therefore, we strongly advise that a comprehensive treatment summary be prepared for each childhood cancer survivor
when feasible, including a record of all therapeutic exposures with applicable dates, details of administration, and cumulative doses of all agents,
including those not currently addressed by these guidelines.
In addition to the treatment summary templates, a “key” for completing the comprehensive version of the treatment summary is also included inAppendix I.

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App I Contents

Summary of Cancer Treatment (Abbreviated)
Demographics
Name

Sex  M  F

Date of birth

Cancer Diagnosis
Diagnosis

Date of diagnosis

Chemotherapy

 Yes

 No

Date therapy completed

If yes, provide information below

Drug name

Additional information††
Anthracyclines: Include cumulative dose in mg/m2 (see section 34 of Guidelines for isotoxic dose conversion);
Carboplatin: Indicate if dose was myeloablative
Methotrexate and Cytarabine: Indicate route of administration (i.e., IV, IM, SQ, PO, IT, IO);IV Methotrexate and Cytarabine: Indicate if “high dose” (any single dose ≥ 1000 mg/m2) or “standard dose” (all single doses < 1000 mg/m2)
Note: Cumulative doses, if known, should be recorded for all agents, particularly for alkylators and bleomycin.

Radiation

 Yes

 No

If yes, provide information below

Site/Field

Total dose* (including boost) (Gy)***For head/brain, neck, chest, abdomen, spine (whole, cervical, thoracic) radiation and TBI, include total doses (including boost dose, if given)**To convert cGy or rads to Gy, divide dose by 100 (example: 2400 cGy = 2400 rads = 24 Gy)

Hematopoietic Cell Transplant

 Yes

 No

If yes, provide information below

Transplant type

Autologous  Yes

Chronic graft-versus-host disease (cGVHD)

Ever diagnosed?  Yes

Surgery

 Yes

 No

Allogeneic  Yes

 No

 No

Currently active?  Yes

 No

If yes, provide information below

Procedure

Other Therapeutic Modalities

 No

Site (if applicable)

 Yes

 No

Laterality (if applicable)

If yes, provide information below

Did the patient receive radioiodine therapy (I-131 thyroid ablation)?
Did the patient receive systemic MIBG (in therapeutic doses)?

 Yes

 Yes

 No

 No

Did the patient receive any other novel therapy from Sections 158-163 (in therapeutic doses)?
Summary prepared by:

 Yes

 No
Date prepared:

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App I Contents

Summary of Cancer Treatment (Comprehensive)
Superscript numbers correspond with lists in "Key for Completing Summary of Cancer Treatment Form"
Demographics
Name
Date of birth

Sex  M  F

Race/Ethnicity1

SS#

COG Reg #Address

Phone

Alternate contact

Relationship

Phone

Cancer Diagnosis
Diagnosis2
Date of diagnosis

Age at diagnosis

Date therapy completed

Sites involved/Stage/Diagnostic details
Hereditary/Congenital history

Laterality  Right  Left  NA

3

Pertinent past medical history
Institution

MD/APN

Relapse(s)

 Yes

 No

Medical record #If yes, provide information below

Date of diagnosis

Age at diagnosis

Date therapy completed

Sites involved/Stage/Diagnostic details
Subsequent malignant neoplasm(s)Laterality  Right  Left  NA
 Yes

 No

If yes, provide information below

Type4
Date of diagnosis

Age at diagnosis

Date therapy completed

Sites involved/Stage/Diagnostic details

Laterality  Right  Left  NA

Cancer Treatment Summary
Protocol(s) YesAcronym/Number

Chemotherapy

 No

If yes, provide information below

Title/Description

 Yes

 No

Initiated

CompletedOn-study

If yes, provide information below

Drug name5

Route6

Additional information†,7

Anthracyclines: Include cumulative dose in mg/m2 and age at first dose (see section 34 of Guidelines for isotoxic dose conversion);
Carboplatin: Indicate if dose was myeloablative
IV Methotrexate and Cytarabine: Indicate if “high dose” (any single dose ≥ 1000 mg/m2) or “standard dose” (all single doses < 1000 mg/m2);
Note: Cumulative doses, if known, should be recorded for all agents, particularly for alkylators and bleomycin.

†

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App I Contents

Summary of Cancer Treatment (Comprehensive) (cont)
Cancer Treatment Summary (cont)
Radiation Yes

Site/Field8

Laterality

 No

If yes, provide information below
Start/Stop
dates

Type9

Fractions

Institution

Dose perfraction(Gy)*

Initialdose (Gy)*

Boost site10

Boost
dose (Gy)*

Total dose(including
boost) (Gy)*Radiation oncologist*Note: To convert cGy or rads to Gy, divide dose by 100 (example: 2400 cGy = 2400 rads = 24 Gy)
Hematopoietic Cell Transplant

 Yes

 No

If yes, provide information below

Tandem?

Type11 Yes

Source12

Date of infusion

 No

Institution

Transplant physician

Graft-Versus-Host Disease (GVHD) Prophylaxis/Treatment (for transplant patients only)

Was the patient ever diagnosed with chronic GVHD?
 Yes

 No

Procedure15

 Yes

 No

 No

If yes, provide information below

Last dose

Does the patient currently have active chronic GVHD?

 Yes

 No

If yes, provide information below
Date

Other Therapeutic Modalities
Therapy YesFirst dose

Type

14

Surgery

Conditioning regimen13

Site (if applicable)

 Yes

 No

Laterality (if applicable)

Institution/Surgeon

If yes, provide information below
Route6

16

Cumulative dose7 (if known)

Additional Clinical Information
Complications/Late Effects

 Yes

Problem17

 No

If yes, provide information below

Date onset

Adverse Drug Reactions/Allergies

 Yes

Drug

Reaction

Date resolved

 No

Status Active Resolved

 Active Resolved

 Active Resolved

 Active Resolved

If yes, provide information below
Date

Status Active

Additional Information/Comments

 Yes

 No

 Resolved

If yes, provide information below

Summary prepared by:Date prepared:

Summary updated by:Date updated:

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App I ContentsKey for Completing Summary of Cancer Treatment (Comprehensive)#1: Race/Ethnicity#2: Cancer Diagnosis (cont)#2: Cancer Diagnosis (cont)

Asian

Germ cell tumor (extracranial) (cont)

Sarcoma (cont)Black/African American

Germ cell tumor, other, specify:

Caucasian (non-Hispanic/non-Latino)Langerhans cell histiocytosis

Soft tissue sarcoma (nonrhabdomyosarcomatous)(cont)

Hispanic or Latino

Leukemia

Native American/Alaskan Native

Acute lymphoblastic leukemia

Native Hawaiian/Pacific Islander

Acute myeloid leukemia

Multi-racial/multi-ethnic

Chronic myeloid leukemia

Race/ethnicity, other, specify:

Myelodysplastic syndrome#2: Cancer Diagnosis

Myeloproliferative disorder

Central Nervous System Tumor

Leukemia, other, specify:

Astrocytoma

Liver tumor

Cerebellar astrocytoma

Hepatoblastoma

Supratentorial astrocytoma

Hepatocellular carcinoma

Synovial sarcoma
Undifferentiated sarcoma
Sarcoma, other, specify:
Skin cancer
Basal cell carcinoma
Malignant melanoma
Squamous cell carcinoma
Skin cancer, other, specify:
Malignancy, other, specify:
Diagnosis, other, specify:#3: Hereditary/Congenital History

Brainstem glioma

Liver tumor, other, specify:

Choroid plexus neoplasm

Lymphoma

Craniopharyngioma

Hodgkin lymphoma

Ependymoma

Non-Hodgkin lymphoma

Germ cell tumor, intracranial

Lymphoblastic lymphoma

Neurofibromatosis
Specify:  Type I  Type II

Optic glioma

Burkitt’s lymphoma

Down syndrome

Pineal tumor

Large cell lymphoma

Syndrome, other, specify:

PNET
Cerebellar (medulloblastoma)
Supratentorial PNET

Congenital heart disease
Congenital disease, other, specify:
Hemihypertrophy

Anaplastic large cell lymphoma

Hereditary condition, other, specify:

Diffuse large B-cell lymphoma

None

Lymphoma, other, specify:

Unknown

Spinal cord tumor, intramedullary

Nasopharyngeal carcinoma#4: Subsequent Malignancy Diagnosis

CNS tumor, other, specify:

Neuroblastoma

Bladder cancer

Endocrine tumor

Ganglioneuroblastoma

Breast cancer

Adrenal tumor (non-neuroblastoma)

Renal tumor

Central nervous system tumor

Thyroid tumor

Wilms tumor

Malignant, specify type and location:

Parathyroid tumor

Clear cell sarcoma

Meningioma, specify location:

Gastroenteropancreatic tumor

Renal cell carcinoma

CNS tumor, other, specify type:Multiple endocrine neoplasia syndrome

Renal tumor, other, specify:

Cervical cancer

Endocrine tumor, other, specify:

Retinoblastoma

Gastrointestinal cancer

Germ cell tumor (extracranial)

Sarcoma

Esophageal cancer

Seminoma

Ewing’s sarcoma/peripheral PNET

Stomach cancer

Germinoma

Osteogenic sarcoma

Colorectal cancer

Dysgerminoma

Rhabdomyosarcoma

Hepatocellular carcinoma

Soft tissue sarcoma (nonrhabdomyosarcomatous)

Pancreatic cancer

Non-seminomas
Yolk sac tumor

Alveolar soft part sarcoma

GI cancer, other, specify:

Embryonal carcinoma

Fibrosarcoma

Leukemia

Choriocarcinoma

Leiomyosarcoma

Acute lymphoblastic leukemia

Liposarcoma

Acute myeloid leukemia

MatureMalignant fibrous histiocytoma

Chronic myeloid leukemia

Immature

Malignant peripheral nerve sheath tumor

Myelodysplastic syndrome

With malignant transformation

Neurofibrosarcoma

Myeloproliferative disorder

Teratoma

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App I ContentsKey for Completing Summary of Cancer Treatment (Comprehensive)(cont)#4 Subsequent Malignancy Diagnosis (cont)#5: Chemotherapy (cont)#6: Route

Leukemia (cont)

Cyclophosphamide

PO

Leukemia, other, specify:

Cytarabine
If IV: any single dose ≥ 1000 mg/m2?  Yes  No

IMLung cancer
Lymphoma

Dacarbazine (DTIC)

SQ

Hodgkin lymphoma

Dactinomycin

IT

Non-Hodgkin lymphoma

Daunorubicin

IO

Lymphoblastic lymphoma

Dexamethasone

Route, other, specify:

Burkitt lymphoma

Docetaxel

Unknown

Large cell lymphoma

DoxorubicinIV#7: Cumulative Dose
(Note: this is a required field for anthracyclines andoptional but suggested for all others )Post-transplant lymphoproliferative disorder (PTLD)

Epirubicin

Lymphoma, other, specify:

Etoposide (VP-16)

Peripheral nerve sheath tumor/
Schwannoma/Acoustic neuroma

Fludarabine

Renal cancer

Gemcitabine

Renal cell carcinoma

Hydrocortisone

Clear cell sarcoma

Hydroxyurea

mg/kg(Note: computer will multiply mg by 30 and display
as mg/m2 )Renal cancer, other, specify:

Idarubicin

Not available

Sarcoma

Ifosfamide

Not applicable

Ewing’s sarcoma/peripheral PNET

Imatinib Mesylate

Cumulative dose, other, specify:

Osteogenic sarcoma

Irinotecan

Unknown

Rhabdomyosarcoma

Lomustine (CCNU)#8: Radiation Site/Field

Soft tissue sarcoma (nonrhabdomyosarcomatous)

Mechlorethamine

Head/brain

Undifferentiated sarcoma

Melphalan

CranialSarcoma, other, specify:

Mercaptopurine

Skin cancer
Basal cell carcinoma

Methotrexate
If IV: Any single dose ≥ 1000 mg/m2?  Yes  No

Orbital/EyeSpecify:  Right  Left  Bilateral

Malignant melanoma

Mitoxantrone

Ear/Infratemporal
Specify:  Right  Left  BilateralSquamous cell carcinoma

Oxaliplatin

Nasopharyngeal

Thyroid cancer

Paclitaxel

Oropharyngeal

Malignancy, other, specify:

Prednisone

Waldeyer’s ring

None

Procarbazine

Head/brain radiation, other, specify:

Unknown

Temozolomide

Neck#5: Chemotherapy

Teniposide (VM-26)

Asparaginase

Thioguanine (6-TG)

Cervical (neck)Specify:  Right  Left  Bilateral

Bleomycin

Thiotepa

SupraclavicularSpecify:  Right  Left  Bilateral

BusulfanTopotecan

Spine

Carboplatin
Myeloablative dose?  Yes  No

Trimetrexate

Spine – cervical

Vinorelbine

Spine – thoracic

Carmustine (BCNU)

Vinblastine

Spine – lumbar

Chlorambucil

Vincristine

Spine – sacral

Cisplatin

Chemotherapy, other, specify:

Spine – whole

Cladribine

None

Clofarabine

Unknown

AxillaSpecify:  Right  Left  Bilateral

mg/m2

Fluorouracil

units/m2

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App I ContentsKey for Completing Summary of Cancer Treatment (Comprehensive)(cont)#8: Radiation Site/Field (cont)#8: Radiation Site/Field (cont)

Chest

Radiation site/field, other, specify:#13: Hematopoietic Cell Transplant (HCT) –Conditioning Regimen (cont)Chest (thorax)

None

Melphalan

Whole lungSpecify:  Right  Left  Bilateral

Unknown

Thiotepa

Add comment:

Total body irradiation (TBI)Mediastinal#9: Radiation TypeHCT conditioning regimen, other, specify:

Chest, other, specify:

Brachytherapy

Unknown

Abdomen

Conformal

Hepatic

External beam (conventional)#14: Graft versus host disease (GVHD)
Prophylaxis/Treatment

Renal
Specify:  Right  Left  Bilateral

Intensity-modulated radiation therapy (IMRT)

Upper quadrant
Specify:  Right  Left  Bilateral

Stereotactic

SpleenSpecify:  Partial  Entire

Proton beam

Cyclosporine
Methotrexate
Myophenolate mofetil (MMF)

Radiation type, other, specify:

Prednisone

None

Psoralen plus ultraviolet-A radiation (PUVA)

Paraaortic

Unknown

Flank/hemiabdomenSpecify:  Right  Left
Specify: Extended below iliac crest:  Yes  No

#10: Radiation Boost

Pelvis

None

PelvicUnknown

Vaginal

Add comment:

Prostate#11: Hematopoietic Cell Transplant (HCT) – Type

Bladder

Autologous

Iliac

Matched related

Inguinal

Mismatched relatedFemoralHaploidentical related

TesticularSpecify:  Right  Left  Bilateral

Syngeneic

Extremity

HCT type, other, specify:

Upper
Specify:  Right  Left  BilateralSpecify:  Proximal  Distal  Entire

Unknown

Lower
Specify:  Right  Left  BilateralSpecify:  Proximal  Distal  Entire

Peripheral blood stem cells

Total Body Irradiation (TBI)

HCT source, other, specify:

Sirolimus
Tacrolimus

Tumor bed, specify location:
Radiation boost location, other, specify:

GVHD prophylaxis/treatment, other, specify:
None
Unknown#15: Surgery
Amputation, specify site:
Specify:  Right  Left  BilateralCentral venous catheter
Cystectomy
Enucleation
Specify:  Right  Left  Bilateral
Hysterectomy

Matched unrelated

Laparotomy
Limb sparing procedure, specify site:
Specify:  Right  Left  Bilateral#12: Hematopoietic Cell Transplant – Source
Bone marrow

Nephrectomy
Specify:  Right  Left  Bilateral
Neurosurgery – brain
Potential to affect hypothalamic-pituitary axis?
 Yes  No

Cord blood

Neurosurgery – spinal cord

Combination Fields:

Unknown

Mantle#13: Hematopoietic Cell Transplant –Conditioning Regimen

Mini-mantle

Anti-thymocyte globulin (ATG)

Oophoropexy
Oophorectomy
Specify:  Right  Left  Bilateral

Extended mantle

Anti-thymocyte globulin (ATG)

Inverted Y

Busulfan

Whole abdomen

Carmustine (BCNU)

Orchiectomy
Specify:  Partial  Unilateral  BilateralIf partial or unilateral, specify:  Right  Left

Total lymphoid irradiation (TLI)

Cyclophosphamide

Pelvic surgery

Subtotal lymphoid irradiation (STLI)

Etoposide

Thoracic surgery*

Fludarabine

Splenectomy

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App I ContentsKey for Completing Summary of Cancer Treatment (Comprehensive)(cont)#15: Surgery (cont)Thyroidectomy#17: Complications/Late Effects (by system)(cont)#17: Complications/Late Effects (by system)(cont)

Surgery, other, specify:

Cardiovascular (cont)Central Nervous System (CNS) (cont)

None

Atherosclerotic heart diseaseOcclusive cerebral vasculopathy

Unknown

Cardiomyopathy

Paralysis

Add comment:

Carotid artery disease

Seizures*Thoracic surgery includes: thoracotomy, chestwall surgery, rib resection, pulmonary lobectomy,
pulmonary metastasectomy, and pulmonary
wedge resection

Congestive heart failure

Shunt malfunction

Infection of retained cuff or line tract

Spasticity

Myocardial infarction

StrokePericardial fibrosis

CNS complication, other, specify:

Pericarditis

DentalPost-thrombotic syndrome

Dental caries

Subclavian artery disease

Ectopic molar eruption

Subclinical left ventricular dysfunction

Enamel dysplasia

Systemic radiation, other, specify:

Thrombosis

Malocclusion

Bioimmunotherapy

Valvular disease

Microdontia

Hematopoietic growth factors:

Vascular insufficiency

Osteoradionecrosis of the jaw

Granulocyte colony stimulating factor (G-CSF)

Cardiovascular complication, other, specify:

Periodontal disease

Erythropoietin

Central Nervous System (CNS)

Root thinning/shortening

Thrombopoietin

AtaxiaSalivary gland dysfunction

Cavernomas

Temporomandibular joint dysfunction

Alpha interferon

Chronic pain, central neuropathic

Tooth/root agenesis

Gamma interferon

Clinical leukoencephalopathy

Xerostomia

Dysarthria

Dental complication, other, specify:

IL-2

Dysphagia

Dermatologic

IL-11

Hemiparesis

Altered skin pigmentation

Other, specify:

Hydrocephalus

Nail dystrophy

Monoclonal antibody, specify type:

Movement disorders

Permanent alopecia

Retinoic acid, specify type:

Moyamoya

Sclerodermatous changes

Bioimmunotherapy, other, specify:

Neurocognitive deficits

Skin fibrosis

Other therapeutic modality, specify:

Academic fluency

Telangiectasias

None

Behavioral change

Vitiligo

Unknown

Diminished IQ

Dermatologic complication, other, specify:#17: Complications/Late Effects (by system)

Executive function (planning and organization)

Endocrine/Metabolic

Auditory

Fine motor dexterity

Central adrenal insufficiency

Conductive hearing loss

Language

Diabetes insipidus

Eustachian tube dysfunction

Learning deficits in math and reading(particularly reading comprehension)

Dyslipidemia

Sensorineural hearing loss

Memory (particularly visual, sequencing,temporal memory)

Growth hormone (GH) deficiency

Tinnitus

Processing speed

Tympanosclerosis

Sustained attention

VertigoVisual-motor integration#16: Other Therapeutic Modalities
Systemic Radiation
Radioiodine therapy (I-131 thyroid ablation)
Systemic Iodine metaiodobenzylguanidine (MIBG)(in therapeutic doses)

Interferon:Interleukin (IL):

Otosclerosis

Auditory complication, other, specify:

Neurogenic bladder

Cardiovascular

Neurogenic bowel

Gonadotropin deficiency (LH/FSH deficiency)
Hyperprolactinemia
Hyperthyroidism
Hypothyroidism, primary(thyroid gland failure)
Hypothyroidism, central/secondary(T4/TSH deficiency)

Arrhythmia

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App I ContentsKey for Completing Summary of Cancer Treatment (Comprehensive)(cont)#17: Complications/Late Effects (by system)(cont)#17: Complications/Late Effects (by system)(cont)#17: Complications/Late Effects (by system)(cont)

Endocrine/Metabolic (cont)

Immune (cont)Ocular (cont)Impaired glucose metabolism/diabetes mellitus

Immune complication, other, specify:

Xerophthalmia (keratoconjunctivitis sicca)

Overweight [Body Mass Index (BMI)]
Age 2–20 yrs: BMI for age ≥ 85 – <95%ile
Age > 20 yrs: BMI 25 to 29.9

Musculoskeletal

Ocular complication, other, specify:

Chronic pain, musculoskeletal

Peripheral Nervous System (PNS)

Contractures

Areflexia

Fibrosis

Chronic pain, peripheral neuropathic

Functional and activity limitations

Dysesthesias

Precocious puberty

Hypoplasia

Foot drop

Thyroid nodule

Impaired cosmesis

Paresthesias

Endocrine/metabolic complication, other, specify:

Increased energy expenditure (related to
amputation/limb salvage)

Vasospastic attacks (Raynaud's phenomenon)

Kyphosis

PNS complication, other, specify:

Limb length discrepancy

Psychosocial

Osteonecrosis (avascular necrosis)

Anxiety
Dependent living

Cirrhosis

Prosthetic malfunction(loosening, non-union, fracture) requiring revision,
replacement or amputation

Esophageal stricture

Radiation-induced fracture

Educational problems

Fecal incontinence

Reduced bone mineral density (BMD)

Fatigue

FistulaReduced or uneven growth

Limitations in healthcare and insurance access

Focal nodular hyperplasia

Residual limb integrity problems

Impaired quality of life

Hepatic dysfunction

Scoliosis

Post-traumatic stress

Hepatic fibrosis

Shortened trunk height

Psychological maladjustment

Iron overload

Musculoskeletal complication, other, specify:

Psychosocial disability due to pain

Sinusoidal obstruction syndrome (SOS) [previously
known as veno-occlusive disease (VOD)]

OcularRelationship problems

Cataract
Chronic painful eye

Risky behavior(behaviors known to increase the likelihood ofsubsequent illness or injury )Gaze paresis

Sleep problems

Glaucoma

Social withdrawal

ImmuneKeratitis

Suicidal ideation

Asplenia - functional

Lacrimal duct atrophy

Under-employment/Unemployment

Asplenia - surgical

Maculopathy

Psychosocial complication, other, specify:

Chronic hepatitis B

Nystagmus

Pulmonary

Chronic hepatitis C

Ocular nerve palsy

Acute respiratory distress syndrome

Chronic graft-versus-host disease (cGVHD)

Optic atrophy

Bronchiectasis

Chronic infection

Optic chiasm neuropathy

Bronchiolitis obliterans

Chronic sinusitis

Orbital hypoplasia

Chronic bronchitis

Decreased B cells

Papilledema

Interstitial pneumonitis

HIV infection

Papillopathy

Obstructive lung disease

Hypogammaglobulinemia

Poor prosthetic fit (related to enucleation)

Pulmonary fibrosis

Secretory IgA deficiency

Retinopathy

Restrictive lung disease

T cell dysfunction

Telangiectasias

Pulmonary complication, other, specify:

ObesityAge 2–20 yrs: BMI for age ≥ 95%ile
Age > 20 yrs, BMI ≥ 30

Gastrointestinal/Hepatic
Abdominal adhesions
Bowel obstruction
Cholelithiasis
Chronic enterocolitis

Strictures
Vitamin B12/folate/carotene deficiency
Gastrointestinal/hepatic complication, other,
specify:

COG LTFU Guidelines Appendix I – Page 29

Weakness

Depression

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App I ContentsKey for Completing Summary of Cancer Treatment (Comprehensive)(cont)#17: Complications/Late Effects (by system)(cont)#17: Complications/Late Effects (by system)(cont)

Reproductive – Female

Urinary (cont)Adverse pregnancy outcome

Chronic urinary tract infection

Delivery complications

Dysfunctional voiding

Fetal malposition

Fanconi syndrome

Adverse pregnancy outcome (cont)

Glomerular injury

Low-birth weight infant

Hemorrhagic cystitis

Neonatal death

Hydrocele

Premature labor

Hydronephrosis

Pregnancy complications

Hyperfiltration

Spontaneous abortion

Hypertension

Breast tissue hypoplasia

Hypophosphatemic rickets

Dyspareunia

Proteinuria

Infertility

Renal dysfunction

Pelvic adhesions

Renal insufficiency

Pelvic floor dysfunction

Renal tubular acidosis

Premature ovarian insufficiency/premature menopause

Reservoir calculi

Psychosexual/sexual dysfunction

Urinary incontinence

Puberty - absence

Urinary tract obstruction

Puberty - delayed/arrested

Vesicoureteral reflux

Reduced fertility

Urinary complication, other, specify:

Symptomatic ovarian cysts

Other, specify:

Uterine vascular insufficiency

No late effects identified

Vaginal fibrosis/stenosis

Unknown

Spontaneous neobladder perforation

Vulvar scarring
Reproductive – female complication, other, specify:
Reproductive – Male
Anejaculation
Azoospermia
Ejaculatory dysfunction
Erectile dysfunction
Infertility
Oligospermia
Puberty - absence
Puberty - delayed/arrested
Reduced fertility
Retrograde ejaculation
Testosterone deficiency/insufficiency
Reproductive – male complication, other, specify:
Urinary
Asymptomatic bacteriuria
Bladder fibrosis

COG LTFU Guidelines Appendix I – Page 30

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Table of Contents

App I Contents

Long-Term
Follow-Up
Guidelines
for Survivors of Childhood, Adolescent,and Young Adult Cancers

Patient-Specific
Guideline
Identification
Tool

Version 6.0
October 2023

Copyright 2023 © Children’s Oncology GroupAll rights reserved worldwide

Instructions:Patient-Specific Guideline Identification Tool (Version 6.0)
To determine Long-Term Follow-Up Guideline sections relevant to an individual patient:
1.

Place a check mark in the “Mark if Patient Received” column for each chemotherapy agent, radiation field, transplant type, surgery, or othertherapeutic modality that the patient received.

2.

Compile a list of all section numbers generated during step 1. Include the following sections as applicable:–

Sections 1 - 7

Applicable to all patients–

Section 8

Patients diagnosed before 1972–

Section 9

Patients diagnosed before 1993–

Section 10

Patients diagnosed between 1977 and 1985–

Section 11

All patients who received chemotherapy–

Sections 44, 45, 96

All patients who received radiation–

Sections 100 - 105

All patients who underwent hematopoietic cell transplant–

Section 164-165–

Section 100 is for males only–

Section 101 is for females only

Applicable to all patients3.

For patients who received radiation for which a minimum dose specification is indicated, follow the "Instructions for Radiation Dose Calculation" in Appendix I. Delete from your list those radiation section(s) for which the patient did not receive the minimum radiation exposure atwhich the section(s) become applicable.

4.

You now have a finalized list of all guideline sections applicable to this patient.

COG LTFU Guidelines Appendix I – Page 32

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Table of Contents

App I Contents

Patient-Specific Guideline Identification Tool
Applicable guideline sections indicated in bold/dark blue; M=Male; F=Female
Name:

Sex:

Cancer Diagnosis:

Date of Diagnosis:

 Sections 1–7 applicable to all patients

Prior to 1972:
Prior to 1993:
1977–1985:

M F

Date of Birth:
End Therapy Date: Section 8
 Section 9
 Section 10

LTFU guidelines are applicable topatients who are ≥ 2 years following
completion of cancer therapy.

CHEMOTHERAPY:  Yes  No
If yes:  Section 11 and applicable guidelines for specific chemotherapy agents below
Mark If
Patient
Received

Chemotherapy Agent

Applicable Guideline Sections

Asparaginase

Section 40

Bleomycin

Section 35

Busulfan**Cumulative dose =mg/m2
Cyclophosphamide isotoxic dose =Sections 12M, 13M, 14F, 15F, 16, 17, 18
mg/m2 = Cumulative dose x 8.823

Carboplatin: All doses

Sections 12M, 13M, 14F, 15F, 16, 23, 24

Carboplatin: Myeloablative dose (conditioning for HCT)

Section 22

Carmustine (BCNU)**
Cumulative dose =mg/m2
Cyclophosphamide isotoxic dose =Sections 12M, 13M, 14F, 15F, 16, 17

Chlorambucil**
Cumulative dose =mg/m2
Cyclophosphamide isotoxic dose =mg/m2 = Cumulative dose x 15

Sections 12M, 13M, 14F, 15F, 16
mg/m2 = Cumulative dose x 14.286

Cisplatin

Sections 12M, 13M, 14F, 15F, 16, 22, 23, 24

Cyclophosphamide**
Cumulative dose =mg/m2
Cyclophosphamide isotoxic dose =Sections 12M, 13M, 14F, 15F, 16, 19, 20
mg/m2 = Cumulative dose x 1

Cytarabine: Low dose IV (all single doses <1000 mg/m2), IO, IT, SQ

Section 26

Cytarabine: High dose IV (any single dose ≥1000 mg/m )Section 25

Dacarbazine (DTIC)

Sections 12M, 13M, 14F, 15F, 16

Dactinomycin

Section 36

Daunorubicin*
Cumulative dose =mg/m2
Doxorubicin isotoxic dose =Section 33, 34

2

mg/m2 = Cumulative dose x 0.5

Dexamethasone

Sections 37, 38, 39

Doxorubicin*
Cumulative dose:
mg/m2
Doxorubicin isotoxic dose =Section 33, 34

Epirubicin*
Cumulative dose:
mg/m2
Doxorubicin isotoxic dose =mg/m2 = Cumulative dose x 1

Section 33, 34
mg/m2 = Cumulative dose x 0.67

Etoposide (VP16)

Section 43

Idarubicin*
Cumulative dose:
mg/m2
Doxorubicin isotoxic dose =Section 33, 34

Ifosfamide**
Cumulative dose =mg/m2
Cyclophosphamide isotoxic dose =mg/m2 = Cumulative dose x 5

Sections 12M, 13M, 14F, 15F, 16, 19, 21
mg/m2 = Cumulative dose x 0.244

COG LTFU Guidelines Appendix I – Page 33

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Table of Contents

App I Contents

Patient-Specific Guideline Identification Tool (cont)Mark If
Patient
Received(cont)

Chemotherapy Agent (cont)

Applicable Guideline Sections (cont)Sections 12M, 13M, 14F, 15F, 16, 17

Lomustine (CCNU)**
Cumulative dose =mg/m2
Cyclophosphamide isotoxic dose =mg/m = Cumulative dose x 16
2

Sections 12M, 13M, 14F, 15F, 16

Mechlorethamine**
Cumulative dose =mg/m2
Cyclophosphamide isotoxic dose =mg/m2 = Cumulative dose x 100

Sections 12M, 13M, 14F, 15F, 16

Melphalan**
Cumulative dose =mg/m2
Cyclophosphamide isotoxic dose =mg/m2 = Cumulative dose x 40

Mercaptopurine (6MP)

Section 27

Methotrexate: High dose IV, Low dose IV, IM, PO

Sections 28, 29, 30

Methotrexate: High dose IV, IO, IT

Sections 31, 32

Mitoxantrone*
Cumulative dose:
mg/m2
Doxorubicin isotoxic dose =Section 33, 34
mg/m2 = Cumulative dose x 10

Prednisone

Sections 37, 38, 39

Procarbazine**
Cumulative dose =mg/m2
Cyclophosphamide isotoxic dose =Sections 12M, 13M, 14F, 15F, 16
mg/m2 = Cumulative dose x 0.857

Temozolomide

Sections 12M, 13M, 14F, 15F, 16

Teniposide (VM26)

Section 43

Thioguanine (6TG)

Section 27

Thiotepa**
Cumulative dose =mg/m2
Cyclophosphamide isotoxic dose =Sections 12M, 13M, 14F, 15F, 16
mg/m2 = Cumulative dose x 50

Vinblastine

Sections 41, 42

Vincristine

Sections 41, 42*Instructions for Anthracycline Dose Calculation: Use formulas below to convert to doxorubicin isotoxic equivalents prior to calculating total cumulative anthracycline dose:

Daunorubicin – multiply total dose x 0.5
Idarubicin – multiply total dose x 5

Doxorubicin – multiply total dose x 1
Mitoxantrone – multiply total dose x 10

Epirubicin – multiply total dose x 0.67**Instructions for Cyclophosphamide Dose Calculation: Use formulas below to convert to cyclophosphamide isotoxic equivalents prior to calculating total cumulative
cyclophophamide dose:

BCNU – multiply total dose x 15
Busulfan – multiply total dose x 8.823
Cyclophosphamide – multiply total dose x 1 Ifosfamide – multiply total dose x 0.244
Mechlorethamine – multiply total dose x 100 Melphalan – multiply total dose x 40
Thiotepa – multiply total dose x 50

Chlorambucil – multiply total dose x 14.286
CCNU – multiply total dose x 16
Procarbazine – multiply total dose x 0.857

Note: There is a paucity of literature to support isotoxic dose conversion; however, the above conversion factors may be used for convenience in order to gauge
screening frequency. Clinical judgment should ultimately be used to determine indicated screening for individual patients.
RADIATION:  Yes  No
If yes:  Sections 44, 45, 96 and applicable guidelines for specific radiation fields below
Mark If
Patient
Received

Radiation Field*

Dose

Applicable Guideline Sections

Any Radiation (not including TBI)

Any

Section 98

Head/Brain

Any

Sections 46, 47, 48, 49, 50, 51, 52, 53, 54M, 55F, 56, 57, 58M,
59F, 61, 62, 64, 65, 67, 68, 69, 70, 71

Head/Brain

Minimum dose specifications apply**

Sections 60, 63, 66

COG LTFU Guidelines Appendix I – Page 34

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Table of Contents

App I Contents

Patient-Specific Guideline Identification Tool (cont)
RADIATION:  Yes  No
If yes:  Sections 44, 45, 96 and applicable guidelines for specific radiation fields below
Mark If
Patient
Received(cont)

Radiation Field* (cont)

Dose (cont)

Applicable Guideline Sections (cont)

Neck

Any

Sections 64, 65, 67, 68, 69, 70, 71, 72, 79

Neck

Minimum dose specifications apply**

Section 66

AxillaAny

Sections 73F, 74F, 75, 76

Chest

Any

Sections 72, 73F, 74F, 75, 76, 79, 97

Chest

Minimum dose specifications apply**

Section 77

AbdomenAny

Sections 79, 80, 81, 82, 83, 84, 85, 86, 87, 97

Abdomen

Minimum dose specifications apply**

Sections 77, 78

PelvisAny

Sections 84, 85, 86, 88, 89, 92F, 93F, 94F, 95F

TestesAny

Sections 90M, 91M

Spine (whole)

Any

Sections 64, 65, 67, 68, 69, 70, 71, 72, 79, 84, 85, 86, 88, 89,
92F, 93F, 94F, 97

Spine (whole)

Minimum dose specifications apply**

Sections 66, 77

Spine (cervical)

Any

Sections 64, 65, 67, 68, 69, 70, 71, 79

Spine (cervical)

Minimum dose specifications apply**

Section 66

Spine (thoracic)

Any

Sections 72, 79, 97

Spine (thoracic)

Minimum dose specifications apply**

Section 77

Spine (lumbar)

Any

Sections 84, 85, 86, 97

Spine (sacral)

Any

Sections 84, 85, 86, 88, 89, 92F, 93F, 94F

TBI

Any

Sections 44, 45, 46, 47, 48, 53, 58M, 59F, 61, 64, 65, 67, 68,
69, 73F, 74F, 75, 76, 80, 81, 86, 87, 91M, 92F, 93F, 94F, 96

TBI

For cumulative dose calculation purposes
only; these sections are not applicable topatients who received TBI alone**

Sections 60, 63, 66, 77, 78*Instructions for Determining Radiation Field
Refer to "Radiation Fields Defined" in COG Long-Term Follow-Up Guidelines Appendix I pages 6-8 to determine applicable radiation fields. Note, for patients who received radiation
to the flank/hemiabdomen, include the pelvis only if the field extended below the iliac crest.
**Instructions for Radiation Dose Calculation:

Five sections of the COG Long-Term Follow-Up Guidelines (sections 60, 63, 66, 77, 78) include radiation dose specifications. These specifications indicate
the minimum dose of radiation that is believed (based on available evidence and the recommendations of the expert panel) to place patients sufficiently atrisk of the referenced late effect to recommend screening. For guideline sections that have a minimum specified dose, the following considerations apply indetermining the applicability of the section for a patient based on his/her radiation exposure.
Sections with minimum dose specifications are applicable to a patient only if:
1. Patient received radiation to any field(s) relevant to the particular guideline section at ≥ the specified minimum dose†OR
2. Patient received a combination of radiation to any relevant field(s)† plus relevant spinal radiation‡ and/or TBI, the sum of which is ≥ the specified minimum
dose†Total dose to each field should include boost dose, if given. If patient received radiation to more than one field relevant to a particular guideline section during
a single planned course of radiation treatment (excluding spinal radiation and TBI), the field that received the largest radiation dose should be used in
making the determination as to the applicability of the indicated guideline section(s). Exception: If patient received radiation to the same field at different
times (e.g., at time of diagnosis AND at relapse), these doses should be added together when considering the applicability of the indicated guideline section.
‡Use the largest dose of radiation delivered to the spinal field(s) specified in the guideline section.
For examples of radiation dose calculations, refer to "Radiation Dose Calculations" in COG Long-Term Follow-Up Guidelines Appendix I page 9.

