Abstract 4357269: Dose-Dependent Effects of Radiation on the Coronary Arteries: Results from Proton Beam Cardiac Radioablation in Swine

Abstract

Background: Cardiac radioablation (CRA) is emerging as a treatment modality for refractory ventricular tachycardia (VT). This study aimed to evaluate the effects of radiation on the coronary arteries in a swine model of proton beam CRA. Methods: Eighteen domestic swine underwent 30–40 Gy pencil-beam scanning proton therapy in a single-fraction targeting the left ventricle with no attempt to spare coronary arteries and were euthanized 12-40 weeks later. Contrast-enhanced cardiac computed tomography (CT) was performed at baseline for treatment planning and at study end. Using dose-volume histograms, the maximum point (D max ), mean (D mean ) doses and the minimal doses received by the highest irradiated volumes of 0.01 cc (D 0.01cc ) for the left main, left anterior descending, circumflex, and right coronary artery, as well as the large diagonal and obtuse marginal branches were calculated. The D max location for each artery was mapped from the baseline planning CT onto the follow-up CT using deformable registration. Coronary artery segments were harvested from the D max sites for histological analysis. Receiver operating characteristic (ROC) analysis was performed to identify dose thresholds for predicting histologically severe coronary stenoses (≥75%). Results: Ninety-six coronary artery segments were analyzed. No stenoses were observed by CT imaging before irradiation. By histological analysis post-euthanasia, 25/96 (26%) coronary segments sampled at the Dmax site per artery had ≥75% stenosis. The median D max was 4.7 Gy for the <75% stenosis group and 29.7 Gy for the ≥75% stenosis group (p<0.001). The AUC-ROC for the association between D max and severe stenosis was 92.2%. A D max value of 20.1 Gy in a single fraction best predicted severe stenosis, with sensitivity of 92.3% and specificity of 87.1%. The AUC-ROC for the association between severe stenosis versus D mean and D 0.01cc was 84.8% and 91.6%, respectively. Based on histopathologic analysis, intimal hyperplasia was the most common coronary artery abnormality at the D max sites. Conclusion: In this pre-clinical model of proton beam CRA, coronary stenoses occurred in a dose-dependent manner, with D max being a better dosimetric predictor of stenosis than D mean and D 0.01cc . These data provide for the first time radiation dose constraint information for the epicardial coronary arteries that can be considered in treatment planning for CRA and radiation for thoracic malignancies.