Apparent absence of a proton beam dose rate effect and possible differences in RBE between Bragg peak and plateau

Purpose: Respiration-gated irradiation for a moving target requires a longer time to deliver single fraction in proton radiotherapy (PRT). Ultrahigh dose rate (UDR) proton beam, which is 10-100 times higher than that is used in current clinical practice, has been investigated to deliver daily dose in single breath hold duration. The purpose of this study is to investigate the survival curve and relative biological effectiveness (RBE) of such an ultrahigh dose rate proton beam and their linear energy transfer (LET) dependence.Methods: HSG cells were irradiated by a spatially and temporally uniform proton beam at two different dose rates: 8 Gy/min (CDR, clinical dose rate) and 325 Gy/min (UDR, ultrahigh dose rate) at the Bragg peak and 1.75 (CDR) and 114 Gy/min (UDR) at the plateau. To study LET dependence, the cells were positioned at the Bragg peak, where the absorbed dose-averaged LET was 3.19 keV/um, and at the plateau, where it was 0.56 keV/um. After the cell exposure and colony assay, the measured data were fitted by the linear quadratic (LQ) model and the survival curves and RBE at 10% survival were compared.Results: No significant difference was observed in the survival curves between the two proton dose rates. The ratio of the RBE for CDR/UDR was 0.98+/-0.04 at the Bragg peak and 0.96+/-0.06 at the plateau. On the other hand, Bragg peak/plateau RBE ratio was 1.15+/-0.05 for UDR and 1.18+/-0.07 for CDR.Conclusions: Present RBE can be consistently used in treatment planning of PRT using ultrahigh dose rate radiation. Because a significant increase in RBE toward the Bragg peak was observed for both UDR and CDR, further evaluation of RBE enhancement toward the Bragg peak and beyond is required