Relative Biological Effectiveness of Carbon Ion Versus Photon Radiation Therapy for Acute Radiation-Induced Esophagitis in Locally Advanced Non-small Cell Lung Cancer Derived From Normal Tissue Complication Probability Modeling

Purpose: This study aimed to evaluate the relative biological effectiveness (RBE) of carbon-ion radiation therapy (CIRT) versus photon radiation therapy for acute radiation-induced esophagitis (ARIE) in patients with locally advanced non-small cell lung cancer, based on TD₅₀ derived from normal tissue complication probability (NTCP) models. Methods and Materials: A total of 165 propensity score-matched pairs of patients with locally advanced non-small cell lung cancer treated with CIRT or photon radiation therapy between January 2016 and December 2023 were analyzed. ARIE (grade ≥2, National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) during or within 3 months postradiation therapy was the primary endpoint. The Lyman-Kutcher-Burman (LKB) NTCP model was developed using maximum-likelihood estimation. Model performance was assessed via 3-fold cross-validation and area under the receiver operating characteristic curve. The estimated RBE value was the TD₅₀ ratio between the photon radiation therapy and CIRT groups. Results: = 0.14, and TD₅₀ = 70.50 Gy for photon radiation therapy (physical). The corresponding mean area under the curves were 0.81 ± 0.14 and 0.66 ± 0.17, respectively. For CIRT, the RBE value derived from the LKB NTCP model was estimated to be 3.02 for grade ≥2 ARIE. Conclusions: LKB-based NTCP modeling offers a clinically oriented framework to estimate RBE value for CIRT. Larger patient cohorts and external validation are required to enhance the model's generalizability and clinical applicability.