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 ± standard deviation [SD], 35.6 ± 8.8 years) had lower mean (± SD) peak oxygen uptake (exposed: 25.74 ± 8.36 mL/kg/min; unexposed: 26.82 ± 8.36 mL/kg/min) than did control subjects (32.69 ± 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.

中文翻译：

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儿童癌症成年幸存者的运动不耐受、死亡率和器官系统损伤

目的运动不耐受与一般人群的心力衰竭和死亡有关，在儿童癌症幸存者中没有得到很好的研究。我们检查了暴露或未接受心脏毒性治疗的幸存者运动不耐受的患病率，以及器官系统功能、运动不耐受和死亡率之间的关联。方法 参与者由 1,041 名在癌症中存活 ≥ 10 年（并且曾或未曾接触过蒽环类药物和/或胸部定向辐射）和 285 名对照受试者组成。运动不耐受被定义为最大摄氧量 < 85%（根据最大心肺运动测试预测）；通过影像学或临床测试确定器官功能。对数据进行多变量回归以比较暴露或未暴露于心脏毒性治疗的幸存者与对照受试者之间的运动能力，并评估治疗与器官功能以及器官功能与运动不耐受之间的关联。事件发生时间分析中的倾向评分方法评估了运动不耐受与死亡率之间的关联。结果 幸存者（平均年龄 ± 标准差 [SD]，35.6 ± 8.8 岁）的平均 (± SD) 峰值摄氧量较低（暴露：25.74 ± 8.36 mL/kg/min；未暴露：26.82 ± 8.36 mL/kg/min）比对照组（32.69 ± 7.75 mL/kg/min；所有 P < .001）。63.8%（95% CI，62.0% 至 65.8%）暴露的幸存者、55.7%（95% CI，53.2% 至 58.2%）的未暴露幸存者和 26.3%（95% CI，24.0% 至28.3%) 的对照组，并且与死亡率相关（风险比，3.9；95% CI，1.09 至 14.14）。整体纵向应变（优势比 [OR]，1.71；95% CI，1.11 至 2.63），变时性无能（OR，3.58；95% CI，1.75 至 7.31）；1 秒用力呼气量 < 80%（OR，2.59；95% CI，1.65 至 4.09）和股四头肌力量下降 1 SD（OR，1.49；95% CI，1.23 至 1.82）与运动不耐受有关。射血分数 < 53% 与运动不耐受无关。结论 运动不耐受在儿童癌症幸存者中普遍存在，并且与全因死亡率相关。与治疗相关的心脏（通过整体纵向应变检测）、自主神经、肺和肌肉损伤增加了风险。