Long-Term Follow-Up Guidelines
for Survivors of Childhood, Adolescent,and Young Adult Cancers
Version 1.2 – March 2004

Copyright 2004 © Children’s Oncology Group. All rights reserved worldwide.

Abstract - Page 1
Version 1.2 – March 2004

Abstract – Version 1.2
The Children’s Oncology Group Long-Term Follow-Up Guidelines
for Survivors of Childhood, Adolescent, and Young Adult Cancers
Release date:

March 2004

Status:Updated from Version 1.1 (name change and other minor modifications)

Overview:

These risk-based, exposure-related clinical practice guidelines provide recommendations
for screening and management of late effects in survivors of pediatric malignancies.
(“Pediatric malignancies” are defined as those malignancies commonly associated with thepediatric population that may arise during childhood, adolescence or young adulthood.) A
complementary set of patient education materials, known as “Health Links” accompany theguidelines in order to enhance patient follow-up visits and broaden the application of theseguidelines. The information provided in these guidelines is important for primary careproviders in the fields of pediatrics, oncology, internal medicine, family practice, andgynecology, as well as subspecialists in many fields. Implementation of these guidelines isintended to increase awareness of potential late effects and to standardize and enhancefollow-up care provided to survivors of pediatric malignancies throughout the lifespan.

Source:The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors ofChildhood, Adolescent, and Young Adult Cancers, and related Health Links, can be
downloaded in their entirety at www.survivorshipguidelines.org.

DISCLAIMER AND NOTICE OF PROPRIETARY RIGHTS
Introduction to Late Effects Guidelines and Health Links: The “Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult
Cancers” and accompanying “Health Links” were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing
Discipline.
For Informational Purposes Only: The information and contents of each document or series of documents made available from by the Children’s Oncology
Group relating to late effects of cancer treatment and care or containing the title "Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, andYoung Adult Cancers" or the title “Health Link”, whether available in print or electronic format (including any digital format, e-mail transmission, or download fromthe website), shall be known hereinafter as “Informational Content”. All Informational Content is for informational purposes only. The Informational Content is notintended to substitute for medical advice, medical care, diagnosis or treatment obtained from a physician or health care provider.
To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with anyquestions you may have regarding a medical condition and do not rely on the Informational Content. The Children’s Oncology Group is a researchorganization and does not provide individualized medical care or treatment.
To physicians and other healthcare providers: The Informational Content is not intended to replace your independent clinical judgment, medical advice, or
to exclude other legitimate criteria for screening, health counseling, or intervention for specific complications of childhood cancer treatment. Neither is theInformational Content intended to exclude other reasonable alternative follow-up procedures. The Informational Content is provided as a courtesy, but
not intended as a sole source of guidance in the evaluation of childhood cancer survivors. The Children’s Oncology Group recognizes that specificpatient care decisions are the prerogative of the patient, family, and healthcare provider.
No endorsement of any specific tests, products, or procedures is made by Informational Content, the Children’s Oncology Group, or affiliated party or member of
the Children’s Oncology Group.
No Claim to Accuracy or Completeness: While the Children's Oncology Group has made every attempt to assure that the Informational Content is accurate
and complete as of the date of publication, no warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or
timeliness of such Informational Content.
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Informational Content, all officers, directors, representatives, employees, agents, and members of the Children’s Oncology Group and affiliated organizations; (ii)by using, reviewing, or accessing the Informational Content, you agree, at your own expense, to indemnify, defend and hold harmless Indemnified Parties from any
and all losses, liabilities, or damages (including attorneys' fees and costs) resulting from any and all claims, causes of action, suits, proceedings, or demands
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Long-Term Follow-Up Guidelines for Survivors ofChildhood, Adolescent, and Young Adult Cancers
Version 1.2 – March 2004

Contributors- Task Force- Panel of Experts- Reviewers- Health Link Authors

Long-Term Follow-Up Guidelines
Task ForceThe Children’s Oncology Group Nursing Discipline and Late Effects Committee developed the Children’s Oncology Group LongTerm Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers collaboratively through the efforts ofthe 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, Tennessee
Wendy Landier, RN, MSN, CPNP, CPON®
Chair – COG Nursing Clinical Practice Subcommittee
Pediatric Nurse Practitioner - Survivorship Clinic
City of Hope Comprehensive Cancer Center
Duarte, California
Debra Eshelman, RN, MSN, CPNP
Late Effects Section Leader– COG Nursing Clinical Practice Subcommittee
Pediatric Nurse Practitioner
After the Cancer Experience (ACE) ProgramChildren’s Medical Center – Dallas
Dallas, Texas
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, Georgia

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, Tennessee
Teresa Sweeney, RN, MSN, CPNP
Pediatric Nurse Practitioner
After Completion of Therapy Clinic
St. Jude Children’s Research Hospital
Memphis, TennesseePanel of Experts 1

Long-Term Follow-Up Guidelines
Panel of Experts
The following members of the Children’s Oncology Group Late Effects Committee participated in comprehensive review and scoringof the Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult
Cancers:
Smita Bhatia, MD, MPH
Chair – COG Late Effects Committee
Director, Epidemiology and Outcomes Researchand Survivorship Clinic
Department of Pediatric Hematology, Oncology,
and Bone Marrow Transplant
City of Hope Comprehensive Cancer Center
Duarte, CA
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
F. Daniel Armstrong, PhD
Professor and Associate Chair, Department of Pediatrics
Director, Mailman Center for Child Development
University of Miami School of Medicine
Miami, FL
Julie Blatt, MD
Professor of Pediatrics
Division of Pediatric Hematology-Oncology
University of North Carolina
Chapel Hill, NC

Louis 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
Joan Darling, PhD
COG Patient Advocacy Committee Representative
Lincoln, NE
Carolyn R. Freeman, MB, BS, FRCPC
Professor and Director
Department 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 Comprehensive Cancer Center
Duarte, CA
Neyssa Marina, MD
Professor of Pediatrics
Director, Long-Term Survivors Clinic
Department of Pediatrics
Stanford University Medical Center
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 School of Medicine
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

Long-Term Follow-Up Guidelines
Reviewers
The following individuals participated in the review process during development of the Children’s Oncology Group Long-Term FollowUp Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers:
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
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

Hope Anne Castoria, BSN, RN, CPON®
Tomorrow Children’s InstituteHackensack University Medical Center
Hackensack, NJ

Smita Bhatia, MD, MPH
Department of Pediatric Hematology/Oncology andBone Marrow Transplant
City of Hope Comprehensive Cancer Center
Duarte, CA

Laurie Cohen, MD
Division of Endocrinology
Dana Farber Cancer InstituteBoston, MA

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, WILouis 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

Nina Kadan-Lottick, MD, MSPH
Department of Pediatrics
Yale University School of Medicine
New Haven, CT

Patty Feist
Patient Advocate
Boulder, CO

Nancy Keene
Patient Advocate
Annandale, VA

Paul Fisher, MD
Neurology and Pediatrics
Stanford University Medical Center
Stanford, CA

Lisa B. Kenney, MD, MPH
Perini Quality of Life Clinic
Dana-Farber Cancer InstituteBoston, MA

Carolyn R. Freeman, MB, BS, FRCPC
Department of Radiation Oncology
McGill University Health Centre
Montreal, Quebec, Canada

Winnie Kittiko, RN, MS
COG Patient Advocacy Committee
Douglasville, GA

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
Mark Greenberg, MB, BCh
Department of Haematology/Oncology
Hospital for Sick Children
Toronto, Ontario, Canada
Wendy Hobbie, MSN, RN, PNP
Division of Oncology
Children’s Hospital of Philadelphia
Philadelphia, PA

Margaret Kulm, RN, MA
COG Patient Advocacy Committee
Port Ludlow, WA
Missy Layfield
COG Patient Advocacy Committee
Cedar Falls, IA
Marcia Leonard, RN, CPNP
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
Louis A. Leone, Esq.
COG Patient Advocacy Committee
Walnut Creek, CA

Reviewers 3

Neyssa Marina, MD
Pediatric Hematology Oncology
Stanford University Medical Center
Stanford,CA

Raymond Mulhern, PhD
Division of Behavioral Medicine
St. Jude Children's Research Hospital
Memphis, TN

Leonard Mattano, MD
Pediatric Hematology/Oncology
Kalamazoo Center for Medical Studies
Michigan State University
Kalamazoo, MIJohn R. Mussman
COG Patient Advocacy Committee
Chicago, IL

Anne Mauck, RN, MSN, CPNP
Pediatric Hematology/Oncology
Virginia Commonwealth University Health System
Richmond, VA

Michael Neel, MD
Division of Orthopedics
St. Jude Children's Research Hospital
Memphis, TNCharlene Maxen, RN, CNP, CPON®
Hematology/Oncology
Childrens Hospital Medical Center - Akron
Akron, OH

Joseph P. Neglia, MD, MPH
Department of Pediatrics
Division of Hematology, Oncology,
Blood and Marrow Transplantation
University of Minnesota School of Medicine
Minneapolis, MN

Lillian Meacham, MD
Division of Pediatric Endocrinology
Children’s Healthcare of Atlanta
Atlanta, GA

Mary Nelson, RN, MS, CPNP, CPON®
Childrens Center for Cancer and Blood Diseases
Childrens Hospital Los Angeles
Los Angeles, CA

Anna T. Meadows, MD
Division of Oncology
Children's Hospital of Philadelphia
Philadelphia, PA

Kevin Oeffinger, MD
Department of Family Practice and Community Medicine
University of Texas Southwestern Medical School
Dallas, TX

Grace Powers Monaco, JD
Childhood Cancer Ombudsman Program
Heathsville, VA

Roger Packer, MD
Department of Neurology
Children's National Medical Center
Washington, DC

Reviewers 4

Arnold Paulino, MD
Department of Radiation Oncology
Children’s Healthcare of Atlanta – Emory Clinic
Atlanta, GA

Cindy Schwartz, MD
Pediatric Oncology
Johns Hopkins Hospital
Baltimore, MD

Rebecca D. Pentz, PhD
COG Patient Advocacy Committee
Atlanta, GA

Susan Shaw, RN, MS, PNP
Center for Children’s Cancer and Blood Disorders
State University of New York at Syracuse
Syracuse, NY

Leslie L. Robison, PhD
Department of Pediatrics
University of Minnesota Cancer Center
Minneapolis, MNDavid Rosenthal, MD
Department of Pediatrics/Cardiology
Lucile Packard Children’s Hospital at Stanford
Palo Alto, CACharles 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

Kathy Ruble, RN, MSN, CPNP, AOCN®
Pediatric Oncology
Johns Hopkins Hospital
Baltimore, MD

Deborah Waber, PhD
Department of Psychiatry
Boston Children's Hospital
Boston, MA

Kathleen Ruccione, RN, MPH, FAAN, CPON®
Childrens Center for Cancer and Blood Diseases
Childrens Hospital Los Angeles
Los Angeles, CA

Susan L. Weiner, PhD
The Children’s Cause, Inc.
Silver Spring, MD

Jean Sanders, MD
Pediatric Marrow Transplantation
Children’s Hospital Regional Medical CenterSeattle, WA

Fran Wiley, RN, MN
COG Patient Advocacy Committee
Los Angeles, CA

Reviewers 5

Suzanne L. Wolden, MD
Department of Radiation Oncology
Memorial Sloan-Kettering Cancer Center
New York, NY
Catherine L. Woodman, MD
COG Patient Advocacy Committee
Iowa City, IA
Lise Yasui
COG Patient Advocacy Committee
Philadelphia, PA

Joseph Zins, PhD
COG Patient Advocacy Committee
Cincinnati, OH
Octavio Zavala
COG Patient Advocacy Committee
Los Angeles, CA

Health Link Authors 1

Long-Term Follow-Up Guidelines
Health Link Authors
The following individuals participated in writing the patient education materials (Health Links) for the Children’s Oncology Group
Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers:
Julie Blatt, MD
Division of Pediatric Hematology-Oncology
University of North Carolina
Chapel Hill, NC

Melissa M. Hudson, MD
After Completion of Therapy Clinic
St. Jude Children’s Research Hospital
Memphis, TN

Debra Eshelman, RN, MSN, CPNP
After the Cancer Experience (ACE) ProgramChildren’s Medical Center – Dallas
Dallas, TX

Asako Komiya, RN, MSN, PNP
Department of Pediatric Hematology/Oncology
City of Hope Comprehensive Cancer Center
Duarte, CA

Sarah Friebert, MD
Division of Hematology/Oncology
Childrens Hospital Medical Center of Akron
Akron, OH

Wendy Landier, RN, MSN, CPNP, CPON®
Department of Pediatric Hematology/Oncology
City of Hope Comprehensive Cancer Center
Duarte, CA

Debra L. Friedman MD, MS
Pediatric Hematology-Oncology
Children's Hospital and Regional Medical CenterSeattle, WA

Deborah Lafond, MS, RNCS, PNP, CPON®
Hematology/Oncology
Children’s National Medical Center
Washington, DC

Sharon Frierdich, RN, MS, CPNP
Pediatric Hematology/Oncology
University of Wisconsin Children’s Hospital
Madison, WI

Marcia Leonard, RN, CPNP
Pediatric Hematology/Oncology and Long-Term Follow-Up Clinic
C.S. Mott Children’s Hospital
Ann Arbor, MI

Allison Hester, RN, MSN, CPNP
After Completion of Therapy Clinic
St. Jude Children’s Research Hospital
Memphis, TN

Anne Mauck, RN, MSN, CPNP
Pediatric Hematology/Oncology
Virginia Commonwealth University Health System
Richmond, VA

Health Link Authors 2

Charlene Maxen, RN, CNP, CPON®
Division of Hematology/Oncology
Childrens Hospital Medical Center of Akron
Akron, OH

Susan Shannon, RN, MSN, CPNP, CPON®
“STAR” Late Effects Program
Miller Children’s HospitalLong Beach, CA

Katherine Myint-Hpu, MSN, MPH, PNP
Leukemia/Lymphoma Clinic
Georgetown University Hospital
Washington, DC

Teresa Sweeney, RN, MSN, CPNP
After Completion of Therapy Clinic
St. Jude Children’s Research Hospital
Memphis, TN

Kathy Ruble, RN, CPNP, AOCN®
Long Term Follow-Up Program
Johns Hopkins University
Baltimore, MD

Sally Wiard, MSW, LCSW
After Completion of Therapy Clinic
St. Jude Children’s Research Hospital
Memphis, TN

Margery Schaffer, RN, MSN, CPNP
Department of Hematology/Oncology
Children’s Medical Center
Dayton, OH

Long-Term Follow-Up Guidelines for Survivors ofChildhood, Adolescent, and Young Adult Cancers
Version 1.2 – March 2004

Introduction &Instructions for UseIntroduction - Page 1
Version 1.2 – March 2004

Introduction – Version 1.2
The Children’s Oncology Group Long-Term Follow-Up Guidelines
for Survivors of Childhood, Adolescent, and Young Adult Cancers
Overview:

The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood,
Adolescent, and Young Adult Cancers (COG-LTFU Guidelines) are risk-based, exposure-related
clinical practice guidelines for screening and management of late effects resulting fromtherapeutic exposures used during treatment for pediatric malignancies. These guidelines
represent a statement of consensus from a panel of experts in the late effects of pediatric cancer
treatment. The guidelines are both evidence-based (utilizing established associations between
therapeutic exposures and late effects to identify high-risk categories) and grounded in thecollective clinical experience of experts (matching the magnitude of the risk with the intensity ofthe screening recommendations). Since therapeutic interventions for a specific pediatricmalignancy may vary considerably based on the patient’s age, presenting features, and treatmentera, a therapy-based design was chosen to permit modular formatting of the guidelines by
therapeutic exposure. The guidelines are therefore organized according to therapeutic agent,and cross-referenced to other topics with related toxicities. Importantly, the recommended
periodic screening underscores the use of a thorough history and physical examination (H&P) as
the primary assessment for cancer-related treatment effects. In this regard, 90 (88%) of thescreening recommendations outlined for the 102 therapeutic exposures in the COG-LTFU
Guidelines comprise assessments derived primarily from the H&P, with 48 (47%) relying solely on
the H&P and 21 (21%) relying on the H&P plus a baseline diagnostic study (e.g., lab, imaging),
whereas 31 (30%) include periodic laboratory, diagnostic imaging, or other testing. Interventions
exceeding minimal screening are provided for consideration in individuals with positive screening
tests. Medical citations supporting the association of each late effect with a specific therapeutic
exposure are indexed by section number and listed in the reference section. Patient educationmaterials complementing the guidelines have been organized into Health Links that feature healthprotective counseling on 33 topics, enhancing patient follow-up visits and broadening applicationof the guidelines.

Goal:

Implementation of these guidelines is intended to increase quality of life and decrease
complication-related healthcare costs for pediatric cancer survivors by providing standardized andenhanced follow-up care throughout the lifespan that (a) promotes healthy lifestyles, (b) provides
for ongoing monitoring of health status, (c) facilitates early identification of late effects, and (d)provides timely intervention for late effects.

Introduction - Page 2
Version 1.2 – March 2004

TargetPopulation:

The recommendations for periodic screening evaluations provided in the Children’s Oncology
Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult
Cancers are appropriate for asymptomatic survivors of childhood, adolescent, or young adultcancers who present for routine exposure-related medical follow-up. More extensive evaluations
are presumed, as clinically indicated, for survivors presenting with signs and symptoms
suggesting illness or organ dysfunction.

Focus:

These guidelines are intended for use beginning two or more years following the completion ofcancer therapy, and provide a framework for ongoing late effects monitoring in childhood cancer
survivors; however, these guidelines are not intended to provide guidance for follow-up of thepediatric cancer survivor’s primary disease.

Intended Users:

The COG-LTFU Guidelines were developed as a resource for clinicians who provide ongoinghealthcare to survivors of pediatric malignancies. The information within these guidelines isimportant for clinician (e.g., physicians, nurse practitioners, physician assistants, nurses) in thefields of pediatrics, oncology, internal medicine, family practice, and gynecology, as well as
subspecialists in many fields (e.g., endocrinology, cardiology, pulmonology). A basic knowledgeof ongoing issues related to the long-term follow-up needs of this patient population is assumed.
Healthcare professionals who do not regularly care for survivors of pediatric malignancies areencouraged to consult with a pediatric oncology long-term follow-up center if any questions orconcerns arise when reviewing or using these guidelines.
Although the information within the guidelines will certainly prove valuable to the survivors
themselves, at this time the only version available is targeted to healthcare professionals.
Therefore, survivors who choose to review these guidelines are strongly encouraged to do so withthe assistance of a healthcare professional knowledgeable about long-term follow-up care forsurvivors of childhood, adolescent, and young adult cancers. This is important in order to put therecommendations in perspective, avoid over-testing, address potential anxieties, and provide acomprehensive evaluation of the survivor’s health status. 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.

Developer:

The COG-LTFU Guidelines were developed as a collaborative effort of the Children’s Oncology
Group Nursing Discipline and the Late Effects Committee. All Children’s Oncology Group
members have complied with the COG conflict of interest policy, which requires disclosure of any
potential financial or other conflicting interests.

Introduction - Page 3
Version 1.2 – March 2004

Funding
Source:This work was supported by the Children’s Oncology Group grant U10 CA098543 from the
National Cancer Institute.