COG LTFU Guidelines Appendix I – Page 35

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Table of Contents

App I Contents

Patient-Specific Guideline Identification Tool (cont)
Hematopoietic Cell Transplant:  Yes  No
If yes:  Sections 100M, 101F, 102, 103, 104, 105 and applicable guidelines below
Mark If
Patient
Received

Transplant Type

Chronic GVHD Status

Applicable Guideline Sections

Autologous

N/A

Section 99

Allogeneic

Without history of chronic GVHD

No additional guideline sections

Allogeneic

With history of chronic GVHD

Sections 106, 107, 108, 109, 110, 112, 113F, 114

Allogeneic

With currently active chronic GVHD

Section 111

Surgery:  Yes  No
If yes, applicable guidelines for specific surgical procedures below
Mark If
Patient
Received

Surgical Procedure

Applicable Guideline Sections

Amputation

Section 115

Central venous catheter

Section 116

Cystectomy

Sections 117, 142, 143, 144M, 145M, 146F

Enucleation

Section 118

Hysterectomy

Section 119F

Laparotomy

Section 120

Limb sparing procedure

Section 121

Nephrectomy

Sections 122M, 123F

Neurosurgery – brain (all types)

Sections 124, 125, 126, 127

Neurosurgery – brain (applies only to neurosurgery withpotential to affect the hypothalamic-pituitary axis)

Sections 128, 129

Neurosurgery – spinal cord

Sections 130, 131, 132M, 133F, 134

Oophoropexy

Section 135F

Oophorectomy – unilateral

Section 136F, 137F

Oophorectomy – bilateral

Section 138F

Orchiectomy – unilateral/partial

Sections 139M, 140M

Orchiectomy – bilateral

Section 141M

Pelvic surgery

Sections 142, 143, 144M, 145M, 146F

Splenectomy

Section 147

Thoracic surgery

Sections 148, 149

Thyroidectomy - total/partial

Section 150, 151

COG LTFU Guidelines Appendix I – Page 36

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Table of Contents

App I Contents

Patient-Specific Guideline Identification Tool (cont)
Other Therapeutic Modalities:  Yes  No
If yes, applicable guidelines for specific modalities below
Mark If
Patient
Received

Other Therapeutic Modality

Applicable Guideline Sections

Radioiodine therapy (I-131 thyroid ablation)

Sections 152, 153, 154

Systemic MIBG

Sections 155, 156, 157

Bioimmunotherapy (e.g., G-CSF, IL-2, erythropoietin)

Section 158

BCR-ABL tyrosine kinase inhibitors (e.g., imatinib, dasatinib)

Section 159, 160

Other targeted biologic therapies

Section 161

B-cell directed antibody-based therapies (e.g., rituximab)

Section 162

Other antibody-based immune therapies, including antibody drug
conjugates (e.g., blinatumomab, brentuximab vedotin, inotuzumab,
gemtuzomab ozogamicin, dinutuximab, naxitamab, pembrolizumab,
ipilimumab, nivolumab, atezolizumab)

Section 163

General Health Screening
All patients:

 Section 164, 165

COG LTFU Guidelines Appendix I – Page 37

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Table of Contents

App I Contents

Long-Term
Follow-Up
Guidelines
for Survivors of Childhood, Adolescent,and Young Adult Cancers

Section Number
Comparison
COG LTFU
Guidelines
Version 6.0 vs 5.0
Version 6.0
October 2023

Copyright 2023 © Children’s Oncology GroupAll rights reserved worldwide

Section Number Comparison
COG LTFU Guidelines Version 6.0 vs 5.0
Version
6.0

Version
5.0
Potential Late EffectVersion
6.0

Any Cancer Experience

Version
5.0
Potential Late Effect29

28

No known renal late effects related tomethotrexate

1

1

Adverse psychosocial/quality of life effects22

Mental health disorders

30

29

Hepatic dysfunction

3

3

Risky behavior

31

30

Neurocognitive deficits

4

4

Psychosocial disability due to pain

32

31

Clinical leukoencephalopathy

55

Fatigue; Sleep problems

33

32

Acute myeloid leukemia

66Limitations in healthcare and insurance
access34

33

Cardiac toxicity

35

34

Pulmonary toxicity

7

N/A

New to V6: Subsequent malignancy; Risk ofmalignancy in offspring

36

35

No known late effects related to dactinomycin

37

36

Reduced bone mineral density (BMD)38

37

Osteonecrosis (avascular necrosis)

39

38

Cataracts

40

39

No known late effects related to asparaginase

41

40

Peripheral sensory or motor neuropathy

42

41

Vasospastic attacks (Raynaud's phenomenon)

43

42

Acute myeloid leukemia

44

43

Subsequent benign or malignant neoplasm
occurring in or near radiation field

Blood/Serum Products
87

Chronic hepatitis B

98Chronic hepatitis C

109

HIV infection
Chemotherapy

11

10

Dental abnormalities

12

11

Testicular hormonal dysfunction

13

12

Impaired spermatogenesis

14

13

Ovarian hormone deficiencies

15

14

Diminished ovarian reserve (DOR), previously
Reduced ovarian follicular pool45

44

Dermatologic toxicity other than neoplasms

46

45

Brain tumor (benign or malignant)

16

15

Acute myeloid leukemia; Myelodysplasia

47

46

Neurocognitive deficits

17

16

Pulmonary fibrosis48

47

Clinical leukoencephalopathy

18

17

Cataracts

49

48

Cerebrovascular complications

19

18

Urinary tract toxicity

20

19

Bladder malignancy

50

49

Craniofacial abnormalities

21

20

Renal toxicity

51

50

Chronic sinusitis

22

21

Ototoxicity

52

51

Overweight; Obesity

23

22

Peripheral sensory neuropathy

53

52

Growth hormone deficiency

24

23

Renal toxicity

54

53

Precocious puberty (male)

25

24

Neurocognitive deficits

55

54

Precocious puberty (female)26

25

No known late effects related to cytarabine(low dose IV, IO, IT, SQ)

56

55

Hyperprolactinemia

57

56

Central hypothyroidism

27

26

Hepatic dysfunction; Sinusoidal obstruction
syndrome (SOS)

58

57

Gonadotropin deficiency (male)59

58

Gonadotropin deficiency (female)28

27

Update in V6: No known BMD late effects
related to methotrexate (IV, IM, PO)

60

59

Central adrenal insufficiency

61

60

Cataracts

Radiation

COG LTFU Guidelines Appendix I – Page 39

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Table of Contents

App I Contents

Section Number Comparison
COG LTFU Guidelines Version 6.0 vs 5.0 (cont)Version
6.0

Version
6.0

Version
5.0
Potential Late EffectVersion
5.0
Potential Late Effect62

61

Ocular toxicity

95

94

Vaginal fibrosis/stenosis

63

62

Ototoxicity

96

95

Musculoskeletal growth problems

64

63

Xerostomia; Salivary gland dysfunction

97

96

Scoliosis/Kyphosis

65

64

Dental abnormalities; Temporomandibular
joint dysfunction

98

97

Radiation-induced fracture66

65

Osteoradionecrosis of the jaw

67

66

Thyroid nodules

68

67

Thyroid cancer

69

68

Hypothyroidism

70

69

Hyperthyroidism

71

70

Carotid artery disease72

71

Subclavian artery disease

73

72

Breast cancer

74

73

Breast tissue hypoplasia

75

74

Pulmonary toxicity

7675

Lung cancer

77

76

Cardiac toxicity

78

77

Functional asplenia

79

78

Esophageal stricture

80

79

Impaired glucose metabolism/diabetes
mellitus

81

80

Dyslipidemia

82

81

Hepatic toxicity

83

82

Cholelithiasis

115

114

Amputation-related complications

84

83

Bowel obstruction

116

115

85

84

Chronic enterocolitis; Fistula; Strictures

86

85

Colorectal cancer

Thrombosis; Vascular insufficiency; Infectionof retained cuff or line tract; Post-thrombotic
syndrome

87

86

Renal toxicity

117

116

Cystectomy-related complications

88

87

Urinary tract toxicity

118

117

89

88

Bladder malignancy

Impaired cosmesis; Poor prosthetic fit; Orbital
hypoplasia

90

89

Testicular hormonal dysfunction

119

118

91

90

Impaired spermatogenesis

Pelvic floor dysfunction; Urinary incontinence;
Sexual dysfunction (female)

92

91

Ovarian hormone deficiencies

120

119

Adhesions; Bowel obstruction

93

92

Diminished ovarian reserve, previously
Reduced ovarian follicular pool

121

120

Complications related to limb sparing
procedure

94

93

Uterine vascular insufficiency

122

121

Hydrocele; Renal toxicity (male)

Hematopoietic Cell Transplant99

98

Acute myeloid leukemia; Myelodysplasia

100

99

Solid tumors (male)

101

100

Solid tumors (female)

102

101

Hepatic toxicity

103

102

Osteonecrosis (avascular necrosis)

104

103

Reduced bone mineral density

105

104

Renal toxicity

106

105

Dermatologic toxicity

107

106

Xerophthalmia (keratoconjunctivitis sicca)

108

107

Oral toxicity

109

108

Pulmonary toxicity

110

109

Immunologic complications

111

110

Functional asplenia

112

111

Esophageal stricture

113

112

Vulvar scarring; Vaginal fibrosis/stenosis

114

113

Joint contractures
Surgery

COG LTFU Guidelines Appendix I – Page 40

Version 6.0 – October 2023
Table of Contents

App I Contents

Section Number Comparison
COG LTFU Guidelines Version 6.0 vs 5.0 (cont)Version
6.0

Version
5.0
Potential Late EffectVersion
6.0

Version
5.0
Potential Late Effect

123

122

Renal toxicity (female)

155

152

Hypothyroidism

124

123

Neurocognitive deficits

156

153

Thyroid nodules

125

124

Motor and/or sensory deficits

157

154

Thyroid cancer

126

125

Seizures

158

155

127

126

Hydrocephalus; Shunt malfunction

Insufficient information currently available
regarding late effects of biologic agents

128

127

Overweight; Obesity

159

N/A

New to V6: Growth attenuation

129

128

Diabetes insipidus

160

N/A

New to V6: Hypothyroidism

130

129

Neurogenic bladder; Urinary incontinence

161

N/A

131

130

Neurogenic bowel; Fecal incontinence

New to V6: Insufficient information currently
available regarding late effects of biologic
agents132

131

Psychosexual dysfunction (male)

162

N/A

New to V6: Immunologic complications

133

132

Psychosexual dysfunction (female)

163

N/A

134

133

Scoliosis/Kyphosis

New to V6: Insufficient information currently
available regarding late effects of biologic
agents135

134

Oophoropexy-related complication

136

135

Ovarian hormone deficiencies

N/A

156

Breast cancer (female)

137

136

Diminished ovarian reserve, previously
Reduced ovarian follicular pool

N/A

157

Cervical cancer (female)

N/A

158

Colorectal cancer

N/A

159

Endometrial cancer (female)

N/A

160

Lung cancer

N/A

161

Oral cancer

N/A

162

Prostate cancer (male)

N/A

163

Skin cancer

N/A

164

Testicular cancer (male)

138

137

Ovarian hormone deficiencies; Loss of ovarianfollicular pool

139

138

Testicular hormonal dysfunction

140

139

Impaired spermatogenesis

141

140

Testosterone deficiency; Azoospermia

142

141

Urinary incontinence; Urinary tract obstruction

143

142

Fecal incontinence

144

143

Psychosexual dysfunction

145

144

Sexual dysfunction (anatomic); Infertility

146

145

Sexual dysfunction

147

146

Asplenia

148

147

Pulmonary dysfunction

149

148

Scoliosis/Kyphosis

150

149

Hypothyroidism

151

N/A

New to V6: Hypothyroidism

Cancer Screening Guidelines

General Health Screening
164

165

General health

165

N/A

New to V6: Vaccinations

Other Therapeutic Models
152

150

Lacrimal duct atrophy

153

151

Hypothyroidism

154

N/A

New to V6: Xerostomia; Salivary gland
dysfunction; Chronic sialadenitis

COG LTFU Guidelines Appendix I – Page 41

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Table of Contents

App I Contents

Long-Term
Follow-Up
Guidelines
for Survivors of Childhood, Adolescent,and Young Adult Cancers

Appendix II

Patient Education
Materials“Health Links”

Version 6.0
October 2023

Copyright 2023 © Children’s Oncology GroupAll rights reserved worldwide

Appendix II p. 3

Index to Patient Education Materials (“Health Links”)
Health Link – Abbreviated Title

Health Link – Full Title

Associated Guideline Section(s)Amputation

Late Effects after Amputation

115

Bladder Health

Bladder Health after Cancer Treatment

19, 20, 88, 89

Bleomycin Alert

Bleomycin Alert

35

Bone Health

Keeping Your Bones Healthy

37, 104

Breast Cancer

Breast Cancer: Are You at Risk?

73

Cardiovascular Risk Factors

Preventing Cardiovascular Complications

21, 24, 34, 52, 71, 72, 77, 80, 81, 87, 105, 122, 123, 128

Cataracts

Cataracts after Cancer Treatment

18, 39, 61

Central Adrenal Insufficiency

Central Adrenal Insufficiency after Cancer Treatment

60

Chronic Pain

Chronic Pain after Cancer Treatment

4

Colorectal Cancer

Colorectal Cancer: Are You at Risk?

86

Cystectomy

Late Effects after Cystectomy

117

Dental Health

Dental Health after Cancer Treatment

11, 64, 65, 77, 108

Eye Health

Keeping Your Eyes Healthy

62, 107, 118

Finding and Paying for Healthcare

Finding and Paying for Healthcare

6

Gastrointestinal Health

Gastrointestinal Health after Cancer Treatment

79, 83, 84, 85, 102, 112, 120

Growth Hormone Deficiency

Growth Hormone Deficiency after Cancer Treatment

53

Hearing Loss

Hearing Loss after Cancer Treatment

22, 63

Heart Health

Keeping Your Heart Healthy

34, 77

Hepatitis

Hepatitis after Cancer Treatment

8, 9

Hyperprolactinemia

Hyperprolactinemia after Cancer Treatment

56

Hypopituitarism

Hypopituitarism after Cancer Treatment

53, 57, 58, 59, 60, 129

Introduction to Long-Term Follow-Up

Introduction to Long-Term Follow-Up after Cancer Treatment

1

Kidney Health

Kidney Health after Cancer Treatment

21, 24, 87, 105, 117, 122, 123

Limb Sparing Procedures

Late Effects after Limb Sparing Procedures

121

Liver Health

Liver Health after Cancer Treatment

27, 30, 82, 102

Mental Health

Mental Health Afer Cancer

1, 2, 3

Neurogenic Bladder

Neurogenic Bladder after Cancer Treatment

130

Nutrition and Physical Activity

Staying Healthy through Nutrition and Physical Activity

34, 52, 71, 72, 77, 80, 81, 128

Osteonecrosis

Osteonecrosis after Cancer Treatment

38, 103

Osteoradionecrosis

Osteoradionecrosis after Cancer Treatment

66

Ovarian Health Issues

Ovarian and Reproductive Health after Cancer Treatment

14, 15, 59, 92, 93, 94, 119, 136, 137, 138, 146

Peripheral Neuropathy

Peripheral Neuropathy after Cancer Treatment

23, 41

Precocious Puberty

Precocious Puberty after Cancer Treatment

54, 55

Pulmonary HealthPulmonary Health after Cancer Treatment

17, 35, 75, 109, 148

Raynaud’s Phenomenon

Raynaud’s Phenomenon after Cancer Treatment

42

Reducing Subsequent Cancers

Reducing the Risk of Subsequent Cancers

16, 33, 43, 44, 76, 99, 100, 101

School After Treatment

School After Cancer Treatment

1, 22, 25, 31, 47, 63, 124

Scoliosis and Kyphosis

Scoliosis and Kyphosis after Cancer Treatment

97, 134, 149

Single Kidney Health

Keeping Your Single Kidney Healthy

122, 123

Skin HealthSkin Health after Cancer Treatment

44, 45, 106

Splenic Precautions

Precautions for People Without a Functioning Spleen

78, 111, 147

Testicular Health Issues

Testicular and Reproductive Health after Cancer Treatment

12, 13, 58, 90, 91, 132, 139, 140, 141, 144, 145

Thyroid Disease

Thyroid Disease after Cancer Treatment

57, 67, 68, 69, 70, 150, 151, 153, 155, 156, 157

Vaccination non-HCT

Vaccination after Treatment - Radiation/Chemotherapy

165

Vaccination HCT

Vaccination after Treatment HCT

165

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Appendix II p. 4

Health Link

Healthy living after treatment of childhood, adolescent, and young adult cancer

Late Effects after Amputation
Treatment for a childhood bone or soft tissue tumor of the arms or legs may include an amputation (removal of a limb orpart of a limb).
What are the potential late effects of amputation?
•

Skin blisters, redness, or bruising from a poorly fitting prosthesis•

Phantom limb pain (perception of pain coming from the area where the limb used to be)•

Shooting pains, severe cramping, or a burning sensation in the amputated limb•

Skin breakdown and slow wound healing of the remaining limb•

Back or other muscle pain (due to increased use of other muscle groups and limbs to make up for decreased
function in the amputated extremity)•

Emotional distress related to change in body image•

Physical fitness limitations that may result in difficulties performing daily activities and maintaining a healthy
weightWhat are the follow-up recommendations for amputees?
•

Keep the residual limb clean and dry•

Check the skin daily for color changes and skin break down•

Regularly wash items that are used in the prosthesis (stump shrinker, elastic garments, stump socks)•

Have an evaluation of the prosthesis fit every 6 months until you are fully grown, then once a year, and if any
problems arise•Work with a physical and occupational therapist to develop a plan for gait training, activities of daily living, and an
exercise plan (including range of motion, strength, agility, and balance)•

Have a yearly physical examination•

Maintain a healthy diet and activity level

What are the signs that your prosthesis needs the attention of a prosthetist?
•

You hear noises of any kind (squeaking, popping, clicking, etc.)•

You break any part of the prosthesis•

You need new supplies•

You have outgrown the prosthesis•

You have chronic pain while wearing your prosthesis

What other issues occur after amputation?
•

Dealing with peer pressure and body image change•

Coping with “being different”•

Feeling anxious, unsure, or sad•

Paying for a new prosthesis
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Healthy living after treatment of childhood, adolescent, and young adult cancer•

Coping with environments that may or may not be accessible•

Using public transportation (airplane, train, bus, etc.)•

In some cases, living with chronic pain (see related Health Link: Chronic Pain after Childhood Cancer)

Where can I get help?
Talk with your healthcare provider regularly to let them know of any difficulties that you may be facing. In addition, thefollowing web sites offer resources for amputees:•

www.amputee-coalition.org
Provides resources for education, advocacy and peer support for amputees.

•

www.amputee-coalition.org/limb-loss-resource-center/publications/
Provides information about “First Step, A Guide for Adjusting to Limb Loss” published by the Amputee Coalition ofAmerica.

Written by Victoria G. Marchese, PhD, PT, University of Maryland/Greenebaum Cancer Center, Baltimore, MD; Rajaram Nagarajan,
MD, MPH, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; and Thomas R. Baker, CP (certified prosthetist), Wolfchase
Limb and Brace, Jackson, TN.
Reviewed by Leeann Carmichael DNP, APN, FNP-BC; Kayla L. Foster, MD, MPH; and Melissa Acquazzino MD, MS.
Reference: Lusardi MM, Jorge M, Orthotics & Prosthetics in Rehabilitation (3rd Ed). St. Louis: Saunders (an imprint of Elsevier
Inc.), 2013.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

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Appendix II p. 6

Health Link

Healthy living after treatment of childhood, adolescent, and young adult cancer

Bladder Health after Cancer Treatment
Certain types of cancer and certain cancer treatments can cause damage to the urinary bladder. The information in thisHealth Link will help you to recognize signs and symptoms of urinary bladder problems that may occur after treatment
with chemotherapy or radiation for childhood cancer.
What is the urinary bladder?
The urinary bladder is a hollow organ that stores urine. It is locatedbehind the pubic bone. The kidneys filter the blood and make urine,
which enters the bladder through two tubes called “ureters.” Urine
leaves the bladder through another tube, the urethra.
What are the risk factors for bladder problems?
•

Chemotherapy with cyclophosphamide and/or ifosfamide•

Radiation therapy to the pelvic area•

Surgery to the pelvic area

What types of bladder problems can occur?
•

Difficulty voiding or incompletely emptying the bladder•

Bleeding into the bladder (hemorrhagic cystitis)•

Scarring (fibrosis) of the bladder•

Bladder cancer•

Neurogenic bladder (see related Health Link: Neurogenic bladder after Cancer Treatment)

Hemorrhagic cystitis•

What is hemorrhagic cystitis? Hemorrhagic cystitis is a condition in which bladder irritation results in blood in
the urine.

•

What are the symptoms of hemorrhagic cystitis? The urine color may range from slightly pink to bright red.
Some people may feel like they have to urinate urgently, or that they cannot release all the urine, but there isusually no pain. Hemorrhagic cystitis may occur off and on for months to years after completion of therapy.

•

How is hemorrhagic cystitis diagnosed? Usually, blood can be seen in the urine. Sometimes, the amount ofblood in the urine is so small that it is seen only during a urinalysis (lab test to examine the urine). When there isblood in the urine, a urine culture is usually done to check for infection.

•

What can I do if I have hemorrhagic cystitis? Usually it is helpful to drink extra fluids to flush out the bladder.
Avoid tea, coffee, cola beverages, and other fluids containing caffeine since they may worsen the sudden urge tourinate. If you have kidney or heart problems, check with your healthcare provider before drinking extra fluid.

•

When should I call my healthcare provider? Call your healthcare provider any time you see blood in theurine. You should also report any fever, pain with urination, difficulty urinating, or the need to urinate urgently or
frequently, because these are common symptoms of a urinary tract infection or other bladder problems.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Bladder fibrosis•

What is bladder fibrosis? Bladder fibrosis is scar tissue in the bladder. This may build up and cause the bladderwall to thicken. When this happens, the pressure inside the bladder increases. This may affect the bladder’sability to store and empty urine. Over time these changes can lead to damage to the kidneys.

•

What are the symptoms of bladder fibrosis? Problems may include difficulty emptying the bladder, leakage ofurine, or blood in the urine. Sometimes, bladder fibrosis may not cause any symptoms at all.

•

How is bladder fibrosis diagnosed? An ultrasound of the bladder may show thickening of the bladder wall.
A urologist, a doctor who specializes in bladder health, may also perform a cystoscopy, a test that allows thedoctor to look directly in the bladder through a thin, lighted tube.

•

What can I do if I think I have bladder fibrosis? If you are at risk for bladder fibrosis and have any of thesymptoms described above, you should ask for a referral to a urologist.

•

When should I call my healthcare provider? Call your healthcare provider if you have symptoms of bladderfibrosis, such as difficulty emptying the bladder, leakage of urine, or blood in the urine.

Bladder cancer•

What is bladder cancer? Bladder cancer is a type of tumor that can develop in people who have been treatedwith cyclophosphamide or radiation involving the bladder. This is a rare type of subsequent cancer due totreatment.

•

What are the symptoms of bladder cancer? The most common symptom is blood in the urine. There may also
be a need to urinate urgently or frequently. If the cancer is advanced at the time of diagnosis, there may be pain
over the bladder, in the genital area, or in the bones.

•

How is bladder cancer diagnosed? The diagnosis is usually made by doing a cystoscopy to obtain a biopsy of
bladder tissue. Sometimes the diagnosis can be made by finding cancer cells in the urine.

•

What can I do if I think I have bladder cancer? If you are concerned about whether your symptoms may
represent bladder cancer, ask for a referral to a urologist.

Neurogenic bladder•

What is neurogenic bladder? A neurogenic bladder is abnormal function of the bladder caused by damage tothe nerves that control the bladder’s ability to fill, store and empty urine.

•

What are the symptoms of neurogenic bladder? Abnormal bladder function can cause the bladder to beunderactive (not emptying completely) or overactive (emptying too frequently or quickly). People with neurogenic
bladders also have a higher risk of urinary tract infections (UTIs) and kidney damage. (see related Health Link:
Neurogenic bladder after Cancer Treatment)•

How is neurogenic bladder diagnosed? Neurogenic bladder can be evaluated by a urologist. To make adiagnosis, your provider may recommend imaging or urodynamic testing.

•

What can I do if I think I have neurogenic bladder? If you are concerned about whether your symptoms may
be caused by neurogenic bladder, your provider can refer you to a urologist for additional evaluation and testing.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Written by Patricia Shearer, MD, MS, Emory Healthcare, Johns Creek, GA; Michael L. Ritchey, MD, Phoenix Childrens Hospital,
Phoenix, AZ; Fernando A. Ferrer, MD, Children’s Hospital and Medical Center of Omaha, Omaha, NE; and Sheri L. Spunt, MD, Lucile
Packard Children’s Hospital Stanford University, Palo Alto, CA.
Reviewed by Linda Rivard, RN, BSN; Kayla L. Foster, MD, MPH; and Christine Yun, MSN, PNP, CPON.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

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Appendix II p. 9

Health Link

Healthy living after treatment of childhood, adolescent, and young adult cancer

Bleomycin Alert
The lungs are very important organs that are responsible for supplying oxygen to the body and ridding it of carbon
dioxide. Sometimes, treatments given for childhood cancer can cause lung damage. Because you received bleomycin
during treatment for childhood cancer, it is important for you to learn about certain lung problems that can sometimes
happen after treatment with bleomycin. We also suggest that you read the Health Link: Pulmonary Health, whichcontains more information about your lungs and how to keep them healthy.
What are the problems that can happen after treatment with bleomycin?
People who received bleomycin during treatment for childhood cancer can sometimes develop lung problems many
years after their treatment has been completed. These problems may include:•

Lung inflammation (interstitial pneumonitis)•

Lung scarring (pulmonary fibrosis)•

Breathing problems associated with high levels of oxygen and/or intravenous fluids (acute respiratory distresssyndrome)

What is interstitial pneumonitis?
Interstitial pneumonitis is inflammation of the thin layer of tissue between the air sacs (alveoli) in the lungs. This
inflammation can worsen if a person develops lung infections, such as pneumonia. Interstitial pneumonitis that occurs
as a result of therapy with bleomycin sometimes develops after exposure to toxic fumes, tobacco, or high levels ofoxygen given over several hours.
What is pulmonary fibrosis?
Pulmonary fibrosis is the formation of scar tissue in the small air sacs (alveoli) of the lungs. This scarring makes thelungs stiffer and affects the exchange of oxygen and carbon dioxide in the alveoli. Pulmonary fibrosis may worsen overtime and can sometimes lead to early heart failure.
What is acute respiratory distress syndrome (ARDS)?
ARDS is a serious condition that occurs when alveoli in the lungs are damaged and can no longer provide oxygento the body. People who received bleomycin in the past may be at risk for developing ARDS, usually as a result of a
combination of high levels of oxygen and large amounts of intravenous fluid given during surgery. However, the riskof developing ARDS is very low. If you need a medical procedure requiring oxygen or general anesthesia, be sure totell your surgeon, anesthesiologist, and other healthcare providers that you have received bleomycin in the past fortreatment of childhood cancer.
What are factors that increase the risk of developing lung problems after treatment withbleomycin?
•

High total doses of bleomycin (400 units/m2 or more in all doses combined)•

Radiation to the chest or lungs, or total body irradiation (TBI)

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Healthy living after treatment of childhood, adolescent, and young adult cancer•

Treatment with other chemotherapy drugs that can also damage the lungs (see related Health Link: Pulmonary
Health)•Exposure to high oxygen levels (such as during general anesthesia or SCUBA diving)•

Smoking•Inhaled drugs, such as smoking marijuana, vaping, or cocaine

What monitoring is recommended for people who have received bleomycin for treatment ofchildhood cancer?
•

A yearly medical check-up is recommended.

•

Pulmonary function tests may show lung problems that are not apparent during a check-up. For this reason, it is
helpful to have these tests done at least once (at least 2 years after completing cancer treatment) to find out if
there are any problems. Your healthcare provider can decide if further testing is needed based on these results.

•

In some cases, your healthcare provider may recommend repeating the pulmonary function tests if you arescheduled for surgery that requires general anesthesia to check for changes in the lungs that could increase therisk of breathing problems during or after anesthesia.

Are there any special precautions I should take?
If you received therapy with bleomycin, you should:•

Avoid SCUBA diving, unless you have had a complete check-up and have been advised by a pulmonologist (lungspecialist) that diving is safe. During SCUBA diving, increased underwater pressures and high oxygen levels candamage the lungs.

•

Tell your surgeon, anesthesiologist, and other healthcare providers about your medical history before anyscheduled procedures that may require oxygen.

•

Avoid breathing high concentrations of oxygen whenever possible, especially for long periods of time (such as
over several hours). If you require oxygen, monitoring of your oxygen levels can usually be done so that you canreceive the lowest oxygen concentration that is necessary.

•

Get the pneumococcal (pneumonia) vaccine.

•

Get yearly influenza (flu) vaccines.

•

Don’t smoke or use inhaled drugs such as marijuana, vaping, or cocaine. If you currently smoke, talk to yourhealthcare provider about a program to help you quit.

Written by Margery Schaffer, RN, MSN, CPNP, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.
Reviewed by Leeann Carmichael, DNP, APN, FNP-BC; Melissa Acquazzino, MD, MS; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Bleomycin Alert I Version 6.0 I October 2023 I Page 2 of 3

Health Links

Appendix II p. 11

Health Link

Healthy living after treatment of childhood, adolescent, and young adult cancer
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Bleomycin Alert I Version 6.0 I October 2023 I Page 3 of 3

Health Links

Appendix II p. 12

Health Link

Healthy living after treatment of childhood, adolescent, and young adult cancer

Keeping Your Bones Healthy
During childhood and into young adulthood, bone formation usually occurs faster than bone loss, causing bones togrow and become heavier (more dense). As a person gets older, the process of bone removal gradually overtakes boneformation, and bones slowly lose strength as part of the normal aging process. However, loss of bone strength may occur
at earlier ages in childhood cancer survivors because of certain cancer treatments. Loss of bone strength may result in acondition known as osteoporosis, which is sometimes referred to as “low bone mineral density.”
Osteoporosis: A Silent Disease
Osteoporosis is a disorder resulting from too little new bone formation or too much bone loss, causing bones to become
weak. Most people do not have symptoms, especially in the early stages. However, as bones become weaker, the risk
for fractures increases. Osteoporosis may occur in any bone, but most commonly affects the wrists, hips, spine, and legbones.
How is osteoporosis diagnosed?
Although osteoporosis may be suspected based on a patient’s symptoms and risk factors, the diagnosis is made bymeasuring bone density with special x-ray techniques, called DXA or bone density scans. These scans do not expose
patients to large amounts of radiation, and generally take less than 20 minutes to perform.
People who have osteoporosis should discuss treatment options with their healthcare provider. Medications, such asbisphosphonates and calcitonin, are available specifically for the treatment of low bone density. In addition, if you have
low levels of sex hormones, or low levels of growth hormone (GH), you may also benefit from hormone replacement
therapy.
What are the risk factors for osteoporosis?
Osteoporosis is more common in people with the following characteristics:•

Female (especially after menopause)•

Family history of osteoporosis•

Caucasian or Asian race•

Small, thin frame•

Older age

The following factors may also increase the risk of osteoporosis:•

Smoking•

Diet low in calcium•

Lack of weight-bearing exercise•

Too much caffeine, alcohol, or soda•

A diet high in salt

Additional causes of osteoporosis in people who have had cancer may include:
A history of treatment with:•Corticosteroids (such as prednisone and dexamethasone)

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Health Link

Healthy living after treatment of childhood, adolescent, and young adult cancer•

Radiation to weight-bearing bones (legs, hips, spine)

Conditions resulting from cancer treatment, including:•

Low levels of sex hormones•

GH deficiency•

High levels of thyroid hormone•

Chronic graft-versus-host disease requiring prolonged therapy with corticosteroids•

Prolonged periods of inactivity (bed rest)

Other medical treatments, including:•

Certain anticonvulsants (phenytoin and barbiturates)•

Aluminum-containing antacids (such as Maalox® or Amphogel®)•

Medications such as Lupron (used for treatment of early puberty and endometriosis)•

High doses of heparin (used to prevent blood clots), especially with prolonged use•

Cholestyramine (used to control blood cholesterol)

Many of the medications on this list are essential treatments for certain medical conditions. If you are taking any of these
medications, do not change your dosage or stop taking your medication without consulting with your healthcare provider.
What lowers the risk of osteoporosis?
Fortunately, there are many things you can do to reduce the risk of osteoporosis. Regular weight-bearing exercise(such as brisk walking, dancing, and jogging) helps to develop and maintain healthy bones. Bicycling and swimmingare excellent exercises for general fitness, but these are NOT weight-bearing exercises, and they do not help to build
strong bones. Exercises that are especially good for bone health include higher-impact weight-bearing activities, such as
hopping, jogging and jumping rope. Resistance exercises, such as light weightlifting, also help to build strong bones andare especially important for bones of the upper body, including the arms and shoulders. If you have problems with yourheart, or have painful bones or joints, be sure to discuss your individual health status and cancer treatment history withyour healthcare provider before starting any new exercise program.
A diet high in calcium also is important in preventing osteoporosis. Most healthcare professionals recommend 1000–1500
mg a day, which means a diet rich in dairy products (milk, cheese, yogurt) and leafy green vegetables. Talking with adietitian may help you design a healthy diet. Over-the-counter calcium supplements also may be useful. See Tables 1
for recommended daily calcium intake. Additional information about calcium-rich diets is available at www.usdairy.com/
dairy-nutrition/products.
Vitamin D is needed to absorb calcium. Your skin makes this vitamin naturally when exposed to sunlight. Many dairy
products also contain vitamin D. In general, at least 400 units of Vitamin D is recommended daily. You should not takemore than 800 units of Vitamin D per day unless your health care provider has recommended a higher dose for you.
Taking too much vitamin D may be harmful, so it’s important to check with your healthcare provider before taking any
vitamin D supplements.
What screening is recommended?
After reviewing your treatment history and risk factors, your healthcare provider can advise you regarding the need forbone density testing. For those at risk, a baseline bone density scan is recommended for childhood cancer survivors when
they enter long-term follow-up (2 or more years after completion of therapy). Follow-up scans may be needed for ongoing
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monitoring of bone density in some patients.
Table 1: Recommendations for Adequate Dietary Calcium Intake in the United States
Age

Recommended Calcium Intake

1–3 years
4–8 years
9–18 years
19–50 years
50–70+ years

700 mg per day
1000 mg per day
1300 mg per day
1000 mg per day
1000-1200 mg per day(National Institutes of Health Office of Dietary Supplements (NIH ODS) Calcium Fact Sheet for Health Professionals)

Written by Julie Blatt, MD, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC; and Lillian R. Meacham, MD, Children’s
Healthcare of Atlanta - Egleston, Atlanta, GA.
Reviewed by Kayla L. Foster, MD, MPH; Sarah Ford, MS, PA-C; and Melissa Acquazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities, or
damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Breast Cancer: Are You at Risk?
The risk of cancer increases for everyone as they age. Depending on the specific treatment you received for childhood
cancer, you may be at increased risk for developing breast cancer. It is important to understand that risk, so that you
can take steps to protect your health.
What are the risk factors?
Several studies have shown that women treated with radiation to the chest for cancer during childhood,adolescence, or young adulthood have an increased risk of developing breast cancer as they get older, compared to
women their same age in the general population. The risk of secondary breast cancer is related to the location anddose of radiation. People treated with higher doses of radiation have the highest risk. Researchers are studying thisproblem to better understand the risk factors and find ways to prevent secondary breast cancer.
When is breast cancer likely to occur?
The risk of secondary breast cancer begins to increase at about ten years following radiation therapy and continues torise thereafter. This means that if a woman develops breast cancer following chest radiation for childhood/adolescentcancer, it usually happens at a much younger age (usually 30 to 40 years old) than in women who develop primarybreast cancer (usually age 50 or older).
What can I do to protect my health?
Most women who received radiation therapy to the chest during childhood, adolescence, or young adulthood will notdevelop breast cancer. However, if you received radiation to the chest, it is important to understand that the risk ishigher for you than it is for women your age who never received radiation. So, the best way for you to protect yourhealth is by taking steps to closely monitor your breasts. That way, if a cancer develops, it will be detected in its
earliest stages, when treatment is most effective. It is also important to tell your healthcare provider about your cancer
treatment history, including the dose of chest radiation that you received. You should ask your treating oncologist or
cancer center for a written summary of your cancer treatment (see related Health Link: Introduction to Long-Term
Follow-Up).
What monitoring is recommended?
If you received radiation therapy to the chest, underarm (axilla), or total body irradiation (TBI) during childhood,adolescence, or young adulthood, you should:
1. Have a clinical breast exam performed by your healthcare provider—at least once a year until you reach age
25—then every 6 months thereafter.
2. Have a yearly mammogram and breast MRI (magnetic resonance imaging test) starting at age 25, or 8 years
after you received radiation (whichever comes last).
If your healthcare provider is not familiar with these monitoring recommendations for women who have received chest
radiation during childhood, adolescence, or young adulthood, we encourage you to share this Health Link with them,and tell them that additional information is also available at www.survivorshipguidelines.org.
Is there anything else I can do to minimize the risk?
The following lifestyle changes may help reduce the risk of developing breast cancer, and will also help you to stay as
healthy as possible:•

Eat more fruits and vegetables (at least 5 servings a day are recommended).

