Abstract
BACKGROUND: The heterogeneity of locally advanced non-small cell lung cancer (LA-NSCLC) has led to varied treatment strategies. Before the immunotherapy era, definitive chemoradiotherapy (CRT) was the standard for inoperable patients. This real-world study evaluates the role of thoracic radiotherapy (RT) in patients receiving first-line immunotherapy-based treatment. METHODS: This retrospective analysis included stage III NSCLC patients from January 2018 to December 2022 who were inoperable or declined surgery and received immunotherapy. Treatment patterns, survival outcomes, and failure modes were assessed. Real-world overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were analyzed using Kaplan-Meier methods. RESULTS: Among 410 eligible patients, 173 received RT (RT group), while 237 underwent chemoimmunotherapy (CIT) alone (non-RT group). The RT group demonstrated significantly longer median OS (55.5 vs. 26.6 months) and PFS (21.3 vs. 14.1 months) compared to the non-RT group (P<0.001). Patients receiving ≤4 CIT induction cycles before RT had improved outcomes versus >4 cycles (P=0.04). No survival difference was observed between RT doses of 50 Gy and 60 Gy. CONCLUSIONS: This study confirms that thoracic RT remains essential for inoperable LA-NSCLC in the immunotherapy era. An exploratory analysis suggests that a potential strategy could involve ≤4 cycles of CIT induction followed by concurrent CRT (cCRT) and immune checkpoint inhibitor maintenance. These findings encourage further investigation into RT integration within multimodal treatment, with 50-60 Gy appearing potentially comparable in selected patients.