Evidence
Collection:

Pertinent information from the published medical literature over the past 20 years (as of
September 2003) was retrieved and reviewed during the development of these guidelines. For
each therapeutic exposure, a complete search was performed via MEDLINE (National Library ofMedicine, Bethesda, MD). Keywords included “childhood cancer therapy” and “complications”
combined with keywords for each therapeutic exposure. References from the bibliographies of
selected articles were used to broaden the search.

Methods:

The leadership of the Children’s Oncology Group Late Effects Committee and Nursing Discipline
appointed a 7-member task force, with representation from the Late Effects Committee, Nursing
Discipline, and Patient Advocacy Committee. The task force was convened to review andsummarize the medical literature and develop a draft of clinical practice guidelines to direct longterm follow-up care for pediatric cancer survivors. The task force followed a modified version of
the guideline development process established by the National Comprehensive Cancer Network(NCCN), integrating available literature with expert opinion using reiterative feedback loops.
The original draft went through several iterations within the task force prior to initial review.
Multidisciplinary experts in the field, including nurses, physicians (pediatric oncologists and othersubspecialists), patient advocates, behavioral specialists, and other healthcare professionals,
were then recruited by the task force to provide an extensive, targeted review of the draft,including focused review of selected guideline sections. Revisions were made based on theserecommendations. The revised draft was then sent out to additional multidisciplinary experts forfurther review. A total of 62 individuals participated in the review process.
The guidelines subsequently underwent comprehensive review and scoring by a 16-member
panel of experts in the late effects of pediatric malignancies, comprised of multidisciplinary
representatives from the COG Late Effects Committee.
In a parallel effort led by the Nursing Clinical Practice Subcommittee, complementary patient
education materials (Health Links) were developed. Each Health Link underwent two levels ofreview; first by the Nursing Clinical Practice Subcommittee to verify accuracy of content andrecommendations, and then by members of the Late Effects Committee (to provide expert
medical review) and Patient Advocacy Committee (to provide feedback regarding presentation ofcontent to the lay public).

Introduction - Page 4
Version 1.2 – March 2004

Grading Criteria:

The guidelines were scored by the multidisciplinary panel of experts using a modified version of
the National Comprehensive Cancer Network “Categories of Consensus” system. Each scorereflects the expert panel’s assessment of the strength of data from the literature linking a specificlate effect with a therapeutic exposure, coupled with an assessment of the appropriateness of thescreening recommendation based on the expert panel’s collective clinical experience. “High-level
evidence” (category 1) was defined as evidence derived from high quality case control or cohort
studies. “Lower-level evidence” (category 2A and 2B) was defined as evidence derived from nonanalytic studies, case reports, case series and clinical experience. Rather than submitting
recommendations representing major disagreements, items scored as “Category 3” were either
deleted or revised by the panel of experts to provide at least a “Category 2B” score for all
recommendations included in the guidelines.

Pre-Release
Review:

The initial version of the guidelines (Version 1.0 – Children’s Oncology Group Late Effects
Screening Guidelines) was released to the Children’s Oncology Group membership in March
2003 for a six-month trial period. This allowed for initial feedback from the COG membership,
resulting in additional review and revision of the guidelines by the Late Effects Committee prior to
public release.

Revisions:

The guidelines were released to the public (Version 1.1 – Childhood Cancer Survivor Long-Term
Follow-Up Guidelines) on the Children’s Oncology Group Website in September 2003. Following
this release, clarification regarding the applicability of the guidelines to the adolescent and young
adult populations of cancer survivors was requested. In response, additional minor modifications
were made and the title of the guidelines was changed. The current version (Version 1.2 – LongTerm Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers)
was released to the public on the Children’s Oncology Group Website in March 2004.

Plan for Updates:

Development of any clinical care guideline is a dynamic process, requiring continual review andrevision in order to keep the document current and clinically meaningful. Task forces havetherefore been organized within the COG Late Effects Committee to monitor the literature andrecommend changes to these guidelines as new information becomes available. A total of 20
task forces have been organized to focus on specific clinical topics (e.g., cardiovascular,
neurocognitive, fertility/reproductive, etc.).
Responsibilities of these task forces include
presentation of an annual report to the Late Effects Committee describing new literature, andpreparation of recommendations for guideline revisions, such as addition of agents/therapeutic
exposures, revision of risk groups, revision of screening recommendations, development and/or
modification of patient education materials, and modification of the reference list. The guidelines
will be updated at least annually to reflect changes recommended by these task forces.

Introduction - Page 5
Version 1.2 – March 2004

Clinicians are advised to check the Children’s Oncology Group website periodically for the latest
updates and revisions to the guidelines, which will be posted at www.survivorshipguidelines.org.
Definitions:“Late effects” are defined as therapy-related complications or adverse effects that persist or arise
after completion of treatment for a pediatric malignancy. “Pediatric malignancies” are defined as
those malignancies commonly associated with the pediatric population that may arise duringchildhood, adolescence or young adulthood. “Consensus” is defined as general agreement
among the panel of experts.

Recommendations Screening and follow-up recommendations are organized by therapeutic exposure and included
throughout the guidelines. Pediatric cancer survivors represent a relatively small but growing
and Rationale:
population at high risk for various therapy-related complications. Although several well-conductedstudies on large populations of childhood cancer survivors have demonstrated associations
between specific exposures and late effects, the size of the survivor population and the rate ofoccurrence of late effects does not allow for clinical studies that would assess the impact ofscreening recommendations on the morbidity and mortality associated with the late effect.
Therefore, scoring of each exposure reflects the expert panel’s assessment of the level ofliterature support linking the therapeutic exposure with the late effect coupled with an assessmentof the appropriateness of the recommended screening modality in identifying the potential lateeffect based on the panel’s collective clinical experience.
Potential Benefits
and Harms:

Potential benefits of implementing these guidelines into clinical practice include earlier
identification of and intervention for late onset therapy-related complications in this at-risk
population, potentially reducing or ameliorating the impact of late complications on the healthstatus of survivors. In addition, ongoing healthcare that promotes healthy lifestyle choices andprovides ongoing monitoring of health status is important for all cancer survivors.
Potential harms of guideline implementation include increased patient anxiety related toenhanced awareness of possible complications, as well as the potential for false-positive
screening evaluations, leading to unnecessary further workup. In addition, costs of long-term
follow-up care may be prohibitive for some patients, particularly those lacking health insurance, or
those with insurance that does not cover the recommended screening evaluations.

Patient
Preferences:

These guidelines are not intended to replace clinical judgment or to exclude other reasonable
alternative follow-up procedures. The Children’s Oncology Group recognizes that specific patientcare decisions are the prerogative of the patient, family, and healthcare provider.

Introduction - Page 6
Version 1.2 – March 2004

Implementation
Considerations:

Initial concerns regarding implementation of the COG-LTFU Guidelines include the practicality
and efficiency of applying these broad guidelines in individual clinical situations. Studies toaddress guideline implementation and refinement are a top priority of the COG Late Effects
Committee, and proposals to study feasibility of guideline use in limited institutions are currently
underway. Issues to be addressed include description of anticipated barriers to application of therecommendations in the guidelines and development of review criteria for measuring changes incare when the guidelines are implemented. Additional concerns surround the lack of current
evidence establishing the efficacy of screening for late complications in pediatric cancer survivors.
While most clinicians believe that ongoing surveillance for these late complications is important inorder to allow for early detection and intervention for complications that may arise, developmentof studies addressing the efficacy of this approach is imperative in order to determine whichscreening modalities are optimal for asymptomatic survivors.

Instructions for Use - Page 1
Version 1.2 – March 2004

Instructions for Use – Version 1.2
The Children’s Oncology Group Long-Term Follow-Up Guidelines
for Survivors of Childhood, Adolescent, and Young Adult Cancers
Using the Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent,and Young Adult Cancers
The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young
Adult Cancers are organized according to therapeutic exposures, arranged by column as follows:
Therapeutic Agent: The therapeutic intervention for malignancy, including chemotherapy, radiation therapy, surgery,blood/blood products, or hematopoietic cell transplant.
Section Number: Corresponds with Reference List and Index.
Potential Late Effects:
intervention.

Lists the most common late treatment complications associated with the therapeutic

Risk Factors: Lists host factors (e.g., age, sex, race, genetic predisposition), treatment factors (e.g., cumulative doseof therapeutic agent, mode of administration, combinations of agents), medical conditions (e.g., pre-morbid or comorbid conditions), and health behaviors (e.g., diet, smoking, alcohol use) that may increase risk of developing thecomplication.
Highest Risk: Lists conditions (host factors, treatment factors, medical conditions and/or health behaviors)
associated with the highest risk for developing the complication.
Periodic Evaluations: Recommended screening evaluations including health history, clinical exams, laboratory
evaluations, diagnostic imaging studies, psychosocial assessments, or other indicated evaluations.
Minimum Recommended Frequency: Recommended minimum frequency of periodic evaluations based on risk
factors and magnitude of risk as supported by medical literature and/or the combined clinical experience of thereviewers and panel of experts.
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 educationmaterials produced specifically to accompany this document. These Health Links are included in the Appendix andare also available on the COG website at www.survivorshipguidelines.org.
Note: Throughout the Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood,adolescence, or young adulthood. Health Links are designed to provide health information for survivors of pediatric cancer, regardless ofwhether the cancer occurred during childhood, adolescence, or young adulthood.

Instructions for Use - Page 2
Version 1.2 – March 2004

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/orreferral, and recommendations 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 such as age, gender, genetic susceptibility, personal or family history, health-related behaviors or comorbidities.
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 from cancer treatment, as well as other factors listed above (e.g., genetic
susceptibility).
Periodic Evaluations:Standard Risk: Guidelines provided under the “Standard Risk” category are per the American Cancer Society
recommendations for standard-risk populations and are included 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).
Highest Risk: Recommendations for 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 the high-risk group.
References are provided immediately following the guidelines. The Reference section contains medical citations
corresponding to each numbered section of the guidelines. Included are references that provide evidence for the
association of the therapeutic intervention 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 orderto determine the location 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 “Explanationof Scoring” following the Index.) A tabulation of the final scores is included in this packet.

Instructions for Use - Page 3
Version 1.2 – March 2004

Importance of Comprehensive Treatment Summary
The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young
Adult Cancers are based on therapeutic exposures received during cancer treatment. Availability of a comprehensive
treatment summary, including all therapeutic agents received by the survivor, is assumed. Patients who do not have acomprehensive treatment summary should be instructed to obtain one from the institution(s) where they received theirtreatment. The comprehensive treatment summary should include the following information:
Diagnosis, including site/stage, date, and relapse(s) if any
Pertinent secondary diagnoses (e.g., second malignancy, Down syndrome)
All chemotherapy agents received during treatment (including route of administration for all agents, cumulative
doses for alkylators, bleomycin, and anthracyclines, and designation of “high dose” versus “standard dose” formethotrexate and cytarabine). Cumulative doses for all other agents should be provided if available.
Radiation therapy summary for all fields, including type, site/volume, dates, total dose (in cGy), dose per fraction,and number of fractions.
Surgical procedures
Hematopoietic cell transplant(s), including type(s), date(s), conditioning regimen(s), and GVHD prophylaxis and/or
treatment
Significant complications, including treatment required
Adverse drug reactions/allergies
We are hopeful that these Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood,
Adolescent, and Young Adult Cancers will enhance the follow-up care provided to this unique group of cancer survivors.
If you have questions, suggestions, or concerns regarding use of these guidelines, please contact:
Melissa M. Hudson, MD

Wendy Landier, RN, CPNP

Vice-Chair – COG Late Effects Committee
St. Jude Children’s Research Hospital
Memphis, Tennessee(901) 495-4781
Melissa.Hudson@stjude.org

Chair – COG Nursing Clinical Practice Subcommittee
City of Hope Comprehensive Cancer Center
Duarte, California(626) 301-8426
wlandier@coh.org

Smita Bhatia, MD, MPH
Chair – COG Late Effects Committee
City of Hope Comprehensive Cancer Center
Duarte, California(626) 301-8426
sbhatia@coh.org

Long-Term Follow-Up Guidelines
for Survivors of Childhood, Adolescent,and Young Adult Cancers
Version 1.2 – March 2004
Copyright 2004 © Children’s Oncology Group. All rights reserved worldwide.

COG Follow-Up Guidelines – Page 1
Version 1.2 – March 2004

Long-Term Follow-Up Guidelines
for Survivors of Childhood, Adolescent, and Young Adult Cancers
Version 1.2 – March 2004
Therapeutic Agent
Any cancer experience
Clinician Info Link
The Children’s
Oncology Group
Long-Term Follow-Up
Guidelines apply topatients who are > 2
years after completionof therapy.

Sec
#
1

Potential Late Effects

Psychosocial Effects
Depression
Anxiety
Post-traumatic stress
Social withdrawal
Educational problems

Risk Factors

Host factors
Female gender
Family history ofdepression, anxiety,or mental illness

Highest Risk

Periodic
Evaluation

Clinical interview
Host factors
CNS cancer or
CNS-directed
therapy
Premorbid learningor emotionaldifficulties

Minimum Recommended

Frequency
YearlySocial factors
Lower household income
Lower educational
Social factors
achievement
Failure to graduate
from high school

For all patients treatedprior to 1993, pleasealso see Sections 81-83
to review screening
recommendations
related to presumed
blood/blood productexposures.

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Psychological consultation in patients
Health Link
Introduction to Long-Term with emotional difficulties related toFollow-Up after Treatment cancer experience including physicalfor Childhood, Adolescent, deformities or chronic disabilities
or Young Adult Cancer
following cancer treatment.
Consider appropriate psychotropic
Emotional Issues after
medications.
Childhood Cancer
Social work consultation.
Educational Issues
Consider evaluation of parent for postFollowing Treatment fortraumatic stress syndrome.
Childhood Cancer
Refer to school liaison in community
or cancer center (psychologist, social
Resources
worker, school counselor) to facilitate"Childhood Cancer
acquisition of educational resources.
Survivors" by Nancy
Keene, Wendy Hobbie &Kathy Ruccione
Sebastopol, CA: O'Reilly& Assoc., 2000
“Educating the Child with
Cancer” edited by Nancy
Keene. CandlelightersChildhood Cancer
Foundation, Bethesda, MD,
2003.

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

Clinical history

YearlySocial work consultation.
Health Link
Finding Appropriate
Healthcare after Childhood
CancerEvery 6 months

Health Link
Dental Health

Any Chemotherapy
Host factors
Any patient who has notdeveloped permanentdentition
Cancer treatment
Any radiation treatment
including oral cavity orsalivary glands.

Dental exam andHost factors
Younger age atcleaning
treatment,
especially < 5 years
oldRegular dental care including fluoride
applications.
Baseline panorex prior to dental
procedures to evaluate root
development.

COG Follow-Up Guidelines – Page 2
Version 1.2 – March 2004
Therapeutic Agent
Alkylating Agents
Mechlorethamine
Cyclophosphamide
Ifosfamide
Melphalan
Chlorambucil
Lomustine (CCNU)
Carmustine (BCNU)
BusulfanThiotepa
Procarbazine

Sec
#
4

Potential Late Effects

Hypogonadism
Infertility
Early menopause(females)See related topics:
Radiation – TBI,
head/brain, abdomen,
pelvis, or testes.
Orchiectomy

Non-classical alkylators:

Clinician Info Link
Extensive information
regarding infertility forphysicians and patientsavailable at American
Society for Reproductive
Medicine website:www.asrm.org

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.

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)

Highest Risk

Host factors
Male gender

Periodic
Evaluation
Females:YearlyPubertal history (onset,
tempo)
Menstrual and pregnancy
history
Physical exam includingheight, weight, Tanner
stage

Treatment factors
MOPP > 3 cycles
Busulfan > 600
mg/m2
FSH, LH, estradiol
Cyclophosphamide> 7.5 g/ m2
cumulativeor > 200 mg/kg forstem cell transplant

Any alkylators
combined with:- testicular radiation- pelvic radiation Males:
Pubertal history (onset,- TBI
tempo)

FSH, LH, testosterone

Acute myeloid leukemia
Myelodysplasia

Frequency

Baseline at about age 11 and as
clinically indicated in patients with:- Delayed puberty, irregular menses
or amenorrhea- Clinical signs and symptoms of
estrogen deficiency
For patients who received
alkylating chemotherapy for stem
cell transplant conditioning, obtainbaseline at age 8 and then yearly
until normal puberty is established.
YearlyHistory of sexual function(erections, nocturnal
emissions, libido)
History of medication use
Physical exam includingheight, weight, Tannerstage, testicular volume
by Prader orchiometry.

See also:
www.fertilehope.org

5

Minimum Recommended

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
Medical conditions:
Splenectomy (conflicting
evidence)

Baseline at about age 11 and as
clinically indicated in patients with:- Delayed puberty- Clinical signs and symptoms of
testosterone deficiency
For patients who received
alkylating chemotherapy for stem
cell transplant conditioning, obtainbaseline at age 9 and then yearly
until normal puberty is established

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Bone density evaluation for
Health Link
Female Health Issues after osteopenia/osteoporosis inChildhood Cancer
hypogonadal patients.
Refer to endocrinologist for delayedorclinical signs of puberty or
Male Health Issues after
persistently abnormal hormone levels
Childhood Cancer
Hormonal replacement therapy for
hypogonadal patients.
Counsel currently
Reproductive
endocrinology/
menstruating women atobstetrics referral for infertility
increased risk of earlymenopause to be cautious evaluation and consultation
regarding assisted reproductive
about delaying
technologies.
childbearing.
Consider 2 months off hormonal
replacement in women with ovarianCounsel regarding needfailure to assess ovarian recovery.
for contraception since
there is tremendous
individual variability ingonadal toxicity after
exposure to radiation
therapy and alkylating
agents. Recovery offertility may occur years
after therapy.
Resources:
American Society for
Reproductive Medicine
website:www.asrm.org
See also:
www.fertilehope.org

Semen analysis

As requested by patient andfor evaluation of infertility

Physical exam
CBC/differential

Yearly up to 15 years after Health Link
exposure to agent
Reducing the Risk ofSecond Cancers
Counsel to promptly
report fatigue, pallor,
petechiae, or bone pain.

Bone marrow exam as clinicallyindicated.

