Clinical relative biological effectiveness of carbon-ion versus photon radiotherapy derived from tumor control probability models in locally advanced non-small cell lung cancer.

BACKGROUND: This study aimed to estimate the clinical relative biological effectiveness (cRBE) of carbon-ion radiotherapy (CIRT) versus photon radiotherapy (PRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving combined radiotherapy and systemic therapy. cRBE was calculated using the equivalent uniform dose (EUD) corresponding to 50% tumor control (D₅₀), derived from tumor control probability (TCP) modeling with 3-year locoregional control (LRC) as the primary endpoint. METHODS: Patients treated between 2016 and 2023 were identified. Propensity score matching was applied to balance CIRT and PRT cohorts. LRC was estimated by the Kaplan-Meier method and Cox regression. Gross tumour volume dose-volume histograms were converted to biologically effective dose (BED) and EUD. Logistic TCP models were fitted by maximum likelihood estimation. cRBE was estimated as the ratio of the D50 physical doses for PRT and CIRT. RESULTS: A total of 244 patients were included. The CIRT group demonstrated significantly improved LRC compared with the PRT group (p = 0.033). The best-fitted TCP parameters for 3-year LRC were D₅₀ = 15.44 Gy, k = 2.52, n = 1.00 for CIRT, and D₅₀ = 59.94 Gy, k = 4.65, n = 1.00 for PRT. The estimated cRBE for locoregional control was 3.88. CONCLUSION: CIRT was associated with improved locoregional tumor control compared with PRT in patients with LA-NSCLC. In addition, to our knowledge, this study is the first to provide a preliminary, model-dependent estimate of the clinical RBE for tumor control in LA-NSCLC using TCP modeling with 3-year LRC as the endpoint.