Version 1.0 - March 2003

DISCLAIMER
Late Effects Screening Guidelines
Version 1.0 – March 2003

The following guidelines were developed by the Children’s Oncology Group - Late Effects and Nursing Committees. These
guidelines provide recommendations for screening and management of late effects potentially arising as a result of therapeutic
exposures used in the treatment of childhood malignancies, and are designed for use beginning two or more years following thecompletion of therapy. The guidelines are not intended to provide guidance for follow-up of the cancer survivor's primary disease.
Children’s Oncology Group is a research organization, and these guidelines were developed within the context of clinical research
involving long term follow-up of childhood cancer survivors. The guidelines are provided at no-cost to Children’s Oncology Group
members who have participated and/or continue to participate in the research that has made these guidelines possible.
These guidelines are provided as a courtesy. They are an informational and educational service and are derived from in-depth
review and assessment of current scientific and clinical information. They are not intended as a sole source of guidance in theevaluation of childhood cancer survivors. Rather, they are designed to assist clinicians by providing a framework for comprehensive,
focused evaluations of childhood cancer survivors based on specific risk factors.
The Children’s Oncology Group assumes no liability for damage resulting from the use or review of this information. While theChildren’s Oncology Group intends for these guidelines to reflect state-of-the-art medical knowledge and, in this regard, diligently
attempts to keep the information current, the Children’s Oncology Group makes no representation or warranty about the accuracy,
reliability, completeness, relevance, or timeliness of the information herein and disclaims any such representation or warranty to such
effect. Further, the Children’s Oncology Group makes no representation or warranty that conforming to these guidelines will ensurecompliance with federal, State, and/or local law. Clinicians and others who review this information are advised to consult with legal
counsel to ensure compliance with federal, State, and/or local law. Further, these guidelines are not intended to supplant thefunctions of an Institutional Review Board (IRB), Privacy Board, or similarly constituted body.
The guidelines are not intended to replace clinical judgment, medical advice, or to exclude other legitimate criteria for screening,
health counseling, or intervention for specific complications of childhood cancer treatment. Neither are they intended to exclude
other reasonable alternative follow-up procedures. The Children’s Oncology Group itself does not provide individualized treatment
advice to patients or their families, and strongly recommends discussing this information with a qualified medical professional. The
Children’s Oncology Group recognizes that specific patient care decisions are the prerogative of the patient, family, and healthcare
provider.

Table of Contents
The following documents are included in this packet:
1. Disclaimer
2. Task Force Members
3. Panel of Experts
4. Review Panel
5. Introduction and Instructions for Using the Guidelines
6. LATE EFFECTS SCREENING GUIDELINES
7. References
8. Index
9. Explanation of Scoring
10. Scoring
11. Appendix - Health Links:
Bone Health After Childhood Cancer (Osteopenia/Osteoporosis)
The Heart & Anthracyclines
The Heart & Radiation
School and Learning Issues After Childhood Cancer
Thyroid Problems after Childhood Cancer
Single Kidney Precautions

Late Effects Screening Guidelines Task ForceThe COG Late Effects Screening Guidelines were developed as a collaborative effort of the Nursing Discipline and Late Effects
Committees through the efforts of the following individuals:
Melissa M. Hudson MD
Vice-Chair – COG Late Effects Committee
Member, Department of Hematology-Oncology
Director, After Completion of Therapy Clinic
St. Jude Children’s Research Hospital
Memphis, TN
Wendy Landier, RN, MSN, CPNP, CPON
Chair – COG Nursing Clinical Practice Subcommittee
Pediatric Nurse Practitioner - Survivorship Clinic
City of Hope National Medical Center
Duarte, CA
Debra Eshelman, RN, MSN, CPNP
Late Effects Section Leader– COG Nursing Clinical Practice Subcommittee
Pediatric Nurse Practitioner
After the Cancer Experience (ACE) Program
University of Texas Southwestern Medical SchoolChildren’s Medical Center – Dallas
Dallas, TX
Kathy Forte, RN, MS, CPNP
Co-Chair – COG Nursing Education Subcommittee
Pediatric Nurse Practitioner – Cancer Survivor Program
AFLAC Cancer Center and Blood Disorders Service
Children’s Healthcare of Atlanta
Atlanta, GA

Joan Darling, PhD
COG Patient Advocate Committee Representative
Lincoln, Nebraska
Allison Hester, RN, MSN, CPNP
Pediatric Nurse Practitioner
After Completion of Therapy Clinic
St. Jude Children’s Research Hospital
Memphis, TN
Teresa Sweeney, RN, MSN, CPNP
Pediatric Nurse Practitioner
After Completion of Therapy Clinic
St. Jude Children’s Research Hospital
Memphis, TNPanel of Experts 1

Late Effects Screening Guidelines Reviewers
Panel of Experts
The following members of the Children’s Oncology Group Late Effects Committee participated in comprehensive review
and scoring of the Late Effects Screening Guidelines:
Smita Bhatia, MD, MPH
Chair – COG Late Effects Committee
Director, Epidemiology and Outcomes Research
Director, Survivorship Clinic
City of Hope Comprehensive Cancer Center
Duarte, CALouis S. Constine, MD
Professor of Radiation Oncology and Pediatrics
Vice Chair, Department of Radiation Oncology
James P. Wilmot Cancer Center
University of Rochester Medical Center
Rochester, NY

Melissa M. Hudson MD
Vice-Chair – COG Late Effects Committee
Member, Department of Hematology-Oncology
Director, After Completion of Therapy Clinic
St. Jude Children’s Research Hospital
Memphis, TN

Joan Darling, PhD
COG Patient Advocate Committee Representative
Lincoln, NE

F. Daniel Armstrong, PhD
Department of Pediatrics
Mailman Center for Child Development
University of Miami School of Medicine
Miami, FL
Julie Blatt, MD
Professor of Pediatrics
University of North Carolina
Division of Pediatric Hematology-Oncology
Chapel Hill, NC

Carolyn Freeman, MB, BS, FRCPC
Professor and Director
Department of Oncology, Division of Radiation Oncology
McGill University Health Centre
Montreal, Quebec, Canada
Debra L. Friedman MD, MS
Assistant Professor of Pediatrics
Director Long-term Follow-up
Children’s Hospital and Regional Medical CenterSeattle, WAPanel of Experts 2

Daniel M. Green, MD
Department of Pediatrics
Roswell Park Cancer Institute
Buffalo, NY
Professor of Pediatrics
School of Medicine and Biomedical Sciences
University at Buffalo, State University of New York
Buffalo, NY
Wendy Landier, RN, MSN, CPNP, CPON
Pediatric Nurse Practitioner
Survivorship Clinic
City of Hope National Medical Center
Duarte, CA
Neyssa Marina, MD
Professor of Pediatrics
Director, Long-Term Survivors Clinic
Stanford University Medical Center
Department of Pediatrics
Stanford, CA
Anna T. Meadows, MD
Professor of Pediatrics
University of Pennsylvania School of Medicine
Director, Follow-up Program
The Children's Hospital of Philadelphia
Philadelphia, PA

Joseph P. Neglia, MD, MPH
Professor of Pediatrics
Division of Hematology, Oncology,
Blood and Marrow Transplantation
University of Minnesota
Minneapolis, MN
Kevin Oeffinger, MD
Director, After the Cancer Experience
Young Adult Program
Professor, University of Texas
Southwestern Medical School
Dallas, TX
Leslie L. Robison, PhD
Professor of Pediatrics
University of Minnesota Cancer Center
Minneapolis, MNCharles A Sklar, MD
Director, Long-Term Follow-Up Program
Memorial Sloan-Kettering Cancer Center
New York, NY

Reviewers 1

Late Effects Screening Guidelines Reviewers
The following individuals participated in the review process during development of the Late Effects Screening Guidelines:
Arlina Ahluwalia, MD
Department of Internal Medicine
Northwestern University
Chicago, IL

Cathy Bourne, RN, BHSc(N)
Pediatric Hematology/Oncology
Cancer Care Manitoba
Winnipeg, Manitoba, Canada

F. Daniel Armstrong, PhD
Department of Pediatrics
Mailman Center for Child Development
University of Miami School of Medicine
Miami, FL

Julianne Byrne, PhD
Department of Hematology-Oncology
Children's National Medical Center
Washington, DC

Lisa Bashore, RN, MS, CPNP
Pediatric Hematology/Oncology
Cook Children’s Medical Center
Fort Worth, TX
Smita Bhatia, MD, MPH
Department of Pediatric Hematology/Oncology andBone Marrow Transplant
City of Hope Comprehensive Cancer Center
Duarte, CA
Julie Blatt, MD
Division of Pediatric Hematology-Oncology
University of North Carolina
Chapel Hill, NC
Susan Bock, BSN, RN
Department of Pediatric Specialities
Gundersen Lutheran Clinic
LaCrosse, WI

Hope Anne Castoria, BSN, RN, CPON
Tomorrow Children’s InstituteHackensack University Medical Center
Hackensack, NJ
Laurie Cohen, MD
Division of Endocrinology
Boston Children's Hospital
Boston, MA
Louis S. Constine, MD
Department of Radiation Oncology
University of Rochester Medical Center
Rochester, NY
Lola Cremer, PT
Division of Rehabilitation Services
St. Jude Children's Research Hospital
Memphis, TNReviewers 2

Sarah Donaldson, MD
Radiation Oncology/Radiation Therapy
Stanford University Medical Center
Stanford, CA
Patty Feist
Patient Advocate
Boulder, COPaul Fisher, MD.
Neurology and Pediatrics
Stanford University Medical Center
Stanford, CA
Carolyn Freeman, MB, BS, FRCPCDivision of Radiation Oncology
McGill University Health Centre
Montreal, Quebec, Canada
Debra L. Friedman MD, MS
Pediatric Hematology-Oncology
Children's Hospital and Regional Medical CenterSeattle, WA
Daniel M. Green, MD
Department of Pediatrics
Roswell Park Cancer Institute
Buffalo, NY
Wendy Hobbie, MSN, RN, PNP
Division of Oncology
Children’s Hospital of Philadelphia
Philadelphia, PA

Nina Kadan-Lottick, MD, MSPH
Department of Pediatrics
Yale University School of Medicine
New Haven, CT
Nancy Keene
Patient Advocate
Annandale, VA
Lisa B. Kenney, MD, MPH
Perini Quality of Life Clinic
Dana-Farber Cancer InstituteBoston, MA
Marcia Leonard, RN, PNP
Department of Pediatric Hematology/Oncology
C.S. Mott Children’s Hospital
Ann Arbor, MI
Mary Leonard, MD, MSCE
Division of Nephrology
Children’s Hospital of Philadelphia
Philadelphia, PA
Neyssa Marina, MD
Pediatric Hematology Oncology
Stanford University Medical Center
Stanford,CA
Leonard Mattano, MD
Pediatric Hematology/Oncology
Kalamazoo Center for Medical Studies
Michigan State University
Kalamazoo, MI

Reviewers 3

Anne Mauck, RN, PNP
Pediatric Hematology/Oncology
Medical College of Virginia
Richmond, VACharlene Maxen, RN, CNP, CPON
Hematology/Oncology
Childrens Hospital Medical Center of Akron
Akron, OH
Lillian Meacham, MD
Division of Pediatric Endocrinology
Children’s Healthcare of Atlanta
Atlanta, GA
Anna T. Meadows, MD
Division of Oncology
Children's Hospital of Philadelphia
Philadelphia, PA
Grace Powers Monaco, JD
Childhood Cancer Ombudsman Program
Heathsville, VA
Ray Mulhern, PhD
Division of Behavioral Medicine
St. Jude Children's Research Hospital
Memphis, TN
Michael Neel, MD
Division of Orthopedics
St. Jude Children's Research Hospital
Memphis, TN

Joseph P. Neglia, MD, MPH
Department of Pediatrics
Division of Hematology, Oncology,
Blood and Marrow Transplantation
University of Minnesota School of Medicine
Minneapolis, MN
Mary Nelson, RN, MS, CPNP, CPON
Childrens Center for Cancer and Blood Diseases
Childrens Hospital Los Angeles
Los Angeles, CA
Kevin Oeffinger, MD
Department of Family Practice and Community Medicine
University of Texas Southwestern Medical School
Dallas, TX
Roger Packer, MD
Department of Neurology
Children's National Medical Center
Washington, DC
Arnold Paulino, M.D
Department of Radiation Oncology
Children’s Healthcare of Atlanta – Emory Clinic
Atlanta, GA
Leslie L. Robison, PhD
Department of Pediatrics
University of Minnesota Cancer Center
Minneapolis, MNDavid Rosenthal, MD
Department of Pediatrics/Cardiology
Lucile Packard Children’s at Stanford
Palo Alto, CA

Reviewers 4

Kathy Ruble, RN, MSN, OCN
Pediatric Oncology
Johns Hopkins Hospital
Baltimore, MD
Kathleen Ruccione, RN, MPH
Childrens Center for Cancer and Blood Diseases
Childrens Hospital Los Angeles
Los Angeles, CA
Jean Sanders, MD
Pediatric Marrow Transplantation
Fred Hutchinson Cancer Research CenterSeattle,WA
Cindy Schwartz, MD
Pediatric Oncology
Johns Hopkins Hospital
Baltimore, MD
Susan Shaw, RN, MS, PNP
Center for Children’s Cancer and Blood Disorders
SUNY Upstate Medical University
Syracuse, NY
Charles A. Sklar, MD
Department of Pediatrics/Endocrinology
Memorial Sloan-Kettering Cancer Center
New York, NY
Jacquie Toia, RN, ND, CPNP
Hematology/Oncology
Children’s Memorial Medical Center
Chicago, IL

Deborah Waber, PhD
Department of Psychiatry
Boston Children's Hospital
Boston, MA
Susan L. Weiner, PhD
The Children’s Cause, Inc.
Silver Spring, MD
Suzanne L. Wolden, MD
Department of Radiation Oncology
Memorial Sloan Kettering Cancer Center
New York, NY

Instructions for Use - 1

The COG Late Effects Screening Guidelines:
Introduction and Instructions for Use
The Children’s Oncology Group Late Effects Screening Guidelines were developed as a collaborative effort of the Nursing Discipline
and the Late Effects Committee. The purpose of these Guidelines is to provide recommendations for screening and management oflate effects that may potentially arise as a result of therapeutic exposures used during treatment for childhood cancer.
These guidelines are designed for use beginning two or more years following the completion of therapy and provide a framework forongoing late effects monitoring. However, these guidelines are not intended to provide guidance for follow-up of the childhood
cancer survivor’s primary disease.
The recommendations in the Guidelines are based on a thorough review of the literature as well as the collective clinical experienceof the Task Force Members, Panel of Experts, and Reviewers. These guidelines are not intended to replace clinical judgment or to
exclude other reasonable alternative follow-up procedures.
This initial release of the Guidelines is limited to COG members only at this time. They may not be cited and may not be
distributed to non-COG members. As new information becomes available, the Guidelines will be updated periodically to reflect
those changes. These Guidelines, and any subsequent revisions, will be posted on the COG website at:
http://members.childrensoncologygroup.org/Disc/lateeffects/default.asp
We recommend that clinicians check the website periodically for the latest updates and revisions. We anticipate (and in fact will
welcome) wide dissemination of the Guidelines in the future; however, at this time, we are releasing them in a limited fashion in
anticipation that some revisions may be required before the document is released to the public.
The Guidelines are organized by column as follows:
Therapeutic Agent: The therapeutic intervention for malignancy, including chemotherapy, radiation therapy, surgery, ortransfusion.
Section Number: Corresponds with Reference List and Index
Potential Late Effects: Lists the most common late treatment complications associated with the therapeutic intervention.
Risk Factors: List host factors (e.g., age, sex, race, genetic predisposition), treatment factors (e.g., cumulative dose oftherapeutic agent, mode of administration, combinations of agents), medical conditions (e.g., pre-morbid or co-morbid
conditions), and health behaviors (e.g, diet, smoking, alcohol use) that may increase risk of developing the complication
Highest Risk: Conditions (host factors, treatment factors, medical conditions and/or health behaviors) associated with the highest
risk for developing the complication

Instructions for Use - 2

Periodic Evaluations: Recommended screening evaluations including health history, clinical exams, laboratory evaluation,
diagnostic imaging, psychosocial assessments, or other indicated evaluations.
Minimum Recommended Frequency: Recommended minimum frequency of periodic evaluations based on risk factors andmagnitude of risk as supported by medical literature and/or the combined clinical experience of the reviewers and panel ofexperts.
Health Protective Counseling: Suggested patient counseling regarding measures to prevent/reduce risk or promote early
detection of the potential treatment complication. “Health Links” listed in the document are health education materials produced
specifically to accompany this document. Some of these educational materials are currently under development. Health Links
available as of the release date of this document are included in the Appendix. Health Links not yet completed will be added tofuture revisions of the document and posted on the COG website as they become available.
Considerations for Further Testing and Intervention: Includes recommendations for further diagnostic evaluations beyond
minimum screening for individuals with positive screening tests, recommendations for consultation and/or referral, andrecommendations for management of exacerbating or predisposing conditions.
Cancer Screening Recommendations are included at the end of the Guidelines. This section is organized as follows:
Organ: The organ at risk for developing malignancy
At Risk Population: Populations generally considered at increased risk for the specified malignancy based on risk factors suchas age, gender, genetic susceptibility, personal or family history, health-related behaviors or co-morbidities.
Highest Risk: Populations considered by the Panel of Experts or other evaluating bodies (such as the American Cancer Society)as being at significantly increased risk for the specified malignancy. Risk factors may include therapeutic exposures resulting fromchildhood cancer treatment, as well as other factors listed above (e.g., genetic susceptibility).
Periodic Evaluations:Standard Risk: Guidelines provided under the “Standard Risk” category in this document are per American Cancer Society
recommendations for standard-risk populations and are included here for reference. In addition, clinicians are encouraged toconsult recommendations from other organizations, such as the U. S. Preventive Services Task Force(http://www.ahrq.gov/clinic/serfiles.htm).
Highest Risk: Recommendations for these high-risk populations, when applicable, are specified and may differ fromrecommendations for the standard risk groups due to the significantly increased risk of the specified malignancy within thehigh-risk group.

Instructions for Use - 3

Also included in the Cancer Screening section are recommendations for periodic evaluations (including minimum recommended
frequency), health protective counseling, and considerations for further testing and intervention.
References are provided immediately following the Guidelines. The Reference section contains medical citations corresponding toeach numbered section of the Guidelines. Included are references that provide evidence for the association of the therapeuticintervention with the specific treatment complication and/or evaluation of predisposing risk factors. In addition, some general review
articles have been included in the Reference section for clinician convenience.
Index - due to significant overlap of toxicities between therapeutic agents, and in order to avoid an enormously lengthy document,
duplicate entries have been avoided as much as possible. Therefore, use of the Index is imperative in order to determine thelocation of each potential late effect associated with each therapeutic agent within this document.
Scoring - Each recommendation in the guidelines was scored by the Panel of Experts (see accompanying “Explanation of Scoring”
following the Index.) A tabulation of the final scores is also included in this packet.
We are hopeful that these Late Effects Screening Guidelines will enhance the follow-up care provided to childhood cancer survivors.
If you have any questions, suggestions, or concerns regarding use of these guidelines, please contact:
Melissa M. Hudson MD
Vice-Chair – COG Late Effects Committee
St. Jude Children’s Research Hospital, Memphis, TN(901) 495-4781
Melissa.Hudson@stjude.org
Wendy Landier, CPNP
Chair – COG Nursing Clinical Practice Subcommittee
City of Hope National Medical Center, Duarte, CA(626) 301-8426
wlandier@coh.org
Smita Bhatia, MD, MPH
Chair – COG Late Effects Committee
City of Hope Comprehensive Cancer Center, Duarte, CA(626) 301-8426
sbhatia@coh.org

COG Late Effects Guidelines 1
Version 1.0 - March 2003

Version 1.0
March 2003

Therapeutic Agent
Any cancer experience
Clinician Info Link
Off therapy guidelines
apply to patients whoare > 2 years after
completion of therapy.

Sec#

Potential Late Effects

Risk Factors

1

Psychosocial Effects
Depression
Anxiety
Post-traumatic stress
Social withdrawal,
isolation

2

Limitations in healthcare Social factors
Lower household income
and insurance accessLower educational
achievement

3

Dental abnormalities
Tooth/root agenesis
Root thinning/ shortening
Enamel dysplasia

Highest Risk

Periodic
Evaluation

Minimum Recommended

Frequency

Clinical interview Yearly
Host factors
Host factors
Female gender
CNS cancer or
Family hx of depression, CNS-directedanxiety, or mental illness therapy
Premorbid learningor emotional
Social factors
Lower household income difficulties
Lower educational
achievement
Social factors
Failure to graduate
from high school
Clinical history

YearlyHealth Protective
CounselingConsiderations for Further Testing
and Intervention

Psychological consultation in patientswith emotional difficulties related tocancer experience including physicaldeformities or chronic disabilities
following cancer treatment.
Resource"Childhood Cancer
Consider appropriate psychotropic
Survivors: A Practical
medications.
Guide to Your Future" by Social work consultation.
Nancy Keene, Wendy
Consider evaluation of parent for postHobbie & Kathy Ruccione traumatic stress syndrome.
Sebastopol, CA: O'Reilly& Assoc., 2000
Social work consultation.
Health Link
Finding appropriate
medical care afterchildhood cancer
Health Link
Emotional issues afterchildhood cancer

Any Chemotherapy
Host factors
Any patient who has notdeveloped permanentdentition

Dental exam andHost factors
Younger age atcleaning
treatment,
especially < 5 years
oldEvery 6 months

Cancer treatment
Any radiation treatment
including oral cavity orsalivary glands.
FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Health Link
Dental HealthRegular dental care including fluoride
applications.
Baseline panorex prior to dental
procedures to evaluate root
development.

COG Late Effects Guidelines 2
Version 1.0 - March 2003
Therapeutic Agent
Alkylating Agents
Mechlorethamine
Cyclophosphamide
Ifosfamide
Melphalan
Chlorambucil
Lomustine (CCNU)
Carmustine (BCNU)
BusulfanThiotepa
Procarbazine

Sec
#
4

Hypogonadism
Infertility
Early menopause
See related topics:
Radiation – TBI,
head/brain, abdomen,
pelvis, or testes.
Clinician Info Link
Extensive information
regarding infertility forphysicians and patientsavailable at American
Society for Reproductive
Medicine website:www.asrm.org

Non-classical alkylators:

Dacarbazine
Temozolamide
Heavy metals:

Cisplatin
Carboplatin
Clinician Info Link
Doses that cause
gonadal dysfunction
show individual
variation.
Sertoli cell function(spermatogenesis) is
impaired at lower doses
compared to Leydig
cell (testosterone
production) function.
Females can typicallymaintain gonadal
function at higher
cumulative doses.
Prepubertal status does
not protect fromgonadal injury inmales.

Potential Late Effects

Risk Factors
Treatment factors
Higher cumulative dosesof alkylators or
combinations ofalkylators
Combined with radiationto:- abdomen/pelvis- CNS- head/neck- testes- craniospinal axis ingirls (from ovarian
scatter)

See also:
www.fertilehope.org

Highest Risk

Periodic
Evaluation

Treatment factors
Less than 10 years since
exposure to agent
Higher cumulative
alkylator dose or
combination of alkylators
Note: Melphalan andmechlorethamine are
more potent leukemogens
than cyclophosphamide

Health Protective
CounselingConsiderations for Further Testing
and Intervention

For females

YearlyPubertal history(onset, tempo)
Menstrual andpregnancy history
Physical exam: height,
weight, Tanner stage

LH, FSH,
testosterone

Acute myeloid leukemia
Myelodysplasia

Frequency

Bone density evaluation for
Health Link
Fertility and pregnancy
oteopenia/osteoporosis in
outcomes after childhood hypogonadal patients.
cancerHormonal replacement therapy for
Treatment factors
hypogonadal patients.
MOPP > 3 cycles
Counsel currently
Reproductive endocrinology/
Busulfan > 600
menstruating women atobstetrics referral for infertility
mg/m2
evaluation and consultation
Baseline at age 11 or older and for: increased risk of early
FSH,
LH,
estradiol
Cyclophosphamide- Delayed puberty, irregularmenopause to be cautious regarding assisted reproductive> 7.5 g/ m2
menses or amenorrhea
about delaying
technologies.
- Clinical signs and symptoms childbearing.
cumulative
Consider 2 months off hormonalof estrogen deficiency
or > 200 mg/kg for
replacement in women with ovarianstem cell transplantCounsel regarding need for failure to assess ovarian recovery.
contraception since there
Any alkylators
For males
is tremendous individual
combined with:Pubertal history
Yearlyvariability in gonadal- testicular radiation (onset, tempo)
toxicity after exposure to- pelvic radiation History of sexual
radiation therapy andfunction (erections,- TBI
alkylating agents.
nocturnal emissions,libido)Recovery of fertility may
History of medication
occur years after therapy.
Host factors
Male genderuse
Physical examincluding height,
weight, Tanner stage,
testicular volume by
Prader orchiometry.

5

Minimum Recommended

Resources:
American Society for
Reproductive Medicine
website:Baseline, at age 11 or older and for: www.asrm.org- Delayed puberty- Clinical symptoms of
testosterone deficiency

See also:
www.fertilehope.org

Semen analysis

As requested by patientand for evaluation ofinfertility

Physical exam
CBC/differential

Yearly up to 15 years after Counsel to promptly report Bone marrow exam as clinically
exposure to agent
fatigue, pallor, petechiae, indicated.
or bone pain.

Medical conditions:
Splenectomy (conflicting
evidence)

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

COG Late Effects Guidelines 3
Version 1.0 - March 2003
Therapeutic AgentBusulfan
Carmustine (BCNU)
Lomustine (CCNU)

Sec
Potential Late Effects#
6 Pulmonary fibrosis
See related topics:
Bleomycin
Chest/thorax radiation

Risk Factors

Highest Risk

Periodic
Evaluation
Treatment factors Physical exam
Treatment factors
Higher cumulative doses BCNU > 600 mg/m2
Busulfan > 500 mg PFTs (including
Combined with otherpulmonary toxic therapy: (transplant doses)
DLCO and- bleomycin
spirometry) and- cyclophosphamide
CXR- doxorubicin- dactinomycin- chest/thoracic radiation- spinal radiation >30 Gy- total body irradiation

Considerations for Further Testing
and Intervention
YearlyPulmonary consultation for
symptomatic pulmonary dysfunction.
Baseline, upon entry into
Influenza and Pneumovax
long-term follow-up
Avoid SCUBA diving due immunization.
Repeat as clinicallyto history of treatment
indicated in patients with with pulmonary–toxic
abnormal or progressive chemotherapy
pulmonary dysfunction
Minimum Recommended

Frequency

Health Protective
Counseling
Health Link
Pulmonary Health

Medical conditions
Atopic history

Cyclophosphamide
Ifosfamide

7

Hemorrhagic cystitis
Bladder fibrosis
Dysfunctional voiding
See related topics:
Pelvic radiation

8

Ifosfamide

9

Bladder malignancy
See related topics:
Pelvic radiation
Renal toxicity:
Glomerular toxicity
Tubular toxicity-Renal tubular acidosis-Fanconi’s syndrome-Hypophosphatemic
rickets

Health behaviors
Cigarette smoking
Treatment factors
Higher cumulative doses(decreased incidence w/
Mesna)
Combined with pelvic
radiation

Treatment factors Urinalysis
Cyclophosphamide
dose > 3 gm/m2

YearlyCounsel to promptly report Urology consultation for culture
dysuria or grossnegative macroscopic hematura.

Urinalysis

YearlyCounsel to promptly report Urology consultation for culture
dysuria or grossnegative macroscopic hematuria.
hematuria.

Blood pressure

Yearly

BUN, creatinine

YearlyHealth Link
Kidney HealthSee also: Single Kidney
Precautions

Urinalysis

YearlyHealth behaviors
Alcohol use
Tobacco use
Treatment factors
Combined with pelvic
radiation
Host factors
Host factors
Younger age at treatment Age < 5 years attime of treatment
Treatment factors
Higher cumulative dose
Treatment factors
Combined with other
Ifosfamide dose
nephrotoxic agents,> 60 grams/m2
such as:- cisplatin/carboplatin- aminoglycosides- amphotericin- immunosuppressants- abdominal radiation

Na, K, Cl, CO2, Ca, Baseline electrolytes at
Mg, P04
entry into LTFU.
If normal, repeat every
5 years.
If abnormal, repeat asclinically indicated.
Creatinine clearance

Medical conditions
Tumor infiltration of
kidney(s)Pre-existing renal
impairment.
Nephrectomy ormononephricor GFR

Baseline at entry into
LTFU. If abnormal,
repeat as clinicallyindicated

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Electrolyte supplements for patientswith persistent electrolyte wasting.
Nephrology consultation for patientswith hypertension, proteinuria, or
progressive renal insufficiency.

COG Late Effects Guidelines 4
Version 1.0 - March 2003
Therapeutic Agent
Heavy Metals
Cisplatin
Carboplatin

Sec
#
10

Potential Late Effects

Ototoxicity:- Sensorineural
hearing loss
- Tinnitus- Vertigo
See related topics:
Ear radiation

Risk Factors

Host factors
Host factors
Age <4 years at treatment CNS neoplasm
Treatment factors
Combined with:- head/neck/cranialradiation- other ototoxic drugs,
e.g.: aminoglycosides- loop diuretics

Clinician Info Link
Prospective studies areneeded to define ototoxic Medical conditions
dose/effect relationship for Chronic otitis
carboplatin.
Cerumen impaction
Renal dysfunction

11

12

13

Peripheral sensory
neuropathy
Clinician Info Link
Neuropathy presents aspersistent effect after
therapy and is not late in
onset.
Renal toxicity:- Glomerular injury- Tubular injury- Renal insufficiency

Highest Risk

Periodic
Evaluation
History andphysical exam

Minimum Recommended

Frequency
YearlyHealth Protective
CounselingConsiderations for Further Testing
and Intervention

Health Link
Hearing Conservation

Audiology consultation for assistive
devices in patients with progressive
hearing loss.
Speech and language therapy forchildren with hearing loss.
Otolaryngology consultation inpatients with chronic infection,
cerumen impaction, or otheranatomical problems exacerbating orcontributing to hearing loss.
Refer to school liaison in community
or cancer center (psychologist, social
worker, school counselor) to facilitate
provision of educational resources,
IEP for preferential classroom seatingor specialized classroom placement,
FM trainer or other assistive devices,and other educational assistance as
indicated.
Physical therapy referral for patientswith symptomatic neuropathy.
Physical therapy and occupational
therapy assessment of hand function.
If significant pain, treatment with
anticonvulsant effective forneuropathic pain (e.g., gabapentin, or
amitriptyline).
Electrolyte supplements forpatients with persistentelectrolyte wasting.
Nephrology consultation forpatients with hypertension,
proteinuria, or progressive
renal insufficiency.