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Healthy living after treatment of childhood, adolescent, and young adult cancer•

Exercise at least 30 minutes per day on most days of the week.

•

Maintain a healthy body weight.

•

Limit your intake of alcohol to no more than one drink per day.

•

Avoid smoking or vaping.

•If you have a baby, try to breastfeed for at least four months.

•

If you need hormone replacement therapy or birth control pills, discuss the risks and benefits with yourhealthcare professional.

If you have questions regarding your risk of developing breast cancer, and how you can best protect your health, besure to discuss this with your healthcare provider.
Written by Melissa M. Hudson, MD, St. Jude Children’s Research Hospital, Memphis, TN; and Wendy Landier, PhD, CPNP, Children’s
Hospital of Alabama, Birmingham, AL. Portions adapted from CCSS Newsletter Winter 2001, used with permission.
Reviewed by Amelia DeRosa, RN, BSN, CPON; Kayla L. Foster, MD, MPH; and Christine Yun MSN, PNP, CPON®.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Preventing Cardiovascular Complications
As people get older, the risk for developing cardiovascular problems, such as heart attack and stroke, increases.
Additional factors that increase the risk of developing cardiovascular problems include:•

Being overweight or obese•

High blood pressure•

Unhealthy cholesterol levels (high LDL, high triglycerides, or low HDL)•

Prediabetes or diabetes mellitus•

Smoking•

Excessive alcohol intake•

Family history of heart disease

Certain cancer treatments given during childhood, adolescence, or young adulthood may increase the risk of developing
cardiovascular complications. It is important for you to be aware of these risks so that you can practice healthy habitsthat can help prevent cardiovascular problems.
What increases the risk for being overweight or obese?
Treatment factors:•

Radiation to the brain or head (especially at doses of 18 Gy or higher)•

Surgery to the brain affecting the “mid-brain” area (containing the pituitary gland)

Other known risk factors:•

Overeating•

Eating a diet that is high in fats and sugar•

Not having regular physical activity•

Having certain medical conditions, like an underactive thyroid (hypothyroidism), or low levels of GH

What increases the risk for high blood pressure?
Treatments factors:•

Ifosfamide•

Cisplatin•

Carboplatin•

Radiation involving the kidneys, including the abdomen, flank, and total body irradiation (TBI)•

Removal of one kidney (see related Health Link: Single Kidney Health)•

Hematopoietic cell transplant (particularly if complicated by chronic graft-versus-host disease)

Other known risk factors:•

Being overweight or obese•

Having a family history of high blood pressure

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Healthy living after treatment of childhood, adolescent, and young adult cancer•

Not getting regular physical activity•

Eating a diet that is high in salt

What increases the risk for unhealthy cholesterol levels (including high triglycerides and low
HDL)?
Treatment factors:•

Total body irradiation (TBI)•

Abdominal radiation

Other known risk factors:•

Being overweight or obese•

Having a family history of unhealthy cholesterol levels•

Not getting regular physical activity•

Eating a diet high in fat

What increases the risk for high blood sugar/diabetes mellitus?
Treatment factors:•

Abdominal radiation•

Total body irradiation (TBI)•

Prolonged treatment with corticosteroids, such as prednisone or dexamethasone

Other known risk factors:•

Being overweight or obese (note that survivors who received TBI may be at increased risk even if they are notoverweight or obese)•

Having a family history of diabetes

How I can I tell if I am overweight or obese?
Visit with your health care provider about your weight to determine if you are at a healthy weight for your height,
age and activity level. The body mass index (BMI) is a tool your provider may use to help determine if you are at ahealthy weight. BMI calculators and information on how to interpret results are available on-line at www.cdc.gov/
healthyweight/assessing/bmi/.
What can I do to lower my risk of cardiovascular complications?
•Get regular check-ups and follow your health care provider’s recommendations regarding how often you needblood pressure checks and blood tests to monitor your cholesterol and/or blood sugar levels.

•

Eat a healthy diet (See related Health Link: Staying Health through Nutrition and Physical Activity).

•

Increase physical activity if you are able (See related Health Link: Staying Health through Nutrition and Physical
Activity).

•

Avoid smoking. If you are interested in quitting smoking, online assistance is available from the National
Institutes of Health at www.smokefree.gov.

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Healthy living after treatment of childhood, adolescent, and young adult cancer•

If you are overweight, obese, have high blood pressure, unhealthy cholesterol levels and/or high blood sugar,
see your health care provider regularly. Follow their recommendations for additional testing, if needed, and forongoing treatment of your health condition.

•

In some cases, medications may be required to treat these conditions. If you are prescribed medications, be sure
to take them regularly and to carefully follow your health care provider’s instructions.

Written by Adam J. Esbenshade, MD, MSci, Vanderbilt University/Ingram Cancer Center, Nashville, TN.
Reviewed by Linda Rivard, RN, BSN, CPON; Melissa Acquazzino, MD, MS; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Cataracts after Cancer Treatment
Childhood cancer treatment sometimes requires the use of medications or radiation that can increase the risk ofdeveloping cataracts. Because vision can have a significant impact on daily living, it is important for survivors who
received these treatments to have their eyes checked regularly.
What is a cataract?
A cataract is clouding of the normally clear lens of the eye. Cataracts often develop slowly, but as the clouding increases,
vision can be affected.
How does a cataract affect vision?
The eyes are remarkable organs, allowing light to be converted into impulses that are transmitted to the brain, whereimages are perceived. Light enters the eye through a clear layer of tissue known as the cornea. The cornea bends andfocuses the light and sends it through the opening of the eye known as the pupil. The pupil controls how much lightenters the eye. Behind the pupil is the lens of the eye, which focuses the light onto the retina, the membrane along theback wall of the eye. The nerve cells in the retina change the light into electrical impulses and send them through theoptic nerve to the brain, where the image is perceived. When the lens becomes cloudy due to a cataract, the image
delivered to the retina becomes blurry.
What are the symptoms of a cataract?
Common symptoms of cataracts include:•

Painless blurring of vision•

Sensitivity to light and glare•

Double vision in one eye•

Poor night vision•

Fading or yellowing of colors•

The need for frequent changes in prescriptions for glasses orcontact lenses

Lens
Retina
Pupil
CorneaConjunctiva
Optic nerve

What cancer therapies increase the risk of developing cataracts?
Certain chemotherapy, including:•Busulfan•Corticosteroids, such as prednisone and dexamethasone

Radiation therapy to the following areas:•

Eye and surrounding tissue (orbits)•

Head or brain•

Total body irradiation (TBI)

The risk for cataracts increases with:•

Higher radiation doses•

Frequent exposure to sunlight•

The passage of time (the longer off therapy the survivor is)

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What monitoring is recommended?
•

Have an eye examination every year during your regular check-up•

See an eye specialist (ophthalmologist or optometrist) for a full eye evaluation every year if you had:–

Total body irradiation (TBI)–

Radiation to the head, brain or eyes–

A tumor involving the eye

How are cataracts treated?
Not all cataracts need treatment. In many cases, an ophthalmologist may monitor the vision closely over many years
and will recommend treatment if and when it becomes necessary. The only treatment for cataracts is surgical removalof the lens and replacement with an artificial lens. Today, cataract surgery is a low-risk procedure that is performed on
an outpatient basis and usually is successful in restoring vision.
How can I keep my eyes as healthy as possible?
•

Wear sunglasses with ultraviolet (UV) protection when in bright sunlight.

•

When participating in sports, be sure to select protective eyewear that is appropriate for the sport. Eyewear worn
for sports should be properly fitted by an eye care professional.

•

Avoid toys with sharp, protruding or projectile parts.

•

Never play with fireworks or sparklers of any kind to avoid accidental injury.

•

Be careful when working with hazardous household chemicals.

•

Wear protective eyewear when using a lawnmower, power trimmer, or edger, and when working with dangerous
equipment in the workshop.

•

If you do experience an eye injury, seek medical attention promptly.

Written by Teresa Sweeney, RN, MSN, CPNP, St. Jude Children’s Research Hospital, Memphis, TN; and Wendy Landier, PhD, CPNP,
Children’s Hospital of Alabama, Birmingham, AL.
Reviewed by Angela Yarbrough DNP, APRN, FNP-BC, CPON®; Kayla L. Foster, MD, MPH; and Christine Yun MSN, PNP, CPON®.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Central Adrenal Insufficiency after Cancer Treatment
Some people who were treated for cancer during childhood may develop endocrine (hormone) problems because ofchanges in the function of a complex system of glands known as the endocrine system.
Pituitary gland

What is the endocrine system?

Hypothalamus

The endocrine system is a group of glands that regulates
many body functions including growth, puberty, energy level,urine production, and stress response. Glands of the endocrine
system include the pituitary, hypothalamus, thyroid, pancreas,
adrenals, ovaries, and testes. The hypothalamus and pituitary
are sometimes called the “master glands” because they control
many of the other glands in the endocrine system. Unfortunately,some treatments given for childhood cancer can damage theendocrine system, resulting in a variety of problems.

Thyroid

Pancreas
Adrenal glands

Ovaries

What are hormones?

TestesHormones are chemical messengers that carry informationfrom the endocrine glands through the bloodstream to thebody’s cells. The endocrine system makes many hormones (such as growth hormone, sex hormones, adrenal and thyroid
hormones) that work together to maintain specific bodily functions.
What is central adrenal insufficiency?
Central adrenal insufficiency is caused by a deficiency of the pituitary hormone known as adrenocorticotropic hormone(ACTH). The adrenal glands (located on top of the kidneys) are stimulated by ACTH to produce a hormone known ascortisol. If the pituitary gland doesn’t make enough ACTH, then cortisol will not be made by the adrenal gland. Cortisol
is important for health because it helps to keep the blood sugar at a normal level and helps the body deal with physicalstress, such as fevers or injuries.
What are the risk factors for central adrenal insufficiency?
•

Radiation to the brain, especially in higher doses (30 Gy or 3000 cGy/rads or higher)•

Surgical removal of the pituitary gland

What are the symptoms of central adrenal insufficiency?
Under normal circumstances, there may be no symptoms at all, or there may be mild symptoms, such as fatigue,
weakness, poor appetite, or dizziness. However, under stressful circumstances, such as fever, infection, surgery, or
injury, symptoms may become severe, and may include vomiting, diarrhea, low blood sugar, low blood pressure, anddehydration.
What screening is recommended?
People who had radiation in a dose of 30 Gy (3000 cGy/rads) or higher to the central area of the brain (hypothalamicpituitary axis) should have a yearly blood test to check the cortisol level or yearly evaluation by an endocrinologist(hormone specialist). Anyone who is having symptoms suggestive of central adrenal insufficiency should also have an
evaluation by an endocrinologist.
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How is central adrenal insufficiency treated?
Central adrenal insufficiency is treated with hydrocortisone, a medication that is given by mouth every day on a regularschedule. In times of increased stress, such as illness or surgery, the dose of hydrocortisone is increased, also known
as stress dosing, and can be administered by injection if necessary. If you have central adrenal insufficiency, you shouldwear a medical alert bracelet so that in case of an accident or sudden illness, emergency medical workers will be awareof your special health needs.
Written by Debra A. Kent, RN, MSN, CPNP, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; and Wendy Landier, PhD,
CPNP, Children’s Hospital of Alabama, Birmingham, AL.
Reviewed by Angela Yarbrough DNP, APRN, FNP-BC, CPON®; Christine Yun MSN, PNP, CPON®; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities, or
damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Chronic Pain after Cancer Treatment
Pain is a common experience during cancer treatment, either from the cancer itself or from the treatment. Usually,
after the treatment is finished, there is no more pain. For some people, however, pain continues to be a side effect ofeither the cancer or its treatment, even when the cancer is in remission and treatment has been completed. For cancer
survivors, long-term pain may occur for a variety of reasons, such as damage to bones, joints, or nerves resulting fromtreatment with radiation, surgery, certain chemotherapy medications, or corticosteroids.
What is the difference between acute and chronic pain?
Acute pain is generally the result of illness (such as cancer), injury and/or surgery and is usually confined to a limited
period of time. Acute pain has a biologic purpose, that is, it tells us that we are hurt or ill, so that we can protect
ourselves.
Chronic pain lasts after the underlying illness or injury has resolved. Chronic pain is a problem because the longer thepain lasts, the more complicated it might become, particularly in the way it could affect a survivor’s quality of life.
Pain is very complex
Healthcare providers used to think that the amount of pain a person had was directly related to the extent of physicaldamage to body tissue. Healthcare providers now know that the pain people feel is affected by many physical,
emotional, and cognitive factors that are unique to everyone.
Recent studies involving new technology to study the brain are confirming that many processes are involved in chronic
pain. The experience of pain is the result of a complex interchange of information from many different areas of thebrain. These studies have also helped us to understand that pain can sometimes persist (even when the original injury
has healed) due to changes in the way the body sends and receives pain signals.
Healthcare providers have learned that different people perceive pain in different ways. These differences can be seenin brain imaging studies as individuals rate their pain to the same source of pain, or “stimulus.” That is, some people
seem to be very sensitive, whereas others may report little pain even with the same stimulus. While you might be bornwith some of these differences, environmental factors tend to play an important role too. Factors such as age, sex,
developmental level, family and cultural traditions, prior pain experience, and circumstances surrounding the injury allcontribute toward how a cancer survivor might interpret, experience, and cope with pain.
Pain and Psychological Health
Psychological factors play a role in the amount of distress that is experienced, or how upsetting the pain might be toeach individual. Furthermore, other factors, such as family or work environment, can also affect the ability to cope withpain.
In the case of chronic pain that lasts for months and years, it is possible for cancer survivors to become increasingly
depressed if they don’t have ways to cope with the pain in a healthy way. Survivors with pain may sometimes become
frustrated and angry, especially if pain is preventing them from doing activities that they used to enjoy. If a survivor
believes that pain controls his or her life, then they may begin to feel powerless, develop low self-esteem, and avoid
taking on challenges and opportunities for growth. Pain can develop into a troublesome cycle. For example, a survivor
might stop moving around and doing physical activities because they are afraid of triggering or worsening their pain.
However, the less active they are, the weaker their muscles become, which can then worsen the pain.

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Sometimes, people begin to anticipate the physical sensations of pain in a fearful way. They may withdraw from social orcommunity activities to avoid having to deal with pain in public situations, and they may increasingly isolate themselves.
Depression, anxiety, and chronic stress may follow, which can make the pain worse. This may also lead to physicalchanges in the body associated with stress, depression, and anxiety, which can lower the pain thresholds.
How is Pain Treated?
Fortunately, there are ways to manage and cope with chronic pain. Chronic pain can be treated with medicine, without
medicine using behavioral treatments (such as relaxation or meditation), or by a combination of the two. Non-medicine
treatments can be used along with medications to manage pain during and after cancer treatment. Studies of patients
suffering from chronic pain show that training in pain-coping skills can help increase self-confidence and reduce distressfrom pain. Changes in how a person copes with pain and what they believe about their pain may also produce positivechanges in behavior, such as increased exercise, improved pacing of activities, better results with medication, andincreased participation in social activities.
Behavioral skills can be helpful in treating and coping with pain. Specific techniques include relaxation, meditation,
guided imagery, distraction, and redirected thinking, as well as changing thoughts and beliefs about pain and what
it means. Other effective approaches include support groups, massage, music, and counseling focused on pain
management and behavioral modification.
Written by Sunita K. Patel, PhD, City of Hope Comprehensive Cancer Center, Duarte, CA.
Reviewed by Kayla L. Foster, MD, MPH; Beth Fisher, DNP, APRN, CPNP; and Melissa Acquazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical
condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities, or
damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Colorectal Cancer: Are You at Risk?
The risk of cancer increases for everyone as they age. Depending on the specific treatment you received for childhood
cancer, you may be at increased risk for developing colorectal cancer (cancer of the colon or rectum). It is important tounderstand that risk, so that you can take steps to protect your health.
What is colorectal cancer?
Colorectal cancer is a type of cancer that occurs in the colon (large intestine) or the rectum (the last several inches ofthe large intestine). Colorectal cancer is the second leading cause of cancer deaths in the United States. Many of these
deaths happen because the cancers are found too late to be cured. If colorectal cancer is found early enough, it canusually be cured.
What are the risk factors?
Several studies have shown those who were treated with radiation to the abdomen, pelvis, spine, or total body
irradiation (TBI) during childhood, adolescence, or young adulthood have an increased risk of developing colorectal
cancer. It is therefore important for you to obtain your radiation treatment records so that you know what radiation you
received.
Other known risk factors for developing colorectal cancer include:• Having had colorectal cancer or large intestinal polyps in the past
• Having a close relative (sibling, parent or child) who has had colorectal cancer before age 50• Having ulcerative colitis or Crohn’s disease•

Having a hereditary colon cancer syndrome (such as familial adenomatous polyposis)

What are the signs of colorectal cancer?
Most colorectal cancers begin as a polyp. A polyp starts as a small, harmless growth in the wall of the colon or
rectum. However, as a polyp gets larger, it can develop into a cancer that grows and spreads. During the early stage ofcolorectal cancer, there are rarely any outward signs or symptoms to alert you or your healthcare provider that cancer
is present. This is why screening is so important. Once the cancer has become more advanced, the following signs
may be evident. If you have any of these signs, you should see your healthcare provider immediately:• Bleeding from your rectum• Blood in your stool or in the toilet after you have a bowel movement• A change in the shape of your stool• Cramping pain in your lower stomach• A feeling of discomfort or an urge to have a bowel movement when there is no need to have one•

A change in the normal frequency of your bowel movements

Other conditions can cause these same symptoms. You should be evaluated by your healthcare provider to find out thereason for your symptoms.
When is colorectal cancer likely to occur?
In the general population, colorectal cancer is most likely to occur between the ages of 45 and 65. In cancer survivors
who were treated with abdominal, pelvic, spinal, or TBI radiation, it may occur earlier. The risk begins to increasearound 10 years after the radiation.
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What can I do to protect my health?
Most people who received radiation therapy to the abdomen, pelvis, spine, or TBI will not develop colorectal cancer.
However, if you received this type of radiation, it is important to understand that the risk is higher for you than it is forother people your age who never received radiation. So, the best way for you to protect your health is by taking steps
to closely monitor your colon. That way, if a cancer develops, it can be detected in its earliest stages, when treatment
is most effective.
What monitoring is recommended?
If you were treated with radiation therapy to the abdomen, pelvis, spine, or TBI during childhood, adolescence, or young
adulthood, you should be screened for colorectal cancer beginning 5 years after radiation or at age 30, whicheveroccurs last. You should talk with your healthcare provider about which screening option is best for you. These options
include stool-based testing every three years or colonoscopy every five years.
What is stool-based testing?
If you choose stool-based testing, you will need to provide a stool sample, which will be sent to a laboratory to checkfor signs of colorectal cancer.
What is a colonoscopy?
A colonoscopy is a procedure where a thin, flexible tube connected to a video camera is inserted into your rectum andslowly guided into your colon. The doctor is able to look at the colon on a monitor, and any polyps or growths can beremoved through the tube during the exam.
A colonoscopy requires a “bowel prep” the day or night before the procedure to empty the intestines. Your healthcare
provider should give you instructions on how to do this.
The procedure may be uncomfortable, but it is usually not painful. Before you have this test, you will be given a
medicine to make you feel relaxed and sleepy.
Is there anything else that I can do to minimize the risk?
The following lifestyle changes may help to reduce the risk of colorectal cancer and will help you stay as healthy as
possible:• Eat a variety of healthy foods, with an emphasis on grains, fruits and vegetables.
– Eat five or more servings of a variety of vegetables and fruits each day.
– Choose whole grains in preference to processed (refined) grains and sugars.
– Limit consumption of red meats, especially processed meats (such as hot dogs or bologna) and those high in
fat.
–
•

Choose foods that help you maintain a healthy weight.

Adopt a physically active lifestyle.
– Engage in at least moderate physical activity (such as brisk walking) for 30 minutes or more on five or moredays of the week.
– Engaging in 45 minutes or more of moderate to vigorous activity (activities such as running, in which you are
not able to carry on a conversation without needing to catch your breath) on five or more days per week may
further reduce your risk of colorectal cancer.

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Written by Kevin C. Oeffinger, MD, Duke University Medical Center, Durham, NC.
Reviewed by Amelia DeRosa, RN, BSN, CPON; Kayla L. Foster, MD, MPH; Christine Yun, MSN, PNP, CPON.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Late Effects after Cystectomy
The information in this Health Link will help you recognize signs and symptoms of urinary bladder problems that may
occur after cystectomy.
What is a cystectomy?
A cystectomy is an operation to remove the urinary bladder.
Who needs a cystectomy?
Two groups of cancer survivors may have undergone a cystectomy during their childhood cancer treatment. The
first group includes those who had a cystectomy as part of their cancer treatment. Successful treatment of
rhabdomyosarcoma of the urinary bladder and prostate, Ewing’s sarcoma, and other sarcomas in the pelvic area
sometimes requires cystectomy. The second group includes people who required a cystectomy because of treatmentcomplications, such as hemorrhagic cystitis (bleeding) or bladder fibrosis (scar tissue).
How does urine exit the body after a cystectomy?
After the urinary bladder is removed, a new passageway is created so that urine can leave the body. Urine is removed
from the kidney in a process called “diversion.” There are three main types of diversions, based on whether urine flows
from the body spontaneously (“incontinent diversion”) or is collected in a reservoir (“continent diversion”).
An “incontinent diversion” is usually made through a loop of small intestine that is separated from the rest of thebowel and called an “ileal conduit” or “urostomy.” The ileal conduit is connected to the outside of the abdomen by
way of an opening called a “stoma”. Internally, the ureters empty into the conduit, which then serves as a pipeline forurine to flow directly through the stoma.
There are two types of “continent diversions.” The first is the cutaneous continent diversion. This reservoir is madefrom intestine and is placed within the abdomen in front of the kidneys. The ureters are then connected to this pouch.
The appendix or another short piece of small intestine is used to create an extension from this pouch through theabdominal wall to the surface of the skin, often around the belly button. This opening is called a “stoma.” This design
prevents urine from flowing back into the kidney (reflux) or spilling out onto the skin. Urine collects in the reservoir andis removed several times a day by insertion of a catheter (tube) into the stoma.
The second type of continent diversion is done by making a new bladder from bowel and is called an “orthotopic
neobladder.” The neobladder is connected directly to the urethra. Some people with a neobladder can urinate naturally,
while others may require catheterization to empty the bladder.
What problems can occur following cystectomy?
People who have an ileal conduit or ileal pouch may have leakage of urine around the stoma. This may lead to irritationof the skin and infection at the site of the stoma. Scar tissue (“strictures”) may form around the ureters or the conduitand block the flow of urine from the kidneys. Reflux of urine into the kidney may also occur, which increases the risk ofa urinary tract infection or kidney stones.
Incontinence, or the inability to control passage of urine, may occur after a neobladder is formed. People with thisproblem may benefit from muscle re-training to control urination effectively. If there is persistent leakage of urine,pressure testing of the neobladder and urethra may help decide about treatment.

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Bladder surgeries involving portions of the small intestine sometimes cause abnormal levels of chemicals and fats inthe blood. These problems may result in diarrhea, kidney stones, and/or low levels of Vitamin B12.
A cystectomy may also increase the risk of sexual dysfunction in both men and women. Surgery and medications
may be used to treat this complication.
What can I do if I have a problem following cystectomy?
If you have had a cystectomy, you will need life-long close follow-up by a urologist. An enterostomal nurse(“ET nurse”) can help by giving advice about skin care, appliance fitting, and supplies. The nurse can also help
“troubleshoot” if there are problems with catheterization.
What monitoring is recommended?
If you had an ileal enterocystoplasty (bladder surgery involving a portion of the small intestine), you should have ayearly blood test to check your Vitamin B12 level starting 5 years after your bladder surgery.
When should I call my healthcare provider?
Call your healthcare provider whenever you have fever, pain in the midback or side, blood in the urine, or severe
irritation of the skin. If you perform self-catheterization and have difficulty inserting the catheter, this is a medical
emergency that needs immediate attention. This complication may mean that the pouch has ruptured, or that thepouch will rupture if the reservoir cannot be drained properly. This can result in serious infection from leakage of urine
into the abdomen or pelvis. If you have had a cystectomy, contact your healthcare provider immediately if you havevomiting or abdominal pain. These symptoms may indicate a bowel blockage (obstruction) from scar tissue.
Written by Patricia Shearer, MD, MS, Emory Healthcare, Johns Creek, GA; Michael L. Ritchey, MD, Phoenix Childrens Hospital,
Phoenix, AZ; Fernando A. Ferrer, MD, Children’s Hospital and Medical Center of Omaha, Omaha, NE; and Sheri L. Spunt, MD, Lucile
Packard Children’s Hospital Stanford University, Palo Alto, CA.
Reviewed by Linda Rivard, RN, BSN, CPON; Kayla L. Foster, MD, MPH; and Christine Yun, MSN, PNP, CPON.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Dental Health after Cancer Treatment
Treatment for cancer during childhood often increases the risk for dental problems. As a childhood cancer survivor, it isimportant for you to understand the reasons why dental care is especially important for maintaining your health.
What are the risk factors for dental problems after childhood cancer treatment?
•

Treatment with chemotherapy before your permanent teeth were fully formed, especially if you were younger
than 5 years old at the time of your treatment•

Radiation that included the mouth and/or salivary glands•

Radioiodine therapy (I-131 thyroid ablation)•

Treatment with azathioprine (sometimes given to patients receiving a hematopoietic cell transplant [HCT])•

Chronic graft-versus-host disease (cGVHD) associated with HCT

What dental problems can occur following treatment for cancer in childhood?
Chemotherapy and radiation can affect the health of the teeth. Survivors of childhood cancer may be at increased riskof developing cavities, having abnormal development of the teeth, roots of the teeth and the protective tooth enamel,
as well as small or absent teeth. It is important to share a history of childhood cancer treatment with your dental
health professional and attend regular dental cleanings every 6 months to preserve dental health.
In addition to affecting the teeth, cancer treatments can also affect your salivary glands, gums, taste buds, the jaw
bones and the joint (called the temporomandibular joint, or “TMJ”) between the upper and lower jaw.
What can be done for these problems?
Taking care of teeth and gums is always important, and it is even more important if you have had radiation or
chemotherapy at a young age. If your gums are not healthy, they can shrink away from your teeth, causing infection in
the bone supporting the roots. This bone can dissolve away slowly, causing the teeth to become loose. This condition iscalled periodontitis (inflammation surrounding a tooth). Periodontitis can be prevented by proper brushing of your teeth
and gums and by flossing between your teeth at least once a day. Taking good care of your teeth and gums, combinedwith routine visits to your dentist, can prevent the development of cavities and gum disease.
If your permanent teeth do not develop normally, you may need caps or crowns to improve your smile and the functionof your teeth. Sometimes reconstructive surgery is needed to correct poor bone growth of the face or jaw. Radiation
can sometimes make it difficult to open your mouth fully (trismus), or cause some scarring and hardening of the jaw
muscles (fibrosis). Stretching exercises for the jaw may reduce fibrosis and improve your ability to open your mouth.
Your dentist will be able to instruct you or refer you to occupational therapy to learn these exercises. If you have crookedor small teeth, this may be improved by bonding (applying a thin coating of plastic material on the front surface of theteeth to cover any flaws). If braces are needed, your dentist will do a panorex x-ray of the teeth to see if the teeth, roots
and supporting bone are strong enough for braces. If you had high doses of radiation to the face or mouth and you
require dental surgery, you may be at increased risk of developing a bone-healing problem (osteoradionecrosis) after
the surgery. Your dentist should discuss this potential problem with a radiation oncologist before any dental surgery. If
you had an allogeneic bone marrow or stem cell transplant (from a donor other than yourself), it is important to let yourdentist know, so that the dentist can check for changes indicating cGVHD.

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What is xerostomia and what should I do if I have it?
Dry mouth, also called “xerostomia” can occur after radiation to the head or neck. Other problems related toxerostomia include persistent sore throat, burning sensation in the mouth and gums, problems speaking, difficulty
swallowing, hoarseness, or dry nasal passages. Dryness of the mouth is a result of decreased saliva and/or thickeningof the saliva, and can lead to the development of cavities.
Drinking liquids frequently and the use of artificial saliva can help relieve the symptoms of xerostomia. Sugar-freecandy stimulates saliva production. Proper brushing habits are very important for people with xerostomia, as is limiting
the intake of candy and other sweets. Your dentist may recommend application of a fluoride gel to your teeth at least
once a day. The fluoride acts on the enamel of your teeth to make it more resistant to decay. Ask your dentist about
whether you should use daily fluoride.
Should I take any special precautions when having dental work done?
Always let your dentist know if you have the following health conditions:•

Splenectomy (surgical removal of the spleen)•

High doses of radiation to the spleen (40 Gy–4000 cGy/rads or more)•

Heart valve replacement or repair with artificial or prosthetic material•

Ventricular shunt (surgical placement of a tube to drain fluid from the brain) that drains into the heart(ventriculoatrial/V-A) or venous system (ventriculovenus/V-V)•

Currently active cGVHD following HCT

In any of these situations, bacteria that normally enter the bloodstream during dental work may increase the risk ofserious infections. As a precaution against infection, if you have any of these conditions, antibiotics may be needed
before any dental work is done.
When dental work is planned, ask your dentist if you need to take antibiotics before the procedure.
What is the risk of developing oral cancer?
People who have had radiation to the head and neck during childhood, or who have cGVHD after bone marrow or stem
cell transplant, may be at increased risk for oral cancers. Using tobacco in any form or using alcohol in combination
with smoking greatly increases this risk. Infection with certain forms of the human papillomavirus (HPV) also increases
this risk. Your dentist should perform an oral cancer screening exam during each visit.
If you notice any of the following, notify your dentist immediately:•

A sore that does not heal or that bleeds easily•

A change in the color of your mouth tissues•

A lump, thickening or rough spot in the mouth•

Pain, tenderness or numbness anywhere in the mouth or on the lips

Most of the time, these symptoms do not indicate any problem, but a dentist can tell if they are the sign of a serious
problem.

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What should I do to keep my teeth and mouth as healthy as possible?
Follow these recommendations (unless your dentist recommends otherwise):•

See your dentist regularly at least every six months. Make sure that your dentist knows your health history
and the treatment you received. (Ask your oncologist for a summary of your treatment). Be sure that your visit
includes an oral cancer screening, and be sure to notify your dentist if you notice any warning signs of oral
cancer.

•Have a panorex x-ray done before dental/orthodontic procedures to evaluate the root development of yourteeth and determine if any modifications need to be made to your dental treatment plan.

•

Brush your teeth at least twice a day.

•–

Use a fluoride-containing toothpaste to help prevent tooth decay.

–

Place your brush at a slight angle toward the gum when brushing along the gum line.

–

Use a soft-bristle toothbrush, as recommended by your dentist.

–

Clean all surfaces of the teeth.

–

Brush your tongue to remove bacteria that can cause bad breath.

Floss your teeth at least once a day.
–Floss carefully between teeth because brushing alone does not remove plaque between teeth.

–

Use a gentle touch to avoid injury to gums.

–

It is normal to have a small amount of bleeding when flossing, but if the bleeding increases or your gums are
red and puffy, this may be a sign of infection and you should notify your dentist.

•

Use antibacterial, alcohol-free fluoride mouth rinses (your dentist can recommend the best ones for you).

•

Drink liquids frequently and/or use artificial saliva (available at most pharmacies without a prescription).

•

Apply fluoride frequently. Your dentist may recommend a daily fluoride rinse or gel that you can use at home
after brushing, in addition to the special fluoride application you may receive at your regular dental cleanings.

•

Limit sweets and carbohydrate-rich foods.

•

Do not use tobacco products and use alcohol only in moderation (check with your healthcare provider tosee if you should drink alcohol at all, since alcohol may increase other problems following childhood cancer
treatment).

•

Notify your dentist immediately if you develop any signs of infection in your mouth or gums, such as
redness, tenderness, excessive bleeding of gums, painful teeth, and/or increased areas of sensitivity.

For more information about dental health issues following childhood cancer treatment:•

American Dental Association’s dental health website at www.mouthhealthy.org

Adapted by Deborah Lafond, MS, RNCS, PNP, CPON®, Children’s National Medical Center, Washington, DC, from “Save Your Smile”
by Melissa Hudson, MD, St Jude Children’s Research Hospital, After Completion of Therapy (ACT) Clinic, used with permission.
Reviewed by Sarah Ford, MS, PA-C; Kayla L. Foster, MD, MPH; and Melissa Acquazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
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Healthy living after treatment of childhood, adolescent, and young adult cancer
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Staying Healthy through Nutrition and Physical Activity
Good nutrition and regular exercise offer many benefits to childhood cancer survivors. These include:•

Promoting healing of tissues and organs affected by cancer and its treatment•

Building strength and endurance•

Reducing the risk of certain types of adult cancers and other diseases suc as diabetes, high blood pressure, andobesity•

Decreasing stress and providing a feeling of well-being

Impact of Childhood Cancer on Nutrition and Physical Activity
The effects of childhood cancer on nutrition and physical activity will be different for each survivor. Cancer affects
nutrition in several ways. Some survivors may have difficulty gaining weight, while others may have problems withgaining too much weight. Physical activity is an important factor in maintaining a healthy body weight. There are manyfactors that can influence a survivor’s ability to be physically active; however, childhood cancer and its treatment should
not be used as an excuse for not eating a healthy diet or staying physically active. Many survivors, just like many people
who have never experienced cancer, have poor health habits. Now is a good time to begin making healthy choices about
what you eat and stay active. These choices can have a positive effect on your health for many years to come.
Developing a Healthy Nutrition Plan
Suggestions for good nutrition include:•

Choosing a variety of foods from all the food groups. Use the interactive
customized guide at www.choosemyplate.gov to help develop a well-balanced
diet and activity plan.

•

Eating five or more servings a day of fruits and vegetables, including citrus fruits
and dark-green and deep-yellow vegetables.

•

Limiting juice to 4 ounces of 100% fruit or vegetable juice per day.

•Eating plenty of high-fiber foods, such as whole grain breads, rice, pasta, and cereals.

•

Limiting refined carbohydrates, including pastries, sweetened cereals, soft drinks, and sugars.

•

Decreasing the amount of fat in your meals by baking, broiling or boiling foods.

•

Limiting intake of red meat and eating fish, poultry, or beans instead. When eating meat, select leaner and smaller
portions.

•

Limiting fried and high-fat foods, such as fries, snack chips, cheeseburgers, and pizza.

•

Choosing low-fat milk and dairy products.

•

Avoiding salt-cured, smoked, charbroiled, and pickled foods.

•

For adults, limiting alcoholic drinks to less than two a day for men and one for women.

If you need to lose or gain weight, consult with your health care team and/or a nutritionist to develop a nutrition plan.
Herbal or dietary supplements should be discussed with your team. There are several questions you should ask yourself
to make sure your nutrition plan will be effective.
•

Do you have a realistic, achievable weight goal?

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Does your plan include foods that you will enjoy eating for the rest of your life, not just a few weeks or months?

•

Does your plan include a variety of foods?

•

Are foods on your plan easily available at your supermarket?

•

Does your plan fit into your lifestyle, daily schedule and budget?

•

Does your plan include lifestyle changes that will help you maintain your weight change?