COG Follow-Up Guidelines – Page 3
Version 1.2 – March 2004
Therapeutic AgentBusulfan
Carmustine (BCNU)
Lomustine (CCNU)

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

7

Cataracts
See related topics:
Prednisone
Dexamethasone
Head/brain radiation
TBI

Cyclophosphamide
Ifosfamide

8

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

9

Ifosfamide

10

Bladder malignancy
See related topics:
Pelvic radiation
Renal toxicity:
Glomerular toxicity
Tubular toxicity-Renal tubular acidosis-Fanconi’s syndrome-Hypophosphatemic
rickets
See related topics:
Cisplatin/Carboplatin
Methotrexate
Abdominal/pelvic
radiation
Cystectomy
Nephrectomy

Minimum Recommended
Periodic
Health Protective
Considerations for Further Testing
Frequency
EvaluationCounselingand Intervention
Pulmonary consultation for
Treatment factors Physical exam
Treatment factors
Health Link
Yearly2Higher cumulative doses BCNU > 600 mg/m
Pulmonary Healthsymptomatic pulmonary dysfunction.
Busulfan > 500 mg
Combined with other
Influenza and Pneumovax
Baseline at entry into long- Due to the potential
pulmonary toxic therapy: (transplant doses) PFTs (including
immunization.
term follow-up and prior pulmonary toxicity of thisDLCO and- bleomycin
to general anesthesia.
spirometry) and- chest/thoracic radiation
therapy, patients who
Repeat as clinically
CXR- spinal radiation >30 Gy
desire to SCUBA diveindicated in patients with should be advised to obtain- total body irradiation
abnormal or progressive medical clearance from a
Medical conditions
pulmonary dysfunction
diving medicine specialist
Atopic history
Health behaviors
Cigarette smoking
Ophthalmology consultation if
Health Link
Treatment factors
Treatment factors Eye exam
YearlyEye Problems after
problem identified.
Combined with:
TBI given in single includingChildhood Cancer
Refer to school liaison in community- total body irradiation
daily fraction
funduscopic exam
or cancer center (psychologist, social- brain/head radiation
Radiation doseand visual acuity
worker, school counselor) to facilitate- corticosteroids> 10 Gy withpotential scatter toacquisition of educational resourceseye(s)(IEP).
Longer interval sincetreatmentCounsel to promptly report Urology consultation for culture
Treatment factors Voiding history
Treatment factors
Yearlydysuria or gross hematuria negative macroscopic hematura.
Higher cumulative doses Cyclophosphamide(decreased incidence with dose > 3 gm/m2
Urinalysis
YearlyMesna)
Combined with pelvic
radiation
Health behaviors
Alcohol use
Tobacco use
Urology consultation for culture
Treatment factors
Health Link
Urinalysis
YearlyCombined with pelvic
Reducing the Risk ofnegative macroscopic hematuria.
radiation
Second Cancers

Risk Factors

Highest Risk

Host factors
Younger age at treatment
Treatment factors
Higher cumulative dose
Combined with othernephrotoxic agents,
such as:- cisplatin/carboplatin- aminoglycosides- amphotericin- immunosuppressants- abdominal radiation
Medical conditions
Tumor infiltration of
kidney(s)Pre-existing renal
impairment
Nephrectomy ormononephricHost factors
Age < 5 years attime of treatment

Blood pressure

Yearly

BUN, creatinine,
U/A

YearlyTreatment factors
Ifosfamide dose
Na, K, Cl, CO2, Ca, Baseline electrolytes at> 60 grams/m2
entry into long-term
Mg, P04
follow-up.
If normal, repeat every
5 years.
If abnormal, repeat asclinically indicated.
Creatinine clearance

or GFR

Baseline at entry into
long-term follow-up.
If abnormal, repeat asclinically indicatedElectrolyte supplements for patientswith persistent electrolyte wasting.
Nephrology consultation for patients
See also:
Single Kidney Precautions with hypertension, proteinuria, or
progressive renal insufficiency.
Health Link
Kidney HealthCOG Follow-Up Guidelines – Page 4
Version 1.2 – March 2004
Therapeutic Agent
Heavy Metals
Cisplatin
Carboplatin

Sec
#
11

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

12

13

14

Peripheral sensory
neuropathy

Periodic
Evaluation
History andphysical exam

Host factors
Family history ofdyslipidemia
Medical conditions
Overweight/Obesity

Minimum Recommended

Frequency
YearlyHealth Protective
CounselingConsiderations for Further Testing
and Intervention

Health Link
Hearing Problems afterChildhood Cancer

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.
Consider treatment with agent
effective for neuropathic pain (e.g.,gabapentin or amitriptyline).

Treatment factors
Cumulative cisplatindose > 360 mg/m2 Audiogram orBaseline at entry into longbrainstem auditory term follow-up.
evoked response If abnormal, follow yearly
until stable.
(ABR, BAER)
If clinical evidence ofprogressive hearing loss,
obtain more frequently as
indicated until stable.

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

Clinician Info Link
Neuropathy presents aspersistent effect after
therapy and is typically notlate in onset.
Renal toxicity:
Treatment factors- Glomerular injury
Combined with other- Tubular injury
nephrotoxic agents,- Renal insufficiency
such as:- ifosfamide- aminoglycosides
See related topics:- amphotericin
Ifosfamide- immunosuppressantsMethotrexate- cyclosporine
Abdominal/pelvic- abdominal radiation
radiationtherapy
Cystectomy
Nephrectomy
Medical conditions
MononephricDiabetes mellitus
Familial hypertension
Dyslipidemia

Highest Risk

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

Yearly, until 2 to 3 years
after therapy. Monitor
yearly if symptoms
persist.

Health Link
Peripheral Neuropathy

YearlyHealth Link
Kidney HealthYearlySee also: Single Kidney
Precautions

Electrolyte supplements forpatients with persistentelectrolyte wasting.
Nephrology consultation forpatients with hypertension,
proteinuria, or progressive
renal insufficiency.

Na, K, Cl, CO2, Ca, Baseline electrolytes at
In patients with saltentry into long-term
Mg, P04
wasting tubular
follow-up.
dysfunction, educate that
If normal, repeat every
low magnesium levels
5 years.
potentiate coronary
If abnormal, repeat as
atherosclerosis.
clinically indicated.
Creatinine clearance Baseline at entry into longor GFR
term follow-up. If
abnormal, repeat asclinically indicatedLipid lowering strategies including
Fasting lipid profile Baseline, at entry into long- Health Link
term follow-up; then as per Health Promotion throughdiet, exercise, weight loss, andUnited States Preventive
Diet and Physical Activity pharmacologic therapy (e.g., statin
Task Forcetherapy).
Recommendations
http://www.ahrq.gov/clinic/pre
venix.htm
If abnormal, refer for
management of dyslipidemia

COG Follow-Up Guidelines – Page 5
Version 1.2 – March 2004
Therapeutic Agent
Antimetabolites
Cytarabine(high-dose IV)
Note: High-dose IV isdefined as any single
dose >1000 mg/m2
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).
Extent of deficit
depends on age attreatment, intensity oftreatment, and timesince treatment.
New deficits may
emerge over time.

Sec
#
15

Potential Late Effects

Risk Factors

Neurocognitive deficits:
Host factors
Diminished IQ (combined Younger age at treatment
with high dose and/or
CNS leukemia/lymphoma
intrathecal methotrexate
and/or cranial radiation.) Treatment factors
High-dose systemic
Functional deficits in:administration
Processing speed
Memory (particularly(> 1000 mg/m2 dose)visual, sequencing,
In combination with:temporal memory)- dexamethasone
Sustained attention
Visual-motor integration - cranial radiation- total body irradiationMath- intrathecal methotrexate
Reading (particularly
reading comprehension)
Planning and organization
Clinician Info Link
Acute toxicity predominates
if administeredsystemically as single
agent.
May contribute to lateneurotoxicity if combinedwith intrathecal
methotrexate and/ or
cranial radiation.
ClinicalTreatment factors
Combined with:leukoencephalopathy(spasticity, ataxia,- intrathecal methotrexate
dysarthria, dysphagia,- dexamethasone
hemiparesis, seizures)- cranial radiation
with or without
imaging abnormalities:- leukoencephalopathy- cerebral lacunes- cerebral atrophy- dystrophic calcifications- mineralizing microangiopathy
Clinician Info Link
Neuroimaging 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.

Highest Risk

Periodic
Evaluation

Minimum Recommended

Frequency

Clinical interview Baseline at entry into
Host factors
Age < 3 years old at including
long-term follow-up,
time of treatment
assessment ofthen yearlyFemale gendereducational or
vocational
Treatment factors progress
Combined withmethotrexate and/or
cranial radiation.
Referral for formal Baseline at entry into
neuropsychological long-term follow-up,
Radiation > 24 Gy
evaluation
TBI with daily
then periodically as
fraction > 2 Gyclinically indicated forpatients with evidence ofimpaired educational or
vocational progress

Treatment factors Clinical evaluation YearlyHigh-dose IV
administration
combined with
Brain MRIAs clinically indicatedcranial radiation
Radiation dose> 24 Gy
TBI with daily
Brain CT plus MRI As clinically indicatedfraction > 2 Gy
with MRangiography

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Health Link
Educational Issues
Following Treatment forChildhood Cancer

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:
microvascular injury
CT: calcifications
Neurology consultation and follow-up.

COG Follow-Up Guidelines – Page 6
Version 1.2 – March 2004
Therapeutic Agent
Mercaptopurine
Thioguanine

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

Clinician Info Link
Osteopenia andosteoporosis occur
more commonly after
methotrexate than does
osteonecrosis.

See related topics:
Corticosteroids
Hematopoietic celltransplant(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

17

See related topics:
Methotrexate
Dactinomycin
Hepatic radiation
Transfusion (chronic
hepatitis B & C)
Hematopoietic celltransplant (liver toxicity)
Host factors
Osteopenia
Both genders at risk
Bone mineral density > 1
and < 2.5 SD below mean
Treatment factors
Osteoporosis
Bone mineral density > 2.5 Corticosteroids
Cranial/spinal, head/neck,SD below mean
gonadal radiation
Clinician Info Link
Hematopoietic cell
The World Health Organization transplantation

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.
Instead, pediatric bone mineraldensity reference data sets
calculate z-scores based on age
and gender, but do not accountfor variations 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)

Minimum Recommended

Frequency
YearlyHealth Protective
Counseling
Health Link
Liver HealthBaseline at entry into longterm follow-up.

Baseline screening at 18 Health Link
years old; consider earlier Keeping Your Bones
screening if clinically
Healthy After Childhood
indicated.
CancerRepeat as clinically
Clinician Info Link
indicated.
Resource:
The optimal
National Osteoporosis
method ofFoundation website
measuring bonewww.nof.org
health 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.

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 history ofmultiple fractures, for otherpharmacologic interventions (e.g.,bisphosphonates, calcitonin, selective
estrogen receptor modulators).

COG Follow-Up Guidelines – Page 7
Version 1.2 – March 2004
Therapeutic Agent
Methotrexate(PO, IV, IM)Sec
Potential Late Effects#
18 Renal dysfunction
Acute toxicities
predominate, from which
the majority of patients
recover without sequelae.
See related topics:
Ifosfamide
Cisplatin/Carboplatin
Abdominal/pelvic
radiation
Cystectomy
Nephrectomy
19

Hepatic dysfunction
Acute toxicities
predominate from which
the majority of patients
recover without sequelae.
See related topics:
Mercaptopurine
Dactinomycin
Hepatic radiation
Transfusion (chronic
hepatitis B &C)
Hematopoietic celltransplant (liver toxicity)

Risk Factors
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

Highest Risk

Periodic
Evaluation
Treatment factors Blood pressure
Treatment before
1970.
BUN, creatinine,
U/A

Minimum Recommended

Frequency
YearlyBaseline at entry into longterm follow-up.

Health Protective
Counseling
Health Link
Kidney HealthSee also: Single Kidney
Precautions

Considerations for Further Testing
and Intervention
Nephrology consultation for patientswith hypertension, proteinuria, or
progressive renal insufficiency.

Obtain in patients withNa, K, Cl, CO2
Ca, Mg, PO4
abnormal BP, urinalysis,
Creatinine
BUN, or creatinine. If
clearance or GFR. abnormal, repeat asclinically indicated.

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

YearlyBaseline at entry into longterm follow-up.

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 or any patient transfusedprior to 1993.
Gastroenterology/hepatology
consultation in patients with persistentliver dysfunction.
Hepatitis A and B immunization inpatients lacking immunity.

COG Follow-Up Guidelines – Page 8
Version 1.2 – March 2004
Therapeutic Agent
Methotrexate(IT, high-dose IV)
Note: High-dose IV isdefined as any single
dose >1000 mg/m2

See related topics:
Head/brain radiation
Cytarabine (high-dose
IV)

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).
Extent of deficit
depends on age attreatment, intensity oftreatment and timesince treatment.
New deficits may
emerge over time.

Sec
Potential Late Effects
Risk Factors##
20 Neurocognitive deficits:
Host factors
Diminished IQ (with high Younger age at treatment
dose and/or intrathecal
CNS leukemia/lymphoma
methotrexate and/or cranialradiation.)
Treatment factors
Intrathecal administration
Functional deficits in:
High-dose systemic
Processing speed
Memory (particularly
administration
visual, sequencing,(> 1000 mg/m2 dose)
temporal memory)
In combination with:- dexamethasone
Sustained attention
Visual-motor integration - cranial radiation- total body irradiation
Math
Reading (particularly- high-dose IV cytarabinereading 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

Minimum Recommended
Periodic
Health Protective
Frequency
EvaluationCounseling
Clinical interview Yearly
Health Link
Host factors
Educational Issues
Age < 3 years old at including
assessment of
Following Treatment fortime of treatment
educational orChildhood Cancer
Female gender
vocational
Treatment factors progress
High-dose and/or IT
methotrexate
combined with
Referral for formal Baseline at entry into
neuropsychological long-term follow-up,
cranial radiation.
evaluation
Radiation dosethen periodically as> 24 Gy
clinically indicated for
TBI with daily
patients with evidence of
fraction > 2 Gy
impaired educational or
vocational progress

Highest Risk

Treatment factors Clinical evaluation Yearly
Host factors
Younger age at treatment High-dose and/or IT
CNS leukemia/lymphoma methotrexate
combined with
Brain MRIAs clinically indicatedcranial radiation.
Treatment factors
Intrathecal administration Radiation dose
> 20 Gy
High-dose systemic
TBI with daily(> 1000 mg/m2 dose)
Brain CT plus MRI As clinically indicatedadministration
fraction > 2 Gy
with MR
Triple intrathecal
angiography
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.

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:
microvascular injury
CT: calcifications
Neurology consultation and follow-up

COG Follow-Up Guidelines – Page 9
Version 1.2 – March 2004
Therapeutic AgentSec
Potential Late Effects#
Anthracycline antibiotics
21 Acute myeloid leukemia
Doxorubicin
Daunorubicin
Idarubicin
Mitoxantrone
Epirubicin
See related topics:
Chest/thorax
radiation

22

Risk Factors

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
Any left-sided upper
Clinician Info Link
Dose levels correlating with abdominal fieldcardiotoxicity are derived
Combined with otherfrom adult studies.
cardiotoxic
Childhood cancer patientschemotherapy:
exhibit clinical and- cyclophosphamide
subclinical toxicity at(100-200 mg/kg as
lower levels.
conditioning for stem
Certain conditions such ascell transplantation)isometric exercise,- amsacrine
pregnancy, and viral
infections, have been
anecdotally reported to
Medical conditions
Congenital heart diseaseprecipitate cardiac
Pregnancy
decompensation.
Febrile illness
Need for prospective
Health behaviors
studies to define risk
Isometric exercise
factors.
Drug use (e.g., cocaine,
Note: pediatric studies ofdiet pills, ephedra,
anthracycline
mahuang)
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.
Cardiomyopathy
Arrhythmias

Highest Risk

Periodic
Evaluation
Physical exam
CBC/ differential

Minimum Recommended

Frequency

Health Protective
Counseling

Yearly up to 10 years post Health Link
exposure to anthracycline Reducing the Risk ofSecond Cancers

Considerations for Further Testing
and Intervention
Bone marrow exam as clinicallyindicated.

Counsel to promptly reportfatigue, pallor, petechiae,
or bone pain.
Cardiology consultation in patients
Detailed history
YearlyHealth Link
Host factorsof exertional
FemaleHeart Problems Following with subclinical abnormalities ontolerance.
Black/ of African
Treatment for Childhood screening evaluations, left ventricular
dysfunction, dysrhythmia, ordescent
Clinician Info Link
Cancerprolonged QT interval.
Younger than age 5 Note: exertional
intolerance is
Additional cardiology evaluation inyears at treatment
Counsel patients with
uncommon in young
patients who received > 300 mg/m2 or
prolonged QT interval< 300 mg/m2 plus chest radiation or
Treatment factors patients (< 25 years).
about use of medications
TBI who are pregnant or planning
Higher cumulative Abdominal symptoms
that may further prolong(nausea, emesis) may
pregnancy to include an EKG anddoses:
QT
interval(e.g.,
tricyclic
be observed moreechocardiogram before and> 550 mg/m2 infrequently thananti- depressants,
patients 18 years or exertional dyspnea or
periodically during pregnancy
antifungals, macrolide
chest pain.
older at time ofantibiotics, metronidazole). (especially during 3rd trimester) andtreatment
monitoring during labor and delivery
EKG for evaluation Baseline at entry into long> 300 mg/m2 indue to risk of cardiac failure.
term follow-up
of QT interval
patients younger
Consider excess risk of isometricthan 18 years at
exercise program in any high risktime of treatment ECHO or MUGA Baseline at entry to long-term
patient defined as needing screening
Any dose in infant
every 1 or 2 years.
for evaluation of follow-up, then periodically,
Longer time elapsed systolic function based on age at treatment,
history of chest radiation andsince treatment
cumulative anthracycline dose(see table).

RECOMMENDED FREQUENCY OF ECHOCARDIOGRAM OR MUGA SCAN
Age at Treatment*

Chest RadiationYes<1 year oldNo
Yes

Anthracycline Dose†Every year

<200 mg/m2

Every 2 years>200 mg/m2

Every year

Any

Every year2

1-4 years oldNoYes>5 years old
No

Recommended Frequency

Any<100 mg/m

Every 5 years>100 to <300 mg/m2

Every 2 years>300 mg/m2

Every year

<300 mg/m2

Every 2 years>300 mg/m2

Every year

<200 mg/m2

Every 5 years>200 to <300 mg/m2

Every 2 years>300 mg/m2

Every year

Any age with decrease in serial function

Every year

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

COG Follow-Up Guidelines – Page 10
Version 1.2 – March 2004
Therapeutic AgentSec#

Anti-Tumor Antibiotics
23
Bleomycin

Potential Late Effects

Risk Factors

Highest Risk

Periodic
Evaluation

Interstitial pneumonitis
Treatment factors Physical exam
Host factors
Younger age at treatment Bleomycin dose
Pulmonary fibrosis> 400 U/m2
Acute respiratory distress(injury observed in PFTs
syndrome (very rare)
Treatment factors
doses 60-100 U/m2 (including DLCO
Higher cumulative dosein children)
Combined with otherand spirometry)pulmonary toxic therapy:
and CXR- busulfan
See related topics:- carmustine (BCNU)
Chest/thorax radiation- lomustine (CCNU)
Busulfan- thoracic radiation
Carmustine- spinal radiation >30 Gy
Lomustine- total body irradiation
Clinician Info Link
Administration of highMedical conditions
Renal dysfunction
concentrations of oxygenHigh dose oxygen support
may result in chronicsuch as during generalprogressive pulmonary
anesthesia
fibrosis.

Minimum Recommended

Frequency
YearlyHealth Protective
Counseling
Health Link
Pulmonary HealthBleomycin Alert
Baseline at entry into longterm follow-up and prior SCUBA diving should beto general anesthesia.
avoided. (Potential
Repeat as clinicallyexacerbation of pulmonary
indicated in patients with fibrosis as a result ofabnormal or progressive increased oxygen
pulmonary dysfunction.
concentrations associatedwith underwater pressures).

Considerations for Further Testing
and Intervention
Pulmonary consultation in patientswith symptomatic or progressive
pulmonary dysfunction.
Influenza and Pneumococcal vaccines.

Notify healthcare providersof history of bleomycin
therapy and risk ofworsening fibrosis withhigh oxygen exposure suchas 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)See related topics:
Mercaptopurine
Methotrexate
Hepatic radiation
Transfusion (chronic
hepatitis B &C)
Hematopoietic celltransplant (liver toxicity)

Treatment factors
Hepatic radiation

Physical exam

Yearly

ALT, AST,
bilirubin

Baseline at entry into longterm follow-up.