Yearly after completion ofTreatment factors Audiogram or
Cumulative cisplatin brainstem auditory therapy for 5 years (forpatients < 10 yrs olddose > 360 mg/m2 evoked response(ABR, BAER)
continue yearly until age10); then every 5 years.
If abnormal, follow yearly
until stable.
Obtain more frequently ifclinical evidence ofprogressive hearing loss.

Treatment factors
Treatment factors Neurologic exam
Combined with vincristine Cisplatin cumulative
dose > 300 mg/m2

Treatment factors
Combined with othernephrotoxic agents,
such as:- ifosfamide- aminoglycosides- amphotericin- immunosuppressants- cyclosporine- abdominal radiation
therapy

Treatment factors Blood pressure
Cisplatin dose
BUN, creatinine> 200 mg/m2

Medical conditions
MononephricDiabetes mellitus
Familial hypertension
Dyslipidemia
Host factors(reports are conflicting that Family history ofcisplatin predisposes todyslipidemia
dyslipidemia)
Medical conditions
Overweight/Obesity

Creatinine clearance

Urinalysis

Yearly, until 2 to 3 years
after therapy. Continue
to follow-up yearly if
symptoms persist.

YearlyYearlyYearlyNa, K, Cl, CO2, Ca, Baseline electrolytes at
Mg, P04
entry into LTFU. If
normal, repeat every 5
years. If abnormal, repeat
as clinically indicated.
or GFR

Health Link
Kidney HealthSee also: Single Kidney
Precautions
In patients with saltwasting tubular
dysfunction, educate that
low magnesium levels
potentiate coronary
atherosclerosis.

Baseline at entry into
LTFU. If abnormal,
repeat as clinicallyindicated.

Fasting lipid profile Baseline, at entry into long-term follow-up; then as per
United States Preventive
Task ForceRecommendations
http://www.ahrq.gov/clinic/pre
venix.htm
If abnormal, refer for
management of dyslipidemia

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Lipid lowering strategies including
diet, exercise, weight loss, statin
therapy.

COG Late Effects Guidelines 5
Version 1.0 - March 2003
Therapeutic Agent
Antimetabolites
Cytarabine(high-dose IV)
See related topics:
Methotrexate
Head/brain radiation

Clinician Info Link
Neurocognitive deficits
in survivors ofleukemia andlymphoma are more
frequently related to
information processing(e.g., learning
disability).
Neurocognitive deficits
in brain tumor
survivors treated withhigher doses of cranialradiation are moreglobal (significant
decline in IQ).
New deficits may
emerge over time;extent of deficit
depends on age attreatment, intensity oftreatment, time sincetreatment.

Sec
#
14

Potential Late Effects

Risk Factors

Highest Risk

Periodic
Evaluation

Minimum Recommended

Frequency

Health Protective
Counseling

Clinical interview Baseline at entry into
Neurocognitive deficits:
Host factors
Host factors
Health Link
Diminished IQ (combined Younger age at treatment Age < 3 years old at including
LTFU, then yearly
School and learning issues
with high dose and/or
assessment of
CNS leukemia/lymphoma time of treatment
after childhood cancer
intrathecal methotrexate
Female gendereducational or
and/or cranial radiation.) Treatment factors
vocational
Functional deficits in:
High-dose systemic
Treatment factors progress
Combined withadministration
Processing speed
Memory (particularly
methotrexate and/or Referral for formal Baseline at entry into(> 1000 mg/m2 dose)
neuropsychological LTFU, then periodically as
visual, sequencing,
cranial radiation.
In
combination
with:evaluation
temporal memory)
Radiation > 24 Gyclinically indicated for- dexamethasone
TBI with daily
patients with evidence ofSustained attention
impaired educational or
Visual-motor integration - cranial radiation > 18 Gy fraction > 2 Gy
total
body
irradiation
vocational progressMath- intrathecal methotrexate
Reading (particularly
reading comprehension)
Planning and organization Medical conditions
CNS leukemia/lymphomawith poor CSF
Clinician Info Link
Acute toxicity predominates reabsorption
if administeredsystemically as single
agent.
May contribute to lateneurotoxicity if combinedwith intrathecal
methotrexate and/ or
cranial radiation.
Clinicalleukoencephalopathy(spasticity, ataxia,
dysarthria, dysphagia,
hemiparesis, seizures)with or without
imaging abnormalities:- leukoencephalopathy- cerebral lacunes- cerebral atrophy- dystrophic calcifications- mineralizing microangiopathy

Treatment factors Clinical evaluation Yearly
Treatment factors
High-dose IV
Combined with:MRI
As clinically indicated- intrathecal methotrexate administration- dexamethasone
CT plus MRI with As clinically indicated- cranial radiation > 18 Gy
MR angiography

Considerations for Further Testing
and Intervention
Formal neuropsychological evaluation
to include tests of processing speed,
computer-based attention, visual
motor integration, memory,comprehension of verbal instructions,verbal fluency, executive function andplanning.
Consider use of psychotropic
medication (stimulant). Caution:
lower starting dose and assessmentof increased sensitivity when
initiating therapy is recommended.
Refer to school liaison in community
or cancer center (psychologist, social
worker, school counselor) to facilitate
acquisition of educational resources(IEP) and/or social skills training.
Refer to community services forvocational rehabilitation or forservices for developmentally disabled.

Neuroimaging with preferred study
based on intracranial lesion to beevaluated:
MRI: White matter
Gadalinium-enhanced MRI:
micro vascular injury
CT: calcifications
Neurology consultation and follow-up

Clinician Info Link
Neuro-imaging changes do
not always correlate with
degree of cognitive
dysfunction. Prospective
studies are needed to define
the dose/effect relationshipof neurotoxic agents.
Note: new deficits may
emerge over time.

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

COG Late Effects Guidelines 6
Version 1.0 - March 2003
Therapeutic Agent
Mercaptopurine
Thioguanine

Sec
Potential Late Effects#
15 Hepatic dysfunction
Veno-occlusive disease

Clinician Info Link
Osteopenia andosteoporosis occur
more commonly after
methotrexate than does
osteonecrosis.
See related topics:
Corticosteroids(continued on next
page)

Medical conditions
Viral hepatitis

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

Clinician Info Link
Acute hepatotoxicity
reported with thioguanine
used in CCG 1952
(regimens B1 and B2) for
ALL maintenance therapy
requires longer follow-up
to determine long-termsequelae.

Methotrexate(PO, IV, IM)

Risk Factors

16

Osteopenia
Bone mineral density > 1
and < 2.5 SD below mean
Osteoporosis
Bone mineral density > 2.5
SD below mean

Host factors
Both genders at risk
Treatment factors
Corticosteroids
Cranial/spinal, head/neck,gonadal radiation
Hematopoietic stem celltransplant

Clinician Info Link
World Health Organization
definition of osteoporosis in
adults is based on comparison
Medical conditionsof a measured bone mineraldensity of young adults at peak Hypogonadism
Premature ovarian failurebone age and defined as a TEarly menopause
score.
A T-score of > 2.5 standard
Growth hormone
deviations below the mean isdeficiency
consistent with a diagnosis of Hyperthyroidism
osteoporosis.
T-scores are not appropriate toassess skeletal health inpediatric patients who have notachieved peak adult bone
mass.
Pediatric bone mineral density
reference data sets calculate zscores based on age andgender, but do not account forvariations related to sexual
maturation and ethnicity.
The ideal reference data should
provide assessment relative tobody size, pubertal status, andage.
Currently available pediatricreference data sets are notlarge enough to accurately
characterize the normal
variability in bone mineraldensity.
Consequently, there are noevidence-based guidelines forclassification of bone health inchildren.

Highest Risk

Periodic
Evaluation
Medical conditions Physical exam
Chronic viral
hepatitis
ALT, AST,
bilirubin

Bone density
evaluation(DEXA orquantitative CT)
Clinician Info Link

The optimal
method ofmeasuring bonehealth in children
is controversial.
Existing
technologies have
limitations.
Dual energy x-ray
absorptiometry(DEXA) provides
an estimate of totalbone mass at agiven site.
Quantitative CT
provides distinct
measures oftrabecular andcortical bonedimension anddensity.

Minimum Recommended

Frequency
YearlyHealth Protective
Counseling
Health Link
Liver HealthBaseline, upon entry into
long-term follow-up.

Baseline screening at 18 Health Link
years old; consider earlier Bone Healthscreening if clinicallyindicated.
Resource:
Repeat prn as clinicallyNational Osteoporosis
indicated.
Foundation website
www.nof.org

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Considerations for Further Testing
and Intervention
Prothrombin time for evaluation ofhepatic synthetic function in patientswith abnormal liver screening tests.
Screen for viral hepatitis in patientswith persistently abnormal liverfunction or any patient transfusedprior to 1993.
Gastroenterology/hepatology
consultation in patients with persistentliver dysfunction.
Hepatitis A and B immunization inpatients lacking immunity.
Nutritional supplements in cases ofosteopenia unresponsive to behavioral
and dietary management:
Calcium 1000-1500 mg daily plus
RDA for vitamin D.
** Caution regarding calcium
supplementation in patients withhistory of renal lithiasis.
Treatment of exacerbating or
predisposing conditions (e.g.,
hormonal replacement therapy for
hypogonadism, growth hormone
deficiency; correction of chronic
metabolic acidosis that could
accelerate bone loss.).
Endocrine consultation for patientswith bone density more than 2.5 SD
below mean, or patients with historyof multiple fractures, for otherinterventions (e.g., bisphosphonates,
calcitonin, selective estrogen receptor
modulators).

COG Late Effects Guidelines 7
Version 1.0 - March 2003
Therapeutic Agent
Methotrexate(PO, IV, IM)Sec
Potential Late Effects#
17 Osteonecrosis(avascular necrosis)
Clinician Info Link
AVN typically occurs
during the acute treatment
phase, may progress overtime or resolve. Multifocal
AVN is significantly morecommon (3:1) thanunifocal.
See related topics:
Corticosteroids
18

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

19

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

Risk Factors
Host factors
Both genders at risk

Highest Risk
Host factors
Older age (>10 years
old) at treatment

Periodic
Evaluation
History

Minimum Recommended

Frequency
YearlyHealth Protective
Counseling
Health Link
Avascular Necrosis

Treatment factors
Combined with:
Treatment factors
Orthovoltage- corticosteroids(dexamethasone effect is radiation(commonly used
more potent than
before 1970) due toprednisone)delivery of greater- high-dose radiation todose to skin andany bonebones.
Medical conditions
Sickle cell disease
Host factors
MononephricCombined with othernephrotoxic agents:- cisplatin/carboplatin- ifosfamide- aminoglycosides- amphotericin- immunosuppresants- cyclosporine- abdominal radiation
Medical conditions
Diabetes mellitus
Familial hypertension
Treatment factors
Abdominal radiation
Medical conditions
Viral hepatitis

Treatment factors Blood pressure
Treatment before
1970.
BUN, creatinine
Urinalysis

YearlyHealth Link
Kidney HealthBaseline, upon entry into See also: Single Kidney
long-term follow-up.
Precautions

Considerations for Further Testing
and Intervention
Diagnostic imaging (radiograph, MRI)in patients with history of chronic
pain.
Orthopedic consultation for history ofchronic joint pain in predisposed
patient.

Nephrology consultation for patientswith hypertension, proteinuria, or
progressive renal insufficiency.

Obtain in patients withNa, K, Cl, CO2
Creatinine
abnormal BP, urinalysis,
clearance or GFR. BUN, or creatinine.
If abnormal, repeat asclinically indicated.

Treatment factors Physical exam
Treatment before
1970
ALT, AST,
bilirubin
Medical conditions
Chronic viral
hepatitis

YearlyBaseline, upon entry into
long-term follow-up.

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Health Link
Liver HealthProthrombin time for evaluation ofhepatic synthetic function in patientswith abnormal liver function onscreening tests.
Gastroenterology/hepatology
consultation in patients with persistentliver dysfunction.
Hepatitis A and B immunization inpatients lacking immunity.

COG Late Effects Guidelines 8
Version 1.0 - March 2003
Therapeutic Agent
Methotrexate(IT, high-dose IV)
See related topics:
Head/brain radiation
Clinician Info Link
Neurocognitive deficits
in survivors ofleukemia andlymphoma are more
frequently related to
information processing(e.g., learning
disability).
Neurocognitive deficits
in brain tumor
survivors treated withhigher doses of cranialradiation are moreglobal (significant
decline in IQ).
New deficits may
emerge over time;extent of deficit
depends on age attreatment, intensity oftreatment, time sincetreatment.

Minimum Recommended
Sec
Potential Late Effects
Risk Factors
Highest Risk
Periodic
Health Protective
Frequency##
EvaluationCounseling
Clinical interview Yearly
20 Neurocognitive deficits:
Host factors
Host factors
Health Link
Diminished IQ (with high Younger age at treatment Age < 3 years old at including
School and learning issues
dose and/or intrathecal
CNS leukemia/lymphoma time of treatment
assessment ofafter childhood cancer
methotrexate and/or cranialeducational or
Female genderradiation.)
vocational
Treatment factors
Intrathecal administration Treatment factors progress
Functional deficits in:
High-dose systemic
High-dose and/or IT
Processing speed
Memory (particularly
administration
Referral for formal Baseline at entry into
methotrexate
neuropsychological LTFU, then periodically as
visual, sequencing,(> 1000 mg/m2 dose)combined withevaluation
temporal memory)
In combination with:clinically indicated for
cranial radiation.
- dexamethasone
patients with evidence ofRadiation dose
Sustained attention
impaired educational or
Visual-motor integration - cranial radiation > 18 Gy > 24 Gy- total body irradiation
TBI with daily
vocational progress
Math
Reading (particularly- high-dose IV cytarabine fraction > 2 Gy
reading comprehension)
Planning and organization
Medical conditions
CNS leukemia/lymphomawith poor CSF
reabsorption

Clinicalleukoencephalopathy(spasticity, ataxia,
dysarthria, dysphagia,
hemiparesis, seizures)with or without
imaging abnormalities:- leukoencephalopathy- cerebral lacunes- cerebral atrophy- dystrophic calcifications- mineralizing microangiopathy

Treatment factors Clinical evaluation Yearly
Host factors
Younger age at treatment High-dose and/or IT
Brain MRIAs clinically indicated
CNS leukemia/lymphoma methotrexate
combined withcranial radiation. Brain CT plus MRI As clinically indicatedTreatment factors
with MR
Intrathecal administration Radiation doseangiography> 24 Gy
High-dose systemic
TBI with daily(> 1000 mg/m2 dose)
administration
fraction > 2 Gy
Triple intrathecal
chemotherapy
In combination with:- dexamethasone- cranial radiation- total body irradiation

Clinician Info Link
Neuro-imaging changes do
not always correlate with Medical conditions
CNS leukemia/lymphoma
degree of cognitive
with poor CSF
dysfunction.
reabsorption
Prospective studies areneeded to define thedose/effect relationship ofneurotoxic agents.
Note: new deficits may
emerge over time.

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Considerations for Further Testing
and Intervention
Formal neuropsychological evaluation
to include tests of processing speed,
computer-based attention, visualmotor integration, memory,comprehension of verbal instructions,verbal fluency, executive function andplanning.
Consider use of psychotropic
medication (stimulant). Caution:
lower starting dose and assessment of
increased sensitivity when initiating
therapy is recommended.
Refer to school liaison in community
or cancer center (psychologist, social
worker, school counselor) to facilitate
acquisition of educational resources(IEP) and/or social skills training.
Refer to community services forvocational rehabilitation or forservices for developmentally disabled.
Neuroimaging with preferred study
based on intracranial lesion to beevaluated:
MRI: White matter
Gadalinium-enhanced MRI:
micro vascular injury
CT: calcifications
Neurology consultation and follow-up

COG Late Effects Guidelines 9
Version 1.0 - March 2003
Therapeutic AgentSec
Potential Late Effects#
Anthracycline antibiotics
21 Acute myeloid leukemia
Doxorubicin
Daunorubicin
Idarubicin
Mitoxantrone
Epirubicin
22 Cardiomyopathy
Arrhythmias
See related topics:
Chest/thorax
radiation

Risk Factors

Highest Risk

Clinician Info Link
Combined with other
Dose levels derived fromcardiotoxic
adult studies.
chemotherapy:Childhood cancer patients- cyclophosphamide
exhibit clinical and(100-200 mg/kg as
subclinical toxicity atconditioning for stem
lower levels.
cell transplantation)
Certain conditions such as
Amsacrineisometric exercise,pregnancy, and viral
infections, have been
Medical conditions
Congenital heart disease
anecdotally reported toPregnancy
precipitate cardiac
Febrile illness
decompensation.
Health behaviors
Need for prospective
Isometric exercise
studies to define risk
Drug use (e.g., cocaine,
factors.
diet pills, ephedra,
Note: pediatric studies ofmahuang)
anthracycline
cardiotoxicity
typically describe risks
based on combined
cumulative doses ofdaunomycin anddoxorubicin assuming anequivalent relative
cardiotoxicity per mg dose.
Idarubicin and mitoxantrone
are more cardiotoxic thandoxorubicin/daunorubicinon a mg per mg dose basis.
In limited studies,
epirubicin has similar dose
equivalency todaunomycin anddoxorubicin.

Minimum Recommended

Frequency

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Physical exam
CBC/ differential

Yearly up to 15 years post Counsel to promptly report Bone marrow exam as clinically
exposure to anthracycline fatigue, pallor, petechiae, indicated.
or bone pain.

Detailed historyof exertional
tolerance.

YearlyHealth Link
The heart andanthracyclines

Age at Treatment* Chest Radiation

Anthracycline Dose*

Recommended Frequency< 1 year old< 1 year old< 1 year old
1-4 years old
1-4 years old
1-4 years old
1-4 years old> 5 years old> 5 years old> 5 years old> 5 years old> 5 years old

Any< 200 mg/m2> 200 mg/m2
Any< 100 mg/m2> 100 to < 300 mg/m2> 300 mg/m2< 300 mg/m2> 300 mg/m2< 200 mg/m2> 200 to < 300 mg/m2> 300 mg/m2

Every year
Every 2 years
Every year
Every year
Every 5 years
Every 2 years
Every year
Every 2 years
Every year
Every 5 years
Every 2 years
Every year
Every year

Treatment factors
Less than 5 years since
exposure to drug
Treatment factors
Combined with radiation
involving the heart:
MantleMediastinal
Total body irradiation
Spinal > 30 Gy
Whole lung
Whole abdomen
Left hemiabdomen/flank

Periodic
Evaluation

Cardiology consultation in patientswith subclinical abnormalities onscreening evaluations, left ventricular
dysfunction, dysrrhythmia, orClinician Info Link
Counsel patients withprolonged QT interval.
Note: exertional
prolonged QT interval
Additional cardiology evaluation in
intolerance isabout use of medications
patients who received > 300 mg/m2 or
uncommon in young< 300 mg/m2 plus chest radiation whothat may further prolong
Treatment factors patients (< 25 years).
QT interval (e.g., tricyclic are pregnant or planning pregnancy toHigher cumulative Abdominal symptoms
include an EKG and echocardiogramanti- depressants,
doses:(nausea, emesis) may
before and periodically during
antifungals, macrolide> 550 mg/m2 in
be observed morepatients 18 years or frequently thanantibiotics, metronidazole). pregnancy (especially during 3rdexertional dyspnea orolder at time oftrimester) and monitoring during labor
chest pain.
treatment
and delivery due to risk of cardiac> 300 mg/m2 in
failure.
EKG
forevaluation
Baseline
at
entry
to
LTFU
patients younger
Consider excess risk of isometricof QT interval
than 18 years at
exercise program in any high risktime of treatment
patient defined as needing screening
ECHO
or
MUGA
Baseline
at
entry
to
LTFU,
Any dose in infant
every 1 or 2 years.
Longer time elapsed for evaluation of then periodically, based onsystolic function age at treatment, history offrom treatment
chest radiation andcumulative anthracycline
dose (see table below).
Host factors
FemaleBlack/African
AmericanYounger than 5
years at treatment

Yes
No
No
Yes
No
No
No
Yes
Yes
No
No
No

Any age with serial decrease in function* Age at time of firstcardiotoxic therapy(anthracycline or chest
irradiation, whichever
was given first)*based on equivalent mg
of doxorubicin/
daunorubicin

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

COG Late Effects Guidelines 10
Version 1.0 - March 2003
Therapeutic AgentSec#

Anti-Tumor Antibiotics
23
Bleomycin

Potential Late Effects
Interstitial pneumonitis
Pulmonary fibrosis

See related topics:
Chest/thorax radiation
Busulfan
Carmustine
Lomustine
Clinician Info Link
Administration of highconcentrations of oxygen
may result in chronic
progressive pulmonary
fibrosis.

Risk Factors

Highest Risk

Periodic
Evaluation

Treatment factors Physical exam
Host factors
Younger age at treatment Bleomycin dose
PFTs
> 400 U/m2
(injury observed in (including DLCO
Treatment factors
doses 60-100 U/m2 and spirometry)
Higher cumulative dosein children)
and CXR
Combined with otherpulmonary toxic therapy:- cyclophosphamide- doxorubicin- busulfan- dactinomycin- carmustine (BCNU)- lomustine (CCNU)- thoracic radiation- spinal radiation >30 Gy- total body irradiation

Minimum Recommended

Frequency
YearlyHealth Protective
CounselingConsiderations for Further Testing
and Intervention

Pulmonary consultation in patientswith symptomatic or progressive
Baseline upon entry to
pulmonary dysfunction.
long-term follow-up and
Influenza and Pneumovax
prior to general anesthesia. Avoid SCUBA diving due immunization.
Repeat as clinicallyto potential exacerbation ofindicated in patients with pulmonary fibrosis withabnormal or progressive high oxygen
pulmonary dysfunction. concentrations.
Health Link
Pulmonary HealthBleomycin Alert

Notify physicians of healthhistory and risk ofworsening fibrosis withhigh oxygen exposure suchas during generalanesthesia.

Medical conditions
Renal dysfunction
High dose oxygen support
such as during generalanesthesia
Health behaviors
Smoking
Dactinomycin

24

No known late effects(Dactinomycin has been
associated with acute venoocclusive disease, fromwhich the majority ofpatients recover without
sequelae)

Treatment factors
Hepatic radiation

Physical exam

Yearly

ALT, AST,
bilirubin

Baseline, upon entry into
long-term follow-up.

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Health Link
Liver HealthProthrombin time for evaluation ofhepatic synthetic function in patientswith abnormal liver screening tests.
Screen for viral hepatitis in patientswith persistently abnormal liverfunction or any patient transfusedprior to 1993.
Gastroenterology/hepatology
consultation in patients with persistentliver dysfunction.
Hepatitis A and B immunizations inpatients lacking immunity.

COG Late Effects Guidelines 11
Version 1.0 - March 2003
Therapeutic Agent
Corticosteroids
Prednisone
Dexamethasone

Sec
#
25

See related topics:
Methotrexate

Potential Late Effects

Risk Factors

Highest Risk

Periodic
Evaluation

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Baseline screening at 18 Health Link
Bone density
Host factors
Older age at time of evaluation
years old; consider earlier Bone Healthtreatment
screening if clinically(DEXA orNational Osteoporosis
indicated.
quantitative CT)
Foundation website:
Repeat prn as clinically
Treatment factors
Dexamethasone
www.nof.org
indicated.
Clinician Info
effect is more
Link
potent thanThe optimal
prednisone.
method ofmeasuring bonehealth in children
peak bone age and defined as a Tis controversial.
score.
Existing
Medical Conditions
A T-score of > 2.5 standard
deviations below the mean is
Hypogonadism
technologies haveconsistent with a diagnosis ofPremature ovarian failure
limitations.
osteoporosis.
Dual energy x-ray
T-scores are not appropriate to assess Early menopause
skeletal health in pediatric patients Growth hormone
absorptiometry
who have not achieved peak adultdeficiency(DEXA) provides
bone mass.
Hyperthyroidism
an estimate of total
Pediatric bone mineral density
reference data sets calculate z-scoresbone mass at a
based on age and gender, but do not
given site.
account for variations related to
Quantitative CT
sexual maturation and ethnicity.
The ideal reference data should
provides distinct
provide assessment relative to bodymeasures ofsize, pubertal status, and age.
trabecular andCurrently available pediatricreference data sets are not large
cortical bone
enough to accurately characterizedimension andthe normal variability in bonedensity.
mineral density.

Nutritional supplements in cases ofosteopenia unresponsive to behavioral
and dietary management:
Calcium 1000-1500 mg daily plus
RDA for vitamin D.

Minimum Recommended

Frequency

Osteopenia
Host factors(Bone mineral density 1-2.5 Both genders at risk
SD below mean)
Osteoporosis
Treatment factors(Bone mineral density > 2.5 Combined with:
SD below mean)- methotrexate- cranial or spinal
Clinician Info Link
radiation
World Health Organization definitionof osteoporosis in adults is based on - other head/neckradiationcomparison of a measured bonemineral density of young adults at- radiation to bones** Caution regarding calcium
supplementation in patients withhistory of renal lithiasis.
Treatment of exacerbating or
predisposing conditions (e.g.,
hormonal replacement therapy for
hypogonadism, growth hormone
deficiency; correction of chronic
metabolic acidosis that could
accelerate bone loss.).
Endocrine consultation for patientswith bone density more than 2.5 SD
below mean, or patients with historyof multiple fractures, for otherinterventions (e.g., bisphosphonates,
calcitonin, selective estrogen receptor
modulators).

Consequently, there are no evidencebased guidelines for classification ofbone health in children.

26

Osteonecrosis(avascular necrosis)

Host factors
Both genders at risk

Clinician Info Link
Treatment factors
AVN typically occurs during
Dexamethasone effect isthe acute treatment phase, may more potent thanprogress over time or resolve.
prednisone.
Multifocal AVN is significantly
Combined with:more common (3:1) than
- high-dose radiation to
unifocal.

any boneSee related topics:
Methotrexate
27

Cataracts

History
Host factors
Older age (>10 years
at time of treatment)

YearlyHealth Link
Avascular Necrosis

Diagnostic imaging (radiograph, MRI)in patients with history of chronic
pain.
Orthopedic consultation for history ofchronic joint pain in predisposed
patient.

Health Link
Vision preservation

Ophthalmology consultation if
problem identified.
Refer to school liaison in community
or cancer center (psychologist, social
worker, school counselor) to facilitate
acquisition of educational resources(IEP).

Treatment factors
Orthovoltage
radiation(commonly used
before 1970) due todelivery of greater
dose to skin andbones.

Medical conditions
Sickle cell disease
YearlyTreatment factors
Treatment factors Eye exam
Combined with:
TBI given in single including- total body irradiation
daily fraction
funduscopic exam
- head and neck radiation Radiation doseand visual acuity- busulfan> 10 Gy withpotential scatter toeye(s)
Longer interval sincetreatment
FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

COG Late Effects Guidelines 12
Version 1.0 - March 2003
Therapeutic Agent
Enzymes
Asparaginase

Sec
#
28

Potential Late Effects

Risk Factors

Highest Risk

Periodic
Evaluation

Minimum Recommended

Yearly, until 2 to 3 years
after therapy; continue tofollow-up yearly if
symptoms persist.

Frequency

Health Protective
CounselingConsiderations for Further Testing
and Intervention

No known late effects.
Acute toxicities
predominate, from which
the majority of patients
recover without sequelae.

Plant Alkaloids
Vincristine
Vinblastine
Clinician Info Link
Acute toxicities mostcommonly occur andusually resolve prior topatients entering longterm follow-up.
Neuropathy can persist
after treatment and is
not late in onset.

Epipodophyllotoxins
Etoposide (VP-16)
Teniposide (VM-26)
Clinician Info Link
Recent administration
schedules have been
modified to reduce therisk of thiscomplication.

29

Peripheral sensory or
motor neuropathy:- areflexia- weakness- foot drop
- parasthesias

Treatment factors
Combined with cisplatin

Treatment factors Neurologic exam
Doses > 6-8 mg

Medical conditions
Anorexia
Severe weight loss

Medical conditions
Charcot-MarieTooth disease30

Vasospastic attacks(Raynaud's phenomenon)(rare)

Health behaviors
Tobacco use
Recreational drug use

31

Acute myeloid leukemia

Medical conditions
Splenectomy(conflicting evidence)

History
Physical exam

Treatment factors Physical exam
Weekly or twice
CBC/ differential
weeklyadministration
Less than 5 years
since exposure to
drug.

Physical therapy referral for patientswith symptomatic neuropathy.
Physical therapy and occupational
therapy assessment of hand function.
Treatment with anticonvulsant
effective for neuropathic pain (e.g.,gabapentin and amitriptyline).

YearlyCounsel to wear
appropriate protective
clothing in cold
environments and to not
use tobacco orrecreational drugs.

Yearly up to 15 years
post exposure to agent

Counsel to promptly report Bone marrow exam as clinicallyfatigue, pallor, petechiae, indicated.
or bone pain.

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Vasodilating medications (calciumchannel blockers, alpha blockers) for
patients with frequent, severevasospastic attacks unresponsive to
behavioral management.

COG Late Effects Guidelines 13
Version 1.0 - March 2003
Therapeutic Agent
Radiation
All fields, including
Total Body Irradiation
Clinician Info Link
General factors
influencing radiation
toxicity:
Daily fraction size
Cumulative dose
Age of patient at
irradiation
Type of radiation used
Toxicity may not be
manifest until growthcompleted or patient
ages.

Sec
#

Potential Late Effects

32

Skin changes:
Fibrosis, telangiectasias

Risk Factors

Highest Risk

Periodic
Evaluation

Physical exam
Host factors
Host factors
Younger age at treatment Prepubertal attreatment
Treatment factors
Higher cumulative dose
Treatment factors

Minimum Recommended

Frequency
YearlyHealth Protective
CounselingConsiderations for Further Testing
and Intervention

Health Link
Skin health

Dose fraction > 200 cGy

Orthovoltage radiation(commonly used
before 1970) due todelivery of greater
dose to skin and bones.