Developing a Healthy Exercise Plan
Check with your healthcare team before starting an exercise plan or taking part in new sports and recreational
activities. Your healthcare provider can make you aware of the activities that you can safely take part in and those you
should avoid.
When choosing an exercise plan, ask yourself these questions:•

Do you have reasonable goals based on your present strength and endurance?

•

Is the activity safe for you to perform?

•

Does the plan fit into your lifestyle and schedule?

•

Does the activity require special equipment or protective gear and will your budget cover the expense?

•

Do you need to make changes in the sport or activity based on a special need?

•Do you enjoy doing the sport or activity?

Here are a few helpful suggestions when implementing your exercise plan:•

Start out slow. Don’t try activities that are too strenuous or put you at risk for muscle strain.

•

Begin your exercise plan with a warm-up program and end with a cool-down activity, such as stretching andslow easy movements.

•

Use correct posture when exercising.

•Exercise until you are tired, but not in pain.

•

Identify the muscles you want to strengthen and choose exercises that work on those muscles.

•

Alternate exercises to work different muscles and different parts of your body.

•

To avoid injury, use the right equipment and shoes. Avoid running, jogging, or aerobic dancing on hard surfaces
such as asphalt or concrete.

The American Cancer Society recommends having a physically active lifestyle. Adults should get at least 150 minutesof moderate physical activity (brisk walking, bicycling, vacuuming, gardening), or 75 minutes of vigorous physicalactivity (running, aerobics, heavy yard work), or a combination of these each week, preferably spread throughout
the week. Children and adolescents should engage in at least 60 minutes each day of moderate to vigorous physicalactivity each day (running, aerobics, heavy yard work), with vigorous activity at least 3 days each week. Here are some
practical suggestions to try to work physical activity into your daily schedule.
•Park a good distance from your place of work and walk the extra distance each day.

•Set aside 30 minutes a day to take a brisk walk.

•

Take the stairs instead of the elevator.

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If you have a sit-down job, get up and stretch your muscles every hour and take a walk during your lunch or
break.

•

Ride a bike to work or for running errands.

•

If you have a dog, take him/her on a brisk walk every day.

•

Plant a garden, wash your car, mow the lawn, paint furniture, clean out the garage and catch up on all thosechores you have been meaning to do—instead of watching TV or playing on the computer.

•

Keep your body moving while watching TV or reading the newspaper on a stationary bike or treadmill.

•Plan active outings with family or friends.

•

Exercise with a partner.

•

Join a sports team.

Physical Activity for Survivors with Special Needs
Survivors who have special needs can take part in most activities, but the help of a physical or occupational therapist
may be needed to adapt the activity for success. A social worker may be able to help find insurance coverage or otherresources for special equipment. Specialized programs for individuals with special needs, organizations and otherresources are often available through your healthcare center, in your local community, and at www.ncpad.org.
Adapted by Sharon A. Frierdich, RN, MS, CPNP, University of Wisconsin Hospital and Clinics, Madison, WI, from “Staying Physically
Healthy, Play Safely, Play Well,” St. Jude Children’s Research Hospital, used with permission.
Reviewed by Linda Rivard, RN, BSN, CPON®; Christine S. Yun, MSN, PNP, CPON®; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

School after Cancer Treatment
Treatment for cancer during childhood or adolescence may affect educational progress due to prolonged absences
or reduced energy levels that frequently occur during or after treatment. In addition, some types of cancer may
require therapy to control or prevent spread of the disease to the brain and/or spinal cord (central nervous system).
This therapy can sometimes affect memory and learning abilities. Parents and teachers should be aware of potential
educational problems that may be related to cancer treatment. You/your child or teen may be eligible for special
accommodations at school which may also require specialized testing.
What increases the risk of educational problems?
Factors that may place children and teens at increased risk for difficulties in school include:•

Diagnosis of cancer at a very young age•

Numerous or prolonged school absences•

A history of learning difficulties before the cancer diagnosis•

Cancer treatment that results in reduced energy levels•

Cancer treatment that affects hearing or vision•

Cancer treatment that results in physical disabilities•

Cancer therapy that includes treatment to the central nervous system (see below).

Are children and teens with certain types of cancer at higher risk of developing educationaldifficulties?
Yes, children and teens with the types of cancer listed below are more likely to have received treatments that may
affect learning and memory. Since treatments for these types of cancer vary widely, not everyone who was treated forthese cancers are at increased risk.
•

Brain tumors•

Tumors involving the eye or ear•

Acute lymphoblastic leukemia (ALL)•

Non-Hodgkin lymphoma (NHL)What types of treatment place children and teens at higher risk for learning and memory
problems?
•

Methotrexate—if given in high doses into the veins intravenously (IV) or injected into the spinal fluid [intrathecally(IT) or intra-ommaya (IO)]•

Cytarabine—if given in high doses intravenously (IV)•Surgery involving the brain•

Radiation to the head/brain or total body irradiation(TBI)•

Cisplatin or carboplatin (may affect hearing)

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What testing is recommended?
Any young person who has had any of the above cancer treatments, or who is having difficulties in school, should
undergo a specialized evaluation by a pediatric psychologist (neuropsychological testing) at the time of entry into
long-term follow-up. This type of testing will measure IQ and school-based skills, along with more detailed information
about how the child or teen processes and organizes information.
Even if the initial neuropsychological evaluation is normal, it is important for parents and teachers to remain watchful.
Further neuropsychological evaluations may be necessary if the child or teen begins having trouble in school ordevelops any of the problems listed in the section below. In addition, repeat testing is often recommended at times
when academic challenges are more likely to occur, such as at entry into elementary school, middle school, highschool, and during pre-college planning.
What learning problems may occur?
The brain is a very complex structure that continues to grow and develop throughout childhood and adolescence.
Some problems may not become apparent until years after therapy is completed. Common problem areas include:•

Handwriting•

Memory•Spelling••

Reading

Processing (ability to complete assignments that
require multiple steps)•

Vocabulary•

Planning

•

Math

•

Organization•

Concentration•

Problem-solving•

Attention span•

Social skills•

Ability to complete tasks on time

What can be done to help with learning problems?
If a problem is identified, special accommodations or services can be requested to help maximize the student’s
learning potential. The first step is to schedule a meeting with the school to develop a specialized educational plan,
this may include a 504 plan or an individualized education plan (IEP).Examples of strategies that are often helpful forchildren and teens with educational problems related to cancer treatment include:•

Seating near the front of the classroom•

Assignment of a classroom aide•

Minimizing the amount of written work required••

Use of tape-recorded textbooks and lectures

Extra help with math, spelling, reading, andorganizational skills•

Use of a computer keyboard instead ofhandwriting•

Access to an elevator•

Extra time for transition between classes•

Use of a calculator for math•Duplicate set of textbooks to keep at home•

Modification of test requirements (extra time, oral
exams instead of written exams)

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What laws protect the rights of students who have undergone treatment for cancer?
In the United States, there are three public laws that protect the rights of students with educational problems related tocancer treatment. These laws are:
The Rehabilitation Act of 1973 – Section 504
This legislation provides accommodations for students with a “physical or mental impairment which substantiallylimits one or more major life activities,” or students who have “a record of such impairment,” or who are “perceived
as having such an impairment” (The Rehabilitation Act, 1973). Qualifying conditions include chronic illnesses suchas cancer, as well as many other disabilities, including hearing problems, vision problems, learning disabilities,
speech disorders, and orthopedic handicaps. All childhood cancer survivors in the United States are eligible foraccommodations under this law, and all educational institutions receiving federal funding (including colleges anduniversities) are required to comply. Accommodations may include modifications in the curriculum (such as allowing
the use of a calculator and extra time for assignments or test-taking) and the environment (such as seating near thefront of the classroom or allowing extra time between classes).
The Individuals with Disabilities Education Act (IDEA)The IDEA legislation (PL 105-17) requires that public schools provide “free and appropriate education in the least
restrictive environment” for disabled students between the ages of 3 and 21 years of age. In order to qualify for special
education services under IDEA, the student must meet qualifications under at least one disability outlined in the law—
those that most commonly apply to students treated for cancer include “specific learning disability,” “traumatic brain
injury,” or “other health impairment.” To access services under the IDEA legislation, parents must initiate the processby requesting that the student be evaluated for an “Individualized Education Plan” or IEP. The student will then undergo
an assessment process to determine what assistance is required. A conference is then held to discuss the resultsof the evaluation and, if the student qualifies, to determine an individualized plan to meet the identified specialized
educational needs. Services available under the IDEA legislation include tutoring, specialized classroom placements(such as a resource room), psychological services, adaptive physical education, physical, occupational and speech/
language therapy, and transportation services. All services and accommodations required by the student should bespecified in the IEP (the written document describing the special education program). The IEP should be reviewed andupdated on an annual basis to assure that it continues to meet the student’s educational needs.
The Americans with Disabilities Act (ADA)The ADA law (PL 101-336) protects against discrimination in employment, transportation, communication, government,
and public accommodations for people with disabilities. It guarantees equal access to public spaces, event, andopportunities and may be particularly helpful for students seeking higher education or employment.
Where can I get more information?
Additional information is available from the Center for Parent Information and Resources www.parentcenterhub.org
American Childhood Cancer Organization, for the free publication: Educating the Child with Cancer, a Guide for Parents
and Teachers (phone: 1-855-858-2226, ext. 101) or www.acco.org
US Department of Education; Office for Civil Rights. Protecting Students with Disabilities www2.ed.gov/about/offices/
list/ocr/index.html

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Written by Wendy Landier, PhD, CPNP, Children’s Hospital of Alabama, Birmingham, AL.
Reviewed by Casey DeBias, MSN, APRN, FNP-BC, CPHON; Christine S. Yun, MSN, PNP, CPON; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Keeping Your Eyes Healthy
Radiation to the brain, eye, or eye socket (orbit) during treatment for childhood cancer can have a long-lasting effect on
the eyes. Radioiodine (I-131) treatment and chronic graft-versus-host disease (an immune response that can develop
after bone marrow or stem cell transplant) can also affect the eyes. Because vision can have a significant impact ondaily living, it is important for survivors who received these treatments to have their eyes checked regularly.
How do the eyes work?
The eyes are remarkable organs, allowing light to be converted into impulses thatare transmitted to the brain, where images are perceived. The eyes are located in
the area of the skull known as the orbit or eye socket. A thin layer of tissue called
the conjunctiva covers and protects the eye and eyelids. Tears are produced in the
lacrimal gland, located in the outer corner of the eye socket, above the eyeball.
Tears flow over the eye, providing lubrication, and drain into a tiny canal at the innercorner of the eye, called the lacrimal duct. Light enters the eye through a clear layerof tissue known as the cornea. The cornea bends and focuses the light and sends
it through the opening of the eye known as the pupil. The pupil controls how muchlight enters the eye. Behind the pupil is the lens of the eye, which focuses the lightonto the retina, the membrane along the back wall of the eye. The nerve cells in
the retina change the light into electrical impulses and send them through the optic
nerve to the brain, where the image is perceived.

Lens
Retina
Pupil
CorneaConjunctiva
Optic nerve

What eye problems can develop following treatment for childhood cancer?
Cataracts: Clouding of the lens of the eye. When this happens, light cannot pass through the lens easily. Common
symptoms of cataracts include painless blurring of vision, sensitivity to light and glare, double vision in one eye, poornight vision, fading or yellowing of colors, and the need for frequent changes in glasses or contact lens prescriptions(see related Health Link: Cataracts).
Xerophthalmia: Dry eyes resulting from decreased tear production due to radiation or chronic graft-versus-hostdisease. Symptoms include pain at the surface of the eye and light sensitivity.
Lacrimal duct atrophy: Shrinking of the lacrimal duct, which drains tears from the eye. Lacrimal duct atrophy can
result in problems with increased tearing. This can be caused by radiation to the eye or orbit, or by radioiodine (I-131)
therapy given for treatment of thyroid cancer.
Other eye problems:
The following eye problems are less common and are usually seen only in survivors who had radiation doses of 30 Gy
or 3000 cGy/rads or higher directed at the eye or orbit:
Orbital hypoplasia: Underdevelopment of the eye and surrounding tissues, caused by radiation to the eye or orbit.
This can result in a small eye and orbit (orbital hypoplasia).
Enophthalmos: Sunken eyeball within the orbit as a result of radiation.
Keratitis: Inflammation of the cornea (the clear, outer surface of the eye). This can cause pain at the surface of the eye
and light sensitivity.
Telangiectasias: Enlargement of blood vessels in the white part of the eye. These do not usually cause any symptoms
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but are sometimes bothersome because of their appearance.
Retinopathy: Damage to the retina (the back surface of the eye where visual information is passed from the eye to thebrain). Painless vision loss is the major symptom of retinopathy.
Maculopathy: Damage to the macula (area of central vision within the retina), which may result in blurred vision.
Optic chiasm neuropathy: Damage to the nerves that send visual information from the eye to the brain. This canresult in vision loss.
Papillopathy: Swelling of the optic disc (area where the optic nerve enters the eye).
Glaucoma: Increased pressure within the eye. This can damage the optic nerve and result in vision loss.
What cancer therapies increase the risk of developing these eye complications?
•Radiation therapy at doses of 30 Gy (3000 cGy/rads) or higher to the following areas increases the risk oftreatment-related eye problems:– Eye– Orbits– Head/Brain•

Other factors that may increase the risk for developing certain eye problems include:– Radioiodine (I-131) treatment for thyroid cancer (increased risk for lacrimal duct atrophy)– Chronic graft-versus-host disease following bone marrow, cord blood, or stem cell transplant (increased risk
for xerophthalmia)– Diabetes mellitus (increased risk for problems involving the retina and optic nerve)– High blood pressure (increased risk of optic chiasm neuropathy)– Frequent exposure to sunlight (increased risk for cataracts)– Certain chemotherapy drugs, such as, actinomycin-D and doxorubicin, which can increase the risk of eye
problems when given together with radiation.

What monitoring is recommended?
•

Evaluation by an eye specialist (ophthalmologist or optometrist) at least once a year is recommended for anyone
who:– Had radiation to the head, brain, eyes, or total body irradiation (TBI)– Had a tumor involving the eye–

Has graft-versus-host disease (as a result of bone marrow, cord blood, or stem cell transplant)

Note : An ophthalmologist is a medical doctor (MD or DO) who specializes in eye problems—this is different
from a doctor of optometry (OD), who is also a vision specialist but not a medical doctor. Examination by aneye specialist should include vision screening, examination for cataracts, and a full examination of the internal
structures of the eye. People who develop vision problems should be followed regularly by an ophthalmologist.
•

Evaluation by an ocularist (a trained person who makes and fits artificial eyes) at least once a year isrecommended for anyone who has had:
– An eye removed because of cancer treatment and/or complications related to treatment–•

An artificial eye (prosthesis) that does not fit well

Evaluation by an ophthalmologist is recommended on an as-needed basis for people who had Radioiodine (I-Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer131) treatment if they develop excessive tearing.
If you develop any of the following symptoms, seek prompt medical evaluation. In some cases, referral to an
ophthalmologist may be needed:– Blurry vision– Double vision– Blind spots– Sensitivity to light– Poor night vision– Persistent irritation of surface of eye or eyelids– Excessive tearing/watering of eyes
– Pain within the eye– Dry eyes
How are eye problems treated?
Cataracts: Not all cataracts need treatment. In many cases, an ophthalmologist may monitor the vision closely overmany years and will recommend treatment if and when it becomes necessary. The only treatment for cataracts issurgical removal of the lens and replacement with an artificial lens. Today, cataract surgery is a low-risk procedure thatis performed on an outpatient basis and works well in restoring vision.
Orbital hypoplasia: Usually no treatment is needed for orbital hypoplasia. In severe cases, rebuilding of the bones
around the eye may be possible.
Enophthalmos: Plastic surgery can be done to build up the orbit.
Lacrimal duct atrophy: A surgical procedure to widen the tear drainage system can be performed if heavy tearing is asignificant problem.
Xerophthalmia: Treatment of dry eye includes the frequent use of artificial tears (eye drops) or ointments to moisten thesurface of the eye. In severe cases, the tear drainage system can be blocked by surgery to reduce the drainage of tears
from the eye.
Keratitis: The frequent use of artificial tears (eye drops) or ointments to moisten the surface of the eye is recommended.
Patching the affected eye during sleep may also promote healing. Keratitis caused by infection is treated with antibiotic
eye drops or ointment. Rarely, surgical replacement (transplant) of the cornea is necessary.
Telangiectasias: No treatment is necessary.
Retinopathy and maculopathy: Retinopathy may require laser or photocoagulation (heat) treatment of the retina.
Rarely, surgery to remove the eye is necessary in severe cases.
Optic chiasm neuropathy: No treatment available.
What can be done if there is impaired vision?
If impaired vision is detected, it is important to follow the recommendations of your ophthalmologist regarding
treatment. If vision is not correctable, services are available in most communities to assist people with visual
impairments.
In addition, in the United States, services are available for people under 22 years of age through the local public school
district or referral agencies (available under the Individuals with Disabilities Education Act, PL 105-17). Sometimes
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special accommodations, such as seating in the front of the classroom are all that is needed, but this usually requiresthat the parent request an Individualized Education Plan (IEP) for the child through the school district (see related Health
Link: “School After Treatment for Childhood Cancer”).
The Americans with Disabilities Act (ADA, PL 101-336) guarantees people with visual impairment equal access to public
events, spaces, and opportunities.
How can I protect my vision?
It’s important to protect your eyes whether or not you have treatment-related eye disorders. Precautions you can takeinclude:• Wear sunglasses with ultraviolet (UV) protection when in bright sunlight.
• When participating in sports, be sure to select protective eyewear that is appropriate for the sport. Eyewear worn
for sports should be properly fitted by an eye care professional.
• Avoid toys with sharp, protruding, or projectile parts.
• Never play with fireworks or sparklers of any kind to avoid accidental injury.
• Be careful when working with hazardous household chemicals.
• Wear protective eyewear when using a lawnmower, power trimmer, or edger, and when working with dangerous
equipment in the workshop.
•

If you do experience an eye injury, seek medical attention promptly.

Written by Teresa Sweeney, RN, MSN, CPNP, St. Jude Children’s Research Hospital, Memphis, TN.
Reviewed by Angela Yarbrough DNP, APRN, FNP-BC, CPON®; Kayla L. Foster, MD, MPH; and Christine Yun MSN, PNP, CPON®.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities, or
damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Ovarian and Reproductive Health after Cancer Treatment
The effects of childhood cancer therapy on reproductive function depend on many factors, including age at the timeof cancer therapy, the specific type and location of the cancer, and the treatment that was given. It is important tounderstand how the ovaries function and how they may be affected by cancer treatment.
The reproductive system
At birth, the ovaries contain all the eggs they will ever have. When the time comes to begin puberty, the pituitary
gland in the brain signals the ovaries by releasing two hormones (FSH and LH). The ovaries secrete the estrogen andprogesterone, which are necessary for reproductive function. Normally, during a monthly menstrual cycle, one egg
matures and is released from the ovaries. If the egg is not fertilized, menstruation begins. The cycle then repeats itself
about every 28 days. With each menstrual cycle, the supply of eggs decreases. When most of the eggs are depleted
from the ovaries, menopause begins. During menopause, the menstrual cycles stop, the ovaries stop making hormones,
and pregnancy progressively becomes less likely.
How does cancer therapy affect the ovaries?
Certain chemotherapy drugs, radiation therapy, and surgery can sometimes damage the ovaries, decreasing ovarian
hormone production and reducing the reserve supply of eggs. When the ovaries are not able to produce sufficienthormones to regulate ovulation and menstruation, otherwise known as premature ovarian insufficiency (POI), an
individual may not begin puberty and menstruation, may have irregular menstrual cycles or menstrual cycles may stopearlier than expected (also known as premature menopause). Additionally, when the ovaries do not function properly,
this can result in infertility or difficulty becoming pregnant.
What are the causes of premature ovarian insufficiency (POI)?
Chemotherapy of the “alkylator” type (such as cyclophosphamide, thiotepa, melphalan and busulfan) is most likely
to affect ovarian function. The total dose of alkylators used during cancer treatment is important in determining the
likelihood of ovarian damage. With higher total doses, the likelihood of damage to the ovaries increases. Heavy metal
chemotherapy (cisplatin and carboplatin) may also damage the ovaries. If treatment for childhood cancer included a
combination of both radiation and these chemotherapies, the risk of POI may be higher .
Radiation therapy can affect ovarian function in two ways:
Radiation aimed at or near the ovaries. The age of the person at the time of radiation and the total radiation dosecan affect whether or not POI occurs. With lower doses of radiation, younger people tend to have less damage to theovaries than those who received equal doses but who were teenagers or young adults at the time of radiation. Highdoses of radiation usually result in a loss of ovarian function and infertility regardless of age.
Radiation to the hypothalamic and pituitary gland regions in the brain. The hypothalamus and pituitary gland
regulate the production of two hormones (FSH and LH) needed for proper ovarian function.
Radiation to the brain at higher doses can damage to these areas of the brain leading to low levels of these hormones.
Surgery. If both ovaries were removed (bilateral oophorectomy) during cancer therapy, this always results in a loss ofovarian function and infertility. This type of POI is sometimes called “surgical menopause.” If one ovary was removed(unilateral oophorectomy), menstruation may stop earlier than it otherwise would have.

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What types of cancer therapy increase the risk of POI?
Individuals who received the following therapy may be at risk for POI:•

Chemotherapy - the class of drugs called “alkylators” can cause POI when given in high doses. Heavy metal
chemotherapy can also affect ovarian function. Examples of these drugs are:Alkylating agents:– Busulfan– Carmustine (BCNU)– Chlorambucil– Cyclophosphamide (Cytoxan®)– Ifosfamide
Heavy metals:– Carboplatin– Cisplatin

•

–
–
–
–

Lomustine (CCNU)
Mechlorethamine (nitrogen mustard)
Melphalan
Procarbazine–

Thiotepa

Non-classical alkylators:– Dacarbazine (DTIC)–

Temozolomide

Radiation therapy to any of the following areas:– Pelvis– Lower spine (sacral area)– Total body irradiation (TBI)– Head/brain especially if dose was 30 Gy (3000cGy/rads) or higher

Surgery:– Removal of one or both ovaries
What are the effects of childhood cancer therapy on the female reproductive system?
•

1. Failure to enter puberty. Pre-pubertal individuals who received cancer therapy that results in ovarian failure willneed hormonal therapy (hormones prescribed by a doctor) to progress through puberty. If this occurs, referral to an
endocrinologist (hormone doctor) should be made for further evaluation and management.
2. Temporary cessation of menstrual cycles. Many who were already menstruating will stop having monthly
periods during their cancer therapy. In most cases, menstrual cycles will resume sometime after cancer treatment
ends, although the timing of this is unpredictable. In some cases, it may take up to several years to restart
menstruation. Since eggs are released before the menstrual cycles, pregnancy can occur before the menstrual
periods resume. If pregnancy is undesired, birth control (contraception) should be used, even if the menstrual
cycles have not resumed.
3. Permanent cessation of menstrual cycles (premature menopause). Menopause (the permanent cessation of
menstrual cycles) occurs at an average age of 51. People who were already menstruating prior to their cancer
therapy sometimes develop ovarian failure as a result of their cancer treatment and never resume menstrual
cycles. Others may resume menstrual cycles, but then stop menstruating much earlier than would normally be
expected. If a person is currently having menstrual periods but received chemotherapy or radiation that can affectovarian function or had one ovary removed, they may still be at risk for entering menopause at an early age. If aperson at risk for premature menopause desires to have children, it is best not to delay childbearing beyond theearly thirties, because the period of fertility may be shortened after having cancer therapy.
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4. Lack of sex hormones. People with ovarian failure do not make enough estrogen. Estrogen is needed forfunctions other than reproduction—it is very important for maintaining strong healthy bones, a healthy heart,and overall well-being. Young people with ovarian failure should see an endocrinologist (hormone specialist) for
hormone replacement therapy, which will be necessary until they reach middle age.
5. Infertility. Infertility is the inability to achieve a pregnancy after at least one year of unprotected intercourse.
Infertility occurs when the ovaries cannot produce eggs (ovarian failure), or when the reproductive organs areunable to sustain a pregnancy. Infertility may be the result of surgery, radiation therapy, chemotherapy, or any
combination of these. There may also be other reasons for infertility that are unrelated to cancer therapy.
If a person has regular monthly menstrual periods and normal hormone levels (FSH, LH and estradiol), they arelikely to be fertile and able to have a baby. If they do NOT have monthly menstrual periods, or if they have monthly
menstrual periods ONLY with the use of supplemental hormones, or if they had to take hormones in order to enteror progress through puberty, they are likely to be infertile.
People who had surgical removal of both ovaries will be infertile. Those who had surgical removal of the uterus(hysterectomy) but still have functioning ovaries can become a parent with the use of a gestational surrogate(another person who carries the pregnancy to term). People who are infertile should discuss their options with afertility specialist and their oncologist. The use of donor eggs may be an alternative for some. Additional options
may include adoption of a biologically unrelated child or child-free living.
6. Pregnancy risks. Certain therapies used during treatment for childhood cancer can sometimes increase therisk of problems that a person may experience during pregnancy, labor, and childbirth. The following may be atincreased risk:–

Those who had radiation to the pelvis, lower spine, or total body (TBI) may have an increased risk of
miscarriage, premature delivery, or problems during labor.

–Those who received anthracycline chemotherapy (such as doxorubicin or daunorubicin), and those who
received radiation to the abdomen, chest or thoracic spine may be at risk for heart problems that can worsenwith pregnancy and labor (see related Health Link: “Heart Health”).

People with these risk factors should be followed closely by an obstetrician who is qualified to care for high-risk
pregnancies.
Fortunately, in most cases, there is no increased risk of cancer or birth defects in children born to childhood cancer
survivors. In rare cases, if the type of cancer in childhood was a genetic (inherited) type, then there may be a risk ofpassing that type of cancer on to a child. You should check with your oncologist if you are not sure whether the type ofcancer you had was genetic.
What monitoring is recommended?
Those who have had any of the cancer treatments that may affect ovarian function should have a yearly checkup that includes careful evaluation of progression through puberty, menstrual and pregnancy history, and sexualfunction. Blood may be tested for hormone levels (FSH, LH, and estradiol) if a problem is suspected. If any problems
are detected, a referral to an endocrinologist (hormone specialist) and/or other specialists may be recommended. For
people with ovarian failure, a bone density test (special type of x-ray) to check for thinning of the bones (osteoporosis)
may also be recommended.

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Written by: Marcia S. Leonard, RN, CPNP, C.S. Mott Children’s Hospital, Ann Arbor, MI.
Reviewed by Katy Tomlinson, BSN, RN; Lillian R. Meacham, MD; Melissa Acquazzino, MD, MS; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Finding and Paying for Healthcare
As a childhood cancer survivor, it is important for you to have regular medical check-ups, since some of the treatmentsthat you received may increase your risk for health problems as you get older. Sometimes it is difficult to find and pay
for the medical care that you need. There are several things you can do to make sure you are getting the best possible
care for your needs. Here are some suggestions.
If possible, find a long-term follow-up clinic. Many childhood cancer programs have long-term follow-up clinics. A
directory of long-term follow-up clinics affiliated with Children’s Oncology Group institutions can be found at this link:
https://www.cogmembers.org/public/lateeffects/default.aspx. If you are still followed in a childhood cancer center, or if
there is a childhood cancer center near where you live, contact that center to discuss your options for obtaining longterm follow-up care. Long-term follow-up clinics usually screen for late effects and educate survivors about ways tolower the risk of health problems after cancer. They are generally an excellent place to get a complete health evaluation,
but are not usually designed to meet the everyday healthcare needs of survivors and may only see survivors until theyreach adulthood. Even if you are attending a long-term follow-up care clinic, it is also important to find a primary
healthcare provider who can take care of your general medical needs.
Choose a primary healthcare provider in your community. The best primary healthcare providers for adults areusually those who specialize in family practice or internal medicine. The chance of finding a primary healthcare provider
who has experience taking care of childhood cancer survivors is low, due to the rarity of cancer in children. However,
it is important to look for a healthcare provider who is thorough, well-trained, and a good listener. Ask friends andfamily members to help you identify healthcare providers with these qualities who are practicing in your area. Make an
appointment for a general check-up and discuss your past medical history and health risks during this visit. It is best to
do this introductory visit at a time when you are well, and not when you are being seen because of an illness.
Tell your healthcare provider about the Childhood Cancer Survivor Long-Term Follow-Up Guidelines, available
on the Children’s Oncology Group website at www.survivorshipguidelines.org. This comprehensive set of healthcare
screening and management guidelines is designed for use by healthcare professionals who are providing ongoing
medical follow-up for childhood cancer survivors.
Organize a medical team to provide your local care. Get advice from your childhood cancer doctor and your primary
healthcare provider about who should be on your medical team. Your team should always include a primary healthcare
provider and a dentist. Depending on your situation, you may also need to include other professionals that are importantfor your continued health, such as a physical therapist or psychologist. Your primary healthcare provider can help you
select these individuals and provide referrals for their services.
Share your medical records with all the members of your medical team. If possible, ask the oncologist who treatedyour childhood cancer to provide you with a survivorship care plan that includes a summary of your diagnosis andtreatment, future health risks, and recommended screening. Ask your oncologist to share a copy of your treatment
summary with all your healthcare providers. Keep a copy of the care plan and important sections of your pediatric
medical records in a personal medical file. Be sure that every new healthcare provider you see is aware of your medical
history and any special health risks you may have because of your cancer treatment. If you need help in obtaining your
medical records, call the hospital, clinic, or medical center where you received your treatment.

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Be a partner in the healthcare that you receive. To find out if you are getting adequate care, ask yourself thefollowing questions:• Do I know my cancer diagnosis and specific treatment I received?
• Do I know about the health problems that can occur after this treatment?
• Have I shared this information with my healthcare providers?
• Does my healthcare provider check periodically for health problems specifically related to my childhood
cancer?
• Does my healthcare provider advise me about things I should or should not do to keep healthy after mytreatment for childhood cancer?
Explore all resources for paying for healthcare. Healthcare is expensive and people who have had a serious illness
often face many hurdles when trying to obtain adequate follow-up care. In the United States, insurance companies are
now required to provide coverage for childhood cancer survivors, regardless of pre-existing medical conditions. The
law also now provides the option of coverage under a parent’s health insurance policy for young adults under age 26.
More information about your rights and protections under the health care law (commonly known as the “Affordable
Care Act”), is available at this link: https://www.healthcare.gov/health-care-law-protections/. If you aren’t insured, you
should seek assistance from a local social service organization or your hospital social worker to identify your coverage
options.
As a survivor of childhood cancer, you have already overcome many obstacles. The process of obtaining and paying for
healthcare can sometimes seem discouraging, but it is worth the effort.
Survivorship Healthcare Coverage Checklist
Define your current healthcare needs. Ask yourself:

•
•
•
•
•

Do I mainly need a healthcare provider for general check-ups?
Do I have chronic health problems that require frequent medical visits?
Do I have problems that need periodic monitoring by specialists?
Am I on expensive prescription medications?
Do I require prosthetic or rehabilitation services?

Explore all resources for healthcare coverage:

•
•
•
•
•

Coverage through a parent’s or spouse’s policy
Health insurance coverage offered by your college or employer
State or federal public assistance programs that may substantially lower the cost of coverage
Discounted or free healthcare through health department clinics or church-based programs
Low cost or free prescription programs provided by some pharmaceutical companies for people with low income

If you are insured, get the facts about your policy.

•
•
•
•
•

What services are covered?
Does your plan offer a discounted prescription program?
Are referrals to specialists controlled through a primary care physician?
Is coverage in effect only while the patient is a full-time student?
Does coverage expire at certain age?

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Ask for help in understanding current resources and locating new ones.

•

Ask family members, friends, hospital or clinic insurance managers, and insurance representatives to explain
unclear details about insurance benefits.
• Call a clinic or hospital social worker to ask for help in finding state or community healthcare resources.
• Check out services offered by national nonprofit organizations (example, Lions Club for ocular prostheses).
• Be proactive in obtaining and maintaining health insurance coverage.
•

Visit www.healthcare.gov to determine your options for insurance coverage and to determine whether you qualify
for discounted or free coverage available to people with low income or disability.
• Avoid lapses in coverage. Plan for transitions in health insurance coverage that occur with college graduation,
aging out of parental coverage, or job changes.
Be aware of the laws that help you keep insurance benefits. The following laws apply to survivors
living in the United States:

ACA (Affordable Care Act), the comprehensive health care reform law enacted in the United States on March
30, 2010, created a Health Insurance Marketplace and new rights and protections that make health insurance
coverage fairer and easier to understand. More information is available at www.healthcare.gov.
• COBRA (Consolidated Omnibus Budget Reconciliation Act) requires employers or larger businesses to makeinsurance available for a limited time to employees (and their dependents) who are fired or laid off.
• HIPAA (Health Insurance Portability and Accountability Act of 1996) allows people with pre-existing conditions tokeep comprehensive insurance coverage when they are changing insurance plans or jobs. Under the new HealthCare Law in the United States, HIPAA eligibility provides greater protections than are otherwise available understate law.
•

Be persistent when meeting obstacles. Try not to get overwhelmed.

•••

Complete and follow through with applications.
Appeal denials with letters of support from your healthcare provider.
Contact groups such as Candlelighters and the National Coalition of Cancer Survivors for more information about
healthcare resources.

Recommended Resources
The National Coalition of Cancer Survivors is a patient-led advocacy organization for cancer survivors. Their website,www.canceradvocacy.org, lists organizations and agencies that offer help regarding specific cancer-related issues,
including finding affordable healthcare. Their phone number is (877) 622-7937.
Cancer Care, a nonprofit organization dedicated to providing emotional support, information, and practical help topeople with cancer and their loved ones. Their site also has a searchable database to assist in finding local and national
resources to help with financial and practical needs. 1-800-813- HOPE (4673) www.cancercare.org.

Written by: Melissa M. Hudson, MD, St. Jude Children’s Research Hospital, Memphis, TN; Sally Wiard, MSW, LCSW, Children’s
Hospital of San Antonio, San Antonio, TX; and Allison Hester, RN, MSN, CPNP, Arkansas Children’s Hospital, Little Rock, AR. Adaptedfrom the CCSS Newsletter, Spring 2003, used with permission.
Reviewed by Amelia DeRosa RN, BSN, CPON; Christine S. Yun, MSN, PNP, CPON; and Kayla L. Foster, MD, MPH.

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Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

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Gastrointestinal Health after Cancer Treatment
Treatment for childhood cancer can sometimes cause scarring and chronic problems of the intestines (bowel) or
other parts of the gastrointestinal (GI) system. It is important to know about the GI system so that you can recognize
symptoms and keep your GI system healthy.
How does the gastrointestinal system work?

The GI system (also known as “the digestive system”) is a group of organs that break down (digest) the food that weeat. This allows the body to use food to build and nourish cells and provide energy.
What types of GI problems can arise after
treatment?

The types of problems can vary depending on the treatmentthat was given. Generally, GI problems occurring after
treatment for childhood cancer are related to surgery orradiation. The effects depend on the location of the surgery,the radiation treatment field, and the dose of radiation
received.

Eshopagus
Liver
Gallbladder
Large intestine (colon)
Intestines

Small intestine

Problems that can develop include:
Rectum• Bowel obstruction (blockage of the intestines)—therisk is higher for people who have had a combinationof abdominal radiation and surgery.
• Esophageal stricture (scarring and narrowing of the tube that delivers food from the mouth to the stomach)—this is usually a result of radiation and can cause problems with swallowing.
• Gallstones (solid deposits of cholesterol or calcium salts that form in the gallbladder or bile ducts)—the risk isincreased in people who had abdominal radiation.
• Hepatic fibrosis or cirrhosis (scarring of the liver)—the risk is increased for people who received radiation to theabdomen, or for those with a chronic liver infection (hepatitis).
• Chronic enterocolitis (inflammation of the intestines resulting in chronic diarrhea and abdominal pain)—the risk
is increased after abdominal or pelvic radiation.
• Colorectal cancer (cancer of the large intestine)—the risk is increased for people who had abdominal or pelvic
radiation (see related Health Link: Colorectal Cancer).
What treatments increase the risk for developing a gastrointestinal problem?

•••

Surgery involving the abdomen or pelvis
Radiation:– Neck– Chest– Abdomen– Pelvis– Spine (cervical, thoracic, lumbar, sacral)
Other risk factors include:– History of bowel adhesions (scarring)

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–
–
–
–
–

History of bowel obstruction (blockage)
History of chronic graft-versus-host disease (cGVHD) of the intestinal tract
Family history of colorectal or esophageal cancer
Family history of gallstones
Tobacco use

What are the possible symptoms of a gastrointestinal problem?

