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

Abstract

ImportanceAtrial fibrillation (AF) can develop following thoracic irradiation. However, the critical cardiac substructure responsible for AF has not been properly studied.ObjectiveTo describe the incidence of AF in patients with lung cancer and determine predictive cardiac dosimetric parameters.Design, Setting, and ParticipantsThis 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.ExposuresRadiation dose exposure to cardiac substructures, including the chambers, coronary arteries, and cardiac conduction nodes, were calculated for each patient.Main Outcomes and MeasuresMain outcomes were AF and overall survival.ResultsOf 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 RelevanceIn 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.

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

“…To the Editor The large interdisciplinary cohort study by Kim et al 1 of atrial fibrillation (AF) in patients completing lung cancer radiotherapy proposes dose constraints for the sinoatrial node (SAN), and we congratulate the authors on their work. We feel this study highlights several of the key challenges in cardio-oncology research.…”

“…5 Third, the pace of change in radiation oncology also restricts the applicability of the results, as unenhanced 3-dimensional scans were used for planning, and a sizeable proportion were treated with the 3-dimensional conformal technique. 1 The autosegmentation tool used was developed on breast can-cer contrast-enhanced scans, yet steps taken to verify the autocontours in this cohort were not outlined in the Methods.…”

Keeping the Heartbeat Off-Target in Cancer Therapy

“…In contrast, in this issue of JAMA Oncology , 2 cohort studies focus on quantifying the association of cancer therapies with elements of the cardiac conduction system and with the electrocardiographic manifestation of myocardial repolarization, each critical for the maintenance of normal cardiac rhythm. Kim et al investigated the outcomes of mediastinal radiation therapy for small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC) by estimating radiation doses to the sinoatrial node (SAN) and neighboring substructures and report the association with new-onset atrial fibrillation (AF) and mortality in both populations. In the article by Richardson and colleagues, the clinical consequences of the formulae used to correct the QT interval for heart rate, a key determinant of ventricular proarrhythmia, were evaluated in a large cohort of patients receiving chemotherapy.…”

“…The present study by Kim et al extends and adds granularity to these findings. In 293 patients with SCLC and 412 patients with NSCLC treated with chemoradiation therapy, the authors applied a recently developed computed tomography–based cardiac contouring atlas enabling them to calculate the maximum radiation doses delivered to individual cardiac substructures.…”

“…While contemporary invasive therapies directed toward AF focus on isolating pulmonary veins at their antra located in the left atrium, the role of the right atrium in instigating and sustaining AF may well be outsized in patients with concomitant lung disease such as cancer. Finally, an important consideration not discussed in the article by Kim et al is the association of radiation therapy with the intrinsic cardiac nervous system, a network of primarily epicardial ganglionated plexi increasingly appreciated for its modulating effects on the cardiac rhythm …”