Early Cardiotoxicity in Patients Receiving Hypofractionated Radiotherapy after Breast Conserving Surgery: Analysis of a Prospective Study

Abstract

To evaluate the early cardiotoxicity of hypofractionated radiotherapy (HFRT) in patients with left-sided breast cancer after breast-conserving surgery, and to investigate the correlation between cardiotoxicity and cardiac dose. A total of 103 women from 2017 to 2018 who received left-sided whole-breast with or without regional nodal irradiation either using deep inspiration breath-hold (DIBH) or free-breathing (FB) technique were prospectively enrolled. N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiogram, and radionuclide myocardial perfusion imaging were conducted before and after HFRT. Logistic regression analyses were performed to determine the association of cancer treatment, cardiac dose, and cardiovascular risk factors with cardiotoxic effects. The mean dose (Dmean) of the heart, left anterior descending coronary artery (LAD), left ventricular (LV), and right ventricular (RV) in all patients was 403 cGy, 1685 cGy, 627 cGy, and 444 cGy, respectively. In comparison to FB, DIBH significantly reduced cardiac dose (heart Dmean 250 cGy vs. 570 cGy, LAD Dmean 1250 cGy vs. 2170 cGy, LV Dmean 420 cGy vs. 850 cGy, RV Dmean 260 cGy vs. 650 cGy; all p<0.001). With a median follow-up of 49 months (range, 2-65 months), no patients had clinical cardiac abnormalities or cardiac-related symptoms, but 42 (41%) patients had subclinical cardiac events. Among them, 41 were electrocardiogram changes, and one had LV ejection fraction decreased by 10% compared with the baseline level. Twenty-five (60%) recovered during follow-up, of which 17 (40%) experienced subclinical changes only once. The mean value of NT-proBNP did not change significantly before and after HFRT. In univariate analyses, DIBH technique significantly decreased the risk of subclinical cardiac events compared with FB (OR 0.31, 95% CI 0.14-0.71; p = 0.006); however, higher mean doses of heart and LV, anthracycline-based chemotherapy, obesity, and hypertension were associated with increased risk of subclinical cardiac events (all p<0.05). Early subclinical cardiac damage after HFRT in left-sided breast cancer is dose-related, and mostly manageable and reversible without medical intervention.