•
•
•
•
•
•
•
•
•
•
•

Chronic acid reflux (heartburn)
Difficult or painful swallowing
Chronic nausea or vomiting
Abdominal pain
Chronic diarrhea
Chronic constipation
Black tarry stools or blood in stool
Weight loss
Changes in appetite
Abdominal distension/Feeling bloatedJaundice/Yellow eyes, yellow skin (see related Health Link: Liver Health)If you develop any of these symptoms, see your healthcare provider. Symptoms that come on quickly or are severe(such as the sudden onset of abdominal pain and vomiting) may indicate a more urgent problem (such as a bowel
obstruction) requiring immediate medical evaluation.
What medical tests are used to screen for a gastrointestinal problem?

Screening for problems affecting the GI system involves an annual physical examination by a qualified health care
professional. X-rays, blood tests, and testing for small amounts of blood in the stool (called the guaiac test) aresometimes needed. An ultrasound may be needed if gallstones or gallbladder problems are suspected. Additionally,certain tests that examine the inside of the colon (colonoscopy) or esophagus (endoscopy) with special instruments
are sometimes needed.
What can be done to prevent gastrointestinal problems?

•

Develop a healthy nutrition plan. Suggestions for a healthy diet include:– Choose a variety of foods from all the food groups. Visit www.choosemyplate.gov for help developing a wellbalanced meal plan.
– Eat 5 or more servings a day of fruits and vegetables, including citrus fruits and dark-green and deep-yellow
vegetables.
– When drinking juice, choose 100% fruit or vegetable juice, and limit to about 4 ounces a day.
– Eat plenty of high fiber foods, such as whole grain breads, rice, pasta and cereals. Avoid foods high in sugars(such as candy, sweetened cereals, and sodas).
– Buy a new fruit, vegetable, low-fat food, or whole grain product each time you shop for groceries.
– Decrease the amount of fat in your meals by baking, broiling or boiling foods and not eating fried foods.
– Limit intake of red meat by substituting fish, chicken, turkey or beans. When you eat meat, select leaner cuts

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and smaller portions.
– Limit fried and high-fat foods, such as fries, snack chips, cheeseburgers, and pizza.
– Choose low-fat milk and dairy products.
– Avoid salt cured, smoked, charbroiled and pickled foods.
– Be sure that you eat foods rich in calcium, such as milk, yogurt and dark green vegetables.
Avoid cancer-promoting habits.
– Do not smoke or use tobacco products.
– Avoid second-hand smoke when at all possible.
If you drink alcohol, use moderation.
– Heavy drinkers (people who drink two or more hard drinks per day), especially those who use tobacco, have ahigher risk of GI cancer and other gastrointestinal problems.
–

Limiting the use of alcohol can reduce these risks.

Written by: Sharon M. Castellino, MD, MSc, Children’s Healthcare of Atlanta - Egleston, Atlanta, GA; and Sheila Shope, RN, FNP, St.
Jude Children’s Research Hospital, Memphis, TN.
Reviewed by Daniel Smith, DNP, FNP; Kayla L. Foster, MD, MPH; and Melissa Acquazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities, or
damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Growth Hormone Deficiency after Cancer Treatment
Some people who were treated for cancer during childhood may develop endocrine (hormone) problems as a result ofchanges in the function of a complex system of glands known as the endocrine system.
What is the endocrine system?
The endocrine system is a group of glands that regulates many body functions including growth, puberty, energy level,urine production, and stress response. Glands of the endocrine system include the pituitary, hypothalamus, thyroid,
pancreas, adrenals, ovaries, and testes. The hypothalamus
Pituitary glandand pituitary are sometimes called the “master glands”
Hypothalamus
because they control many of the other glands in the
Thyroid
endocrine system. Unfortunately, some treatments given
for childhood cancer can damage the endocrine system,
resulting in a variety of problems.
Pancreas

What are hormones?

Adrenal glands

Hormones are chemical messengers that carryinformation from the endocrine glands through thebloodstream to the body’s cells. The endocrine system
makes many hormones (such as growth hormone), sex
hormones, adrenal and thyroid hormones) that work
together to maintain specific bodily functions.

Ovaries

TestesWhat is growth hormone deficiency?
Growth hormone (GH) is made by the pituitary gland. In order for children to grow to their full height potential, theyneed adequate amounts of GH. GH works with thyroid hormone, exercise, proper nutrition, and rest to help children andteenagers grow. GH also helps maintain normal blood sugar levels and is needed for the normal development of teeth.
In addition to helping with bone growth, GH affects how well the heart and blood vessels work, how the body uses fat,makes muscle, and strengthens bones, and generally influences overall health throughout life. In healthy people, GH
production continues into adulthood. Adults need small amounts of GH to maintain proper amounts of fat, muscle andbone. GH may also play a role in regulating mood and emotion.
Cancer treatments, such as radiation or surgery to structures in the head or brain, may cause malfunction of the glands
that control growth. As a result, the pituitary gland may not make enough GH, resulting in GH deficiency. GH deficiency
can also occur in people who have never had cancer treatment.
What are the signs and symptoms of growth hormone deficiency?
Slowing of growth (height) is one of the most obvious signs of GH deficiency in children. A GH deficient child usually
grows less than 2 inches per year. Children with GH deficiency are smaller and tend to look younger than children theirsame age, but they usually have normal body proportions.
Adults who have GH deficiency may have a variety of different physical symptoms, such as thinning of the bones,
decreased muscle strength, increased body fat, or high blood cholesterol levels. Adults may also have symptoms suchas feeling tired, anxious, irritable, gloomy, unmotivated, or having a decreased interest in sex.

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What are the risk factors for growth hormone deficiency?
Risk factors related to treatment for cancer during childhood include:• Cancer treatment before reaching adult height, especially in very young patients• Radiation to:– Head/brain– Total body irradiation (TBI)• Surgery to the brain, especially the central region of the brain where the pituitary gland is located (suprasellar
region)What screening is recommended?
All childhood cancer survivors should have a yearly comprehensive health check-up including measurement of height
and weight, assessment of pubertal status, nutritional status, and overall well-being. For patients with the risk factors
listed above, this screening should be done every 6 months until growth is completed. If there are signs of poor
growth, an x-ray of the wrist (bone age x-ray) should be done. Other possible causes of growth problems, such as low
thyroid function, should also be checked.
If GH deficiency is suspected, your healthcare provider should refer you to an endocrinologist (hormone specialist) for
further evaluation and treatment.
How is growth hormone deficiency treated?
Endocrinologists may suggest treatment options that involve supplementing or replacing GH that your pituitary glandis not making on its own with synthetic GH given by injection. GH is usually given for several years, until the person
reaches an acceptable adult height or the greatest possible height. Your endocrinologist can give you information about
how much growth is possible on GH therapy. Treatment options for GH deficiency that persists into adulthood should be
discussed on an individual basis with your endocrinologist.
Written by: Debra A. Kent, RN, MSN, CPNP, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.
Reviewed by Lillian R. Meacham, MD; Angela Yarbrough DNP, APRN, FNP-BC, CPON; Christine Yun MSN, PNP, CPON; and Kayla L.
Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

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Hearing Loss after Cancer Treatment
Some chemotherapy drugs, other medications, or radiation needed for treatment of childhood cancer can damage
hearing. Hearing loss interferes with daily living. If you received these treatments, it is important to have your hearing
checked and to obtain treatment if hearing loss is found.
How do the ears work?
It’s easier to understand hearing loss if you understand how theears work. The ear is made up of three main parts, known as theouter, middle, and inner ear.
Outer earSound waves travel through the air and first enter the bodythrough the outer ear. The part of the ear that can be seenoutside the body is called the pinna. The pinna collects andfunnels sound into the auditory (ear) canal. The auditory canal islike a tunnel. It makes the sound louder and directs it toward the
middle ear.
Middle Ear
The eardrum separates the outer ear from the middle ear, a chamber that is normally filled with air. Inside the middle
ear are three tiny bones (ossicles) that form a chain connecting the eardrum to the opening of the inner ear. Sound
waves cause the eardrum to vibrate. These vibrations cause the three tiny bones in the middle ear to move, transmitting
the sound to the inner ear.
Inner EarThe inner ear is known as the cochlea, and it is filled with fluid. The cochlea contains thousands of tiny nerve endings,
known as sensory hair cells. Sounds travel in waves through the fluid of the inner ear. The sensory hair cells change
the sound waves into nerve impulses that are sent to the brain by way of the auditory nerve (also known as the eighth
cranial nerve). In the cochlea, the sensory hair cells are arranged in order of pitch, from low-pitched sounds (such asa man’s voice) to very high-pitched sounds (such as a bird’s chirping). Each hair cell is sensitive to a specific range ofpitches.
What are the types of hearing loss?
Hearing loss that occurs in the outer or middle ear is called conductive hearing loss. This means that the hearing
loss is due to a problem in transmission of sound from the air to the inner ear. An example of this would be changes
in hearing because of fluid collection in the middle ear. Sometimes this happens when people have ear infections. The
fluid “muffles” the sound when it is traveling through the middle ear.
Hearing loss that results from damage to the inner ear or auditory nerve is called sensorineural hearing loss. An
example of this would be damage to the sensory hair cells in the inner ear from chemotherapy. Even though soundwaves still move through the inner ear fluid, they can no longer be changed into nerve impulses, so the sound does notreach the brain. Sensory hair cells that process high-pitched sounds are usually damaged first, followed by damage tothe sensory hair cells that process lower-pitched sounds.
Hearing loss with both conductive and sensorineural components is called mixed hearing loss.
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What types of cancer therapy increase the risk of hearing loss?
The following cancer treatments can potentially cause hearing loss:• Cisplatin chemotherapy• Carboplatin chemotherapy if given in high doses for hematopoietic cell transplant (HCT) conditioning• High doses of radiation (30 Gy or 3000 cGy/rads or higher) to the head or brain• Surgery involving the brain, ear or auditory (eighth cranial) nerve• Certain antibiotics (medicines used to treat infections) and diuretics (medicines that help the body get rid ofexcess water)
What are the effects of childhood cancer treatment on hearing?
High doses of radiation to the ear or brain can cause inflammation or ear wax buildup in the outer ear, problems withfluid buildup in the middle ear, or stiffness of the eardrum or middle ear bones. Any of these problems can result in
conductive hearing loss. Radiation can also damage the sensory hair cells in the inner ear, causing sensorineural hearing
loss. Damage from radiation may affect one or both ears, depending on the area of radiation treatment. Conductive
hearing loss may improve over time, but sensorineural hearing loss is usually permanent.
Platinum chemotherapy (cisplatin and/or carboplatin) can cause damage to sensory hair cells in the inner ear, resulting
in sensorineural hearing loss. Most often, the effect is similar in both ears and is permanent.
What are the symptoms of hearing loss?
Symptoms of hearing loss may include:• Ringing or tinkling sounds in the ear• Difficulty hearing in the presence of background noises• Not paying attention to sounds (such as voices, environmental noises)• School problems (see related Health Link: School after Cancer Treatment)• Some people may have no symptoms at all
What monitoring is recommended?
People who are age 6 or older should be screened with a pure tone audiogram (hearing screening test). Children
younger than age 6 or those who have abnormal results on their screening test should be evaluated by an experienced
audiologist (a professional trained in hearing disorders).
•

 earing is usually evaluated by a series of tests. During an audiogram, the person wears earphones and listens forHsounds of different pitches and different degrees of loudness. Speech audiometry tests the person’s ability hearsingle words and sentences. Tympanometry tests the status of the middle ear and the movement of the eardrum
in response to a puff of air.

•People who are not able to have an audiogram (such as those who are too young or who cannot understand thetest instructions) can have their hearing tested using Auditory Brainstem Response (ABR). The person having thistest is usually given medicine so that they go to sleep, and then their brainwave responses to various sounds arerecorded.

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How often should hearing be tested?
Everyone who had cancer treatment that can affect the ears (such as cisplatin and high doses of carboplatin, highdoses of radiation to the brain) should have their hearing tested yearly until they are 6 years old, then every 2 years
until they are 12 years old and then every 5 years. If hearing loss is found, testing should be repeated yearly or asadvised by an audiologist. In addition, hearing should be tested anytime a hearing problem is suspected.
What can be done if hearing loss is detected?
If hearing loss is detected, it is important to be under the care of an audiologist or otologist (doctor who specializes
in hearing disorders). Hearing loss can cause problems with a person’s ability to communicate and carry out daily
activities. Younger children are at higher risk for school, learning, and social difficulties, and problems with language
development. It is therefore very important for a person with hearing loss to find the services that will best help tomake the most of their ability to communicate well. There are many options available, and these can be used invarious combinations, depending on the hearing problem.
•

Hearing aids make sounds louder. Several types are available, depending on the age and size of the person
and the extent of hearing loss. Most children under 12 years of age wear a behind-the-ear model to allow foradjustments as the child grows. These are available in a variety of colors—allowing for personalization andassisting with the child’s acceptance of the hearing aid. Teenagers and adults may benefit from a smaller,
in-the-ear or in-the-canal model. It is very important that the hearing aid batteries are fresh and that thehearing aid is turned to the “on” position when in use.

•

Auditory trainers (also known as “FM trainers”) are devices that are particularly useful in the school setting.
The person who is speaking (usually the teacher) wears a microphone that transmits sound over FM radio
waves. The person with hearing loss wears a receiver that picks up the sound. This device can be worn
alone or attached to the hearing aid and allows the person with hearing loss to hear the speaker clearly,
even in a noisy environment.

•

Other assistive devices are also available for people with hearing loss. These include telephone
amplifiers and teletypewriters (TTYs—sometimes also referred to as Telephone Devices for the Deaf or
TDDs). Specialized appliances designed for people with hearing loss include alarm clocks that vibrate andsmoke detectors with flashing lights. Closed captioning for television is widely available. The Internet isalso a helpful communication tool for people with hearing loss, providing options such as e-mail, online
discussions, and access to information via websites. Additionally, cell phones offer text messaging, instantmessaging, Internet access, and photo transmission.

•

Telecommunication relay services are available in video and voice/text formats. The video relay service
is internet-based and allows a person using signed language to communicate via a video interpreter, whotranslates the signed language into voice or text. The voice/text relay service allows a person using ateletypewriter to communicate through an operator, who then relays the message to the hearing person in
spoken form.

•

Cochlear implants may be an option for people with profound hearing loss who are unable to benefit fromhearing aids. These electronic devices are surgically placed behind the ear and electrodes are threaded
into the inner ear. A microphone and speech processor are then used to transmit sound to the electrodes,
stimulating the auditory nerve and allowing sound perception by the brain. After the cochlear implant isinstalled, auditory training is given for a period of time to teach the individual to recognize and interpretsounds.

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Alternate or supplementary communication methods, including speechreading, signed language andcued speech, are available for people with significant hearing loss. Spoken language may also be an option,
but usually requires an intensive educational approach with speech therapy. In the United States, healthcareorganizations that receive federal funding are required to provide sign language interpreters when requested
by a patient.

•Community and educational resources in the United States include services through local public school
districts or referral agencies (available under the IDEA legislation, PL 105-17), such as intensive speechtherapy and auditory trainers for classroom use. Sometimes special accommodations, such as seatingin the front of the classroom are all that is needed, but this usually requires that the parent request an
Individualized Education Plan (IEP) for the child through the school district (see related Health Link: School
after Cancer Treatment). Many hospitals have a teacher or school liaison that can assist with arranging for
the IEP and other specialized services that may be needed. The Americans with Disabilities Act (ADA, PL
101-336) guarantees people with hearing loss equal access to public events, spaces and opportunities,
including text telephones and telephone amplifiers in public places, and assistive listening devices intheaters. Some theaters also offer special showings of newly released movies with captioning.

What can I do to protect my hearing?
If you have experienced hearing loss, or have received therapy that has the potential to damage your hearing, you
should discuss this with your healthcare provider. Be sure to obtain prompt evaluation and treatment for ear infections,swimmer’s ear, and earwax impaction. Whenever possible, ask your healthcare provider to consider alternatives to
medications that have the potential to cause further hearing loss, including certain antibiotics (aminoglycosides suchas gentamicin), certain diuretics (“loop diuretics, such as furosemide), salicylates (such as aspirin) and medications
for high iron levels. You should also take care to protect your ears from loud noises. In fact, loud noises can causesignificant damage to your ears. Examples of items and activities that can be hazardous to your hearing include:
Appliances
Power saws
Vacuum cleaners
Lawn mowers
Yard trimmers or leaf blowers

Occupations
Firefighters
Construction workers
Farmers
Airport workers
Cab, truck, and bus drivers
Hair stylists: constant exposure to loud hair dryers

Recreation
HuntingBoating or water skiing
Motorcycling or four-wheeling
Stereo headphones
Amplifiers

If you cannot avoid exposure to noise, you should:• Wear hearing protectors such as ear plugs or ear muffs• Limit periods of exposure to noise (for example, if you are at a loud concert go to a quieter area for a while togive your ears a break)•Be aware of the noise in your environment and take control of it when you canWritten by Wendy Landier, PhD, CPNP, Children’s Hospital of Alabama, Birmingham, AL. Portions adapted from “Noise and Hearing
Loss, Do You Know…An Educational Series for Patients and Their Families,” St. Jude Children’s Research Hospital, Memphis, TN(used with permission).
Reviewed by L. Foster, MD, MPH; Beth Fisher, DNP, APRN, CPNP; and Melissa Acquazzino, MD, MS.
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Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

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Keeping Your Heart Healthy
Most childhood cancer survivors do not develop heart problems; however, certain types of cancer treatment given
during childhood can result in damage to the heart. Because heart problems may occur many years after cancer
treatment, it is important for childhood cancer survivors to be aware of any treatments they may have received that canaffect the heart. With this knowledge, steps can be taken to keep their heart healthy, including regular medical checkups and tests to monitor heart function. And if a problem develops, it can be detected and treated early.
How does the heart work?
The heart is a muscular organ that is at the center of the body’s
circulatory system. The heart is responsible for pumping blood withoxygen and nutrients to body tissues. There are four chambers (twoatria and two ventricles) within the heart that work together to pumpblood. Valves direct the flow of blood through the heart chambers andinto the blood vessels. The rhythm of heart contraction and rate of theheartbeat are coordinated by nerves that send electrical impulses todifferent parts of the heart. A thin membrane (pericardium) surrounds
and protects the heart and anchors it within the chest.
What types of cancer treatments can cause heart
problems?
Some types of chemotherapy and radiation involving the heart can cause problems.
Anthracycline chemotherapy
The anthracyclines are a type of chemotherapy used to treat many childhood cancers. This type of chemotherapy cansometimes affect the heart. Commonly used anthracyclines include:• Doxorubicin (Adriamycin®)• Daunorubicin/Daunomycin (Cerubidine®)• Idarubicin (Idamycin®)• Mitoxantrone (Novantrone®)• Epirubicin
Radiation therapy
Heart problems may also result from radiation therapy to the heart or surrounding tissues. This includes radiation to thefollowing areas:• Chest• Spine (chest or “thoracic” portion)• Abdomen• Total body irradiation (TBI)

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What heart problems can occur after treatment for childhood cancer?
There are several types of heart problems that may result from cancer treatments:• The muscle cells of the heart may be damaged so that the heart doesn’t contract and relax normally (leftventricular dysfunction, cardiomyopathy).
• The electrical pathways that conduct impulses to control heart rhythm may be scarred or damaged, resulting inabnormally fast, slow, or irregular heartbeats (arrhythmias).
• The valves and blood vessels of the heart may be damaged, resulting in stiff or leaky valves (valvular stenosis
or insufficiency).
• The protective covering of the heart may become inflamed (pericarditis) or scarred (pericardial fibrosis).
• The blood vessels of the heart may become scarred or blocked (coronary artery disease), preventing deliveryof oxygen and nutrients to the heart and other tissues.
In severe cases, these problems may result in the death of heart tissue (heart attack or myocardial infarction), a
dangerous heart rhythm (arrhythmia), or an inability of the heart to pump blood properly (congestive heart failure).
Which types of cancer treatment are associated with which heart problems?
• Anthracyclines: can cause problems with heart muscle function (left ventricular dysfunction, cardiomyopathy)
and abnormal heart rhythms (arrhythmias).
• Radiation therapy: can cause scarring and stiffening of heart tissues which can result in an abnormal heart
rhythm (arrhythmia) and/or problems with the heart muscle (cardiomyopathy), heart valves (valvular stenosis
or insufficiency), blood vessels (coronary artery disease), or membrane surrounding the heart (pericarditis or
pericardial fibrosis).
Are there other risk factors for heart problems?
Some other medical conditions may also increase the risk of heart problems from chemotherapy or radiation therapy.
These include obesity, high blood pressure, high cholesterol or triglyceride levels in the blood, and diabetes. You may
have a higher risk of having heart problems if these conditions run in your family. Heart disease is also more common
in people who have gone through menopause, so survivors who go through an early menopause may be at higher risk.
Many health behaviors can add to the risk of heart disease including smoking, having an inactive (sedentary) lifestyle,and eating a diet high in fat.
Who is at risk for developing heart problems?
The risk of developing a heart problem after childhood cancer treatment is related to several factors:• The total dose of anthracycline chemotherapy• The total dose of chest radiation• The amount of the heart tissue included in the radiation treatment field• Treatment with other medications that affect heart function• The presence of other conditions that affect heart function
Most childhood cancer survivors who were treated with anthracyclines or chest radiation have no heart damage atall. Some survivors have very mild changes in heart size or function that have not gotten worse over time. Only asmall number of survivors have developed severe heart problems leading to heart failure or dangerous heart rhythms.
Overall, the risk of developing heart problems after childhood cancer therapy is highest in survivors treated with higher
doses of anthracyclines or chest radiation, especially those who received both treatments at a young age.
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Because we do not understand why some survivors develop heart problems after treatment for childhood cancer andothers do not (even when they have gotten the same treatment), it is important for each childhood cancer survivor
treated with anthracyclines or chest radiation to continue to have regular medical check-ups so that if a problem withthe heart develops, it can be detected and treated early.
What are the symptoms of heart problems?
• No symptoms may be noted with mild to moderate heart problems. Identification of problems may only bedetected by cardiac tests such as ECHO, EKG, or MUGA.
• Shortness of breath• Dizziness• Lightheadedness, fainting or near-fainting• Severe fatigue preventing exercise or normal play
• Chest pain that feels like a heavy pressure or fullness and travels to the arm, chin, or face
• Sweating, nausea, or shortness of breath with chest pain
• Sharp piercing pain in the center or the left side of the chest (often worsens with taking a deep breath)• Very swollen feet or ankles (so swollen that if a finger is pressed firmly on the area for a few seconds it leaves
an indentation)• Cough and wheezing that doesn’t go away
• Periods of feeling your heart racing while at rest or skipping beats• Abdominal symptoms (nausea or emesis)
How does exercise affect the heart?
Aerobic exercise (brisk walking, running) is generally safe and healthy for the heart. However, some types of intensive
exercise are particularly stressful to the heart.
Survivors treated with high doses of anthracyclines (250 mg/m2 or higher), or chest radiation therapy (30 Gy or 3000
cGy/rads or higher), or with a combination of anthracyclines (any dose) and chest radiation (≥15 Gy) should check with
their healthcare provider before beginning any intensive exercise program. Those who plan to engage in strenuous orvarsity team sports may benefit from evaluation by a heart specialist (cardiologist).
What other conditions or activities can make heart problems worsen?
A heart exposed to anthracyclines and/or chest radiation may not adapt well to situations that increase the workload of
the heart. This includes:• Pregnancy• Use of stimulant medications or drugs (amphetamines, cocaine, diet pills, ephedra, mahuang, or performanceenhancing drugs)
Illicit drugs should always be avoided. If you are at risk of heart problems from childhood cancer therapy and planning
to use stimulant medications or become pregnant, it is important to discuss this with your healthcare provider. It may
be recommended that you undergo heart testing such as an echocardiogram before becoming pregnant or taking
certain types of medications that may cause excess stress to the heart.

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Are there any other special precautions?
Survivors with prosthetic heart valves and those with currently active chronic graft-versus-host disease (cGVHD)
following hematopoietic cell transplant (HCT) may need to take an antibiotic prior to dental work or other invasive
medical procedures (such as those involving the respiratory, gastrointestinal, or urinary tracts) to prevent an infection
called endocarditis. If you have a prosthetic heart valve or if you have active cGVHD, ask your doctor, heart specialist,
and/or dentist if you should take antibiotics to prevent endocarditis before dental or other medical procedures.
What monitoring is required for potential heart problems?
Anyone treated with anthracycline chemotherapy or chest radiation for childhood cancer should have a yearly checkup with special attention to any symptoms relating to the heart. In addition, an electrocardiogram (ECG, EKG) should
be done at the time the survivor enters long-term follow-up (usually about 2 years from completion of therapy). An
echocardiogram or comparable imaging is also recommended at the first long-term follow-up visit, then according to
the following schedule (or as recommended by your healthcare provider):Cardiac Imaging Schedule Recommendations
Anthracycline Dose*
None to <100 mg/m2

Radiation Dose**
None to < 15 Gy
15 to < 30 Gy
None to < 15 Gy≥15 Gy≥30 GyNone to Any

Recommended Frequency of ECHONo screening

None to <100 mg/m2 or None
Every 5 years≥ 100 to < 250 mg/m2≥ 100 to < 250 mg/m2
None to Any
Every 2 years≥ 250 mg/m2*Based on doxorubicin isotoxic equivalent dose**Based on radiation dose with potential impact to heart (radiation to chest, abdomen, spine [thoracic, whole], total
body [TBI])
Survivors who received radiation at a dose of 30 Gy (3000 cGy) or higher to the heart or surrounding tissues orradiation at a dose of 15 Gy (1500 cGy) or higher plus anthracycline chemotherapy may be advised to undergo
evaluation by a cardiologist for stress testing 5 to 10 years following radiation, with repeat testing as recommended by
the cardiologist.
Survivors who received radiation to the heart or surrounding tissues should also have periodic blood tests to check forother cardiac risk factors (lipid profile and fasting glucose or hemoglobin A1C).
Additional evaluation by a cardiologist is recommended for survivors who are pregnant or planning pregnancy andreceived any of the following therapy:•

Anthracycline chemotherapy at a dose of 250 mg/m2 or more•

Radiation at a dose of 30 Gy (3000 cGy) or higher to the heart or surrounding tissues•

Radiation to the heart (15 Gy) or higher in combination with anthracycline chemotherapy (at any dose)Heart monitoring may be necessary due to the extra strain on the heart during the later stages of pregnancy andduring labor and delivery. Suggested monitoring includes an echocardiogram before and periodically during pregnancy,
especially during the third trimester, and cardiac monitoring during labor and delivery.

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How are the heart tests done?
An electrocardiogram (ECG, EKG) is a test used to evaluate heart rate and rhythm. Electrodes (small sticky patches)are placed on the chest, arms, and legs. Wires are attached to the electrodes and the electrical impulses of the heart
are then recorded.
An echocardiogram (ECHO; heart ultrasound) is used to test the muscle function of the heart and how well the heartpumps. The person lies on a table and has conductive jelly applied to the chest. Then a transducer (device that emits
the ultrasound waves) is placed on the chest to obtain different views of the heart. Slight pressure is applied on thetransducer and can sometimes cause discomfort. The test results are displayed on a monitor for the doctor to study
later. Many measurements are done during this test to help find out if the heart muscle is pumping blood well. The
ultrasound test also looks at the valves of the heart to see that they open and close normally. Electrodes are usuallyplaced on the chest to monitor the heart’s electrical impulses during the test.
Cardiac magnetic resonance imaging (MRI) uses a large magnet, radio waves, and a computer to create detailed
images of the heart. Radiation is not used during the MRI. The person lies on the scanning table, which slides into thecircular opening of the MRI machine. Jewelry, eyeglasses, hearing aids, or other objects that may interfere with the
MRI must be removed prior to the test. If contrast is needed, it will be injected into a vein. The scanner can be noisy,
so you will be given earplugs to wear or music to listen to during the test to help block out the noise. Because of thestrong magnet, people who have metal devices (such as a pacemaker, implanted infusion pump, or iron-based metal
implant) cannot have MRIs.
A cardiac stress test measures heart function during periods when the heart is working hard. During this test, theheart and blood pressure are usually monitored while the person walks on a treadmill.
What happens if a problem with the heart is detected?
Your healthcare provider will advise you about the follow-up care you need. Sometimes, a referral to a cardiologist isneeded for additional evaluation and/or treatment with medications.
What can be done to prevent heart problems?
With increasing age, the risk of certain types of heart disease (such as heart attacks and hardening of the arteries) also
increases. Lifestyle factors that may increase the risk of heart problems include smoking, being overweight, eating ahigh fat diet, and not exercising. Medical conditions that increase the risk include diabetes, high blood pressure, andhigh blood cholesterol. You can reduce your risk of heart problems by:•

Avoid smoking and excessive alcohol intake.

•

Maintaining a healthy body weight.

•

Limiting the fat in your diet to no more than 30% of calories.

•

Exercising regularly for at least 30 minutes on most days of the week.

Medical conditions that increase the risk of heart problems include obesity, high blood pressure, high cholesterol or
triglyceride levels in the blood, and diabetes. If you have any of these conditions it is important to take medications or
adjust your lifestyle as recommended by your healthcare provider.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Written by Debra L. Friedman, MD, Vanderbilt University/Ingram Cancer Center, Nashville, TN; Melissa M. Hudson, MD, St. JudeChildren’s Research Hospital, Memphis, TN; and Wendy Landier, PhD, CPNP, Children’s Hospital of Alabama, Birmingham, AL.
Reviewed by Linda Rivard, RN, BSN; Kayla L. Foster, MD, MPH; and Melissa Acquazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Hepatitis after Cancer Treatment
Treatment for childhood cancer often requires transfusions of blood and blood products. Unfortunately, some of theselife-saving blood products may have contained viruses that can cause hepatitis (infection of the liver). There are twomain types of hepatitis that can be transmitted through blood products (hepatitis B and hepatitis C). Before the blood
supply was routinely screened for these infections, people who received blood products may have been infected withthese viruses. In the United States, routine screening of blood donors for hepatitis B began in 1971. The most accurate
screening test for hepatitis C has been in use since 1992. Survivors who received blood products prior to these dates
may have been infected with these viruses. (Note: The dates that blood donor screening for hepatitis began in countries
outside of the United States may be different.)
Hepatitis B and C can also be spread through other types of blood contact (such as needle-sharing among drug users,
tattoos, body piercing, kidney dialysis and organ transplantation). These infections can also be spread through sexual
contact, or passed from mother to newborn baby during the birth process, but this is more likely to occur with hepatitis
B than with hepatitis C.
What is the liver?

The liver is a triangular-shaped organ tucked under the rib cage on the right side of the body. In an average adult,
the liver is about the size of a football and weighs about three pounds. It is responsible for filtering out toxins fromthe blood, aiding with digestion and metabolism, and producing many important substances including blood-clotting
proteins.
What are the signs and symptoms of hepatitis?

Many people do not have symptoms of hepatitis when first infected. Some people have symptoms similar to the flu,such as fatigue, loss of appetite, nausea, vomiting, or low-grade fever. Some people may have symptoms indicatingthat the liver is not working well, such as yellow eyes and skin (jaundice), dark urine, severe itching, or pale (claycolored) stools. In rare cases, people may become seriously ill and develop liver failure. Hepatitis may completely
resolve and cause no further health problems. Unfortunately, some people who become infected with hepatitis B or
C during childhood become “chronically” infected. Chronic infection is more common with hepatitis C. People withchronic hepatitis may have no symptoms and feel well, but they are at risk for scarring (cirrhosis) of the liver andother complications. In rare cases, liver cancer can develop. People with chronic hepatitis infections are also at risk for
spreading the infection to others.
What are the signs of liver damage?

Most people with chronic hepatitis have no signs or symptoms. Chronic infection over a long time may cause
progressive liver damage. Signs of liver damage include enlargement of the liver and spleen, swelling or collection of
fluid in the abdomen, yellow color of the eyes and skin (jaundice), and problems with blood clotting.
What tests are done to check for hepatitis?

A blood test can be done to check for viral hepatitis. A positive antibody test for hepatitis B or C means that the person
has been exposed to the virus. Additional testing may then be done to determine if there is an active infection.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Who is at risk for hepatitis B and C?

Anyone who received the following blood or serum products are at risk for hepatitis B (if transfused before 1972) andhepatitis C (if transfused before 1993):• Packed red blood cells• Whole blood• White blood cells (granulocytes)• Platelets• Fresh frozen plasma• Cryoprecipitate• Immunoglobulin preparations (IVIG, VZIG)• Bone marrow or stem cells from an allogeneic donor (someone other than yourself)
Other risk factors include:

•
•
•
•
•
•
•
•

Blood clotting factors (such as Factor VIII or Factor IX) made before 1987
Solid organ transplants (such as kidney, liver, or heart) before 1993
Long-term kidney dialysis (lasting for at least several months)
Illicit drug use
Body piercing, tattoos
Sharing razors, nail clippers, or toothbrushes with people who have hepatitis
Occupational exposure to blood and body fluids
High-risk sexual behavior (such as having multiple sexual partners, not using a condom, or having anal sex)

What follow up is needed for those at risk?

•

Anyone who is at risk for hepatitis B or C should have blood tests done to see if they are infected.

If you have chronic hepatitis, you should also:

•
•
•
•

See a liver specialist for evaluation and possible treatment.
Tell your healthcare providers about all over-the-counter medications and supplements that you are taking.
Do not drink alcohol, which can cause further liver damage.
Avoid over-the-counter pain or fever-reducing medications containing acetaminophen (such as Tylenol® or“aspirin-free” products).
• Have a blood test to see if you have immunity to hepatitis A and B. If you do not have immunity, get immunizedagainst these common infections to protect your liver (there is currently no vaccine to protect against hepatitis C).
• Discuss your hepatitis status with your healthcare providers. (If you are pregnant, discuss this with both yourobstetrician and the baby’s pediatrician.)

How can the spread of chronic hepatitis be prevented?

Hepatitis B and C are not spread by casual contact, such as hugging or shaking hands. However, if you have hepatitis B
or C, to prevent spreading the infection to others you should:• Avoid direct contact of your blood and body fluids with others.
• Clean any spilled blood or body fluids with bleach.
Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

•
•
•
•
•

Cover cuts or other open sores.
Avoid sharing sharp personal objects, such as razors, toothbrushes, nail clippers, ear or body rings, or any object
that may come in contact with blood.
Be sure that new sterile needles are used for body piercing, injections, tattoos, or acupuncture. Never shareneedles.
Make sure all close household members and sexual partners are screened for hepatitis B. If they do not have
immunity, they should be given the hepatitis B vaccine.
If you are sexually active, use barrier precautions (such as latex condoms) during intimate sexual contact.

Talk with your healthcare provider about whether your sexual partner should be tested for hepatitis C.
What else can I do to keep my liver healthy?

•
•
•
•
•
•
•
•
•

Drink plenty of water.
Eat a well-balanced, high-fiber diet.
Cut down on fatty, salty, smoked and cured foods.
Do not take more than the recommended doses of medications.
Avoid taking unnecessary medications.
Do not mix drugs and alcohol.
Do not use illicit drugs.
Be careful about using herbs and natural supplements, especially when combined with medications.
Avoid exposure to chemicals (solvents, aerosol cleaners, insecticides, paint thinners, and other toxins) that canbe harmful to the liver. If you must use these substances, wear a mask and gloves and work in a well-ventilated
area.

Written by Wendy Landier, PhD, CPNP, Children’s Hospital of Alabama, Birmingham, AL.
Reviewed by Daniel Smith, DNP, FNP; Kayla L. Foster, MD, MPH; and Melissa Acqazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Hyperprolactinemia after Cancer Treatment
Some people who were treated for cancer during childhood may develop endocrine (hormone) problems as a result ofchanges in the function of a complex system of glands known as the endocrine system.
Pituitary gland

What is the endocrine system?

Hypothalamus

The endocrine system is a group of glands that regulate
many body functions including growth, puberty, energy
level, urine production, and stress response. Glands ofthe endocrine system include the pituitary, hypothalamus,
thyroid, pancreas, adrenals, ovaries, and testes. The
hypothalamus and pituitary are sometimes called the“master glands” because they control many of the otherglands in the endocrine system. Unfortunately, sometreatments given for childhood cancer can damage theendocrine system, resulting in a variety of problems.

