The proton RBE and the distal edge effect for acute and late normal tissue damage in vivo

In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used toreach an isoeffective biological response between photon and proton doses. However, the RBE varies with biological endpoints and linear energy transfer (LET), two key parameters in radiotherapy. Few in vivo studies have investigated the increasing RBE with increasing LET. This study aims to test the hypothesis that the RBE varies between endpoints and has a distal edge effect in vivo.

Unanesthetized micewere restrainedin jigs where their right hind legs were irradiated with a single dose of protons at the center (LET, _all = 5.3 keV/μm) and distal edge (LET, _all = 7.6 keV/μm) of a spread-out Bragg peak (SOBP). 6 MV photons were used as reference. The acute damage and skin toxicity were scored daily until day 30, and the late damage was evaluated using a joint contracture assay for one year after treatment.

An acute damage RBE of 1.06 ± 0.02(1.02-1.10) and late damage RBE of 1.16 ± 0.08(1.00-1.32) were found, displaying an enhanced RBE for late damage in the center SOBP. The distal edge RBE for acute and late damage was 1.15 ± 0.02(1.10-1.19) and 1.26 ± 0.09(1.07-1.43), showing a similar center-to-distal edge RBE enhancement of 8 % and 9 % for acute and late damage.

The findings demonstrate an increased RBE for late damage than acute damage and the distal edge effect is evident with increased RBE at the distal end of the proton SOBP in vivo.