Dataset Information

Association of Exercise With 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.

SUBMITTER: Scott JM

PROVIDER: S-EPMC6181767 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundChildhood cancer survivors are at risk for adverse psychological outcomes. Whether exercise can attenuate this risk is unknown.MethodsIn total, 6199 participants in the Childhood Cancer Survivor Study (median age, 34.3 years [range, 22.0-54.0 years]; median age at diagnosis, 10.0 years [range, 0-21.0 years]) completed a questionnaire assessing vigorous exercise and medical/psychological conditions. Outcomes were evaluated a median of 7.8 years (range, 0.1-10.0 years) later and were defined as: symptom level above the 90th percentile of population norms for depression, anxiety, or somatization on the Brief Symptom Inventory-18; cancer-related pain; cognitive impairment using a validated self-report neurocognitive questionnaire; or poor health-related quality of life. Log-binomial regression estimated associations between exercise (metabolic equivalent [MET]-hours per week-1 ) and outcomes adjusting for cancer diagnosis, treatment, demographics, and baseline conditions.ResultsThe prevalence of depression at follow-up was 11.4% (95% CI, 10.6%-12.3%), anxiety 7.4% (95% CI, 6.7%-8.2%) and somatization 13.9% (95% CI, 13.0%-14.9%). Vigorous exercise was associated with lower prevalence of depression and somatization. The adjusted prevalence ratio for depression was 0.87 (95% CI, 0.72-1.05) for 3 to 6 MET hours per week-1 , 0.76 (95% CI, 0.62-0.94) for 9 to 12 MET-hours per week-1 , and 0.74 (95% CI, 0.58-0.95) for 15 to 21 MET-hours per week-1 . Compared with 0 MET hours per week-1 , 15 to 21 MET-hours per week-1 were associated with an adjusted prevalence ratio of 0.79 (95% CI, 0.62-1.00) for somatization. Vigorous exercise also was associated with less impairment in the physical functioning, general health and vitality (Ptrend < .001), emotional role limitations (Ptrend = .02), and mental health (Ptrend = .02) domains as well as higher cognitive function in the domains of task completion, organization, and working memory (P < .05 for all), but not in the domain of cancer pain.ConclusionsVigorous exercise is associated with less psychological burden and cognitive impairment in childhood cancer survivors.

Project description:BackgroundAdult childhood cancer survivors are at risk for frailty, including low muscle mass and weakness (sarcopenia). Using peripheral blood mitochondrial DNA copy number (mtDNAcn) as a proxy for functional mitochondria, this study describes cross-sectional associations between mtDNAcn and sarcopenia among survivors.MethodsAmong 1762 adult childhood cancer survivors (51.6% male; median age = 29.4 years, interquartile range [IQR] = 23.3-36.8), with a median of 20.6 years from diagnosis (IQR = 15.2-28.2), mtDNAcn estimates were derived from whole-genome sequencing. A subset was validated by quantitative polymerase chain reaction and evaluated cross-sectionally using multivariable logistic regression for their association with sarcopenia, defined by race-, age-, and sex-specific low lean muscle mass or weak grip strength. All statistical tests were 2-sided.ResultsThe prevalence of sarcopenia was 27.0%, higher among female than male survivors (31.5% vs 22.9%; P < .001) and associated with age at diagnosis; 51.7% of survivors with sarcopenia were diagnosed ages 4-13 years (P = .01). Sarcopenia was most prevalent (39.0%) among central nervous system tumor survivors. Cranial radiation (odds ratio [OR] = 1.84, 95% confidence interval [CI] = 1.32 to 2.59) and alkylating agents (OR = 1.34, 95% CI = 1.04 to 1.72) increased, whereas glucocorticoids decreased odds (OR = 0.72, 95% CI = 0.56 to 0.93) of sarcopenia. mtDNAcn decreased with age (β = -0.81, P = .002) and was higher among female survivors (β = 9.23, P = .01) and among survivors with a C allele at mt.204 (β = -17.9, P = .02). In adjusted models, every standard deviation decrease in mtDNAcn increased the odds of sarcopenia 20% (OR = 1.20, 95% CI = 1.07 to 1.34).ConclusionsA growing body of evidence supports peripheral blood mtDNAcn as a biomarker for adverse health outcomes; however, this study is the first to report an association between mtDNAcn and sarcopenia among childhood cancer survivors.

Project description:ImportanceExercise intolerance is associated with increased risk for morbidity and mortality in childhood cancer survivors. However, an association between exercise intolerance and psychosocial outcomes has not been fully explored.ObjectiveTo examine the associations between exercise intolerance and emotional distress, attainment of social roles, and health-related quality of life in childhood cancer survivors.Design, setting, and participantsA cross-sectional study including 1041 adult survivors of childhood cancer and 286 community controls in the St Jude Lifetime Cohort was conducted at St Jude Children's Research Hospital. The study was performed from April 1, 2012, to March 15, 2020.ExposuresExercise intolerance was defined as relative peak oxygen uptake less than 85% of age- and sex-estimated levels from maximal cardiopulmonary exercise testing.Main outcomes and measuresEmotional distress was measured with the 18-item Brief Symptom Inventory-18, which includes overall Global Severity Index and depression, anxiety, and somatization subscales. Participants with T scores greater than or equal to 63 were classified as having elevated levels of distress. Social attainment was evaluated using patient-reported educational, employment, and marital status. Health-related quality of life was examined with the Medical Outcomes Survey Short Form-36. Participants with T scores less than or equal to 40 were classified as reporting poor health-related quality of life.ResultsOf the 1041 participants, 528 were women (50.7%). The prevalence of exercise intolerance among survivors (mean [SD] age, 35.5 [9.2] years) was higher than that among controls (age, 34.5 [10.0] years) (survivors: 634 [60.9%] vs controls: 75 [26.2%], P < .001). After adjusting for age at diagnosis and cardiopulmonary exercise testing, sex, race/ethnicity, smoking, physical activity, and exercise intolerance were associated with an increased risk for anxiety (prevalence rate ratio [PRR], 1.95; 95% CI, 1.20-3.16), somatization (PRR, 1.86; 95% CI, 1.23-2.80), and unemployment (PRR, 1.76; 95% CI, 1.23-2.52); an inverse association was noted with having a college degree (PRR, 0.67; 95% CI, 0.50-0.88). Exercise intolerance was associated with an increased the risk for scoring less than or equal to 40 on the physical component summary of the Medical Outcomes Survey Short Form-36 (PRR, 3.69; 95% CI, 2.34-5.84). These associations persisted when either cancer treatment exposures or chronic health conditions were added to the model.Conclusions and relevanceThe findings of this study suggest that exercise intolerance is independently associated with emotional distress, attainment of social roles, and health-related quality of life of long-term survivors of childhood cancer. The results also suggest that improving physiologic capacity may benefit general health and wellness, as well as emotional health, ability to participate in social roles, and health-related quality of life.