Long Term Evaluation of Cardiac Events and Outcomes Following Breast Cancer Irradiation

Abstract

Although whole heart dose has been associated with cardiac toxicity in patients receiving radiation therapy for breast cancer, data detailing the clinical significance of cardiac substructures, particularly the left anterior descending artery (LAD), are limited. We investigated whether dose to the LAD correlates with adverse cardiac events and death. We identified 190 female patients treated from 2002 to 2019 who received breast or chest wall irradiation, with or without regional nodal irradiation. Ninety-three patients were treated on their right side, 95 on their left, and two were bilateral. Medical records were queried in healthcare software to identify cardiac events after radiation therapy. Mean and maximum LAD and heart doses, as well as V15LAD, were calculated. Univariate and multivariate Cox regression analyses were performed to determine their association with cardiac toxicity as well as death. Cumulative incidence curves for death and cardiac toxicity were also calculated for the patient population. Median follow-up time was 68 months. Thirty patients experienced a cardiac event (15.7%), with three of these being grade 3 or higher. On univariate analyses, left side (hazard ratio 8, P<0.001), increased Mean LAD Dose per cGy (1.001, P = 0.01), Mean Heart Dose (1.16, P = 0.01), and anatomic stage (3.5, P = 0.003) were statistically significant predictors of death but not of adverse cardiac events. Statistically significant predictors of adverse cardiac events were the receipt of chemotherapy (2.68, p = 0.046) which remained significant even after adjusting for radiation parameters. There was no association with hormonal therapy use. Cumulative incidence curves predicted a 14.11% probability of a cardiac event 5 years after treatment and a 25.7% probability at 10 years after treatment. They also predicted a 9.43% probability of death at both 5- and 10-years post-treatment. On this long-term analysis, doses to the heart seemed to negatively impact survival, but did not have a clear association between cardiac events. In contrast, utilizing cytotoxic systemic therapy seemed have an association, even when adjusted for on multivariable models for cardiac events.