Increased Risk of Cardiac Events With High Heart Dose in High-Dose Thoracic Radiotherapy
In a single-center pooled analysis reported in the Journal of Clinical Oncology, Wang et al found that a higher dose of radiation to the heart was associated with an increased risk of cardiac events in patients receiving high-dose radiation therapy for stage III non–small cell lung cancer (NSCLC).
Study Details
The study included 112 patients in 6 prospective trials at the University of North Carolina between 1996 and 2009 who received dose-escalated radiation therapy to 70 to 90 Gy. Radiation therapy was given by three-dimensional conformal radiation therapy, usually using a four-field technique. Intensity-modulated radiation therapy was not used.
The primary endpoints for the analysis were symptomatic cardiac events, including symptomatic pericardial effusion, acute coronary syndrome, pericarditis, significant arrhythmia, and heart failure. Baseline cardiac risk was determined by the presence or absence of coronary artery disease and the World Health Organization/International Society of Hypertension score.
Increased Risk
Median follow-up among surviving patients was 8.8 years. Patients received a median radiation therapy dose of 74 Gy. One or more cardiac events occurred in 26 patients (23%), at a median of 26 months to the first event, with events consisting of effusion in 7, myocardial infarction in 5, unstable angina in 3, pericarditis in 2, arrhythmia in 12, and heart failure in 1.
On univariate analysis, heart mean dose (hazard ratio [HR] = 1.03/Gy, P = .002,), coronary artery disease (P < .001), and hypertension score (P = .04) were associated with an increased risk of events. On multivariate analysis accounting for baseline risk, heart mean dose remained a significant predictor of risk (HR = 1.04/Gy, P = .001). On competing risk analysis, 2-year adjusted event rates were 4%, 7%, and 21% for mean heart doses of ≤ 10, 10 to 20, and > 20 Gy, respectively. There was no significant association of heart dose with overall survival.
The investigators concluded: “Cardiac events were relatively common after high-dose thoracic [radiation therapy] and were independently associated with both heart dose and baseline cardiac risk. [Radiation therapy]–associated cardiac toxicity after treatment of stage III NSCLC may occur earlier than historically understood, and heart doses should be minimized.”
The study was supported by a grant from the National Institutes of Health.
Kyle Wang, MD, of the University of North Carolina Hospitals, is the corresponding author of the Journal of Clinical Oncology article.
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