The Impact of Cardiac Sparing Techniques on Major Cardiac Events for Patients Undergoing Breast Radiotherapy

Abstract

In radiotherapy, studies with historical estimates have shown a linear relationship between cardiac dose and risk of major cardiac events with no safe dose threshold. This study investigates the relationship between cardiac dose and event rates for patients undergoing breast radiotherapy with modern heart-sparing techniques, where substantially lower cardiac doses are achieved. From 2008 to 2018, all patients undergoing curative whole breast or chest wall radiotherapy at a tertiary care center were included. In this study, the deep-inspiration breath hold (DIBH) technique was implemented in 2013 as the standard of care for left-sided patients. Cardiacdosimetricdata from the clinical treatment plan was extracted and matched to patients from the ongoing, prospectively collected Alberta Provincial Project for Outcome Assessment in Coronary Heart disease (APPROACH) database that experienced a major adverse cardiac event (MACE). MACE was defined as myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure,or clinically indicated coronary revascularization.For all the left- and right-sided patients, the population event rates, the median time to event, and the average (± standard deviation) of the mean heart physical dose is reported. The proportion of left- and right-sided patients experiencing a major cardiac event were tested for independence using a two-sample z-test for proportions. A student's t-test was used to measure significance for mean heart dose. An alpha of 0.05 was used to indicate significance for both tests. A total of 4893 patients received breast radiotherapy with 2429 left-sided, 2429 right-sided, and 35 synchronous bilateral. For all patients, Table 1 describes laterality, treatment characteristics, and prescription. The median (range) age at the time of first radiotherapy treatment was 59 (23-94). Of these patients with contours available, 96 left-sided (3.9%) and 69 right-sided (2.8%) patients experienced a MACE (p = 0.03) with a mean heart dose of 1.4 (±0.7)Gyand 0.5 (±0.2)Gy, in the event cohorts respectively (p < 0.001). The mean time to event was 4.7 (±3.2) years and 4.8 (±3.0) years for left- and right-sided patients, respectively (p = 0.83). For the left-sided cohort treated with DIBH, the mean heart dose is 1.0 (±0.8)Gy. In the era of modern radiotherapy and cardiac-sparing techniques, mean heart dose and corresponding event rates are stillsignificantlyhigher for left-sided patients than right-sided patients. Future work will aim to test whether there is a safe threshold for cardiac dose in the context of these results.