Prediction of ischemic heart disease and stroke in survivors of childhood cancer Journal Article


Authors: Chow, E. J.; Chen, Y.; Hudson, M. M.; Feijen, E. A. M.; Kremer, L. C.; Border, W. L.; Green, D. M.; Meacham, L. R.; Mulrooney, D. A.; Ness, K. K.; Oeffinger, K. C.; Ronckers, C. M.; Sklar, C. A.; Stovall, M.; van der Pal, H. J.; van Dijk, I. W. E. M.; van Leeuwen, F. E.; Weathers, R. E.; Robison, L. L.; Armstrong, G. T.; Yasui, Y.
Article Title: Prediction of ischemic heart disease and stroke in survivors of childhood cancer
Abstract: 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. © 2017 by American Society of Clinical Oncology.
Keywords: adolescent; adult; cancer chemotherapy; child; controlled study; preschool child; school child; major clinical study; area under the curve; hypertension; cancer radiotherapy; comparative study; brain radiation; outcome assessment; antineoplastic metal complex; incidence; cohort analysis; obesity; alkylating agent; risk factor; childhood cancer; radiation exposure; risk assessment; cardiovascular risk; diabetes mellitus; dyslipidemia; neck; vinca alkaloid; high risk population; sibling; anthracycline; ischemic heart disease; cerebrovascular accident; thorax; abdominal radiotherapy; childhood cancer survivor; low risk population; human; male; female; priority journal; article; intermediate risk population; sex allocation
Journal Title: Journal of Clinical Oncology
Volume: 36
Issue: 1
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2018-01-01
Start Page: 44
End Page: 52
Language: English
DOI: 10.1200/jco.2017.74.8673
PROVIDER: scopus
PMCID: PMC5756324
PUBMED: 29095680
DOI/URL:
Notes: Article -- Export Date: 1 February 2018 -- Source: Scopus
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MSK Authors
  1. Charles A Sklar
    262 Sklar