33

Host factors
Secondary benign ormalignant neoplasm in or Cancer predisposing
mutations:near radiation field
p53, RB1, NF1
Treatment factors
Higher cumulative dose
Large treatment volumes

34

Dysplastic nevi
Skin cancer:
Basal cell carcinoma
Squamous cell carcinoma
Melanoma

Host factors
Gorlin's syndrome(nevoid basal cell
carcinoma syndrome)

35

Bone malignancies

Host factors
Adolescent at treatment
Cancer-predisposing
mutation(e.g., p53, RB1, NF1)

Treatment factors Physical exam with Yearly
Orthovoltage
inspection/
radiation
palpation of(commonly usedirradiated skin andbefore 1970) due to soft tissues.
delivery of greater
dose to skin andOther evaluations
bones.
based on treatment
volumes (seerecommendations
for specific fields)
YearlyTreatment factors Physical exam
Orthovoltage
radiation(commonly used
before 1970) due todelivery of greater
dose to skin andbones.
YearlyTreatment factors Physical exam
Radiation dose > 30 Gy

Orthovoltage
radiation(commonly used
before 1970) due todelivery of greater
Treatment factors
dose to skin andHigher radiation dose
Combined with alkylating bones.
agentsSurgical and/or oncology consultation
Health Link
Reducing the risk of second as clinically indicated.
cancers

Dermatology consultation for
Health Link
Skin healthevaluation and monitoring of atypical
Reducing the risk of second nevi.
cancers
Oncology consultation as clinicallyindicated.

Counsel patient to report
X-ray or other diagnostic imaging insymptoms promptly (bone patients with clinical symptoms.
pain, bone mass,
Oncology consultation as clinicallypersistent fevers, etc.)
indicated.

Total Body Irradiation (TBI)

Potential complications related to total body irradiation (TBI) are addressed throughout this document.
In order to obtain a complete list of potential complications related to total body irradiation,with associated recommendations, refer to all of the following radiation sections in this document:

Radiation - All Fields, Head/Brain, Eye, Ear, Neck, Trunk, Chest/Thorax, Abdomen/Pelvis, Testicular

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COG Late Effects Guidelines 14
Version 1.0 - March 2003
Therapeutic AgentSec#

Potential Late Effects

Risk Factors

Highest Risk

Periodic
Evaluation

Minimum Recommended

Frequency

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Head/Brain Radiation
Total Body Irradiation

Cranial (whole brain)
Craniospinal
Nasopharyngeal
Oropharyngeal
Orbital/Eye
Ear/Infratemporal

36(continued on next
page)

Clinical interview Baseline and yearly
Neurocognitive deficits:
Host factors
Health Link
Host factors
Younger age at treatment Age < 3 years at
School and learning issues
including
Diminished IQ (< 85)
Primary CNS tumor
after childhood cancer
time of treatment
assessment of
Functional deficits in:
ALL or relapsed ALL
Female gendereducational orProcessing speed
Memory (particularly
Head/neck tumors with
Tumor site in
vocational
visual, sequencing,brain in radiation field
cerebral hemisphere progress
temporal memory)
Sustained attention
Treatment factors
Treatment factors Referral for formal Baseline at entry into
neuropsychological LTFU, then periodically as
Cranial irradiation
Visual-motor integration Combined with:evaluation
clinically indicated for- methotrexate
Math
Reading (particularly
patients with evidence of(IT, high-dose IV)
Social factors
reading comprehension)
impaired educational or- dexamethasone
Low SES
vocational progress
Predisposing or
Planning and organization - cytarabine (high-doseIV)family history of
Increased risk for social
difficulties, psychological - high dose chemotherapy learning or attention
with autologous orproblems.
maladjustment.
allogeneic hematopoietic
Clinician Info Link
stem cell transplantation.
Neurocognitive deficits insurvivors of leukemia andlymphoma are more frequently
related to information
processing (e.g., learning
disability).
Neurocognitive deficits in brain
tumor survivors treated withhigher doses of cranialradiation are more global(significant decline in IQ).
New deficits may emerge overtime. The extent of deficit
depends on age at treatment
intensity of treatment, timesince treatment.

37

See related topics:
Methotrexate
Cytarabine
Neurosurgery
Clinicalleukoencephalopathy(spasticity, ataxia,
dysarthria, dysphagia,
hemiparesis, seizures)with or without
imaging abnormalities:- leukoencephalopathy- cerebral lacunes- cerebral atrophy- dystrophic calcifications- cavernous hemangioma- mineralizing microangiopathy

Clinical evaluation Yearly
Host factors
Host factors
Younger age at treatment Age < 2 years attime of treatment Brain MRI
As clinically indicatedTreatment factors
Higher radiation dose
Treatment factors Brain CT plus MRI As clinically indicatedCombined with:
Dose > 55 Gy
with MR- high-dose methotrexate Fraction dose > 2 Gy angiography- intrathecal methotrexate
or cytarabine
Medical conditions
Hydrocephalus requiring
shunt
Posterior fossa syndrome

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Formal neuropsychological evaluation
to include tests of processing speed,
computer-based attention, visualmotor integration, memory,comprehension of verbal instructions
verbal fluency, executive function andplanning.
Consider use of psychotropic
medication (stimulant). Caution:
lower starting dose and assessment of
increased sensitivity when initiating
therapy is recommended.
Refer to school liaison in community
or cancer center (psychologist, social
worker, school counselor) to facilitate
acquisition of educational resources(IEP) and/or social skills training.
Refer to community services forvocational rehabilitation or forservices for developmentally disabled.

Neuroimaging with preferred study
based on intracranial lesion to beevaluated:
MRI: White matter
Gadalinium-enhanced MRI:
micro vascular injury
CT: calcifications
Neurology consultation and follow-up

COG Late Effects Guidelines 15
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Therapeutic Agent(continued fromprevious page)

Sec
Potential Late Effects#
38 Stroke/moyamoya
Occlusive cerebral
vasculopathy

Total Body Irradiation
Cranial (whole brain)
Craniospinal
Nasopharyngeal
Oropharyngeal
Orbital/Eye
Ear/Infratemporal(continued on next
page)
39

40

41

Minimum Recommended
Periodic
Frequency
Evaluation
Host factors
Treatment factors Clinical evaluation Yearly
Hypothalamic/chiasmatic Dose > 40 Gy
Brain MRI with
As clinically indicatedgliomadiffusion-weighted
imaging with MR
Clinician Info Link
Medical conditions
Moyamoya syndrome is the Sickle cell diseaseangiography
complete occlusion of one Neurofibromatosis
or more of the three major
cerebral vessels with thedevelopment of small,
immature collateral vessels
which reflect an attempt torevascularize the ischemic
portion of the brain.
History & physical Yearly
Brain tumor:
Host factors
Host factors
High-grade astrocytoma
Younger age at treatment Age < 6 years at
Neurologic exam
Meningioma
Thiopurine methyl
time of treatment
Sarcomatransferase (TPMT)
Ataxia telangiectasia Brain MRI
Baseline at maturity for all
genetic polymorphism
patients
Neurofibromatosis
Every other year forpatients with neurofibromatosis, beginning
Treatment factors
Higher radiation dose
2 years after radiation
As clinically indicated for
symptomatic patients

Growth hormone
deficiency

Hyperprolactinemia

Risk Factors

Highest Risk

Host factors
Treatment factors Assess nutritional
Younger age at treatment Radiation dose
status.
> 18 Gy
Monitor height,
Pretransplant cranial weight
Treatment factors
radiation
Higher radiation doses
BMI percentiles
Single daily fraction Tanner staging
Surgery in suprasellar
TBI dose
regionPretransplant radiation
Bone age
Total body irradiation:> 10 Gy single fraction> 12 Gy fractionatedTreatment factors
Higher radiation dose

42

Central hypothyroidism(thyroid-releasing andthyroid-stimulating
hormone deficiency)

Treatment factors
Higher radiation dose
Total body irradiation

Treatment factors Free T4, TSH
Radiation dose> 30 Gy

Considerations for Further Testing
and Intervention
Neurology consultation and follow-up.
Physical and occupational therapy asclinically indicated.

Neurosurgical consultation for tissue
diagnosis and/or resection.
Neuro-oncology consultation for
medical management.

Every 6 months until
growth is completed.

Endocrine consultation for:- drop in %ile on growth grid- growth velocity < 4-5 cm/year
during childhood- growth below 3rd %ile
- lack of pubertal growth spurt.

Obtain in poorly growing
children.

Evaluate thyroid function in any poorly
growing child.

Treatment factors Review of systems: Yearly- galactorrhea
Radiation dose- menstrual history> 50 Gy- pregnancy history
Prolactin level

Health Protective
Counseling

In patients withgalactorrhea or
amenorrhea
YearlyFOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

CT evaluation of sella turcica for
pituitary adenoma in patients withhyperprolactinemia.
Endocrine consultation for patientswith hyperprolactinemia, amenorrhea,
or galactorrhea.
Consider TSH surge testing.
Endocrine consultation for thyroid
hormone replacement.

COG Late Effects Guidelines 16
Version 1.0 - March 2003
Therapeutic Agent(continued fromprevious page)

Sec
Potential Late Effects#
43 Central adrenal
insufficiency

Risk Factors
Treatment factors
Higher radiation dose

Periodic
Evaluation

Treatment factors Review of systems:- failure to thrive
Radiation dose
- anorexia> 30 Gy

Minimum Recommended

Frequency
Yearly- dehydration- hypoglycemia- lethargy- unexplained
hypotension

Total Body Irradiation
Cranial (whole brain)
Craniospinal
Nasopharyngeal
Oropharyngeal
Orbital/Eye
Ear/Infratemporal(continued on next
page)

Highest Risk

Health Protective
Considerations for Further TestingCounselingand Intervention
Corticosteroid replacement Endocrine consultation for further
and precautions about
evaluation and replacement steroids.
replacement therapy.
Recommend wearing
Medic Alert bracelet.

Resource: PediatricEndocrine Nurses (PENS)
Baseline on entry into long or Magic Foundation for
8:00 AM serum
cortisol in patientsterm follow-up andhypopituitarism.
treated with > 30 Gy periodically as clinicallyradiation toindicated
44

Precocious Puberty

Host factors
Female gender
Younger age at treatment
Treatment factors
Radiation doses > 18 Gy

hypothalamicpituitary axis
Physical exam
Yearlyincluding height,
weight, Tanner stage

LH, FSH, estradiol As clinically indicated inpatients with signs of
testosterone
accelerated pubertal
progression and growth.
Bone age

45

Gonadotropin deficiency(LH and FSH)

Treatment factors
Higher radiation dose

Endocrine consultation for accelerated
puberty (puberty in girl < 8 years oldand boy < 9 years old).
Consider pelvic ultrasound.

Obtain in rapidly growing
children.

Bone density evaluation for
Health Link
osteopenia/osteoporosis in
Fertility and pregnancy
outcomes after childhood hypogonadal patients.
Menstrual andHormonal replacement therapy forcancerpregnancy history
hypogonadal patients.
Counsel currently
Reproductive endocrinology/ obstetrics
FSH, LH, estradiol Baseline at age 11 or older and for: menstruating women atreferral for infertility evaluation and- Delayed puberty
increased risk of early
consultation regarding assisted- Irregular menses ormenopausetobecautious
amenorrhea
reproductive technologies.
- Clinical signs and symptoms about delaying childbearing. Consider 2 months off hormonalof estrogen deficiency
replacement in women with ovarianCounseling regarding need
Males:
failure to assess ovarian recovery.
for contraception since there
Pubertal history (onset, Yearly

Treatment factors Females:
Pubertal history
Radiation dose
(onset, tempo)> 30 Gy

tempo)
History of sexualfunction (erections,nocturnal emissions,libido).
History of medicationuse.
Physical exam includingheight, weight, Tannerstage, testicular volume
by Prader orchiometry.

LH, FSH,
testosterone
Semen analysis

Yearlyis tremendous individual
variability in gonadal
toxicity after exposure toradiation therapy andalkylating agents. Recoveryof fertility may occur many
years after therapy.

Resources:
American Society for
Baseline, at age 11 or older and for: Reproductive Medicine
website: www.asrm.org- Delayed puberty
See also:- Clinical symptoms ofwww.fertilehope.org
testosterone deficiency.
As requested by patient andfor evaluation of infertility.

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COG Late Effects Guidelines 17
Version 1.0 - March 2003
Therapeutic Agent(continued fromprevious page)

Sec
Potential Late Effects#
46 Overweight/Obesity

Risk Factors
Host factors
Younger at treatment

Definition by adultstandards:
Treatment factors
body mass index (BMI) = Higher cranial radiationdose
wt (kg)/ht (M2)
Overweight: BMI > 25-29.9 Combined withcorticosteroids
Obese: BMI > 30
BMI calculator available
on-line at:Medical conditions
http://nhlbisupport.com/bmi/
Familial dyslipidemia
Growth hormone
Definition by pediatricdeficiency
standards for < 16 years
Hypothyroidism
old:Overweight is defined by
sex-and age-specific
95%ile cutoff
points of CDC/NCHS
growth charts.
Growth charts available
on-line at:www.cdc.gov/growthcharts/

Total Body Irradiation
Cranial (whole brain)
Craniospinal
Nasopharyngeal
Oropharyngeal
Orbital/Eye
Ear/Infratemporal(continued on next
page)

47

48

49

50

Chronic sinusitis

Treatment factors
Higher cumulative
radiation doses to sinuses(> 30 Gy)

Highest Risk

Periodic
Evaluation
Blood pressure

Minimum Recommended

Fasting insulin

Obtain baseline forpatients with acanthosis
nigricans.
Consider testing inoverweight or obese
patients withdyslipidemia.
If abnormal, refer toendocrinologist

History
Physical exam

YearlyCT sinuses

As clinically indicatedFrequency

YearlyHost factors
Age < 4 years old attime of treatment Growth percentile YearlyFemale genderorBody mass index
Treatment factors
Hypothalamic dose Fasting lipid profile Every 3-5 years in> 20 Gy
overweight or obese
patients.
If abnormal, refer for
Medical conditions
Inability to exercise
management ofdyslipidemia

Medical conditions
Atopic history
Hypogammaglobulinemia
Xerostomia
Medical conditions
Treatment factors History
Salivary gland dysfunction Head and neck radiation Salivary gland dose Physical exam
involving the parotid> 30 Gy
gland
Higher radiation doses
Medical conditions
Total body irradiation
Chronic GVHD
Dental exam and
Dental abnormalities
Host factors
Host factors
Tooth/root agenesis
Younger age at treatment Age < 5 years at
cleaning
Microdontia
Gorlin's syndrome
time of treatment
Root thinning/shortening
Enamel dysplasia
Treatment factors
Treatment factors
Periodontal disease
Higher radiation dose
Dose > 30 Gy(may occur in young
Tooth decay
children at 10 Gy)
Malocclusion
Temporo-mandibular joint
dysfunction
Physical exam
Host factors
Craniofacial
Host factors
Younger age at treatment Age < 5 years atabnormalities
time of treatment Psychosocial
assessment ofTreatment factors
Higher radiation dose
adjustment

Health Protective
Considerations for Further TestingCounselingand Intervention
Obesity-related health
Consider evaluation for other corisks.
morbid conditions including:
Health promotion through dyslipidemia, hypertension, glucose
diet and physical activity intolerance, diabetes mellitus,
hyperinsulinism, insulin resistance.
Nutritional counseling.
Endocrine consultation for patientswith dyslipidemia or hyperglycemia.

Otolaryngology consultation asclinically indicated.

YearlyHealth Link
Dental HealthSupportive care with saliva substitutes,
moistening agents, and sialogogues(pilocarpine).
Regular dental care including fluoride
applications.

Every 6 months

Health Link
Dental HealthRegular dental care including fluoride
applications.
Consultation with orthodontist
experienced in management of
irradiated childhood cancer survivors.
Baseline panorex prior to dental
procedures to evaluate root
development.

YearlyResource:
FACES - The National
Craniofacial Associationwww.faces-cranio.org/

Plastic surgery/craniofacial surgery
consultation for facial reconstruction.
Consultation with psychologist in
patients with adjustment disorders
related to facial asymmetry/deformity.

YearlyFOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

COG Late Effects Guidelines 18
Version 1.0 - March 2003
Therapeutic AgentSec#

Potential Late Effects

Risk Factors

Highest Risk

Periodic
Evaluation

Minimum Recommended

Frequency

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Eye radiation
Total Body Irradiation

Orbital/Eye
Cranial (whole brain)
Craniospinal
Clinician Info Link:
Complications otherthan cataracts are
generally associatedonly with orbital/eye
radiation.

51

Cataracts

Treatment factors
Higher radiation dose
Combined with:- corticosteroids- busulfan

Yearly for patients who
Treatment factors Ophthalmology
Dose > 10 Gy
evaluation
received > 30 Gy or TBI
TBI given in single including
Every 3 years for patients
daily fraction
funduscopic exam who received < 30 Gy
and visual acuity(these patients also need

Reduced visual acuity
Orbital hypoplasia

Treatment factors
Treatment factors
Higher radiation dose
Fraction dose > 2 Gy
Higher daily fraction dose

Lacrimal duct atrophy

Treatment factors
Higher radiation dose
Combined with- doxorubicin- dactinomycin

Treatment factors
Dose > 40 Gy

Xerophthalmia (severe)

Treatment factors
Higher radiation dose

Treatment factors
Dose > 30 Gy

Keratitis

Treatment factors
Higher radiation dose

Treatment factors
Dose > 50 Gy

Keratoconjunctivitis sicca Treatment factors
Higher radiation dose
Corticosteroids

Treatment factors
Dose > 50 Gy

yearly funduscopic
exams during annual
LTFU visits)

Medical conditions
Chronic GVHD
Telangiectasias

Treatment factors
Higher radiation dose

Treatment factors
Dose > 50 Gy

Retinopathy

Treatment factors
Higher radiation dose

Treatment factors
Dose 45-65 Gy

Medical conditions
Diabetes mellitus
Optic chiasm neuropathy Treatment factors
Higher radiation dose

Treatment factors
Dose 50- 65 Gy

Medical conditions
Diabetes mellitus
Hypertension
Endophthalmos
Chronic painful eye

Treatment factors
Higher radiation dose

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Health Link
Vision preservation
Resource:
FACES - The National
Craniofacial Associationwww.faces-cranio.org/

Ongoing ophthalmology follow-up for
identified problems.
Consider every 6 month
ophthalmology evaluation for patientswith corneal damage (usuallyassociated with sicca) or complex
ocular problems.
Refer to school liaison in community
or cancer center (psychologist, social
worker, school counselor) to facilitate
acquisition of educational resources.

COG Late Effects Guidelines 19
Version 1.0 - March 2003
Therapeutic Agent
Ear radiation
Total body irradiation
Ear/Infratemporal
Cranial (whole brain)
Craniospinal
Nasopharyngeal

Sec#

Potential Late Effects

52

Tympanosclerosis
Otosclerosis
Eustachian tube
dysfunction
Conductive hearing loss

Risk Factors
Host factors
Younger age at treatment

Neck radiation
Any radiation withpotential impact tothe neck/thyroid,
including:
Total Body Irradiation
Cervical
Cranial (whole brain)
Craniospinal
Nasopharyngeal
Oroparyngeal
MantleMediastinal
Whole lung
Spinal53

54

Thyroid nodules

Thyroid cancer

Treatment factors
Dose > 50 Gy

Periodic
Evaluation

Treatment factors
Doses > 30-40 Gy

Treatment factors
Higher radiation dose
Combined with otherototoxic agents, such as:- cisplatin- aminoglycosides
Host factors
Younger age at treatment
Female gender

Minimum Recommended

Frequency

History and physical exam Yearly

Audiogram orbrainstem auditory
evoked response(ABR, BAER)

Treatment factors
Higher radiation dose

Medical conditions
Chronic otitis
Chronic cerumen impaction
Sensorineural hearing loss Host factors
Younger age at treatment
Tinnitus
CNS tumor
CSF shunting

See related topics:
Cisplatin, Carboplatin

Highest Risk

For patients who received≥ 30 Gy:
Yearly after completion oftherapy for 5 years (forpatients < 10 yrs old continue
yearly until age 10); thenevery 5 years.
If abnormal, follow yearly
until stable.
Obtain more frequently ifclinical evidence ofprogressive hearing loss.

Health Protective
Counseling
Health Link
Hearing conservation

Audiology consultation for assistive
devices in patients with progressive
hearing loss.
Speech and language therapy for children
with hearing loss.
Otolaryngology consultation in patientswith chronic infection, cerumen
impaction, or other anatomical problems
exacerbating or contributing to hearing
loss.
Refer to school liaison in community orcancer center (psychologist, social
worker, school counselor) to facilitate
provision of educational resources, IEP
for preferential classroom seating or
specialized classroom placement, FM
trainer or other assistive devices, andother educational assistance as indicated.

For patients who received< 30 Gy:
Baseline at entry into longterm follow-up, then as
clinically indicatedTreatment factors Physical exam
Cervical radiationdose > 25 Gy

YearlyHealth Link
Thyroid problems afterchildhood cancer.

Ultrasound for evaluation of palpablenodule(s).
Endocrine and/or surgical consultation
for diagnostic biopsy or
thyroidectomy.

Physical exam

YearlyHealth Link
Thyroid problems afterchildhood cancer.

Ultrasound for evaluation of palpablenodule(s).
Surgical consultation for resection.
Nuclear medicine consultation for
ablation of residual disease.
Endocrine consultation for
postoperative medical management..
Endocrine consultation for medical
management.

Treatment factors
Higher radiation dose
Cervical or total body
irradiation
Host factors
Younger age at treatment
Female gender
Treatment factors> 5-10 years after irradiation
Cervical or total body irradiation

55

Hypothyroidism

Host factors
Female gender
Treatment factors
Higher radiation dose
Cervical or total body irradiation

56

Hyperthyroidism

57

Carotid artery disease58

Esophageal stricture

Treatment factors History
Cervical radiation Physical exam
TSH, free T4
dose > 20 Gy

Yearly; consider more
Health Link
frequent screening during Thyroid problems after
periods of rapid growthchildhood cancer.

Note: must be freeT4 in females on OCP

History
YearlyPhysical exam
TSH, free T4
dose > 35 Gy
Treatment factors Clinical evaluation Yearly
Dose > 40 Gy
Doppler ultrasound As clinically indicatedof carotid vessels
YearlyTreatment factors History
Dose > 40 Gy

Treatment factors
Treatment factors
Higher radiation dose
Cervical radiation
Cervical or total body irradiation

Treatment factors
Higher radiation doseRadiomimetic chemotherapy:- dactinomycin- anthracyclines

Considerations for Further Testing
and Intervention

Medical conditions
Gastroesophageal reflux

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Health Link
Thyroid problems afterchildhood cancer.

Endocrine consultation for medical
management.
MRI with diffusion-weighted imaging
with MR angiography andcardiovascular surgery consultation asclinically indicated.
Surgical and/or gastroenterology
consultation for symptomatic patients.

COG Late Effects Guidelines 20
Version 1.0 - March 2003
Therapeutic Agent
Trunk radiation
Any field fromshoulders to pelvis
including:
Total Body Irradiation
Spinal (> 12 Gy)

Sec
#
59

60

Potential Late Effects

Risk Factors

Musculoskeletal growth
Host factors
Younger age at treatment
problems:- Hypoplasia- Fibrosis
Treatment factors- Reduced or uneven growth Higher cumulative dose
Larger treatment field- Shortened trunk height
Higher dose per fraction

Scoliosis

Highest Risk
Host factors
Prepubertal attreatment

Periodic
Evaluation
Physical exam

Treatment factors
Orthovoltage
radiation(commonly used
before 1970) due todelivery of greater
dose to skin andbones.
Epiphysis intreatment field.
Dose > 20 Gy
Host factors
Treatment factors Physical exam
Younger age at irradiation Radiation doses
Paraspinal malignancies > 20 Gy (lower
Neurofibromatosis
doses for infants)
Orthovoltage
radiation
Spine films
Treatment factors
Hemithoracic or(commonly used
abdominal radiation
before 1970) due to
Hemithoracic, abdominal delivery of greateror spinal surgery
dose to skin andbones.
Clinician Info Link:
Scoliosis is usuallyassociated with radiation
combined with surgery to
the hemithorax, abdomenor spine

Minimum Recommended

Frequency

Health Protective
Counseling

YearlyConsiderations for Further Testing
and Intervention
Orthopedic consultation if clinicallysignificant or for any deficit noted in
growing child.
Plastic surgery consultation forreconstruction.

Yearly until growth
Health Link
completed; may need
Scoliosis/kyphosis
more frequent assessment
during puberty
In patient with clinicallyapparent curve

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Orthopedics consultation as indicatedbased on radiographic exam.

COG Late Effects Guidelines 21
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Therapeutic AgentSec#

Chest/thorax radiation
Any field involving the 61
chest/thorax,
including:
Total Body Irradiation
MantleMediastinal
Whole lung
Spinal (> 30 Gy)
Whole abdomen
Any upper abdominal
field
62

Chest/thorax radiation
with potential impact
to the breast:
Total Body Irradiation
MantleMediastinal
Whole lung
Spinal (> 30 Gy)

63

Potential Late Effects
Kyphosis

Esophageal stricture

Breast cancer

Risk Factors

Highest Risk

Periodic
Evaluation

Host factors
Treatment factors Physical exam
Younger age at irradiation Radiation doses
Paraspinal malignancies> 20 Gy (lower
Neurofibromatosis
doses for infants)
Orthovoltage
radiation
Spine films(commonly used
before 1970) due todelivery of greater
dose to skin andbones.
Treatment factors
Treatment factors History
Higher radiation dose to Dose > 40 Gy
esophagus
Radiomimetic
chemotherapy:- dactinomycin- anthracyclines
Medical conditions
Gastroesophageal reflux
Host factors
Family history of breast
cancerTreatment factors
Higher radiation doseLonger time fromradiation (> 5-9 years
since radiation)

Host factors
Female gender

Breast tissue hypoplasia

Host factors
Prepubertal at time ofbreast irradiation
Treatment factors
Higher radiation dose

Frequency

Health Protective
Counseling

Yearly until growth
Health Link
completed; may need
Scoliosis/kyphosis
more frequent assessment
during puberty

Considerations for Further Testing
and Intervention
Orthopedics consultation as indicatedbased on radiographic exam.

In patient with clinicallyapparent curve

YearlyFor females only:
Breast selfMonthly, beginning at
examination
puberty
Clinical breast
exam

Yearly, beginning at
puberty until age 25, thenevery 6 months.

Mammogram

Yearly,beginning 8 years afterradiation or at age 25(whichever occurs last)

Clinician Info Link

64

Minimum Recommended

Mammography iscurrently limited in
its ability toevaluatepremenopausal
breasts.
Physical exam
YearlyFOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Surgical and/or gastroenterology
consultation for symptomatic patients.

Surgical consultation for diagnostic
Health Link
Reducing the risk of second procedure.
cancers
Precautions about the use of HRT.

Surgical consultation for breastreconstruction after completion of
growth.

COG Late Effects Guidelines 22
Version 1.0 - March 2003
Therapeutic Agent
Chest/thorax radiation
with potential impact
to the heart:
Total Body Irradiation
MantleMediastinal
Whole lung
Spinal (> 30 Gy)
Whole abdomen
Left hemiabdomen/
flank

Sec
Potential Late Effects#
65 Congestive heart failure
Cardiomyopathy
Pericarditis
Pericardial fibrosis
Valvular disease
Myocardial infarction
Arrhythmia
Atherosclerotic heartdiseaseSee related topics:
Anthracycline
chemotherapy

Risk Factors

Highest Risk

Periodic
Evaluation

Minimum Recommended

Frequency

Baseline, at entry into longHost factors
Treatment factors EKG
term follow-up and asYounger age at irradiation Dose > 40-45 Gy
clinically indicatedAnteriorly-weighted
Family history ofradiation fields
dyslipidemia
ECHO
Baseline, at entry into longLack of subcarinal
Coronary artery diseaseterm follow-up, thenshielding
periodically based on age at
Treatment factors
treatment, radiation dose, andcumulative anthracycline
Higher radiation dose todose (see table below).
chest/thorax
Combined with
For patients who received
Cardiology
radiomimetic
consultation for stress > 40 Gy: obtain baseline
chemotherapy:
testing5-10 years after radiation- dactinomycin- anthracyclines
Fasting glucose and Every 3 to 5 years.
lipid profile
If abnormal, refer for ongoing
Total body irradiation

Health Protective
Counseling
Health Link
The Heart and Radiation

Additional cardiology evaluation inpatients who are pregnant or planning
pregnancy who received TBI or> 30 Gy chest/thorax radiation.
Evaluation to include echocardiogram
before and periodically during
pregnancy (especially during third
trimester) and monitoring during laborand delivery due to risk of cardiac
failure.

management

Medical conditions
Hypertension
Obesity
Dyslipidemia
Diabetes mellitus
Premature ovarian
failure (untreated)
Health behaviors
Smoking

Age at Treatment* Anthracycline Dose*None< 1 year oldAny< 1 year old
None
1-4 years oldAny
1-4 years old
None, RT < 30 Gy> 5 years old
None, RT > 30 Gy> 5 years old< 300 mg/m2> 5 years old> 300 mg/m2> 5 years old
Any age with serial decrease in function

Considerations for Further Testing
and Intervention
Cardiology consultation in patientswith subclinical abnormalities onscreening evaluations or with left
ventricular dysfunction, dysrhythmia
or prolonged QT interval.

Recommended Frequency
Every 2 years
Every year
Every 2 years
Every year
Every 5 years
Every 2 years
Every 2 years
Every year
Every year

* Age at time of first * Based on equivalent mg of
doxorubicin/ daunorubicin
cardiotoxic therapy(anthracycline orchest irradiation,
whichever was given
first)

Chest/thorax radiation
with potential impact
to the lungs:
Total Body Irradiation
MantleMediastinal
Whole lung
Spinal (> 30 Gy)
Whole abdomen
Any upper abdominal
field

66

Pulmonary fibrosis
Delayed interstitial
pneumonitis
Restrictive/obstructive
lung disease
See related topics:
Carmustine
Lomustine
Bleomycin
BusulfanYearlyPulmonary consultation for patients
Treatment factors Physical exam
Health Link
Whole lung > 20 Gy
Pulmonary Healthwith symptomatic pulmonary
PFTs
Baseline at entry into longdysfunction.
Treatment factors
termfollow-up(including
DLCO
Avoid
SCUBA
divingdue
Influenza
and Pneumococcal
Higher radiation dose to lungs
and spirometry) Repeat as clinicallyto history of treatment
vaccinations.
Total body irradiation
indicated in patients with with pulmonary-toxic
and CXR
Combined with:abnormal or progressive irradiation- dactinomycin- bleomycin
pulmonary dysfunction.
Host factors
Younger age at irradiation- busulfan- carmustine (BCNU)- lomustine (CCNU)- cyclophosphamide- doxorubicin

Medical conditions
Atopic history
Health behaviors
Smoking

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

COG Late Effects Guidelines 23
Version 1.0 - March 2003
Therapeutic Agent
Abdomen/Pelvis> 30 Gy to:
Whole abdomen
Left upper quadrant
Entire spleen

Total Body Irradiation
Renal
Para-Aortic
Whole abdominal
Spinal (> 15 Gy)

Sec#Potential Late Effects

Risk Factors

Highest Risk

Periodic
Evaluation

Minimum Recommended

Frequency

Health Protective
Counseling

67

Functional asplenia
Treatment factors
Life-threatening infection Higher radiation dose towith encapsulated
entire spleenorganisms(Hemophilus influenzae,
Streptococcus pneumoniae,
Meningococcus).