Thyroid

Pancreas
Adrenal glands

Ovaries

TestesWhat are hormones?
Hormones are chemical messengers that carry informationfrom the endocrine glands through the bloodstream to the body’s cells. The endocrine system makes many hormones(such as growth hormone, sex hormones, adrenal and thyroid hormones) that work together to maintain specific bodilyfunctions.
What is hyperprolactinemia?
Hyperprolactinemia occurs when there is too much of the hormone known as prolactin in the body. Prolactin isa hormone made by the pituitary gland. Prolactin is important in breast development during pregnancy and milk
production after childbirth. Too much prolactin can cause problems with functioning of the ovaries or testes. Highlevels of prolactin can cause galactorrhea (breast milk production by a person who is not breastfeeding), irregular
or absent menstrual periods, or decreased testosterone levels that may result in a diminished sex drive (libido). In
preteens and teens, high prolactin levels may interfere with normal pubertal development..
What are risk factors for hyperprolactinemia?
• Radiation to the pituitary gland in very high doses• Development of a second tumor (usually non-cancerous) in the pituitary region• Pregnancy• Taking certain medications and drugs (such as marijuana and alcohol)•

Thyroid failure (a condition in which the thyroid gland fails to secrete enough thyroid hormone)

What screening is recommended?
All childhood cancer survivors should have a yearly comprehensive health check-up. If hyperprolactinemia issuspected, your healthcare provider may order a prolactin blood test, additional imaging (such as a CT scan or MRI of
the brain), and should refer you to an endocrinologist (hormone specialist) for further evaluation and treatment.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

How is hyperprolactinemia treated?
Correcting the thyroid problem may correct the high prolactin level. Endocrinologists may use medications to suppress
prolactin production. If a tumor is detected, surgery or radiation is sometimes needed. The length and type of treatment
varies for each patient and should be discussed with your doctor.
Written by Debra A. Kent, RN, MSN, CPNP, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
Reviewed by by Lillian R. Meacham, MD; Daniel Smith, DNP, FNP; Christine Yun MSN, PNP, CPON®; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities, or
damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Hyperprolactinemia | Version 6.0 | October 2023 | Page 2 of 2

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Appendix II p. 79

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Hypopituitarism after Cancer Treatment
Some people who were treated for cancer during childhood may develop endocrine (hormone) problems as a result ofchanges in the function of a complex system of glands known as the endocrine system.
Pituitary gland

What is the endocrine system?

Hypothalamus

The endocrine system is a group of glands that regulate many
body functions including growth, puberty, energy level, urine
production, and stress response. Glands of the endocrine
system include the pituitary, hypothalamus, thyroid, pancreas,
adrenals, ovaries, and testes. The hypothalamus and pituitary
are sometimes called the “master glands” because they control
many of the other glands in the endocrine system. Unfortunately,some treatments given for childhood cancer can damage theendocrine system, resulting in a variety of problems.

Thyroid

Pancreas
Adrenal glands

Ovaries

What are hormones?

TestesHormones are chemical messengers that carry informationfrom the endocrine glands through the bloodstream to the body’s cells. The endocrine system makes many hormones(such as growth hormone, sex hormones, adrenal and thyroid hormones) that work together to maintain specific bodilyfunctions.
What is hypopituitarism?
Hypopituitarism is the decrease or lack of one or more of the pituitary hormones. The lack of three or more of thepituitary hormones is referred to as panhypopituitarism.
Pituitary hormones include:• Growth hormone (GH)—stimulates the growth of bone and other body tissues, and also affects how the bodyuses fat, makes muscle, strengthens bones, and generally influences overall health throughout life
• Adrenocorticotropic hormone (ACTH)—stimulates the adrenal gland to produce cortisol• Thyroid stimulating hormone (TSH)—stimulates the thyroid gland to produce thyroid hormones• Reproductive hormones (gonadotropins), including luteinizing hormone (LH) and follicle stimulating
hormone (FSH)—stimulate the testes and ovaries to make sex hormones• Antidiuretic hormone (ADH)—helps to control the balance of water in the body by controlling urine output•

Prolactin—controls milk production during breastfeeding

What are risk factors for hypopituitarism?
Risk factors related to childhood cancer treatment include:• Radiation to the brain, especially in doses of 30 Gy (3000 cGy/rads) or higher• Surgical removal of the pituitary gland• Damage to the hypothalamus or pituitary gland, which can occur during brain surgery, or can be caused by atumor in or near the pituitary or hypothalamus• Infections
Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer•

Severe head trauma•

Lack of development of the pituitary from birth

What are the symptoms of hypopituitarism?
The symptoms depend on the specific hormones that are lacking. One or more of the following hormones may beaffected:•

Growth hormone (GH) deficiency - GH affects the growth of body tissues and bone as well as fat,muscle, and sugar metabolism. For more information about growth hormone problems, see the related Health
Link: Growth Hormone Deficiency after Cancer Treatment•

Adrenocorticotropic hormone (ACTH) deficiency - The adrenal glands (located on top of the kidneys)
are stimulated by ACTH to produce cortisol. If the pituitary gland doesn’t make enough ACTH, then cortisol will
not be made. Cortisol helps keep the body’s blood sugar at a normal level and helps the body deal with physicalstress, such as fever or injury. For more information about ACTH deficiency, see the related Health Link: Central
Adrenal Insufficiency after Cancer Treatment•

Thyroid Stimulating Hormone (TSH) deficiency - TSH stimulates the thyroid gland to releasethyroxine, which is important for brain development, growth, and metabolism. People with too little thyroxine
may develop the following symptoms: tiredness, sleeping too much, weight gain, slow growth, poor appetite,cold intolerance, dry skin, constipation, or hair that is dry, coarse, and thin. For more information about thyroid
problems, see the related Health Link: Thyroid Disease after Cancer Treatment•

Gonadotropin (FSH, LH) deficiency - LH and FSH control the production of sex hormones. LH and FSH
stimulate the testicles to make testosterone, and the ovaries to make estrogen and progesterone, resulting
in development of sexual characteristics during puberty. If the body doesn’t have enough LH and FSH duringpuberty, there can be problems with pubertal development. For more information, see the related Health Links:
Testicular and Reproductive Health after Cancer Treatment and Ovarian and Reproductive Health after Cancer
Treatment•

Antidiuretic Hormone (ADH) deficiency - ADH (also known as “vasopressin”) is a hormone producedin the hypothalamus and stored in the pituitary gland. When the amount of water in the body is low, the pituitary
gland releases ADH, sending a message to the kidneys to conserve water. This slows down the productionof urine. When there is not enough ADH, too much urine will be produced, resulting in a condition known asdiabetes insipidus. Symptoms of diabetes insipidus include excessive thirst and frequent urination.

What screening is recommended?
All cancer survivors should have a yearly comprehensive health check-up including measurement of height andweight, assessment of their progression through puberty, and assessment of overall well-being. If hypopituitarism issuspected, your healthcare provider should refer you to an endocrinologist (hormone specialist) for further evaluationand treatment.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Written by: Debra A. Kent, RN, MSN, CPNP, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.
Reviewed by Lillian R. Meacham, MD; Shekinah Andrews, FNP; Christine Yun MSN, PNP, CPON®; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Introduction to Long-Term Follow-Up after Cancer Treatment
Congratulations! You are transitioning to long-term follow-up after completing treatment. In long-term follow-up,
the goal is to support your physical and emotional health, provide education about your diagnosis and treatment, andfacilitate your success at home, school and work.
Even though you may not have seen a primary care provider during treatment, it is important to reestablish yourrelationship with a primary care provider for regular medical care. In some cases, your long-term follow-up care may
continue at the same hospital or clinic where you received your treatment, but you may be seen by different doctors andnurses in a special long-term follow-up or survivorship program. In other cases, you may receive cancer follow up carefrom a healthcare provider who is closer to your home. No matter where you receive your care, it is important that you
learn about your treatment, its impact on your long-term health and the follow up care you need so that you can stay inthe very best health possible.
Your cancer treatment summary
When you transition to long-term follow-up care, it is important that you get a record of the cancer treatment that you
received. This record, known as a Summary of Cancer Treatment, should contain the following information:• Name of the disease that you had, the date when you were diagnosed, and the site/stage of the disease

•

•

–

Date(s) and description(s) of any relapses–

Name, address, and phone number of hospital(s) or clinic(s) where you received your care–Name, address, and phone numbers of your cancer doctor (oncologist) and other health team members
responsible for your care

– Date that your cancer treatment was completed
Names of all the chemotherapy medicines that you received and specific information about certain
chemotherapy drugs as follows:–

Total doses of anthracycline chemotherapy (such as doxorubicin, daunorubicin, idarubicin, epirubicin, andmitoxantrone)–

Total doses of alkylating chemotherapies (such as cyclophosphamide, procarbazine, BCNU, melphalan,nitrogen mustard, ifosfamide, chlorambucil, CCNU, Thiotepa, and busulfan)–

For cytarabine and methotrexate: How they were given (such as by mouth or into the vein), and if into thevein, whether you received “high dose” (1000 mg/m2 or more in any single dose) or “standard dose”
therapy–

For carboplatin: Whether or not the dose was myeloablative (given during preparation for a bone marrow, cord
blood, or stem cell transplant)– Total doses of other chemotherapy agents and how they were given should be included, if available
Radiation therapy summary, including:–Part(s) of body that received radiation (radiation site or field)–

Total radiation dose (including any boost doses) to each field•

Name and dates of any treatment-related surgeries that you had•

Whether or not you received a hematopoietic cell transplant (bone marrow, cord blood, or stem cell transplant),
and if so, whether or not you developed chronic graft-versus-host disease

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Healthy living after treatment of childhood, adolescent, and young adult cancer•

Names of any other cancer treatment(s) that you received (such as radioiodine therapy or bioimmunotherapy)•

Names and dates of any significant complication(s), and treatments received for the complication(s)Keep a copy of your cancer treatment summary in a safe place, and give a copy to each of your healthcare providers.
Your follow-up schedule
Most cancer survivors need long-term follow-up visits about once a year. During these visits, it is important to talkabout your progress and check for problems that can happen after treatment for cancer. Talk with your healthcare
provider about your individual situation and determine a schedule for follow-up care that best meets your needs.
Between visits
Once you transition to long-term follow-up care, you will usually need to identify a local healthcare provider that you
can visit or call if you are injured or sick. Make an appointment for a check-up with this healthcare provider so thatthey can get to know you before an illness arises. If a problem comes up that may be related to your cancer treatment,
your local healthcare provider can discuss this with your long-term follow-up team.
Late effects after treatment for childhood, adolescent, or young adult cancer
Problems that happen after treatment for cancer are known as “late effects.” Fortunately, most long-term survivors
don’t have serious late effects, but it is important to catch any problems early. You may have already learned aboutsome of the possible late effects that can happen after treatment for cancer. Some of the more common ones arereviewed here.
GrowthTreatment for cancer during childhood, especially radiation to the brain or spine, can sometimes slow or stunt growth.
Yearly measurements help to predict whether you will reach a normal height. If you are “at risk” for being short as anadult, your healthcare provider may also recommend other specialized tests and treatments.
Heart
A small percentage of survivors treated with chest radiation or certain chemotherapy drugs known as “anthracyclines”(such as doxorubicin or daunomycin) have problems with the heart. This is most likely to happen in people who
received higher doses of anthracycline chemotherapy or chemotherapy combined with radiation affecting the heart.
Your healthcare provider may recommend tests to check your heart function, and may arrange for a cardiologist (heart
specialist) to see you if the tests show any sign of problems.
Fertility
Radiation to the reproductive organs or brain and certain chemotherapy drugs can affect sexual development andreproduction. Some survivors may be at risk for delayed puberty, infertility (inability to have children), or premature
ovarian insufficiency (early menopause). Check-ups and certain blood tests can help determine if you have any ofthese problems. These issues are important, and if you have any concerns, you should be sure to discuss them withyour healthcare provider. If there is a problem, arrangements may be made for you to see a specialist.
Thyroid
Head or neck radiation can sometimes cause the thyroid gland to stop working properly. This gland helps regulate

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growth, weight, and the balance of body chemicals. Blood tests can be done to check thyroid hormone levels. Low
thyroid levels are easily treated with oral medication.
Subsequent Cancers
Some chemotherapy drugs and radiation can increase the risk of a subsequent (different) cancer. Some survivors may
have genetic changes that put them at risk for second cancers. Tobacco, excessive sun exposure, and other chemicals
and behaviors can also increase this risk. Talk with your healthcare provider about ways to lower your risk and to
detect common cancers at an early stage.
School and work
Problems with schoolwork or job performance can occur as a result of some types of cancer treatment. Psychologists
can work with your local school system to make sure that any special needs are met. Also, financial assistance foreducation and job training may be available through government programs. Social workers can help to explain these
programs.
Moving toward the future
Thinking about developing late effects after surviving cancer can be anxiety provoking. Your long-term follow-up
program is here to help you navigate the emotional and physical challenges of cancer survivorship. Regular healthchecks and recommended screening and surveillance testing are meant to put you in control of your health andprovide the best chance of early detection of problems, if they occur, before they become severe. Work with your healthcare team to develop a follow up plan that works best for you.
Make healthy choices. Keep your follow-up appointments. And always remember that you are the most importantmember of your healthcare team!
Written by Wendy Landier, PhD, CPNP, Children’s Hospital of Alabama, Birmingham, AL. Portions adapted from “Introduction to theAfter Completion of Therapy Clinic,” St. Jude Children’s Hospital, Memphis, TN, used with permission.
Reviewed by Beth Fisher, DNP, APRN, CPNP, CPON, CHPPN; Christine S. Yun, MSN, PNP, CPON; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.

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Healthy living after treatment of childhood, adolescent, and young adult cancer
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Kidney Health after Cancer Treatment
The kidneys are vital organs responsible for filtering out waste products from the blood, controlling blood pressure,and stimulating red blood cell production. Treatment for childhood cancer can sometimes damage the kidneys. It is
important to understand how the kidneys function so that you can keep your kidneys as healthy as possible.
How do the kidneys work?

The kidneys are two bean-shaped organs, each approximately the size of an adult fist,
located below the rib cage near the middle of the back. The kidneys filter about 200 quartsof blood each day, removing harmful waste products and excess water, and returning
important elements (such as calcium, sodium and potassium) to the blood. Filtering occurs
in tiny units inside the kidneys, known as nephrons. Each kidney has approximately one
million nephrons. After the blood is filtered by the nephrons, the excess water and waste
products become urine. The urine flows from the kidneys to the bladder through tubes
called ureters. The bladder then stores the urine until it is full, at which time the waste is
emptied from the body through the urethra.
How is kidney function measured?

Kidney function is measured by calculating a glomerular filtration rate, or GFR. The GFR isa measure of how much blood your kidneys can filter each minute. The GFR is calculatedusing blood test results and information like your age, sex and height. A GFR of greaterthan 90 mL/min/1.73 m2 is considered normal. If your GFR is below 90 mL/min/1.73 m2,
your provider may order additional tests such as a urinalysis to see if there is protein or
blood in your urine.
What treatments for childhood cancer can cause kidney problems?

Certain treatments used for childhood cancer can sometimes cause kidney problems. There may also be other risk
factors present that can increase the chance of kidney problems. If you have any of the following risk factors, you
should take extra care to keep your kidneys healthy:
Radiation involving the kidneys, including:• Kidney (renal or flank) radiation• Abdominal radiation•

Total body irradiation (TBI)

Certain medications that can cause kidney damage, including:• Cisplatin• Carboplatin• Ifosfamide• Certain antibiotics used to treat bacterial and fungal infections, such as tobramycin, gentamicin, and amphotericin•

Certain medications used to treat graft-versus-host disease, such as cyclosporine and FK-506 (tacrolimus)

Other risk factors that may increase the chance of kidney problems include:• Nephrectomy (surgical removal of a kidney)—see the related Health Link: Single Kidney Health• Hematopoietic cell transplant (HCT)

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Medical conditions that may affect the kidney, such as high blood pressure, diabetes, or a tumor involving thekidney• History of urinary tract problems, such as frequent urinary tract infections, back-flow of urine into the kidney(reflux), or other urinary tract abnormalities• Cystectomy (removal of the bladder)—this increases the risk of chronic urinary tract infections and other kidney
problems•

What are the signs and symptoms of a kidney problem?

•
•
•
•

Swelling, especially of the feet and ankles (edema)
Low red blood count (anemia)
High blood pressure (hypertension)
People who have signs of serious kidney problems, such as edema, low red blood count, and hypertension, mayalso have other symptoms, including fatigue, nausea and vomiting, drowsiness, itchy skin, or headaches

What follow up is recommended?

Have a medical check-up at least yearly. This should include a blood pressure check.
Have blood test for kidney function (BUN and creatinine) and electrolytes (blood salts and minerals) at yourfirst long-term follow up visit (at least 2 years after completing cancer treatment). Depending on the treatment
you received and the results of this lab work, your provider may recommend labs to assess your kidney function at
regular intervals.
• If you had a cystectomy (bladder removal), you should also have an evaluation by an urologist (urinary tract
specialist) at least once a year.
••

What can I do to keep my kidneys healthy?

••

Drink plenty of water, especially when playing sports, while out in the sun, and during hot weather.
Call your healthcare provider immediately if you have symptoms of a urinary tract infection (burning when you
urinate, urinating more frequently than usual, and/or feeling an urgent sensation to urinate).
• Use non-steroidal anti-inflammatory drugs with caution. These include pain or fever medicines (over-the-counterand by prescription) that contain aspirin, ibuprofen, or naproxen. These medications have been known to cause
kidney damage (analgesic nephropathy), especially when taken in high doses or over long periods of time (morethan 10 days). If you require long-term medications for management of pain, be sure to discuss options with yourhealthcare provider, and to choose medications that are safe for your kidneys.
Written by Anne Mauck, RN, MSN, CPNP, Virginia Commonwealth University/Massey Cancer Center, Richmond, VA.
Reviewed by Kayla L. Foster, MD, MPH; and Melissa Acquazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Late Effects after Limb Sparing Procedures
What is a “limb sparing procedure”?
A limb sparing procedure is a surgical operation that replaces a diseased bone and reconstructs a functional limb byusing a metal implant, a bone graft from another person (allograft), or a combination bone graft and metal implant (alloprosthetic composite).
What are the potential late effects after a limb sparing procedure?
• Nonunion—For people who had reconstruction with a bone graft, nonunion (non-healing) of the bones is apossible late complication. In the allograft procedure, the portion of bone removed due to tumor is replaced withdonated bone. Nonunion occurs when one or both ends of the replaced bone do not heal, making fracture more
likely, especially if the area is stressed. Surgery for additional bone grafting may be necessary.
• Limb-length discrepancy—Bones are constantly growing during childhood and adolescence, until adult heightis reached. Each bone has a growth plate (area where growth activity occurs). Often, bone cancers are locatednear the growth plate, requiring removal of this area during the limb sparing procedure. Since the reconstructed
section of bone cannot grow, a difference (discrepancy) in limb-length may occur over time. Surgeries or otherprocedures may be necessary to allow for growth.
• Prosthetic loosening—Sometimes the implanted joint can loosen or wear out, especially in people who are
active. These complications may require further surgery to tighten or replace part or all of the implant. Anyloosening of the implant should be reported to your orthopedic surgeon.
• Contractures—After a limb sparing procedure, muscles, tendons and ligaments sometimes stiffen or shrink,forming contractures (permanent tightening of the joint). This is more likely to occur in people who are notphysically active. Periodic follow-up with a physical and/or occupational therapist helps prevent contractures fromforming.
• Difficulty engaging in physical activities to maintain a healthy weight.
•

Chronic pain and/or infection—some people may develop persistent problems with pain and/or infection.

What is the recommended follow-up care after a limb sparing procedure?
• Follow-up visits are usually done by the orthopedic surgeon (bone specialist) every 6 months until the person is
fully grown, then every year. These visits may include x-rays of the limb and follow-up intervals may lengthen as
time progresses.
• Life-long follow-up by an orthopedic surgeon (ideally by an orthopedic oncologist) is recommended.
•

Limitation of certain physical activities is sometimes necessary.

What can you do to promote health after limb sparing surgery?
• Physical and occupational therapy are important for successful rehabilitation after limb sparing surgery. Bothpassive and active range-of-motion exercises help maintain the best limb function.
• If there is pain, swelling, redness or any other signs of infection at the surgical site, or if you develop fever,contact your healthcare provider promptly.
• If your limb sparing surgery was complicated, your orthopedic surgeon may recommend antibiotics prior todental procedures (including teeth cleaning), and for other invasive medical procedures such as those involving
the respiratory, gastrointestinal, or urinary tracts. Infection can result if bacteria enter the bloodstream during
these procedures and become attached to the internal metal components (screws, plates, rods, joints) of theendoprosthesis. The potential need for antibiotics should be discussed with your orthopedic surgeon and yourdentist.
• Some metal implants may pose a problem when going through security screening, such as at the airport. It isgood idea to carry a medical letter indicating that you received treatment for bone cancer and have a metal
implant.
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Written by Asako Komiya, RN, MSN, PNP, City of Hope Comprehensive Cancer Center, Duarte, CA.
Reviewed by Leeann Carmichael DNP, APN, FNP-BC; Kayla L. Foster, MD, MPH; and Melissa Acquazzino MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Liver Health after Cancer Treatment
Treatment for childhood cancer can sometimes damage the liver. It is important to know about how the liver functions
so that you can keep your liver as healthy as possible.
What is the liver?
The liver is a triangular-shaped organ tucked under the rib cage on the right side of the body. In an average adult, theliver is about the size of a football and weighs about three pounds. The liver is responsible for filtering out toxins fromthe blood, aiding with digestion and metabolism, and producing many important substances, including blood-clotting
proteins.
What are the signs and symptoms of liver damage?
Many people with liver damage have no symptoms at all. Some people may develop jaundice (yellowish eyes and skin),dark urine, pale (clay-colored) stools, severe itching, easy bruising or bleeding, chronic fatigue, nausea, loss of appetite,or other symptoms. The liver sometimes enlarges (hepatomegaly), and as liver damage increases, the liver may
become hard (fibrosis) and scarred (cirrhosis). Eventually, there can be accumulation of fluid in the abdomen (ascites),swelling of the spleen (splenomegaly), or bleeding into the esophagus or stomach. Very rarely, liver cancer may develop.
Who is at risk?
People who had radiation to the abdomen or received certain chemotherapy medicines (methotrexate, mercaptopurine,
and/or thioguanine) may be at risk for liver problems. Liver problems related to medications typically occur duringcancer therapy and are unlikely to occur long after the end of treatment.
Other risk factors include:• Medical conditions that involve the liver, such as a liver tumor or surgical removal of a large portion of the liver• Development of sinusoidal obstruction syndrome (SOS, previously known as veno-occlusive disease [VOD]) during
treatment• Pre-existing liver problems• Excessive alcohol use• Chronic liver infection (hepatitis)—see related Health Link: Hepatitis after Childhood Cancer• History of multiple transfusions•

Chronic graft-versus-host disease (as a result of bone marrow, cord blood, or stem cell transplant)

What tests are done to monitor the liver?
The following blood tests are used to monitor the liver.
• Liver enzyme tests monitor levels of specialized proteins that are normally present inside liver cells. If liver cells
are damaged, these proteins can leak out, causing high blood levels of liver enzymes. The most common liver
enzyme tests are:– Alanine aminotransferase (ALT), sometimes also called SGPT– Aspartate aminotransferase (AST), sometimes also called SGOT
• Liver function tests are indicators of how well the liver is working. Common liver function tests include:– Bilirubin (a waste product formed during the breakdown of red blood cells)– Albumin (a major blood protein that is produced by the liver)– Prothrombin Time (PT), a measure of blood clotting
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Tests for liver infection, including specific tests for viral hepatitis A, B, and C•

Test to check for iron overload (ferritin) related to multiple transfusions

What follow up is needed for those at risk?
A blood test to evaluate the liver (including ALT, AST, and bilirubin) should be done when the survivor enters into
long-term follow-up. Those who have undergone a bone marrow, cord blood, or stem cell transplant should also havea blood test to check for iron overload (ferritin). The liver should also be checked for enlargement by a healthcare
professional during yearly physical examinations. If problems are identified, additional tests and a referral to a liver
specialist may be recommended. People at risk for hepatitis may need further testing (see related Health Link:
Hepatitis after Cancer Treatment).
What can I do to keep my liver healthy?
• If you do not have immunity to hepatitis A and B, get immunized against these common infections in orderto protect your liver (there is currently no vaccine to protect against hepatitis C). You can find out if you have
immunity to hepatitis A and B by having a blood test (Hepatitis A IgG antibody and Hepatitis B surface antibody).
• If you drink alcohol, do so in moderation.
• Drink plenty of water.
• Eat a well-balanced, high-fiber diet. Cut down on fatty, salty, smoked and cured foods.
• Do not take more than the recommended doses of medications.
• Avoid taking unnecessary medications.
• Do not mix drugs and alcohol.
• Do not use illicit drugs.
• Check with your healthcare provider before starting any new over-the-counter medications or herbs andsupplements to be sure that they do not have harmful effects on the liver.
• If you are sexually active, use barrier protection (such as latex condoms) during intimate sexual contact toprevent infection by viruses that can damage the liver.
• Avoid exposure to chemicals (solvents, aerosol cleaners, insecticides, paint thinners, and other toxins) that canbe harmful to the liver. If you must use these substances, wear a mask and gloves and work in a well-ventilated
area.
Written by Wendy Landier, PhD, CPNP, Children’s Hospital of Alabama, Birmingham, AL.
Reviewed by Daniel Smith, DNP, FNP; Kayla L. Foster, MD, MPH; and Melissa Acquazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

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Mental Health after Cancer Treatment
The Cancer Experience
Diagnosis and Treatment
Diagnosis and treatment are difficult times for people with cancer and their families. During diagnosis, children or
teens have tests and procedures that are new, sometimes painful and often scary. For parents, the anxiety of waiting
for the results of these tests and procedures can be the worst part of this time. Learning the diagnosis can be a relief,
especially when effective treatments are available. These treatments, though, can be unpleasant for children to haveand upsetting for families to watch or give. Tests and procedures are repeated during treatment to find out if thetreatment plan is working or should change. Children and teens with cancer and their parents are frequently at thehospital, sometimes away from other family, friends, home, work, or school for long periods of time. Parents worry
about whether their child’s cancer will be cured, how to minimize their suffering, and how to make the most of life.
Brothers and sisters also worry about, and are sometimes jealous of the sibling with cancer. Childhood cancer survivors
and their siblings can be concerned about their parents, and keep worries and feelings to themselves to try to protect
their parents. As a result, people diagnosed with cancer, their parents, and their siblings can feel angry, lonely, sad, andafraid during treatment. Periods of anxiety and depression can occur.
After Treatment Ends
For survivors and their families, the end of treatment can bring new feelings as they come to know the good (andsometimes not so good) outcomes of successful treatment. During treatment, people tend to be concerned withgetting through the day-to-day. It is after treatment that people can begin to think about and come to terms with theirexperience. People can have a range of feelings after treatment ends, and the blend of feelings can be as unique as
each person. Survivors and their families often fear that the original cancer will return. Regular testing for recurrent
cancer or late effects, and even just talking about possible late effects can cause stress. The diagnosis of a late effectrelated to cancer treatment or a new health problem unrelated to childhood cancer can also be sources of distress.
Anniversaries of cancer events, such as the date of diagnosis or end of treatment, and life changes such as school
entry or the normalization of peer relationships can bring on feelings that include relief and happiness, sadness about
the loss of a regular childhood, and guilt over having survived when others did not. Some survivors may feel vulnerable
because of their cancer experience and can be concerned about their health and act with caution. Parents of childhood
cancer survivors very much want to protect all their children from harm. These protective feelings can increase usual
tensions between parents and teenagers over issues related to growing independence, especially in matters that canaffect health. Other individuals who have had cancer believe that having survived cancer, they can do anything—and
this makes them feel invincible. These feelings can lead some survivors to undertake difficult studies, work, or hobbies.
The same feelings can lead other survivors to take part in unhealthy or risky behaviors.
Some Reactions to the Stresses of Survivorship
For the most part, childhood cancer survivors and their family members respond well to the stresses of survivorship.
Sometimes though, physical problems or other stresses related to childhood cancer and everyday life can lead tointensely distressing emotions that need medical attention. Some survivors, and their family members, can experience
periods of high anxiety that may or may not be triggered by reminders of the upsetting aspects of treatment. They
may develop three types of symptoms typically seen in people with posttraumatic stress disorder (PTSD), including (1)unwanted recall of unpleasant memories of cancer, (2) physical or emotional overreactions, and (3) going out of the way
to avoid reminders of cancer. For the most part, childhood cancer survivors and their family members do not develop all
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three types of symptoms and PTSD. Yet one or two of these symptoms can nonetheless get in the way of relationships,
school, work, and other key areas of daily life after cancer.
Personal growth can be another reaction to the stresses of life after cancer. After years of living with childhood cancer,
some survivors and their family members may find that they have undergone meaningful and beneficial changes inthemselves, their relationships with other people, and their values as a result of their experiences. Furthermore, they may
have been able to find some positive changes in their lives as a result of surviving the cancer experience. Experiencing
these positive changes is sometimes referred to as posttraumatic growth.
Risk Factors
Several factors can affect the development of depression and anxiety with symptoms of posttraumatic stress after
diagnosis and treatment of childhood cancer, including:• Female gender• Adolescent or young adult age• Prior trauma• Mental health or learning difficulties before childhood cancer• Developing health problems or physical limitations due to cancer treatment• Low levels of social support• Parental history of depression, anxiety, or PTSD
• Central nervous system (CNS) cancers (brain or spine) or treatment (radiation to the head/spine or intrathecal
chemotherapy)• Treatment with hematopoietic cell transplant (bone marrow or stem cell transplant)
When to Seek Help
People with distress that (1) lasts two weeks or more, and/or (2) interferes with their ability to do daily home, schoolor work tasks, should call their healthcare provider to discuss the need for a referral to a mental health professional.
Because physical health problems can cause these same symptoms, a thorough check-up by your primary healthcare
professional is recommended if they occur. Some possible signs that help is needed can include:• Changes in appetite and weight• Crying easily or being unable to cry• Constant tiredness and low energy level• Sleeping more than usual or being unable to sleep• Feeling hopeless• Thoughts of hurting yourself or others• Engaging in self-harm behaviors (ie. cutting)• Alcohol or drug use to avoid unpleasant feelings• Increased irritability• Decreased interest in activities that had been pleasurable in the past
• Unwanted recall of painful aspects of cancer• Feeling extremely fearful, upset, or angry when thinking about cancer• Physical reactions (rapid heart rate, shortness of breath, nausea) when thinking about cancer• Avoiding health care visits•

Refusing to talk about cancer

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Share Your Concerns with Your Healthcare Provider
If you experience distress, discuss it with your primary health care provider or childhood cancer specialist. Your
distress may be related to your cancer experience, worries about late effects, or other events in your life. In any
case, there is treatment. Talking with others about your fears and worries is a first step in gaining control over them.
In addition to receiving help from a health care provider, some people also find support through support groups,
participation in activities at their place of worship, or their faith.
Treatment Options
Treatments for depression, anxiety and posttraumatic stress symptoms include counseling in group or individual
sessions and, sometimes, medication. Medication usually works in combination with some form of counseling. Mental
health professionals (including mental health nurse practitioners, psychiatrists, psychologists, and social workers)
provide treatment for depression and anxiety in a variety of community settings. Your primary healthcare provider canhelp you find a suitable mental health professional in your community.
Resources
Support is available to childhood cancer survivors and their families who have anxiety and depression after treatment.
These are just a few of the many resources available:
American Cancer Society www.cancer.org
This site provides web-based support network, other programs and services, and stories of hope for cancer survivors
and their families.
American Psychiatric Association www.psychiatry.org
This site provides guidelines for choosing a psychiatrist.
The Anxiety and Depression Association of America www.adaa.org
This site provides information that can help people with anxiety disorders and depression find treatment and develop
self-help skills.
American Childhood Cancer Organization www.acco.org
This site offers education, support, service, and advocacy for childhood cancer survivors, their families and theprofessionals who care for them.
Childhood Cancer Guides www.childhoodcancerguides.org
This site provides articles related to psychosocial aspects of survivorship.
Children’s Oncology Group www.childrensoncologygroup.org
This site provides parents and families with information related to specific cancer type, treatment stage and age groupas well as tips on navigating the health care system, getting and giving support, and maintaining a healthy lifestyle.
National Institute of Mental Health www.nimh.nih.gov
This site provides general information about anxiety or depression, available treatments, finding a mental healthprovider, and access to research reports and other relevant information. See these specific areas of the web site:www.nimh.nih.gov/health/topics/anxiety-disorders
www.nimh.nih.gov/health/topics/depression

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Revised by Sheila J. Santacroce, PhD, APRN, CPNP, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC. Originallyadapted by Debra A. Kent, RN, MSN, CPNP, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, from “Dealing with
Emotions after Childhood Illness” by Melissa Hudson, MD, After Completion of therapy (ACT) Clinic, St. Jude Children’s Research
Hospital, Memphis, TN.
Reviewed by by Leeann Carmichael, DNP, APN, FNP-BC; Christine S. Yun, MSN, PNP, CPON; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Testicular and Reproductive Health after Cancer Treatment
The effects of childhood cancer therapy on reproductive function depend on many factors, including the specific typeand location of the cancer, and the treatment that was given. It is important to understand how the testes function andhow they may be affected by cancer treatment.
The reproductive system
The reproductive system contains many structures and is controlled by thepituitary gland in the brain. The testes are located in the scrotum (the loose
pouch of skin behind the penis). The testes are made up of leydig cells (cells
that produce the hormone—testosterone) and sertoli cells (cells that support
the sperm production). At the time of puberty, the pituitary gland in thebrain releases two hormones (FSH and LH) that signal the testes to begin
producing sperm and testosterone. As puberty progresses, testosterone
causes deepening of the voice, enlargement of the penis and testes, growthof facial and body hair, and muscular development of the body.

UreterVas deferens
Seminal
VesicleProstate
Gland

UrethraEpididymis

Testicle
Scrotum
Penis

How does cancer therapy affect the testes?
Cancer therapy can cause infertility (the inability to initiate a pregnancy).
Infertility can occur following treatment with certain types of chemotherapy,
radiation to the brain or testes, or surgery involving the reproductive system.
Another possible effect of cancer therapy is testosterone deficiency, also known as “hypogonadism”. When this occurs,
the testes are unable to produce enough testosterone hormone. If this happens before the age of puberty, puberty may
not start without hormone medication prescribed by a doctor. If it develops after puberty, testosterone therapy may beneeded to maintain muscular development, bone and muscle strength, proper distribution of body fat, sex drive, and theability to have erections.
What are the causes of male reproductive problems after childhood cancer treatment?
Chemotherapy of the “alkylator” type (such as cyclophosphamide, thiotepa, melphalan and busulfan) and heavy
metals (such as cisplatin and carboplatin) may cause testicular damage. The total dose of chemotherapy used duringcancer treatment is important in determining the likelihood of damage. The higher the total dose, the more potential fordeveloping problems such as infertility or testosterone deficiency. If alkylating or heavy metal chemotherapy was used in
combination with radiation, the risk for testicular damage is increased.
Radiation therapy can affect testicular function in two ways:•

Radiation aimed directly at or near the testes. The sperm-producing cells are very sensitive to the effects ofradiation therapy. Most individuals who receive radiation to the testes at doses of 6 Gy (600 cGy/rads) or higher
will be infertile. The testosterone producing cells are more resistant to the effects of radiation and chemotherapy,
but if testicular radiation was given in doses of 12 Gy (1200 cGy/rads) or higher, the leydig cells may be damaged,
resulting in testosterone deficiency (in addition to infertility).

•

Radiation to the hypothalamic and pituitary gland regions in the brain. The hypothalamus and pituitary gland
regulate the production of two hormones (LH and FSH) needed to signal the testes to make testosterone andsperm. People with low levels of these hormones will need to take testosterone hormone replacement. For some

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survivors, it is possible to regain fertility with the use of specialized hormone treatments. Individuals who haveinfertility as a result of brain radiation and wish to achieve fertility should see a fertility specialist.
Surgery that involves removal of both testicles (bilateral orchiectomy) will result in infertility and testosterone
deficiency. Pelvic surgery, such as retroperitoneal lymph node dissection (RPLD), or spinal surgery sometimes results innerve damage that may prevent the ejaculation of sperm. Removal of the prostate or bladder may result in difficulties
achieving an erection and/or ejaculation. In these situations, sperm production may be unaffected and fertility may still
be possible by using specialized techniques, such as sperm harvesting and artificial insemination. If fertility is desired,consultation with a fertility specialist is recommended.
What types of cancer therapy increase the risk of problems with testicular function?
•

Chemotherapy - the class of drugs called “alkylators” can cause infertility when given in high doses. Very highdoses may occasionally cause testosterone deficiency. Heavy metal chemotherapy can also affect testicularfunction. Examples of these drugs are:Alkylating agents:– Busulfan– Carmustine (BCNU)– Chlorambucil– Cyclophosphamide (Cytoxan®)– Ifosfamide
Heavy metals:– Carboplatin– Cisplatin

•

–
–
–
–

Lomustine (CCNU)
Mechlorethamine (nitrogen mustard)
Melphalan
Procarbazine– Thiotepa
Non-classical alkylators:– Dacarbazine (DTIC)– Temozolomide
Radiation therapy to any of the following areas may cause infertility:– Testes– Total body irradiation (TBI)– Head/brain especially if dose was 30 Gy (3000 cGy/rads) or higher
In addition to causing infertility, high doses of radiation to the testes (usually 12 Gy or higher) or brain (usually
30 Gy or higher) may also cause testosterone deficiency.

