F. B. Guo1, H. J. No2, S. S. Butler2, G. Merchant3, S. Jackson2, J. W. Rhee4, D. E. Clark5, C. M. Marquez2, K. C. Horst2, and M. S. Binkley2; 1University of Rochester School of Medicine and Dentistry, Rochester, NY, 2Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 3Kansas College of Osteopathic Medicine, Wichita, KS, 4Department of Medicine, Division of Cardiology, City of Hope Comprehensive Cancer Center, Duarte, CA, 5Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA
Purpose/Objective(s): Concern for radiation exposure to the heart during breast radiotherapy (RT) necessitates understanding of clinical factors that may increase risk of grade =3 cardiac events. Our study evaluates coronary artery calcification (CAC) and radiotherapy (RT) dose to cardiac structures as predictive post-RT cardiotoxicity risk factors. Materials/
Methods: We retrospectively analyzed serial patients presenting for stage I-III breast cancer from 2005-2014. The left ventricle, right atrium (RA), four major coronary arteries, and a TotalLeft structure (sum of LAD, left main, and left circumflex coronary arteries) were contoured. RT doses were recorded in 2-Gray (Gy) equivalent units, and Agatson scoring determined CAC burden. We measured cumulative incidence of cardiac events after treatment adjusted for the competing risk of death. Results: We identified 227 patients with a median follow-up of 114 months (IQR 96.6-139.8) and median age at treatment of 47.0 years (IQR 40.2-56.8). 173 (76.2%) received adjuvant RT with chemotherapy (chemoRT) after surgery, and 54 received chemotherapy only. In the full cohort, anthracyclines were used for 149 (65.6%) patients, and 41 (18.1%) received HER2 targeted therapy. 11 (6.4%), 78 (45.1%), and 84 (48.6%) patients were irradiated for bilateral, left, and right-sided disease, respectively. 139 (80.3%) irradiated patients received regional nodal irradiation (RNI). The 5-year incidence of grade =3 cardiac events for the chemoRT and chemotherapy groups was 6.2% (95% CI 3.1-10.6) and 2.0% (95% CI 0.2-9.4), respectively (P=0.35), with 13 events observed in the chemoRT group, and 3 in the chemotherapy-only cohort. 146 (73.7%) of 198 patients with CT imaging had no measurable CAC. On univariable regression analysis, nodal positivity (P<0.001), smoking (P=0.03), the ER/PR- HER2+ subtype (P<0.001), right-sided tumors (P=0.002) and RNI (P<0.001) were associated with increased cardiac risk. Triple positive tumors (P<0.001) and deep inspiratory breath hold (DIBH) (P<0.001) were negatively associated with cardiac events. Upon adjusting for age, smoking, nodal positivity, RNI, tumor side, tumor subtype, and mean RA dose on multivariable analysis, age, nodal positivity, the ER/PR-, HER2+ subtype, and mean RA dose were associated with cardiac events (P<0.05). Conclusion: In our cohort, doses to cardiac structures were generally low with low rates of cardiotoxicity. Overall, CAC burden was low, suggesting CAC scoring may not usefully identify risk of cardiotoxicity after adjuvant chemoRT for patients with breast cancer. Our study finds that risk of cardiac toxicity appears low for patients treated for breast cancer using modern RT techniques like DIBH, but patients with the HR-negative, HER2-positive subtype or with nodal positivity treated with larger radiotherapy fields may be at higher risk. Our study enables clinicians to better understand risk factors of cardiac events for breast cancer patients after radiotherapy.