Treatment factors Physical exam
Blood culture
Dose > 30 Gy

When febrile T > 101

Health Link
Splenic precautions

68

Renal insufficiency
Hypertension

Treatment factors Blood pressure
Dose > 15 Gy towhole kidney
BUN, Creatinine
Urinalysis
14 Gy TBI without
renal shielding
Na, K, Cl, CO

YearlyHealth Link
Kidney HealthSee also: Single Kidney
Precautions

See related topics:
Cisplatin
Carboplatin
Ifosfamide

Treatment factors
Higher radiation dose tokidneys
Combined with:- doxorubicin,- dactinomycin
Hyperfractionated radiation
Total body irradiation
Combined with othernephrotoxic agents such as:- cisplatin/carboplatin- ifosfamide- aminoglycosides- amphotericin- immunosuppressants- cyclosporine

2Creatinine clearance

or GFR

YearlyConsiderations for Further Testing
and Intervention
Prophylactic antibiotics at onset offebrile illness, if not taking daily.
Counsel to seek immediate medical
evaluation for temperature > 101 forphysical exam and blood culture.
Counsel to advise all healthcare
providers, including dentists,
regarding functional asplenia.
Immunize with Pneumococcal
Meningococcal, HIB vaccines.
Pneumococcal booster immunization
after 5 years.
Medical alert bracelet/card noting
functional asplenia.
Nephrology consultation for patientswith hypertension, proteinuria, or
progressive renal insufficiency.

Obtain in patients withabnormal BP, urinalysis
BUN or creatinine.
If abnormal, repeat asclinically indicated.

Medical conditions
MononephricDiabetes mellitus
Hypertension

Total Body Irradiation
Whole abdomen
Hepatic

69

Hepatic fibrosis
Cirrhosis

Treatment factors
Higher radiation dose to
liver
Medical conditions
Chronic hepatitis

Treatment factors Physical exam
Dose > 40 Gy
to at least 1/3 of
ALT, AST,
liver volume
bilirubin
Dose 20-30 Gy
to entire liver

YearlyBaseline, upon entry into
long-term follow-up.

Health behaviors
Alcohol use
70

Hepatocellular
carcinoma

Medical conditions
Chronic hepatitis B or C
Cirrhosis
Treatment factors
Higher radiation dose to
liver

AFP

Yearly in patients withchronic hepatitis

Liver ultrasoundYearly in patients withcirrhosis

Health behaviors
Alcohol use
FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Health Link
Liver HealthProthrombin time for evaluation ofhepatic synthetic function in patientswith abnormal liver screening tests.
Screen for viral hepatitis in patients withpersistently abnormal liver function or
any patient transfused prior to 1993.
Gastroenterology/hepatology consultationin patients with persistent liver
dysfunction.
Hepatitis A and B immunizations inpatients lacking immunity.

Oncology consultation for medical
management.

COG Late Effects Guidelines 24
Version 1.0 - March 2003
Therapeutic Agent
Total Body Irradiation
All abdominal andpelvic fields
Spinal > 20 Gy

Total Body Irradiation
All abdominal andpelvic fields > 25 Gy
Spine > 25 Gy

SecPotential Late Effects#
71 Bowel obstruction

72

Chronic enterocolitis
Fistula, Strictures

73

Gastrointestinal
malignancy

Risk Factors
Treatment factors
Higher radiation dose tobowel
Abdominal surgery

Highest Risk

Periodic
Evaluation
Treatment factors Physical exam
Dose > 45 Gy but
KUB
obstruction may
occur in children at> 30 Gy.

Minimum Recommended

Frequency
With clinical symptoms
of obstruction.

Health Protective
Counseling

Clinician Info Link
Bowel obstruction is rarely
seen in individuals treatedwith abdominal radiation
who have not had
abdominal surgery.
YearlyTreatment factors History
Treatment factors
Higher radiation dose to Dose > 45 Gy
bowel
Serum protein and Yearly in patients with
albuminchronic diarrhea or fistula
Host factors
Hepatoblastoma
Familial polyposis

Treatment factors
Radiation dose> 25 Gy

Treatment factors
Higher radiation dose tobowel
Higher daily fraction dose
Combined withchemotherapy(especially alkylators)

Considerations for Further Testing
and Intervention
Surgical consultation in patients who
fail medical management.

Surgical and/or gastroenterology
consultation for symptomatic patients.

Surgical and/or oncology consultation
Monitoring to begin 10 years after radiation or Health Link
Reducing the risk of second as needed.
at age 25 years (whichever occurs last).
cancers
Choose from one of the following 3 options.
Monitor more frequently if clinically indicatedFecal occult blood Yearly(minimum 3 cards)
AND
Flexible
sigmoidoscopy

Every 5 years
OR

Double contrast
barium enema

Every 5 years
OR

Total body irradiation
Whole abdomen
PelvicIliac/inguinal
Para-aortic

74

Uterine vascularinsufficiency
resulting in adverse
outcomes such as
spontaneous abortion,
neonatal death, low-birthweight infant, fetal
malposition prematurelabor

Host factors
Females with Wilms'
tumor and associatedMullerian anomalies
Clinician Info Link:
10% of girls with Wilms'
tumor have uterine
anomalies

Host factors
Prepubertal attreatment

Colonoscopy

Every 10 years

History

Yearly and as clinicallyindicated

Consider high-level As clinically indicated inultrasoundpatient contemplating
evaluation ofpregnancy.
genitourinary tract
Treatment factors after pubertal
development.
Dose > 20-30 Gy
TBI

Treatment factors
Higher radiation dose topelvisFOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

High-risk obstetrical care during
Health Link
pregnancy.
Fertility and pregnancy
outcomes after childhood High level ultrasound in women withWilms' tumor.
cancerResources:
American Society for
Reproductive Medicine
website: www.asrm.org
See also:
www.fertilehope.org

COG Late Effects Guidelines 25
Version 1.0 - March 2003
Therapeutic Agent
Total body irradiation
Whole abdomen
PelvicIliac/inguinal
Para-aortic
Spinal > 24 Gy

SecPotential Late Effects
Risk Factors#
75 Ovarian dysfunction:
Host factors- Delayed/arrested puberty Older age at irradiation- Primary amenorrhea- Secondary amenorrhea
Treatment factors- Premature ovarian failure Higher radiation dose to- Early menopause
pelvis- Infertility
Combined with:- cranial radiation

See related topics:
Alkylating agents

Whole abdomen
PelvicIliac/inguinal
Para-aortic
Spinal > 30 Gy

76

Hemorrhagic cystitis
See related topics:
Cyclophosphamide
Ifosfamide

77

Bladder fibrosis
Dysfunctional voiding

78

Bladder malignancy
See related topics:
Cyclophosphamide
Ifosfamide

Minimum Recommended
Periodic
Health Protective
Considerations for Further Testing
Frequency
EvaluationCounselingand Intervention
Gynecology or endocrinology
YearlyHealth Link
Treatment factors Pubertal history
Fertility and pregnancy(onset, tempo)
consultation for hormonal
Dose > 10-20 Gy.
TBI
outcomes after childhood replacement therapy.
Symptoms of
Combined withcancermenopause (hotConsider evaluation for conditions
cyclophosphamide flashes, poor
exacerbated by hypogonadism
dose > 200 mg/kg libido)
Risks and benefits of(e.g., osteopenia/osteoporosis).
(conditioning forhormonal replacement
Menstrual history
Reproductive endocrinology
stem cell transplant) Physical exam withtherapy
consultation for infertile couples
Counseling regarding need interested in assisted reproductive
height, weight,
Combined with alkylating
for contraception sinceTanner stage
technologies.
agent chemotherapy
there is tremendous
LH, FSH, Estradiol Baseline at age 11 or older and for: individual variability in- Delayed puberty
gonadal toxicity after- Irregular menses or
exposure to radiation
amenorrhea
therapy and alkylating- Clinical signs andagents. Recovery ofsymptoms of estrogen
fertility may occur many
deficiency
years after therapy.
Resources:
American Society for
Reproductive Medicine
website: www.asrm.org
See also:
www.fertilehope.org

Treatment factors
Higher radiation dose
Health behaviors
Alcohol use
Tobacco use
Treatment factors
Higher cumulative
radiation dose (> 45 Gy)
Combined with:- cyclophosphamide- ifosfamide
Treatment factors
Radiation to pelvis
Combined with:- cyclophosphamide- ifosfamide

Highest Risk

Treatment factors Urinalysis
Combined withcyclophosphamide
and/or ifosfamide

YearlyVoiding history

YearlyUrinalysis

YearlyFOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Counsel to promptly report Urology consultation for culturedysuria or gross hematuria negative macroscopic hematuria.

Urologic consultation for patients withincontinence or dysfunctional voiding.

Counsel to promptly report Urology consultation for culturedysuria or gross hematuria negative macroscopic hematuria.

COG Late Effects Guidelines 26
Version 1.0 - March 2003
Therapeutic Agent
Testicular radiation
Total body irradiation
Testicular
PelvicInguinal/femoral
Spinal > 24 Gy

Sec
#
79

Potential Late Effects

Risk Factors

Testicular dysfunction- Azoospermia- Infertility

Treatment factors
Radiation to testes
1 to 3 Gy: azoospermia
may be reversible.
3 to 6 Gy: azoospermia
possibly reversible (butunlikely)-Hypogonadism-Delayed/arrested
puberty

Testicular irradiation
combined withhead/brain irradiation

See related topics:
Alkylating agentsHighest Risk

Periodic
Evaluation

Minimum Recommended

Frequency

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Urology or endocrinology consultation
Health Link
for hormonal replacement therapy.
Fertility and pregnancy
outcomes after childhood Consider evaluation for conditions
cancer.
exacerbated by hypogonadism: e.g.,
Clinician Info Link
osteopenia/osteoporosis.
Late recovery of gonadal Counseling regarding need Reproductive endocrinology
function has been reported for contraception sinceconsultation for infertile couples.
interested in assisted reproductive
there is tremendous
technologies.
individual variability ingonadal toxicity after> 20 Gy Leydig cell History of sexual Yearlydamage (affecting function
exposure to radiation
testosterone
therapy and alkylating(erections,production)
agents. Recovery of
nocturnal
Radiation combined emissions, libido).
fertility may occur many
Yearlywith alkylating
years after therapy.
History ofagentsmedication use.
YearlyCombined with
Resources:
Physical exam
cyclophosphamide including height,
American Society fordose > 200 mg/kg weight, Tanner
Reproductive Medicine(conditioning forwebsite: www.asrm.org
stage, testicular
See also:
stem cell transplant) volume by Prader
www.fertilehope.org
TBI
orchiometry.
Treatment factors Semen analysis
Radiation to testes> 6 Gy: azoospermia
likely permanent

As requested by patientand for evaluation ofinfertility.

LH, FSH,
Testosterone

Baseline, at age 11 or older and for:Physical exam

Yearly- Delayed puberty- Clinical symptoms of
testosterone deficiency

Extremity radiation
80

Musculoskeletal growth
Host factors
Younger age at treatment
problems:- Hypoplasia- Fibrosis
Treatment factors- Reduced or uneven growth Higher cumulative dose
- Limb length discrepancy Larger treatment field
Higher dose per fraction

Host factors
Prepubertal attreatment
Treatment factors
Orthovoltage
radiation(commonly used
before 1970) due todelivery of greater
dose to skin andbones.
Epiphysis intreatment field.
Dose > 20 Gy

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Counsel regarding
increased risk of fracturesin radiated bones

Orthopedic consultation if clinicallysignificant (limb length discrepancy,
chronic pain) or for any deficit noted
in growing child.
Plastic surgery consultation forreconstruction.

COG Late Effects Guidelines 27
Version 1.0 - March 2003
Therapeutic Agent
Transfusion
Clinician Info Link
Consider any blood orserum productincluding:
Packed red cells
Whole blood
White cells
Platelets
Fresh frozen plasma
Cryoprecipitate
Immunoglobulin
preparations:
IVIG, VZIG
Note dates screening ofblood donors initiated:1971 Hepatitis BsAg
1985 HIVAB HIV-1
EIA
1986 Surrogate ALT
screening
1990 HCV EIA-I
screening
1992 HCV EIA-II
screening
Note: International
screening policies may
not include thesemeasures.

Sec
#
81

82

83

Potential Late Effects
Chronic Hepatitis B

Risk Factors

Host factors
Living in hyperendemic
area
Treatment factors
Transfusion before 1972
Health behaviors
IV drug use
unprotected sex
multiple partners
high-risk sexual behavior
sexually transmitted
diseasestattoos, body piercing
Chronic Hepatitis C
Host factors
Living in hyperendemic
area
Treatment factors
Transfusion before 1993
Health behaviors
IV drug use
unprotected sex
multiple partners
high-risk sexual behavior
sexually transmitted
diseasestattoos, body piercing
Complications related to Treatment factors
Stem cell transplantation
chronic hepatitis:- Cirrhosis
Medical conditions- Hepatic failure
Chronic hepatitis C- Hepatocellular carcinoma Health behaviors
Alcohol use
IV drug use
unprotected sex
multiple partners
high-risk sexual behavior
sexually transmitted
diseasestattoos, body piercing
HIV infection
Treatment factors
Transfusion before 1986
Health behaviors
IV drug use
unprotected sex
multiple partners
high-risk sexual behavior
sexually transmitted
diseasestattoos, body piercing
Medical conditions
HPV infection

Highest Risk
Host factors
Chronic immunosuppression

Periodic
Evaluation

Minimum Recommended

Frequency

Hepatitis B surface Once in patients who
antigen (HBsAg) received any blood orANDserum product prior to
Hepatitis B core1972
antibody(anti HBc, HBcAb)

Treatment factors Hepatitis C
Transfusion before antibody
1986 whensurrogate screeningof blood donors
with ALT initiated PCR to establish
and donors withchronic infection
self-reported highrisk behaviors
deferred.
Chronic
immunosuppression

Once in patients who
received any blood orserum product prior to
1993

Medical conditions Physical exam
Chronic co-infection ALT, AST,
with hepatotoxic
bilirubin
viruses: Hepatitis B, Prothrombin time
Hepatitis C, and/orHIV
AFP

Yearly in patients withchronic hepatitis B or C
(PCR positive)

Health behaviors HIV 1 & 2
High-risk behaviors antibodies

Once in patients who
received any blood orserum product prior to
1986

Health Protective
Counseling
Health Link
Liver Health

Considerations for Further Testing
and Intervention
Gastroenterology or hepatology
consultation for patients with chronic
infection.
Hepatitis A immunization in patientslacking immunity.

Health Link
Liver HealthOnce in patients withpositive hepatitis C
antibody

Screen for viral hepatitis in patientswith persistently abnormal liverfunction regardless of transfusion
history.
Consider HCV PCR screening in alltransfused at risk patients (especiallythose with abnormal liver function) orin patients with persistentimmunosuppression (stem celltransplant recipients).
Gastroenterology or hepatology
consultation for management ofpatients with chronic infection,
progressive liver dysfunction, or otherhepatitis-related sequelae.
Hepatitis A and B immunization inpatients lacking immunity.

Yearly in patients withchronic hepatitis

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Standard counselingregarding safe sex,
universal precautions,exacerbating high-risk
behaviors

Infectious diseases consultation forpatients with chronic infection.

COG Late Effects Guidelines 28
Version 1.0 - March 2003
Therapeutic Agent
Surgery
Amputation

Sec#

Potential Late Effects

Risk Factors

84

Cosmesis
Functional and activity
limitations
Residual limb integrity
problems
Phantom pain
Thrombosis
Vascular insufficiency
Infection of retained
cuff or line tract
Chronic urinary tract
infection
Renal dysfunction

Host factors
Skeletally immature/
growing children

Central venous
catheter

85

Cystectomy

86

Enucleation

87

Host factors
Younger age at
enucleation
Treatment factors
Combined with radiation
Treatment factors
Combined with radiation

88

Adhesive/obstructive
Complications

Limb sparing
procedure

89

Functional and activity
limitations
Contractures
Loosening ofendoprosthesis
Chronic infection
Chronic pain
Limb length discrepancy

Nephrectomy

90

Proteinuria
Hyperfiltration
Renal insufficiency
Hydrocele

Periodic
Evaluation

Health Protective
CounselingConsiderations for Further Testing
and Intervention
Psychological consultation in patientswith emotional difficulties related tocosmesis and adaptation following
amputation.
Vocational rehabilitation referral.

History
Physical exam

Yearly until completion of Counsel regarding skin
growth, or every 3 years checks, signs of poor
if skeletally mature.
prosthetic fit, residual
Biannually until skeletally limb and prosthetic
mature, then annually
hygiene.
thereafter.
Yearly, and as clinicallyindicated.

Blood pressure

Yearly

BUN, creatinine
Urinalysis

YearlyNephrology consultation for patientswith hypertension, proteinuria, or
progressive renal insufficiency.

Urine culture

Yearly and as clinicallyindicated

Na, K, Cl, CO2

YearlyPhysical exam
Prosthetic
evaluation

Cosmesis
Poor prosthetic fit
Orbital hypoplasia

Laparotomy

Highest Risk

Minimum Recommended

Frequency

Urology evaluation YearlyPhysical exam
YearlyOphthalmology
Ocularist

Physical exam

When symptomatic

Physical exam

Yearly and as neededRadiographYearlyHealth behaviors
Higher risk of loosening inpatients with high levelof physical activity.
Higher risk of contractures
or functional limitations
in patients with low levelof physical activity.

Orthopedic
follow-up

Every 6 months until
skeletally mature, andannually thereafter

Treatment factors
Combined with othernephrotoxic therapy:- cisplatin, carboplatin- ifosfamide- kidney irradiation- abdominal irradiation- aminoglycosides- amphotericin- immunosuppresants- cyclosporine

Blood pressure

Yearly

BUN, creatinine
Urinalysis

YearlyNa, K, Cl, CO2.

Obtain in patients withabnormal BP, urinalysis,
BUN or creatinine.
If abnormal, repeat asclinically indicated.

Host factors
Younger age at surgery
Rapid growth spurt

Creatinine clearance

or GFR.

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Psychological consultation in patientswith emotional difficulties related tocosmesis and visual impairment.
Vocational rehabilitation referral.
Surgical consultation for patientsunresponsive to medical management.
Counseling regarding:
Psychological consultation in patients- appropriate level of activity with emotional difficulties related to- recommended recreational
cosmesis and adaptation following
activities
limb-sparing procedure.
- signs of prosthetic loosening
Vocational rehabilitation referral.
- need for informing healthcare providers about
endoprosthesis- need for antibiotic
prophylaxis prior to dental
and invasive procedures

Nephrology consultation for patients
Health Link
Single Kidney Precautions: with hypertension, proteinuria, or
progressive renal insufficiency.

COG Late Effects Guidelines 29
Version 1.0 - March 2003
Therapeutic Agent
Neurosurgery

Orchiectomy

Minimum Recommended
Sec
Potential Late Effects
Risk Factors
Highest Risk
Periodic
Health Protective
Frequency#
EvaluationCounseling
Neurology
91 Neurocognitive deficits
Yearly, until 2 to 3 years Health Link
Host factors
Host factors
vary with extent of surgery Younger age at diagnosis Younger age atevaluation
after surgery or stable;
School and learning issues
and postoperative
treatment
continue to monitor if
after childhood cancer
complications. In general, Treatment factors(< 3 years)
symptoms persist.
mild delays occur in most Combined with:Supratentorial tumor
Every 6 months forareas of- brain radiation
patients with seizure
neuropsychological- high-dose chemotherapy Treatment factors
disorder.
- intrathecal chemotherapy High-dose and/or IT Rehabilitation
function compared toYearly, or more frequently
methotrexate
healthy children.
medicine/
as clinically indicated in
combined with
Intracranial bleed/stroke Medical conditions
physiatrist
patients with motor
Hydrocephalus
cranial radiation.
Motor deficits
evaluation
dysfunction
Radiation dose
Paralysis
Neurosurgery
Yearly for patients with> 60 Gy
Movement disorders
evaluation
shunts.
AtaxiaMedical conditions
Abdominal x-ray At puberty growth spurt
Posterior fossa
Seizuresfor patients with shunts tosyndromeassure distal shunt tubing
CNS infection
Hydrocephalus
in peritoneum
Shunt malfunction
Clinical assessment Baseline and yearlySocial factorsof educational or
Low SES
vocational
Predisposing family
Clinician Info Link
progresshistory of learning
New deficits may emerge
Referral for formal Baseline at entry into
or attention
over time. Extent of deficit
neuropsychological LTFU, then periodicallyproblems
depends on age atevaluation
as clinically indicated fortreatment, intensity ofpatients with evidence oftreatment, and time since
impaired educational ortreatment.
vocational progress
History of sexual
92 Infertility
For patients with single
YearlyTreatment factors
function (erections,Bilateral orchiectomy
testis: counsel to wear
Hypogonadism
nocturnal emissions,
Unilateral orchiectomy
athletic supporter withlibido).
combined with pelvic orprotective cup during
History of
testicular radiation and/or
athletic activities.
medication use.
alkylating agents
Physical examincluding height,
weight, Tannerstage, testicularvolume by Prader
orchiometry.

LH, FSH,
Testosterone

Baseline, at age 11 or older and for:Semen analysis

As requested by patientand for evaluation ofinfertility.

- Delayed puberty- Clinical symptoms of
testosterone deficiency.

Clinician Info Link
Late recovery of gonadal
function has been reported.

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Considerations for Further Testing
and Intervention
Formal neuropsychological evaluation to
include tests of processing speed,
computer-based attention, visual- motor
integration, memory, comprehension ofverbal instructions verbal fluency,
executive function and planning.
Consider use of psychotropic medication(stimulant). Caution: lower starting doseand assessment of increased sensitivity
when initiating therapy is recommended.
Refer to school liaison in community orcancer center (psychologist, social
worker, school counselor) to facilitate
acquisition of educational resources(IEP) and/or social skills training.
Speech, physical, and occupational
therapy in patients with persistent
deficits. Consider nutrition, endocrine,
and psychiatric (obsessive-compulsive
behaviors) consultations in patients withhypothalamic pituitary axis tumors.

Neuroimaging with preferred study
based on intracranial lesion to beevaluated:
MRI: White matter
Gadalinium-enhanced MRI:
micro vascular injury
CT: calcifications
Surgical placement of testicular
prosthesis.

COG Late Effects Guidelines 30
Version 1.0 - March 2003
Therapeutic Agent
Pelvic surgery

Pulmonary lobectomy

Sec
Potential Late Effects#
93 Retrograde ejaculation
Impotence
Bowel incontinence
Bladder incontinence
Hydrocele
94 Pulmonary insufficiency

Risk Factors
Treatment factors
Retroperitoneal nodedissection
Treatment factors
Chest radiation
Combined with pulmonary
toxic therapy:- bleomycin- busulfan- carmustine (BCNU)- lomustine (CCNU)- cyclophosphamide- doxorubicin- dactinomycin- chest/thoracic radiation- spinal radiation >30Gy- total body irradiation

Highest Risk

Periodic
Evaluation
History

YearlyPhysical exam

YearlyPFTs(including DLCO
and spirometry)
and CXR

Baseline, upon entry to
long-term follow-up.
Avoid SCUBA diving due
Repeat as clinicallyto history of pulmonary
Influenza and Pneumococcal
indicated in patients with lobectomy
vaccinations.
abnormal or progressive
pulmonary dysfunction.

Physical exam
Blood culture

When febrile T > 101

Minimum Recommended

Frequency

Health Protective
Counseling

Health Link
Pulmonary Health

Considerations for Further Testing
and Intervention
Urologic consultation for patients withincontinence, dysfunctional voiding,or sexual dysfunction.
Pulmonary consultation for patientswith symptomatic pulmonary
dysfunction.

Medical conditions
Atopic history
Health behaviors
Smoking
Splenectomy95Life-threatening infection
with encapsulatedorganisms(Hemophilus influenzae,
Streptococcus pneumoniae,
Meningococcus)

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Health Link
Splenic precautions

Prophylactic antibiotics at onset offebrile illness, if not taking daily.
Counsel to seek immediate medical
evaluation for temperature > 101 forphysical exam, and blood culture.
Counsel to advise all healthcare
providers, including dentists,
regarding functional asplenia.
Immunize with Pneumococcal
Meningococcal, HIB vaccines.
Pneumococcal booster immunization
after 5 years.
Medical alert bracelet/card noting
asplenia.

COG Late Effects Guidelines 31
Version 1.0 - March 2003
Therapeutic AgentSec
Potential Late Effects
Risk Factors#
Hematopoietic Stem Cell Transplantation
Clinician Info Link
Immune system
Complications after
96 Secretory IgA deficiency Medical conditions
hematopoietic stem cell
Hypogammaglobulinemia Chronic GVHD
transplantation have
Chronic infections, such
multifactorial etiology:
as conjunctivitis, sinusitis,
1. prior therapy forand bronchitis
primary malignancy
2. intensity ofLivertransplant conditioning 97 Chronic hepatitis
Treatment factors
3. stem cell productHistory of multiple
Cirrhosis(e.g., marrow, cord
transfusions
Iron overload
blood, peripheral stem
Radiation to the liver
cells)
4. donor (e.g.,
Medical conditions
autologous, allogeneic,
Chronic GVHD
unrelated)
Viral hepatitis
5. quality of donor torecipient match
Health behaviors
6. complication of
Alcohol use
transplant process(immunosuppression
and GVHD.)
7. complications in the
post-transplant period. Lungs
8. underlying disease
98 Bronchiolitis obliterans
Treatment factors
9. host genetic factors
Allogeneic transplant
Chronic bronchitis
10. lifestyle behaviors
Thoracic radiation
Bronchiectasis
Total body irradiation
This section includes
late treatment
Medical conditions
complications that may
Chronic GVHD
be observed inhematopoietic celltransplant recipients notcovered elsewhere inthese guidelines
Refer to other sectionsof these guidelines for
specific details related
to late complications ofradiation and of
specific
chemotherapeutic
agentsHighest Risk

Host factors
Low CD4 T-cell
count

Periodic
Evaluation

Minimum Recommended

Frequency

History

Yearly

ALT, AST,
bilirubinYearlyFerritin

Baseline at entry into longterm follow-up

Medical conditions Physical exam
Prolonged
immunosuppression PFTs
related to GVHD
(including DLCO
prophylaxis
and spirometry)
and CXR

YearlyBaseline, upon entry to
long-term follow-up
Repeat as clinicallyindicated in patients withabnormal or progressive
pulmonary dysfunction.

(continued on next
page)

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Immunology or infectious diseases
consultation for assistance withmanagement of chronic infections.

Health Link
Liver HealthProthrombin time for evaluation ofhepatic synthetic function in patientswith abnormal liver function onscreening tests.
Screen for viral hepatitis in patientswith persistently abnormal liverfunction.
Note: PCR testing may be required in
immunosuppressed patients who are
negative for antibody.
Gastroenterology or hepatology
consultation if abnormal.
Hepatitis A and B immunization inpatients lacking immunity.

Pulmonary consultation for patientswith symptomatic pulmonary
dysfunction.
Avoid SCUBA diving due Influenza and Pneumovax vaccination.
to pulmonary compromise
Health Link
Pulmonary HealthCOG Late Effects Guidelines 32
Version 1.0 - March 2003
Therapeutic Agent
Hematopoietic stem
cell transplantation(continued fromprevious page)(continued on next
page)

Sec
Potential Late Effects#
Muscles/Bones
99 Joint contractures
100 Osteopenia
Bone mineral density 1-2.5
SD below mean
Osteoporosis
Bone mineral density >2.5
SD below mean

Risk Factors
Medical conditions
Chronic GVHD
Treatment factors
Corticosteroids
Radiation therapy
Medical conditions
Hypogonadism
Chronic GVHD

Clinician Info Link
World Health Organization Behavioral factors
definition of osteoporosis Physical inactivity
in adults is based oncomparison of a measured
bone mineral density ofyoung adults at peak bone
age and defined as a Tscore.
A T-score of > 2.5 standard
deviations below the mean
is consistent with adiagnosis of osteoporosis.
T-scores are not appropriate
to assess skeletal health inpediatric patients who havenot achieved peak adultbone mass.
Pediatric bone mineraldensity reference data sets
calculate z-scores based onage and gender, but do notaccount for variations
related to sexual
maturation and ethnicity.
The ideal reference data
should provide assessment
relative to body size,
pubertal status, and age.
Currently available
pediatric reference data
sets are not large enough toaccurately characterize thenormal variability in bonemineral density.
Consequently, there are noevidence-based guidelines
for classification of bonehealth in children.

Highest Risk

Periodic
Evaluation
Physical exam

Treatment factors Bone density
Prolonged steroid
evaluation
therapy for GVHD (DEXA orquantitative CT)
Clinician Info
Link
The optimal
method ofmeasuring bonehealth in children
is controversial.
Existing
technologies have
limitations.
Dual energy x-ray
absorptiometry(DEXA) provides
an estimate of totalbone mass at agiven site.
Quantitative CT
provides distinct
measures oftrabecular andcortical bonedimension anddensity.

Minimum Recommended

Frequency

Health Protective
CounselingConsiderations for Further Testing
and Intervention

YearlyConsultation with rehabilitation
medicine/physiatrist.

Baseline screening at 18 Health Link
years old; consider earlier Bone Healthscreening if clinicallyNational Osteoporosis
indicated.
Foundation website:
Repeat prn as
www.nof.org
clinically indicated.

Nutritional supplements in cases ofosteopenia unresponsive to behavioral
and dietary management:
Calcium 1000-1500 mg daily plus
RDA for vitamin D

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE** Caution regarding calcium
supplementation in patients withhistory of renal lithiasis.
Treatment of exacerbating or
predisposing conditions (e.g.,
hormonal replacement therapy for
hypogonadism, growth hormone
deficiency; correction of chronic
metabolic acidosis that could
accelerate bone loss.).
Endocrine consultation for patientswith bone density > 2.5 SD below
mean, or patients with history ofmultiple fractures, for otherinterventions (e.g., bisphosphonates,
calcitonin, selective estrogen receptor
modulators).

