Sinoatrial Node Radiation During CRT May Increase Risk of Atrial Fibrillation in SCLC and NSCLC

Patients with lung cancer may develop atrial fibrillation after receiving a sinoatrial node (SAN) radiation dose during chemoradiotherapy (CRT), and could lead to increased mortality, according to a study published in JAMA Oncology.

At the median follow-up of 32.7 months, 9 patients with small cell lung cancer (SCLC) and 17 with non–small cell lung cancer (NSCLC) experienced new-onset atrial fibrillation. Among patients who received the maximum dose of SAN, investigators reported the highest value in predicting the likelihood of atrial fibrillation. In patients with SCLC, higher maximum dose of SAN led to increased risk of atrial fibrillation (adjusted HR [aHR], 14.91; 95% CI, 4.00-55.56; P <.001); similar results were observed with NSCLC (aHR, 15.67; 95% CI, 2.08-118.20; P = .008).

A total of 239 patients with SCLC and 321 with NSCLC were included in the analysis. In patients with NSCLC, consolidation therapy was given to 20.9% of patients and included durvalumab (Imfinzi), pembrolizumab (Keytruda), or nivolumab (Opdivo) followed by CRT. After receiving CRT, 1 patient with SCLC and 8 with NSCLC had chest surgery which included removal of empyema and local recurrence.

Cardiac events occurred in 9 patients at a median follow-up of 25.7 months. There were 5 non-atrial fibrillation cardiac events in patients with SCLC including 2 patients who had undergone coronary revascularizations, 1 patient with ST-segment elevation myocardial infarction, and 2 patients who were hospitalized due to heart failure with reduced ejection fraction. In patients with NSCLC, there were 17 who had new-onset atrial fibrillation and 6 with non-atrial fibrillation cardiac events with a median follow-up of 36.2 months. There were 6 patients who had coronary revascularizations and 1 patient with a non-ST segment elevation myocardial infarction.

Investigators reported that the maximum dose delivered to SAN resulted in the highest C index (HR, 0.66; 95% CI, 0.56-0.74) in terms of predicting atrial fibrillation for both patient groups. The optimal SAN maximum cutoff was 53.5 Gy (95% CI, 48.9-53.7) in patients with SCLC. In those who received more than the optimal dose, there was a significantly increased in 3-year cumulative incidence of atrial fibrillation at 25.0% (95% CI, 8.4%-74.1%) compared with 2.7% (95% CI, 1.1%-6.7%) among those who received less than 53.5 Gy.

For patients with NSCLC, the optimal level cutoff for predicting atrial fibrillation was 20.0 Gy (95% CI, 2.5-43.5). The 3-year cumulative incidence of atrial fibrillation was 9.9% (95% CI, 5.9%-16.4%) for patients who received a SAN maximum dose of 20.0 Gy or greater compared with 0.7% (95% CI, 0.0%-5.1%) who received less than 20.0 Gy.

In both groups, pericardial effusion after chemoradiotherapy was observed in 14 patients and 18 patients in the SCLC and NSCLC groups, respectively. Factors that were not significantly associated with new-onset atrial fibrillation included pericardial effusion, chest surgery after chemoradiotherapy, presence of coronary artery calcium, and extent of coronary artery calcium.

In the SCLC group, the 3-year overall survival (OS) in patients who received less than the SAN maximum dose of 53.5 Gy was 30.9% (95% CI, 13.8%-69.0%) compared with 48.5% (95% CI, 41.3%-57.0%; P = .008) those who received more than the maximum dose. For patients with NSCLC, the 3-year OS in patients who received less than the SAN maximum dose of 20.0 Gy was 35.0% (95% CI, 28.3%-43.3%) compared with 54.5% (95% CI, 46.5%-63.9%) who received more than the maximum dose. Investigators noted that a significant association was maintained between poor OS in patients with SCLC (aHR, 2.68; 95% CI, 1.53-4.71; P <.001) vs those with NSCLC (aHR, 1.97; 95% CI, 1.45-2.68; P <.001) and the maximum dose.

Patients who received the maximum radiation dose to both the left and right atriums showed a predictive value of new onset atrial fibrillation and poorer OS in both groups. The multivariate analysis showed that a higher maximum radiation dose in the SCLC group (aHR, 20.54; 95% CI, 5.57-75.65; P <.001) and the NSCLC group (aHR, 5.97; 95% CI, 1.34-26.57; P = .02) was associated with new-onset atrial fibrillation. Additionally, the significant association between poorer OS and maximum radiation dose in patients with SCLC (aHR, 2.29; 95% CI, 1.34-3.91; P = .002) and NSCLC (aHR, 1.57; 95% CI, 1.14-2.17; P = .005) was maintained.

Reference

Kim KH, Oh J, Yang G, et al. Association of sinoatrial node radiation dose with atrial fibrillation and mortality in patients with lung cancer. JAMA Oncol. Published online September 22, 2022. doi:10.1001/jamaoncol.2022.4202