Relative Biological Effectiveness Derived from NTCP Analysis of Carbon Ion vs. Photon Radiation Therapy in Locally Advanced Non-Small Cell Lung Cancer.

Abstract

To estimate the relative biological effectiveness (RBE) of carbon-ion radiation therapy (CIRT) compared to photon radiation therapy using the equivalent uniform dose corresponding to a 50% complication probability (TD₅₀) values derived from normal tissue complication probability (NTCP) modeling for acute radiation pneumonitis (RP) in patients with locally advanced non-small cell lung cancer. Patients with locally advanced non-small cell lung cancer treated between January 2016 and December 2023 were selected. Propensity score matching was performed to pair patients who received CIRT with those treated with photon radiation therapy. The primary endpoint was the incidence of grade ≥2 acute RP. NTCP models based on the Lyman-Kutcher-Burman formalism were developed using the lung's dose-volume histogram data. Model performance was evaluated via 5-fold cross-validation and the area under the receiver operating characteristic curve. RBE was estimated as the TD₅₀ ratio between photon radiation therapy and CIRT groups. A total of 158 matched patients per group were analyzed. For grade ≥2 acute RP, the optimal Lyman-Kutcher-Burman model parameters were m = 0.50, n = 0.83, and TD₅₀ = 15.70 Gy (CIRT); and m = 0.28, n = 0.57, and TD₅₀ = 41.79 Gy (photon radiation therapy). The mean area under the receiver operating characteristic curve was 0.63 ± 0.16 for CIRT and 0.71 ± 0.11 for photon radiation therapy. The derived estimated RBE for acute RP was 2.66. The NTCP model for acute RP provides a basis for RBE estimation using TD₅₀ values. Further validation with larger clinical datasets is necessary to confirm these findings.