COG Late Effects Guidelines 33
Version 1.0 - March 2003
Therapeutic Agent
Hematopoietic stem
cell transplantation(continued fromprevious page)

Sec
Potential Late Effects#
Second Cancers
101 Myelodysplasia
Acute myeloid leukemia

Solid cancers
most common are:
- Basal/squamous cell
- Melanoma- Oral cavity cancers- Liver cancer- CNS cancer- Thyroid cancer- Connective tissue- Cervical cancer
LymphomaSkin
102 Alopecia
Nail dysplasia
Vitiligo
Scleroderma

Risk Factors

Highest Risk

Periodic
Evaluation

Treatment factors
Radiation therapy
Stem cell priming withetoposide
Alkylating agent
chemotherapy
Epipodophyllotoxins
Anthracyclines
Autologous transplant
Host factors
Younger age at transplant
Fanconi's anemia

Host factors
Autologoustransplant for
non-Hodgkin's
lymphoma andHodgkin's disease

Physical exam
CBC/differential

Minimum Recommended

Frequency

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Yearly up to 15 years after Counsel to promptly report Bone marrow exam as clinically
exposure to agent.
fatigue, pallor, petechiae, indicated.
or bone pain.

Treatment factors Physical exam
Higher dose TBI

YearlyOncology consultation as clinically
Health Link
Reducing the risk of second indicated.
cancers

Physical exam

YearlyOncology consultation as clinicallyindicated.

Physical exam

YearlyTreatment factors
Radiation therapy
Medical conditions
Hepatitis C infection
Human papilloma virus
infection
Chronic GVHD of skin
Treatment factors
Chemotherapy
Stem cell transplant
Treatment factors
Radiation therapy

Health Link
Skin health

Medical conditions
Chronic GVHD

General Health Screening
103

Refer to United States Preventive Task Force recommendations at http://www.ahrq.gov/clinic/prevenix.htm

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

COG Late Effects Guidelines 34
Version 1.0 - March 2003

Cancer Screening Guidelines
Organ

Sec
#

At Risk Population

Highest Risk

Periodic Evaluations

Minimum Recommended
Frequency

Health Protective
CounselingConsiderations for Further Testing andInterventions

Note to Clinicians: "Highest Risk" guidelines below include suggested periodic evaluations for childhood cancer survivors who are at increased risk of a specific cancer due to prior therapy, co-morbid conditions, family
history, genetic susceptibility or other factors. "Standard Risk" guidelines below are per American Cancer Society recommendations for standard-risk populations and are provided here for reference. In addition, clinicians areencouraged to consult recommendations from other organizations, such as the U.S. Preventive Services Task Force (http://www.ahrq.gov/clinic/serfiles.htm). Specific decisions regarding cancer screening are the prerogativeof the patient, family, and healthcare provider.
Breast104

Over age 40
Family history of breast
cancer in first degree
relative
Early onset of
menstruation
Late onset of menopause(age 55 or older)
Older than 30 at birth offirst child
Never pregnant
ObesityPrevious breast biopsy
with atypical hyperplasia

Chest/thorax radiation withpotential impact to the breast
including :Total Body Irradiation
MantleMediastinal
Whole lung
Spinal >30 Gy

For females only:Standard Risk:
Breast self-examination
Clinician breast exam

Every 3 years between ages
20-40; then yearly beginningat age 40

BRCA1, BRCA2, ATMmutation

MammogramHighest Risk:
Breast self-examination

Every year beginning age 40

Clinician breast exam

Yearly, beginning at puberty
until age 25, then every 6months

Mammogram

Yearly, beginning 8 years afterradiation or at age 25(whichever occurs last)

Clinician Info Link

Mammography is currently
limited in its ability toevaluate premenopausal
breasts..
Cervical105

Early age at firstintercourse
Multiple lifetime sex
partners
Cigarette smoking
Sexually transmitted
diseases

Personal history of cervical
dysplasia.
Prenatal DES exposure
HPV infection
Immunosuppression
Chronic steroid use

Monthly, beginning at age 20

Health Link
Reducing the risk of
second cancers

Monthly beginning at puberty.

Begin screening 3 years after Health Link
first vaginal intercourse, or at Reducing the risk ofage 21, whichever comes first. second cancers
Standard Risk:
Pelvic exam
Cervical PAP smear

Surgery and/or oncology consultation as clinicallyindicated.

Every 1-2 years
Yearly for regular PAP test;
Every 2 years for liquid-based
PAP test. After age 30: If
patient has had 3 normal PAP
tests in a row, may screen
every 2-3 years.

Highest Risk:
Pelvic exam

YearlyCervical PAP smear

YearlyFOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Gynecology and/or oncology consultation asclinically indicated.

COG Late Effects Guidelines 35
Version 1.0 - March 2003
Organ
Colorectal

Sec
#
106

At Risk Population
High fat/low fiber dietAge 50 to 75 years
Obesity

Highest Risk
Total body irradiation
Abdominal or pelvic radiation>25 GySpinal radiation >25 Gy

Periodic Evaluations

Minimum Recommended
Frequency

Standard Risk:
Fecal occult blood(minimum of 3 cards)

Yearly, beginning at age 50

Health Protective
Counseling
Health Link
Reducing the risk of
second cancers

AND/OR
Personal history of ulcerative
Flexibile sigmoidoscopy
Every 5 years beginning at age
colitis, gastrointestinal
50.
malignancy, adenomatous
polyps or hepatoblastoma
Note:The combination of yearly fecal occult blood testing andFamilial polyposis
every 5 year flexible sigmoidoscopy is preferable to either
Family history of colorectal
test done alone.
cancer or polyps
OR
Double contrast barium
enema

Every 5 years beginning at age
50.
ORColonoscopy

Every 10 years beginning atage 50Highest Risk:
Monitoring to begin 10 years after radiation or at age 25
years (whichever occurs last). Monitor more frequently ifclinically indicated. Choose from one of the following three
options:
Fecal occult blood (minimum Yearly, beginning 10 yearsof 3 cards)
after radiation or at age 25(whichever occurs last).
AND
Flexibile sigmoidoscopy

Every 5 years
OR

Double contrast barium
enema

Every 5 years
OR

Endometrial

107

History of or at risk forhereditary nonpolyposis
colon cancer (HNPCC)

Colonoscopy

Every 10 years

Highest Risk:
Endometrial biopsy

Yearly, beginning at age 35 for Health Link
patients at highest risk.
Reducing the risk of
second cancers

FOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Considerations for Further Testing andInterventions
Gastroenterology, surgery and/or oncology
consultation as clinically indicated.

COG Late Effects Guidelines 36
Version 1.0 - March 2003
Organ
Lung

Oral

Prostate

Skin

Testicular

Sec
#
108

109

110

111

112

At Risk Population

Highest Risk

Periodic Evaluations

Cigarette smoking
Workplace exposures toasbestos, arsenic,
radiation
Second hand smoke (innon- smokers)

Chest/thorax radiation withpotential impact to the lungs,
including
Total body irradiation
MantleMediastinal
Whole lung
Spinal >30 Gy
Whole abdomen
Any upper abdominal field
Head/brain radiation
Neck radiation

Highest Risk:
History and Physical exam

YearlyImaging

As clinically indicatedTobacco use (smoking
cigars cigarettes, or pipe;
dipping, chewing),
Alcohol abuse
Excessive sun exposure
increases risk of cancerof lower lip.
Older age, with steadily
increasing risk after age
40.

Light skin color
Chronic exposure to sun
Atypical moles or> 50 moles

African-American race
Family history of prostatecancer in first degree relative

Any history of radiation
Personal history of melanoma
or skin cancer.
Dysplastic nevi
Family history of melanoma
or skin cancer.
History of severe sunburn at
young age
History of undescended
testicle
History of testicular cancer or
carcinoma- in-situ incontralateral testis.
History of gonadal dysgenesis
Klinefelter's syndrome
Family history of testicularcancerHighest Risk:
Oral cavity exam

Standard Risk:
Digital rectal exam

Minimum Recommended
Frequency

Yearly if smoker or history ofhead/neck radiation

Yearly, beginning at age 50

Prostate specific antigen(PSA)
Highest Risk:
Digital rectal exam

Yearly, beginning at age 50

Prostate specific antigen(PSA)
Standard Risk:
Clinical skin exam

Yearly, beginning at age 45

Highest Risk:
Skin self exam

Considerations for Further Testing andInterventions
Surgery and/or oncology consultation as clinicallyindicated.

Health Link
Reducing the risk of
second cancers

Head and neck/otolaryngology consultation as
indicated.

Health Link
Reducing the risk of
second cancers

Urology and/or oncology consultation as clinicallyindicated.

Yearly, beginning at age 45

Health Link
Every 3 years, from ages 20-39 Reducing the risk ofYearly, beginning at age 40.
second cancers

Surgery, dermatology, and/or oncology
consultation as clinically indicated.

Monthly

Clinical skin exam with
Yearlyattention to pigmented nevi
in radiation field.
Standard Risk:
Testicular self-exam
Not indicatedClinical testicular exam

Health Protective
Counseling
Health Link
Reducing the risk of
second cancers

Every 3 years, ages 20-39,
then yearly.

Highest Risk:
Testicular self-exam

Monthly, beginning at puberty

Clinical testicular exam

YearlyFOR USE BY COG MEMBERS ONLY – DO NOT CITE OR DISTRIBUTE

Health Link
Reducing the risk of
second cancers

Urology and/or oncology consultation as clinicallyindicated.

COG Late Effects Guidelines – March 2003 – References 1

SectionReferences

1

Zeltzer LK, Chen, E, Weiss R, et al. Comparison of psychologic outcome in adult survivors of childhood acute lymphoblastic leukemia versus sibling controls: a Cooperative Children's
Cancer Group and National Institutes of Health study. J Clin Oncol 1997; 15: 547- 556.
Elkin TD, Phipps S, Mulhern RK, et al. Psychological functioning of adolescent and young adult survivors of pediatric malignancy. Med Pediatr Oncol 1997; 29: 582-588.
Rourke MT, Stuber ML, Hobbie WL, et al. Posttraumatic stress disorder: understanding the psychosocial impact of surviving childhood cancer into young adulthood. J Pediatr Oncol
Nursing 1999; 16 (3): 126-135.
Hobbie WL, Stuber M, Meeske K, et al. Symptoms of posttraumatic stress in young adult survivors of childhood cancer. J Clin Oncol 2000; 18: 4060-4066.
Zebrak BJ, Zeltzer LK, Whitton J, et al. Psychological outcomes in long-term survivors of childhood leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma: a report from theChildhood Cancer Survivor Study. Pediatrics 2002; 110:42-52.

2

Keene N, Hobbie W, Ruccione K. Childhood Cancer Survivors: A Practical Guide to Your Future. Oreilly, Sebastopol, 2000.
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3

Sonis AL, Tarbell N, Valachovic RW, et al. Dento- facial development in long-term survivors of acute lymphoblastic leukemia. Cancer 1990; 66: 2645-2652.
Goho C. Chemoradiation therapy: effect on dental development. Pediatric Dentistry 1993;15 (1): 6-12.
Raney RB, Asmar L, Vassilopoulou-Sellin R, et al. Late complications of therapy in 213 children with localized, nonorbital soft-tissue sarcoma of the head and neck: a descriptive reportfrom the Intergroup Rhabdomyosarcoma studies (IRS)-II and -III. Med Pediatr Oncol 1999; 33:362-371.

4

DaCunha MF, Meistrich ML, Fuller LM, et al. Recovery of spermatogenesis after treatment for Hodgkin's disease: limiting dose of MOPP chemotherapy. J Clin Oncol 1984; 2(6):571577.
B yr n e J, Fears TR, Gail MH, et al. Early menopause in long-term survivors of cancer during adolescence. Am J Obstet Gynecol 1992; 166:788-793.
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Bokemeyer C, Schmoll HJ, van Rhee J, et al. Long-term gonadal toxicity after therapy for Hodgkin's and non-Hodgkin's lymphoma. Ann Hematol 1994; 68:105-110.
Teinturier C, Hartmann, O, Valteau-Couanet D, et al. Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure.
BMT 1998; 22(10): 989-94.
Papadakis V, Vlachopapadopoulou E, Van Syckle K, et al. Gonadal function in young patients successfully treated for Hodgkin's disease. Med Pediatr Oncol 1999; 32:366-372.
Sklar C. Reproductive physiology and treatment related loss of sex hormone production. Med Pediatr Oncol 1999; 33:2-8.
Howell SJ, Shalet SM. Testicular function following chemotherapy. Hum Reprod Update 2001; 7(4): 363-369.
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
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Relander T, Cavallin-Stahl E, Garwicz S, et al. Gonadal and sexual function in men treated for childhood cancer. Med Pediatr Oncol 2000: 35(1) 52-63.
Bath LE, Hamish W, Wallace, et al. Late effects of the treatment of childhood cancer on the female reproductive system and the potential for fertility preservation. Br J Obstet Gynecol
2002; 109:107-124.
Petersen PM, Hansen SW, Giwercman A, et al. Dose-dependent impairment of testicular function in patients treated with cisplatin based chemotherapy. Ann Oncol 1994; 5:355-358.

COG Late Effects Guidelines – March 2003 – References 2

Section5

References
Greene MH, Harris EL, Gershenson DM, et al. Melphalan may be a more potent leukemogen than cyclophosphamide. Ann Int Med1986; 105:360-367.
Meadows AT, Obringer AC, Marrero O, et al. Second malignant neoplasms following childhood Hodgkin's disease: treatment and splenectomy as risk factors. Med Ped Oncol 1989;
17:477-484.
Beaty O, Hudson MM, Greenwald C, et al. Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease. J Clin Oncol 1995; 13: 603-609.
Bhatia S, Robison LL, Oberlin O, et al. Breast cancer and other second neoplasms after childhood Hodgkin's disease. N Engl J Med 1996; 334:745-751.
Schellong G, Riepenhausen M, Creutzig U, et al. Low risk of secondary leukemias after chemotherapy without mechlorethamine in childhood Hodgkin's disease. J Clin Oncol 1997; 15:2247-2253.
Cheruku R, Hussain M, Tyrkus M, et al. Myelodysplastic syndrome after cisplatin therapy. Cancer 1993; 72:213:218.
Schneider DT, Hilgenfeld E, Schwabe D, et al. Acute myelogenous leukemia after treatment for malignant germ cell tumors in children. J Clin Oncol 1999; 17: 3226-3233.

6

Ginsberg SJ, Comis RL. The pulmonary toxicity of antineoplastic agents. Semin Oncol 1982; 8(1): 34-51.
O'Driscoll BR, Hasleton PS, Taylor PM, et al. Active lung fibrosis up to 17 years after chemotherapy with carmustine (BCNU) in childhood. N Engl J Med 1990; 323:378-382.
Kreisman H, Wolkove N: Pulmonary toxicity of anti-neoplastic therapy. Semin Oncol 1992; 19(5): 508-20.
Risks associated with SCUBA diving in childhood cancer survivors (personal communication with Brett Stolp MD, PhD, Duke University), 8-23-02

7

Stillwell TJ, Benson RC, Burgert EO. Cyclophosphamide-induced hemorrhagic cystitis in Ewing's sarcoma. J Clin Oncol 1988; 6:76-82.
Stillwell TJ, Benson RC. Cyclophosphamide-induced hemorrhagic cystitis: a review of 100 patients. Cancer 1988; 61:451-457.

8

Pederson-Bjergaardd J, Erbsoll J, Hansen VL, et al. Carcinoma of the urinary bladder after treatment with cyclophosphamide for non- Hodgkin's lymphoma. N Engl J Med 1988; 10281032.

9

Burk CD, Restaino I, Kaplan BS, et al. Ifosfamide-induced renal tubular dysfunction and rickets in children with Wilms tumor. J Pediatr 1990; 117: 331-335.
Skinner R, Sharkey IM, Pearson ADJ, et al. Ifosfamide, mesna, and nephrotoxicity in children. J Clin Oncol 1992; 11:173-190.
Raney B, Ensign LG, Foreman J, et al. Renal toxicity of ifosfamide in pilot regimens of the Intergroup Rhabdomyosarcoma Study for patients with gross residual tumor. Am J Pediatr
Hematol Oncol 1994; 16(4): 286-295.

10

McHaney V, Thibadoux G, Hayes F, et al. Ototoxicity with cisplatin therapy. Pediatr 1983; 103: 1006-1007.
Schell MJ, McHaney VA, Green AA, et al. Hearing loss in children and young adults receiving cisplatin with or without prior cranial irradiation. J Clin Oncol 1989; 7:754-760.
McHaney VA, Kovnar E, Meyer WH, et al. Effects of radiation therapy and chemotherapy on hearing. In DM Green & GJ D'Angio (Eds), Late Effects of Treatment for Childhood
Cancer. (pp 7-10). New York; Wiley-Liss, 1992.
Macdonald MR, Harrison RV, Wake M, et al. Ototoxocity of carboplatin: comparing animal and clinical models at the Hospital for Sick Children. J Otolaryngology 1994; 23: 151-159.

11

Tuxen MK, Hansen SW. Neurotoxicity secondary to antineoplastic drugs. Cancer Treat Rev 1994; 20: 191- 214.
Cvitkovic E. Cumulative toxicities from cisplatin therapy and current cytoprotective measures. Cancer Treat Rev 1998; 24:265-281.
Bosnjak S, Jelic S, Susnjar S, et al. Gabapentin for relief of neuropathic pain related to anticancer treatment: a preliminary study. J Chemother 2002 Apr; 14(2): 214-9.

COG Late Effects Guidelines – March 2003 – References 3

Section
12

References
Dentino M, Luft FC, Yum MN, et al. Long-term effect of cis-diamminedichloride platinum (CDDP) on renal function and structure in man. Cancer 1978; 41:1274-1281.
Hutchison FN, Perez EA, Gandara DR, et al. Renal salt wasting in patients treated with cisplatin. Ann Intern Med 1988; 108:21-5.
Blanchetti MG, Kanaka C, Ridolfi-Luthy A, et al. Persisting renotubular sequelae after cisplatin in children and adolescents. Am J Nephrol 1991; 11:127-130.
Liao F, Folsom AR, Brancati FL. Is low magnesium concentration a risk factor for coronary artery disease? The Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 1998;
136: 480-490.
Ceremuzinski L, Gebalska J, Wolk R, et al. Hypomagnesemia in heart failure with ventricular arrhythmias. Beneficial effects of magnesium supplementation. J Int Med 2000; 247:78-86
Marina NM, et al. Comparative renal toxicity of chemotherapy regimens including ifosfamide in patients with newly diagnosed sarcomas. J Pediatr Hematol 2000;22(2):112-118.

13

Raghavan D, Cox K, Childs A, et al. Hypercholesterolemia after chemotherapy for testis cancer. J Clin Oncol 1992; 10: 1386-1389.
Ellis PA, Fitzharris BM, George PM, et al. Fasting plasma lipid measurements following cisplatin chemotherapy in patients with germ cell tumors. J Clin Oncol 1992; 10: 1609-1614.

14

Nand S, Messmore HL, Patel R, et al. Neurotoxicity associated with systemic high-dose cytosine arabinoside. J Clin Oncol 1986; 4:571-575.
Baker WJ, Royer GL, Weiss RB. Cytarabine and neurologic toxicity. J Clin Oncol 1991; 9: 679-683.
Truxen MK, Hansen SW. Neurotoxicity secondary to antineoplastic drugs. Cancer Treat Rev 1994; 20:191.
Vera P, Rohrlich P, Stievenart JL, et al. Contribution of single-photon emission computed tomography in the diagnosis and follow-up of CNS toxicity of a cytarabine-containing regimen
in pediatric leukemia. J Clin Oncol 1999; 17:2804-2810.

15

Einhorn M, Davidson I. Hepatotoxicity of mercaptopurine. JAMA 1964; 188 (9): 802-806.
Children’s Oncology Group, Urgent Advisory for CCG-1952 (April 27, 2001).

16

Schwartz AM, Leonidas JC. Methotrexate osteopathy. Skeletal Radiol 1984; 11: 13-16.
Gilsanz V, Carlson ME, Roe TF, et al. Osteoporosis after cranial radiation for acute lymphoblastic leukemia. J Pediatr 1990;117: 238-244.
Aisenberg J, Hsieh K, Kalaitzoglou G, et al. Bone mineral density in young adult survivors of childhood cancer. J Pediatr Hematol Oncol 1998; 20(3): 241-245.
Nysom K, Holm K, Michaelsen KF, et al. Bone mass after treatment for acute lymphoblastic leukemia in childhood. J Clin Oncol 1998; 16 (12): 3752-3760.
Arikoski P, Komulainen J, Voutilainen R, et al. Reduced bone mineral density in long-term survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 1998; 20(3):234-240.
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No manuscripts found to describe this late treatment effect in children.

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Raney RB, Asmar L, Vassilopoulou-Sellin R, et al. Late complications of therapy in 213 children with localized, nonorbital soft-tissue sarcoma of the head and neck: a descriptive reportfrom the Intergroup Rhabdomyosarcoma studies (IRS)-II and -III. Med Pediatr Oncol 1999; 33:362-371.
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Probert JC, Parker BR. The effects of radiation therapy on bone growth. Radiology 1975; 114:155-62.
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Dodd RY. The risk of transfusion-acquired infection. N Engl J Med 1992; 327:419-421.

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Fink FM, Hocker-Schulz S, Mor W, et al. Association of hepatitis C virus infection with chronic liver disease in pediatric cancer patients. Eur J Pediatr 1991; 152:490-492.
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Paul IM, Sanders IM, Ruggiero F, et al. Chronic hepatitis C virus infections in leukemia survivors: prevalence, viral load, and severity of liver disease. Blood 1999; 93 (11): 3672-3677.
Strasser SL, Sullivan KM, Myerson D, et al. Cirrhosis of the liver in long-term marrow transplant survivors. Blood 1999; 93 (100: 3259-3266.
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Dodd RY. The risk of transfusion-acquired infection. N Engl J Med 1992; 327:419-421.

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Rougraf BT, Simon MA, Skeisl JS, et al. Limb salvage compared with amputation for osteosarcoma of the distal end of the femur. J Bone Joint Surgery 1994; 75 (5) 649-656.

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Wilimas JA, Hudson MM, et al. Late Vascular Occlusion of Central Lines in Pediatric Malignancies. Pediatrics 1998; 101: 1-5.

86

Raney Jr B, Heyn R, Hays DM, et al. Sequelae of treatment of 109 patients followed for 5-15 years after diagnosis of sarcoma of the bladder and prostate. Cancer 1993; 71:2387-2394.
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Kaste SC, Chen G, Fontanesi J, et al. Orbital development in long-term survivors of retinoblastoma. J Clin Oncol 1997; 15; 1183-1189.

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Kaiser CW. Complications from staging laparotomy for Hodgkin's disease. J Surg Oncol 1981; 16:319-325.
Jockovich M, Mendenhall NP, Sombeck MD, et al. Long-term complications of laparotomy in Hodgkin's disease. Ann Surgery 1994; 219 (6): 615-624.
Ritchey ML, Green DM, Thomas PRM, et al. Renal failure in Wilms' tumor patients: a report from the National Wilms' Tumor Study Group. Med Pediatr Oncol 1996; 26:75-80.
Paulino A, Wen BC, Brown CK, et al. Late effects in children treated with radiation therapy for Wilms tumor. Int Journal of Radiation Oncology 2000; 46(5): 1239-1246.

COG Late Effects Guidelines – March 2003 – References 20

Section89

References
Frieden RA, Ryniker D, Kenan S, et al. Assessment of patient function after limb-sparing surgery. Arch Phys Med Rehabil 1993; 74:38-43.
Rougraf BT, Simon MA, Skeisl JS, et al. Limb salvage compared with amputation for osteosarcoma of the distal end of the femur. J Bone Joint Surgery 1994; 75 (5) 649-656.
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 2002;
20(22): 4493-4501.

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Mitus A, Tefft M, Feller FX. Long-term follow-up of renal function of 108 children who underwent nephrectomy for malignant disease. Pediatrics 1969; 44: 912-921.
Ritchey ML, Green DM, Thomas PRM, et al. Renal failure in Wilms' tumor patients: a report from the National Wilms' Tumor Study Group. Med Pediatr Oncol 1996; 26: 75-80.
Paulino A, Wen BC, Brown CK, et al. Late effects in children treated with radiation therapy for Wilms tumor. Int Journal of Radiation Oncology 2000; 46(5): 1239-1246.
American Academy of Pediatrics: Committee on Sports Medicine and Fitness. Medical conditions affecting sports participation. Pediatrics 2001; 107:1205-09.

91

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 2003; 40:2634.

92

Lin WW, Kim ED, Quesada ET, et al.. Unilateral testicular injury from external trauma: evaluation of semen quality and endocrine parameters. J Urology 1998; 159:841-843.
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
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Green DM, Whitton JA, Stovall M, et al. Pregnancy outcome of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Am J Obstet Gynecol 2002;
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93

Heyn R, Raney RB, Hays DM, et al. Late effects of therapy in patients with paratesticular rhabdomyo-sarcoma. J Clin Oncol 1992; 10 (4): 614-623.

94

Berend N, Woodcock AJ, Marlin GE. Effects of lobectomy on lung function. Thorax 1980; 35: 145-150.
Pelletier C, Lapointe L, LeBlanc P. Effects of lung resection on pulmonary function and exercise capacity. Thorax 1990; 45:4970502.
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95

Kaiser CW. Complications from staging laparotomy for Hodgkin's disease. J Surg Oncol 1981; 16:319-325.
Jockovich M, Mendenhall NP, Sombeck MD, et al. Long-term complications of laparotomy in Hodgkin's disease. Ann Surgery 1994; 219 (6): 615-624.
Immunization in special clinical circumstances. Report of the Committee on Infectious Diseases, 25th edition, American Academy of Pediatrics. 1997; 66-67.

96

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
1997; 54:131-138.
Nordoy T, Kolstad A, Endresen P, et al. Persistent changes in the immune system 4-10 years after ABMT. Bone Marrow Transplant 1999; 24: 873-878.
Storek J, Dawson MA, Storer B, et al. Immune reconstitution after allogeneic transplantation compared with blood stem cell transplantation. Blood 2001; 97:3380-3389.

COG Late Effects Guidelines – March 2003 – References 21

SectionReferences

97

Paul IM, Sanders IM, Ruggiero F, et al. Chronic hepatitis C virus infections in leukemia survivors: prevalence, viral load, and severity of liver disease. Blood 1999; 93 (11): 3672-3677.
Strasser SL, Sullivan KM, Myerson D, et al. Cirrhosis of the liver in long-term marrow transplant survivors. Blood 1999; 93: 3259-3266.
Strasser SL, Myerson D, Spurgeon CL, et al. Hepatitis C virus infection and bone marrow transplantation: a cohort study with 10-year follow-up. Hepatology 1999; 29:1893-1899.

98

Kader HA, Khanna S, Hutchinson RM, et al. Pulmonary complications of bone marrow transplantation: the impact of variations in total body irradiation parameters. Clin Oncol 1994; 6:
96-101.
Nenadov Beck M, Meresse V, et al. Long-term pulmonary sequelae after autologous bone marrow transplantation in children without total body irradiation. Bone Marrow Transplant
1995; 16:771-775.
Nysom K, Holm K, Hesse B, et al. Lung function after allogeneic bone marrow transplantation for leukemia or lymphoma. Arch Dis Child 1996; 74: 432-436.
Gore EM, Lawton CA, Ash RC, et al. Pulmonary function changes in long-term survivors of bone marrow transplantation. Int J Radiat Oncol Biol Phys 1996; 36:67-75.
Fanfulla F, Locatelli F, Zoia MC, et al. Pulmonary complications and respiratory function changes after bone marrow transplantation in children. Eur Respir J 1997; 10:2301-2306.
Palmas A, Tefferi A, Meyers JL, et al. Late onset noninfectious pulmonary complications after allogeneic bone marrow transplantation. Br J Haematol 1998; 100:680-687.
Griese M, Rampf U, Hofmann D, et al. Pulmonary complication after bone marrow transplantation in children: twenty-four years of experience in a single pediatric center. Pediatr
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Antin JH. Long-term care after hematopoietic-cell transplantation in adults. N Engl J Med 2002; 347 (1):36-42

100

Nysom K, Holm K Michaelson KF, et al. Bone mass after allogeneic BMT for childhood leukemia or lymphoma. Bone Marrow Transpl 1996; 16:395-400.
Stern JM, Chesnut CH, Bruemmer B, et al. Bone density loss during treatment of chronic GVHD. Bone Marrow Transpl 1996; 17:395-400.
Bhatia S, Ramsey NK, Weisdorf D, et al. Bone mineral density in patients undergoing bone marrow transplantation for myeloid malignancies. Bone Marrow Transpl 1998; 20:241-245.
Sklar C, Boulad F, Small T, et al. Endocrine complications of pediatric stem cell transplantation. Frontiers in Bioscience 2001; 6: 17-22.

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Lishner M, Patterson B, Kandel R, et al. Cutaneous and mucosal neoplasms in bone marrow transplant recipients. Cancer 1990; 65:473-476.
Stone RM, Neuberg D, Soiffer R, et al. Myelodysplastic syndrome after autologous transplantation for lymphoma. J Clin Oncol 1994; 12: 12: 2535-2542.
Bhatia S, Ramsay NKC, Steinbuch M, et al. Malignant neoplasms following bone marrow transplantation Blood 1996; 87: 3633-3639.
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 2000; 95: 1588-1593.
Socie G, Curtis RE, Deeg HJ, et al. New malignant diseases after allogeneic transplantation for childhood acute leukemia. J Clin Oncol 2000; 18: 348-357.
Bhatia S, Louie AD, Bhatia R, et al. Solid Cancers following Bone Marrow Transplantation. J Clin Oncol 2001;19:464-71.

COG Late Effects Guidelines – March 2003 – References 22

SectionReferences

102

Antin JH. Long-term care after hematopoietic-cell transplantation in adults. N Engl J Med 2002; 347 (1): 36-42.

103

Refer to United States Preventive Task Force recommendations at http://www.ahrq.gov/clinic/prevenix.htm

104

Bhatia S, Robison LL, Oberlin O, et al. Breast cancer and other second neoplasms after childhood Hodgkin's disease. N Engl J Med 1996; 334: 745-751.
Kaste SC, Hudson MM, Jones DJ, et al. Breast masses in women treated for childhood cancer. Cancer 1998; 82:784-792.
Goss PE, Sierra S. Current perspectives on radiation-induced breast cancer. J Clin Oncol 1998; 16:338-347.
American Cancer Society Cancer Prevention and Early Detection: Facts and Figures 2003, p. 27.
National Comprehensive Cancer Network Practice Guidelines in Oncology - v.1.2002
See also: http://www.ahrq.gov/clinic/serfiles.htm

105

American Cancer Society Cancer Prevention and Early Detection: Facts and Figures 2003, p. 27.
See also: http://www.ahrq.gov/clinic/serfiles.htm

106

American Cancer Society Cancer Prevention and Early Detection: Facts and Figures 2003, p. 27.
See also: http://www.ahrq.gov/clinic/serfiles.htm

107

American Cancer Society Cancer Prevention and Early Detection: Facts and Figures 2003, p. 27.

