Association of Cardiac Substructure Radiation Dose and Risk of Late Cardiac Disease in Survivors of Childhood Cancer

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In an analysis from the Childhood Cancer Survivor Study (CCSS) reported in the Journal of Clinical Oncology, Bates et al identified relationships among radiation therapy doses, cardiac substructures, and risk of late-onset cardiac disease in survivors of childhood cancer.

Study Details

The analysis involved data on coronary artery disease, heart failure, valvular disease, and arrhythmias from 25,481 5-year survivors treated between 1970 and 1999 in the CCSS. Among survivors receiving radiation therapy, doses to coronary arteries, chambers, valves, and the whole heart were reconstructed.

Key Findings

Among the entire cohort, the cumulative incidence at 35 years from diagnosis was 3.9% (95% confidence interval [CI] = 3.4%–4.3%) for coronary artery disease, 3.8% (95% CI = 3.4%–4.2%) for heart failure, 1.2% (95% CI = 1.0%–1.5%) for valvular disease, and 1.4% (95% CI = 1.1%–1.6%) for arrhythmia. A total of 12,288 survivors (48.2%) were exposed to radiation therapy.

Excess relative rate models of dose-response relationship indicated that a quadratic rather than linear relationship best described the association of mean whole-heart radiation doses and risk for coronary artery disease, heart failure, and arrhythmias—suggesting the potential for a threshold dose for risk. However, linear dose-response relationships were observed for most cardiac substructures.

Mean radiation doses of 5 to 9.9 Gy to the whole heart did not increase the risk of any cardiac diseases. However, mean doses of 5 to 9.9 Gy to the right coronary artery (rate ratio [RR] = 2.6, 95% CI = 1.6–4.1) and left ventricle (RR = 2.2, 95% CI = 1.3–3.7) were associated with an increased risk of coronary artery disease, and mean doses of 5 to 9.9 Gy to the tricuspid valve (RR = 5.5, 95% CI = 2.0–15.1) and right ventricle (RR = 8.4, 95% CI = 3.7–19.0) were associated with an increased risk of valvular disease.

The investigators concluded, “Among children with cancer, there may be no threshold dose below which radiation to the cardiac substructures does not increase the risk of cardiac diseases. This emphasizes their importance in modern treatment planning.”

James E. Bates, MD, of the Department of Radiation Oncology, Winship Cancer Institute, Emory University, is the corresponding author for the Journal of Clinical Oncology article.  

Disclosure: The study was supported by the National Cancer Institute and American Lebanese-Syrian Associated Charities. For full disclosures of the study authors, visit

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