Cardiac Radiation Dose Distribution and Cardiotoxicity in Early-Stage Non–small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy

Abstract

Cardiac dose has been associated with overall survival in locally advanced lung cancer. The impact of radiation dose to the heart in early-stage NSCLC patients treated with definitive SBRT is not known. We therefore conducted a study to determine whether greater radiation doses to cardiac substructures, tumor location near the heart, pre-existing cardiac disease and medical comorbidities would lead to an increase in cardiac toxicity. 44 patients with 46 tumors treated definitively with SBRT for early-stage NSCLC were retrospectively analyzed. Patients were selected for tumor locations within 6 cm of the heart. The whole heart and cardiac substructures including atria, ventricles, heart valves, AV node and four major coronary artery branches were contoured using commercial treatment planning software. For each structure multiple dose-volume parameters were recorded including mean and max dose (Gy). The relation between radiation doses to cardiac substructures, tumor location, and preexisting medical conditions (e.g. cardiovascular diseases, diabetes (DM) and hypercholesterolemia (HCL)) with the development of cardiac events following SBRT was assessed. The average follow-up was 3.2 years (range 2 mo-10.8 yrs). The median prescribed dose was 48 Gy in 4 fractions (range 40-60 Gy in 3-8 fractions). Overall, there was considerable variability in dose to different cardiac substructures: mean heart dose (MHD) averaged 2.62 Gy (range 0.1-10.7) and average max dose to the left anterior descending artery was 5.92 Gy (range 0.1-21.1). As expected lower lobe tumors and tumors with central tumor location had significantly higher heart doses compared to upper lobe tumors (p=0.0006) and peripheral location (p=0.022). Distance between heart and tumor was correlated with the mean heart dose (R2=0.39). No patient with a distance of > 5 cm between PTV edge and heart in this cohort had a MHD > 5 Gy. 10 patients developed cardiac complications on average at 2 years (range 3 mo-4.1 yrs). Complications included defibrillator placement, arrhythmia development and worsening heart failure. 7/19 patients with a history of cardiac disease developed cardiac events compared to 3/25 of the patients with no history of cardiac events (p=0.051). While radiation dose to the cardiac substructures was not different between patients with and without post SBRT cardiac events, patients with cardiac complications more frequently had DM (5/10 vs 5/34, p=0.019) and HCL (7/17 vs 3/27, p=0.02). Conclusion: Doses to the heart and its substructures show large variability and depend on the tumor location. Cardiac events occurred more frequently in patients with a history of heart problems, diabetes and hypercholesterolemia and do not depend on the radiation dose to the cardiac substructures. Longer follow up is needed to determine the impact of radiation dose on cardiac toxicity after SBRT.