Variability of the Relative Biological Effectiveness of Carbon Ions Among Human Cancer Cell Lines Under Clinically Relevant Irradiation Conditions

Background/Aim: In Japan, carbon-ion radiotherapy treatment planning uses relative biological effectiveness (RBE) values derived from a single reference cell line. Accumulating evidence indicates that carbon-ion RBE varies among different cancers. However, the magnitude of this variability remains unclear owing to the heterogeneity of the experimental conditions among the studies. This study aimed to elucidate carbon-ion RBE variability across a large panel of human cancer cell lines using clinically relevant irradiation conditions and consistent clonogenic assay methods. Materials and Methods: Clonogenic survival in 41 human cancer cell lines after X-ray or carbon-ion irradiation was analyzed. Carbon-ion irradiation was performed at the center of a 6-cm spread-out Bragg peak (290 MeV/nucleon; dose-averaged linear energy transfer, approximately 50 keV/μm). RBE values at doses corresponding to 10% and 50% survival (D10 and D50, respectively) were calculated and compared with population-representative RBE values derived by linear regression and with those of the reference human salivary gland (HSG) cell line. Results: Population-representative RBE values were 2.09 and 2.28 for D10 and D50, respectively, closely approximating those of HSG cells (1.92 and 2.37). However, approximately 32% of the cell lines exhibited RBE values that deviated by at least 24% from the population-representative values. This variability was greater for D50 than for D10. No association was found between RBE and primary organ or histological subtype. Conclusion: Substantial inter-cell line RBE variability was observed under consistent and clinically relevant irradiation conditions, indicating that the current fixed-RBE approach contributes to potential overtreatment or undertreatment in a subset of patients.