Association of Exercise With Mortality in Adult Survivors of Childhood Cancer | Cancer Screening, Prevention, Control | JAMA Oncology | JAMA Network
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1.
Armstrong  GT, Liu  Q, Yasui  Y,  et al.  Late mortality among 5-year survivors of childhood cancer: a summary from the Childhood Cancer Survivor Study.  J Clin Oncol. 2009;27(14):2328-2338. doi:10.1200/JCO.2008.21.1425PubMedGoogle ScholarCrossref
2.
Yeh  JM, Nekhlyudov  L, Goldie  SJ, Mertens  AC, Diller  L.  A model-based estimate of cumulative excess mortality in survivors of childhood cancer.  Ann Intern Med. 2010;152(7):409-417, W131-8. doi:10.7326/0003-4819-152-7-201004060-00005PubMedGoogle ScholarCrossref
3.
Fidler  MM, Reulen  RC, Winter  DL,  et al; British Childhood Cancer Survivor Study Steering Group.  Long term cause specific mortality among 34 489 five year survivors of childhood cancer in Great Britain: population based cohort study.  BMJ. 2016;354:i4351. doi:10.1136/bmj.i4351PubMedGoogle ScholarCrossref
4.
Reulen  RC, Winter  DL, Frobisher  C,  et al; British Childhood Cancer Survivor Study Steering Group.  Long-term cause-specific mortality among survivors of childhood cancer.  JAMA. 2010;304(2):172-179. doi:10.1001/jama.2010.923PubMedGoogle ScholarCrossref
5.
Armstrong  GT, Chen  Y, Yasui  Y,  et al.  Reduction in late mortality among 5-year survivors of childhood cancer.  N Engl J Med. 2016;374(9):833-842. doi:10.1056/NEJMoa1510795PubMedGoogle ScholarCrossref
6.
Scott  JM, Koelwyn  GJ, Hornsby  WE,  et al.  Exercise therapy as treatment for cardiovascular and oncologic disease after a diagnosis of early-stage cancer.  Semin Oncol. 2013;40(2):218-228. doi:10.1053/j.seminoncol.2013.01.001PubMedGoogle ScholarCrossref
7.
Manson  JE, Greenland  P, LaCroix  AZ,  et al.  Walking compared with vigorous exercise for the prevention of cardiovascular events in women.  N Engl J Med. 2002;347(10):716-725. doi:10.1056/NEJMoa021067PubMedGoogle ScholarCrossref
8.
Paffenbarger  RS  Jr, Hyde  RT, Wing  AL, Lee  IM, Jung  DL, Kampert  JB.  The association of changes in physical-activity level and other lifestyle characteristics with mortality among men.  N Engl J Med. 1993;328(8):538-545. doi:10.1056/NEJM199302253280804PubMedGoogle ScholarCrossref
9.
Lear  SA, Hu  W, Rangarajan  S,  et al.  The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries: the PURE study.  Lancet. 2017;390(10113):2643-2654. doi:10.1016/S0140-6736(17)31634-3PubMedGoogle ScholarCrossref
10.
Wen  CP, Wai  JP, Tsai  MK,  et al.  Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study.  Lancet. 2011;378(9798):1244-1253. doi:10.1016/S0140-6736(11)60749-6PubMedGoogle ScholarCrossref
11.
Robison  LL, Armstrong  GT, Boice  JD,  et al.  The Childhood Cancer Survivor Study: a National Cancer Institute-supported resource for outcome and intervention research.  J Clin Oncol. 2009;27(14):2308-2318. doi:10.1200/JCO.2009.22.3339PubMedGoogle ScholarCrossref
12.
Brown  WJ, Trost  SG, Bauman  A, Mummery  K, Owen  N.  Test-retest reliability of four physical activity measures used in population surveys.  J Sci Med Sport. 2004;7(2):205-215. doi:10.1016/S1440-2440(04)80010-0PubMedGoogle ScholarCrossref
13.
Ainsworth  BE, Haskell  WL, Herrmann  SD,  et al.  2011 Compendium of Physical Activities: a second update of codes and MET values.  Med Sci Sports Exerc. 2011;43(8):1575-1581. doi:10.1249/MSS.0b013e31821ece12PubMedGoogle ScholarCrossref
14.
Jones  LW, Liu  Q, Armstrong  GT,  et al.  Exercise and risk of major cardiovascular events in adult survivors of childhood Hodgkin lymphoma: a report from the Childhood Cancer Survivor study.  J Clin Oncol. 2014;32(32):3643-3650. doi:10.1200/JCO.2014.56.7511PubMedGoogle ScholarCrossref
15.
Ness  KK, Hudson  MM, Jones  KE,  et al.  Effect of temporal changes in therapeutic exposure on self-reported health status in childhood cancer survivors.  Ann Intern Med. 2017;166(2):89-98. doi:10.7326/M16-0742PubMedGoogle ScholarCrossref
16.
Schmid  D, Leitzmann  MF.  Association between physical activity and mortality among breast cancer and colorectal cancer survivors: a systematic review and meta-analysis.  Ann Oncol. 2014;25(7):1293-1311. doi:10.1093/annonc/mdu012PubMedGoogle ScholarCrossref
17.
Moslehi  J.  The cardiovascular perils of cancer survivorship.  N Engl J Med. 2013;368(11):1055-1056. doi:10.1056/NEJMe1215300PubMedGoogle ScholarCrossref
18.