•

Surgeries that may cause infertility or disrupt normal sexual functioning include:–

Removal of both testicles (this surgery will always result in infertility)–

Removal of one testicle or a portion of one testicle–

Retroperitoneal lymph node dissection (RPLD)–

Removal of tumor in the retroperitoneal area–

Pelvic surgery–

Cystectomy (removal of the bladder)–

Prostatectomy (removal of the prostate)

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Spinal surgery–

Removal of tumor near the spinal cord

In addition, removal of both testicles will result testosterone deficiency, and removal of one testicle or a portion of
one testicle may result in low testosterone levels.
What monitoring is recommended?
Individuals whose treatment places them at risk for problems with the reproductive system should have a yearly
check-up that includes careful evaluation of their sexual development. Blood may be tested for hormone levels (AMtestosterone, LH, FSH, and inhibin). If any problems are detected, a referral to an endocrinologist (hormone specialist),
urologist (specialist in the reproductive system) and/or fertility specialist may be recommended. Individuals who have
had both testes removed should begin seeing an endocrinologist starting at about age 11 for hormone replacement.
People who have had fertility preservation procedures (saving sperm outside of the body or “cryopreserved”), should
review previous fertility counseling and current options for family building with a fertility specialist.
What can be done for testosterone deficiency?
Individuals with low testosterone levels should receive testosterone replacement therapy. Testosterone is available inseveral forms, including skin patches, injections, and topical gel. Your endocrinologist will determine which form of
therapy is best for you.
How will I know if I am infertile?
Infertility, the inability to initiate a pregnancy after a year of unprotected intercourse, can occur after cancer treatment.
Recovery of the ability to make sperm may occur in some survivors. When recovery occurs, it usually happens in thefirst few years after completion of cancer treatment. The best way to assess the ability to make sperm is a semen
analysis which evaluates the number of sperm produced, the motility (movement of the sperm) and morphology (whatthe sperm look like). The specimen is produced after several days of abstinence. If the patient is unable to produce asemen specimen or prefers not to, an FSH and inhibin level may provide some insight into the ability to make sperm. A
high FSH or low inhibin suggest impaired ability to make sperm.
A semen analysis that shows azoospermia (no sperm in the semen sample) on more than one sample is an indicatorof infertility. Patients with oligospermia (low sperm count) may still be able to have children with the help of fertility
specialists.
In general, contraception should be used unless pregnancy is desired.
What if only one testicle or a portion of one testicle was surgically removed?
Although fertility and testosterone production are not usually affected if only one testicle or a portion of one testicle
was surgically removed, you should take precautions to protect the remaining testicle from injury by always wearing
an athletic supporter with a protective cup when participating in any activities that may potentially cause injury to thegroin area (such as contact sports, baseball, etc.).
What are the risks if pregnancy occurs after childhood cancer treatment?
Fortunately, in most cases, there is no increased risk of cancer or birth defects in children born to childhood cancer
survivors. In rare cases, if the type of cancer in childhood was a genetic (inherited) type, then there may be a risk ofpassing that type of cancer on to a child. You should check with your oncologist if you are not sure whether the type ofcancer you had is associated with a genetic risk that can be passed on.
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Written by Marcia S. Leonard, RN, CPNP, C.S. Mott Children’s Hospital, Ann Arbor, MI.
Reviewed by Katy Tomlinson, RN, BSN; Lillian R. Meacham, MD; Melissa Acquazzino, MD, MS; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Neurogenic Bladder after Cancer Treatment
Certain types of cancer and certain cancer treatments can cause damage to the urinary bladder. The information in thisHealth Link will help you to recognize the signs and symptoms of a neurogenic bladder.
What is the urinary bladder?
The urinary bladder is a hollow organ that stores urine. It is located behind the pubic
bone. The kidneys filter the blood and make urine, which enters the bladder throughtwo tubes called “ureters.” Urine leaves the bladder through another tube, the urethra.
What are the risk factors for neurogenic bladder?
•

Tumors involving the bladder, prostate, pelvis, or spine•

Radiation therapy to these areas•

Surgery to these areas

What is a neurogenic bladder?
A neurogenic bladder is abnormal function of the bladder caused by damage to the nerves that control the bladder’sability to fill, store and empty urine. Abnormal bladder function can cause the bladder to be underactive (not emptying
completely) or overactive (emptying too frequently or quickly). People with neurogenic bladders also have a higher riskof urinary tract infections (UTIs) and kidney damage.
What are the symptoms of a neurogenic bladder?
There may be a sudden urge to urinate or the need to urinate frequently. There may also be dribbling during urination,straining to urinate, or the inability to urinate.
Who is at risk of a neurogenic bladder?
People who have had tumors involving the bladder, prostate, pelvis, or spine are at risk of developing neurogenic
bladder. Also, people who had surgery or radiation in these areas may be at risk.
How is a neurogenic bladder diagnosed?
If a neurogenic bladder is suspected, an evaluation should be done by a urologist. A urologist is a physician who
specializes in disorders of the urinary tract. The urologist will order tests to determine how well the bladder is able tostore and empty urine, such as a voiding cystourethrogram (VCUG) or bladder cystometry.
What can I do if I have a neurogenic bladder?
Treatment of neurogenic bladder is based on your individual needs. Medications may be useful for an overactive
bladder or for a bladder that fails to store urine properly. Surgery to enlarge the size of the bladder may be needed if
the medications are not successful.
Removal of urine by insertion of a small, clean tube in the urethra several times a day (intermittent catheterization)
may be necessary if you cannot completely empty your bladder. This helps prevent high pressure in the bladder thatinterferes with flow of urine from the ureters and kidneys.

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When should I call my healthcare provider?
Call your healthcare provider if you are awakened more than usual during the night to urinate, if leakage of urine occurs,
any time fever or pain is present, or if blood is seen in the urine.
Written by Patricia Shearer, MD, MS, Emory Healthcare, Johns Creek, GA; Michael L. Ritchey, MD, Phoenix Childrens Hospital,
Phoenix, AZ; Fernando A. Ferrer, MD, Children’s Hospital and Medical Center of Omaha, Omaha, NE; and Sheri L. Spunt, MD, Lucile
Packard Children’s Hospital Stanford University, Palo Alto, CA.
Reviewed by Linda Rivard, RN, BSN, CPON; Kayla L. Foster, MD, MPH; and Christine Yun, MSN, PNP, CPON.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities, or
damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Osteonecrosis after Cancer Treatment
What is osteonecrosis?
Osteonecrosis is a disorder resulting from a temporary or permanent loss of blood supply to the bone. Blood carries
essential nutrients and oxygen to the bones. When the blood supply is disrupted, the bone tissues (osteo) begin to break
down (necrosis). This can weaken the bone and eventually result in its collapse. If this occurs near a joint, it can leadto the collapse of the joint surface, resulting in pain and inflammation (arthritis). Osteonecrosis is also referred to as
avascular necrosis or “AVN,” “aseptic necrosis,” and “ischemic bone necrosis.”
Osteonecrosis can occur in any bone, but most commonly affects the ends (epiphysis) of long bones such as the thighbone (femur), causing hip and knee problems. Other common sites include the bones of the upper arms, shoulders, andankles. Osteonecrosis can occur in a single bone, but more commonly occurs in several bones at one time (multifocal
osteonecrosis).
Osteonecrosis can sometimes be disabling, depending on what part of the bone is affected, how large an area isinvolved, and how well the bone rebuilds itself. Normal bone continuously breaks down and rebuilds itself. This process
keeps the bones strong. Osteonecrosis is the result of bone tissues breaking down faster than the body can repair them.
If the disorder progresses, it can lead to pain and arthritis.
What causes osteonecrosis?
Osteonecrosis is caused by interruption of the blood supply to the bone. If blood vessels are blocked with fat, become
too thick or too small, or get too weak, they may not be able to provide the amount of blood necessary for the bone
tissue to survive.
What are the risk factors for osteonecrosis?
Corticosteroids (such as prednisone and dexamethasone) given during cancer treatment can affect the bone andblood vessels, resulting in osteonecrosis. People who have undergone hematopoietic cell transplant (bone marrow,cord blood, or stem cell transplant) are also at risk for developing osteonecrosis. Other factors that increase the risk ofosteonecrosis in people who received corticosteroid therapy or hematopoietic cell transplant (HCT) include treatment
with high doses of radiation to weight bearing bones, treatment with older radiation approaches (before 1970), being
pubertal or post-pubertal at the time of treatment, having sickle cell disease, receiving total body irradiation (TBI),
undergoing an allogeneic transplant (from a donor) and having prolonged treatment with corticosteroids for chronic
graft-versus-host disease following HCT. Osteonecrosis is most likely to occur during the time that cancer is being
treated, but it can also sometimes happen after completion of cancer therapy.
Steroids and osteonecrosis
Corticosteroids (such as prednisone and dexamethasone) are commonly used for treatment of many cancers, such as
leukemia and lymphoma. Dexamethasone is also sometimes used for treatment of nausea and vomiting associatedwith chemotherapy and to control brain swelling. There is no clear explanation as to how corticosteroids cause
osteonecrosis, but it is believed that they may interfere with the body’s ability to break down fatty substances. These
substances can clog the blood vessels, causing them to narrow. This reduces the amount of blood that gets into thebone.

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What are the symptoms of osteonecrosis?
People in the early stages of osteonecrosis may not have any symptoms. For some individuals, the first symptoms may
be mild joint pain either with movement or at rest and, when caught early, may heal with conservative treatment. Moresevere osteonecrosis can result in significant pain and impaired mobility.
How is osteonecrosis diagnosed?
If you or your child develops joint pain concerning for osteonecrosis, your provider may recommend images of the joint.
This can include an X-Ray, MRI, CT or bone scan.
How is osteonecrosis treated?
The goals of treatment for osteonecrosis are pain control, maintaining joint function and preventing further damage.
Treatment can be conservative or surgical. To decide the best treatment, the following factors are considered:• The person’s age• The stage of the disorder (early or late)• The location and the amount of bone affected (small or large)• The status of cancer and cancer treatment
Conservative treatment• Medication—to reduce pain
• Reduced weight bearing—to slow the damage and promote natural healing. Crutches may be recommended tolimit weight or pressure on the affected joint• Range of motion exercises—to keep the joints flexible. This is also important to maintain movement and increase
circulation in the joints. This can promote healing and may relieve pain. Physical therapists can teach the correct
exercises•

Electrical stimulation—to induce bone growthConservative treatments may be used alone or in combination, but they may not provide lasting improvement. Somepeople may require surgery to permanently repair or replace the joint.
Surgical Treatment• Core decompression—is a surgery that removes the inner layer of bone. This may reduce pressure within thebone and create an open area for new blood vessels to grow. Sometimes a piece of healthy bone with good bloodvessels (bone graft) is put in this area to speed up the process. This procedure works best in the early stages ofosteonecrosis and should help relieve pain and promote healing.
• Osteotomy—is a surgery that involves taking out a piece of bone, usually a wedge, to reposition the bone so thatthe tissue lacking blood supply (avascular area) bears less weight than nearby healthy bone.
• Arthroplasty—is also referred to as joint replacement. The affected bone is removed and replaced with anartificial joint. This treatment may be needed in the late stages of osteonecrosis and when a joint is destroyed.
Health Promoting Behaviors/Interventions• Avoid activities that put a lot of stress on your joints. Activities that stress the joints include running, jumping,football, soccer, volleyball, basketball, and similar sports. Low impact activities, such as swimming and bicycling,
can be good for joint health.
• Be consistent with recommended exercises.
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Rest joints when they hurt.

•

Let your healthcare provider or physical therapist know if there are any changes in your symptoms.

•

Take pain or anti-inflammatory medications as prescribed.

•

MInd-body therapies such as massage, acupuncture, biofeedback, and relaxation techniques may improve pain
control, increase blood flow and reduce stress.

Resources•

National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institutes of Health, 1 AMS Circle, Bethesda, MD 20892-3675
Phone: 301-495-4484 or 877-226-4267 (toll free), TTY: 301-565-2966
Fax: 301-718-6366. Web: https://www.niams.nih.gov/health-topics/osteonecrosis•

American Academy of Orthopaedic Surgeons
9400 West Higgins Road, Rosemont, IL 60018
Phone: 847-823-7186 (toll free). Web: www.aaos.org

Adapted by Katherine Myint-Hpu, MSN, MPH, PNP, National Institutes of Health Clinical Center, Washington, DC, from “Health
Topics: Questions and Answers about Avascular Necrosis” by the National Institute of Arthritis and Musculoskeletal andSkin Diseases, January 2001, and “Avascular Necrosis – Do You Know” by St. Jude Children’s Research Hospital, used withpermission.
Reviewed by Leeann Carmichael, DNP, APN, FNP-BC; Kayla L. Foster, MD, MPH; and Melissa Acquazzino MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

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Osteoradionecrosis after Cancer Treatment
What is osteoradionecrosis?
Osteoradionecrosis (ORN) is a problem with bone healing that can occur in people who received high doses of radiation,
particularly to the jaw. This complication can occur after dental surgery or extraction of teeth. High doses of radiation
can decrease the bone’s blood supply. If this happens, the bone gets less oxygen than it needs, resulting in the death(necrosis) of bone tissue. The most commonly affected bone is the jawbone (mandible).
Who is at risk for osteoradionecrosis?
Survivors who received high doses of radiation to the jaw area (40 Gy or 4000 cGy/rads or higher) are at risk for thiscomplication. Radiation fields that often include the jawbone are as follows:•

Head/brain

•

Neck

•

Spine (“cervical” portion)

It is important to obtain your medical records so that you know exactly how much radiation you received and where theradiation was directed. For example, survivors exposed to radiation doses of 50 Gy or higher to the jawbone have thehighest risk for the development of ORN.
When does osteoradionecrosis occur?
Although it is uncommon, ORN most often occurs when a survivor undergoes a dental procedure (such as pulling of
tooth) or other surgery involving the jawbone.
What are the symptoms of osteoradionecrosis?
Symptoms of ORN may occur months to years after radiation. Common symptoms include mouth pain, jaw swelling anddifficulty opening the mouth fully (trismus).
How is osteoradionecrosis diagnosed?
ORN can be diagnosed by physical examination and imaging studies (x-ray, CT scan and/or MRI). Sometimes, a surgeon
may need to take a sample (biopsy) of the problem area to make a definite diagnosis. Radiation therapy records should
be reviewed to determine the location and dose of radiation that was given.
How is osteoradionecrosis treated?
Treatment of ORN is mainly through control of uncomfortable symptoms. Salt-water rinses and light scrubbing ofaffected tissues may be helpful. Antibiotics may help if a wound becomes infected. Hyperbaric oxygen therapy (oxygen
delivered in a pressurized chamber) is sometimes used to increase the amount of oxygen given to the affected tissues
and improve the chance of healing.
Is there anything I can do to prevent osteoradionecrosis?
People who received radiotherapy involving the jaw should:•

Tell their dentist that they received radiation. The dentist will then be able to get details about the radiation
treatment before doing any tooth extractions that could lead to ORN.

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Have regular dental care and take good care of their teeth and gums, since the risk for cavities is higher in people
who received large doses of radiation. The dentist may order daily fluoride treatments to reduce the risk of cavities
and the need for extracting teeth in the future. (See related Health Link: Dental Health)Resources
The Oral Cancer Foundation
3419 Via Lido #205, Newport Beach, CA 92663
Phone 949-723-4400
Web: https://oralcancerfoundation.org/complications/osteoradionecrosis/
Written by Arnold Paulino, MD, MD Anderson Cancer Center, Houston, TX.
Reviewed by Kayla L. Foster, MD, MPH; Sarah Ford, MS, PA-C; and Melissa Acquazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities, or
damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Peripheral Neuropathy after Cancer Treatment
What is peripheral neuropathy?
Peripheral neuropathy, or damage to the peripheral nerves (nerves outside the brain or spinal cord), is a potential side
effect of chemotherapy drugs and may cause the hands or feet to hurt, tingle, and feel numb or weak. Though thediscomfort is felt in a muscle or joint, the real damage is to the nerves that control the muscles. Nerves are made upof special cells that carry messages to and from the brain and spinal cord. Damage to the nerve is often caused by abreakdown of the myelin sheath, the coating around nerve fibers that acts as an electrical insulator. There may also
be direct damage to the nerve cells from pressure or trauma (for example from a tumor or surgery). Symptoms usually
start during treatment and persist and are not late in onset. Symptoms often improve once treatment has stopped, but
for some survivors, symptoms may persist for months or years.
Symptoms•

Burning, tingling, or prickling sensation usually in the hands or feet•

Numbness or sensitivity to pain or temperature•

Extreme sensitivity to touch•

Sharp shooting pain•

Poor balance or coordination•

Loss of reflexes•

Muscle weakness•

Noticeable changes in the way you walkMuscle weakness may begin around the arch of the foot and in the palm of the hand. It may be difficult to grip thingsor to perform certain tasks or activities such as writing, buttoning clothes, or tying shoes. The muscles that pull the footup may weaken and the reflexes may be lost, causing the front part of the foot to fall flat to the floor. This may resultin poor balance or coordination, especially when tired. There may be a tendency to drag the feet or lift them high to prevent the feet from dragging.
Who is at risk?
People who have received any of the following chemotherapy drugs may be at risk:•

Vincristine•

Vinblastine•

Cisplatin•

Carboplatin

People at highest risk for peripheral neuropathy are those who have received higher doses of these drugs or combinations of these drugs. Other risk factors include surgery, severe weight loss, and diabetes or a pre-existing nerve disease. Prolonged pressure on nerves from artificial limbs, wheelchairs, or crutches can also contribute to nerve damage.

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Treatment
Rehabilitation services
Because there is no treatment that can cure or reverse nerve damage, treatment is directed toward symptom management. Physical therapy is often helpful in providing exercises to improve strength, balance, and coordination. Occupational therapy can provide help to improve hand/eye coordination and other skills needed for daily life.
Orthotic devices
Support for feet or ankles can be improved with orthotic devices. Arch supports or splints help prevent the arch fromflattening and help improve walking. Splints called ankle-foot-orthoses (AFOs) may be recommended to prevent theankle from moving too much from side to side and to support the foot when walking.
Pain management
Your healthcare provider may prescribe medication to control the pain, tingling, and burning sensation. The type of
medication depends on the frequency and severity of pain. It is also important to know that some medications will
have side effects of their own. Elastic stockings, warm packs, or exercise may also help with the discomfort. These
measures will not replace medication but may decrease the need for them. They may also assist in improving mobility
and independence.
Additional recommendations•

Avoid shoes that are too tight or too loose—Just as shoes that are too tight can cause throbbing, rubbing,and cramping, shoes that are too loose can worsen pain and may not provide enough support for already wobbly
feet. Well-fitting sneakers or shoes that provide support but are also flexible are best.

•

Be sensitive to temperature—Many people report that neuropathy feels worse in hot weather or when feet areheavily covered, which may prevent adequate air circulation.

•

Keep feet uncovered in bed—Bed sheets resting on toes can cause discomfort due to friction between the
sheet and toes.

•

Massage—Massaging your hands or feet or having someone else massage them can be extremely soothing
and relaxing and can increase circulation and boost endorphins (chemicals produced in the body that help control pain).

•

Cool soaks—Cool water soaks to painful hands or feet can sometimes dull pain enough to fall asleep or until
pain medication has time to work.

For additional information, contact:
The Foundation for Peripheral Neuropathy
485 Half Day Road, Suite 350, Buffalo Grove, IL 60089
Phone: 877-883-9942
Website: www.foundationforpn.org

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Written by Susan V. Shannon, RN, MSN, CPNP, CPON®, Miller Children’s and Women’s Hospital Long Beach, Long Beach, CA.
Reviewed by Kayla L. Foster, MD, MPH; Beth Fisher, DNP, APRN, CPNP; and Melissa Acquazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Precocious Puberty after Cancer Treatment
Some people who were treated for cancer during childhood may develop endocrine (hormone) problems as a result ofchanges in the function of a complex system of glands known as the endocrine system.
Pituitary gland

What is the endocrine system?

Hypothalamus

The endocrine system is a group of glands that regulate
body functions including growth, puberty, energy level, urine
production, and stress response. Glands of the endocrine
system include the pituitary, hypothalamus, thyroid, pancreas,
adrenal, ovaries, and testes. The hypothalamus and pituitary
are sometimes called the “master glands” because they control
many of the other glands in the endocrine system. Unfortunately,some treatments given for childhood cancer can damage theendocrine system, resulting in a variety of problems.

Thyroid

Pancreas
Adrenal glands

Ovaries

What are hormones?

TestesHormones are chemical messengers that carry information fromthe endocrine glands through the bloodstream to the body’s
cells. The endocrine system makes many hormones (such as growth hormone, sex hormones, adrenal and thyroid
hormones) that work together to maintain specific bodily functions.
What is the normal age for puberty to begin?
Puberty normally begins between the ages of 8 and 13 in children born with ovaries, and 9 and 14 in children bornwith testes. The timing of puberty is influenced by a person’s genetic background, and the onset of puberty at a young
age may run in families. Most children born with ovaries begin to develop breasts and then pubic hair at around age 10
or 11. Menstrual periods usually start at around 12 to 13 years of age but may occur earlier or later and still be normal.
Children born with testes usually begin to develop enlargement of the testicles and then pubic hair between 11 and 12
years of age.
What is precocious puberty?
Precocious puberty means having signs of puberty (such as pubic hair or breast growth) at an age younger than isnormally expected. Most healthcare providers agree that a child born with ovaries has precocious puberty if sexual
traits develop earlier than age 8, and a child born with testes has precocious puberty if sexual traits develop prior toage 9.
The early release of hormones that cause precocious puberty also causes a growth spurt, with rapid bone growth. Earlybone maturation results in less time for growth, so the child with precocious puberty will have a final adult height thatis actually much shorter than expected.
What are the risk factors for developing precocious puberty?
• Radiation to the head or brain, especially doses of 18 Gy (1800 cGy/rads) or higher• Children with ovaries• Younger age at the time of cancer treatment• Being overweight or obese
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Why does precocious puberty happen?
The hypothalamus and pituitary gland in the brain may be damaged after radiation treatments. The damage causes
them to signal the ovaries or testicles to make sex hormones at an earlier time. In other cases, signs of puberty occur
early because of abnormalities in the ovaries, testes or adrenal glands. Tests are done to learn if the cause of precocious
puberty is in the brain or in another part of the body.
What screening is recommended?
All childhood cancer survivors should have a yearly comprehensive health check-up including measurement of height
and weight, and evaluation of pubertal progress. If there are signs of accelerated growth or precocious puberty, yourhealthcare provider may order a blood test to check sex hormones produced in the brain (FSH—follicle stimulating
hormone; LH—luteinizing hormone), testes (testosterone) or ovaries (estradiol) as well as possibly order an x-ray thatmeasures the developmental age or maturation of bone (bone age). Your healthcare provider should refer you to an
endocrinologist (hormone specialist) for further evaluation and treatment.
How is precocious puberty treated?
Endocrinologists may use medications to temporarily stop puberty and to decrease the rate of bone maturation. It isalso important to evaluate and manage the psychological effects of beginning puberty too early. Although children withprecocious puberty may have a mature physical appearance, their thoughts, emotions, and behaviors may still be that of
their actual (chronological) age.
Written by Debra A. Kent, RN, MSN, CPNP, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.
Reviewed by Lillian R. Meacham, Daniel Smith, DNP, FNP; Christine Yun MSN, PNP, CPON®; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s
Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by
the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification:(i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities,
or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational
Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Pulmonary Health after Cancer Treatment
The lungs are very important organs that supply oxygen to the body. Sometimes, treatments given for childhood cancer
can cause lung damage. If you received any treatments that may cause lung problems, it is important to learn about thelungs, and what you can do to keep them as healthy as possible.
How the lungs function
The lungs transfer oxygen from the air to the blood, where it is circulated to the body tissues. The lungs also remove
carbon dioxide, a waste product made by the body’s cells. For oxygen to reach the blood, it must move through tiny air
sacs (alveoli) in the lungs and into tiny blood vessels (capillaries) that surround each air sac. When the air sacs become
damaged or scarred, there is less area for oxygen to enter the bloodstream, and less oxygen reaches the blood. The
person may then need to breathe faster in order to get enough oxygen. This can make the person feel short of breath.
Other lung problems can be caused by inflammation (swelling) of the air passages in the lungs or increased mucous
production as a result of irritation or infection. Symptoms can include cough, wheezing, chest pain, and shortness ofbreath.
Am I at risk for lung problems?
If you received any of the following treatments during your cancer therapy, you may be at risk for developing lungproblems:• Bleomycin (See the “Bleomycin Alert” Health Link for more information)• Carmustine (also known as BCNU)• Lomustine (also known as CCNU)• Busulfan• Radiation to the chest or axilla (underarm area)• Total body irradiation (TBI)• Surgery involving the chest or lung (this does NOT include surgery for placement of a central line, such as a
Hickman, Broviac, Port-a-Cath or Mediport)• Chronic graft-versus-host disease (cGVHD) following bone marrow transplant or stem cell transplant from a donor
other than yourself (allogeneic transplant)• Certain chemotherapy drugs known as anthracyclines, such as daunorubicin (Daunomycin®), doxorubicin(Adriamycin®), Mitoxantrone (Novantrone®), idarubicin (Idamycin®) and epirubicin can damage the heart andmay contribute to lung problems, especially if given in combination with bleomycin, BCNU, CCNU, and radiation
treatment.
Other factors that may increase your risk are:
• Younger age at the time of cancer treatment• A history of lung infections, asthma or other lung problems• Tobacco use or exposure to secondhand smoke•

Inhaled drugs, such as smoking marijuana, vaping, or cocaine

What problems can develop?
Problems can include scarring of the lungs (pulmonary fibrosis), repeated lung infections (such as chronic bronchitis,
bronchiectasis, or recurrent pneumonia), inflammation of the lung tissues and small airways within the lungs
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Healthy living after treatment of childhood, adolescent, and young adult cancer(bronchiolitis obliterans), and rupture of the tiny air sacs in the lungs or thickening and blockage of air passages within
the lungs (restrictive/obstructive lung disease).
What are the symptoms of lung damage?
Symptoms may include shortness of breath, frequent coughing and/or wheezing, chest pain, and frequent lunginfections, such as bronchitis or pneumonia. Becoming easily fatigued or short of breath during mild exercise (exercise
intolerance) is sometimes an early symptom of lung damage. If you begin to experience these symptoms, discuss themwith your healthcare provider. A consultation with a lung specialist (pulmonologist) may be recommended.
What monitoring is recommended if I have no symptoms?
• A yearly medical check-up is recommended.
• Pulmonary function tests (including DLCO and spirometry) may show lung problems that are not apparent
during a check-up. For this reason, it is helpful to have these tests done at least once (at least two years after
completing cancer treatment) to find out if there are any problems. Your healthcare provider can decide if further
testing is needed based on these results.
Are there any special precautions I should take?
If you have had any of the treatments listed above you should:• Get the pneumococcal (pneumonia) vaccine.
• Get yearly influenza (flu) vaccines.
• Avoid SCUBA diving, unless you have had a complete check-up and have been advised by a pulmonologist (lungspecialist) that diving is safe.
What can I do to prevent lung problems?
• Avoid or quite smoking.
• Avoid second-hand smoke.
• Get regular physical exercise.
• Avoid inhaled drugs, such as marijuana, vaping, or cocaine.
• Avoid breathing toxic fumes from chemicals, solvents, and paints.
• Follow all safety rules in your workplace, such as the use of protective ventilators in some work environments.
Report any unsafe working conditions to the Occupational Safety and Health Administration (OSHA).
Where can a smoker find help in order to quit?
Your most important resources for quitting smoking are your family, friends and your healthcare provider. Listed below
are some additional sources of education and support:
Telephone Resources
If you don’t have access to the Internet, you can call the following organizations to request educational materials(usually free) about how to quit smoking:American Cancer Society: 1-800-ACS-2345
American Heart Association: 1-800-AHA-USA1
American Lung Association: 1-800-LUNG-USA
National Cancer Institute: 1-800-QUIT-NOW
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On-Line Resources
If you have access to the Internet, you may find the following websites helpful:
Information from the National Institutes of Health to help you quit smoking is available at: www.smokefree.gov
The Center for Disease Control’s Tobacco Information and Prevention Source (TIPS) includes guides for quitting the
tobacco habit and is available online at: www.cdc.gov/tobacco/campaign/tips
The American Lung Association’s free online “Stop Smoking” program is available online: www.lung.org/stop-smoking/Where can I find more information about how to keep my lungs healthy?
More information about the lungs, and how to keep them healthy, is available at:
The National Heart, Lung and Blood Institute’s web site with general information for: www.nhlbi.nih.gov/health-topics/
The National Lung Health Education Program has information about how to keep lungs healthy: www.nlhep.org
Written by Charlene Maxen, RN, CNP, CPON®, Childrens Hospital Medical Center of Akron, Akron, OH; and Sarah E. Friebert, MD,
Childrens Hospital Medical Center of Akron, Akron, OH.
Reviewed by Leeann Carmichael, DNP, APN, FNP-BC; Melissa Acquazzino, MD, MS; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Raynaud’s Phenomenon after Cancer Treatment
What is Raynaud’s Phenomenon?
Raynaud’s is a condition that may cause some areas of your body to feel numb and cool in response to cold
temperatures or stress. Raynaud’s causes occasional narrowing of blood vessels, limiting blood flow for brief periodsof time. This is called a vasospasm. During periods of vasospasm, the skin is deprived of oxygen and may become pale
and then turn a bluish color. As the blood vessels relax and blood flow resumes, the skin may become red. The hands
and feet are most affected, but Raynaud’s may also involve the nose, lips, cheeks, and earlobes.
Symptoms• Changes in skin color (often from white to blue to red)
• Changes in skin temperature (affected areas feel cooler)• Numbness or prickly feeling in the fingers (not thumbs) and toes•

Occasional episodes of pain (described as throbbing) and swelling

What happens during an attack?
For most people, cold temperature or stress triggers an attack. Typically, when the body is exposed to cold, the hands
and feet lose heat rapidly. To conserve heat, the body reduces blood flow near the skin surface and moves it deeper inthe body. For people with Raynaud’s, this normal response is exaggerated by sudden spasms of the small blood vesselsthat supply blood to the fingers and toes. This greatly reduces the blood supply to the hands and feet, causing changes
in the skin color and temperature. The first sign is often pallor (or whiteness), in response to the spasm. The skin may
then appear blue (cyanotic) and feel numb or cold, because of a lack of oxygen-rich blood. Finally, the skin may turn
red and become swollen, as the small blood vessels relax and dilate, and blood flow returns. Commonly, throbbing andtingling may occur in the fingers and toes as the attack ends. Raynaud’s attacks can last from seconds to hours.
Who is at risk?
Childhood cancer survivors who received treatment with vinblastine or vincristine sometimes develop Raynaud’s.
Prevention
Raynaud’s is usually a chronic condition that you may need to manage for life. Some people may see improvement
slowly over several years. Prevention of attacks is key:
• Dress warmly when outdoors.
• Take precautions indoors. Wear socks. Avoid drafts (i.e. refrigerator or freezer). Wear mittens when handlingcold items. Use the air conditioner sparingly. Use insulated drinking glasses.
• Avoid putting unprotected hands in cold water.
• Do not use tobacco or drugs as such as cocaine. Nicotine and cocaine constrict blood vessels and causes theskin temperature to drop, which may lead to an attack.
• Exercise. Regular exercise can enhance circulation and help control stress.
• Manage stress. Since stress is often a trigger for Raynaud’s attacks, managing stress may help make the attacks
shorter and less frequent.

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Treatment
Treatment is directed at reducing the number and severity of attacks to prevent tissue damage. People with Raynaud’s
should follow all the above recommendations for preventing attacks. In addition, if attacks are triggered by exposure
to cold, placing the affected body part in warm water may help to stop symptoms. Other treatment methods include
medications and biofeedback.
Medications
Medications that help to dilate blood vessels and promote circulation are sometimes prescribed for management ofsevere symptoms.
Certain prescription medications can sometimes make symptoms worse. These include birth control pills and someheart and blood pressure medicines. If you are taking any of these medications and are having symptoms of Raynaud’s,
consult with your healthcare provider regarding possible alternatives.
Certain over-the-counter cold or diet pills can make symptoms worse and should be avoided. These include drugs that
contain pseudoephedrine (such as Actifed® and Sudafed®).
Biofeedback
Using your mind to control stress and body temperature may help to decrease the severity and frequency of attacks. This
may include guided imagery and/or deep breathing exercises. A psychologist may be helpful in designing a biofeedback
program that meets your needs.
Written by Susan V. Shannon, RN, MSN, CPNP, CPON®, Miller Children’s and Women’s Hospital Long Beach, Long Beach, CA.
Reviewed by Kayla L. Foster, MD, MPH; Beth Fisher, DNP, APRN, CPNP; and Melissa Acquazzino, MD, MS

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities, or
damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Reducing the Risk of Subsequent Cancers
The risk of cancer increases for everyone as they age. Several studies have shown that as childhood cancer survivors
become older, they have a slightly higher risk of developing (a subsequent) cancer compared to people their sameage in the general population. Things that can contribute to this risk are the person’s age during cancer therapy, their
specific treatment, and their genetic and family history.
Who is at risk for a subsequent cancer?

•

People who received certain chemotherapy drugs. Some treatments for childhood cancer increase the risk ofdeveloping subsequent cancer as survivors age. The risk of developing a leukemia from treatment is increased
for people who were treated with high doses of alkylating agents (such as cyclophosphamide or nitrogenmustard), heavy metals (such as cisplatin or carboplatin, epipodophyllotoxins (such as etoposide or teniposide),and anthracycline chemotherapy drugs (such as doxorubicin or daunorubicin), and for those who received an
autologous hematopoietic cell transplant. While leukemias from treatment are rare, the risk is highest within thefirst 10 years after completing cancer treatment and then decreases over time.

•

People who received radiation therapy, especially at a young age. Radiation therapy given for childhood
cancer increases the risk of developing a secondary solid tumor as a person ages. The most common sites
include the skin, breast, central nervous system (the brain and spine), thyroid gland, lungs and bones. In contrast
to secondary leukemias, secondary solid tumors most commonly occur 10 or more years after treatment. The riskof developing a secondary solid tumor is increased when radiation is delivered at high doses and over large fields
to children at a young age.

•

People who have a history of cancer in their family. Some cancer patients have inherited gene changes(mutations) that increase the chances of getting a second cancer. But overall, these inherited changes are
relatively uncommon and account for less than 10 percent of patients with cancer. Doctors suspect the presenceof a cancer gene when a family history shows multiple cancers among young people in every generation, or whencancer occurs in both sides of paired organs (such as the eyes, breasts, kidneys, etc.) If you have any questionsor think that cancer may “run in your family” you should talk to your healthcare provider. A review of your family
medical history will tell whether genetic counseling or testing is needed.

What should you do to decrease your risk and detect a subsequent cancer early?

Reviewing your cancer treatment and family history with your healthcare provider or cancer specialist is important tounderstand your risk for developing a subsequent cancer. Depending on your treatment and what cancer you may atrisk of developing, early or more frequent screening for adult cancers such as color and breast may be recommended
to promote early detection and treatment of subsequent cancers, when they are most likely to be cured. Be sure to get
all screening tests that are recommended for you.
What monitoring is recommended?

By practicing health maintenance behaviors, you can improve your awareness of changes in your body and increase
the likelihood that problems will be detected at earlier stages. All childhood cancer survivors should have a yearly
comprehensive health check-up. You should also have any cancer screening evaluations appropriate for you basedon your age, sex, and treatment history. Knowing the details of your previous medical history, including exposures tochemotherapy, radiation, and surgery, is vital to your future health. This information should be available to you or yourhealthcare provider from the hospital or clinic where you received your cancer therapy. Developing a relationship witha primary care provider who knows your cancer treatment history, risks of late complications, and recommended
screening evaluations will improve the chances of catching problems at earlier, more treatable stages.
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What symptoms should I be alert for?

Be sure to report any new or persistent symptoms to your healthcare provider promptly.
Symptoms that you should report include:• Easy bruising or bleeding• Excessive fatigue• Changes in moles• Lumps• Changes in bowel habits• Blood in the stools• Persistent cough or hoarseness• Bloody sputum• Discolored areas or sores in the mouth that do
not heal

•
•
•
•
•
•
•
•
•
•

Persistent headaches
Paleness of the skin
Bone pain
Sores that do not heal
Difficulty swallowing
Persistent abdominal pain
Painful urination or defecation
Shortness of breath
Vision changes
Persistent early morning vomiting

What can I do to lower the risk of getting a second cancer?

