Childhood Cancer and
Functional Impacts
Across the Care Continuum

Committee on Childhood Cancers and Disability

Paul A. Volberding, Carol Mason Spicer, Tom Cartaxo, and
Laura Aiuppa, Editors

Board on Health Care Services

Health and Medicine Division

A Consensus Study Report of

THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu

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This activity was supported by Contract/Task Order No. 28321318D00060015/00003 between the National Academy of Sciences and the U.S. Social Security Administration. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-68349-4
International Standard Book Number-10: 0-309-68349-1
Digital Object Identifier: https://doi.org/10.17226/25944

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Printed in the United States of America

Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2021. Childhood cancer and functional impacts across the care continuum. Washington, DC: The National Academies Press. https://doi.org/10.17226/25944.

COMMITTEE ON CHILDHOOD CANCERS AND DISABILITY

PAUL A. VOLBERDING (Chair), Professor Emeritus, Department of Epidemiology and Biostatistics, University of California, San Francisco

JASON R. FANGUSARO, Director, Developmental Therapeutics Program, Carter S. Martin Endowed Chair, Children’s Healthcare of Atlanta and Aflac Cancer and Blood Disorders Center; Associate Professor of Pediatrics, Emory University School of Medicine

JULIA GLADE BENDER, Vice Chair for Clinical Research, Department of Pediatrics, Memorial Sloan Kettering Cancer Center

ANDREA HAYES-JORDAN, Professor, Lineberger Cancer Center, Surgeon-in-Chief, North Carolina Children’s Hospital, Division Chief, Pediatric Surgery, University of North Carolina Health Care

BRANDON HAYES-LATTIN, Medical Director, Division of Hematology and Medical Oncology, Oregon Health & Science University

TARA HENDERSON, Director, Childhood, Adolescent and Young Adult Cancer Survivor Center; Interim Section Chief, Pediatric Hematology, Oncology and Stem Cell Transplantation, The University of Chicago

PAMELA S. HINDS, The William and Joanne Conway Chair in Nursing Research, Children’s National Health System

BARBARA L. JONES, University Distinguished Professor and Associate Dean for Health Affairs, Steve Hicks School of Social Work; Chair, Department of Health Social Work, Dell Medical School, The University of Texas at Austin

JENNIFER I. KOOP, Associate Professor of Neurology and Neurosurgery, Medical College of Wisconsin

VALERAE O. LEWIS, John Murray Endowed Professor and Chair, Department of Orthopaedic Oncology, The University of Texas MD Anderson Cancer Center

SCOTT L. POMEROY, Bronson Crothers Professor of Neurology, Harvard Medical School; Chair, Department of Neurology, Boston Children’s Hospital

DAVID W. PRUITT, Professor, Clinical Pediatrics and Physical Medicine & Rehabilitation, Cincinnati Children’s Hospital Medical Center

LESLIE L. ROBISON, Chair, Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital

NANCY J. TARBELL, C.C. Wang Professor of Radiation Oncology, Harvard Medical School; Department of Radiation Oncology, Massachusetts General Hospital, Francis H. Burr Proton Therapy Center

EMILY S. TONOREZOS, Director, Office of Cancer Survivorship, National Cancer Institute

BRIGITTE WIDEMANN, Chief, Pediatric Oncology Branch, National Cancer Institute

Study Staff

CAROL MASON SPICER, Study Director

LAURA AIUPPA, Senior Program Officer

TOM CARTAXO, Associate Program Officer

CLAIRE SAUNDERS, Senior Program Assistant (until April 2020)

VICTORIA BROWN, Senior Program Assistant (from April 2020)

SHARYL NASS, Senior Director, Board on Health Care Services

Reviewers

This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.

We thank the following individuals for their review of this report:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions of this report, nor did they see the final draft before its release. The review of this report was overseen by ROBERT S. LAWRENCE, Johns Hopkins Bloomberg School of Public Health, and ELLEN WRIGHT CLAYTON, Vanderbilt University Medical Center. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

Acknowledgments

The study committee and the project staff of the National Academies of Sciences, Engineering, and Medicine’s Health and Medicine Division take this opportunity to recognize and thank the many individuals who shared their time and expertise to support the committee’s work and inform its deliberations.