108

Henschke CI, McCauley DI, Yankelevitz DF, et al. Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet 1999; 354: 99-105.

109

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110

American Cancer Society Cancer Prevention and Early Detection: Facts and Figures 2003, p. 27.
See also: http://www.ahrq.gov/clinic/serfiles.htm

111

Ferrini RL, Perlman M, Hill L. American College of Preventive Medicine policy statement: screening for skin cancer. Am J Prev Med 1998; 14:80-82.
Ferrini RL, Perlman M, Hill L. American College of Preventive Medicine practice policy statement: Skin protection from ultraviolet light exposure. Am J Prev Med 1998; 14: 83-86.
American Cancer Society Cancer Prevention and Early Detection: Facts and Figures 2003, p. 23-24.
See also: http://www.ahrq.gov/clinic/serfiles.htm

112

American Cancer Society Cancer Prevention and Early Detection: Facts and Figures 2003, p. 27
National Cancer Institute, Screening for Testicular Cancer PDQ. www.nci.nih.gov , accessed 01/26/03.

COG Late Effects Guidelines – Version 1.0 – March 2003
Index
Therapy

Therapy
Melphalan

SectionAny Cancer Experience
Psychosocial effects
Limitations in healthcare access1
2

Any Chemotherapy
Dental abnormalities

3

Alkylating AgentsBusulfan
AML/MDS
Hypogonadism, infertility, early menopause

5
4

Pulmonary fibrosis
Carmustine (BCNU)

6

AML/MDS
Hypogonadism, infertility, early menopause
Pulmonary fibrosis
Chlorambucil

5
4
6

AML/MDS
Hypogonadism, infertility, early menopause
Cyclophosphamide

5
4

AML/MDS
Bladder malignancy
Hemorrhagic cystitis, bladder fibrosis, dysfunctional
voiding
Hypogonadism, infertility, early menopause
Ifosfamide
AML/MDS
Bladder malignancy
Renal toxicity
Hemorrhagic cystitis, bladder fibrosis, dysfunctional
voiding

5
8
7
4
5
8
9
7

Hypogonadism, infertility, early menopause
Lomustine (CCNU)

4

AML/MDS
Hypogonadism, infertility, early menopause
Pulmonary fibrosis
Mechlorethamine

54
6

AML/MDS
Hypogonadism, infertility, early menopause

54Section

AML/MDS
Hypogonadism, infertility, early menopause
Procarbazine

54

AML/MDS
Hypogonadism, infertility, early menopause
Thiotepa

5
4

AML/MDS
Hypogonadism, infertility, early menopause
Non-classical alkylators
Dacarbazine

54

AML/MDS
Hypogonadism, infertility, early menopause
Temozolamide

5
4

AML/MDS
Hypogonadism, infertility, early menopause
Heavy Metals
Cisplatin

5
4

AML/MDS
Dyslipidemia
Hypogonadism, infertility, early menopause
Ototoxicity
Peripheral sensory neuropathy
Renal toxicity
Carboplatin

5
13
4
10
11
12

AML/MDS
Dyslipidemia
Hypogonadism, infertility, early menopause
Ototoxicity
Peripheral sensory neuropathy
Renal toxicity

5
13
4
10
11
12

Antimetabolites
Cytarabine (high-dose IV)
Neurocognitive deficits
Clinical leukoencephalopathy(with or without imaging abnormalities)
Mercaptopurine
Hepatic dysfunction, veno-occlusive disease

1

14
14

15

COG Late Effects Guidelines – Version 1.0 – March 2003
Index
Therapy
Methotrexate (po, IV, IM)

Section

Osteopenia, Osteoporosis
Osteonecrosis
Renal dysfunction
Hepatic dysfunction
Methotrexate(IT, high-dose IV)

16
17
18
19

Neurocognitive deficits
Clinical leukoencephalopathy(with or without imaging abnormalities)
Thioguanine

20
20

Hepatic dysfunction, veno-occlusive disease

Therapy

SectionCorticosteroids
Dexamethasone

15

Cataracts
Osteonecrosis
Osteopenia, Osteoporosis
Prednisone

27
26
25

Cataracts
Osteonecrosis
Osteopenia, Osteoporosis

27
26
25

Enzymes
Asparaginase

Anthracycline antibiotics
Doxorubicin

No known late effects

28

AML
Cardiomyopathy/Arrhythmias
Daunorubicin

21
22

Plant aklaloids
Vinblastine

AML
Cardiomyopathy/Arrhythmias
Epirubicin

21
22

Peripheral sensory or motor neuropathy
Vasospastic attacks (Raynaud's phenomenon)
Vincristine

29
30

AML
Cardiomyopathy/Arrhythmias
Idarubicin

21
22

Peripheral sensory or motor neuropathy
Vasospastic attacks (Raynaud's phenomenon)
Epipodophyllotoxins
Etoposide (VP-16)

29
30

AML
Cardiomyopathy/Arrhythmias
Mitoxantrone

21
22

AML
Teniposide (VM-26)

31

AML
Cardiomyopathy/Arrhythmias

21
22

AML

Anti-tumor antibiotics
Bleomycin
Interstitial pneumonitis
Pulmonary fibrosis
Dactinomycin

23
23

No known late effects

24

2

31

COG Late Effects Guidelines – Version 1.0 – March 2003
Index
Therapy

Therapy

Section

Gastrointestinal malignancy
Gonadotropin deficiency
Growth hormone deficiency
Hepatic fibrosis
Hepatocellular carcinoma
Hyperprolactinemia
Hypertension
Hyperthyroidism
Hypothyroidism
Kyphosis
Musculoskeletal growth problems
Myocardial infarction
Neurocognitive deficits
Occlusive cerebral vasculopathy
Otosclerosis
Ovarian dysfunction
Overweight/obesity
Pericardial fibrosis
Pericarditis
Precocious puberty
Pulmonary fibrosis
Renal insufficiency
Restrictive/obstructive lung disease
Scoliosis
Sensorineural hearing loss
Stroke/moyamoya
Testicular dysfunction
Thyroid cancer
Thyroid nodules
Tinnitus
Tympanosclerosis
Uterine vascular insufficiency
Valvular disease (cardiac)
Xerostomia

Radiation
Note: Refer to individual radiation fields for potential
late effects. In addition, potential late effects
applicable to all radiation fields are listed
in the shaded box below.
Radiation - all fields
Note: The following are potential late effects for
all radiation fields:
Bone malignancies
Dysplastic nevi, skin cancer
Secondary benign or malignant neoplasms
Skin changes (fibrosis, telangiectasias)

35
34
33
32

Total Body Irradiation (TBI)
Arrhythmia
Atherosclerotic heart disease
Brain tumor
Breast cancer
Breast tissue hypoplasia
Bowel obstruction
Cardiomyopathy
Carotid artery disease
Cataracts/adverse effects on eye

65
65
39
63
64
71
65
57
51

Central adrenal insufficiency
Central hypothyroidism
Chronic enterocolitis
Chronic sinusitis
Cirrhosis
Clinical leukoencephalopathy(with or without neuro-imaging abnormalities)
Conductive hearing loss
Congestive heart failure
Craniofacial abnormalities
Delayed interstitial pneumonitis
Dental abnormalities
Esophageal stricture
Eustachian tube dysfunction
Fistula, stricture (bowel)

43
42
72
47
69
37
52
65
50
66
49
58
52
72

3

Section
73
45
40
69
70
41
68
56
55
61
59
65
36
38
52
75
46
65
65
44
66
68
66
60
52
38
79
54
53
52
52
74
65
48

COG Late Effects Guidelines – Version 1.0 – March 2003
Index
Therapy
Head/Brain Radiation
Cranial (whole brain)
Brain tumor
Carotid artery disease
Cataracts/adverse effects on eye
Central adrenal insufficiency
Central hypothyroidism
Chronic sinusitis
Clinical leukoencephalopathy(with or without neuro-imaging abnormalities)
Conductive hearing loss
Craniofacial abnormalities
Dental abnormalities
Esophageal stricture
Eustachian tube dysfunction
Gonadotropin deficiency
Growth hormone deficiency
Hyperprolactinemia
Hyperthyroidism
Hypothyroidism
Neurocognitive deficits
Occlusive cerebral vasculopathy
Otosclerosis
Overweight/obesity
Precocious puberty
Sensorineural hearing loss
Stroke/moyamoya
Thyroid cancer
Thyroid nodules
Tinnitus
Tympanosclerosis
Xerostomia

Therapy

Section

39
57
51
43
42
47
37
52
50
49
58
52
45
40
41
56
55
36
38
52
46
44
52
38
54
53
52
52
48

37

Conductive hearing loss
Craniofacial abnormalities
Dental abnormalities
Esophageal stricture
Eustachian tube dysfunction
Gonadotropin deficiency
Growth hormone deficiency
Hyperprolactinemia
Hyperthyroidism
Hypothyroidism
Neurocognitive deficits
Occlusive cerebral vasculopathy
Otosclerosis
Overweight/obesity
Precocious puberty
Sensorineural hearing loss
Stroke/moyamoya
Thyroid cancer
Thyroid nodules
Tinnitus
Tympanosclerosis
Xerostomia

52
50
49
58
52
45
40
41
56
55
36
38
52
46
44
52
38
54
53
52
52
48

Nasopharyngeal

Craniospinal
Brain tumor
Carotid artery disease
Cataracts/adverse effects on eye
Central adrenal insufficiency
Central hypothyroidism
Chronic sinusitis

SectionClinical leukoencephalopathy(with or without neuro-imaging abnormalities)

39
57
51
43
42
47

4

Brain tumor
Carotid artery disease
Central adrenal insufficiency
Central hypothyroidism
Chronic sinusitis
Clinical leukoencephalopathy(with or without neuro-imaging abnormalities)

39
57
43
42
47
37

Conductive hearing loss
Craniofacial abnormalities
Dental abnormalities
Esophageal stricture
Eustachian tube dysfunction
Gonadotropin deficiency

52
50
49
58
52
45

COG Late Effects Guidelines – Version 1.0 – March 2003
Index
Therapy
Growth hormone deficiency
Hyperprolactinemia
Hyperthyroidism
Hypothyroidism
Neurocognitive deficits
Occlusive cerebral vasculopathy
Otosclerosis
Overweight/obesity
Precocious puberty
Sensorineural hearing loss
Stroke/moyamoya
Thyroid cancer
Thyroid nodules
Tinnitus
Tympanosclerosis
Xerostomia

Therapy

SectionXerostomia

40
41
56
55
36
38
52
46
44
52
38
54
53
52
52
48

48

Orbital/Eye

Oropharyngeal
Brain tumor
Carotid artery disease
Central adrenal insufficiency
Central hypothyroidism
Chronic sinusitis
Clinical leukoencephalopathy(with or without neuro-imaging abnormalities)
Craniofacial abnormalities
Dental abnormalities
Esophageal stricture
Gonadotropin (LH/FSH) deficiency
Growth hormone deficiency
Hyperprolactinemia
Hyperthyroidism
Hypothyroidism
Neurocognitive deficits
Occlusive cerebral vasculopathy
Overweight/obesity
Precocious puberty
Stroke/moyamoya
Thyroid cancer
Thyroid nodules

Section

39
57
43
42
47
37
50
49
58
45
40
41
56
55
36
38
46
44
38
54
53

Brain tumor
Cataracts
Central adrenal insufficiency
Central hypothyroidism
Chronic painful eye
Chronic sinusitis
Clinical leukoencephalopathy(with or without neuro-imaging abnormalities)

39
51
43
42
51
47
37

Craniofacial abnormalities
Dental abnormalities
Endophthalmos
Gonadotropin deficiency
Growth hormone deficiency
Hyperprolactinemia
Keratitis
Keratoconjunctivitis sicca
Lacrimal duct atrophy

50
49
51
45
40
41
51
51
51

Neurocognitive deficits
Occlusive cerebral vasculopathy
Optic chiasm neuropathy
Orbital hypoplasia
Overweight/obesity
Precocious puberty
Reduced visual acuity
Retinopathy
Stroke/moyamoya
Telangiectasias
Xerophthalmia (severe)
Xerostomia

36
38
51
51
46
44
51
51
38
51
51
48

Ear/Infratemporal
Brain tumor
Central adrenal insufficiency
Central hypothyroidism
Chronic sinusitis
Clinical leukoencephalopathy(with or without neuro-imaging abnormalities)

5

39
43
42
47
37

COG Late Effects Guidelines – Version 1.0 – March 2003
Index
Therapy
Conductive hearing loss
Craniofacial abnormalities
Dental abnormalities
Eustachian tube dysfunction
Gonadotropin (LH/FSH) deficiency
Growth hormone deficiency
Hyperprolactinemia
Neurocognitive deficits
Occlusive cerebral vasculopathy
Otosclerosis
Overweight/obesity
Precocious puberty
Sensorineural hearing loss
Stroke/moyamoya
Tinnitus
Tympanosclerosis
Xerostomia

Section

Therapy

52
50
49
52
45
40
41
36
38
52
46
44
52
38
52
52
48

Neck Radiation
CervicalCarotid artery disease
Esophageal stricture
Hyperthyroidism
Hypothyroidism
Thyroid cancer
Thyroid nodules

57
58
56
55
54
53

Spinal Radiation
Any dose:
Carotid artery disease
Esophageal stricture
Hyperthyroidism
Hypothyroidism
Thyroid cancer
Thyroid nodules>12 Gy:

57
58
56
55
54
53

Musculoskeletal growth problems
Scoliosis>15 Gy:59
60

Hypertension

68

SectionRenal insufficiency>20 Gy:68

Bowel obstruction
Chronic enterocolitis
Fistula, stricture (bowel)>24 Gy:71
72
72

Ovarian dysfunction
Testicular dysfunction>25 Gy:75
79

Gastrointestinal malignancy>30 Gy73

Arrhythmia
Atherosclerotic heart disease
Bladder fibrosis/dysfunctional voiding
Bladder malignancy
Breast cancer
Breast tissue hypoplasia
Cardiomyopathy
Congestive heart failure
Delayed interstitial pneumonitis
Esophageal stricture
Hemorrhagic cystitis
Kyphosis
Myocardial infarction
Pericardial fibrosis
Pericarditis
Pulmonary fibrosis
Restrictive/obstructive lung disease
Valvular disease (cardiac)

65
65
77
78
63
64
65
65
66
62
76
61
65
65
65
66
66
65

Chest/Thorax Radiation
MantleArrhythmia
Atherosclerotic heart disease
Breast cancer
Breast tissue hypoplasia
Cardiomyopathy
Carotid artery disease
Congestive heart failure
Delayed interstitial pneumonitis

6

65
65
63
64
65
57
65
66

COG Late Effects Guidelines – Version 1.0 – March 2003
Index
Therapy

Therapy

SectionEsophageal stricture
Hyperthyroidism
Hypothyroidism
Kyphosis
Musculoskeletal growth problems
Myocardial infarction
Pericardial fibrosis
Pericarditis
Pulmonary fibrosis
Restrictive/obstructive lung disease
Scoliosis
Thyroid cancer
Thyroid nodules
Valvular disease (cardiac)Mediastinal

62
56
55
61
59
65
65
65
66
66
60
54
53
65

Arrhythmia
Atherosclerotic heart disease
Breast cancer
Breast tissue hypoplasia
Cardiomyopathy
Carotid artery disease
Congestive heart failure
Delayed interstitial pneumonitis
Esophageal stricture
Hyperthyroidism
Hypothyroidism
Kyphosis
Musculoskeletal growth problems
Myocardial infarction
Pericardial fibrosis
Pericarditis
Pulmonary fibrosis
Restrictive/obstructive lung disease
Scoliosis
Thyroid cancer
Thyroid nodules
Valvular disease (cardiac)

65
65
63
64
65
57
65
66
62
56
55
61
59
65
65
65
66
66
60
54
53
65

Atherosclerotic heart disease
Breast cancer
Breast tissue hypoplasia
Cardiomyopathy
Carotid artery disease
Congestive heart failure
Delayed interstitial pneumonitis
Esophageal stricture
Hyperthyroidism
Hypothyroidism
Kyphosis
Musculoskeletal growth problems
Myocardial infarction
Pericardial fibrosis
Pericarditis
Pulmonary fibrosis
Restrictive/obstructive lung disease
Scoliosis
Thyroid cancer
Thyroid nodules
Valvular disease (cardiac)

Whole lungArrhythmia

65

7

Section
65
63
64
65
57
65
66
62
56
55
61
59
65
65
65
66
66
60
54
53
65

COG Late Effects Guidelines – Version 1.0 – March 2003
Index
Therapy

Section

TherapyNote: The following are potential late effects for
all abdominal and pelvic fields:
Any radiation dose:
Bone malignancies
Bowel obstruction
Chronic enterocolitis
Dysplastic nevi, skin cancer
Fistula, strictures (bowel)
Musculoskeletal growth problems
Scoliosis
Secondary benign or malignant neoplasms
Skin changes (fibrosis, telangiectasias)
Dose >25 Gy:

35
71
72
34
72
59
60
33
32

Gastrointestinal malignancy

73

68
66
74
65

Functional asplenia
Life-threatening infection

67
67

Any upper abdominal field
Delayed interstitial pneumonitis
Esophageal stricture
Kyphosis
Pulmonary fibrosis
Restrictive/obstructive lung disease

66
62
61
66
66

Left Upper Quadrant (>30 Gy)

Abdominal/Pelvic Radiation
Whole abdomen
Any dose:
Arrhythmia
Atherosclerotic heart disease
Bladder fibrosis/dysfunctional voiding
Bladder malignancy
Bowel obstruction
Cardiomyopathy
Cirrhosis
Congestive heart failure
Delayed interstitial pneumonitis
Esophageal stricture
Hemorrhagic cystitis
Hepatic fibrosis
Hepatocellular carcinoma
Hypertension
Kyphosis
Myocardial infarction
Ovarian dysfunction
Pericardial fibrosis
Pericarditis
Pulmonary fibrosis

SectionRenal insufficiency
Restrictive/obstructive lung disease
Uterine vascular insufficiency
Valvular disease (cardiac)>30 Gy:Functional asplenia
Life-threatening infection
65
65
77
78
71
65
69
65
66
62
76
69
70
68
61
65
75
65
65
66

67
67

Entire spleen (>30 Gy)
Functional asplenia
Life-threatening infection

67
67

Renal
Hypertension
Renal insufficiency

68
68

Hepatic
Cirrhosis
Hepatic fibrosis
Hepatocellular carcinoma

69
69
70

Left hemiabdomen/Left flankArrhythmia
Atherosclerotic heart disease
Cardiomyopathy
Congestive heart failure
Myocardial infarction
Pericardial fibrosis
Pericarditis

8

65
65
65
65
65
65
65

COG Late Effects Guidelines – Version 1.0 – March 2003
Index
Therapy
Valvular disease (cardiac)

Therapy

SectionPara-aortic
Bladder fibrosis/dysfunctional voiding
Bladder malignancy
Hemorrhagic cystitis
Hypertension
Ovarian dysfunction
Renal insufficiency
Uterine vascular insufficiency

SectionSurgery
Amputation

65

Cosmesis
Functional and activity limitations
Residual limb integrity problems
Phantom pain

77
78
76
68
75
68
74

84
84
84
84

Central venous catheter
Infection of retained cuff or line tract
Thrombosis
Vascular insufficiency

85
85
85

PelvicBladder fibrosis/dysfunctional voiding
Bladder malignancy
Hemorrhagic cystitis
Ovarian dysfunction
Testicular dysfunction
Uterine vascular insufficiency

77
78
76
75
79
74

Cystectomy

77
78
76
75
74

Laparotomy

Chronic urinary tract infection
Renal dysfunction
Enucleation
Cosmesis
Orbital hypoplasia
Poor prosthetic fit

86
86
87
87
87

Iliac/inguinal
Bladder fibrosis/dysfunctional voiding
Bladder malignancy
Hemorrhagic cystitis
Ovarian dysfunction
Uterine vascular insufficiency
Inguinal/femoral
Testicular dysfunction

Adhesive/obstructive complications
Limb sparing procedure
Chronic infection
Chronic pain
Contractures
Functional and activity limitations
Limb length discrepancy
Loosening of endoprosthesis

79

Other Radiation Fields
Testicular
Testicular dysfunction

88

89
89
89
89
89
89

79
Nephrectomy

Extremity Radiation
Musculoskeletal growth problems
Transfusion
Chronic Hepatitis B
Chronic Hepatitis C
Complications related to chronic hepatitis
HIV infection

Hydrocele
Hyperfiltration
Proteinuria
Renal insufficiency

80

81
82
82
83

9

90
90
90
90

COG Late Effects Guidelines – Version 1.0 – March 2003
Index
Therapy
Neurosurgery
Hydrocephalus
Intracranial bleed/stroke
Motor deficits
Neurocognitive deficits
Seizures
Shunt malfunction

Therapy

Section
91
91
91
91
91
91

Orchiectomy
Hypogonadism/infertility

92

Pelvic surgery
Bladder incontinence
Bowel incontinence
Hydrocele
Impotence
Retrograde ejaculation

93
93
93
93
93

Pulmonary lobectomy
Pulmonary insufficiency

94

SplenectomyLife-threatening infection
Hematopoietic stem cell transplantation
Alopecia
AML
Bronchiectasis
Bronchiolitis obliterans
Chronic bronchitis
Chronic infection
Chronic hepatitis
Cirrhosis
Hypogammaglobulinemia
Iron overload
Joint contractures
Lymphoma
Myelodysplasia
Nail dysplasia
Osteopenia

95

102
101
98
98
98
96
97
97
96
97
99
101
101
102
100

10

Section

Osteoporosis
Scleroderma
Secretory IgA deficiency
Solid cancers
Vitiligo

100
102
96
101
102

General Health Screening

103

Cancer Screening
BreastCervicalColorectal
Endometrial
Lung
Oral
Prostate
Skin
Testicular

104
105
106
107
108
109
110
111
112

Explanation of Scoring for the Late Effects Guidelines
These guidelines represent a statement of consensus from a multidisciplinary panel of experts in the late effects of treatment forpediatric malignancies. The guidelines outline minimum recommendations for specific health screening evaluations in order to detect
potential late effects arising as a result of therapeutic exposures received during treatment for childhood cancer. The
recommendations are based on identified risk factors supported by the literature as well as by collective clinical experience.
Each score relates to the strength of the association of the identified late effect with the specific therapeutic exposure basedon current literature, and is coupled with a recommendation for periodic health screening based on the collective clinicalexperience of the panel of experts. This is due to the fact that there are no randomized clinical trials (and none forthcoming in theforeseeable 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 of care”.
Each item was scored based on the level of evidence currently available to support it. Scores were assigned according to thefollowing categories:
Category 1: There is uniform consensus that the recommendation is appropriate based on high-level evidence of an
association between the therapeutic agent and the late effect.
Category 2A: There is uniform consensus that the recommendation is appropriate based on lower-level evidence, including
clinical experience, of an association between the therapeutic agent and late effect.
Category 2B: There is nonuniform consensus that the recommendation is appropriate based on lower-level evidence,
including clinical experience, of an association between the therapeutic agent and late effect.
Category 3: There is major disagreement that the recommendation is appropriate.
“High-level evidence” was defined as evidence derived from high quality case control or cohort studies. “Lower-level evidence” wasdefined as evidence derived from non-analytic studies, case reports, case series and clinical experience.
All “Category 1” recommendations reflect uniform consensus among the reviewers. “Category 2” recommendations are designatedas “2A” (there is uniformity of consensus among the reviewers regarding strength of evidence for the association/recommendation) or“2B” (there is nonuniform consensus among the reviewers regarding the strength of evidence for the association/recommendation).
Rather than submitting recommendations representing major disagreements, items scored as “Category 3” were either deleted orrevised by the panel of experts to provide at least a “Category 2B” score for all recommendations included in the guidelines.

COG Late Effects Screening Guidelines - Scoring by Panel of Experts
Version 1.0 – March 2003
THERAPY
Any cancer experience
Any chemotherapy
Alkylating agentsClassical alkylators:
Mechlorethamine
Cyclophosphamide
Ifosfamide
Melphalan
Chlorambucil
Lomustine (CCNU)
Carmustine (BCNU)
BusulfanThiotepa
Procarbazine
Non-classicalalkylators:
Dacarbazine
Temozolamide
Cisplatin
Carboplatin
Heavy Metals
Cisplatin
Carboplatin

Busulfan
Carmustine (BCNU)
Lomustine (CCNU)

LATE EFFECT
Psychosocial effects

SCORE
2A

Limitations in healthcare access

2A

Dental abnormalities

1

Hypogonadism
Infertility
Early menopause

1

AML/MDS

1

Hypogonadism
Infertility
Early menopause

2A

AML/MDS

2A

Ototoxicity

1

Peripheral Neuropathy

2A

Renal toxicity

1

Dyslipidemia

2B

Pulmonary fibrosis

1

THERAPY
Cyclophosphamide
Ifosfamide

SCORE
1

Bladder malignancy

1

Renal Toxicity

1

Osteopenia, Osteoporosis

2B

Osteonecrosis

2A

Renal dysfunction

2A

Hepatic dysfunction

2A

Methotrexate(IT, high-dose IV)

Neurocognitive deficits
Clinical leukoencephalopathy (with orwithout imaging abnormalities)

1

Cytarabine(high-dose IV)

Neurocognitive deficits
Clinical leukoencephalopathy (with orwithout imaging abnormalities)

2A

Mercaptopurine
Thioguanine

Hepatic dysfunction
Veno-occlusive disease

2A

AML

1

Cardiomyopathy
Arrhythmia

1

No known late effects

1

Interstitial pneumonitis
Pulmonary fibrosis

1

Antimetabolites
Methotrexate(po, IV, IM)

Anthracyclines
Doxorubicin
Daunorubicin
Idarubicin
Mitoxantrone
Epirubicin
Anti-tumor antibiotics
Dactinomycin

Bleomycin

1

LATE EFFECT
Hemorrhagic cystitis
Bladder fibrosis
Dysfunctional voiding

COG Late Effects Screening Guidelines - Scoring by Panel of Experts
Version 1.0 – March 2003

THERAPY
Corticosteroids
Prednisone
Dexamethasone

Enzymes
Asparaginase
Plant alkaloids
Vinca alkaloids
Vincristine
Vinblastine
Epipodophyllotoxins
Etoposide
Teniposide
Radiation
All fields including TBI

TBI

LATE EFFECT

SCORE

Osteopenia, Osteoporosis

1

Osteonecrosis

1

Cataracts

1

No Known Late Effects

1

Peripheral sensory or motor neuropathy

2A

Vasospastic attacks (Raynaud’s
phenomenon)

2A

AML

1

Skin changes

1Secondary benign or malignant
neoplasms

1

Dysplastic nevi
Skin cancer

1

Bone malignancies

1

Complications scored under individual
radiation fields

N/A

THERAPY
LATE EFFECT
Head and brain radiation
TBI
Neurocognitive deficits
Cranial (whole brain)
Clinical leukoencephalopathy (with orwithout neuro-imaging abnormalities)

2

SCORE
1
1

Stroke/moyamoya
Occlusive cerebral vasculopathy

1

Brain tumor

1Growth hormone deficiency

1

Hyperprolactinemia

1

Central hypothyroidism

1

Central adrenal insufficiency

1

Precocious puberty

1

Gonadotropin deficiency

1

Overweight/obesity

1

Chronic sinusitis

1

Xerostomia

1

Dental abnormalities

1

Craniofacial abnormalities

1

COG Late Effects Screening Guidelines - Scoring by Panel of Experts
Version 1.0 – March 2003
THERAPY
Eye radiation
TBI
Orbital/Eye
Cranial (whole brain)
Craniospinal

Ear radiation
TBI
Ear/Infratemporal
Cranial (whole brain)
Craniospinal
Nasopharyngeal

Neck radiation
Any radiation to theneck, including:
TBI
CervicalMantleCranial (whole brain)
Craniospinal
Nasopharyngeal
Oropharyngeal
SpinalLATE EFFECTSCORE

All adverse effects on eye:Cataracts
Reduced visual acuity
Orbital hypoplasia
Lacrimal duct atrophy
Xerophthalmia (severe)
Keratitis
Keratoconjunctivitis sicca
Telangiectasias
Retinopathy
Optic chiasm neuropathy
Endophthalmos
Chronic painful eye

1

Tympanosclerosis
Otosclerosis
Eustachian tube dysfunction
Conductive hearing loss

1

Sensorineural hearing loss
Tinnitus

1

Thyroid nodules

1

Thyroid cancer

1

Hypothyroidism

1

Hyperthyroidism

1

Carotid artery disease

2A

Esophageal stricture

1

THERAPY
Trunk radiation
Any field fromshoulders to pelvis
including:
TBI
Spinal (>12 Gy)
Chest/thorax radiation
Any field involving thechest/thorax:
TBI
MantleMediastinal
Whole lung
Spinal > 30 Gy
Whole abdomen
Any upper abdominal
field
Chest/thorax radiation
with potential impact tothe breast:
TBI
MantleMediastinal
Whole lung
Spinal >30 Gy
Chest/thorax radiation
with potential impact tothe heart:
TBI
MantleMediastinal
Whole lung
Spinal >30 Gy
Whole abdomen
Left hemiabdomen/
Left flank

3

LATE EFFECT

SCORE

Musculoskeletal growth1

Scoliosis

1

Kyphosis

1

Esophageal stricture1

Breast cancer

2A

Breast tissue hypoplasia

1Congestive heart failure
Cardiomyopathy
Pericarditis
Pericardial fibrosis
Valvular disease
Myocardial infarction
Arrhythmia
Atherosclerotic heart disease1

COG Late Effects Screening Guidelines - Scoring by Panel of Experts
Version 1.0 – March 2003

THERAPY
Chest/thorax radiation
with potential impact tothe lungs:
TBI
MantleMediastinal
Whole lung
Spinal >30 Gy
Whole abdomen
Any field involving theupper abdomen

LATE EFFECT
Pulmonary fibrosis
Delayed interstitial pneumonitis
Restrictive/obstructive lung disease

Abdominal/Pelvic radiation
Functional asplenia>30 Gy to:Life-threatening infection
Whole abdomen
Left upper quadrant
Entire spleen

SCORE
1

1

THERAPY
TBI
Whole abdomen
PelvicIliac/Inguinal
Para-aortic

LATE EFFECT
Uterine vascular insufficiency

TBI
Whole abdomen
PelvicIliac/Inguinal
Para-aortic
Spinal >24 Gy

Ovarian dysfunction

1

Whole abdomen
PelvicIliac/Inguinal
Para-aortic
Spinal >30 Gy

Hemorrhagic cystitis

2A

Bladder fibrosis
Dysfunctional voiding

1

Bladder malignancy

1

Testicular dysfunction

1

Musculoskeletal growth1

Chronic Hepatitis B

1

Chronic Hepatitis C

1

Complications related to chronic hepatitis

1

HIV infection

1

TBI
Renal
Para-aortic
Spinal (>15 Gy)