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 Follow-Up Guidelines – Page 11
Version 1.2 – March 2004
Therapeutic Agent
Corticosteroids
Prednisone
Dexamethasone

Sec
#
25

Potential Late Effects

Risk Factors

Highest Risk

Periodic
Evaluation

Minimum Recommended

Frequency

Health Protective
Counseling

Baseline screening at 18 Health Link
Bone density
Host factors
years old; consider earlier Keeping Your Bones
Older age at time of evaluation
screening if clinically
Healthy After Childhood
treatment(DEXA orCancerquantitative CT) indicated.
Repeat as clinically
Treatment factors
Dexamethasone
indicated.
National Osteoporosis
Clinician Info
effect is moreFoundation website:
Link
potent thanwww.nof.org
The optimal
prednisone.
method ofmeasuring bonehealth in children
defined as a T-score.
is controversial.
A T-score of > 2.5 standard
Existing
Medical Conditions
deviations below the mean isconsistent with a diagnosis of
Hypogonadism
technologies haveosteoporosis.
Premature ovarian failure
limitations.
T-scores are not appropriate to assess
Dual energy x-ray
skeletal health in pediatric patients Early menopause
who have not achieved peak adult
Growth hormone
absorptiometry
bone mass.
deficiency(DEXA) provides
Instead, pediatric bone mineralan estimate of total
density reference data sets calculate Hyperthyroidismz-scores based on age and gender,
bone mass at abut do not account for variations
given site.
See related topics:
related to sexual maturation and
Quantitative CT
Methotrexate
ethnicity.
The ideal reference data should
provides distinct
Hematopoietic cellprovide assessment relative to bodymeasures oftransplantsize, 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.
Host factors
Osteopenia(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
The World Health Organization
radiation
definition of osteoporosis in adults
otherhead/neckis based on comparison of aradiationmeasured bone mineral density ofyoung adults at peak bone age and- radiation to bones

Considerations for Further Testing
and Intervention
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 otherpharmacologic interventions (e.g.,bisphosphonates, calcitonin, selective
estrogen receptor modulators).

Consequently, there are no evidencebased guidelines for classificationof bone health in children.

26

Avascular necrosis (AVN) Host factors
Both genders at risk
(Osteonecrosis)
Treatment factors

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

Medical conditions
Sickle cell disease
27

Cataracts
See related topics:
Busulfan
Head/brain radiation
TBI

Treatment factors
Combined with:- total body irradiation- brain/head radiation- busulfan

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

YearlyTreatment factors
Orthovoltage
radiation(commonly used
before 1970) due todelivery of greater
dose to skin andbones.
YearlyTreatment factors Eye exam
TBI given in single including
funduscopic exam
daily fraction
and visual acuity
Radiation dose> 10 Gy withpotential scatter toeye(s)
Longer interval sincetreatment

Health 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
Eye Problems afterChildhood Cancer

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).

COG Follow-Up Guidelines – Page 12
Version 1.2 – March 2004
Therapeutic Agent
Enzymes
Asparaginase

Sec
#
28

Potential Late Effects

Risk Factors

Highest Risk

Periodic
Evaluation

Minimum Recommended

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Yearly, until 2 to 3 years Health Link
after therapy; continue to Peripheral Neuropathy
monitor yearly if
symptoms persist.

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).

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

Frequency

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 istypically not late in
onset.

Epipodophyllotoxins
Etoposide (VP-16)
Teniposide (VM-26)
Clinician Info Link
Administration
schedules since ~1990
have been modified toreduce the risk of thiscomplication.

29

30

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

Treatment factors
Combined with cisplatin

Vasospastic attacks(Raynaud's phenomenon)

Health behaviors
Tobacco use
Illicit drug use

Medical conditions Neurologic exam
Charcot-MarieTooth disease

Medical conditions
Anorexia
Severe weight loss
History
Physical exam

Health Link
Raynaud’s PhenomenonCounsel to wear
appropriate protective
clothing in cold
environments and to not
use tobacco or illicit
drugs.

31

Acute myeloid leukemia

Medical conditions
Splenectomy(conflicting evidence)

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

Yearly up to 10 years
post exposure to agent

Health Link
Reducing the Risk ofSecond Cancers
Counsel to promptly reportfatigue, pallor, petechiae,
or bone pain.

Bone marrow exam as clinicallyindicated.

COG Follow-Up Guidelines – Page 13
Version 1.2 – March 2004
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,
permanent hair loss,
altered skin pigmentation

33

Risk Factors

Host factors
Younger age at treatment
Treatment factors
Higher cumulative dose

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

34

35

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

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

Bone malignancies

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

Highest Risk

Periodic
Evaluation

Physical exam
Host factors
Prepubertal attreatment
Treatment factors

Minimum Recommended

Frequency
YearlyHealth Protective
CounselingConsiderations for Further Testing
and Intervention

Health Link
Skin Health

Dose fraction > 2 Gy

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

Treatment factors Physical exam with Yearly
Health Link
Orthovoltage
inspection andReducing the Risk ofradiation
palpation ofSecond Cancers(commonly usedirradiated skin andbefore 1970) due to soft tissues.
delivery of greater
dose to skin andbones.
Other evaluations See recommendations forbased on treatment specific fields
volumes

Surgical and/or oncology consultation
as clinically indicated.

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

Dermatology consultation forevaluation and monitoring of atypicalnevi.
Oncology consultation as clinicallyindicated.

Radiation dose > 30 Gy

Orthovoltage
radiation(commonly used
before 1970) due todelivery of greater
Treatment factors
dose to skin andHigh radiation dose
Combined with alkylating bones.
agentsYearlyHealth Link
Skin Health
Reducing the Risk ofSecond Cancers

YearlyCounsel 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COG Follow-Up Guidelines – Page 14
Version 1.2 – March 2004
Therapeutic Agent
Head/Brain Radiation
Any field involving thehead/brain, including:
Total Body Irradiation
Cranial (whole brain)
Craniospinal
Nasopharyngeal
Oropharyngeal
Orbital/Eye
Ear/Infratemporal

Sec
#
36

(continued on next
page)

Potential Late Effects

Risk Factors

Highest Risk

Periodic
Evaluation

Minimum Recommended

Frequency

Health Protective
Counseling

Clinical interview Baseline and yearly
Neurocognitive deficits:
Host factors
Health Link
Host factors
including
Younger age at treatment Age < 3 years at
Educational Issues
Diminished IQ (< 85)
Primary CNS tumor
Following Treatment fortime of treatment assessment of
Functional deficits in:educational or
ALL or relapsed ALL
Childhood Cancer
Female gender
Processing speed
Memory (particularly
vocational progress
Head/neck tumors with
Tumor site invisual, sequencing,brain in radiation field
cerebral hemisphere
temporal memory)
Sustained attention
Treatment factors
Treatment factors Referral for formal Baseline at entry into
Cranial irradiation neuropsychological long-term follow-up, then
Visual-motor integration Combined with:- methotrexateMathevaluation
periodically as clinicallyReading (particularly(IT, high-dose IV)
Social factors
indicated for patients withreading comprehension)- dexamethasone
Low SESevidence of impaired
Premorbid or family
Planning and organization - cytarabine (high-dose
educational or vocationalIV)
history of learning
Increased risk for social
progressdifficulties, psychological - high dose chemotherapy or attention
with autologous orproblems.
maladjustment.
allogeneic hematopoietic
Clinician Info Link
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).
The extent of deficit depends on
age at treatment intensity oftreatment and time sincetreatment.
New deficits may emerge overtime.

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.

See related topics:
Methotrexate
Cytarabine
Neurosurgery
37

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

Host factors
Younger age at treatment

Host factors
Age < 2 years attime of treatment

Clinical evaluation Yearly

Brain MRIAs clinically indicatedTreatment factors
Higher radiation dose
Treatment factors
Brain CT plus MRI As clinically indicated
Dose > 30 Gy
Combined with:- high-dose methotrexate Fraction dose > 2 Gy with MRangiography- intrathecal methotrexate
or cytarabine
Medical conditions
Hydrocephalus requiring
shunt
Posterior fossa syndrome

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

COG Follow-Up Guidelines – Page 15
Version 1.2 – March 2004
Therapeutic Agent

Minimum Recommended
Periodic
Frequency
Evaluation
Treatment factors Clinical evaluation Yearly
Host factors
Hypothalamic/chiasmatic Dose > 40 Gy
gliomaHead/Brain Radiation(continued fromprevious page)

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

Any field involving thehead/brain, including:
Total Body Irradiation
Cranial (whole brain)
Craniospinal
Nasopharyngeal
Oropharyngeal
Orbital/Eye
Ear/Infratemporal

Clinician Info Link
Moyamoya syndrome is thecomplete occlusion of one ormore of the three major
cerebral vessels with thedevelopment of small,
immature collateral vessels,
which reflect an attempt torevascularize the ischemic
portion of the brain.

Medical conditions
Sickle cell disease
Neurofibromatosis

Brain tumor:
High-grade astrocytoma
Meningioma
Sarcoma

Host factors
Younger age at treatment
Thiopurine methyltransferase (TPMT)
genetic polymorphism
Neurofibromatosis

39(continued on next
page)

Risk Factors

Treatment factors
Higher radiation dose40

Growth hormone
deficiency

Host factors
Younger age at treatment
Treatment factors
Higher radiation doses
Surgery in suprasellar
regionPretransplant radiation
Total body irradiation:> 10 Gy single fraction> 12 Gy fractionatedHighest Risk

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

Brain MRI with
As clinically indicateddiffusion-weighted
imaging with MRangiography

History & physical Yearly
Host factors
Age < 6 years at
Neurologic examtime of treatment
Ataxia telangiectasia Brain MRI
Baseline at maturity for all
patients
Every other year forpatients withneurofibromatosis,
beginning 2 years afterradiation
As clinically indicated for
symptomatic patients
Treatment factors Assess nutritional
Radiation dose
status.
> 18 Gy
Monitor height,
Pretransplant cranial weightradiation
BMI percentiles
Single daily fraction Tanner staging
TBI dose
Bone age

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

Endocrine consultation for:- drop in %ile on growth grid- growth velocity < 4-5 cm/year
during childhood
See also: Hypopituitarism- growth below 3rd %ile
www.magicfoundation.org - lack of pubertal growth spurt.
Evaluate thyroid function in any poorly
growing child.
Obtain in poorly growing
children.

Every 6 months until
growth is completed.

Health Link
Growth Hormone
Deficiency

41

Hyperprolactinemia

Treatment factors
Higher radiation dose
Surgery or tumor in
hypothalamic area

CT evaluation of sella turcica for
Health Link
Treatment factors Review of systems: YearlyHyperprolactinemia
Radiation dose
Female:pituitary adenoma in patients with> 50 Gy- galactorrhea
hyperprolactinemia.
- menstrual history
Endocrine consultation for patients
www.magicfoundation.org with hyperprolactinemia, amenorrhea,Male:- decreased libido
or galactorrhea.
- galactorrhea
Prolactin level
In all patients withgalactorrhea; females withamenorrhea; males withdecreased libido

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

YearlyHealth Link
Thyroid Problems afterChildhood Cancer.
See also: Hypopituitarism

Consider TSH surge testing.
Endocrine consultation for thyroid
hormone replacement.

COG Follow-Up Guidelines – Page 16
Version 1.2 – March 2004
Therapeutic Agent
Head/Brain Radiation(continued fromprevious page)

Sec
Potential Late Effects#
43 Central adrenal
insufficiency

Risk Factors
Treatment factors
Higher radiation doseHighest Risk

Periodic
Evaluation

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

Minimum Recommended

Frequency
Yearly- dehydration- hypoglycemia- lethargy- unexplained
hypotension
Baseline at entry into long
8:00 AM serum
term follow-up andcortisol in patientstreated with > 30 Gy periodically as clinicallyradiation toindicatedhypothalamicpituitary axis

Any field involving thehead/brain, including:
Total Body Irradiation
Cranial (whole brain)
Craniospinal
Nasopharyngeal
Oropharyngeal
Orbital/Eye
Ear/Infratemporal
44

Precocious puberty(continued on next
page)

Host factors
Female gender
Younger age at treatment

Physical exam
Yearlyincluding height,
weight, Tanner stage

Treatment factors
Radiation doses > 18 Gy

LH, FSH, estradiol or As clinically indicated in
testosterone
patients with signs ofaccelerated pubertal
progression and growth.
Bone age

45

Gonadotropin deficiency(LH and FSH)

Treatment factors
Higher radiation dose

Health Protective
Counseling
Health Link
Central Adrenal
Insufficiency
See also: Hypopituitarism
Corticosteroid replacement
therapy & stress dosing.
Medic Alert bracelet.
www.magicfoundation.org

Endocrine consultation for accelerated
puberty (puberty in girl < 8 years oldand boy < 9 years old).
www.magicfoundation.org Consider pelvic ultrasound in females
to evaluate for ovarian tumor
Health Link
Precocious Puberty

Obtain in rapidly growing
children.

Bone density evaluation for
Health Link
Female Health Issues after osteopenia/osteoporosis inChildhood Cancer
hypogonadal patients.
Refer to endocrinologist for delayedorclinical signs of puberty or
Male Health Issues after
persistently abnormal hormone levels
Childhood Cancer
Hormonal replacement therapy for
Baseline at age 8, and then yearly See also: Hypopituitarism
hypogonadal patients.
until normal puberty is established,
AND as clinically indicated inCounsel currently menstruating Reproductive endocrinology/ obstetrics
patients with:women at increased risk ofreferral for infertility evaluation and- Delayed puberty, irregular menses early menopause to be
consultation regarding assisted
or amenorrhea
cautious about delaying- Clinical signs and symptoms ofreproductive technologies.
childbearing.
estrogen deficiency
Consider 2 months off hormonalCounseling regarding need for replacement in women with ovarian
contraception since there isYearlyfailure to assess ovarian recovery.

Treatment factors Females:
YearlyPubertal history (onset,
Radiation dose
tempo)> 30 Gy
Menstrual and pregnancy
history
Physical exam includingheight, weight, Tanner
stage
FSH, LH, estradiol

Males:
Pubertal history (onset,
tempo)
History of sexual function(erections, nocturnal
emissions, libido)
History of medication use
Physical exam includingheight, weight, Tannerstage, testicular volume
by Prader orchiometry.

Considerations for Further Testing
and Intervention
Endocrine consultation for further
evaluation and replacement steroids.

tremendous individual
variability in gonadal toxicity
after exposure to radiation
therapy and alkylating agents.
Recovery of fertility may
occur many years after
therapy.

FSH, LH, testosterone

Baseline at age 9, and then yearly Resources:
until normal puberty is established,
American Society for
AND as clinically indicated inpatients with:
Reproductive Medicine- Delayed puberty
website: www.asrm.org- Clinical signs and symptoms of
testosterone deficiency

Semen analysis

As requested by patient and forevaluation of infertility

See also:
www.fertilehope.org

COG Follow-Up Guidelines – Page 17
Version 1.2 – March 2004
Therapeutic Agent
Head/Brain Radiation(continued fromprevious page)
Any field involving thehead/brain, including:
Total Body Irradiation
Cranial (whole brain)
Craniospinal
Nasopharyngeal
Oropharyngeal
Orbital/Eye
Ear/Infratemporal
Mantle(sections 48 & 49 only)
Cervical Spine(sections 48 & 49 only)

Sec
Potential Late Effects
Risk Factors#
46 Overweight/Obesity
Host factors
Younger at treatment
Definition by adultstandards:
body mass index (BMI) = Treatment factors
Higher cranial radiation
wt (kg)/ht (M2)
Overweight: BMI > 25-29.9 dose
Combined with
Obese: BMI > 30
corticosteroids
BMI calculator available
on-line at:Medical conditions
http://nhlbisupport.com/bmi/
Familial dyslipidemia
Definition by pediatric
Growth hormone
standards for < 16 years
deficiency
old:Hypothyroidism
Overweight is defined byHighest Risk
Host factors
Age < 4 years old attime of treatment
Female gender

Periodic
Evaluation
Blood pressure

Chronic sinusitis

Treatment factors
Higher cumulative
radiation doses to sinuses(> 30 Gy)
Radiomimetic chemotherapy(e.g., doxorubicin, dactinomycin)

48

Medical conditions
Atopic history
Hypogammaglobulinemia
Xerostomia
Treatment factors
Salivary gland dysfunction Head and neck radiation
involving the parotid
gland
Higher radiation doses
Total body irradiation

Frequency
YearlyGrowth percentile Yearly
Treatment factors or
Hypothalamic dose Body mass index> 20 Gy
Fasting lipid profile Every 3-5 years in
Medical conditions
overweight or obese
Inability to exercise
patients
Fasting insulin

Obtain baseline forpatients with acanthosis
nigricans.
Consider testing inoverweight or obese
patients withdyslipidemia.

History
Physical exam

YearlyCT sinuses

As clinically indicatedsex-and age-specific
95%ile cutoff
points of CDC/NCHS
growth charts.
Growth charts available
on-line at:www.cdc.gov/growthcharts/
47

Minimum Recommended

Treatment factors History
Salivary gland dose Physical exam
> 30 Gy

Health Protective
Considerations for Further TestingCounselingand Intervention
Consider evaluation for other coHealth Link
Health Promotion through morbid conditions including:Diet and Physical Activity dyslipidemia, hypertension, glucose
intolerance, diabetes mellitus,
Obesity-related healthhyperinsulinism, insulin resistance.
risks.
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/

Reconstructive craniofacial surgicalconsultation.
Consultation with psychologist in
patients with adjustment disorders
related to facial asymmetry/deformity.

