2322 - Patterns of Failure and Toxicity in Patients with N2 vs. N3 Disease Undergoing Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer
Presenter(s)
M. Berger1, C. Friedes1, N. Yegya-Raman1, W. P. Levin2, K. A. Cengel1, J. D. Bradley3, S. J. Feigenberg1, and M. Iocolano1; 1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 2Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 3University of Pennsylvania/Abramson Cancer Center, Philadelphia, PA
Purpose/Objective(s): To compare the patterns of failure (PoF), toxicity, and oncologic outcomes of patients with N2 vs N3 locally advanced non-small cell lung cancer (LA-NSCLC) treated with definitive chemoradiation (CRT) +/- immunotherapy (IO).
Materials/Methods: Patients with LA-NSCLC undergoing CRT +/- IO from January 2011 to November 2021 were analyzed. Eligible patients had clinical or biopsy proven N2 or N3 involvement (AJCC 8th edition). Site of first failure was classified as locoregional (LRF), distant (DF), or synchronous. The cumulative incidence of PoFs and toxicities were calculated with death as a competing risk, and groups were compared with Gray’s test. Progression free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method, with group comparisons assessed via the log-rank test. Fine-Gray regression was used to analyze associations of clinical characteristics and time-to-event endpoints. Subgroup analyses were performed for patients treated in the IO era. The primary objective was to compare PoFs and toxicity between N2 and N3 disease. Secondary objectives assessed differences in PFS and OS.
Results: The median PFS and OS for the 631 eligible patients were 12.2 and 28.4 months (mo), respectively. 461 (73.1%) had N2 and 170 (26.9%) had N3 disease. The N2 group had fewer adenocarcinomas (52.7% vs. 64.7%, p<0.001) and received more concurrent carboplatin/paclitaxel (66.6% vs. 55.9%, p=0.013). The median RT dose delivered was 6,600 cGy for both N2 and N3 patients. There was no difference between N2 and N3 for whether patients were treated in the IO era (43.8% vs 40.0%, p=0.390) or received consolidative IO (30.4% vs 28.8%, p=0.707). There was no significant difference in median PFS or OS between N2 and N3 disease in the overall cohort (PFS: 12.3 vs. 11.6 mo, p=0.95; OS: 26.5 vs. 32.4 mo, p=0.40) or in the IO era (PFS: 13.9 vs. 15.5 mo, p=0.71; OS: 31.7 vs. 38.8 mo, p=0.76). In all patients, the cumulative incidence of LRF and DF did not differ between N2 and N3 disease (2-year LRF 9.2% vs 11%, p= 0.67; 2-year DF 31% vs 33%, p=0.48). However, in the IO era, patients with N3 disease had a higher 2-year incidence of LRF vs N2 patients (17% vs 6.6%, p=0.008), with no difference in DF (28% vs 33%, p=0.22). On multivariable analysis, N3 disease (sHR 2.82, 95% CI 1.42-5.57, p=0.003) and squamous histology (sHR 2.41, 95% CI 1.13-5.12, p=0.023) were predictors of LRF in the IO era. There was no difference in the incidence of G2+ pneumonitis between groups (27% vs 26%, p=0.85), but G3+ esophagitis was more common in N3 patients (11% vs 4.6%, p=0.007).
Conclusion: N3 patients had higher rates of G3+ esophagitis. There were no differences in OS or PFS between N2 and N3 patients. However, in the IO era, N3 disease was associated with increased LRF, highlighting the importance of aggressive local therapy in these patients.