Eric J. Chow Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA; Yan Chen, University of Alberta, Edmonton, Alberta, Canada; Melissa M. Hudson, Daniel M. Green, Daniel A. Mulrooney, Kirsten K. Ness, Leslie L. Robison, Gregory T. Armstrong, and Yutaka Yasui, St Jude Children's Research Hospital; Daniel A. Mulrooney, University of Tennessee, Memphis, TN; Elizabeth A.M. Feijen, Leontien C. Kremer, Cécile M. Ronckers, Helena J. van der Pal, and Irma W.E.M. van Dijk, Emma Children's Hospital, Academic Medical Center; Irma W.E.M. van Dijk, Academic Medical Center; Flora E. van Leeuwen, The Netherlands Cancer Institute, Amsterdam; Leontien C. Kremer and Helena J. van der Pal, Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands; William L. Border and Lillian R. Meacham, Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Kevin C. Oeffinger, Duke University Medical Center, Durham, NC; Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY; and Marilyn Stovall and Rita E. Weathers, The University of Texas MD Anderson Cancer Center, Houston, TX.
J Clin Oncol. 2018 Jan 1;36(1):44-52. doi: 10.1200/JCO.2017.74.8673. Epub 2017 Nov 2.
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.
我们旨在预测儿童癌症 5 年幸存者的缺血性心脏病和中风的个体风险。
参与儿童癌症幸存者研究（CCSS；n = 13060）的患者在 50 岁之前观察缺血性心脏病和中风的发生情况。同胞（n = 4023）建立了基线人群风险。使用向后选择的分段指数模型估计潜在预测因子与每种结果之间的关系。圣裘德终身队列研究（n = 1842）和艾玛儿童医院队列（n = 1362）用于验证 CCSS 模型。
265 例 CCSS 患者发生缺血性心脏病，295 例患者发生中风。基于包括性别、化疗和放疗（颅、颈和胸部）暴露的标准预测模型的风险评分，缺血性心脏病的曲线下面积和一致性统计分别为 0.70 和 0.70，中风的曲线下面积和一致性统计分别为 0.63 和 0.66。验证队列的曲线下面积和一致性统计值分别为缺血性心脏病 0.66-0.67 和中风 0.68-0.72。风险评分被合并为统计学上不同的低、中、高危组。在 CCSS 低危组中，50 岁时的累积发生率<5%，而高危组则约为 20%（P<0.001）；兄弟姐妹的累积发生率仅为 1%（P<0.001 比低危幸存者）。
在儿童癌症治疗完成后不久，临床医生可获得的信息可以以合理的准确性和区分度预测个体随后发生缺血性心脏病和中风的风险，直至 50 岁。这些模型为未来的筛查策略和干预措施提供了框架。
