Purpose We aimed to predict individual risk of ischemic heart disease and stroke in 5-year survivors of childhood cancer. Patients and Methods Participants in the Childhood Cancer Survivor Study (CCSS; n = 13,060) were observed through age 50 years for the development of ischemic heart disease and stroke. Siblings (n = 4,023) established the baseline population risk. Piecewise exponential models with backward selection estimated the relationships between potential predictors and each outcome. The St Jude Lifetime Cohort Study (n = 1,842) and the Emma Children's Hospital cohort (n = 1,362) were used to validate the CCSS models. Results Ischemic heart disease and stroke occurred in 265 and 295 CCSS participants, respectively. Risk scores based on a standard prediction model that included sex, chemotherapy, and radiotherapy (cranial, neck, and chest) exposures achieved an area under the curve and concordance statistic of 0.70 and 0.70 for ischemic heart disease and 0.63 and 0.66 for stroke, respectively. Validation cohort area under the curve and concordance statistics ranged from 0.66 to 0.67 for ischemic heart disease and 0.68 to 0.72 for stroke. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups. The cumulative incidences at age 50 years among CCSS low-risk groups were < 5%, compared with approximately 20% for high-risk groups ( P < .001); cumulative incidence was only 1% for siblings ( P < .001 v low-risk survivors). Conclusion Information available to clinicians soon after completion of childhood cancer therapy can predict individual risk for subsequent ischemic heart disease and stroke with reasonable accuracy and discrimination through age 50 years. These models provide a framework on which to base future screening strategies and interventions.

中文翻译：

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预测儿童癌症幸存者的缺血性心脏病和中风

目的 我们旨在预测 5 年儿童癌症幸存者患缺血性心脏病和中风的个体风险。患者和方法 儿童癌症幸存者研究 (CCSS；n = 13,060) 的参与者在 50 岁时被观察到缺血性心脏病和中风的发展。兄弟姐妹 (n = 4,023) 确定了基线人口风险。具有后向选择的分段指数模型估计了潜在预测因子与每个结果之间的关系。圣裘德终身队列研究（n = 1,842）和艾玛儿童医院队列（n = 1,362）用于验证 CCSS 模型。结果 缺血性心脏病和中风分别发生在 265 和 295 名 CCSS 参与者中。基于标准预测模型的风险评分，包括性别、化疗和放疗（颅骨、颈部、和胸部）暴露的曲线下面积和一致性统计对于缺血性心脏病分别为 0.70 和 0.70，对于中风分别为 0.63 和 0.66。曲线下的验证队列面积和一致性统计数据范围为缺血性心脏病的 0.66 至 0.67 和中风的 0.68 至 0.72。风险评分被折叠以形成统计上不同的低、中和高风险组。CCSS 低危组 50 岁时的累积发病率 < 5%，而高危组约为 20% ( P < .001)；兄弟姐妹的累积发病率仅为 1%（P < .001 v 低风险幸存者）。结论 完成儿童癌症治疗后不久临床医生可获得的信息可以在 50 岁时以合理的准确性和区分度预测随后发生缺血性心脏病和中风的个体风险。这些模型提供了一个框架，可作为未来筛查策略和干预措施的基础。