1. Ischemic Heart Disease Following Left Breast Irradiation with Active Breathing Control (ABC): 10 year Outcomes and Risk Modeling Abstract 1027 Presenter: Harriet Eldredge-Hindy, MD

2. Cardiac Outcomes Following Radiotherapy with ABC Have Not Been Characterized Most literature surrounding cardiac-sparing radiotherapy (RT) for breast cancer has focused on dosimetric outcomes. Recently published randomized trial demonstrated that despite a reduction in dose to the heart with ABC, the technique did not prevent RT-induced myocardial perfusion deficits as assessed by SPECT. 1 It is unknown whether the clinical ramifications of these perfusions changes, if any, will include ischemic heart disease. Obstacles in assessing the clinical effects of cardiac-sparing RT techniques like ABC: (1) Prolonged latency for the development of RT-related ischemic heart disease (2) Large sample size needed—estimates range 2,000 to 15,000. 2 Due to these barriers, risk modeling is an attractive method to examine outcomes.

3. Are the Dosimetric Benefits Owed to ABC Clinically Significant? Absolute reduction in cardiac risk owed to ABC was small (<2%) in most patients; however, this may be clinically significant given the high incidence of breast cancer. Largest lifetime absolute risk reduction was 3.5% and observed in patients at the highest risk for cardiac ischemia, implying that these patients will benefit the most from ABC. This dose-effect model has been used to analyze cardiac risk in patients treated in the prone position with comparable findings. 3 Findings translate to other methods for cardiac-sparing RT. ABC technique should not be abandoned as it may provide a clinically significant reduction in the risk of ischemic heart disease in well-selected patients.

4. Study Strengths 1. Used patient-level data for dosimetry and cardiac risk 2. Findings may guide patient selection for RT with ABC. 3. Provide data to counsel patients regarding risks & benefits of RT with ABC or conventional techniques. 4. First available report of cardiac events following left breast RT with ABC. Limitations 1. Dose-effect model by Darby et al. has specific limitations and has not been validated in a cohort treated with modern RT techniques. 4 2. Model does not consider other dose metrics that could predict toxicity (e.g. dose to coronary arteries or left ventricle). 3. Sample size, follow up time, cardiac event rate too low to draw definitive conclusions.

5. Works Cited 1.Zellars R, Bravo PE, Tryggestad E, et al. SPECT analysis of cardiac perfusion changes after whole-breast/chest wall radiation therapy with or without active breathing coordinator: Results of a randomized phase 3 trial. Int J Radiat Oncol Biol Phys 2014;88:778-85. 2.Evans SB, Sioshansi S, Moran MS, et al. Prevalence of poor cardiac anatomy in carcinoma of the breast treated with whole-breast radiotherapy: Reconciling modern cardiac dosimetry with cardiac mortality data. Am J Clin Oncol 2012;35:587-592. 3.Brenner DJ, Shuryak I, Jozsef G, et al. Risk and risk reduction of major coronary events associated with contemporary breast radiotherapy. JAMA Intern Med 2014;174:158-60. 4.Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 2013;368:987-98.