Predictive Model for Ischemic Heart Disease and Stroke in Childhood Cancer Survivors

Key Points

  • A risk model including sex, chemotherapy, and radiotherapy exposure was accurate in predicting the risk of ischemic heart disease and stroke in 5-year survivors of childhood cancer.
  • Risk scoring distinguishes low-, moderate-, and high-risk groups with a cumulative incidence of < 5% in the low-risk group and approximately 20% in the high-risk group.

As reported in the Journal of Clinical Oncology, Chow et al have developed a model that distinguishes risk groups for ischemic heart disease and stroke in 5-year survivors of childhood cancer.

Study Details

The study included data from 13,060 participants in the Childhood Cancer Survivor Study (CCSS) observed through age 50 years for development of ischemic heart disease and stroke. Baseline population risk was defined as risk in participant siblings (n = 4,023). Relationships between potential predictors and outcomes were estimated using piecewise exponential models with backward selection. The CCCS risk models were validated in cohorts from the St. Jude Lifetime Cohort Study (n = 1,842) and the Emma Children’s Hospital cohort (n = 1,362).

Predictive Model

Overall, ischemic heart disease and stroke occurred in 265 and 295 CCSS participants, respectively. Risk scores based on a standard prediction model including sex; chemotherapy; and cranial, neck, and chest radiotherapy exposures produced AUC values and concordance statistics of 0.70 and 0.70 for ischemic heart disease and 0.63 and 0.66 for stroke, respectively. In the validation cohorts, AUC values and concordance statistics were 0.66 to 0.67 for ischemic heart disease and 0.68 to 0.72 for stroke, respectively.

Risk Groups

Risk scores were sorted to distinguish low-, moderate-, and high-risk groups (P < .01 for between group differences), with the lowest-risk survivor group having a greater event rate ratio than siblings (P < .001). The cumulative incidence of events by age 50 for low-, moderate-, and high-risk groups were 2.3%, 11.9%, and 19.9% for ischemic heart disease and 2.4%, 6.9%, and 19.9% for stroke (1.2% and 1.1% for siblings), respectively. For ischemic heart disease, rate ratios were 3.2 for moderate vs low risk and 2.5 for high vs moderate risk. For stroke, rate ratios were 2.1 for moderate vs low risk and 4.2 for high vs moderate risk.

The investigators concluded: “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.”

The study was supported by the National Institutes of Health, PanCareSurFup EU, American Lebanese Syrian Associated Charities, Dutch Cancer Society, Foundation for Pediatric Cancer Research (the Netherlands), and Leukemia and Lymphoma Society.

Eric J. Chow, MD, MPH, of the Fred Hutchinson Cancer Research Center, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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