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Abstract
Importance: Atrial fibrillation (AF) can develop following thoracic irradiation. However, the critical cardiac substructure responsible for AF has not been properly studied.

Objective: To describe the incidence of AF in patients with lung cancer and determine predictive cardiac dosimetric parameters.

Design, setting, and participants: 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.

Exposures: Radiation dose exposure to cardiac substructures, including the chambers, coronary arteries, and cardiac conduction nodes, were calculated for each patient.

Main outcomes and measures: Main outcomes were AF and overall survival.

Results: 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).

Conclusions and relevance: 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.

소세포성 폐암 코호트(위 그림)에서 동방결절에 선량이 높은 경우 심방세동 발생이 25%로 선량이 낮았던 환자군(2.7%)에 비해 높게 나타났다. 비소세포성폐암 코호트에서도 역시 동방결절 선량이 높은 경우 심방세동 발생이 9.9%로 선량이 낮았던 환자군(0.7%)에 비해 높게 나타났다.

Affiliations

Kyung Hwan Kim 1, Jaewon Oh 2, Gowoon Yang 1, Joongyo Lee 1, Jihun Kim 1, Seo-Yeon Gwak 2, Iksung Cho 2, Seung Hyun Lee 3, Hwa Kyung Byun 1, Hyo-Kyoung Choi 4, Jinsung Kim 1, Jee Suk Chang 1, Seok-Min Kang 2, Hong In Yoon 1
1Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
2Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
3Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.
4Research Group of Healthcare, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of Korea.