Cardiac Substructure Radiation Dose and Associations With Tachyarrhythmia and Bradyarrhythmia After Lung Cancer Radiotherapy

Katelyn M Atkins; Samuel C Zhang; Christopher Kehayias; Christian Guthier; John He; Jordan O Gasho; Mina Bakhtiar; Katrina D Silos; David E Kozono; Paul C Zei; Anju Nohria; Andriana P Nikolova; Raymond H Mak

doi:10.1016/j.jaccao.2024.07.005

Cardiac Substructure Radiation Dose and Associations With Tachyarrhythmia and Bradyarrhythmia After Lung Cancer Radiotherapy

JACC CardioOncol. 2024 Aug 20;6(4):544-556. doi: 10.1016/j.jaccao.2024.07.005. eCollection 2024 Aug.

Authors

Affiliations

¹ Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
² Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
³ Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
⁴ Department of Cardiovascular Medicine, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Abstract

Background: Arrhythmias are common following radiotherapy for non-small cell lung cancer.

Objectives: The aim of this study was to analyze the association of distinct arrhythmia classes with cardiac substructure radiotherapy dose.

Methods: A retrospective analysis was conducted of 748 patients with locally advanced non-small cell lung cancer treated with radiotherapy. Cardiac substructure dose parameters were calculated. Receiver-operating characteristic curve analyses for predictors of Common Terminology Criteria for Adverse Events grade ≥3 atrial fibrillation (AF), atrial flutter, non-AF and non-atrial flutter supraventricular tachyarrhythmia (SVT), bradyarrhythmia, and ventricular tachyarrhythmia (VT) or asystole were calculated. Fine-Gray regression models were performed (with noncardiac death as a competing risk).

Results: Of 748 patients, 128 (17.1%) experienced at least 1 grade ≥3 arrhythmia, with a median time to first arrhythmia of 2.0 years (Q1-Q3: 0.9-4.2 years). The 2-year cumulative incidences of each arrhythmia group were 8.0% for AF, 2.7% for atrial flutter, 1.8% for other SVT, 1.4% for bradyarrhythmia, and 1.1% for VT or asystole. Adjusting for baseline cardiovascular risk, pulmonary vein (PV) volume receiving 5 Gy was associated with AF (subdistribution HR [sHR]: 1.04/mL; 95% CI: 1.01-1.08; P = 0.016), left circumflex coronary artery volume receiving 35 Gy with atrial flutter (sHR: 1.10/mL; 95% CI: 1.01-1.19; P = 0.028), PV volume receiving 55 Gy with SVT (sHR: 1.03 per 1%; 95% CI: 1.02-1.05; P < 0.001), right coronary artery volume receiving 25 Gy with bradyarrhythmia (sHR: 1.14/mL; 95% CI: 1.00-1.30; P = 0.042), and left main coronary artery volume receiving 5 Gy with VT or asystole (sHR: 2.45/mL; 95% CI: 1.21-4.97; P = 0.013).

Conclusions: This study revealed pathophysiologically distinct arrhythmia classes associated with radiotherapy dose to discrete cardiac substructures, including PV dose with AF and SVT, left circumflex coronary artery dose with atrial flutter, right coronary artery dose with bradyarrhythmia, and left main coronary artery dose with VT or asystole, guiding potential risk mitigation approaches.

Keywords: arrhythmia; atrial fibrillation; bradyarrhythmia; cardiac toxicity; lung cancer; radiotherapy.