Medical conditions
Chronic GVHDRadiomimetic chemotherapy(e.g., doxorubicin, dactinomycin)

49

50

Dental abnormalities
Tooth/root agenesis
Microdontia
Root thinning/shortening
Enamel dysplasia
Periodontal disease
Tooth decay
Malocclusion
Temporomandibular joint
dysfunction
Craniofacialabnormalities

Dental exam andcleaning

Host factors
Younger age at treatment
Gorlin's syndrome

Host factors
Age < 5 years attime of treatment

Treatment factors
Higher radiation dose

Treatment factors
Dose > 20 Gy(may occur in young
children at 10 Gy)

Host factors
Younger age at treatment

Physical exam
Host factors
Age < 5 years attime of treatment
Treatment factors Psychosocial
Dose > 30 Gy
assessment ofadjustment

Treatment factors
Higher radiation doseYearlyCOG Follow-Up Guidelines – Page 18
Version 1.2 – March 2004
Therapeutic AgentEye radiation
Any field involving theeye, including:
Total Body Irradiation
Orbital/Eye
Cranial (whole brain)
Craniospinal

Sec
#
51

Potential Late Effects

Cataracts

Orbital hypoplasia
Clinician Info Link:
Complications otherthan cataracts are
generally associatedonly with orbital/eye
radiation.
Reduced visual acuity
may be associated withcataracts, retinal
damage, and optic
nerve damage

Lacrimal duct atrophy(resulting in excessive
tearing)
Xerophthalmia (severe)(resulting from atrophy oflacrimal gland)
Keratitis

Risk Factors

Highest Risk

Minimum Recommended

Frequency

Yearly for patients who
Treatment factors
Treatment factors Ophthalmology
evaluation
Higher radiation dose
received > 30 Gy or TBI
Dose > 10 Gy
Combined with:
TBI given in single including
Every 3 years for patientsfunduscopic exam who received < 30 Gy- corticosteroids
daily fraction- busulfan
Fraction dose > 2 Gy and visual acuity(these patients also need
Longer interval since
yearly funduscopic
treatment
exams during yearly
Treatment factors
Treatment factors
long-term follow-up
Dose > 30 Gy
Higher radiation dose
visits)Higher daily fraction dose Fraction dose > 2 Gy
Treatment factors
Higher radiation doseRadiomimetic chemotherapy(e.g., doxorubicin, dactinomycin)

Treatment factors
Higher radiation doseRadiomimetic chemotherapy(e.g., doxorubicin, dactinomycin)

Treatment factors
Higher radiation doseRadiomimetic chemotherapy(e.g., doxorubicin, dactinomycin)

Keratoconjunctivitis sicca Treatment factors
Higher radiation dose
Corticosteroids

Treatment factors
Dose > 40 Gy
Fraction dose > 2 Gy
Treatment factors
Dose > 30 Gy
Fraction dose > 2 Gy
Treatment factors
Dose > 40 Gy
Fraction dose > 2 Gy
Treatment factors
Dose > 40 Gy
Fraction dose > 2 Gy

Radiomimetic chemotherapy(e.g., doxorubicin, dactinomycin)

Medical conditions
Chronic GVHD

Telangiectasias

Treatment factors
Higher radiation dose

Treatment factors
Dose > 50 Gy
Fraction dose > 2 Gy

Retinopathy

Treatment factors
Higher radiation dose

Treatment factors
Dose 45-65 Gy
Fraction dose > 2 Gy

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

Treatment factors
Dose 50- 65 Gy
Fraction dose > 2 Gy

Medical conditions
Diabetes mellitus
Hypertension
Enophthalmos
Chronic painful eye

Periodic
Evaluation

Treatment factors
Higher radiation dose

Fraction dose > 2 Gy

Health Protective
Counseling
Health Link
Eye Problems afterChildhood Cancer
Resource:
FACES - The National
Craniofacial Associationwww.faces-cranio.org/

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

COG Follow-Up Guidelines – Page 19
Version 1.2 – March 2004
Therapeutic Agent
Ear radiation
Any field involving theear, including:
Total body irradiation
Ear/Infratemporal
Cranial (whole brain)
Craniospinal
Nasopharyngeal

Sec#

Potential Late Effects

52

Tympanosclerosis
Otosclerosis
Eustachian tube
dysfunction
Conductive hearing loss

For Cervical Spine& Mantle see also:
Section 48(Xerostomia)
and Section 49(Dental Abnormalities)

Host factors
Younger age at treatment

53

54

Thyroid nodules

Thyroid cancer

Highest Risk

Periodic
Evaluation

Treatment factors History
Dose > 50 Gy
Physical exam
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

Neck radiation
Any radiation withpotential impact to theneck/thyroid,
including:
Total Body Irradiation
Cervical
Cranial (whole brain)
Craniospinal
Nasopharyngeal
Oropharyngeal
MantleMediastinal
Whole lung
Spinal

Risk Factors

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
YearlyFor 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
CounselingConsiderations for Further Testing
and Intervention

Health Link
Hearing Problems afterChildhood Cancer

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
Note: must be freeT4 in females on OCP

History
YearlyPhysical exam
dose > 35 Gy
TSH, free T4
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(e.g., doxorubicin, dactinomycin

Medical conditions
Gastroesophageal reflux

Yearly; consider more
Health Link
frequent screening during Thyroid Problems after
periods of rapid growthChildhood Cancer.

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 Follow-Up Guidelines – Page 20
Version 1.2 – March 2004
Therapeutic Agent
Trunk radiation
Any field fromshoulders to pelvis
including:
Total Body Irradiation
Spinal (> 12 Gy)

Sec
#
59

60

Potential Late Effects

Risk Factors

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

Scoliosis

Highest Risk

Host factors
Prepubertal attreatment

Periodic
Evaluation
Physical exam

Frequency

Health Protective
CounselingConsiderations for Further Testing
and Intervention

YearlyOrthopedic consultation if clinicallysignificant or for any deficit noted in
growing child.
Plastic surgery consultation forreconstruction.

Yearly until growth
Health Link
completed; may need more Scoliosis and Kyphosis
frequent assessment during after Treatment for
pubertyChildhood Cancer

Orthopedics consultation as indicatedbased on radiographic 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
doses for infants)
Neurofibromatosis
Orthovoltage
radiation
Treatment factors
Hemithoracic or(commonly used
abdominal radiation
before 1970) due to Spine films
Hemithoracic, abdominal delivery of greateror spinal surgery
dose to skin andRadiation of only abones.
portion of (rather thanwhole) vertebral body
Clinician Info Link:
With contemporary
treatment approaches,
scoliosis is infrequently
seen as a consequence ofradiation unless thepatient has also
undergone surgery to thehemithorax, abdomen or
spine

Minimum Recommended

In patient with clinicallyapparent curveCOG Follow-Up Guidelines – Page 21
Version 1.2 – March 2004
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

Potential Late Effects

Kyphosis

Esophageal stricture

Risk Factors

Highest Risk

Periodic
Evaluation

Host factors
Treatment factors Physical exam
Younger age at irradiation Radiation doses
Paraspinal malignancies> 20 Gy (lower
doses for infants)
Neurofibromatosis
Orthovoltage
radiation(commonly used
Spine films
before 1970) due todelivery of greater
dose to skin andbones.
Treatment factors
Higher radiation dose toesophagus

Treatment factors History
Dose > 40 Gy

Minimum Recommended

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Yearly until growth
Health Link
completed; may need more Scoliosis and Kyphosis
frequent assessment during after Treatment for
pubertyChildhood Cancer

Orthopedics consultation as indicatedbased on radiographic exam.

Frequency

In patient with clinicallyapparent curve

YearlySurgical and/or gastroenterology
consultation for symptomatic patients.

Radiomimetic chemotherapy(e.g., doxorubicin, dactinomycin

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

63

Breast cancer

Host factors
Family history of breast
cancerTreatment factors
Higher radiation doseLonger time fromradiation (> 5-9 years
since radiation)

Host factors
Female gender

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

Surgical consultation for diagnostic
Health Link
Breast Cancer after
procedure.
Treatment for Childhood Precautions about the use of HRT.
Cancer: Are You at Risk?

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

Mammogram

Yearly, beginning 8
years after radiation or at
Clinician Info Link age 25 (whichever occurs
Mammography is last)currently limited in
its ability toevaluatepremenopausal
breasts.

64

Breast tissue hypoplasia

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

Physical exam

YearlySurgical consultation for breastreconstruction after completion of
growth.

COG Follow-Up Guidelines – Page 22
Version 1.2 – March 2004
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
Any left-sided upper
abdominal field

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

Health behaviors
Smoking

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
Busulfan

Host factors
Younger age at irradiation
Treatment factors
Higher radiation dose to lungs
Total body irradiation
Combined with:- bleomycin- busulfan- carmustine (BCNU)- lomustine (CCNU)

Medical conditions
Atopic history
Health behaviors
Smoking

Periodic
Evaluation

Minimum Recommended

Considerations for Further Testing
and Intervention
Baseline, at entry into longCardiology consultation for patients
Treatment factors EKG
Host factors
term follow-up and asYounger age at irradiation Anteriorly-weighted
Heart Problems Following with subclinical abnormalities onclinically indicatedradiation fields
Family history ofTreatment for Childhood screening evaluations or with left
ventricular dysfunction, dysrhythmia
Lack of subcarinal
dyslipidemia
CancerECHOBaseline, at entry into longor prolonged QT interval.
shieldingCoronary artery diseaseterm follow-up, thenAdditional cardiology evaluation for
periodically based on age at
Health Promotion through patients who are pregnant or planning
Doses >30 Gy in
Treatment factors
treatment, radiation dose, andcumulative anthracycline dose Diet and Physical Activity pregnancy who: (1) received > 30 Gy
Radiation dose >20 Gy to patients who have(see table).
chest/thorax
chest/thorax radiation, or (2) received
received
TBI in combination with cardiotoxic
anthracyclines
Combined withchemotherapy (anthracyclines or highradiomimetic chemotherapy
Cardiology
Forpatients
who
received(e.g., doxorubicin, dactinomycin) Doses > 40 Gy indose cyclophosphamide). Evaluation
consultation for stress > 40 Gy chest radiation alone
patients who have testing
to include echocardiogram before andCombined with otheror > 30 Gy chest radiation plus
cardiotoxic chemotherapy:
not received
periodically during pregnancy
anthracycline: obtain baseline- anthracyclines
anthracyclines(especially during third trimester) and
5-10 years after radiation- cyclophosphamide
monitoring during labor and delivery(100-200 mg/kg as
due to risk of cardiac failure.
Fasting glucose and Every 3 to 5 years.
conditioning for stem
lipid
profileIfabnormal,referforongoingcell transplantation)
management- amsacrine
RECOMMENDED FREQUENCY. OF ECHOCARDIOGRAM
Total body irradiation
Medical conditions
Hypertension
Obesity
Dyslipidemia
Diabetes mellitus
Premature ovarian
failure (untreated)

Highest Risk

Detailed history ofexertional tolerance

Frequency

YearlyClinician Info Link
Exertional intolerance
is uncommon inpatients younger than
25 years old.
Abdominal symptoms(nausea, emesis)
may be observed
more frequently
than exertional
dyspnea or chest
pain in young
patients

Treatment factors Physical exam
Whole lung radiation

Health Protective
Counseling
Health Link

Age atTreatment*

RadiationDose<5 years oldAny>5 years old

Anthracycline
Dose†

Recommended
Frequency

None

Every 2 years

Any

Every year

<30 GyNone

Every 5 years>30 GyNone

Every 2 years<300 mg/m2

Every 2 years>300 mg/m2

Every year

Any

Any age with serial decrease in function

Every year

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

YearlyPulmonary consultation for patientswith symptomatic pulmonary
dysfunction.
Influenza and Pneumococcal
PFTs
Baseline at entry into long- Due to the potential
pulmonary toxicity of this vaccinations.
(including DLCO term follow-up
therapy, patients whoand spirometry)
Repeat as clinicallyand CXR
indicated in patients with desire to SCUBA diveabnormal or progressive should be advised toobtain medical clearance
pulmonary dysfunction.
from a diving medicine
specialist
Health Link
Pulmonary HealthCOG Follow-Up Guidelines – Page 23
Version 1.2 – March 2004
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)

Total Body Irradiation
Whole abdomen
Hepatic
See related topics:
Mercaptopurine
Methotrexate
Dactinomycin
Transfusion (chronic
hepatitis B &C)
Hematopoietic celltransplant (liver
toxicity)Sec#

Potential Late Effects

Risk Factors

Frequency

Health Protective
Counseling
Health Link
Splenic Precautions

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
Medical conditions
MononephricDiabetes mellitus
Hypertension

Treatment factors Blood pressure
Dose > 15 Gy towhole kidney
BUN, creatinine,
14 Gy TBI without
U/A
renal shielding

YearlyHealth Link
Kidney Health

Treatment factors
Higher radiation dose toliver

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

68

Renal insufficiency
Hypertension

Hepatic fibrosis
Cirrhosis

Minimum Recommended

When febrile T > 101º

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

69

Periodic
Evaluation

Treatment factors Physical exam
Blood culture
Dose > 30 Gy

67

See related topics:
Ifosfamide
Methotrexate
Cisplatin/Carboplatin
Cystectomy
Nephrectomy

Highest Risk

Medical conditions
Chronic hepatitis

Na, K, Cl, CO2

Ca, Mg, PO4
Creatinine clearance

or GFR

YearlyIn patients with T > 101º (38.3°C), or othersigns of serious illness, administer a longacting, broad-spectrum parenteral antibiotic
Medical alert bracelet/card (e.g., ceftriaxone), and continue close
medical monitoring while awaiting bloodnoting functional asplenia. culture results.
Counsel to avoid malaria Hospitalization and broadening ofand tick bites if living in
antimicrobial coverage (e.g., addition ofor visiting endemic areas. vancomycin) may be necessary undercertain circumstances, such as the presenceof marked leukocytosis, neutropenia, or
significant change from baseline CBC;
toxic clinical appearance; fever >104°F;
meningitis, pneumonia, or other serious
focus of infection; signs of septic shock; orprevious history of serious infection.
Immunize with Pneumococcal,
Meningococcal, and HIB vaccines. All
patients should receive Pneumococcal
booster 3 - 5 years after initial dose.

See also: Single Kidney
Precautions

Hepatocellular
carcinoma

Medical conditions
Chronic hepatitis B or C
Cirrhosis
Treatment factors
Higher radiation dose to
liver
Health behaviors
Alcohol use

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

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

YearlyHealth 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.

Baseline at entry into longterm follow-up.

Health behaviors
Alcohol use
70

Considerations for Further Testing
and Intervention

AFP

Yearly in patients withchronic hepatitis

Health Link
Reducing the Risk ofSecond Cancers

Liver ultrasoundYearly in patients withcirrhosis

Hepatitis after Childhood
CancerCOG Follow-Up Guidelines – Page 24
Version 1.2 – March 2004
Therapeutic Agent
Total Body Irradiation
All abdominal andpelvic fields
Spinal > 20 Gy

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

SecPotential Late Effects#
71 Bowel obstruction

Periodic
Evaluation
Treatment factors Physical exam
Treatment factors
Higher radiation dose to Dose > 45 Gy
KUB(Obstruction may
bowel
occur in people who
Abdominal surgery
received lower
Clinician Info Link
doses of abdominal
Bowel obstruction is rarely radiation during
seen in individuals treated childhood)with abdominal radiation
who have not had
abdominal surgery.

72

Treatment factors
Higher radiation dose tobowel
Abdominal surgery

Treatment factors History
Dose > 45 Gy
Serum protein,
albuminHost factors
Hepatoblastoma
Familial polyposis

Treatment factors
Radiation dose> 25 Gy

73

Chronic enterocolitis
Fistula, Strictures

Gastrointestinal
malignancy

Risk Factors

Minimum Recommended

Highest Risk

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

Frequency
With clinical symptoms
of obstruction.

Health Protective
Counseling

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

Surgical and/or gastroenterology
consultation for symptomatic patients.

Yearly in patients withchronic diarrhea or fistula

The following monitoring is to begin 15 years Health Link
after radiation or at age 35 years (whichever Reducing the Risk ofoccurs last). Monitor more frequently if
Second Cancers
clinically indicated.
Choose one of the following three options:

Surgical and/or oncology consultation
as needed.

Fecal 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

Host factors
Uterine vascular
Females with Wilms
insufficiency
tumor and associatedresulting in adverse
müllerian anomalies
outcomes such as
spontaneous abortion,
neonatal death, low-birth Clinician Info Link:
10% of girls with Wilms
weight infant, fetal
malposition, and premature tumor have congenitallaboruterine anomalies
Treatment factors
Higher radiation dose topelvisHost factors
Prepubertal attreatment

Colonoscopy

Every 10 years

History

Yearly and as clinicallyindicated

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

High-risk obstetrical care during
Health Link
Female Health Issues after pregnancy.
High level ultrasound in women withChildhood Cancer
Wilms tumor.
Resources:
American Society for
Reproductive Medicine
website: www.asrm.org
See also:
www.fertilehope.org

COG Follow-Up Guidelines – Page 25
Version 1.2 – March 2004
Therapeutic Agent
Total body irradiation
Whole abdomen
PelvicIliac/inguinal
Para-aortic
Spinal > 24 Gy

SecPotential Late Effects#
75 Ovarian dysfunction:- Delayed/arrested puberty- Primary amenorrhea- Secondary amenorrhea- Premature ovarian failure- Early menopause- Infertility

Minimum Recommended
Periodic
Frequency
Evaluation
YearlyHost factors
Treatment factors Pubertal history(onset, tempo)
Older age at irradiation
Dose > 10-20 Gy
TBI
Symptoms of
Combined withmenopause (hotTreatment factors
Radiation dose to pelvis
cyclophosphamide flashes, poor
6-10 Gy
dose > 200 mg/kg libido)(conditioning for
Combined with:
Menstrual history
stem cell transplant) Physical exam with- cranial radiation
height, weight,
Combined with alkylating
Tanner stageagent chemotherapy

Risk Factors

See related topics:
Alkylating agents
Head/brain radiation

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

76

77

78

Hemorrhagic cystitis
See related topics:
Cyclophosphamide
Ifosfamide
Bladder fibrosis
Dysfunctional voiding

Bladder malignancy
See related topics:
Cyclophosphamide
Ifosfamide

Treatment factors
Higher radiation doseHighest Risk

Health Protective
Considerations for Further TestingCounselingand Intervention
Refer to endocrinologist for delayed
Health Link
Female Health Issues after clinical signs of puberty or
persistently abnormal hormone levels
Childhood Cancer
Gynecology or endocrinology
Risks and benefits ofconsultation for hormonal
hormonal replacement
replacement therapy.
therapy
Consider evaluation for conditions
Counseling regarding need exacerbated by hypogonadism
for contraception since(e.g., osteopenia/osteoporosis).
there is tremendous
Reproductive endocrinology
individual variability inconsultation for infertile couples
gonadal toxicity after
interested in assisted reproductive
exposure to radiation
technologies.
LH, FSH, Estradiol Baseline at age 8, and then therapy and alkylating
yearly until normal
agents. Recovery ofpuberty is established,fertility may occur many
AND as clinically
years after therapy.
indicated in patients with:
Resources:- Delayed puberty,
American Society forirregular menses orReproductive Medicine
amenorrhea
website: www.asrm.org- Clinical signs and
See also:
symptoms of estrogenwww.fertilehope.org
deficiency

Treatment factors Urinalysis
Combined withcyclophosphamide
and/or ifosfamide

YearlyTreatment factors
Higher cumulative
radiation dose (> 45 Gy)
Combined with:- cyclophosphamide- ifosfamide

Voiding history

YearlyTreatment factors
Radiation to pelvis
Combined with:- cyclophosphamide- ifosfamide
Health behaviors
Alcohol use
Tobacco use

Urinalysis

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

Urologic consultation for patients withincontinence or dysfunctional voiding.

Health Link
Reducing the Risk ofSecond Cancers
Counsel to promptly reportdysuria or gross hematuria

Urology consultation for culturenegative macroscopic hematuria.

COG Follow-Up Guidelines – Page 26
Version 1.2 – March 2004
Therapeutic Agent
Testicular radiation
Total body irradiation
Testicular
PelvicInguinal/femoral
Spinal > 24 Gy

Sec
#
79

Potential Late Effects

Testicular dysfunction- Azoospermia- Infertility-Hypogonadism-Delayed/arrested
puberty
See related topics:
Alkylating agents
Head/brain radiation

Risk Factors

Highest Risk

Periodic
Evaluation

Treatment factors Semen analysis
Radiation to testes> 6 Gy: azoospermia
likely permanent

Minimum Recommended

Frequency

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Refer to endocrinologist for delayed
clinical signs of puberty or
persistently abnormal hormone levels
Urology or endocrinology consultation
Clinician Info Link
Counseling regarding need for hormonal replacement therapy.
Late recovery of gonadal for contraception since
Consider evaluation for conditions
function has been reported there is tremendous
exacerbated by hypogonadism: e.g.,.
individual variability inosteopenia/osteoporosis.
gonadal toxicity after
Reproductive endocrinology
exposure to radiation
consultation for infertile couples
Radiation to testes History of sexual Yearly
Testicular irradiation
therapy and alkylatinginterested in assisted reproductivefunction (erections,combined with head/brain > 20 Gy: Leydig
agents. Recovery oftechnologies.
nocturnal
cell damage
irradiation
fertility may occur many
emissions, libido).
(affecting
years after therapy.
testosterone
History ofYearlyproduction)
Resources:
Radiation combined medication use.
American Society forwith alkylating
Reproductive Medicine
agentsPhysical exam
Yearlywebsite: www.asrm.org
Combined withincluding height,
See also:
cyclophosphamide weight, Tannerwww.fertilehope.org
dose > 200 mg/kg stage, testicular(conditioning forvolume by Prader
stem cell transplant) orchiometry.
TBI
Baseline at age 9, and then
LH, FSH,
yearly until normal puberty is
Testosterone
Treatment factors
Radiation to testes
1 to 3 Gy: azoospermia
may be reversible.
3 to 6 Gy: azoospermia
possibly reversible (butunlikely)

As requested by patientand for evaluation ofinfertility.

