Cardiac adverse events following post-operative radiation therapy in patients with thymic malignancies.

Abstract

Radiation therapy (RT) for thymic malignancies often exposes cardiac structures to ionizing radiation with associated cardiac adverse events risks. Given the curative intent and extended survival of patients with thymic malignancies, identifying modifiable predictors of cardiac risk is essential. While cardiac substructure dosimetry has been studied in other thoracic cancers, its role in thymic malignancies, where the target volume often abuts or overlaps the heart, is less well characterized. We retrospectively identified patients treated with surgery and postoperative RT for thymic malignancies at a single tertiary center between 2004-2021 with treatment planning information available. Cardiac substructures were segmented and dose-volume metrics were extracted for 18 individual cardiac regions. The primary outcome was heart failure (HF). Secondary exploratory outcomes included a composite of cardiovascular events (coronary artery disease, atrial fibrillation, valve replacement, stroke, and pacemaker insertion). 101 patients were available for analysis; with a median follow-up of 10 years, 30 patients experienced 40 cardiac adverse events. The most common event was HF (n = 12). Mean left ventricular dose above 15 Gy was associated with significantly higher risk of HF (OR of HF 0.17, 95% CI 0.05-0.61, p = 0.007). The risk increased by 6% per 1 Gy (95% CI 1-12%, p = 0.027). This association remained significant after adjusting for age and cardiac comorbidity. No significant association was detected between right heart dose and HF. Limited event numbers precluded definitive assessment of associations between arterial dose and ischemia or nodal dose and arrhythmia. Survival at 5, 10, and 15 years was high but was modestly lower among patients with major cardiovascular events. Higher radiation dose to the left ventricle was independently associated with increased risk of HF in thymoma survivors. These findings support incorporating substructure-based cardiac dose guidance-particularly left ventricular dose limits-into treatment planning for thymoma, and highlight the need for long-term cardiac surveillance in this population.