277 - The Association of Left Anterior Descending Coronary Artery Radiation Dose with Major Adverse Cardiac Events Following Modern Breast Radiotherapy

S. Quirk¹, K. M. Atkins², R. J. Miller³, C. V. Guthier⁴, K. Silos⁵, J. Braun³, N. Logie³, K. K. English⁶, I. R. Marsh⁷, R. H. Mak⁴, A. Al-Rashdan⁸, and M. B. Roumeliotis⁷; ¹Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, ²Cedars-Sinai Medical Center, Los Angeles, CA, ³University of Calgary, Calgary, AB, Canada, ⁴Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, ⁵Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, ⁶Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD, ⁷Johns Hopkins School of Medicine, Baltimore, MD, ⁸Dalhousie University, Halifax, NS, Canada

Purpose/Objective(s): The objective of this study is to perform comprehensive left anterior descending artery (LAD) dosimetric analysis to identify predictors of major adverse cardiac events (MACE). Materials/

Methods: The analysis included women with non-metastatic breast cancer treated with RT between 2012 and 2018. With validated artificial intelligence software, the whole heart and LAD were contoured and dosimetric data was extracted for the clinically treated tangent fields. Patients were cross matched to the ongoing, prospective Alberta Provincial Project for Outcome Assessment in Coronary Heart disease (APPROACH) database to identify MACE; defined as myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, or clinically indicated coronary revascularization. Dose volume variables analyzed were mean, maximum, and binned 1 Gy increments to 10 Gy and 5 Gy increments to 50 Gy. Receiver operator curve (ROC) and cut-point analyses estimating MACE were performed. Cox regression was performed to identify dosimetric predictors of MACE, adjusting for baseline cardiac risk.
Results: Over the period, 3313 patients were included in the analysis, with a median age of 60 years (interquartile range 51-68) and with a median follow-up of 7.0 years (IQR 5.3-8.9). The most common prescription was 42.5 Gy in 16 fractions (81.3%), 36.4% had regional nodal irradiation, and 24.1% received a breast and/or chest wall boost. The median volume of the LAD was 10.5 cm³ (IQR 9.2-11.8). The median of the LAD maximum dose (D_max) for right- and left-sided treatments was 0.3 Gy (IQR 0.2-0.4) and 11.3 Gy (IQR 6.8-29.2), respectively. There were 87 MACE events with median time to event of 6.9 years (IQR 5.2-8.8), resulting in a 10-year MACE rate of 3.7%. In ROC analysis, the area under the curve predicting MACE was greater for the top LAD dose variables (LAD V1Gy [0.60] and LAD D_max in left-sided, LAD D_max [0.56] in right-sided), compared mean heart dose (MHD; 0.53 for left-sided, 0.46 for right-sided). Cutpoint analysis identified thresholds of LAD V1Gy = 9 cm³, LAD D_max = 17 Gy, and MHD = 1 Gy for left-sided treatments (for right-sided, only LAD D_max [0.56] had AUC > 0.51). After adjusting for cardiovascular risk factors, including age, hypertension, diabetes, hyperlipidemia, chronic kidney disease, and RT risk factors, including laterality and year of RT, there was an increased risk of MACE with LAD V1Gy = 9 cm³ (adjusted hazard ratio [aHR] 1.73, 95% confidence interval [95% CI]; p = 0.047), but not LAD D_max = 17 Gy (aHR 1.67, 95% CI, 0.78-3.58; p = 0.19) or MHD = 1 Gy (aHR 0.72, 95% CI, 0.41-1.29; p = 0.28). The 10-year MACE rate doubled from 3.0% to 5.7% for patients with LAD V1Gy < 9 cm³ versus = 9 cm³ (p = 0.028).
Conclusion: In a modern cohort of breast cancer RT, overall MACE rates were low, but remained associated with LAD radiation dose. Dose to the LAD outperformed mean heart dose in predicting MACE, further supporting the need to determine LAD dose effect relationships.