This study was sponsored by the U.S. Social Security Administration (SSA). We thank Cassandra Assefa, Stephanie Bovell, Megan Butson, Gina Clemons, Alayna Ness, Vincent Nibali, Mary Beth Rochowiak, and Mark Warshawsky for their guidance and support. The committee also acknowledges SSA for verifying relevant technical content pertaining to the disability determination process for accuracy. The committee benefited greatly from discussions with individuals who presented at the committee’s open sessions: Nicole M. Alberts, Gregory J. Aune, Megan P. Elam, Kristina K. Hardy, Elliot Krane, Kirsten K. Ness, Christopher J. Recklitis, Leslie L. Robison, Victoria Sardi-Brown, Lisl Schweers, and Stacia Wagner. The committee is grateful to these presenters for volunteering to share their expertise, knowledge, data, and opinions not only with the committee but also with members of the public who participated in the committee’s open sessions.

The committee acknowledges the many staff within the Health and Medicine Division who provided support in various ways to this project, including Carol Mason Spicer (study director), Laura Aiuppa (senior program officer), Tom Cartaxo (associate program officer), Victoria Brown (senior program assistant), Claire Saunders (senior program assistant), Karen Helsing (senior program officer), and Julie Wiltshire (senior finance

business partner). The committee extends great thanks and appreciation to Sharyl Nass, Health Care Services senior board director, who oversaw the project. Research assistance was provided by Anne Marie Houppert (senior librarian, National Academies). The committee also thanks Rikeenkumar Dhaduk and Kirsten K. Ness at St. Jude Children’s Research Hospital for their assistance in generating the incidence and outcome data from the Surveillance, Epidemiology, and End Results registry. Finally, Rona Brière and Allie Boman are to be credited for the superb editorial assistance they provided in preparing the final report.

Contents

ACRONYMS AND ABBREVIATIONS

SUMMARY

1 INTRODUCTION

Context for This Study

Study Charge and Scope

Study Approach

Report Organization

References

2 EPIDEMIOLOGY OF CHILDHOOD CANCER IN THE UNITED STATES

Incidence

Mortality and Survival

Cancer-Specific Information

Etiologic Risk Factors

Therapy-Related Morbidity

Findings and Conclusions

References

3 TREATMENT MODALITIES FOR CHILDHOOD CANCERS

Pediatric Cooperative Groups

Multimodal Therapies

Standard Treatment Modalities

Emerging Treatments

Summary

Findings and Conclusions

References

4 CHILDHOOD CANCERS AND FUNCTION

Physical Functioning

Cognitive Functioning

Psychosocial and Emotional Functioning

Summary

Findings and Conclusions

References

5 SELECTED HEMATOLOGIC MALIGNANCIES AND HISTIOCYTOSES

Overview

Diagnosis, Prognosis, Treatment, and Outcomes by Malignancy

Findings and Conclusions

References

6 SELECTED CENTRAL NERVOUS SYSTEM TUMORS

Overview

Diagnosis, Prognosis, Treatment, and Outcomes by Tumor Type

Findings and Conclusions

References

7 SELECTED NON–CENTRAL NERVOUS SYSTEM SOLID TUMORS

Overview

Diagnosis, Prognosis, Treatment, and Outcomes by Tumor Type

Findings and Conclusions

References

8 THE TRANSITION FROM ADOLESCENCE TO YOUNG ADULTHOOD

The Disability Determination Process

Epidemiology of Cancers in Adolescents and Young Adults

Clinical Differences Between Adolescence and Young Adulthood

Late Effects

Fertility Preservation

Functional Impacts Unique to Adolescence and Young Adulthood

Findings and Conclusions

References

9 OVERALL CONCLUSIONS

Overall Conclusions

Selected Findings and Conclusions in Support of the Committee’s Overall Conclusions

