2476 - Dosimetric Predictors of Pneumonitis in Unresectable Locally Advanced NSCLC: Impact of Chemoradiation with or without Immunotherapy

Purpose/Objective(s): The standard of care for unresectable locally advanced NSCLC patients is chemoradiation (CRT) followed by consolidative immunotherapy (IO). Both pneumonitis and esophagitis remain a major concern for lung radiation treatment-related toxicities in this population. Our study evaluates dosimetric values as predictors of these toxicities in patients treated with CRT, with or without IO.

Materials/Methods: In our retrospective study, 182 patients with locally advanced NSCLC treated between 2009 and 2024 were evaluated. Dosimetric parameters for pneumonitis were recorded. Patients were stratified into two subgroups, receiving CRT alone versus CRT with IO. Toxicity outcomes were assessed using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 during radiation treatment and follow up.

Results: The median age was 66 years [IQR 58.7-75]. 51.1% (n=93) patients were females. 72.5% (n=132) were former smokers and 14.8% (n=27) were current smokers. 89.6% (n=163) had ECOG PS 0-1. Adenocarcinoma was the most common histology (n=96; 52.7%) followed by squamous cell carcinoma (n=72; 39.6%) and mixed histology (7.7%; n=14). Stage III disease was present in 163 patients (89.5%), while stage IIB was present in 19 patients (10.5%). 55% (n=100) patients received definitive CRT, while 45% (n=82) patients received CRT-IO. Of the patients receiving CRT-IO, 62 patients received consolidative IO, while 20 patients received concurrent IO. The median duration of follow-up was 30 months. The median Dmean, V20Gy and V5Gy radiation dose for lungs was 18.6 Gy, 32% and 55% in CRT group while Dmean, V20Gy and V5Gy radiation dose for was 16.4Gy, 30% and 56% in CRT-IO group respectively. In the overall cohort, G2 pneumonitis was seen in 19.2% (n=35) and G3 pneumonitis was seen in 4.9% (n=9) patients. On logistic regression analysis, IO use was significantly associated with higher risk of development of G2-G3 pneumonitis (p=0.006) as compared to CRT alone. Further analysis of IO sequencing revealed 15% G2-G3 pneumonitis in both consolidative IO and concurrent IO subgroups (p=NS). Larger PTV volume showed a trend towards increased pneumonitis (p=0.078)

Conclusion: Adding IO to CRT increases pneumonitis risk in Stage III NSCLC patients, though concurrent IO does not elevate risk compared to sequential IO with careful treatment planning. Further dosimetric evaluations are needed to establish constraints for modern RT with IO.