Improved Locoregional Recurrence-Free Survival With Carbon Ion Versus Photon Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: Carbon ion radiotherapy (CIRT) delivers high linear energy transfer radiation with superior dose conformity compared with photon radiotherapy (PRT). However, whether these physical advantages translate into clinical benefit for locally advanced non-small cell lung cancer (LA-NSCLC) in the era of modern systemic therapy remains unclear. METHODS: We performed a retrospective, propensity score-matched cohort study of patients with Stage III LA-NSCLC treated with definitive CIRT or PRT as part of multimodality therapy between January 2016 and December 2023. The primary endpoint was locoregional recurrence-free survival (LRFS). Secondary endpoints included progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and acute grade ≥ 2 radiation-related adverse events (AEs). RESULTS: A total of 292 patients were matched (146 per group). With a median follow-up of 32.5 months, CIRT group demonstrated significantly longer median LRFS (57.7 vs. 25.0 months; HR, 0.59; 95% CI, 0.39-0.88; p = 0.01) and median PFS (17.7 vs. 16.7 months; HR, 0.70; 95% CI, 0.53-0.94; p = 0.02) compared with PRT group, whereas OS and DMFS were similar between groups. CIRT group also had fewer acute grade ≥ 2 radiation-related AEs. CONCLUSIONS: CIRT demonstrated improved locoregional control and fewer acute toxicities compared with PRT in LA-NSCLC in this retrospective matched cohort. Prospective randomized trials are warranted to validate these findings.