Avoid cancer-promoting habits. Survivors should not smoke, vape, or chew tobacco and should avoid exposure tosecondhand smoke when at all possible. Because skin cancers are one of the most common second cancers afterchildhood cancer, especially for those treated with radiation therapy, you should take extra care to protect your skinfrom sun exposure. This includes regularly using sunscreen with sun protection factor (SPF) of 15 or more, wearing
protective clothing, avoiding outdoor activities from 10 am to 2 pm when the sun’s rays are most intense, and nottanning.
Drink alcohol only in moderation. Heavy drinkers, especially those who use tobacco, have a high risk of cancer ofthe mouth, throat, and esophagus. The risk of breast cancer may be increased in women who drink alcohol. Limiting
the use of alcohol can reduce these cancer risks and decrease the chances of other alcohol-related problems, such as
liver disease.
Eat healthy. A high intake of dietary fat has been linked to the risk of several common adult cancers. People who eat
high-fat diets have a greater risk of getting colon cancer; this may also be true for breast and prostate cancers. Highfat diets are also associated with obesity, heart disease, and other health problems. To reduce all of these risks, daily
fat intake should be limited to 30% or less of your total calories.
Dietary fiber is found in whole grains, several types of vegetables, and certain fruits. Fiber reduces the time it takes for
waste to pass through the intestinal tract. High-fiber foods also tend to be low in fat.
Eating cruciferous vegetables also helps reduce cancer risk. Cruciferous vegetables include cabbage, Brussel sprouts,
broccoli, and cauliflower. Eating these vegetables is thought to protect against cancer by blocking the effects ofcancer-causing chemicals in other foods. Cruciferous vegetables are also high in fiber and low in fat. These foods
should be included frequently in the diet.
Some chemicals used to preserve foods are cancer-promoting (carcinogenic) in large quantities. Diets high in saltcured and pickled foods and lunchmeats that contain preservatives like nitrites can increase the risk of cancer in thestomach and esophagus. Some of these foods, especially lunchmeats, are also high in fat. Foods of this kind should be
eaten rarely and in small portions.
Diets rich in vitamins C and A have been shown to reduce cancer risk in animal studies. People whose diets are rich invitamin C appear less likely to get cancer, especially cancer of the stomach and esophagus. The best way to get these
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nutrients is to eat lots of fresh fruits and vegetables. Citrus fruits, melons, cruciferous vegetables, and greens are high invitamin C. Good sources of vitamin A are dark green and deep yellow vegetables and certain fruits. If your diet is low invitamins, a vitamin supplement may help, but avoid extra high doses, since these can cause serious side effects.
Get vaccinated. Certain cancers are associated with preventable infections. Two of the most common are hepatitis
B and human papillomavirus virus (HPV). Vaccines are now available to protect against these cancer-causing viruses.
Check with your health care provider to determine if either of these vaccines is recommended for you.
Start today by taking time to review your health habits, and practice healthy behaviors that will help keep your risk of
second cancers to a minimum.
Written by Melissa M. Hudson, MD, St. Jude Children’s Research Hospital, Memphis, TN; and Allison Hester, RN, MSN, CPNP,
Arkansas Children’s Hospital, Little Rock, AR. Portions adapted from CCSS Newsletter, Fall 1999 and Winter 2001, used withpermission.
Reviewed by Smita Bhatia, MD, MPH; Debra L. Friedman, MD; Fran Wiley, RN, MN; and Jill Meredith RN, BSN, OCN®.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities, or
damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Scoliosis and Kyphosis after Cancer Treatment
The spine, or “backbone” is a group of bones stacked in a straight line down the middle of the back, held together withmuscles and ligaments. Treatment for childhood cancer can sometimes result in abnormal curvatures of the spine,
known as scoliosis and kyphosis.
What is scoliosis?
Scoliosis is a sideways rotation of the spine. Instead of appearing as a straight line when viewed from the back, thespine appears curved, like the letter “S” or the letter “C.”
Signs of scoliosis may include:• Uneven shoulder blades• Uneven hips
• Uneven waist• “Leaning” of the back to one side
• Head not centered above pelvis•

One leg longer than the other

What is kyphosis?
Kyphosis is an abnormal rounding of the upper part of the back. When viewed from the side, it may appear as if theperson is slouching or has a “hump” on the back.
What causes scoliosis?
Scoliosis occurs in many young people, especially teenagers, and is most often “idiopathic,” meaning that the cause is
not known. However, people who underwent surgery involving the spine or chest, or those who received radiation to thechest, abdomen, or spine, especially when combined with surgery, are at increased risk for uneven development of themuscles, bones, and soft tissues of the back, resulting in scoliosis.
What causes kyphosis?
Kyphosis sometimes develops from stretching of the spinal ligaments, causing the natural curve of the spine toincrease. Kyphosis can also be caused by uneven development of the back muscles and ligaments as a result ofradiation.
What are the risk factors for scoliosis after treatment for childhood cancer?
Cancer treatment-related risks include:• Surgery involving the spine or chest (not including placement of a central line)• Radiation to the trunk (including any area from the shoulders down to the pelvis), especially if:– The dose was 20 Gy (2000 cGy/rads) or higher.
– Younger age at the time of radiation treatment.
– The radiation treatment area was to one half of the chest or abdomen.
– There was also surgery to the chest, abdomen, or spine.
• A tumor in or near the spine•

Individuals with neurofibromatosis are also at increased risk.

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How is the diagnosis made?
Signs of scoliosis or kyphosis may be detected on physical examination. X-rays of the spine confirm the diagnosis.
Scoliosis is diagnosed when there is at least a 10-degree lateral (side-to-side) curve on the x-ray. Kyphosis is diagnosed
when there is at least a 50-degree curve on the x-ray.
What treatment is needed?
Treatment for kyphosis and scoliosis is usually done in stages. The first stage is usually “observation.” During this stage,
the curve is closely monitored, especially during periods of rapid growth, such as during puberty. If the curve does not
get worse, observation may be all that is necessary.
If the curve progresses, the next step is usually bracing (a plastic body brace worn under the clothing). The goal of
bracing is to halt progression or help correct the abnormal spinal curvature.
The final treatment step is surgery. This is done in cases of serious curves that are not manageable with observation or
bracing alone.
What monitoring is required?
If scoliosis or kyphosis is suspected, an x-ray of the spine should be obtained. If the curve is more than 10 degrees forscoliosis or more than 50 degrees for kyphosis, a referral is usually made to an orthopedic (bone) specialist.
Written by Wendy Landier, PhD, CPNP, Children’s Hospital of Alabama, Birmingham, AL.
Reviewed by Leeann Carmichael, DNP, APN, FNP-BC; Kayla L. Foster, MD, MPH; and Melissa Acquazzino, MD, MS.
Image by Emiri Matsuda, BA, Children’s Hospital of Alabama, Birmingham, AL. of Elsevier Inc.), 2013.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities,
or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational
Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Keeping Your Single Kidney Healthy
The kidneys are vital organs responsible for filtering out waste products from the blood, controlling blood pressure,and stimulating red blood cell production. Treatment for childhood cancer sometimes requires removal of one kidney(nephrectomy). Although you can live a healthy life with only one kidney, it is important that you take steps to protect
your remaining kidney to keep it as healthy as possible.
What follow up is recommended?
•

Have a medical check-up at least yearly. This should include a blood pressure check and urine test.

•

Have a blood test for kidney function (BUN, creatinine) and electrolytes (blood salts and minerals) at yourfirst long-term follow-up visit (at least 2 years after completing cancer treatment), and then yearly testing tomonitor kidney function.

•

If you have high blood pressure, protein in the urine, or other signs of worsening kidney problems, you shouldhave an evaluation by a nephrologist (kidney specialist).

What can I do to keep my kidney healthy?
•

Drink plenty of water, especially when playing sports, while out in the sun, and during hot weather.

•Call your healthcare provider immediately if you have symptoms of a urinary tract infection (burning when
you urinate, urinating more frequently than usual, and/or feeling an urgent sensation to urinate).

•

Check with your healthcare provider or pharmacist before taking any new medicines (prescription, overthe-counter, or herbal). Be sure that your healthcare provider or pharmacist is aware that you have a single
kidney.

•Use non-steroidal anti-inflammatory drugs with caution. These include pain or fever medicines (over-thecounter and by prescription) that contain aspirin, ibuprofen, or naproxen. These medications have been known
to cause kidney damage (analgesic nephropathy), especially when taken in high doses or over long periods oftime (more than 10 days). If you require long-term medications for management of pain, be sure to discuss thealternatives with your healthcare provider, and to choose medications that are safe for your kidneys.

•

Physical activity, including sports, is good for your health. Kidney injuries from sports are uncommon, andthose that do occur rarely cause permanent damage or kidney loss. Overall, most physical activity poses little
or no risk to the kidney and is strongly encouraged to maintain good general health. Talk with your health careprovider about your kidney health to help you decide whether to participate in certain sports.

•

Serious kidney injuries are rare. When they do occur, they are most commonly caused by car accidents,
all-terrain vehicles, and falls. To protect your single kidney, always wear your seatbelt properly when riding in a
vehicle. Lap belts should be worn across the hips, not around the waist. If you are involved in an accident and akidney injury is suspected, seek medical attention right away.

Are there any other risk factors for kidney problems?
Certain treatments for childhood cancer can sometimes cause kidney problems. These include radiation to the kidney,
chemotherapy that can affect the kidney (cisplatin, carboplatin, and/or ifosfamide), other medications that can affectthe kidney (certain antibiotics or medications used for treatment of graft versus host disease) or hematopoietic celltransplant (HCT). In addition, other risk factors that may increase the chance of kidney problems include medical
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conditions, such as high blood pressure or diabetes, urinary tract problems such as frequent urinary infections or backflow of urine into the kidney (reflux), or bladder removal (cystectomy). If you have any of these risk factors, please readthe related Health Link: Kidney Health.
Written by Wendy Landier, PhD, CPNP, Children’s Hospital of Alabama, Birmingham, AL.
Revised by Maki Okada, CPNP, FNP-BC, CPON®, Miller Children’s and Women’s Hospital Long Beach, Long Beach, CA.
Reviewed by Kayla L. Foster, MD, MPH; and Melissa Acquazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology
Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed by theChildren’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms of indemnification: (i)“Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliatedorganizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any and all losses, liabilities, or
damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Group retains
excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology Group secure
all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal documents andlimiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Skin Health after Cancer Treatment
The skin is the largest organ in the body and it is the body’s first line of defense against outside invaders. It also keeps
the body temperature normal and stores water, fat, and vitamin D. This important organ requires care and monitoring.
Treatment for childhood cancer sometimes causes damage to the skin.
Who is at risk?
• Survivors who received radiation to any part of the body, including total body irradiation (TBI).
•

Survivors with chronic graft-versus-host disease (GVHD) following bone marrow or stem cell transplant.

What problems can occur?
The following are possible long-term skin effects that may be seen after cancer therapy.
Telangiectasias
These small blood vessels on the surface of the skin are commonly referred to as “spider veins,” and in the cancer
survivor they can occur in the field of radiation. Telangiectasias are caused by changes to the lining of blood vessels
resulting from radiation. These do not typically cause any health problems and require no specific care.
Fibrosis
Fibrosis is caused by scarring of the lining of blood vessels, resulting in a “woody” skin texture. The skin may not be
as flexible in the fibrotic area and may be more easily injured. Care of fibrotic skin should include routine moisturizing
and avoidance of trauma. Because the blood supply is not as good in fibrotic skin, healing may be slow after cuts andscrapes, so avoiding these when at all possible is important.
Scleroderma
People who have chronic GVHD following bone marrow or stem cell transplant sometimes develop scleroderma. In thiscondition, the donor white blood cells do not recognize the patient’s skin cells as their own, and begin to attack them.
This causes the skin to become stiff and inflexible. This may happen anywhere on the body, but if it happens to the skinaround joints, it can make the joints less mobile. The therapy for scleroderma is treatment of the underlying GVHD. It isalso important to avoid injury to this skin, since healing time will be prolonged.
Vitiligo
Vitiligo is loss of pigment on patches of the skin. This can occur after bone marrow or stem cell transplant from aperson other than yourself (allogeneic transplant) and may be due to GVHD or other autoimmune reactions seen after
transplant. In this situation, the white blood cells do not recognize certain normal skin cells (melanocytes) and so they
attack and destroy them. Melanocytes are the cells in the body that control skin color. Without melanocytes, the skin has
a milky white appearance. Vitiligo usually occurs only in patches. The therapy for vitiligo is treatment of the underlying
GVHD or autoimmune process. Even the skin because the damage to the melanocytes may be permanent. While all skinshould be protected from sun, skin that has lost its pigment is very vulnerable, and sunscreen should always be applied
to these areas before going outdoors.
Hyperpigmentation
Hyperpigmentation is a darkening of the skin that may occur after radiation or some types of chemotherapy.
The chemotherapy agents most commonly associated with hyperpigmenation include bleomycin, busulfan,

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cyclophosphamide, dactinomycin, 5-flourouracil, hydroxyurea and methotrexate. The dark discoloration can occur on
the skin or nails. There is no specific treatment for hyperpigmentation associated with cancer therapy, but it usuallycontinues to fade over time without any treatment.
Skin Cancers
People who have received radiation are at risk for developing skin cancers, usually in the radiation field. Other risk
factors include light skin color, chronic sun exposure, severe sunburn, atypical moles or a large number of moles on
the body, and a family history of skin cancer. The good news about skin cancer is that if it is diagnosed early, it isusually very treatable. There are three major forms of skin cancer:• Basal cell carcinoma (BCC) is the most frequent form of skin cancer. BCC usually appears as a rough, raised,area of skin. As the BCC progresses, it may become an ulcer or sore that does not heal. BCC can occur anywhereon the skin, but is seen most frequently in areas of sun and/or radiation exposure. Protecting your skin from thesun is the most important thing you can do to avoid developing BCC. Treatment for BCC is surgical removal of theaffected skin. BCC can spread to surrounding tissues but does not usually spread throughout the body and is not
usually life threatening.
• Squamous cell carcinoma (SCC) is another form of skin cancer that can develop from exposure to sun orradiation. Its appearance is similar to BCC, usually an ulcerated sore that does not heal. SCC can be moreaggressive than BCC and can spread more readily to surrounding tissues and even to other parts of the body.
With early surgical treatment SCC is usually curable, so it is important to report any suspicious sores to yourhealthcare provider right away.
• Melanoma is a much more serious form of skin cancer. Unlike BCC, left untreated it can spread to other organs
and can be lethal. Melanoma often arises from moles. The key to successful treatment of melanoma is early
diagnosis. Moles should be monitored for changes. Monitoring of moles can be remembered using the “ABCD”
warning signs:
A is for Asymmetry (one half of the mole looks different than the other half)
B is for Border (moles that have an irregular, scalloped or poorly defined border)
C is for Color (variations in color from one area of the mole to another, such as different shades of tan andbrown or black, or colors such as white, red, or blue within a mole)
D is for Diameter (moles larger than 6 millimeters – about the diameter of a pencil eraser – should be
evaluated).
If you notice any of the “ABCD” warning signs, have your healthcare provider check the mole. Moles that have any ofthese warning signs usually need to be removed.
What monitoring is needed?
If you have any of the following risk factors, you should routinely check your skin for changes, and have athorough skin examination by a healthcare provider at least once a year:• You received radiation to any area, including total body irradiation (TBI)• You underwent a hematopoietic cell transplant• You have ever had skin cancer or melanoma, or you have a family history of skin cancer or melanoma• You have “dysplastic” (atypical) moles•

You had a severe sunburn at a young age

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What can I do to keep my skin healthy?
The most important thing to remember in caring for your skin is to protect it from the sun. Here are some things you
can do:• Wear protective clothing or sunscreen at all times when your skin is exposed to the sun, even on cloudy or hazydays. The American Cancer Society recommends a sunscreen with an SPF (sun protection factor) of 15 or higher.
• Sand, snow, concrete, water and high altitudes all increase the risk of sun damage—take extra caution toprotect your skin in these environments.
• Do not attempt to tan your skin—avoid tanning booths.
• Avoid outdoor activities from 10 am to 2 pm when the sun’s rays are most intense (11 am to 3 pm during
daylight savings time). Plan outdoor activities in the early morning or late afternoon hours.
• Reapply sunscreen frequently or use a water-resistant sunscreen when swimming or perspiring heavily. This
will not only help to protect you from developing skin problems but will also help you to maintain a youthfulappearance.
If you have any questions or concerns about your skin, contact your healthcare provider. Take good care of your skinand it will take care of you!
Written by Kathy J. Ruble, RN, MSN, CPNP, AOCN®, Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, MD.
Reviewed by Amelia DeRosa RN, BSN, CPON®; Kayla L. Foster, MD, MPH; and Christine Yun MSN, PNP, CPON®.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Precautions for People Without a Functioning Spleen
The spleen is an organ about the size of a person’s fist that is located in the upper left sideof the abdomen under the rib cage. The spleen helps the body fight infection by filtering theblood. Individuals who lack a functioning spleen are at increased risk for developing serious
infections by specific bacteria (Streptococcus pneumoniae, Haemophilus influenzae, andNeisseria meningitidis) and some parasites transmitted by insects (malaria and Babesia).
Who is at risk for a non-functioning spleen and infections?

••Individuals who had their spleen surgically removed (splenectomy)
Individuals who received a high dose of radiation (at least 40 Gy/4000 cGy) to theabdomenIndividuals with active chronic graft-versus-host disease following a bone marrow orstem cell transplant•

What are the signs of infection and when should I seek treatment?
•

Fever is an important sign of infection. A fever is a temperature at or above 101°F (38.3°C).
–

If you have a fever and a non-functional spleen (or have undergone splenectomy),
you should seek urgent medical attention. Fever may be a sign of a serious bacterial
infection and requires blood work and the administration of antibiotics to determine if abacterial infection is present.

•

Other symptoms of infection include unusual tiredness, muscle aches, chills, headache, vomiting, diarrhea, and abdominal
pain. These symptoms can be warning signs of infection even without a fever. Take your temperature regularly any time you
develop symptoms of infection or appear ill.

•

If you are having symptoms that you are not sure are related to an infection, contact your healthcare provider for further
recommendations.

Is there anything I can do to decrease the risk of infection?
•

Vaccinations against haemophilus influenza (HiB), pneumococcus (PCV and PPSV), meningococcus (Men-ACWY, MenB), andinfluenza can decrease the risk of a serious infection.

•

In some cases your health care provider may recommend antibiotics to prevent an infection. These antibiotics are called“prophylactic” antibiotics and are taken daily. Antibiotics can decrease the risk of infection in younger children or individuals
who are at higher risk of infection.

What vaccines should an individual receive if they have a non-functioning spleen?
•

In addition to the recommended vaccinations for all children and adolescents, individuals with a non-functioning spleenshould receive the following immunizations:-Due to the increased risk of pneumococcal infections, individuals over 2 years of age should receive the PPSV23 vaccine
at least 8 weeks after their last dose of routine pneumococcal vaccination and then revaccinate with PPSV23 vaccine 5
years after the first dose.

-

Vaccination to meningococcus is recommended for individuals without a functional spleen as early as 2 months of age.
The number and timing of doses is dependent on the type of vaccine received and age at initiation. Vaccination formeningococcal serogroup B is also recommended above 10 years of age.

•

Vaccines can be given by your primary care provider.

•

Some primary care providers may not be familiar with your specific catch up or booster vaccine schedule. Make sure to give
your primary care provider your cancer team’s contact information for questions.

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Other precautions
Individuals with a non-functioning spleen are at increased risk for other infections:•

Malaria: If you travel to countries where malaria is common, take special precautions to avoid getting malaria. Ask yourhealthcare provider for anti-malarial medications before travel to infested areas. During travel, use insect repellants andother protective measures, such as netting and protective clothing.

•Animal/Human Bites: Animal and human bites can result in serious bacterial infections in individuals with anonfunctioning spleen. If you receive a bite that breaks the skin, seek immediate medical attention for treatment with
antibiotics.

•

Ticks: People without a nonfunctioning spleen are at increased risk for an infection caused by Babesia, a parasitetransmitted by deer ticks. Deer ticks are most commonly found in the northeastern United States. You should wear
protective clothing and use insect repellants when going outdoors in tick-infested areas. If you receive a tick bite while inan area infested with Babesia, you should remove the tick and talk to your healthcare provider about what to do.

How will my healthcare providers know about my non-functioning spleen?

•••

Be sure to tell your doctors, dentists, and other healthcare providers that you do not have a functioning spleen.
You should wear a medical alert emblem (bracelet or necklace) in case of a medical emergency.
Consider carrying a wallet card, with guidelines for healthcare professionals regarding the management of feverin people without a functioning spleen.

Written by S. Ashley Speckhart, MD, MPH, Maine Children’s Cancer Program, Teresa Sweeney, RN, MSN, CPNP, St. Jude Children’s Research
Hospital, Memphis, TN; and Wendy Landier, PhD, CPNP, Children’s Hospital of Alabama, Birmingham, AL.
Reviewed by Kayla L. Foster, MD, MPH and Melissa Acquazzino, MD, MS.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Wallet Card for Patients Without a Functioning Spleen

Physician Phone: _____________________________
Physician Name: _____________________________
Patient Name: _______________________________

Asplenic Patient

MEDICAL ALERTFold here

MEDICAL ALERT: Asplenic PatientThis patient is asplenic and at risk for potentially fatal, overwhelming infections. Immediate medical attention is required for fever of ≥101°F (38.3°C)
or other signs of serious illness. Suggested management includes:
1. Physical exam, CBC and blood culture.
2. Administration of a long-acting, broad-spectrum parenteral antibiotic(e.g., ceftriaxone) accompanied by close clinical monitoring while awaiting blood culture results.
3. Hospitalization and broadening of antimicrobial coverage (e.g., additionof vancomycin) may be necessary under certain circumstances, such as
the presence of marked leukocytosis, neutropenia, or significant change
from baseline CBC; toxic clinical appearance; fever ≥ 104°F; meningitis,
pneumonia, or other serious focus of infection; signs of septic shock; orprevious history of serious infection.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Thyroid Disease after Cancer Treatment
Some people who were treated for cancer during childhood may develop endocrine (hormone) problems as a resultof changes in the function of a complex system of glands known as the endocrine system.
What is the endocrine system?
Pituitary gland

The endocrine system is a group of glands
that regulate many body functions including
growth, puberty, energy level, urine production,and stress response. Glands of the endocrine
system include the pituitary, hypothalamus,
thyroid, pancreas, adrenals, ovaries, and testes.
The hypothalamus and pituitary are sometimes
called the “master glands” because they control
many of the other glands in the endocrine
system. Unfortunately, some treatments given
for childhood cancer can damage the endocrine
system, resulting in a variety of problems.

Hypothalamus
Thyroid

Pancreas
Adrenal glands

Ovaries

TestesWhat are hormones?
Hormones are chemical messengers that carryinformation from the endocrine glands throughthe bloodstream to the body’s cells. The
endocrine system makes many hormones (suchas growth hormone, sex hormones, adrenal
and thyroid hormones) that work together to maintain specific bodilyfunctions.
What is the thyroid gland?
The thyroid gland is located in the lower part of the neck in frontof the throat. The gland makes two hormones, thyroxine (T4) andtriiodothyronine (T3), that play an important role in growth and brain
development and help to regulate the body’s metabolism. The thyroid
gland is controlled by the pituitary, a gland in the brain that makes
thyroid stimulating hormone (TSH). TSH is released from the pituitary
in response to the levels of T4 and T3 in the blood. If the levels are
low, the pituitary makes more TSH to signal the thyroid to increase
the production of thyroid hormones. If T4 and T3 are high, the pituitary
makes less TSH to signal the thyroid gland to slow down production.

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What are the possible late effects?
Damage to the thyroid gland after childhood cancer can be caused by surgical removal of all or part of
the thyroid gland, treatment with tyrosine kinase inhibitors, high doses of MIBG (sometimes used in thetreatment of neuroblastoma), and/or treatment with radiation to the head, brain or neck. This damage
is usually very easy to treat, although it may not show up for years after treatment. Regular check-ups
may help find thyroid problems early so that the proper treatment can be started. Several different typesof thyroid problems may develop including an underactive thyroid (hypothyroidism), overactive thyroid(hyperthyroidism), and growths on the thyroid that may be benign (nodules) or malignant (cancer).
What is hypothyroidism?
Hypothyroidism occurs when the thyroid gland is not active enough. This is the most common thyroid
problem seen in childhood cancer survivors. This can occur if the brain doesn’t make TSH to properly
signal the thyroid gland to work or if the thyroid gland is damaged or has been removed and cannot
make enough thyroid hormone. When the thyroid gland is underactive, thyroid hormone levels are low
and the body’s metabolism slows down.
Signs and symptoms of hypothyroidism may include:• Slowing of normal growth•

Mood changes•

Weight gain•

Feeling cold all of the time•

Dry skin•

Difficulty concentrating•

Brittle hair/hair loss•

Delayed puberty•

Constipation•

Irregular menstrual cycles•

Weakness•

Muscle and joint aches•High cholesterol level•

Poor exercise tolerance•

Feeling tired and listless•

Puffiness around the eyes•

Hoarse voice•

Low heart rate or blood pressure

What is hyperthyroidism?
Hyperthyroidism occurs when the thyroid gland is too active. In this condition thyroid hormone levels arehigh and the body’s metabolism speeds up.
Signs and symptoms of hyperthyroidism may include:• Jitteriness•Feeling hot all of the time•

Anxiety•

Diarrhea•

Problems concentrating•

Weight loss•

Feeling tired•

Irregular menstrual periods•

Muscle weakness•

Bulging or protruding eyes•

Tremors•

Neck tenderness and swelling•

Fast or irregular heartbeat•

Poor exercise tolerance•

Increased sweating

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What are thyroid nodules and thyroid cancer?
Thyroid nodules and thyroid cancer are growths that usually begin as slow-growing, painless lumps in the neck.
Most thyroid growths do not cause any symptoms. They may occur many years after cancer treatment.
Who is at risk for thyroid problems?
People who received radiation that may have affected the thyroid gland directly are at risk for primary hypothyroidism,
compensated hypothyroidism, thyroid nodules, and/or thyroid cancer. People who received radiation to the thyroid
gland in high doses, especially more than 30 Gy or 3000 cGy/rads, are also at risk for hyperthyroidism. The following
radiation fields have the potential to affect the thyroid gland directly:•

Head/brain

•

Neck

•

Spine (cervical/neck portion)•

Total body irradiation (TBI)

In addition, people who received radioiodine therapy (I-131), high doses of MIBG, or tyrosine kinase inhibitors or had
their thyroid gland partially or completely removed surgically (thyroidectomy) are also at risk for hypothyroidism.
People who received high doses of radiation (30 Gy or 3000 cGy/rads or higher) to the head/brain are at risk for
hypothyroidism.
Other factors that have been shown to increase the risk of thyroid problems after childhood cancer include being:•

Treated with higher radiation doses•

Treated at a young age•

Born with ovaries

Thyroid problems may occur soon after radiation, but generally do not occur until several years later. If treatedpromptly, thyroid problems are easily managed.
What screening is recommended?
All childhood cancer survivors should have a yearly comprehensive health check-up including measurement of height
and weight, examination of the thyroid gland, and blood tests to measure the levels of TSH and T4. During periods ofrapid growth, healthcare providers may recommend more frequent monitoring of thyroid levels.
Survivors at risk for thyroid problems who are planning to become pregnant should have their thyroid levels checked
before attempting pregnancy. It is important to do this before becoming pregnant, as there is a higher chance of
having babies with developmental problems if untreated thyroid disease is present. It is also important to monitor
thyroid levels periodically during pregnancy.
How are thyroid problems treated?
If problems with thyroid levels are identified, you may be referred to an endocrinologist (hormone specialist) for
evaluation and to discuss treatment, such as medication, if needed. If a lump is detected on the thyroid, you may also
be referred to a surgeon or other specialist for further evaluation and management.

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Written by Melissa M. Hudson, MD, St. Jude Children’s Research Hospital, Memphis, TN; and Wendy Landier, PhD, CPNP, Children’s
Hospital of Alabama, Birmingham, AL.
Reviewed by Charles A. Sklar, MD; Debra L. Friedman, MD, Julie Blatt, MD; Joan Darling, PhD; and Susan F. Shaw, RN, MS, PNP.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any andall losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of
the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Vaccines after Treatment for Cancer Survivors Treated with
Chemotherapy and/or Radiation (Non-HCT)
Vaccines are an important tool to protect against infections and prevent infection-related deaths. Vaccines help theimmune system recognize and fight serious infections. Most vaccines are given during childhood and provide protection against infection into adulthood. After cancer treatment, survivors may need to catch up on recommended
childhood vaccines that were missed during treatment or get booster vaccines to protect against vaccine-preventable infections.
Sometimes recommended vaccine doses are delayed during cancer treatment. After completing treatment for cancer,
it is important to make a plan to catch up on missed vaccines, even if delayed by months or years.
For childhood cancer survivors who have not missed any vaccinations during treatment, an extra dose of a vaccine (a“booster” vaccine) may be recommended to strengthen the immune system against vaccine-preventable infections.

Who should get booster vaccines?
• All children and adolescents who have received chemotherapy and/or abdominal radiation should discuss vaccines with their cancer team and primary care provider.
• Your child’s provider may recommend boosters with or without checking antibody levels (also called titers) that
confirms loss of immunity before vaccines are given.
Why should childhood cancer survivors receive vaccines or booster doses?
• Vaccines and booster shots after cancer treatment protect from infection and infection-related death.
How do vaccines and booster doses work?
• Vaccines protect you from infection by creating an immune response which makes antibodies and memory
cells, your body’s tools to effectively fight off viruses and bacteria. These antibodies and cells remain in the bodyfor many years and protect against infections into adulthood.
• A booster vaccine is an additional dose of a vaccine. Booster vaccines “boost” the number of antibodies andcells to fight an infection that you have been vaccinated for in the past and provides greater protection against
infection.
What are the risks of booster vaccines?
• Booster vaccines are considered very safe.
• Common side effects include swelling and/or discomfort at the vaccination site and low-grade fever.
• Serious reactions are rare. If you have concerns about vaccine safety, more information can be found at theCenters for Disease Control website: https://www.cdc.gov/vaccines/schedules/index.html

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Where should my child go to receive vaccines?
• Vaccines can be given by your primary care provider.
• Some primary care providers may not be familiar with your specific catch up or booster vaccine schedule.
Make sure to give your primary care provider your cancer team’s contact information for questions.
When should my child get vaccines after cancer treatment?
• Most vaccines are delayed at least six months after cancer treatment ends.
• The timing of vaccination should be given to you by your cancer team. Certain treatments such as steroids,
IVIG, and immune suppression drugs may affect your vaccine schedule.
Are there any vaccines that protect against cancer?
• Yes!
- The Hepatitis B virus vaccine protects against liver cancer caused by the Hepatitis B virus.
- The human papilloma virus (HPV) vaccine protects against a virus known to cause many different
types of cancer (head and neck cancers, cervical cancer, vaginal cancer, anal cancer, penile cancer,
and vulvar cancer).
˚ Survivors of childhood cancer are at increased risk of HPV-related cancers and should receive athree-dose series of the vaccination, regardless of the age at which the first vaccine was given.
Written by S. Ashley Speckhart, MD, MPH, Maine Children’s Cancer Program, Scarborough, ME; and Kayla L. Foster, MD, MPH,
Baylor College of Medicine/Texas Children’s Hospital, Houston, TX.
Reviewed by Melissa Acquazzino, MD, MS; Greg Guilcher, MD; Hesham Eissa, MD; Linda Rivard, RN, BSN, CPON®, Daniel Smith
DNP, FNP; and Christine Yun MSN, PNP, CPON®.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health Links
were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s Oncology
Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate criteria
for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable alternative
follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s
Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any andall losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review or access of
the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Appendix II p. 138

Health Link

Healthy living after treatment of childhood, adolescent, and young adult cancer

Vaccines after Treatment for Cancer Survivors Treated with
Hematopoietic Cell Transplant (HCT)
Vaccines are an important tool to protect against infections and prevent infection-related deaths. Vaccines help theimmune system recognize and fight serious infections. Most vaccines are given during childhood and provide protection against infection into adulthood. After cancer treatment, survivors may need to catch up on recommended
childhood vaccines that were missed during treatment or get booster vaccines to protect against vaccine-preventable infections.

Who should be revaccinated?
• All individuals who received either an allogeneic HCT (transplant from a donor) or an autologous HCT (transplant with your own cells) should repeat the vaccination series for most vaccines.
• An individualized plan for you or your child should be discussed with your transplant team.
Why should individuals who received a hematopoietic transplant be revaccinated?
• Infection is one of the most common causes of illness and death following a transplant.
• Revaccination after a hematopoietic transplant can protect from infection and infection-related death.
How do vaccines work?
• Vaccines protect you from infection by creating an immune response which makes antibodies and memory
cells, your body’s tools to effectively fight off viruses and bacteria. These antibodies and cells remain in the
body for many years and protect against infections into adulthood.
What are the risks of revaccination?
• Vaccines and revaccination are considered very safe.
• Common side effects include swelling and/or discomfort at the vaccination site and low-grade fever.
• Serious reactions are rare. If you have concerns about vaccine safety, more information can be found at theCenters for Disease Control website: https://www.cdc.gov/vaccines/schedules/index.html
Where should my child go to receive vaccines?
• Your transplant team will provide you and your primary care provider a list of the recommended vaccinations.
• Vaccines can be given by your transplant team or your primary care provider.
When should my child get vaccines after treatment?
• The timing of vaccination should be given to you by your transplant team. Certain treatments such as steroids, IVIG, and immune suppression drugs or conditions such as graft vs. host disease may affect yourvaccine schedule.
• Most vaccines are delayed for 6 months following the date of transplant. Some vaccines called live vaccines
are delayed even longer (up to two years after transplant) and should only be started after confirming with theprimary transplant team.
Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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Healthy living after treatment of childhood, adolescent, and young adult cancer

Are there any vaccines that protect against cancer?
• Yes!
- The Hepatitis B virus vaccine protects against liver cancer caused by the Hepatitis B virus.
- The human papilloma virus (HPV) vaccine protects against a virus known to cause many different
types of cancer (head and neck cancers, cervical cancer, vaginal cancer, anal cancer, penile cancer,
and vulvar cancer).
˚Survivors of childhood cancer are at increased risk of HPV-related cancers and should receive a threedose series of the vaccination, regardless of the age at which the first vaccine was given.

Written by S. Ashley Speckhart, MD, MPH, Maine Children’s Cancer Program, Scarborough, ME; and Kayla L. Foster, MD, MPH,
Baylor College of Medicine/Texas Children’s Hospital, Houston, TX.
Reviewed by Melissa Acquazzino, MD, MS; Greg Guilcher, MD; Hesham Eissa, MD; Linda Rivard, RN, BSN, CPON®, Daniel Smith
DNP, FNP; and Christine Yun MSN, PNP, CPON®.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or young
adulthood.
Disclaimer and Notice of Proprietary Rights
Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
Oncology Group’s Long-Term Follow-Up Guidelines Core Committee and its associated Task Forces.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a research organization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or to exclude other legitimate
criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is the Informational Content intended to exclude other reasonable
alternative follow-up procedures. The Informational Content is provided as a courtesy, but not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children’s Oncology Group has made every attempt to assure that the Informational Content is accurate and complete as of the date of publication, no
warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of such Informational Content.
No Liability on Part of Children’s Oncology Group and Related Parties/Agreement to Indemnify and Hold Harmless the Children’s Oncology Group and Related Parties: No liability is assumed
by the Children’s Oncology Group or any affiliated party or member thereof for damage resulting from the use, review, or access of the Informational Content. You agree to the following terms ofindemnification: (i) “Indemnified Parties” include authors and contributors to the Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology
Group and affiliated organizations; (ii) by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys’ fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands related to or arising out of use, review oraccess of the Informational Content.
Proprietary Rights: The Informational Content is subject to protection under the copyright law and other intellectual property law in the United States and worldwide. The Children’s Oncology Groupretains excursive copyright and other right, title, and interest to the Informational Content and claims all intellectual property rights available under law. You hereby agree to help the Children’s Oncology
Group secure all copyright and intellectual property rights for the benefit of the Children’s Oncology Group by taking additional action at a later time, action which could include signing consents and legal
documents and limiting dissemination or reproduction of Informational Content.

Copyright 2023 © Children’s Oncology Group. All rights reserved worldwide.

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