Association of Sinoatrial Node Radiation Dose With Atrial Fibrillation and Mortality in Patients With Lung Cancer

Abstract

Atrial fibrillation (AF) can develop following thoracic irradiation. However, the critical cardiac substructure responsible for AF has not been properly studied. To describe the incidence of AF in patients with lung cancer and determine predictive cardiac dosimetric parameters. This retrospective cohort study was performed at a single referral center and included 239 patients diagnosed with limited-stage small cell lung cancer (SCLC) and 321 patients diagnosed with locally advanced non-small cell lung cancer (NSCLC) between August 2008 and December 2019 who were treated with definitive chemoradiotherapy. Radiation dose exposure to cardiac substructures, including the chambers, coronary arteries, and cardiac conduction nodes, were calculated for each patient. Main outcomes were AF and overall survival. Of the 239 and 321 patients with SCLC and NSCLC, the median (IQR) age was 68 (60-73) years and 67 (61-75) years, and 207 (86.6%) and 261 (81.3%) were men, respectively. At a median (IQR) follow-up time of 32.7 (22.1-56.6) months, 9 and 17 patients experienced new-onset AF in the SCLC and NSCLC cohorts, respectively. The maximum dose delivered to the sinoatrial node (SAN Dmax) exhibited the highest predictive value for prediction of AF. A higher SAN Dmax significantly predicted an increased risk of AF in patients with SCLC (adjusted hazard ratio [aHR], 14.91; 95% CI, 4.00-55.56; P < .001) and NSCLC (aHR, 15.67; 95% CI, 2.08-118.20; P = .008). However, SAN Dmax was not associated with non-AF cardiac events. Increased SAN Dmax was significantly associated with poor overall survival in patients with SCLC (aHR, 2.68; 95% CI, 1.53-4.71; P < .001) and NSCLC (aHR, 1.97; 95% CI, 1.45-2.68; P < .001). In this cohort study, results suggest that incidental irradiation of the SAN during chemoradiotherapy may be associated with the development of AF and increased mortality. This supports the need to minimize radiation dose exposure to the SAN during radiotherapy planning and to consider close follow-up for the early detection of AF in patients receiving thoracic irradiation.