The Association of right atrium and sinoatrial node irradiation with atrial fibrillation and radiation-induced heart disease in non-small cell lung cancer

BACKGROUND AND PURPOSE: Radiotherapy (RT) is a key treatment for locally advanced non-small cell lung cancer (NSCLC). Tumours near the heart may result in unintended cardiac radiation exposure, increasing the risk of cardiotoxicity, such as de novo atrial fibrillation (DNAF) and de novo heart diseases (DNHD) as ischemic heart disease, heart failure, arterial hypertension or sudden cardiac death. This study investigated associations between radiation dose to cardiac substructures and risk of DNAF and DNHD. Patient/material and methods: This retrospective cohort study included patients treated between January 1, 2010, and December 31, 2020 for NSCLC with definitive RT. The heart, right atrium (RA) and sinoatrial node (SAN) were delineated. Associations between dose-volume parameters and cardiac outcomes were analysed using multivariable models adjusted for relevant confounders. Kaplan-Meier curves estimated survival; p-values < 0.05 were significant. RESULTS: Among 273 included patients, 9.5% had AF pre-RT and 12.8% developed DNAF. DNAF was significantly associated with SAN Dmax (hazard ratio [HR] = 1.01), RA Dmax (HR = 1.02), RA Dmean (HR = 1.03), mean heart dose (MHD) (HR = 1.04) and heart V40Gy (HR = 1.03). One-year probabilities of DNAF and DNHD were 9.3% and 11%, increasing to 12.2% and 13.2% at 2 years. DNHD was significantly associated with SAN Dmax (HR = 1.02), RA Dmax (HR = 1.02), RA Dmean (HR = 1.04), MHD (HR = 1.06), heart V25Gy (HR = 1.03) and V40Gy (HR = 1.03). INTERPRETATION: The RA and SAN may be considered organs at risk in future RT planning. Minimising cardiac radiation is important to reduce DNAF and DNHD risk. Validation in an independent cohort is warranted.