Renal insufficiency
Hypertension

TBI
Whole abdomen
Hepatic

Hepatic fibrosis
Cirrhosis

1

Hepatocellular carcinoma

2A

TBI
All abdominal andpelvic fields
Spinal (>20 Gy)

Bowel obstruction

1

Testicular radiation
TBI
Testicular
PelvicInguinal/femoral
Spinal >24 Gy
Extremity radiation

Chronic enterocolitis
Fistula, strictures

1

Transfusion

TBI>25 Gy to:
All abdominal andpelvic fields
Spine

Gastrointestinal malignancy

2A

1

4

SCORE
2B

COG Late Effects Screening Guidelines - Scoring by Panel of Experts
Version 1.0 – March 2003

THERAPY
Surgery
Amputation

LATE EFFECTSCORE

Cosmesis
Functional and activity limitations
Residual limb integrity problems
Phantom pain

1

Functional and activity limitations
Contractures
Loosening of endoprosthesis
Chronic infection
Chronic pain
Limb length discrepancy

1

Enucleation

Cosmesis
Poor prosthetic fit
Orbital hypoplasia

1

Neurosurgery

Neurocognitive deficits
Intracranial bleed/stroke
Motor deficits
SeizuresHydrocephalus
Shunt malfunction

1

Laparotomy

Adhesive/obstructive complications

Orchiectomy
Pelvic surgery

Limb sparing procedure

Splenectomy

THERAPY
Nephrectomy

LATE EFFECT
Proteinuria
Hyperfiltration
Renal insufficiency
Hydrocele

SCORE
1Cystectomy

Chronic urinary tract infection
Renal dysfunction

1

Placement of central
venous catheter

Thrombosis
Vascular insufficiency
Infection of retained cuff or line tract

1

Hematopoietic stem cell transplantation
Hematopoietic stem cell Secretory IgA deficiency
transplantation
Hypogammaglobulinemia
Chronic infection
Alopecia
Nail dysplasia
Vitiligo
Scleroderma

11Myelodysplasia
AML

1

1

Solid cancers

1

Infertility
Hypogonadism

1

Lymphoma

11Bronchiolitis obliterans
Chronic bronchitis
Bronchiectasis

1

Retrograde ejaculation
Impotence
Bowel incontinence
Bladder incontinence
Hydrocele

Chronic viral hepatitis
Cirrhosis
Iron overload

1Life-threatening infection

1

Joint contractures

1

Osteopenia
Osteoporosis

15

COG Late Effects Screening Guidelines - Scoring by Panel of Experts
Version 1.0 – March 2003

GENERAL HEALTH SCREENING
General Health Screening

Organ
BreastCervicalEndometrial
Colorectal
Lung
Prostate
Testicular
Skin
Oral

Not scored

CANCER SCREENING
Standard Risk
Highest Risk - Score
Not scored
2A(ACS recommendation)
Not scored
2A(ACS recommendation)
N/A
Not scored(ACS recommendation)
Not scored
2A(ACS recommendation)
N/A
1
Not scored
Not scored(ACS recommendation)(ACS recommendation)
Not scored
2A(ACS recommendation)
Not scored
2A(ACS recommendation)
N/A
1

6

COG Late Efffects Guidelines
Version 1.0 – March 2003

APPENDIX:
Patient Education Materials(Health Links)
The following Health Links are included in this packet:
Bone Health after Childhood Cancer (Osteopenia/Osteoporosis)
The Heart and Anthracyclines
The Heart and Radiation
School and Learning Issues after Childhood Cancer
Thyroid Problems after Childhood Cancer
Single Kidney Precautions
The following Health Links are planned for future release:
Emotional Issues after Childhood Cancer
Finding Appropriate Medical Care after Childhood Cancer
Dental HealthAvascular Necrosis
Kidney Health
Liver HealthHearing Conservation
Fertility and Pregnancy Outcomes after Childhood Cancer
Pulmonary HealthBleomycin Alert
Vision Preservation
Skin Health
Reducing the Risk of Second Cancers
Scoliosis/Kyphosis
Splenic Precautions

Health Links
Healthy living after treatment for childhood cancer

Bone Health
Version 1.0 – March 2003

Bone Health After Childhood Cancer
Strong bones are the foundation of a healthy body. They support our muscles andprotect our internal organs. Treatment for childhood cancer sometimes damages thebones, causing an increased risk for developing osteoporosis (weak bones).
Fortunately, there are several things you can do to strengthen your bones and avoid or
minimize this problem.
Bone Mass (Strength) and Osteoporosis
Bones are made of calcium and other minerals. Throughout life, new bone tissue iscontinually being formed and old bone tissue is being removed, so calcium is always
needed. During childhood and into young adulthood, bone formation usually occurs
faster than bone loss, causing bones to grow and become heavier (more dense). In
fact, nearly half of the bone in an adult’s body is formed during the teen years. The
average person reaches their peak bone density (bone strength) in the young adultyears, usually between the ages of 25 and 30. As a person gets older, the process ofbone removal gradually overtakes bone formation, and bones slowly lose strength aspart of the normal aging process.

Healthy living after treatment for childhood cancer

Health Link

Osteoporosis: A Silent Disease
When not enough new bone tissue is formed, or when too much bone tissue isremoved, the bones can become weak (brittle) and less dense (thin). If this happens,there is a much higher risk for breaking a bone of the hip, wrist, ribs, or other bones,
from a simple fall. Also, the bones of the spine can collapse, which makes the person
shorter and can lead to a curvature of the spine. This often causes many problems,
including chronic pain. Weakening of the bones is called osteoporosis (osteo = bone;
porosis = porous). Osteoporosis is sometimes called a “silent bone disease” because
people often don’t know that their bones have weakened until they break one or haveback pain.
Risk Factors for Osteoporosis
There are certain factors that you cannot change that may affect your chances ofdeveloping osteoporosis. Genes are important—if you have someone in your family withosteoporosis, you are more likely to develop it. Women, especially those who havegone through menopause, are more likely to have this disease than men. People who
are Caucasian or Asian, or people who are short or have small, thin frames, are also
more likely to have osteoporosis. And the chances of developing osteoporosis increase
for all people as they get older.
There are several things that can lead to osteoporosis at a young age. Smoking, a diet
low in calcium, and lack of weight-bearing exercise can all increase the risk ofosteoporosis. Consuming too much caffeine, drinking a lot of alcohol or carbonatedbeverages, and eating too much salt may also increase the risk.

Bone Health 2

Certain medications, when taken on a regular basis, can also increase the risk ofosteoporosis. These include:
·
·
·
·
·
·
·

Glucocorticoids (steroids such as prednisone and dexamethasone)High doses of thyroid hormone
Certain anticonvulsants (phenytoin and barbiturates)
Aluminum-containing antacids (such as Maaloxâ or Amphogelâ)Gonadotropin-releasing hormone analogues (used for treatment ofendometriosis)
High doses of heparin (used to prevent blood clots)
Cholestyramine (used to control blood cholesterol)

Many of these medications 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.
Childhood Cancer Survivors and Their Bones
Some survivors of childhood cancer have an increased chance of getting osteoporosis.
We know that treatment can affect the bones in two different ways. First, because ofcancer treatment during childhood or adolescence, the survivor may never reach anormal peak bone density during the young adult years. This is shown in the figure
below (Example 1), illustrating what happens to bone mineral density (bone strength)with aging. Note that in the average person, after reaching peak strength in young
adulthood, the bone density gradually decreases with age. But the survivor may neverreach normal peak bone density, and as a result, may develop osteoporosis at a
younger age.
Another way that cancer treatment can affect the chances of getting osteoporosis is bycausing the loss of bone at a faster rate than normal, as shown in the next figure(Example 2).
Some survivors may have both problems—a lower peak bone density and a faster rateof bone loss, which may lead to osteoporosis at a much younger age.

Lower Peak Bone Density

20

30

40

50
60
Age (years)

Average Person

Bone Mineral Density

Bone Mineral Density

Average Person

70

80

Example 1: Lower Peak Bone Density

Health Link
Healthy living after treatment for childhood cancer

Increased Rate of Calcium Loss

20

30

40

50
60
Age (years)

70

80

Example 2: Increased Rate of Calcium Loss

Bone Health 3

Osteoporosis and Childhood Cancer Treatment
Survivors who received cancer treatment that included any of the following may be atincreased risk for osteoporosis:·

Methotrexate.

·

Steroids (glucocorticoids), such as prednisone and dexamethasone.

·

Stem cell or bone marrow transplant, especially with associated chronic graftversus-host disease.

·

Treatments that result in premature (early) puberty.

·

Treatments that result in ovarian or testicular failure, such as radiation therapy
to the brain, radiation therapy to the testicles or ovaries, surgical removal of thetesticles or ovaries, or high doses of alkylating chemotherapy(cyclophosphamide, ifosfamide, nitrogen mustard, melphalan, busulfan, BCNU,
CCNU, and procarbazine).

·

Treatments, such as radiation therapy to the brain, that result in growth
hormone deficiency.

·

Treatments, such as radiation therapy to the brain, neck, or chest that result inhigh levels of thyroid hormone (hyperthyroidism).

·

Treatments that result in premature (early) menopause.

·

Radiation to the bones.

·

Prolonged periods of inactivity (bed rest).

What Lowers the Risk of Osteopososis?
Fortunately, there are many things you can do to reduce the risk of osteoporosis. If you
could pick the one thing that would have the greatest impact on your life and lower yourrisk for a number of late effects and common adult health problems, it would be to makea lifetime habit of being physically active. Regular exercise, at least four times a week
for about thirty minutes, makes a huge difference in the strength of bones.
Suggestions for exercise:·

Brisk walking is GREAT!

·

Dancing, jazzercise and jogging are also excellent forms of exercise.

·If you are not active, begin slowly and build up each week.

·

Exercise for short periods several times a day.

·

Alternate the types of exercise to keep it fun.

·Find other ways to increase your activity level: Use the stairs rather than theelevator; When weather permits, park a few blocks from your destination andwalk; Mow your own lawn; Take an exercise break at work or between classes.

Some people are limited to certain types of activity because of surgeries or othertreatments for their cancer. If you have a problem with deciding how to best exercise or
be active, discuss the options with your healthcare provider.

Health Link
Healthy living after treatment for childhood cancer

Bone Health 4

Most people do not have an adequate amount of calcium in their diet. The National
Osteoporosis Foundation recommends that all adults have a daily dietary intake of 1000
to 1200 mg of calcium each day. Some healthcare providers recommend that survivorsof childhood cancer get 1500 mg a day. The main sources of calcium in the diet are
dairy products (milk, yogurt, cheese) and green, leafy vegetables.
Food
Milk
YogurtCheeseBroccoli
Pinto beans

Calcium in Foods
Serving Size
8 ounces
8 ounces
1 ounce
½ cup
½ cup

Calcium
300 mg
400 mg
200 mg
47 mg
40 mg

If your diet is low in calcium and you are unable to consume 1200 to 1500 mg per day,then a calcium supplement pill is recommended. A wide variety of calcium supplements
are available at the grocery or health food store.
Vitamin D is needed in order to absorb calcium. Skin makes this vitamin naturally when
exposed to sunlight. Many dairy products also contain vitamin D. In general, you should
not take more than 800 units of Vitamin D per day. Taking too much vitamin D can beharmful, so it’s best to check with your healthcare provider before taking any vitamin D
supplements.
Other important things that you can do to lower the risk for osteoporosis:·

Don’t smoke, dip, or chew tobacco products (if you do now, quit!)·

Don’t drink more than one alcoholic beverage per day (for example, 12 ouncesof beer, 5 ounces of wine or 1.5 ounces of 80-proof distilled spirits)·

Avoid excessive intake of caffeinated products (such as coffee, cola, or tea)·

Avoid excessive consumption of carbonated soft drinks

What Follow-Up is Needed for Those at Risk?
Peak bone mass can be measured by a number of different methods. Dual energy x-ray
absorptiometry (DEXA) is the most widely used technique. From this special x-ray of
two or three sites (hip, wrist, low back), the bone density can be calculated. DEXA has a
low radiation dose and is fairly precise and accurate. The bone mineral density isreported as a “T-score,” which is a comparison to the peak bone mass of young adults
in the general population. Osteopenia (low bone mass) is a T-score between –1.0 and–2.5 SD (standard deviations—a unit of variation), while osteoporosis is defined as a Tscore of –2.5 SD or more.
A single test, such as a DEXA, evaluates bone mass only at one point in time andtherefore does not tell you how rapidly bone loss is occurring. A follow-up DEXA,
generally one or two years later, can show how the bone density is changing over time.
After reviewing your treatment history and risk factors, your healthcare provider canadvise you regarding the need for bone density testing. Generally, a baseline test is

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Healthy living after treatment for childhood cancer

Bone Health 5

done at age 18, but this can be done at an earlier age if needed, and the timing of thetest is based on evaluation of each individual patient.
People who have osteopenia or osteoporosis should discuss treatment options with
their healthcare provider. Medications, such as bisphosphonates and calcitonin, areavailable specifically for the treatment of low bone density. In addition, if you have lowlevels of male or female hormones, or low levels of growth hormone, you may also
benefit from hormone replacement therapy.

Adapted by Wendy Landier, CPNP, March 2003, from: “Bone Health After Childhood Cancer” by
Nancy Keene and Kevin Oeffinger MD, Candlelighters Quarterly, Spring 2002, with permission
from Candlelighters Childhood Cancer Foundation (phone: 800-366-2223, internet:
www.candlelighters.org), and “Strong Bones: A Foundation for Life”, St. Jude Children’s
Research Hospital, After Completion of Therapy (ACT) Clinic, with permission.
Nancy Keene is co-author of Childhood Cancer Survivors: A Practical Guide to Your Future(O’Reilly & Associates, Sebastopol, CA, 2000)
Kevin Oeffinger, MD directs the After the Cancer Experience Young Adult Program for childhood
cancer survivors and is a Professor at the University of Texas Southwestern Medical Center in
Dallas, TX
Melissa Hudson, MD directs the After Completion of Therapy (ACT) clinic at St. Jude Children’s
Research Hospital in Memphis, TN
Wendy Landier, RN, MSN, CPNP, CPON, is a pediatric nurse practitioner and coordinates theSurvivorship Clinic at City of Hope National Medical Center in Duarte, CA

Health Link
Healthy living after treatment for childhood cancer

The Heart & Anthracyclines
Version 1.0 – March 2003

The Heart & Anthracyclines
Anthracyclines
Anthracyclines are a type of chemotherapy used to treat many childhood cancers.
Included in the anthracycline group are doxorubicin (Adriamycinâ), daunorubicin(daunomycin, Cerubidineâ), idarubicin (Idamycinâ), mitoxantrone (Novantroneâ), andepirubicin. The use of anthracyclines has resulted in significant improvement in survival
for children and adolescents with cancer, but it has also sometimes led to problems withthe heart that may not become apparent until many years after treatment is completed.
It is therefore important for each childhood cancer survivor who has received
anthracyclines to continue to have regular medical check-ups so that if a problem withthe heart develops, it can be detected and treated early.
The Heart
The heart is a large muscle that is divided into four chambers and is designed to pumpblood throughout the body. The upper chambers are called “atria” and the lower
chambers are called “ventricles.” The blood returning from the body enters the rightatrium, is squeezed into the right ventricle, and then is pumped into the blood vessels in
the lungs. It is here that the oxygen we breathe is transferred into the many small bloodvessels in the lungs. The oxygen-rich blood returns to the left atrium and is thensqueezed into the left ventricle, the largest and most powerful of the chambers. The left
ventricle contracts to circulate the blood to the entire body.

Healthy living after treatment for childhood cancer

Health Link

The Problem
The cells of the heart muscle are called cardiomyocytes (cardio=heart, myo=muscle,cytes=cells). In ways that are not well understood, anthracyclines can damage thecardiomyocytes of the left ventricle. Over time, this can lead to thinning of the outside
wall or muscle of the left ventricle, resulting in a stiff, noncompliant (loss of normal
resiliency) left ventricle. The medical term for this condition is cardiomyopathy(cardio=heart, myo=muscle, pathy=abnormal, weakened).
Generally, this is not a problem while at rest, but when the heart needs to work harder,
such as during exercise or strenuous physical activity, the stiff left ventricle may not becapable of increased pumping action. If this happens, the blood that is being pumped
through the left side of the heart (atrium and ventricle) does not get pumped out fastenough and some of it “backlogs” in the small blood vessels of the lungs. Because theoxygen in the lungs is transferred to these small blood vessels, when the vessels
become engorged with the backlogged blood, the oxygen cannot be transferredproperly. Though this problem (called congestive heart failure) can be quite serious,
there are medications that can help.
Who is at Risk?
Many childhood cancer survivors who received anthracyclines have no heart damage atall. Others may have mild changes in heart functioning, but no progressive weakeningof the heart muscle. However, some survivors experience progressive weakening of theThe Heart & Anthracyclines 2heart muscle (cardiomyopathy), and may also develop congestive heart failure.
Survivors treated with a total anthracycline dose of 300 mg/m2 (milligrams per square
meter of body surface area) or more when younger than 18 years of age, or 550 mg/m2
or more when 18 years or older, are at highest risk. Other risk factors are:
·
·
·
·

·
·

Female gender.
African American race.
Young age when treated. Anyone treated before the age of 5 years, andespecially those treated as infants, are at increased risk.
Treatment with both anthracyclines and radiation to the heart. The types ofradiation that can damage the heart are chest/thorax, mantle, mediastinal, lung,total body, whole or upper abdominal, left abdominal, left flank, or higher dose(>30 Gy) spinal radiation.
High doses of cyclophosphamide (Cytoxan) given as conditioning for stem celltransplant
Treatment with Amsacrine.

In addition, a history of congenital heart disease (heart problems present at birth), or afamily history of heart disease may also increase the risk of heart problems after
treatment for childhood cancer.
What are the symptoms of anthracycline-related heart problems?
Possible symptoms of congestive heart failure include:
·
·
·
·
·
·
·
·
·

Increasing shortness of breath or difficulty breathing during exercise
Shortness of breath when lying flat, especially at night
Chest pain (generally a smothering-type sensation)
Increasing fatigue
Poor appetite
Swelling of the feet or ankles
Persistent cough (which may produce white or pink-tinged phlegm)
Wheezing
Rapid heartbeat (feeling of heart racing or throbbing)

These symptoms may be caused by a variety of other medical conditions, so it is very
important to see your healthcare provider if you have any of these symptoms.
Is there anything that could worsen the weakened heart muscle or cause
symptoms to occur?
Yes, the following things can potentially worsen a weakened heart:Pregnancy: During pregnancy, the increased volume of blood can stress the heart.
Thus, the first time a female survivor may develop symptoms of heart problems may
be during pregnancy or labor. It is therefore very important that a physician
knowledgeable about this late effect evaluate a pregnant survivor who has beentreated with an anthracycline.

Health Link
Healthy living after treatment for childhood cancer

The Heart & Anthracyclines 3

High fevers: High fevers can cause the heart to pump faster and can place extra
strain on a weakened heart.
Cocaine, diet pills, ephedra, mahuang: Use of these drugs can cause lifethreatening heart rhythm disturbances in a person whose heart has been weakened
by an anthracycline.
Weight lifting/exercise: Isometric exercises, such as weight lifting, can cause asudden worsening of heart function. Heavy weight lifting, or any vigorous isometric
exercise (especially if associated with breath holding) can be dangerous if a survivor
already has some weakening of the heart muscle. Limited high repetition weight lifting(using low weights to perform an exercise no more than 15 to 20 times in a row withease) is much less stressful to the heart and is more likely to be safe. Aerobic
exercise (brisk walking, running) is generally safe and actually healthy for the heart.
However, survivors with any symptoms of heart weakening should check with theirhealthcare provider before beginning any exercise program.
What monitoring is required for potential heart problems?
Anyone who has received anthracycline chemotherapy to treat childhood cancer shouldhave a yearly medical evaluation, which should include specific evaluation of any
symptoms relating to the heart. In addition, an electrocardiogram (ECG, EKG) should bedone at the time the survivor enters long-term follow-up (usually about 5 years fromdiagnosis or 2 years from completion of therapy). An echocardiogram or MUGA scan is
also recommended at the first long-term follow-up visit, then according to the following
schedule (or as recommended by your healthcare provider):Age at treatment*

Chest radiation

Total
anthracycline
dose**

Recommended
frequency
of
ECHO or MUGA

< 1 yearYes

Any

Every year

1 to 4 years oldNo<200 mg/m

No>200 mg/m2

Every year

Yes

Any

Every year

No<100 mg/m2

No>5 years old

2>100 to <300 mg/m

Every 2 years

Every 5 years22

Every 2 years

No>300 mg/m

Yes<300 mg/m2

Every 2 years

Yes>300 mg/m2

Every year

No<200 mg/m2

NoNo>200 to <300 mg/m
>300 mg/m

2Every year

Every 5 years
2

Every 2 years
Every year

* treatment with anthracycline or chest radiation (whichever was given first)** based on total doses of doxorubicin/daunorubicin or the equivalent doses of other anthracyclines

Health Link
Healthy living after treatment for childhood cancer

The Heart & Anthracyclines 4

In addition, female survivors who are pregnant or planning pregnancy may also requireevaluation by a cardiologist. Cardiac monitoring during pregnancy/delivery may benecessary due to the extra strain on the heart that pregnancy (and especially labor) can
produce.
How are these 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 areattached to the electrodes and the electrical impulses of the heart are then recorded.
An echocardiogram is an ultrasound of the heart that measures the thickness of themuscle of the left ventricle (main pumping chamber) and evaluates the pumping ability of
the heart. The two primary measures are the ejection fraction and the shortening
fraction. The ejection fraction is a ratio, calculated by measuring the amount of bloodthat is pumped out with each beat and dividing it by the amount of blood that waits forthe next cycle. The normal value for the ejection fraction depends on sex and age, but isgenerally 55% or higher. The shortening fraction is also a ratio, determined by thediameter change of the left ventricle between the relaxation and the contraction phases
divided by the diameter of the left ventricle in the relaxation phase. Generally a value of
30% or higher is considered normal. A decrease in the shortening fraction is usuallyseen before a decrease in the ejection fraction.
A technician, nurse, or doctor administers the echocardiogram. The survivor lies on atable and has conductive jelly applied to the chest. Then the technician puts atransducer (which emits the ultrasound waves) on the jelly and moves the device aroundon 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 onvideotape and photographed for later interpretation.
A MUGA (multiple-gated acquisition) scan is another way of testing the motion of theheart and how well it pumps blood to the body. During this test, a small amount ofradioactive isotope is injected into a vein. The survivor then lies on a table and a special
camera moves above the table to obtain pictures of the heart in motion. Electrodes arealso placed on the chest to monitor the heart’s electrical impulses during the test.
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 (heart specialist) is needed for additional evaluation and/or
treatment with medications
What can be done to prevent heart problems?
With increasing age, the risk of other types of heart disease (such as heart attacks andhardening of the arteries) also increases. Factors that can increase the risk of heart
problems include smoking, being overweight, eating a high fat diet, and not exercising.

Health Link
Healthy living after treatment for childhood cancer

The Heart & Anthracyclines 5

Medical conditions that increase the risk include diabetes, high blood pressure, and highblood cholesterol. You can reduce your risk of heart problems by:····

Not smoking (or quitting if you currently smoke).
Maintaining a healthy body weight.
Limiting the fat in your diet to no more than 30% of calories.
Exercising moderately for at least 30 minutes most days of the week.

If you have diabetes, high blood pressure, or high blood cholesterol, keep these undergood control with diet or medication as recommended by your healthcare provider. Be
sure to promptly report any symptoms of heart problems to your healthcare provider.

Adapted by Wendy Landier, CPNP, March 2003, from “Anthracyclines and the Heart” by Nancy
Keene and Kevin Oeffinger MD, Candlelighters Quarterly, Autumn 2000, with permission from
CandlelightersChildhood
CancerFoundation(phone:800-366-2223,
internet:www.candlelighters.org); and “Staying Healthy: Know Your Risk” by Melissa Hudson MD,
Childhood Cancer Survivor Study Newsletter, Summer 2001, used with permission.
Nancy Keene is co-author of Childhood Cancer Survivors: A Practical Guide to Your Future(O’Reilly & Associates, Sebastopol, CA, 2000)
Kevin Oeffinger, MD directs the After the Cancer Experience Young Adult Program for childhood
cancer survivors and is a Professor at the University of Texas Southwestern Medical Center in
Dallas, TX
Melissa Hudson, MD directs the After Completion of Therapy (ACT) clinic at St. Jude Children’s
Research Hospital in Memphis, TN
Wendy Landier, RN, MSN, CPNP, CPON, is a pediatric nurse practitioner and coordinates theSurvivorship Clinic at City of Hope National Medical Center in Duarte, CA

Health Link
Healthy living after treatment for childhood cancer

The Heart & Radiation
Version 1.0 – March 2003

The Heart & Radiation
Radiation therapy is often an important part of the treatment for many childhood cancers.
The use of radiation has made a tremendous difference in treating cancer in children
and adolescents, leading to improved survival rates. Unfortunately, radiation given inchildhood also has the potential to cause problems with the heart many years after
treatment. Therefore it is important for each childhood cancer survivor who has received
radiation to the heart to continue to have regular medical check-ups so that if a problem
with the heart develops, it can be detected and treated early.
The Heart

Healthy living after treatment for childhood cancer

Health Link

The heart is a large muscle that is divided into four chambers and is designed to pumpblood throughout the body. The upper chambers are called “atria” and the lower
chambers are called “ventricles”. The blood returning from the body enters the rightatrium, is squeezed into the right ventricle, and then is pumped into the blood vessels in
the lungs. It is here that the oxygen we breathe is transferred into the many small bloodvessels in the lungs. Then the oxygen-rich blood returns to the left atrium and is thensqueezed into the left ventricle, the largest and most powerful of the chambers. The left
ventricle contracts to circulate the blood to the entire body.
Blood flow between the heart chambers is controlled by four valves: aortic, mitral,pulmonary, and tricuspid. Each valve opens as blood flows into its respective chamber
and then closes as the chamber contracts and squeezes the blood out. On the outside of
the heart is a network of blood vessels (coronary arteries) that carry oxygen andnutrients to the hard-working heart muscle.
The Problem with Radiation
Most survivors who received radiation do not develop heart problems. But sometimes
radiation can damage the heart in one of several ways, including damage to the heart
muscle, the valves, or the coronary arteries. Each of these problems is quite different, so
let’s discuss them one at a time.
Damage to the heart muscle is called cardiomyopathy (cardio = heart, myo = muscle,
pathy = abnormal, weakened). This term is used when the muscle does not work as wellas it should. It generally affects the left ventricle more than the other parts of the heart,causing it to be stiff and less responsive to changes. Usually when someone is at rest
the heart does not have to work hard. But when the heart needs to work harder, such as
during pregnancy or strenuous physical activity, the stiff left ventricle may not be able toincrease its pumping action. If this happens, the blood that is being pumped through theleft side of the heart (atrium and ventricle) does not get pumped out fast enough andsome of it “backlogs” in the small blood vessels of the lungs. The oxygen in the lungs istransferred to these small blood vessels, and so when the vessels become engorgedwith the backlogged blood, the oxygen cannot be transferred properly. Though thisproblem—called congestive heart failure—can be quite serious, there are medications
that can help.

The Heart & Radiation 2

Radiation can also damage the valves in the heart, especially the two valves on the left
side of the heart (mitral and aortic). If a valve is damaged, it can either become “leaky”
so that blood flows backwards into the chamber it came from, or it can become “stiff” andnot open very well, slowing the flow of blood. Problems with valves can cause the heart
to work too hard, and lead to congestive heart failure and other heart problems.
A third problem that can be caused by radiation is premature coronary artery disease.
The network of small blood vessels on the outside of the heart feeds the heart muscle
with oxygen and nutrition. The interior of normal, healthy blood vessels is smooth.
Radiation can roughen the inside of blood vessels, and these rough spots are sites
where fatty deposits (plaques) may develop. Calcium deposits can harden the plaques,
resulting in atherosclerosis (hardening of the arteries). Coronary artery disease(coronary = heart; artery = blood vessel) is when one or more of the blood vessels
becomes clogged with plaque. It is similar to a clogged pipe that does not allow much
liquid to flow through it. If this happens, the heart muscle cannot get enough oxygen andnutrition for all of its work. So when the heart needs to work harder and it cannot getenough oxygen or nutrition, a person may experience chest pain (angina), which will lasta few minutes until the oxygen gets through the partially clogged artery. If the bloodvessel is fully blocked, the part of the muscle that was depending upon the oxygen fromthat vessel dies (a heart attack). If it is a small blood vessel supplying a small amount ofheart muscle, then the person has a small or minor heart attack. But if it is a larger
vessel feeding a larger amount of heart muscle, the heart attack is serious and can belife-threatening.
Occasionally, other radiation-related problems affecting the heart can occur, including
pericarditis (an inflammation of the thin membrane that surrounds the heart), pericardial
fibrosis (scarring of the thin membrane that surrounds the heart) and arrhythmias(abnormal heart rhythms).
Who is at risk of radiation-related heart problems?
Children or teens who received radiation to the following areas (fields) may be at risk:· Chest/thorax· Mantle (from the chin to the upper abdomen)· Mediastinal (central part of the chest)· Lung· Spine, if dose was 30 Gy (3000 cGy/rads) or higher· Whole or upper abdomen· Left abdomen or left flank· Total body irradiation (TBI)
Whether the heart sustains injury after radiation treatment depends on several factors
including:· Total radiation dose ¾ Survivors who received doses of 40 Gy (4000cGy/rads) or more are highest risk.

Health Link
Healthy living after treatment for childhood cancer

The Heart & Radiation 3··

Amount and areas of the heart treated.
Chemotherapy drugs used. Anthracyclines such as doxorubicin (Adriamycin),daunorubicin (daunomycin, Cerubidine), idarubicin (Idamycin), mitoxantrone(Novantrone), and epirubicin. Dactinomycin (Actinomycin-D) also can increase
the risk

Modern radiation techniques using lower total doses and cardiac (subcarinal) shielding
are less likely to cause damage.
Other factors that may also increase the risk of subsequent heart problems include:· Young age when treated. Anyone treated before the age of 5 years, andespecially those treated as infants are at increased risk.
· Family history of high blood cholesterol or coronary artery disease· Smoking· Obesity· High blood pressure· High blood cholesterol levels· Diabetes· Premature menopause (if not taking hormone replacement therapy)
What are the symptoms of a heart problem from radiation?
The signs and symptoms of radiation-induced heart damage vary widely. Possible
symptoms of congestive heart failure (resulting from a weakened heart or valve
problems) include:
·
·
·
·
·
·
·
·
·

Increasing shortness of breath or difficulty breathing during exercise
Shortness of breath when lying flat, especially at night
Chest pain (generally a smothering-type sensation)
Increasing fatigue
Poor appetite
Swelling of the feet or ankles
Persistent cough (which may produce white or pink-tinged phlegm)
Wheezing
Rapid heartbeat (feeling of heart racing or throbbing)

These symptoms may be caused by a variety of other medical conditions, so it is very
important to see your healthcare provider if you have any of these symptoms.
Possible symptoms of coronary artery disease (resulting from clogged blood vessels in
the heart) include:·

Uncomfortable pressure, fullness, squeezing or pain in the center of the chestthat lasts a few minutes, or goes away and comes back.