Friedenreich  CM, Neilson  HK, Farris  MS, Courneya  KS.  Physical activity and cancer outcomes: a precision medicine approach.  Clin Cancer Res. 2016;22(19):4766-4775. doi:10.1158/1078-0432.CCR-16-0067PubMedGoogle ScholarCrossref
19.
Irwin  ML, McTiernan  A, Manson  JE,  et al.  Physical activity and survival in postmenopausal women with breast cancer: results from the Women’s Health Initiative.  Cancer Prev Res (Phila). 2011;4(4):522-529. doi:10.1158/1940-6207.CAPR-10-0295PubMedGoogle ScholarCrossref
20.
Meyerhardt  JA, Giovannucci  EL, Ogino  S,  et al.  Physical activity and male colorectal cancer survival.  Arch Intern Med. 2009;169(22):2102-2108. doi:10.1001/archinternmed.2009.412PubMedGoogle ScholarCrossref
21.
Holmes  MD, Chen  WY, Feskanich  D, Kroenke  CH, Colditz  GA.  Physical activity and survival after breast cancer diagnosis.  JAMA. 2005;293(20):2479-2486. doi:10.1001/jama.293.20.2479PubMedGoogle ScholarCrossref
22.
Jones  LW, Kwan  ML, Weltzien  E,  et al.  Exercise and prognosis on the basis of clinicopathologic and molecular features in early-stage breast cancer: the LACE and Pathways studies.  Cancer Res. 2016;76(18):5415-5422. doi:10.1158/0008-5472.CAN-15-3307PubMedGoogle ScholarCrossref
23.
Fong  DY, Ho  JW, Hui  BP,  et al.  Physical activity for cancer survivors: meta-analysis of randomised controlled trials.  BMJ. 2012;344:e70. doi:10.1136/bmj.e70PubMedGoogle ScholarCrossref
24.
Schmitz  KH, Courneya  KS, Matthews  C,  et al; American College of Sports Medicine.  American College of Sports Medicine roundtable on exercise guidelines for cancer survivors.  Med Sci Sports Exerc. 2010;42(7):1409-1426. doi:10.1249/MSS.0b013e3181e0c112PubMedGoogle ScholarCrossref
25.
Jones  LW.  Precision oncology framework for investigation of exercise as treatment for cancer.  J Clin Oncol. 2015;33(35):4134-4137. doi:10.1200/JCO.2015.62.7687PubMedGoogle ScholarCrossref
26.
Scott  JM, Nilsen  TS, Gupta  D, Jones  LW.  Exercise therapy and cardiovascular toxicity in cancer.  Circulation. 2018;137(11):1176-1191. doi:10.1161/CIRCULATIONAHA.117.024671PubMedGoogle ScholarCrossref
27.
Blair  SN, Kohl  HW  III, Barlow  CE, Paffenbarger  RS  Jr, Gibbons  LW, Macera  CA.  Changes in physical fitness and all-cause mortality: a prospective study of healthy and unhealthy men.  JAMA. 1995;273(14):1093-1098. doi:10.1001/jama.1995.03520380029031PubMedGoogle ScholarCrossref
28.
Ashcraft  KA, Peace  RM, Betof  AS, Dewhirst  MW, Jones  LW.  Efficacy and mechanisms of aerobic exercise on cancer initiation, progression, and metastasis: a critical systematic review of in vivo preclinical data.  Cancer Res. 2016;76(14):4032-4050. doi:10.1158/0008-5472.CAN-16-0887PubMedGoogle ScholarCrossref
29.
Koelwyn  GJ, Quail  DF, Zhang  X, White  RM, Jones  LW.  Exercise-dependent regulation of the tumour microenvironment.  Nat Rev Cancer. 2017;17(10):620-632. doi:10.1038/nrc.2017.78PubMedGoogle ScholarCrossref
30.
Vallance  JK, Courneya  KS, Plotnikoff  RC, Yasui  Y, Mackey  JR.  Randomized controlled trial of the effects of print materials and step pedometers on physical activity and quality of life in breast cancer survivors.  J Clin Oncol. 2007;25(17):2352-2359. doi:10.1200/JCO.2006.07.9988PubMedGoogle ScholarCrossref
31.
Troped  PJ, Wiecha  JL, Fragala  MS,  et al.  Reliability and validity of YRBS physical activity items among middle school students.  Med Sci Sports Exerc. 2007;39(3):416-425. doi:10.1249/mss.0b013e31802d97afPubMedGoogle ScholarCrossref
32.
Ainsworth  BE, Richardson  MT, Jacobs  DR  Jr, Leon  AS, Sternfeld  B.  Accuracy of recall of occupational physical activity by questionnaire.  J Clin Epidemiol. 1999;52(3):219-227. doi:10.1016/S0895-4356(98)00158-9PubMedGoogle ScholarCrossref
33.
Sotos-Prieto  M, Bhupathiraju  SN, Mattei  J,  et al.  Association of changes in diet quality with total and cause-specific mortality.  N Engl J Med. 2017;377(2):143-153. doi:10.1056/NEJMoa1613502PubMedGoogle ScholarCrossref
34.
Jones  LW, Habel  LA, Weltzien  E,  et al.  Exercise and risk of cardiovascular events in women with nonmetastatic breast cancer.  J Clin Oncol. 2016;34(23):2743-2749. doi:10.1200/JCO.2015.65.6603PubMedGoogle ScholarCrossref
35.
Myers  J, Prakash  M, Froelicher  V, Do  D, Partington  S, Atwood  JE.  Exercise capacity and mortality among men referred for exercise testing.  N Engl J Med. 2002;346(11):793-801. doi:10.1056/NEJMoa011858PubMedGoogle ScholarCrossref
Original Investigation
October 2018