Health Link
Male Health Issues afterChildhood Cancer

established,
AND as clinically indicated inpatients with:- Delayed puberty- Clinical signs and symptomsof 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

Physical exam

YearlyCounsel regarding
increased risk of fractures
in weight-bearing
irradiated bones

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

COG Follow-Up Guidelines – Page 27
Version 1.2 – March 2004
Therapeutic AgentSec#

Potential Late Effects

Risk Factors

Highest Risk

Periodic
Evaluation

Minimum Recommended

Frequency

Health Protective
CounselingConsiderations for Further Testing
and Intervention

Blood/blood products
Clinician Info Link
Consider exposure to any blood or serum product, including packed red cells, whole blood, white cells, platelets, fresh frozen plasma, cryoprecipitate, allogeneic marrow or stem cells, immunoglobulin preparations (e.g., IVIG,
VZIG), and clotting factor concentrates. Since the vast majority of patients received some type of blood product during childhood cancer treatment, screening for Hepatitis and HIV (as indicated based on dates of treatment) is
recommended unless there is absolute certainty that the survivor did not receive any blood or blood products.
Screening of blood donors was initiated in the United States as follows (note - International screening policies may not include these measures):1971 Hepatitis BsAg
1985 HIVAB HIV-1 EIA
1986 Surrogate ALT screening
1990 HCV EIA-I screening
1992 HCV EIA-II screening
Blood or serum productprior to initiation of
Hepatitis B screeningof blood supply (prior
to 1972 in the UnitedStates - date may differ
in other countries).

Blood or serum productprior to initiation of
Hepatitis C screeningof blood supply (prior
to 1993 in the UnitedStates - date may differ
in other countries).

81

Chronic Hepatitis B

Host factors

Living in hyperendemic
See related topics:area
Mercaptopurine
Treatment factors
Methotrexate
Blood products before
Dactinomycin
1972
Hepatic radiation
Health behaviors
Chronic hepatitis C
IV drug use
Hematopoietic celltransplant (liver toxicity) 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
Chronic hepatitis B, C
- Hepatic failure- Hepatocellular carcinoma Health behaviors
Alcohol use
82

Chronic Hepatitis C

Host factors

Living in hyperendemic
See related topics:area
Mercaptopurine
Treatment factors
Methotrexate
Blood products before
Dactinomycin
1993
Hepatic radiation
Healthbehaviors
Chronic hepatitis B
IV drug use
Hematopoietic celltransplant (liver toxicity) 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
Chronic hepatitis B, C
- Hepatic failure- Hepatocellular carcinoma Health behaviors
Alcohol use

Host factors
Chronic immunosuppression

Hepatitis B surface Once in patients who
Health Link
Hepatitis after Childhood
antigen (HBsAg) received treatment forANDcancer prior to 1972 (date Cancer
Hepatitis B core
may vary for international
antibody
patients)(anti HBc or
HBcAb)

Medical conditions Physical exam
Chronic co-infection ALT, AST, AFP,
with hepatotoxic
bilirubin,
viruses: Hepatitis B, prothrombin time
Hepatitis C, and/or Liver ultrasoundHIV

Gastroenterology or hepatology
consultation for patients with chronic
infection.
Hepatitis A immunization in patientslacking immunity.

Yearly in patients withchronic hepatitis
Yearly in patients withcirrhosis

Treatment factors Hepatitis C
Blood products prior antibody
to 1986 whensurrogate screeningof blood donors
with ALT initiatedand donors with
PCR to establish
self-reported high- chronic infection
risk behaviors
deferred.
Chronic
immunosuppression

Once in patients who
Health Link
Hepatitis after Childhood
received treatment forcancer prior to 1993 (date Cancer
may vary for international
patients)

Medical conditions Physical exam andChronic co-infection ALT, AST, AFP,
with hepatotoxic
bilirubin, andviruses: Hepatitis B, prothrombin time
Hepatitis C, and/or Liver ultrasoundHIV

Yearly in patients withchronic hepatitis

Once in patients withpositive hepatitis C
antibody

Yearly in patients withcirrhosis

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.

COG Follow-Up Guidelines – Page 28
Version 1.2 – March 2004

Therapeutic Agent
Blood or serum productafter emergence of HIV
in the blood supply andprior to initiation of
HIV screening of blood
supply (from 1977
through 1985 in the
United States - dates
may differ in othercountries).

Sec
Potential Late Effects#
83 HIV infection

Risk Factors
Treatment factors
Blood products between
1977 and 1985
Health behaviors
IV drug use
unprotected sex
multiple partners
high-risk sexual behavior
sexually transmitted
diseasestattoos, body piercing
Medical conditions
HPV infection

Highest Risk

Periodic
Evaluation
Health behaviors HIV 1 & 2
High-risk behaviors antibodies

Minimum Recommended

Frequency
Once in patients who
received treatment forcancer between 1977 and1985 (dates may vary forinternational patients).

Health Protective
CounselingStandard counselingregarding safe sex,
universal precautions,exacerbating high-risk
behaviors

Considerations for Further Testing
and Intervention
Infectious diseases consultation forpatients with chronic infection.

COG Follow-Up Guidelines – Page 29
Version 1.2 – March 2004
Therapeutic Agent
Surgery
Amputation

Sec#

Potential Late Effects

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

Central venous
catheter

85

Cystectomy

86

Risk Factors

Host factors
Skeletally immature/
growing children

Highest Risk

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 if checks, signs of poor
skeletally mature.
prosthetic fit, residual
limb and prosthetic
Every 6 months until
hygiene.
skeletally mature, thenyearly thereafter.
Yearly, and as clinicallyindicated.

Blood pressure

Yearly

BUN, creatinine,
U/A

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

Urine culture

Yearly and as clinicallyindicated

Physical exam
Prosthetic
evaluation

See related topics:
Ifosfamide
Cisplatin/Carboplatin
Methotrexate
Abdominal/pelvic
radiation
Nephrectomy

87

Cosmesis
Poor prosthetic fit
Orbital hypoplasia

Laparotomy

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
See related topics:
Ifosfamide
Cisplatin/Carboplatin
Methotrexate
Abdominal/pelvic radiation
Cystectomy

Frequency

Health Link
Kidney HealthUrology evaluation Yearly
Na, K, Cl, CO2.
Ca, Mg, PO4

Creatinine clearance

Enucleation

Minimum Recommended

Host factors
Younger age at enucleation

Treatment factors
Combined with radiation
Treatment factors
Combined with radiation
Host factors
Younger age at surgery
Rapid growth spurt

or GFR.
Physical exam
Ophthalmology
Ocularist

Obtain in patients withabnormal BP, U/A, BUN, or
creatinine. If abnormal, repeat
as clinically indicatedYearlyPhysical exam

When symptomatic

Physical exam

Yearly and as neededRadiographYearlyOrthopedic
follow-up

Every 6 months until
skeletally mature, andyearly thereafter

Blood pressure

Yearly

BUN, creatinine,
U/A

YearlyNa, K, Cl, CO2.
Ca, Mg, PO4

Obtain in patients withabnormal BP, U/A, BUN,
or creatinine. If abnormal,
repeat as clinicallyindicated

Health behaviors
Higher risk of loosening inpatients with high level ofphysical activity.
Higher risk of contractures orfunctional limitations inpatients with low level ofphysical activity.
Treatment factors
Combined with othernephrotoxic therapy:- cisplatin, carboplatin- ifosfamide- kidney irradiation- abdominal irradiation- aminoglycosides- amphotericin- immunosuppresants- cyclosporine- methotrexate

Creatinine clearance

or GFR.

Psychological consultation in patientswith emotional difficulties related tocosmesis and visual impairment.
Vocational rehabilitation referral.
Surgical consultation for patientsunresponsive to medical management.
Health Link
Limb Salvage after Bone
CancerCounsel regarding needfor antibiotic
prophylaxis prior todental and invasive
procedures

Psychological consultation in patientswith emotional difficulties related tocosmesis and adaptation following
limb-sparing procedure.
Vocational rehabilitation referral.
Antibiotic prophylaxis prior to dental
and invasive procedures

Nephrology consultation for patients
Health Link
Single Kidney Precautions with hypertension, proteinuria, or
progressive renal insufficiency.
See also: Kidney HealthCOG Follow-Up Guidelines – Page 30
Version 1.2 – March 2004
Therapeutic Agent
Neurosurgery

Orchiectomy

Minimum Recommended
Sec
Potential Late Effects
Risk Factors
Highest Risk
Periodic
Health Protective
Frequency#
EvaluationCounseling
91 Neurocognitive deficits
Neurology
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;
Educational Issues
treatment
and postoperative
continue to monitor if
Following Treatment for(< 3 years)
complications. In general, Treatment factors
symptoms persist.
Childhood Cancer
Supratentorial tumor
mild delays occur in most Combined with:
Every 6 months for- brain radiation
areas ofpatients with seizure- high-dose chemotherapy Treatment factors
neuropsychologicaldisorder.
- 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
Posterior fossa
Seizures
Abdominal x-ray At puberty growth spurt
syndrome
for patients with shunts to
CNS infection
Hydrocephalus
assure distal shunt tubing
Shunt malfunctionin peritoneum
Social factors
Clinical assessment Baseline and yearly
Low SESof educational orPredisposing family vocational
Clinician Info Link
Extent of deficit depends on
history of learning progress
age at treatment, intensity
or attention
Referral for formal Baseline at entry into longof treatment, and time since
problems
neuropsychological term follow-up, thentreatment.
periodically as clinicallyevaluation
New deficits may emerge
indicated for patients withover time.
evidence of impaired
educational or vocational
progress

92

Infertility
Hypogonadism

Treatment factors
Bilateral orchiectomy
Unilateral orchiectomy
combined with pelvic or
testicular radiation and/or
alkylating agents

History of sexual
Yearlyfunction (erections,nocturnal emissions,libido).
History of medication Yearlyuse.
Physical exam
Yearlyincluding height,
weight, Tanner stage,
testicular volume by
Prader orchiometry.
LH, FSH,For patients with bilateral
Testosterone
orchiectomy, refer toendocrinology at about age 9.
For patients with unilateralorchiectomy, obtain asclinically indicated for:
- Delayed puberty- Clinical signs and symptomsof testosterone deficiency
Semen analysis

As requested by patient andfor evaluation of infertility

Health Link
Male Health Issues afterChildhood Cancer
For patients with single
testis - counsel to wear
athletic supporter withprotective cup during
athletic activities.

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
Gadolinium-enhanced MRI:
microvascular injury
CT: calcifications

Refer to endocrinologist for bilateralorchiectomy, delayed clinical signs ofpuberty, or persistently abnormal
hormone levels
Consider surgical placement of
testicular prosthesis.

COG Follow-Up Guidelines – Page 31
Version 1.2 – March 2004
Therapeutic Agent
Pelvic surgery

Pulmonary lobectomy,
pulmonary wedge
resection, pulmonary
metastasectomy

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)- chest/thoracic radiation- spinal radiation >30Gy- total body irradiation

Highest Risk

Minimum Recommended

Periodic
Evaluation
History

YearlyPhysical exam

YearlyPFTs(including DLCO
and spirometry)
and CXR

Baseline at entry into long- Patients who desire to
SCUBA dive should beterm follow-up.
advised to obtain medical
Repeat as clinicallyindicated in patients with clearance from a diving
abnormal or progressive medicine specialist
pulmonary dysfunction.

Physical exam
Blood culture

When febrile T > 101ºFrequency

Health Protective
Counseling
Health Link
For males: Male Health
Issues after Childhood
CancerConsiderations for Further Testing
and Intervention
Urologic consultation for patients withincontinence, dysfunctional voiding,or sexual dysfunction.

Health Link
Pulmonary HealthPulmonary consultation for patientswith symptomatic pulmonary
dysfunction.
Influenza and Pneumococcal
vaccinations.

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

In patients with T > 101º (38.3°C), or
other signs of serious illness,
administer a long-acting, broadMedical alert bracelet/card spectrum parenteral antibiotic (e.g.,
noting asplenia.
ceftriaxone), and continue close
Counsel to avoid malaria
medical monitoring while awaiting
and tick bites if living inblood culture results.
or visiting endemic areas. Hospitalization and broadening of
antimicrobial coverage (e.g., additionof vancomycin) may be necessary
under certain circumstances, such as
the presence of marked leukocytosis,
neutropenia, or significant change
from baseline CBC; toxic clinicalappearance; fever >104°F; meningitis,
pneumonia, or other serious focus of
infection; signs of septic shock; orprevious history of serious infection.
Immunize with Pneumococcal,
Meningococcal, and HIB vaccines.
All patients should receive
Pneumococcal booster 3 - 5 years
after initial dose.
Health Link
Splenic Precautions

COG Follow-Up Guidelines – Page 32
Version 1.2 – March 2004
Therapeutic AgentSec
Potential Late Effects#
Hematopoietic Cell Transplantation
Clinician Info Link
Immune system
Complications after
96 Secretory IgA deficiency
hematopoietic cell
Hypogammaglobulinemia
transplantation have
Chronic infections, such
multifactorial etiology:
as conjunctivitis, sinusitis,- prior therapy forand bronchitis
primary malignancy- intensity of transplant Liverconditioning
97 Chronic hepatitis- stem cell productCirrhosis(e.g., marrow, cord
Iron overload
blood, peripheral
See related topics:
stem cells)
Mercaptopurine- donor (e.g.,
Methotrexate
autologous,
Dactinomycin
allogeneic, unrelated)
Hepatic radiation- quality of donor toTransfusion (chronic
recipient match
hepatitis B & C)
- complication oftransplant process(immunosuppression
and GVHD.)- complications in the
Lungs
post-transplant
98 Bronchiolitis obliterans
period.
Chronic bronchitis- underlying disease
Bronchiectasis- host genetic factors- lifestyle behaviors
This section includes
late treatmentcomplications that may
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
agents(continued on next
page)

Risk Factors

Medical conditions
Chronic GVHD

Treatment factors
History of multiple
transfusions
Radiation to the liver

Highest Risk

Host factors
Low CD4 T-cell
count

Periodic
Evaluation

Minimum Recommended

Frequency

Health Protective
Counseling

History

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

ALT, AST,
bilirubin

Baseline at entry into long Health Link
Liver Healthterm follow-up,

Ferritin

Baseline at entry into longterm follow-up

Prothrombin 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.

Medical conditions
Chronic GVHD
Viral hepatitis

Note: PCR testing for HCV may berequired in immunosuppressed
patients who are negative for
antibody.

Health behaviors
Alcohol use

Treatment factors
Allogeneic transplantThoracic radiation
Total body irradiation
Pulmonary toxic
chemotherapy
Medical conditions
Chronic GVHD

Considerations for Further Testing
and Intervention

Gastroenterology/hepatology consultationin patients with persistent liver
dysfunction.
Hepatitis A and B immunizations inpatients lacking immunity.

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

YearlyHealth Link
Pulmonary HealthPatients who desire to
Baseline at entry into long- SCUBA dive should beterm follow-up
advised to obtain medical
Repeat as clinically
clearance from a diving
indicated in patients with medicine specialist
abnormal or progressive
pulmonary dysfunction
and prior to generalanesthesia.

Pulmonary consultation for patientswith symptomatic pulmonary
dysfunction.
Influenza and Pneumovax vaccination.

COG Follow-Up Guidelines – Page 33
Version 1.2 – March 2004
Therapeutic Agent

Hematopoietic celltransplantation(continued fromprevious page)
Clinician Info Link
Sources of donor stem
cells for transplantation
include:Autologous (patient’s
own marrow or stem
cells are harvested prior
to ablative therapy)
Allogeneic (marrow orstem cells are harvested
from a related or
unrelated donor)
Cord blood (stem cells
harvested fromumbilical cord blood)
Donors are usuallymatched to the patient
based on HLA (Human
Leukocyte Antigen)typing(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
Medical conditions
Hypogonadism

Behavioral factors
Physical inactivity
Clinician Info Link
The World HealthOrganization definition of
osteoporosis in adults isbased on comparison of ameasured bone mineraldensity of young adults at
peak bone age and defined
as a T-score.
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.
Instead, pediatric bonemineral density reference
data sets calculate z-scoresbased on age and gender,
but do not account forvariations 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

Minimum Recommended

Frequency

Health Protective
Counseling

YearlyBaseline screening at 18 Health Link
Treatment factors Bone density
years old; consider earlier Keeping Your Bones
Prolonged
evaluation
screening if clinically
Healthy After Childhood
corticosteroid(DEXA orindicated.
Cancertherapy for chronic quantitative CT)
Repeat as clinically
GVHD
indicated.
National Osteoporosis
Clinician InfoFoundation website:
Link
www.nof.org
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.

Considerations for Further Testing
and Intervention
Consultation with rehabilitation
medicine/physiatrist.
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 > 2.5 SD below
mean, or patients with history ofmultiple fractures, for otherpharmacologic interventions (e.g.,bisphosphonates, calcitonin, selective
estrogen receptor modulators).

COG Follow-Up Guidelines – Page 34
Version 1.2 – March 2004
Therapeutic Agent

Hematopoietic celltransplantation(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

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

Highest Risk

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

Periodic
Evaluation
Physical exam
CBC/differential

Minimum Recommended

Frequency

Health Protective
Counseling

Yearly up to 15 years after Health Link
exposure to agent.
Reducing the Risk ofSecond Cancers

Considerations for Further Testing
and Intervention
Bone marrow exam as clinicallyindicated.

Counsel to promptly reportfatigue, pallor, petechiae,
or bone pain.

Treatment factors Physical exam
Higher dose TBI

YearlyPhysical exam

YearlyPhysical exam

YearlyHealth Link
Reducing the Risk ofSecond Cancers

Oncology consultation as clinicallyindicated.

Treatment 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

Oncology consultation as clinicallyindicated.

Health Link
Skin Health

Medical conditions
Chronic GVHD

General Health Screening
103

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

COG Follow-Up Guidelines – Page 35
Version 1.2 – March 2004

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 survivors of childhood, adolescent, or young adult cancers who are at increased risk of a specific cancer due to prior therapy, comorbid 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 are encouraged 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 prerogative of 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
Hormone replacement
therapy

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
Clinical breast exam

Every 3 years between ages
20-39; then yearly beginningat age 40

BRCA1, BRCA2, ATMmutation

MammogramHighest Risk:
Breast self-examination

Every year beginning at age 40

Clinical 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

Cervical PAP smear

Surgery and/or oncology consultation as clinicallyindicated.

Monthly beginning at puberty.

