Exercise intolerance, mortality, and organ system impairment in adult survivors of childhood cancer

Kirsten K. Ness, Juan C. Plana, Vijaya M. Joshi, Russell V. Luepker, Jean B. Durand, Daniel M. Green, Robyn E. Partin, Aimee K. Santucci, Rebecca M. Howell, Deo Kumar Srivastava, Melissa M. Hudson, Leslie L. Robison, Gregory T. Armstrong

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


PURPOSE Exercise intolerance, associated with heart failure and death in general populations, is not well studied in survivors of childhood cancer. We examined prevalence of exercise intolerance in survivors exposed or not to cardiotoxic therapy, and associations among organ system function, exercise intolerance, and mortality. METHODS Participants consisted of 1,041 people who had survived cancer $ 10 years (and had or did not have exposure to anthracyclines and/or chest-directed radiation) and 285 control subjects. Exercise intolerance was defined as peak oxygen uptake, 85% predicted from maximal cardiopulmonary exercise testing; organ functions were ascertained with imaging or clinical testing. Multivariable regression of the data was performed to compare exercise capacity between survivors exposed or unexposed to cardiotoxic therapy and control subjects, and to evaluate associations between treatment and organ function, and organ function and exercise intolerance. Propensity score methods in time-to-event analyses evaluated associations between exercise intolerance and mortality. RESULTS Survivors (mean age 6 standard deviation [SD], 35.6 6 8.8 years) had lower mean (6 SD) peak oxygen uptake (exposed: 25.74 6 8.36 mL/kg/min; unexposed: 26.82 6 8.36 mL/kg/min) than did control subjects (32.69 6 7.75 mL/kg/min; P for all, .001). Exercise intolerance was present in 63.8% (95% CI, 62.0% to 65.8%) of exposed survivors, 55.7% (95% CI, 53.2% to 58.2%) of unexposed survivors, and 26.3% (95% CI, 24.0% to 28.3%) of control subjects, and was associated with mortality (hazard ratio, 3.9; 95% CI, 1.09 to 14.14). Global longitudinal strain (odds ratio [OR], 1.71; 95% CI, 1.11 to 2.63), chronotropic incompetence (OR, 3.58; 95% CI, 1.75 to 7.31); forced expiratory volume in 1 second, 80% (OR, 2.59; 95% CI, 1.65 to 4.09), and 1 SD decrease in quadriceps strength (OR, 1.49; 95% CI, 1.23 to 1.82) were associated with exercise intolerance. Ejection fraction, 53% was not associated with exercise intolerance. CONCLUSION Exercise intolerance is prevalent among childhood cancer survivors and associated with all-cause mortality. Treatment-related cardiac (detected by global longitudinal strain), autonomic, pulmonary, and muscular impairments increased risk. Survivors with impairments may require referral to trained specialists to learn to accommodate specific deficits when engaging in exercise.

Original languageEnglish (US)
Pages (from-to)29-42
Number of pages14
JournalJournal of Clinical Oncology
Issue number1
StatePublished - 2020

Bibliographical note

Funding Information:
Supported by a grant to St Jude Children’s Research Hospital provided by the National Cancer Institute (Grant No. U01 CA195547, M.M.H.; and R01 CA157838, G.T.A.); Cancer Center Support Grant No. P30 CA21765; and the American Lebanese-Syrian Associated Charities (K.K.N.).

Publisher Copyright:
© 2019 by American Society of Clinical Oncology


  • Adult
  • Anthracyclines/administration & dosage
  • Cancer Survivors/statistics & numerical data
  • Exercise Test
  • Exercise Tolerance/physiology
  • Female
  • Heart Diseases/epidemiology
  • Humans
  • Male
  • Multiple Organ Failure/epidemiology
  • Neoplasms/drug therapy
  • Oxygen Consumption/physiology
  • Randomized Controlled Trials as Topic

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural


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