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Exercise Intolerance in Adult Survivors of Childhood Cancer


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In a study reported in the Journal of Clinical Oncology, Ness et al found a high rate of exercise intolerance among adult survivors of childhood cancer, irrespective of exposure to cardiotoxic treatment. Exercise intolerance was associated with poorer overall survival.

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The study involved 1,041 patients with (exposed group, n = 666) or without (unexposed group, n = 375) exposure to anthracyclines or chest-directed radiotherapy who had survived ≥ 10 years and 285 community control subjects without a history of cancer who met all other study eligibility requirements. Survivors had a mean age of 35.6 years.

Key Findings

Mean peak oxygen uptake was 25.74 ± 8.36 mL/kg/min in exposed survivors and 26.82 ± 8.36 mL/kg/min in unexposed survivors vs 32.69 ± 7.75 mL/kg/min in the control group (P < .001 for each survivor group vs controls; P = .03 for exposed vs unexposed survivors).

Exercise intolerance—defined as peak oxygen uptake < 85% predicted from maximal cardiopulmonary exercise testing—was present in 63.8% of the exposed group and 55.7% of the unexposed group vs 26.3% of the control group (P < .001 for each survivor group vs control group and for exposed vs unexposed survivors) and was associated with mortality.

After a median follow-up of 4.0 years, death occurred in 21 survivors (3.3%) with exercise intolerance vs 3 (0.7%) without exercise intolerance (P = .007). The adjusted hazard ratio for mortality for those with vs without exercise intolerance was 3.9 (95% confidence interval = 1.09–14.14).

“Exercise intolerance is prevalent among childhood cancer survivors and associated with all-cause mortality.”
— Ness et al

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Factors other than treatment exposure significantly associated with increased risk of exercise intolerance among all survivors included chronotropic incompetence (< 80% heart rate reserve; odds ratio [OR] = 4.12, P <.001), forced expiratory volume in 1 second < 80% (OR = 2.35, P < .001), and one standard deviation decrease in quadriceps strength (OR = 1.50, P < .001).

Factors associated with exercise intolerance among exposed survivors included impaired cardiac global longitudinal strain (OR = 1.71, P < .01), chronotropic incompetence (OR = 3.58, P <.001), forced expiratory volume in 1 second < 80% (OR = 2.59, P < .001), and one standard deviation decrease in quadriceps strength (OR = 1.49, P < .001). Ejection fraction < 53% was not associated with exercise intolerance.

The investigators concluded, “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.”

Kirsten K. Ness, PT, PhD, of the Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by National Cancer Institute grants and American Lebanese-Syrian Associated Charities. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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