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J Clin Oncol. 2018 Jan 1;36(1):44-52. doi: 10.1200/JCO.2017.74.8673. Epub 2017 Nov 2.

Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer.

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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.


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.

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