medwireNews: Incidental irradiation of the sinoatrial node (SAN) during lung cancer chemoradiotherapy may be associated with an increased risk for atrial fibrillation (AF) and death, research suggests.
Seok-Min Kang (Yonsei University College of Medicine, Seoul, Republic of Korea) and colleagues say their findings account for “the need to minimize radiation dose exposure to the SAN during radiotherapy [RT] planning and to consider close follow-up for the early detection of AF in patients receiving thoracic irradiation.”
The retrospective study included data for 239 patients (median age 68 years, 87% men) with limited-stage small-cell lung cancer (SCLC) and 321 patients (median age 67 years, 81% men) with locally advanced non-small-cell lung cancer (NSCLC) who were treated with definitive chemoradiotherapy between 2008 and 2019.
Chemotherapy was etoposide with cisplatin or carboplatin for four to six cycles among the patients with SCLC and weekly paclitaxel with carboplatin for up to six cycles among those with NSCLC, while RT was given at a total dose of 60–63 Gy in fractions of 1.8–2.1 Gy using 3-dimensional conformal RT or intensity-modulated RT techniques.
Kang et al report in JAMA Oncology that during a median 32.7 months of follow-up, nine people in the SCLC cohort and 17 in the NSCLC cohort developed new-onset AF.
When they investigated the maximum radiation doses (Dmax) delivered to individual cardiac substructures, the researchers found that the Dmax delivered to the SAN was the strongest predictor of AF.
In the SCLC cohort, the optimal cutoff for SAN Dmax was 53.5 Gy. Patients who received a SAN Dmax above this threshold had a significantly higher 3-year cumulative incidence of AF than those who received a lower dose, at 25.0% versus 2.7%, corresponding to a significant 14.9-fold increased risk for AF with the higher dose, after adjustment for potential confounders.
In addition, the 3-year overall survival (OS) rate was significantly worse among patients who received SAN Dmax of 53.5 Gy or greater relative to those who received a lower dose, at 30.9% versus 48.5% and a corresponding adjusted hazard ratio (HR) for death of 2.7.
For the patients with NSCLC, the optimal SAN Dmax cutoff was 20.0 Gy. Participants who received this dose or higher had a 3-year cumulative AF incidence of 9.9% compared with a significantly lower 0.7% among those who received a lower dose, corresponding to a 15.7-fold increased risk for AF with the higher dose.
The 3-year OS rates were 35.0% and 54.5% with SAN Dmax doses above and below the optimal NSCLC threshold and the risk for death was a significant 2.0-fold greater with the higher dose in the participants with NSCLC.
Kang and co-authors say that the lower SAN Dmax cutoff and higher AF incidence in the NSCLC cohort may “indicate that patients in the NSCLC cohort may have been more sensitized to the effect of radiation compared with the SCLC cohort.” They suggest that these differences “may be partially explained through the different chemotherapy regimen used in the 2 cohorts.”
The investigators also found that Dmax at the right atrium (RA) was significantly associated with new-onset AF and OS in both cohorts.
“Considering the proximity of SAN and RA, the strong correlation between SAN Dmax and RA Dmax may have led to the similar results between the 2 parameters,” Kang et al remark.
They add: “The current study data imply that if there are limitations in defining SAN, RA Dmax may be able to serve as an alternative.”
The authors conclude that “[f]urther validation studies are required to confirm the optimal cutoff value.”
In the meantime, they “suggest keeping SAN Dmax as low as reasonably allowable while satisfying the dose constraints to other organs at risk and maintaining tumor coverage.”
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JAMA Oncol 2022; doi:10.1001/jamaoncol.2022.4202