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Original Research |17 January 2017

Effect of Temporal Changes in Therapeutic Exposure on Self-reported Health Status in Childhood Cancer Survivors

Kirsten K. Ness, PhD *; Melissa M. Hudson, MD *; Kendra E. Jones, MS; Wendy Leisenring, ScD; Yutaka Yasui, PhD; Yan Chen, MS; Marilyn Stovall, PhD; Todd M. Gibson, PhD; Daniel M. Green, MD; Joseph P. Neglia, MD; Tara O. Henderson, MD; Jacqueline Casillas, MD; Jennifer S. Ford, PhD; Karen E. Effinger, MD, MS; Kevin R. Krull, PhD; Gregory T. Armstrong, MD, MSCE; Leslie L. Robison, PhD; Kevin C. Oeffinger, MD †; Paul C. Nathan, MD †

Kirsten K. Ness, PhD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Melissa M. Hudson, MD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Kendra E. Jones, MS

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Wendy Leisenring, ScD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Yutaka Yasui, PhD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Yan Chen, MS

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Marilyn Stovall, PhD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Todd M. Gibson, PhD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Daniel M. Green, MD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Joseph P. Neglia, MD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Tara O. Henderson, MD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Jacqueline Casillas, MD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Jennifer S. Ford, PhD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Karen E. Effinger, MD, MS

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Kevin R. Krull, PhD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Gregory T. Armstrong, MD, MSCE

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Leslie L. Robison, PhD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Kevin C. Oeffinger, MD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Paul C. Nathan, MD

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;

Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.

Article, Author, and Disclosure Information

This article was published at www.annals.org on 8 November 2016.

* Drs. Ness and Hudson are co–first authors.

† Drs. Oeffinger and Nathan are co–senior authors.

From St. Jude Children's Research Hospital, Memphis, Tennessee; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Alberta, Edmonton, Alberta, Canada; The University of Texas MD Anderson Cancer Center, Houston, Texas; University of Minnesota Medical School, Minneapolis, Minnesota; University of Chicago, Chicago, Illinois; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California;
Memorial Sloan Kettering Cancer Center, New York, New York; Emory University, Atlanta, Georgia; and The Hospital for Sick Children, Toronto, Ontario, Canada.
Grant Support: By the National Cancer Institute (grant CA55727 [Dr. Armstrong]), with support to St. Jude Children's Research Hospital provided by the Cancer Center Support grant (CA21765 [Dr. Roberts]) and the American Lebanese-Syrian Associated Charities.
Disclosures: Dr. Ness reports grants from National Institutes of Health during the conduct of the study. Dr. Leisenring reports grants from National Institutes of Health and the National Cancer Institute during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0742.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol, statistical code, and data set: Available from Dr. Ness (e-mail, kiri.ness@stjude.org).
Requests for Single Reprints: Kirsten K. Ness, PT, PhD, Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS-735, Memphis, TN 38105; e-mail, kiri.ness@stjude.org.
Current Author Addresses: Drs. Ness, Hudson, Yasui, Gibson, Green, Krull, Armstrong, and Robison, and Ms. Jones: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS-735, Memphis, TN 38105.
Dr. Leisenring: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109.
Ms. Chen: University of Alberta, 116 Street and 85 Avenue, Edmonton, Alberta T6G 2R3, Canada.
Dr. Stovall: Department of Radiation Physics, Division of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, 1220 Holcombe Boulevard, Houston, TX 77030.
Dr. Neglia: Department of Pediatrics, University of Minnesota Medical School, 2450 Riverside Avenue, 6th Floor, East Building, Delivery Code 8952A, Minneapolis, MN 55454.
Dr. Henderson: Department of Pediatrics, University of Chicago, 5721 South Maryland Avenue, Rm K-160, MC8000, Chicago, IL 60637.
Dr. Casillas: David Geffen School of Medicine at University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095.
Dr. Ford: Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065.
Dr. Effinger: Emory University, 201 Dowman Drive, Atlanta, GA 30322.
Dr. Oeffinger: Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065.
Dr. Nathan: Department of Paediatrics, Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Author Contributions: Conception and design: K.K. Ness, M.M. Hudson, W. Leisenring, J.P. Neglia, J. Casillas, J.S. Ford, G.T. Armstrong, K.C. Oeffinger, P.C. Nathan.
Analysis and interpretation of the data: K.K. Ness, M.M. Hudson, K.E. Jones, W. Leisenring, J.P. Neglia, J.S. Ford, K.R. Krull, L.L. Robison, K.C. Oeffinger, P.C. Nathan.
Drafting of the article: K.K. Ness, W. Leisenring, Y. Yasui, Y. Chen, M. Stovall, T.M. Gibson, D.M. Green, J.S. Ford, K.E. Effinger, K.C. Oeffinger, P.C. Nathan.
Critical revision of the article for important intellectual content: K.K. Ness, M.M. Hudson, W. Leisenring, M. Stovall, T.M. Gibson, D.M. Green, J.P. Neglia, T.O. Henderson, J.S. Ford, K.E. Effinger, K.R. Krull, L.L. Robison, K.C. Oeffinger, P.C. Nathan.
Final approval of the article: K.K. Ness, M.M. Hudson, W. Leisenring, Y. Yasui, M. Stovall, T.M. Gibson, D.M. Green, J.P. Neglia, J. Casillas, T.O. Henderson, J.S. Ford, K.E. Effinger, K.R. Krull, G.T. Armstrong, L.L. Robison, K.C. Oeffinger, P.C. Nathan.
Provision of study materials or patients: J.P. Neglia, J. Casillas, G.T. Armstrong.
Statistical expertise: K.K. Ness, K.E. Jones, W. Leisenring, Y. Yasui.
Obtaining of funding: J.P. Neglia, G.T. Armstrong, L.L. Robison.
Administrative, technical, or logistic support: K.K. Ness, J.P. Neglia, L.L. Robison.
Collection and assembly of data: K.K. Ness, M.M. Hudson, K.E. Jones, J.P. Neglia, J. Casillas, K.R. Krull, G.T. Armstrong, L.L. Robison.

