OBJECTIVE To investigate the impact of modifications to contemporary cancer protocols, which minimize exposures to cardiotoxic treatments and preserve long term health, on serious cardiac outcomes among adult survivors of childhood cancer. DESIGN Retrospective cohort study. SETTING 27 institutions participating in the Childhood Cancer Survivor Study. PARTICIPANTS 23 462 five year survivors (6193 (26.4%) treated in the 1970s, 9363 (39.9%) treated in the 1980s, and 7906 (33.6%) treated in the 1990s) of leukemia, brain cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal tumors, neuroblastoma, soft tissue sarcomas, and bone sarcomas diagnosed prior to age 21 years between 1 January 1970 and 31 December 1999. Median age at diagnosis was 6.1 years (range 0-20.9) and 27.7 years (8.2-58.3) at last follow-up. A comparison group of 5057 siblings of cancer survivors were also included. MAIN OUTCOME MEASURES Cumulative incidence and 95% confidence intervals of reported heart failure, coronary artery disease, valvular heart disease, pericardial disease, and arrhythmias by treatment decade. Events were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. Multivariable subdistribution hazard models were used to estimate hazard ratios by decade, and mediation analysis examined risks with and without exposure to cardiotoxic treatments. RESULTS The 20 year cumulative incidence of heart failure (0.69% for those treated in the 1970s, 0.74% for those treated in the 1980s, 0.54% for those treated in the 1990s) and coronary artery disease (0.38%, 0.24%, 0.19%, respectively), decreased in more recent eras (P<0.01), though not for valvular disease (0.06%, 0.06%, 0.05%), pericardial disease (0.04%, 0.02%, 0.03%), or arrhythmias (0.08%, 0.09%, 0.13%). Compared with survivors with a diagnosis in the 1970s, the risk of heart failure, coronary artery disease, and valvular heart disease decreased in the 1980s and 1990s but only significantly for coronary artery disease (hazard ratio 0.65, 95% confidence interval 0.45 to 0.92 and 0.53, 0.36 to 0.77, respectively). The overall risk of coronary artery disease was attenuated by adjustment for cardiac radiation (0.90, 0.78 to 1.05), particularly among survivors of Hodgkin lymphoma (unadjusted for radiation: 0.77, 0.66 to 0.89; adjusted for radiation: 0.87, 0.69 to 1.10). CONCLUSIONS Historical reductions in exposure to cardiac radiation have been associated with a reduced risk of coronary artery disease among adult survivors of childhood cancer. Additional follow-up is needed to investigate risk reductions for other cardiac outcomes. TRIAL REGISTRATION ClinicalTrials.gov NCT01120353.

中文翻译：

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1970年至1999年间诊断为儿童癌症成年幸存者的主要心脏事件：儿童癌症幸存者研究队列的报告。

目的研究对当代癌症方案的修改对儿童癌症成年幸存者严重心脏结局的影响，该方案可最大程度地减少心脏毒性治疗的暴露并保持长期健康。设计回顾性队列研究。设置了27家参与儿童癌症幸存者研究的机构。参与者有白血病，脑癌，霍奇金淋巴瘤，非霍奇金淋巴瘤的23462名五年幸存者（1970年代治疗的6193人（26.4％），1980年代治疗的9363（39.9％）人和1990年代治疗的7906（33.6％）人）在1970年1月1日至1999年12月31日期间21岁之前诊断出的淋巴瘤，肾肿瘤，神经母细胞瘤，软组织肉瘤和骨肉瘤。诊断时的中位年龄为6.1岁（范围0-20.9）和27.7岁（8.2-58.3）在最后的随访中。还包括了5057个癌症幸存者兄弟姐妹的比较组。主要观察指标：按治疗十年计，报告的心力衰竭，冠状动脉疾病，瓣膜性心脏病，心包疾病和心律不齐的累积发生率和95％置信区间。根据美国国家癌症研究所的不良事件通用术语标准对事件进行分级。多变量子分布危害模型用于按十年估算危害比率，而调解分析则检查了有或没有心脏毒性治疗的风险。结果20年心力衰竭的累积发生率（1970年代为0.69％，1980年代为0.74％，1990年代为0.54％）和冠心病（0.38％，0.24％，0.19％分别在最近的时代有所下降（P <0。01），但不适用于瓣膜疾病（0.06％，0.06％，0.05％），心包疾病（0.04％，0.02％，0.03％）或心律不齐（0.08％，0.09％，0.13％）。与1970年代诊断出的幸存者相比，心衰，冠状动脉疾病和瓣膜性心脏病的风险在1980年代和1990年代有所降低，但对于冠状动脉疾病仅显着降低（危险比0.65、95％置信区间0.45至0.92和分别为0.53、0.36至0.77）。通过调整心脏辐射量（0.90，0.78至1.05）降低了冠状动脉疾病的总体风险，特别是在霍奇金淋巴瘤幸存者中（未调整辐射量：0.77，0.66至0.89;调整辐射量：0.87，0.69至1.10）。结论历史减少的心脏辐射暴露与儿童癌症成年幸存者降低冠状动脉疾病的风险有关。需要进行其他随访以调查降低其他心脏结局的风险。试验注册ClinicalTrials.gov NCT01120353。