APPENDIXES

A Public Session Agendas

B Epidemiology and Attributes of Specific Childhood Cancers

C Selected Resources

D Biographical Sketches of Committee Members

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Boxes, Figures, and Tables

BOXES

S-1 Conditions Addressed in the Report

1-1 Statement of Task

2-1 Metrics Used in the Epidemiology of Cancer and/or Disease Outcomes

9-1 Overall Conclusions and Selected Chapter-Specific Findings and Conclusions

FIGURES

1-1 International Classification of Functioning, Disability and Health model of functioning and disability

2-1-A Age-specific annual incidence rates per million population of cancer diagnosed among those aged 0–17 years in the United States overall

2-1-B Age-specific annual incidence rates per million population of cancer diagnosed among those aged 0–17 years in the United States by sex

2-1-C Age-specific annual incidence rates per million population of cancer diagnosed among those aged 0–17 years in the United States by White and Black race and Hispanic ethnicity

2-2 Temporal trend in the annual incidence rate of cancer (per 100,000 population) in the United States among those diagnosed at ages 0–15

2-3 Survival for individuals diagnosed with cancer at ages 0–17 in the United States, by year of diagnosis

2-4 Distribution of the cumulative burden of serious, disabling, and life-threatening chronic physical health conditions (severity grades 3 and 4 according to modification of the Common Terminology Criteria for Adverse Events [Hudson et al., 2017]) at 18 and 26 years of age

6-1 Elements of brain anatomy

8-1 Overall annual U.S. incidence of cancer for adolescents and young adults

8-2 Sex-specific annual U.S. incidence of cancer for adolescents and young adults

8-3 Standardized incidence ratios (SIRs) and frequency for secondary malignant neoplasms in survivors of early-AYA (adolescent and young adult) cancer and matched survivors of childhood cancer by attained age and time since diagnosis

TABLES

2-1 Annual Incidence Rates and Proportional Distribution of Cancer Diagnoses Among Those Aged 0–17 in the United States

2-2 5- and 10-Year Survival by Year of Diagnosis for Individuals Diagnosed with Cancer at Ages 0–17 in the United States

2-3 Examples of Syndromes and Cancer Predisposition Genes Associated with Cancers Diagnosed During Childhood

8-1 Annual Incidence of Various Cancers in Adolescents and Young Adults

ANNEX TABLES

Annex Table 3-1 Acute and Long-Term Sequelae of Cancer Surgery

Annex Table 3-2 Acute and Long-Term Sequelae of Radiation Therapy

Annex Table 3-3 Acute and Long-Term Sequelae of Different Classes of Chemotherapy Agents

Annex Table 3-4 Targeted Therapy Agents: Selected Current (2020) U.S. Food and Drug Administration (FDA) Approved, with Pediatric Labeling, and/or in Development Through Clinical Trials

Annex Table 4-1 Selected Instruments Used to Measure Physical Functioning in Survivors of Childhood Cancer

Annex Table 4-2 Functional Impairments Associated with Amputation and Limb-Sparing Surgery

Annex Table 4-3 Selected Standardized Measures of Cognitive Functioning

Annex Table 4-4 Selected Instruments Used to Measure Psychosocial and Emotional Functioning in Survivors of Childhood Cancer and to Measure Parental Stress

Annex Table 5-1 Selected Hematologic Malignancies and Histiocytoses: Diagnostic and Prognostic Information

Annex Table 5-2 Selected Hematologic Malignancies and Histiocytoses: Treatment Information

Annex Table 6-1 Selected Central Nervous System (CNS) Tumors: Diagnostic and Prognostic Information

Annex Table 6-2 Selected Central Nervous System (CNS) Tumors: Treatment Information

Annex Table 7-1 Selected Non–Central Nervous System (CNS) Solid Tumors: Diagnostic and Prognostic Information

Annex Table 7-2 Selected Non–Central Nervous System Solid Tumors: Treatment Information

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Acronyms and Abbreviations