Health Link
Healthy living after treatment for childhood cancer

The Heart & Radiation 4··

Pain that spreads to the shoulders, neck or arms.
Chest discomfort with lightheadedness, fainting, sweating, nausea or
shortness of breath.

Possible symptoms of other heart problems (such as pericarditis or arrhythmia) include:··

Sharp piercing pain in the center or the left side of the chest (often worsens
with a deep breath).
Rapid heartbeat, palpitations, dizziness, fainting or near fainting.

These symptoms may indicate a serious heart problem and require immediate medical
attention. It is important for the childhood cancer survivor to have regular check-ups,
including tests of heart function, in order to catch problems early when they may beeasier to correct.
Is there anything that could worsen weakened heart muscle or cause symptoms tooccur?
Yes, the following things can potentially worsen a weakened heart:Pregnancy: During pregnancy, the increased volume of blood can stress the heart.
Thus, the first time a female survivor may develop symptoms of heart problems may
be during pregnancy or labor. It is very important that a physician knowledgeable
about this late effect evaluate any pregnant survivor who received:· Total body irradiation (TBI).
· Chest radiation at a dose of 30 Gy (3000 rads/cGy) or higher.
· Any dose of chest radiation if the survivor also received anthracycline
chemotherapy.
High fevers: High fevers can cause the heart to pump faster and can place extra
strain on a weakened heart.
Cocaine, diet pills, ephedra, mahuang: Use of these drugs can cause lifethreatening rhythm disturbances in a person whose heart has been weakened bychest radiation.
Weight lifting/exercise: Isometric exercises, such as weight lifting, can cause
sudden worsening of heart function. Heavy weight lifting, or any vigorous isometric
exercise (especially if associated with breath holding) may be dangerous if a survivor
already has some weakening of the heart muscle. Limited high repetition weight lifting(using low weights to perform an exercise no more than 15 to 20 times in a row withease) is less stressful to the heart and more likely to be safe. Aerobic exercise (brisk
walking, running) is generally safe and actually healthy for the heart. However,survivors with any symptoms of heart weakening or heart disease should check with
their healthcare provider before beginning any exercise program.

Health Link
Healthy living after treatment for childhood cancer

The Heart & Radiation 5

What monitoring is required for potential heart problems?
Anyone who has received radiation during treatment for childhood cancer should have ayearly medical evaluation (which should include specific evaluation of any symptoms
relating to the heart). In addition, an electrocardiogram (ECG, EKG) should be done at
the time of entry into long-term follow-up (usually about 5 years from diagnosis or 2
years after completion of therapy), and then as recommended by your healthcare
provider. A blood test to check for diabetes and high cholesterol levels (fasting glucose
and lipid profile) should be done every 3 to 5 years. An echocardiogram or MUGA scanis also recommended at the first long-term follow-up visit, then according to the following
schedule (or as recommended by your healthcare provider):Age at treatment*

Chest
dose

Total
radiation anthracycline
dose**<1 to 4 years old

Any

None

Every 2 years

Any

Every year

< 30 Gy

None

Every 5 years> 30 Gy

None> 5 years old

Recommended
frequency of
ECHO or MUGA

Every 2 years2

Any<300 mg/m

Any>300 mg/m2

Every 2 years
Every year

* treatment with anthracycline or chest radiation (whichever was given first)** based on total doses of doxorubicin/daunorubicin or the equivalent doses of other anthracyclines

Childhood cancer survivors who received a radiation dose of 40 Gy (4000 cGy/rads) or
higher to fields involving the heart (as listed above) should also see a cardiologist (heart
specialist) for baseline cardiac stress testing 5 to 10 years after the radiation was given.
In addition, female survivors who are pregnant or planning pregnancy may also requireevaluation by a cardiologist. Cardiac monitoring during pregnancy/delivery may benecessary due to the extra strain on the heart that pregnancy (and especially labor) can
produce.
How are these 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 areattached to the electrodes and the electrical impulses of the heart are then recorded.
An echocardiogram is an ultrasound of the heart that measures the thickness of themuscle of the left ventricle (main pumping chamber) and evaluates the pumping ability of
the heart. The two primary measures are the ejection fraction and the shortening
fraction. The ejection fraction is a ratio, calculated by measuring the amount of bloodthat is pumped out with each beat and dividing it by the amount of blood that waits forthe next cycle. The normal value for the ejection fraction depends on sex and age, but is

Health Link
Healthy living after treatment for childhood cancer

The Heart & Radiation 6

generally 55% or higher. The shortening fraction is also a ratio, determined by thediameter change of the left ventricle between the relaxation and the contraction phases
divided by the diameter of the left ventricle in the relaxation phase. Generally a value of
30% or higher is considered normal. A decrease in the shortening fraction is usuallyseen before a decrease in the ejection fraction.
A technician, nurse, or doctor administers the echocardiogram. The survivor lies on atable and has conductive jelly applied to the chest. Then the technician puts atransducer (which emits the ultrasound waves) on the jelly and moves the device aroundon 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 onvideotape and photographed for later interpretation.
A MUGA (multiple-gated acquisition) scan is another way of testing the motion of theheart and how well it pumps blood to the body. During this test, a small amount ofradioactive isotope is injected into a vein. The survivor then lies on a table and a special
camera moves above the table to obtain pictures of the heart in motion. Electrodes arealso placed on the chest to monitor the heart’s electrical impulses during the test.
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 is needed for additional evaluation and/or treatment withmedications
What can be done to prevent heart problems?
With increasing age, the risk of other types of heart disease (such as heart attacks andhardening of the arteries) also increases. Factors that can increase the risk of heart
problems include smoking, being overweight, eating a high fat diet, and not exercising.
Medical conditions that increase the risk include diabetes, high blood pressure, and highblood cholesterol. You can reduce your risk of heart problems by:· Not smoking or quitting if you currently smoke.
· Maintaining a healthy body weight.
· Limiting the fat in your diet to no more than 30% of calories.
· Exercising moderately for at least 30 minutes most days of the week.
If you have diabetes, high blood pressure, or high blood cholesterol, keep these undergood control with diet or medication as recommended by your healthcare provider. Be
sure to promptly report any symptoms of heart problems to your healthcare provider.

Health Link
Healthy living after treatment for childhood cancer

The Heart & Radiation 7

Adapted by Wendy Landier, CPNP, March 2003, from “Radiation and the Heart” by Nancy Keeneand Kevin Oeffinger MD, Candlelighters Quarterly, Winter 2000, with permission from
Candlelighters Childhood Cancer Foundation (phone: 800-366-2223, internet:
www.candlelighters.org); and “Staying Healthy: Know Your Risk” by Melissa Hudson MD,
Childhood Cancer Survivor Study Newsletter, Summer 2001, used with permission.
Nancy Keene is co-author of Childhood Cancer Survivors: A Practical Guide to Your Future(O’Reilly & Associates, Sebastopol, CA, 2000)
Kevin Oeffinger, MD directs the After the Cancer Experience Young Adult Program for childhood
cancer survivors and is a Professor at the University of Texas Southwestern Medical Center in
Dallas, TX
Melissa Hudson, MD directs the After Completion of Therapy (ACT) clinic at St. Jude Children’s
Research Hospital in Memphis, TN
Wendy Landier, RN, MSN, CPNP, CPON, is a pediatric nurse practitioner and coordinates theSurvivorship Clinic at City of Hope National Medical Center in Duarte, CA

Health Link
Healthy living after treatment for childhood cancer

School and Learning Issues
Version 1.0 – March 2003

School and Learning Issues After Childhood Cancer:
Information for Parents and Teachers
As treatment for childhood cancer has improved, more and more children are becoming
long-term survivors. Often, treatment received for childhood cancer includes therapy tocontrol or prevent spread of the disease to the brain and/or spinal cord (central nervous
system). Although very effective for treatment of cancer, chemotherapy, radiation, or
surgery to the brain sometimes causes problems with thinking, remembering, andlearning. These types of problems are called “cognitive late effects.” Very young
children (less than 5 and particularly less than 2 years old at the time of treatment),
whose brains are growing and developing, are more at risk than older children or teens.
Each child is unique, and many will not have any cognitive late effects. However, it iswise for parents and teachers to be aware of the potential for these problems, so thatchildren and teens at risk can be monitored closely and provided with extra help if theneed arises.

Healthy living after treatment for childhood cancer

Health Link

What learning problems are associated with childhood cancer treatment?
The brain is a very complex structure that continues to grow and develop throughout
childhood and adolescence. Although problems are occasionally evident right away
(such as after brain surgery or high doses of brain radiation), many problems do not
become apparent until years after therapy is completed.
Signs of common learning problems include trouble with:· Handwriting (ability to write quickly and accurately).
· Spelling.
· Reading (particularly reading comprehension).
· Understanding math concepts, remembering math facts, comprehending
math symbols, sequencing, and working with columns and graphs· Difficulty in using calculators or computers.
· Auditory or visual language processing (trouble with vocabulary, blending
sounds, and syntax).
· Concentration or attention span (“spacing out”). Some children become either
inattentive or hyperactive or both.
· Slow processing speed (taking longer to comprehend and respond to new
information), including trouble keeping pace with new material and trouble
completing tasks within allotted time.
· Memory, especially problems with short-term memory, storage of new
information, and information retrieval (such as trouble following multi-part
instructions).
· Planning and organizational skills (sequencing).
· Coordination of visual and motor abilities (such as problems rememberingand copying shapes).
· Social maturity and social skills (such as problems detecting social cues).
· Problem-solving (particularly when the problem has not been previously
encountered).

School and Learning Issues

2

These late effects can cause changes in learning style as well as social behavior. Somechildren and teens will have an overall decline in intellectual ability (IQ) over time, butmany survivors do not. Significant declines in IQ scores are usually associated with highradiation doses, such as those given for brain tumors, especially when given to a very
young child.
For children with brain tumors, the tumor location also influences the type and severity oflearning disabilities that may develop. For example, children with temporal lobe tumors
may have problems with memory. Surgery to the brain can also cause many late effects,
and can vary in severity depending on the part of the brain that was operated on, theamount of healthy tissue removed, and complications occurring after surgery. Learning
may also be affected by hydrocephalus, vision problems, hearing problems, and by
medications used to treat seizures.
Cognitive late effects can affect survivors’ education, social life, relationships, and job
performance. The effect on individual children is quite variable. Some children have nolate effects, and some develop very subtle disabilities, while others develop life-altering
problems.
What testing is recommended?
Any child who has had any of the following treatment(s) for childhood cancer should
undergo a formal neuropsychological evaluation by a pediatric psychologist at entry into
long-term follow-up:····

Methotrexate. High-dose intravenous (IV) or intrathecal (IT)Cytarabine. High-dose intravenous (IV)
Neurosurgery. Surgery involving the brain or spinal cord
Radiation to the head/brain, including any of the following areas (fields):
 Total body irradiation (TBI) Cranial (whole brain) Craniospinal Nasopharyngeal
 Oropharyngeal
 Orbital
 Eye
 Ear
 Infratemporal (mid-facial area behind the cheekbones)

These tests usually take four to six hours, and can be done over two days for younger
children or those who fatigue easily. The psychologist gives a series of general tests
appropriate for age level, then another series of more and more specific subtests basedon the results of the general ones. Pediatric psychologists usually make the testing fun
for children. Parent(s) are usually interviewed separately. Neuropsychological tests arevery different from tests that measure educational level. If problems are identified,referrals for appropriate educational interventions can then be initiated.

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School and Learning Issues

3

Even if the baseline neuropsychological evaluation is normal and the child is having nolearning problems, it is important for parents and teachers to remain vigilant. Further
neuropsychological evaluations may be indicated if:····

The child begins experiencing any of the learning problems listed earlier
The child’s school performance is declining
It takes much longer than usual for the child to complete assignments
The child is becoming frustrated with school

It is sometimes difficult to recognize the need for evaluation because children affected byradiation and/or chemotherapy can often think clearly and reason well and they may be
above average academically in several areas. They may fall behind their classmates,
however, on tasks that rely on processing skills, short-term memory, sequential
operations, and organizational ability (especially visual). If a learning problem is
identified, special accommodations or services can be requested to help maximize thechild’s learning potential. Many children with learning problems do extremely well inschool with appropriate accommodations.
What can be done to help with learning problems?
The first step is usually to schedule a meeting with the child’s school in order to develop
a plan. An Individualized Educational Plan (IEP) will probably be needed (see further
information about this below). Examples of strategies that are often helpful for children
with learning problems related to cancer treatment include:
·
·
·
·
·
·
·
·
·

Seating near the front of the classroom to diminish distraction.
Minimizing the amount of written work required. Children with learning
difficulties are often better able to demonstrate their knowledge verbally rather
than in written form.
Use of tape-recorded (audio) textbooks.
Tape-recording classroom lectures instead of taking notes.
Use of a computer keyboard instead of handwriting.
Use of a calculator for math.
Modification of test requirements, including extending or eliminating time limits
and avoiding computerized answer sheets (such as “scan sheets” or“bubbles”).
Assignment of a classroom aide.
Extra help with math, spelling, reading, and organizational skills.

Legal rights related to appropriate public education (in the United States)
In the United States, three public laws protect rights of people with disabilities, including
learning problems related to cancer treatment. These laws are:
The Americans with Disabilities Act (ADA)
This law protects against discrimination in employment, transportation,communication, government and public accommodations for people with disabilities.
Children who have had cancer are protected from discrimination under this law.

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Healthy living after treatment for childhood cancer

School and Learning Issues

4

The Individuals with Disabilities Education Act (IDEA)IDEA requires that every public school must provide free and appropriate education in
the least restrictive environment to all eligible individuals between the ages of 3 and21 years. This means that for children who qualify, the school must provide (free ofcharge) special education programs, speech therapy, occupational therapy, physicaltherapy, psychological services, augmentative communication techniques andtechnology, and other interventions as needed to help the child learn. The major
provisions of these laws are as follows:· All children, regardless of disability, are entitled to a free and appropriate
public education and necessary related services. Schools are required toprovide an individually designed instructional program for every eligible
child, including early intervention programs for at-risk infants and toddlers.
· Children will receive fair testing to determine if they need special education
services.
· Parents of children with disabilities may participate in the planning anddecision-making for their child’s special education.
· Children with disabilities will be educated in the least restrictive
environment, usually with children who are not disabled.
· Parents have the right to challenge the decisions of the school system, withdisputes being resolved by an impartial third party.
See http://www.ed.gov/offices/OSERS/IDEA/ for the full text of the IDEA act, withrelated information and updates.
The Rehabilitation Act (“Section 504”)
Childhood cancer survivors may also be eligible for services and accommodations
under Section 504 of the federal Rehabilitation Act. This law applies when the childdoes not meet the eligibility requirements for specially designed instruction, but stillneeds accommodations to perform successfully in school. For example, special
accommodations to address health needs can include a water bottle on the desk,
additional time to get to class, more time to finish written assignments, or eliminationof timed test requirements.
These laws cover survivors of cancer whose medical problems affect theireducational performance, under the categories known as “other health impaired”(OHI), “traumatically brain injured,” or “learning disabled.” Special education services
are also available for children with visual or hearing impairments or if the child’s
medical condition limits energy, alertness, or strength. Many survivors do not needspecial help in school, but those who do have a legal right to it.
If special educational services are needed, how can they be obtained?
Several steps are necessary in order to obtain specialized educational services: The
steps needed are: (1) referral, (2) evaluation, (3) eligibility, (4) developing an
individualized education plan (IEP) and (5) annual review.
Referral: Parents, teachers, or healthcare providers can make a referral by
writing to the school principal to request special education testing. The request
should state that the child is “health impaired” due to treatment for cancer,

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Healthy living after treatment for childhood cancer

School and Learning Issues

5

provide an outline of relevant problems, and request assessments and an IEP
meeting.
Evaluation: Once the referral is made, an evaluation is necessary to determine if
the child needs additional help, and if so, what types of help would be mostbeneficial. Neuropsychological testing (if not yet performed) should be done at
this time.
Eligibility: After the evaluation, a conference is held to discuss the results andreach conclusions about what actions will be necessary in the future.
Individualized Education Plan (IEP): This is a written document describing thespecial education program and any other related services specifically designed tomeet the individual needs of the child identified with learning problems. Parents
and professional educators develop it together. Any specific accommodations
needed by the child should be included.
Annual Review: The written IEP plan should be reviewed and updated annuallyto assure that it continues to meet the child’s educational needs.
Early intervention services for preschoolers
Federal law also mandates early intervention services for disabled infants and toddlers,and in some cases, children at risk of having developmental delays. Infants, toddlers, orpreschoolers with cancer may be eligible for these services in order to avoid
developmental delays caused by cancer treatments. These services are administeredeither by the school system or the state health department. You can find out which
agency to contact by asking the hospital social worker or by calling the special education
director for your school district. The law requires services not only for the infants orpreschoolers, but for the family as well. Therefore, instead of an IEP, an Individualized
Family Service Plan (IFSP) is developed.
Services for older students
Transition planning (for college or job training) should begin in the early years of middle
school, when the student’s peers are beginning to gain work skills and amass credits
toward high school graduation. For some survivors, extra support will be needed to help
make the transition from high school to adulthood go smoothly. The written transition
plan is contained in the Individual Transition Plan (ITP). Students planning to attend
trade school, a two-year community college program, or a four-year college program
need information far in advance regarding which high school courses will be required forentry. This is especially important for those students with disabilities who carry a lightercourse load, as they may need to make up some credits in summer school or via
correspondence courses.
Transition programs should address the move from high school to trade school,community college, or a four-year college program. Students are eligible for publicly
funded education and/or services until age 22 if needed. Tuition in some programs may
be covered for some students, in full or in part. Special education services and help forstudents with learning disabilities are available on campus and in the dormitories atmany colleges.

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Healthy living after treatment for childhood cancer

School and Learning Issues

6

Additional information from the National Information Center for Children and Youth with
Disabilities (phone: 1-800-695-0285, website: www.nichcy.org).

Adapted by Wendy Landier, CPNP, March 2003, from “Cognitive Late Effects in Leukemia
Survivors” by Nancy Keene and Kevin Oeffinger MD, Candlelighters Quarterly, Summer 2001,
and “Cognitive Late Effects to the Brain, Part II”, by Nancy Keene and Kevin Oeffinger MD,
Candlelighters Quarterly, Fall 2001, with permission from Candlelighters Childhood Cancer
Foundation (phone: 800-366-2223, internet: www.candlelighters.org.)
Nancy Keene is co-author of Childhood Cancer Survivors: A Practical Guide to Your Future(O’Reilly & Associates, Sebastopol, CA, 2000)
Kevin Oeffinger, MD directs the After the Cancer Experience Young Adult Program for childhood
cancer survivors and is a Professor at the University of Texas Southwestern Medical Center in
Dallas, TX
Wendy Landier, RN, MSN, CPNP, CPON, is a pediatric nurse practitioner and coordinates theSurvivorship Clinic at City of Hope National Medical Center in Duarte, CA

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Healthy living after treatment for childhood cancer

Thyroid Problems
Version 1.0 – March 2003

Thyroid Problems After Childhood Cancer
Treatment for childhood cancer sometimes damages the thyroid gland. Fortunately, lateeffects to the thyroid gland are usually very easy to treat. It is therefore important to findout if you are at risk so that problems can be identified early and treated appropriately.
What is the thyroid gland?
The thyroid is a small butterfly-shaped gland located in front of the trachea (windpipe) in
the lower part of the neck. It is a very sensitive gland that enlarges and becomes more
active during puberty, pregnancy, or times of great stress. It also alters its size andshape during women’s menstrual cycles.

Healthy living after treatment for childhood cancer

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Some glands produce chemical messengers, called “hormones,” that travel throughout
the body to coordinate complicated processes such as growth, puberty, and reaction tostress. Disruptions in the balance of these chemical messengers can profoundly affectboth health and quality of life.
Two hormones secreted by the thyroid gland, thyroxine (T4) and triiodothyronine (T3),have far-reaching effects on almost all tissues in the body and are intimately involved inphysical growth, metabolism, and mental development. Basically, the thyroid hormones,
T3 and T4, can be thought of as regulators of metabolism. Thus, when the thyroid
hormones are low, the body’s metabolism slows, resulting in fatigue, a lowered heart
rate and blood pressure, slowing of the intestines (leading to constipation), and aconstant feeling of being cold. On the other hand, when one or both of the thyroid
hormone levels is high, the body’s metabolism is increased, resulting in an increased
heart rate and blood pressure, increased activity of the intestines (leading to diarrhea),
and a constant feeling of being hot.
The pituitary, a gland in the brain, makes a chemical called thyroid-stimulating hormone(TSH), which travels in the bloodstream to the thyroid. As you might guess from thename, thyroid-stimulating hormone stimulates the thyroid gland to make the thyroid
hormones T3 and T4. When levels of T3 and T4 are low, then the brain increases the
production of TSH, which in turn stimulates the thyroid gland to produce more T3 andT4. Conversely, if the level of either T3 or T4 is too high, the brain senses this anddecreases the production of TSH, which leads to less production of T3 and T4.
The possible late effects
Damage to the thyroid gland resulting from childhood cancer therapy is usually the
result of radiation to the brain or neck. Several different types of thyroid problems candevelop.
Primary hypothyroidism. (primary = damage to the thyroid gland; hypo = low;
thyroidism = disease of the thyroid). In this type of hypothyroidism, the TSH is elevatedin response to low levels of thyroid hormone (T3 and T4), resulting from direct damage
to the thyroid gland.

Thyroid Problems 2

Central hypothyroidism. (central = damage in the pituitary gland/brain). In this type of
hypothyroidism, both the TSH and T4 levels are low due to damage to the thyroid’scontrol center (pituitary gland) in the brain.
Compensated hypothyroidism. This occurs when the thyroid is working too hard trying
to maintain the correct hormone levels. There are usually no symptoms, but blood tests
show normal T4 with slightly elevated TSH levels. An over-stimulated thyroid gland is atincreased risk for developing tumors, both benign and malignant. Survivors withcompensated hypothyroidism are sometimes given supplemental thyroid hormone toallow the gland to rest.
Hyperthyroidism. (hyper = high) This occurs when too much T3 or T4 is produced,
causing the body to use energy faster than it should.
Thyroid nodules and thyroid cancer. Radiation to the neck can cause abnormal
growths (nodules) or cancer of the thyroid gland.
What are the symptoms of thyroid damage?
Signs and symptoms of an under active thyroid (hypothyroidism) can include:
·
·
·
·
·
·
·
·
·
·
·
·
·
·
·
·
·
·
·

Fatigue or lethargy
HoarsenessDifficulty concentrating
Depression or mood changes
Constipation
Weakness
Intolerance to cold
Swelling around the eyes
Poor growth
Delayed puberty
Puffy face and hands
Weight gain
Dry or rough skin
Brittle hair
Joint or muscle aches
Slow heart rate
Low blood pressure
High cholesterol
Decreased tolerance for exercise

Signs and symptoms of an overactive thyroid (hyperthyroidism) can include:
·
·
·
·
·

Nervousness or anxiety
Difficulty concentrating
Fatigue
Muscle weakness or tremor
Rapid or irregular heartbeat

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Healthy living after treatment for childhood cancer

Thyroid Problems 3

·
·
·
·
·
·
·
·

Excessive perspiration
Heat intolerance
Diarrhea
Weight loss
Menstrual irregularities
Protruding eyes
Tenderness in the neck
Decreased tolerance for exercise

Thyroid cancer is generally a slow-growing cancer with few signs or symptoms. Usually,a painless, hard mass (lump) in the thyroid gland can be felt. One might also experiencehoarseness, problems with swallowing, enlarged lymph nodes in the neck and difficulty
breathing.
Who is at risk?
People who received radiation that may have affected the thyroid gland directly are at
risk for primary hypothyroidism, compensated hypothyroidism, hyperthyroidism, thyroid
nodules, and/or thyroid cancer. The following radiation fields have the potential to impact
the thyroid gland directly:
·
·
·
·
·
·

Neck (cervical or mantle)
Head/brain (cranial)
Spine
Nose, mouth, and/or throat (nasopharyngeal, oropharyngeal)
Chest (mediastinal, whole lung)
Total body irradiation (TBI)

People who received radiation that may have affected the pituitary gland in the brain are
at risk for central hypothyroidism. The following radiation fields have the potential toimpact the pituitary gland:
·
·
·
·
·

Head/brain (cranial)
Eye/orbit
Ear/infratemporal region (midfacial area behind the cheekbones)
Nose, mouth, and/or throat (nasopharyngeal, oropharyngeal)
Total body irradiation (TBI)

Female gender, higher radiation dose, and treatment at a young age also increase thelikelihood of developing a thyroid problem after childhood cancer treatment. Thyroid
dysfunction can occur soon after radiation, but generally does not occur until several
years later. If treated promptly, thyroid problems are easily managed.
What follow up is needed for those at risk?
TSH and Free T4 levels should be checked (by blood test) every year and any time
symptoms develop. During yearly follow-up visits, the thyroid gland should be palpated(felt by hand) and growth for children and teens should be plotted on a growth chart.
During periods of rapid growth, healthcare providers may recommend more frequent

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Healthy living after treatment for childhood cancer

Thyroid Problems 4monitoring of thyroid levels. Thyroid problems can occur years or decades after cancer
treatment, so a yearly check is necessary for the rest of your life if you are at risk.
Female 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, because mothers with thyroid disease have a higher
chance of having babies with neurological defects. It is also important to monitor thyroid
levels periodically during pregnancy.
How is damage to the thyroid treated?
Treatment for thyroid problems is generally easy and effective. If problems with thyroid
levels are identified, you may be referred to an endocrinologist (hormone specialist) for
continuing treatment. If a lump is detected on the thyroid, you may be referred to asurgeon or other specialist for evaluation and management.
Primary hypothyroidism (high TSH, low or normal T4): Daily treatment with synthetic
thyroid hormone (levothyroxine) in pill form is required. Treatment is for life. Stopping the
medication will result in a recurrence of the symptoms of hypothyroidism.
Compensated hypothyroidism (mildly elevated TSH, normal T4): Daily treatment withlevothyroxine (pills) may be used to suppress an overactive gland.
Central hypothyroidism (low TSH, low T4): Daily treatment with levothyroxine.
Hyperthyroidism (low TSH, high T3 or T4): The overproduction of the thyroid
hormones, T3 or T4, can cause life-threatening changes to the body, so moreaggressive therapies are required to make the thyroid produce less thyroid hormone, or
to completely stop thyroid hormone production. There are three options to treat
hyperthyroidism:· Medication that prevents thyroid hormone production (generally only atemporary treatment).
· Surgery to remove most of the gland.
· Thyroid ablation (destroying the hormone-producing cells in the gland bydrinking a radioactive liquid called I-131).
The goal of treatment for hyperthyroidism is to make the patient either euthyroid (normal
thyroid level) or hypothyroid (low thyroid level), which can then be treated with a daily pillof levothyroxine.
Thyroid nodules: People with nodules detected by palpation need additional testing.
This is generally done with an ultrasound (picture made using sound-waves) and biopsy(sampling the thyroid tissue to check for cancer cells).
Thyroid cancer: Thyroid cancer is usually very treatable. Depending upon the type andstage of thyroid cancer, treatment generally includes surgery to remove almost all of the

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Thyroid Problems 5

gland followed by thyroid gland ablation (destroying any remaining thyroid tissue by
drinking a radioactive liquid called I-131). The person then takes daily levothyroxine pills
and gets periodic check ups.
Thyroid problems are common in childhood cancer survivors who had head or neckradiation. However, treatment is generally easy and effective. Be sure to discuss yourthyroid gland with your healthcare provider at your yearly follow-up visits.

Adapted by Wendy Landier, CPNP, March 2003, from “Late Effects to the Thyroid Gland” byNancy Keene and Kevin Oeffinger MD, Candlelighters Quarterly, Spring 2001, with permission
from Candlelighters Childhood Cancer Foundation (phone: 800-366-2223, internet:
www.candlelighters.org).
Nancy Keene is co-author of Childhood Cancer Survivors: A Practical Guide to Your Future(O’Reilly & Associates, Sebastopol, CA, 2000)
Kevin Oeffinger, MD directs the After the Cancer Experience Young Adult Program for childhood
cancer survivors and is a Professor at the University of Texas Southwestern Medical Center in
Dallas, TX
Wendy Landier, RN, MSN, CPNP, CPON, is a pediatric nurse practitioner and coordinates theSurvivorship Clinic at City of Hope National Medical Center in Duarte, CA

Health Link
Healthy living after treatment for childhood cancer

Single Kidney Precautions
Version 1.0 – March 2003

PRECAUTIONS FOR PEOPLE WITH SINGLE KIDNEY¨ To avoid injury to the remaining kidney, it is best NOT toparticipate in martial arts and boxing. (If you insist on
participating in these sports, USE A KIDNEY GUARD).
¨ USE A KIDNEY GUARD for other sports such as football,soccer, baseball, basketball, etc.
¨ DRINK PLENTY OF WATER, WATER, WATER, especiallywhen playing sports, while out in the sun, and during hot
weather.

Healthy living after treatment for childhood cancer

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¨ CALL THE DOCTOR IMMEDIATELY if you have symptoms ofa possible urinary tract infection (burning when you urinate,having to urinate more frequently than usual, having thesensation when you have to urinate that you need to urinate
immediately—you cannot “wait” or “hold it”).
¨ DO NOT TAKE ANY NEW MEDICINES (prescription, over-thecounter, or herbal) WITHOUT CHECKING WITH YOURDOCTOR AND/OR PHARMACIST—and make sure they knowthat you only have one kidney.
¨ DO NOT TAKE any non-steroidal anti-inflammatory drugs, (forexample, ASPIRIN, BUFFERIN, ASCRIPTIN, IBUPROFEN,
ADVIL, MOTRIN, ALEVE, NAPROXEN, NUPRIN), unless yourdoctor advises you to.
¨ Remind all healthcare providers that you had a nephrectomy(kidney removal) and the reason why.
¨ Have a health checkup at least once a year that includes a
blood pressure measurement, a urine test for protein, and ablood test measuring kidney function.