Association of Exercise With Mortality in Adult Survivors of Childhood Cancer

Author Affiliations
  • 1Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Weill Cornell Medical College, New York, New York
  • 3St Jude Children's Research Hospital, Memphis, Tennessee
  • 4University of Alberta, Edmonton, Alberta, Canada
  • 5Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 6The Hospital for Sick Children, Toronto, Ontario, Canada
  • 7City of Hope, Duarte, California
  • 8The Norwegian School of Sport Sciences, Oslo, Norway
  • 9Duke University Medical Center, Durham, North Carolina
JAMA Oncol. 2018;4(10):1352-1358. doi:10.1001/jamaoncol.2018.2254
Key Points

Question  Is vigorous exercise and change in exercise associated with a reduction in mortality in adult survivors of childhood cancer?

Findings  In this cohort analysis using a questionnaire after a median follow-up of 10 years among 15 450 adult survivors of childhood cancer, there was a significant inverse association across quartiles of exercise and all-cause mortality after adjustment for chronic health conditions and treatment exposures. Increased exercise over 8 years was associated with a 40% reduction in all-cause mortality rate compared with maintenance of low exercise.

Meaning  Vigorous exercise in early adulthood and increased exercise over 8 years is associated with lower risk of mortality in adult survivors of childhood cancer.

Abstract

Importance  Adult survivors of childhood cancer are at excess risk for mortality compared with the general population. Whether exercise attenuates this risk is not known.

Objective  To examine the association between vigorous exercise and change in exercise with mortality in adult survivors of childhood cancer.

Design, Setting, and Participants  Multicenter cohort analysis among 15 450 adult cancer survivors diagnosed before age 21 years from pediatric tertiary hospitals in the United States and Canada between 1970 and 1999 enrolled in the Childhood Cancer Survivor Study, with follow-up through December 31, 2013.

Exposures  Self-reported vigorous exercise in metabolic equivalent task (MET) hours per week. The association between vigorous exercise and change in vigorous exercise and cause-specific mortality was assessed using multivariable piecewise exponential regression analysis to estimate rate ratios.

Main Outcomes and Measures  The primary outcome was all-cause mortality. Secondary end points were cause-specific mortality (recurrence/progression of primary malignant neoplasm and health-related mortality). Outcomes were assessed via the National Death Index.

Results  The 15 450 survivors had a median age at interview of 25.9 years (interquartile range [IQR], 9.5 years) and were 52.8% male. During a median follow-up of 9.6 years (IQR, 15.5 years), 1063 deaths (811 health-related, 120 recurrence/progression of primary cancer, 132 external/unknown causes) were documented. At 15 years, the cumulative incidence of all-cause mortality was 11.7% (95% CI, 10.6%-12.8%) for those who exercised 0 MET-h/wk, 8.6% (95% CI, 7.4%-9.7%) for 3 to 6 MET-h/wk, 7.4% (95% CI, 6.2%-8.6%) for 9 to 12 MET-h/wk, and 8.0% (95% CI, 6.5%-9.5%) for 15 to 21 MET-h/wk (P < .001). There was a significant inverse association across quartiles of exercise and all-cause mortality after adjusting for chronic health conditions and treatment exposures (P = .02 for trend). Among a subset of 5689 survivors, increased exercise (mean [SD], 7.9 [4.4] MET-h/wk) over an 8-year period was associated with a 40% reduction in all-cause mortality rate compared with maintenance of low exercise (rate ratio, 0.60; 95% CI, 0.44-0.82; P = .001).

Conclusions and Relevance  Vigorous exercise in early adulthood and increased exercise over 8 years was associated with lower risk of mortality in adult survivors of childhood cancer.

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