Begin screening (in patients with a cervix) 3 years after firstvaginal intercourse, or at age 21, whichever occurs firstStandard Risk:
Pelvic exam

Health Link
Breast Cancer after
Treatment forChildhood Cancer:
Are You at Risk?

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
annual PAP tests in a row,
may screen every 2-3 years.

Highest Risk:
Pelvic exam

YearlyCervical PAP smear

YearlyGynecology and/or oncology consultation as
Health Link
Reducing the Risk of clinically indicated.
Second Cancers

COG Follow-Up Guidelines – Page 36
Version 1.2 – March 2004
Organ
Colorectal

Sec
#
106

At Risk Population
High fat/low fiber dietAge >50 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
Considerations for Further Testing andCounselingInterventions
Gastroenterology, surgery and/or oncology
Health Link
Reducing the Risk of consultation as clinically indicated.
Second Cancers

AND/OR

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

Every 5 years beginning at age
50.
ORColonoscopy

Every 10 years beginning atage 50Highest Risk:
Monitoring to begin 15 years after radiation or at age 35
years (whichever occurs last). Monitor more frequently ifclinically indicated.
Choose from one of the following three options:Fecal occult blood (minimum Yearly, beginning 15 yearsof 3 cards)
after radiation or at age 35(whichever occurs last).
AND
Flexible sigmoidoscopy

Every 5 years
OR

Double contrast barium
enema

Every 5 years

OR

Endometrial

107

Obesity
Older age
Unopposed estrogentherapy

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 ofSecond Cancers

COG Follow-Up Guidelines – Page 37
Version 1.2 – March 2004
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 indicatedHighest Risk:
Oral cavity exam

Head and neck/otolaryngology consultation as
Health Link
Yearly if tobacco use or
Reducing the Risk of indicated.
history of head/neck radiation Second Cancers

Tobacco 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

Young males

Minimum Recommended
Frequency

Health Protective
Considerations for Further Testing andCounselingInterventions
Surgery and/or oncology consultation as clinically
Health Link
Reducing the Risk of indicated.
Second Cancers

Dental Health

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 cryptorchidism
History of testicular cancer or
carcinoma- in-situ incontralateral testis.
History of gonadal dysgenesis
Klinefelter's syndrome
Family history of testicularcancerStandard Risk:
Digital rectal exam

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

Yearly, beginning at age 45

Surgery, dermatology, and/or oncology
Health Link
Every 3 years, from ages 20-39 Reducing the Risk of consultation as clinically indicated.
Yearly, beginning at age 40.
Second Cancers
Monthly

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

Urology and/or oncology consultation as clinically
Health Link
Reducing the Risk of indicated.
Second Cancers

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

Highest Risk:
Testicular self-exam

Monthly, beginning at puberty

Clinical testicular exam

YearlySkin HealthUrology and/or oncology consultation as clinically
Health Link
Reducing the Risk of indicated.
Second Cancers

Long-Term Follow-Up Guidelines for Survivors ofChildhood, Adolescent, and Young Adult Cancers
Version 1.2 – March 2004

References

COG Long-Term Follow-Up Guidelines Version 1.2 – March 2004 – References 1

Section1

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2

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4

Bath LE, Hamish W, Wallace B, et al. Late effects of the treatment of childhood cancer on the female reproductive system and the potential for fertility preservation. Br J Obstet
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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 Jun; 2(6):571-577.
Howell SJ, Shalet SM. Testicular function following chemotherapy. Hum Reprod Update 2001 Jul-Aug; 7(4): 363-369.
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2001 Feb; 91(3): 613-21.

COG Long-Term Follow-Up Guidelines Version 1.2 – March 2004 – References 2

SectionReferences
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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 Jul: 35(1): 52-63.
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6

Ginsberg SJ, Comis RL. The pulmonary toxicity of antineoplastic agents. Semin Oncol 1982 Mar; 9(1): 34-51.
Kreisman H, Wolkove N: Pulmonary toxicity of anti-neoplastic therapy. Semin Oncol 1992 Oct; 19(5): 508-20.
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 Aug 9; 323(6):378-382.
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7

Dahlgren S, Holm G, Svanborg N, et al. Clinical and morphological side-effects of busulfan (Myleran) treatment. Acta Med Scand. 1972 Jul-Aug;192(1-2):129-35.
Holmstrom G, Borgstrom B, Calissendorff B. Cataract in children after bone marrow transplantation: relation to conditioning regimen. Acta Ophthalmol Scand. 2002 Apr;80(2):211-5.
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8Stillwell TJ, Benson RC. Cyclophosphamide-induced hemorrhagic cystitis: a review of 100 patients. Cancer 1988 Feb 1; 61(3):451-457.
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9Pederson-Bjergaardd J, Ersboll J, Hansen VL, et al. Carcinoma of the urinary bladder after treatment with cyclophosphamide for non- Hodgkin's lymphoma. N Engl J Med 1988 Apr 21;
318(16):1028-1032.

COG Long-Term Follow-Up Guidelines Version 1.2 – March 2004 – References 3

Section
10

References
Burk CD, Restaino I, Kaplan BS, et al. Ifosfamide-induced renal tubular dysfunction and rickets in children with Wilms tumor. J Pediatr 1990 Aug; 117(2 Pt1): 331-335.
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Skinner R, Sharkey IM, Pearson ADJ, et al. Ifosfamide, mesna, and nephrotoxicity in children. J Clin Oncol 1993 Jan; 11(1):173-190.

11

Macdonald MR, Harrison RV, Wake M, et al. Ototoxocity of carboplatin: comparing animal and clinical models at the Hospital for Sick Children. J Otolaryngol 1994 Jun; 23(3):151-59.
Mahoney DH, Weaver T, et al. Ototoxicity with cisplatin therapy. J Pediatr 1983 Dec; 103(6): 1006-1007.
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
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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 Jun; 7(6):754-760.

12

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.
Cvitkovic E. Cumulative toxicities from cisplatin therapy and current cytoprotective measures. Cancer Treat Rev 1998 Aug; 24(4):265-281.
Tuxen MK, Hansen SW. Neurotoxicity secondary to antineoplastic drugs. Cancer Treat Rev 1994 Apr; 20(2): 191- 214.

13

Blanchetti MG, Kanaka C, Ridolfi-Luthy A, et al. Persisting renotubular sequelae after cisplatin in children and adolescents. Am J Nephrol 1991; 11(2):127-130.
Ceremuzynski L, Gebalska J, Wolk R, et al. Hypomagnesemia in heart failure with ventricular arrhythmias. Beneficial effects of magnesium supplementation. J Int Med 2000 Jan;247(1):78-86.
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 Apr; 41(4):1274-1281.
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14

Ellis PA, Fitzharris BM, George P, et al. Fasting plasma lipid measurements following cisplatin chemotherapy in patients with germ cell tumors. J Clin Oncol 1992 Oct;10 (10):1609-14.
Gietema JA, Meinardi MT, Messerschmidt J et al. Circulating plasma platinum more than 10 years after cisplatin treatment for testicular cancer. Lancet 2000 Mar 25;355(9209):1075-6.
Meinardi MT, Gietema JA, van der Graaf WT et al. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol. 2000 Apr;18(8):1725-32.
Raghavan D, Cox K, Childs A, et al. Hypercholesterolemia after chemotherapy for testis cancer. J Clin Oncol 1992 Sep; 10: 1386-1389.

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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
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Nysom K, Holm K Michaelson KF, et al. Bone mass after allogeneic BMT for childhood leukemia or lymphoma. Bone Marrow Transpl 2000 Jan; 25(2): 191-196.
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Long-Term Follow-Up Guidelines for Survivors ofChildhood, Adolescent, and Young Adult Cancers
Version 1.2 – March 2004

Index

Index – Page 1 of 12
Version 1.2 – March 2004

Index
Therapy

SectionAny Cancer Experience

Therapy

SectionMelphalan

Psychosocial effects

1

AML/MDS

5

Limitations in healthcare access2

Hypogonadism, infertility, early menopause

4

Procarbazine
Any Chemotherapy
Dental abnormalities

3

Busulfan
AML/MDS

5

Cataracts

7

Hypogonadism, infertility, early menopause

4

Pulmonary fibrosis

6

Carmustine (BCNU)
AML/MDS

5

Hypogonadism, infertility, early menopause

4

Pulmonary fibrosis

6

Chlorambucil
AML/MDS

5

Hypogonadism, infertility, early menopause

4

Cyclophosphamide
AML/MDS

5

Bladder malignancy

9

Hemorrhagic cystitis, bladder fibrosis, dysfunctional voiding

8
4

4

AML/MDS

5

Hypogonadism, infertility, early menopause

4Non-classical alkylators
Dacarbazine
AML/MDS

5

Hypogonadism, infertility, early menopause

4Temozolamide
AML/MDS

5

Hypogonadism, infertility, early menopause

4

Heavy Metals
Cisplatin
AML/MDS

5

Dyslipidemia

14

Hypogonadism, infertility, early menopause

4

Ototoxicity

11

Peripheral sensory neuropathy

12

Renal toxicity

13

Carboplatin

Ifosfamide
AML/MDS

5

Hypogonadism, infertility, early menopause
Thiotepa

Alkylating Agents

Hypogonadism, infertility, early menopause

AML/MDS

5

Bladder malignancy

9

Renal toxicity

10

Hemorrhagic cystitis, bladder fibrosis, dysfunctional
voiding

8

Hypogonadism, infertility, early menopause

AML/MDS

5

Dyslipidemia

14

Hypogonadism, infertility, early menopause

4

Ototoxicity

11

Peripheral sensory neuropathy

124Renal toxicity

13

AML/MDS

5

Antimetabolites

Hypogonadism, infertility, early menopause

4

Cytarabine (high-dose IV)

Pulmonary fibrosis

6

Neurocognitive deficits

15

Clinical leukoencephalopathy

15

Lomustine (CCNU)

Mechlorethamine
AML/MDS

5

Hypogonadism, infertility, early menopause

4(with or without imaging abnormalities)

Index – Page 2 of 12
Version 1.2 – March 2004

Index
Therapy

SectionAntimetabolites, continued

Dexamethasone
16

Methotrexate (po, IV, IM)
Osteopenia, Osteoporosis

17

Renal dysfunction

18

Hepatic dysfunction

19

Methotrexate(IT, high-dose IV)
Neurocognitive deficits

20

Clinical leukoencephalopathy

20(with or without imaging abnormalities)

26

Cataracts

27

Osteopenia, Osteoporosis

25

Prednisone
Avascular necrosis (AVN)

26

Cataracts

27

Osteopenia, Osteoporosis

25

Asparaginase
16

Anthracycline antibiotics

No known late effects

28

Plant aklaloids

Doxorubicin
AML

21

Cardiomyopathy/Arrhythmias

22

Daunorubicin
AML

21

Cardiomyopathy/Arrhythmias

22

Epirubicin
AML

21

Cardiomyopathy/Arrhythmias

22

Idarubicin
AML

21

Cardiomyopathy/Arrhythmias

22

Mitoxantrone
AML

21

Cardiomyopathy/Arrhythmias

22

Anti-tumor antibiotics
Bleomycin
Acute respiratory distress syndrome (ARDS)

23

Interstitial pneumonitis

23

Pulmonary fibrosis

23

Dactinomycin
No known late effects

Avascular necrosis (AVN)

EnzymesThioguanine
Hepatic dysfunction, veno-occlusive disease

SectionCorticosteroids

Mercaptopurine
Hepatic dysfunction, veno-occlusive disease

Therapy24

Vinblastine
Peripheral sensory or motor neuropathy

29

Vasospastic attacks (Raynaud's phenomenon)

30

Vincristine
Peripheral sensory or motor neuropathy

29

Vasospastic attacks (Raynaud's phenomenon)

30

Epipodophyllotoxins
Etoposide (VP-16)
AML

31

Teniposide (VM-26)
AML

31

Index – Page 3 of 12
Version 1.2 – March 2004

Index
Therapy

SectionRadiation

Therapy
Total Body Irradiation (TBI) (continued)

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

35

Dysplastic nevi, skin cancer

34

Secondary benign or malignant neoplasms

33

Skin changes

32

Total Body Irradiation (TBI)

Section72

Gastrointestinal malignancy

73

Gonadotropin deficiency

45

Growth hormone deficiency

40

Hepatic fibrosis

69

Hepatocellular carcinoma

70

Hyperprolactinemia

41

Hypertension

68

Hyperthyroidism

56

Hypothyroidism

55

Kyphosis

61

Musculoskeletal growth problems

59

Myocardial infarction

65

Neurocognitive deficits

36
38
52

Arrhythmia

65

Occlusive cerebral vasculopathy

Atherosclerotic heart disease

65

Otosclerosis

39

Ovarian dysfunction

75

Breast cancer

63

Overweight/obesity

46

Breast tissue hypoplasia

64

Pericardial fibrosis

65

71

Pericarditis

65

Cardiomyopathy

65

Precocious puberty

44

Carotid artery disease57

Pulmonary fibrosis

66

Cataracts/adverse effects on eye

51

Renal insufficiency

68

Central adrenal insufficiency

43

Restrictive/obstructive lung disease66

42

Scoliosis

60

72

Sensorineural hearing loss

52

47

Stroke/moyamoya

38

Cirrhosis

69

Testicular dysfunction

79

Clinical leukoencephalopathy

37

Thyroid cancer

54

Thyroid nodules

53
52

Brain tumor

Bowel obstruction

Central hypothyroidism
Chronic enterocolitis
Chronic sinusitis(with or without neuro-imaging abnormalities)
Conductive hearing loss

52

Tinnitus

Congestive heart failure

65

Tympanosclerosis

52

Craniofacial abnormalities

50

Uterine vascular insufficiency

74

Delayed interstitial pneumonitis

66

Valvular disease (cardiac)

65

49

Xerostomia

48

Dental abnormalities
Esophageal stricture

58

Eustachian tube dysfunction

52

Index – Page 4 of 12
Version 1.2 – March 2004

Index
Therapy

SectionHead/Brain Radiation

Therapy

Section

Craniospinal (continued)

Cranial (whole brain)

Central hypothyroidism

42

Brain tumor

39

Chronic sinusitis

47

Carotid artery disease57

Clinical leukoencephalopathy

37

Cataracts/adverse effects on eye

51

Central adrenal insufficiency

43

Conductive hearing loss

Central hypothyroidism

42

Craniofacial abnormalities

50

Chronic sinusitis

47

Dental abnormalities

49

Clinical leukoencephalopathy

37

Esophageal stricture

58

Eustachian tube dysfunction

5245(with or without neuro-imaging abnormalities)(with or without neuro-imaging abnormalities)
52

Conductive hearing loss

52

Gonadotropin deficiency

Craniofacial abnormalities

50

Growth hormone deficiency

40

Dental abnormalities

49

Hyperprolactinemia

41

Esophageal stricture

58

Hyperthyroidism

56

Eustachian tube dysfunction

52

Hypothyroidism

55

Gonadotropin deficiency

45

Neurocognitive deficits

36

Growth hormone deficiency

40

Occlusive cerebral vasculopathy

38

Hyperprolactinemia

41

Otosclerosis

52

Hyperthyroidism

56

Overweight/obesity46

Hypothyroidism

55

Precocious puberty

44

Neurocognitive deficits

36

Sensorineural hearing loss

52

Occlusive cerebral vasculopathy

38

Stroke/moyamoya

38

Otosclerosis

52

Thyroid cancer

54

Overweight/obesity46

Thyroid nodules

53

Precocious puberty

44

Tinnitus

52

Sensorineural hearing loss

52

Tympanosclerosis

52

Stroke/moyamoya

38

Xerostomia

48

Thyroid cancer

54

Spinal dose >12 Gy:

Thyroid nodules

53

Musculoskeletal growth problems

59

Tinnitus

52

Scoliosis

60

Tympanosclerosis

52

Spinal dose >15 Gy:

Xerostomia

48

Hypertension

68

Renal insufficiency

68

Craniospinal

Spinal dose >20 Gy:

Brain tumor

39

Bowel obstruction

71

Carotid artery disease57

Chronic enterocolitis

72

Cataracts/adverse effects on eye

51

Fistula, stricture (bowel)

72

Central adrenal insufficiency

43(continued next page)Index – Page 5 of 12
Version 1.2 – March 2004

Index
Therapy

Section

Craniospinal (continued)

Therapy

SectionNasopharyngeal (continued)

Spinal dose >24 Gy:

Eustachian tube dysfunction

52

Ovarian dysfunction75

Gonadotropin deficiency

45

Testicular dysfunction

79

Growth hormone deficiency

40

Hyperprolactinemia

41

Spinal dose >25 Gy:
Gastrointestinal malignancy

73

Spinal dose >30 Gy

Hyperthyroidism

56

Hypothyroidism

55

Arrhythmia

65

Neurocognitive deficits

36

Atherosclerotic heart disease65

Occlusive cerebral vasculopathy

38

Bladder fibrosis/dysfunctional voiding

77

Otosclerosis

52

Bladder malignancy

78

Overweight/obesity

46

Breast cancer

63

Precocious puberty

44

Breast tissue hypoplasia

64

Sensorineural hearing loss

52

Cardiomyopathy

65

Stroke/moyamoya

38

Congestive heart failure

65

Thyroid cancer

54

Delayed interstitial pneumonitis

66

Thyroid nodules

53

Esophageal stricture

62

Tinnitus

52

Hemorrhagic cystitis

76

Tympanosclerosis

52

Kyphosis

61

Xerostomia

48

Myocardial infarction

65

Pericardial fibrosis

65

Oropharyngeal

Pericarditis

65

Brain tumor

39

Pulmonary fibrosis

66

Carotid artery disease57

Restrictive/obstructive lung disease

66

Central adrenal insufficiency

43

Valvular disease (cardiac)

65

Central hypothyroidism

42

Nasopharyngeal

Chronic sinusitis

47

Clinical leukoencephalopathy

37

Brain tumor

39

Carotid artery disease57(with or without neuro-imaging abnormalities)
Craniofacial abnormalities

50

Central adrenal insufficiency

43

Dental abnormalities

49

Central hypothyroidism

42

Esophageal stricture

58

Chronic sinusitis

47

Gonadotropin (LH/FSH) deficiency

45

Clinical leukoencephalopathy

37

Growth hormone deficiency

40

Hyperprolactinemia

41(with or without neuro-imaging abnormalities)
52

Hyperthyroidism

56

Craniofacial abnormalities

50

Hypothyroidism

55

Dental abnormalities

49

Neurocognitive deficits

36

58(continued next page)