Abstract

Background:

The effect of temporal changes in cancer therapy on health status among childhood cancer survivors has not been evaluated.

Objective:

To compare proportions of self-reported adverse health status outcomes among childhood cancer survivors across 3 decades.

Design:

Cross-sectional. (ClinicalTrials.gov: NCT01120353)

Setting:

27 North American institutions.

Participants:

14 566 adults, who survived for 5 or more years after initial diagnosis (median age, 27 years; range, 18 to 48 years), treated from 1970 to 1999.

Measurements:

Patient report of poor general or mental health, functional impairment, activity limitation, or cancer-related anxiety or pain was evaluated as a function of treatment decade, cancer treatment exposure, chronic health conditions, demographic characteristics, and health habits.

Results:

Despite reductions in late mortality and the proportions of survivors with severe, disabling, or life-threatening chronic health conditions (33.4% among those treated from 1970 to 1979 and 21.0% among those treated from 1990 to 1999), those reporting adverse health status did not decrease by treatment decade. Compared with survivors diagnosed in 1970 to 1979, those diagnosed in 1990 to 1999 were more likely to report poor general health (11.2% vs. 13.7%; P < 0.001) and cancer-related anxiety (13.3% vs. 15.0%; P < 0.001). From 1970 to 1979 and 1990 to 1999, the proportions of survivors reporting adverse outcomes were higher (P < 0.001) among those with leukemia (poor general health, 9.5% and 13.9%) and osteosarcoma (pain, 23.9% and 36.6%). Temporal changes in treatment exposures were not associated with changes in the proportions of survivors reporting adverse health status. Smoking, not meeting physical activity guidelines, and being either underweight or obese were associated with poor health status.

Limitation:

Considerable improvement in survival among children diagnosed with cancer in the 1990s compared with those diagnosed in the 1970s makes it difficult to definitively determine the effect of risk factors on later self-reported health status without considering their effect on mortality.

Conclusion:

Because survival rates after a diagnosis of childhood cancer have improved substantially over the past 30 years, the population of survivors now includes those who would have died in earlier decades. Self-reported health status among survivors has not improved despite evolution of treatment designed to reduce toxicities.

Primary Funding Source:

The National Cancer Institute.

FULL TEXT

Not Available

©

2016 American College of Physicians

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