Conductive hearing loss

Esophageal strictureIndex – Page 6 of 12
Version 1.2 – March 2004

Index
Therapy

SectionOropharyngeal (continued)
Occlusive cerebral vasculopathy

Therapy

SectionOrbital/Eye (continued)
38

Xerostomia

48

Overweight/obesity

46

Precocious puberty

44

Ear/Infratemporal

Stroke/moyamoya

38

Brain tumor

39

Thyroid cancer

54

Central adrenal insufficiency

43

Thyroid nodules

53

Central hypothyroidism

42

48

Chronic sinusitis

47

Clinical leukoencephalopathy

37(with or without neuro-imaging abnormalities)
Conductive hearing loss

52

Xerostomia
Orbital/Eye
Brain tumor

39

Cataracts

51

Central adrenal insufficiency

43

Central hypothyroidism

42

Chronic painful eye

51

Chronic sinusitis

47

Clinical leukoencephalopathy

37(with or without neuro-imaging abnormalities)
Craniofacial abnormalities

50

Dental abnormalities

49

Enophthalmos

51

Gonadotropin deficiency

45

Growth hormone deficiency
Hyperprolactinemia
Keratitis

40
41
51

Craniofacial abnormalities

50

Dental abnormalities

49

Eustachian tube dysfunction

52

Gonadotropin (LH/FSH) deficiency

45

Growth hormone deficiency

40

Hyperprolactinemia

41

Neurocognitive deficits

36

Occlusive cerebral vasculopathy

38

Otosclerosis

52

Overweight/obesity

46

Precocious puberty

44

Sensorineural hearing loss

52

Stroke/moyamoya

38

Tinnitus

52
52
48

Keratoconjunctivitis sicca

51

Tympanosclerosis

Lacrimal duct atrophy

51

Xerostomia

Neurocognitive deficits

36

Occlusive cerebral vasculopathy

38

Optic chiasm neuropathy

51

Orbital hypoplasia

51

Overweight/obesity

46

Precocious puberty

44

Reduced visual acuity

51

Retinopathy

51

Stroke/moyamoya

38

Telangiectasias

51

Xerophthalmia (severe)

51

Neck Radiation
CervicalCarotid artery disease57

Dental abnormalities

49

Esophageal stricture

58

Hyperthyroidism

56

Hypothyroidism

55

Thyroid cancer

54

Thyroid nodules

53

Xerostomia

48Index – Page 7 of 12
Version 1.2 – March 2004

Index
Therapy

SectionSpinal Radiation

Therapy

SectionSpinal Radiation >30 Gy (continued)

Any dose:

Pericarditis

65

Carotid artery disease57

Pulmonary fibrosis

66

Esophageal stricture

58

Restrictive/obstructive lung disease66

Hyperthyroidism

56

Valvular disease (cardiac)

65

Hypothyroidism

55

Thyroid cancer

54

Chest/Thorax Radiation

Thyroid nodules

53

Mantle>12 Gy:Arrhythmia

65

Musculoskeletal growth problems

59

Atherosclerotic heart disease65

Scoliosis

60

Breast cancer

63

Breast tissue hypoplasia

64>15 Gy:Hypertension

68

Cardiomyopathy

65

Renal insufficiency

68

Carotid artery disease

57

Congestive heart failure

65>20 Gy:Bowel obstruction

71

Delayed interstitial pneumonitis

66

Chronic enterocolitis

72

Dental abnormalities

49

Fistula, stricture (bowel)

72

Esophageal stricture

62

Hyperthyroidism

56>24 Gy:Ovarian dysfunction

75

Hypothyroidism

55

Testicular dysfunction

79

Kyphosis61>25 Gy:Gastrointestinal malignancy

73>30 GyMusculoskeletal growth problems

59

Myocardial infarction

65

Pericardial fibrosis

65

Arrhythmia

65

Pericarditis

65

Atherosclerotic heart disease

65

Pulmonary fibrosis

66

Bladder fibrosis/dysfunctional voiding

77

Restrictive/obstructive lung disease

66

Bladder malignancy

78

Scoliosis

60

Breast cancer

63

Thyroid cancer

54

Breast tissue hypoplasia

64

Thyroid nodules

53

Cardiomyopathy

65

Valvular disease (cardiac)

65

Congestive heart failure

65

Xerostomia

48

Delayed interstitial pneumonitis

66

Esophageal stricture

62

Mediastinal

Hemorrhagic cystitis

76

Arrhythmia

65

Kyphosis61

Atherosclerotic heart disease

65

Myocardial infarction

65

Breast cancer

63

Pericardial fibrosis

65(continued next page)Index – Page 8 of 12
Version 1.2 – March 2004

Index
Therapy

SectionMediastinal (continued)

Therapy

SectionWhole lung (continued)

Breast tissue hypoplasia

64

Pulmonary fibrosis

66

Cardiomyopathy

65

Restrictive/obstructive lung disease66

Carotid artery disease57

Scoliosis

60

Congestive heart failure

65

Thyroid cancer

54

Delayed interstitial pneumonitis

66

Thyroid nodules

53

Esophageal stricture

62

Valvular disease (cardiac)

65

Hyperthyroidism

56

Hypothyroidism

55

Kyphosis

61

Musculoskeletal growth problems

59

Myocardial infarction

65

Pericardial fibrosis

65

Pericarditis

65

Pulmonary fibrosis

66

Restrictive/obstructive lung disease66

Scoliosis

60

Thyroid cancer

54

Thyroid nodules

53

Valvular disease (cardiac)

65

Whole lungArrhythmia

65

Atherosclerotic heart disease

65

Breast cancer

63

Breast tissue hypoplasia

64

Cardiomyopathy

65

Carotid artery disease

57

Congestive heart failure

65

Delayed interstitial pneumonitis

66

Esophageal stricture

62

Hyperthyroidism

56

Hypothyroidism

55

Kyphosis

61

Musculoskeletal growth problems

59

Myocardial infarction

65

Pericardial fibrosis

65

Pericarditis

65Index – Page 9 of 12
Version 1.2 – March 2004

Index
Therapy

Section

Abdominal/Pelvic Radiation

Therapy

SectionWhole abdomen (continued)

Note: The following are potential late effects for
all abdominal and pelvic fields:
Any radiation dose to an abdominal or pelvic field:

Pulmonary fibrosis

66

Renal insufficiency

68

Restrictive/obstructive lung disease

66

Uterine vascular insufficiency

74
65

Bone malignancies

35

Valvular disease (cardiac)

Bowel obstruction

71>30 Gy:Chronic enterocolitis

72

Functional asplenia

67

Dysplastic nevi, skin cancer

34

Life-threatening infection

67

Fistula, strictures (bowel)

72

Musculoskeletal growth problems

59

Scoliosis

60

Secondary benign or malignant neoplasms

33

Skin changes (fibrosis, telangiectasias)

32

Dose >25 Gy to an abdominal or pelvic field:
Gastrointestinal malignancy

73

Whole abdomen

Any upper abdominal field
Delayed interstitial pneumonitis

66

Esophageal stricture

62

Kyphosis

61

Pulmonary fibrosis

66

Restrictive/obstructive lung disease

66

Left Upper Quadrant

Any dose:
Arrhythmia

65

Atherosclerotic heart disease

65

Bladder fibrosis/dysfunctional voiding

77

Bladder malignancy

78

Bowel obstruction

71

Cardiomyopathy

65

Cirrhosis

69

Congestive heart failure

65

Delayed interstitial pneumonitis

66

Esophageal stricture

62

Hemorrhagic cystitis

76

Hepatic fibrosis

69

Hepatocellular carcinoma

70

Hypertension

68

Kyphosis61

Myocardial infarction

65

Ovarian dysfunction

75

Pericardial fibrosis

65

Pericarditis

65

Arrhythmia

65

Atherosclerotic heart disease65

Cardiomyopathy

65

Congestive heart failure

65

Delayed interstitial pneumonitis

66

Esophageal stricture

62

Functional asplenia (>30 Gy)

67

Kyphosis61

Life-threatening infection (>30 Gy)

67

Myocardial infarction

65

Pericarditis, pericardial fibrosis

65

Pulmonary fibrosis

66

Restrictive/obstructive lung disease66

Valvular disease (cardiac)

65

Entire spleen
Arrhythmia

65

Atherosclerotic heart disease65

Cardiomyopathy

65(continued next page)Index – Page 10 of 12
Version 1.2 – March 2004

Index
Therapy

SectionEntire spleen (continued)

Therapy

SectionLeft hemiabdomen/Left flank (continued)

Congestive heart failure

65

Esophageal stricture

62

Delayed interstitial pneumonitis

66

Kyphosis

61

Esophageal stricture

62

Myocardial infarction

65

Functional asplenia (>30 Gy)

67

Pericarditis, pericardial fibrosis

65

Kyphosis

61

Pulmonary fibrosis

66

Life-threatening infection (>30 Gy)

67

Restrictive/obstructive lung disease

66

Myocardial infarction

65

Valvular disease (cardiac)

65

Pericarditis, pericardial fibrosis

65

Pulmonary fibrosis

66

Restrictive/obstructive lung disease

66

Bladder fibrosis/dysfunctional voiding

Valvular disease (cardiac)

65

Bladder malignancy

78

Hemorrhagic cystitis

76

Hypertension

68

Renal (see also: Left hemiabdomen/Left flank)

Para-aortic
77

Delayed interstitial pneumonitis

66

Ovarian dysfunction

75

Esophageal stricture

62

Renal insufficiency

68

Hypertension

68

Uterine vascular insufficiency

74

Kyphosis

61

Pulmonary fibrosis

66

PelvicRenal insufficiency

68

Bladder fibrosis/dysfunctional voiding

Restrictive/obstructive lung disease

66

Bladder malignancy

78

Hemorrhagic cystitis

76

Hepatic

77

Ovarian dysfunction

75

69

Testicular dysfunction

79

Delayed interstitial pneumonitis

66

Uterine vascular insufficiency

74

Esophageal stricture

62

Hepatic fibrosis

69

Hepatocellular carcinoma

70

Bladder fibrosis/dysfunctional voiding

Kyphosis61

Bladder malignancy

78

Pulmonary fibrosis

66

Hemorrhagic cystitis

76

Restrictive/obstructive lung disease66

Ovarian dysfunction

75

Uterine vascular insufficiency

74

Cirrhosis

Iliac/inguinal77

Left hemiabdomen/Left flankArrhythmia

65

Atherosclerotic heart disease65

Cardiomyopathy

65

Congestive heart failure

65

Delayed interstitial pneumonitis

66

Inguinal/femoral
Testicular dysfunction

79Index – Page 11 of 12
Version 1.2 – March 2004

Index
Therapy

Section

Other Radiation Fields
79

Extremity Radiation
Musculoskeletal growth problems

SectionLimb sparing procedure (continued)

Testicular
Testicular dysfunction

Therapy
Contractures

89

Functional and activity limitations

89

Limb length discrepancy

89

Loosening of endoprosthesis

89

80
Nephrectomy

Blood/Blood products

Hydrocele

90
90

Chronic Hepatitis B and related complications

81

Hyperfiltration

Chronic Hepatitis C and related complications

82

Proteinuria

90

HIV infection

83

Renal insufficiency

90

Surgery

Neurosurgery

Amputation

Hydrocephalus

91

Cosmesis

84

Intracranial bleed/stroke

91

Functional and activity limitations

84

Motor deficits

91

Residual limb integrity problems

84

Neurocognitive deficits

91

Phantom pain

84

Seizures91

Shunt malfunction

91

Central venous catheter
Infection of retained cuff or line tract

85

Thrombosis

85

Vascular insufficiency

85

Orchiectomy
Hypogonadism/infertility

92

Pelvic surgery
Cystectomy

Bladder incontinence

93

Chronic urinary tract infection

86

Bowel incontinence

93

Renal dysfunction

86

Hydrocele

93

Enucleation
Cosmesis93

Retrograde ejaculation

93

87

Orbital hypoplasia

87

Poor prosthetic fit

87

Laparotomy
Adhesive/obstructive complications

Impotence

88

Limb sparing procedure
Chronic infection

89

Chronic pain

89

Pulmonary lobectomy, wedge resection
Pulmonary insufficiency

94

SplenectomyLife-threatening infection

95Index – Page 12 of 12
Version 1.2 – March 2004

Index
Therapy

SectionHematopoietic cell transplantation

Therapy
General Health Screening

Alopecia

102

AML

101

Section103

Cancer Screening

Bronchiectasis

98

Breast104

Bronchiolitis obliterans

98

Cervical105

Chronic bronchitis

98

Colorectal

106

Chronic infection

96

Endometrial

107

Chronic hepatitis

97

Lung

108

Cirrhosis

97

Oral

109

Hypogammaglobulinemia

96

Prostate

110

Iron overload

97

Skin

111

Joint contractures

99

Testicular

112

Lymphoma101

Myelodysplasia

101

Nail dysplasia

102

Osteopenia

100

Osteoporosis

100

Scleroderma

102

Secretory IgA deficiency

96

Solid cancers

101

Vitiligo

102

Long-Term Follow-Up Guidelines for Survivors ofChildhood, Adolescent, and Young Adult Cancers
Version 1.2 – March 2004

Scoring

Version 1.2 – March 2004
Scoring Explanation

Explanation of Scoring for the Long-Term Follow-Up 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 of childhood, adolescent, and young adultcancers.
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 amodified version of the National Comprehensive Cancer Network “Categories of Consensus,” as follows:
Category

Statement of Consensus

1

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

2A

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

2B

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

3

There is major disagreement that the recommendation is appropriate

Uniform consensus: Near-unanimous agreement of the panel with some possible neutral positions.
Non-uniform consensus: The majority of panel members agree with the recommendation; however, there is recognition among panel members that,given the quality of evidence, clinicians may choose to adopt different approaches.
High-level evidence: Evidence derived from high quality case control or cohort studies.
Lower-level evidence: Evidence derived from non-analytic studies, case reports, case series, and 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 and appropriateness of the screening
recommendation) or “2B” (there is non-uniform consensus among the reviewers regarding strength of evidence and appropriatenessof the screening 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.

Scoring by Panel of Experts –Page 1 of 6
Version 1.2 – March 2004

Scoring
THERAPY
Any cancer experience
Any chemotherapy
Alkylating agentsClassical alkylators:
Mechlorethamine
Cyclophosphamide
Ifosfamide
Melphalan
Chlorambucil
Lomustine (CCNU)
Carmustine (BCNU)
BusulfanThiotepa
Procarbazine

LATE EFFECT
Psychosocial effects

SCORE
2A

Limitations in healthcare access

2A

Dental abnormalities

1

Hypogonadism
Infertility
Early menopause (females)

1

AML/MDS

1

Hypogonadism
Infertility
Early menopause (females)

2A

AML/MDS

2A

Ototoxicity

1

Peripheral neuropathy

2A

Renal toxicity

1

Dyslipidemia

2B

Busulfan
Carmustine (BCNU)
Lomustine (CCNU)

Pulmonary fibrosis

1

Busulfan

Cataracts

Non-classicalalkylators:
Dacarbazine
Temozolamide
Cisplatin
Carboplatin
Cisplatin
Carboplatin

THERAPY
Cyclophosphamide
Ifosfamide

1

Ifosfamide

Renal toxicity

1

Antimetabolites
Methotrexate(po, IV, IM)

Osteopenia, Osteoporosis

2B

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

Acute respiratory distress syndrome

2B

Anti-tumor antibiotics
Dactinomycin
Bleomycin

1

SCORE
1

Bladder malignancy

Anthracyclines
Doxorubicin
Daunorubicin
Idarubicin
Mitoxantrone
Epirubicin

2B

LATE EFFECT
Hemorrhagic cystitis
Bladder fibrosis
Dysfunctional voiding

Scoring by Panel of Experts –Page 2 of 6
Version 1.2 – March 2004

Scoring
THERAPY
Corticosteroids
Prednisone
Dexamethasone

Enzymes
Asparaginase
Plant alkaloids
Vincristine
Vinblastine

Epipodophyllotoxins
Etoposide
Teniposide
Radiation
All fields including TBI

TBI

LATE EFFECTSCORE

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

SCORE
1

Osteopenia, Osteoporosis

1

Avascular necrosis (AVN)

1

Cataracts

1

No known late effects

1

Stroke/moyamoya
Occlusive cerebral vasculopathy

1

Peripheral sensory or motor neuropathy

2A

Brain tumor

1

Vasospastic attacks (Raynaud’s
phenomenon)

2A

Growth hormone deficiency

1

Hyperprolactinemia

1

Central hypothyroidism

1

Central adrenal insufficiency

1

Precocious puberty

1

Gonadotropin deficiency

1

Overweight/obesity

1

Chronic sinusitis

1

Craniofacial abnormalities

1

Dental abnormalities

1

Xerostomia

1

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

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

2

1

Scoring by Panel of Experts –Page 3 of 6
Version 1.2 – March 2004

Scoring
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
Cranial (whole brain)
Craniospinal
Nasopharyngeal
Oropharyngeal
CervicalMantleMediastinal
Whole lung
SpinalLATE EFFECTSCORE

All adverse effects on eye:Cataracts
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)

SCOREMusculoskeletal growth problems

1

Scoliosis

1

Kyphosis

1

Esophageal stricture

1

Chest/thorax radiation
with potential impact tothe breast:
TBI
MantleMediastinal
Whole lung
Spinal >30 Gy

Breast cancer

2A

Breast tissue hypoplasia

1

Chest/thorax radiation
with potential impact tothe heart:
TBI
MantleMediastinal
Whole lung
Spinal >30 Gy
Whole abdomen
Left hemiabdomen/
Left flank
Any left-sided upper
abdominal field

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

1

Chest/thorax radiation
Any field involving thechest/thorax, including:
TBI
MantleMediastinal
Whole lung
Spinal > 30 Gy
Whole abdomen
Any upper abdominal
field

3

LATE EFFECT

Scoring by Panel of Experts –Page 4 of 6
Version 1.2 – March 2004

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

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

Abdominal/Pelvic radiation>30 Gy to:Functional asplenia
Whole abdomenLife-threatening infection
Left upper quadrant
Entire spleen
TBI
Renal
Para-aortic
Whole abdomen
Spinal (>15 Gy)
TBI
Whole abdomen
Hepatic
TBI
All abdominal andpelvic fields
Spinal (>20 Gy)
TBI>25 Gy to:
All abdominal andpelvic fields
Spine

SCORE
1

1

Renal insufficiency
Hypertension

1

Hepatic fibrosis
Cirrhosis

1

Hepatocellular carcinoma

2A

Bowel obstruction

1

Chronic enterocolitis
Fistula, strictures

1

Gastrointestinal malignancy

2A

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 growth problems

1

Chronic Hepatitis B

1

Chronic Hepatitis C

1

Complications related to chronic hepatitis

1

HIV infection

1

Testicular radiation
TBI
Testicular
PelvicInguinal/femoral
Spinal >24 Gy

SCORE
2B

Extremity radiation
Blood/blood products4

Scoring by Panel of Experts –Page 5 of 6
Version 1.2 – March 2004

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

11Myelodysplasia
AML

1

1

Solid cancers

1

Infertility
Hypogonadism

1

Lymphoma

1

Retrograde ejaculation
Impotence
Bowel incontinence
Bladder incontinence
Hydrocele

1

Bronchiolitis obliterans
Chronic bronchitis
Bronchiectasis

11Life-threatening infection

1

Chronic hepatitis
Cirrhosis
Iron overload
Joint contractures

1

Osteopenia
Osteoporosis

1

5

Scoring by Panel of Experts –Page 6 of 6
Version 1.2 – March 2004

Scoring
GENERAL HEALTH SCREENING
General Health Screening

Organ
BreastNot scored

CervicalEndometrial
Colorectal
Lung
Prostate
Testicular
Skin
Oral

6

CANCER SCREENING
Standard Risk
Not scored(ACS recommendation)
Not scored(ACS recommendation)
N/A
Not scored(ACS recommendation)
N/A
Not scored(ACS recommendation)
Not scored(ACS recommendation)
Not scored(ACS recommendation)
N/A

Highest Risk - Score
2A
2A
Not scored(ACS recommendation)
2A
1
Not scored(ACS recommendation)
2A
2A
1Health Links
Healthy living after treatment for childhood cancer

Version 1.2 – March 2004

All 33 Health Links can be downloaded
in a single PDF file (“Appendix”)
or in individual PDF files
at www.survivorshipguidelines.org