In vivo determinations of RBE in a high energy modulated proton beam using normal tissue reactions and fractionated dose schedules

Abstract

In preparation for a clinical trial of proton radiation therapy, we have performed a series of in vivo radiobiological experiments to determine the relative biological effectiveness (RBE) of protons as compared to 60Co using normal tissue reaction in mice as the biological endpoint. The first assay studied was the survival of jejunal crypt cells in both the spread out Bragg Peak (SOBP) and the unmodulated portion (valley) of the proton beam. Experiments were performed using both single fraction and 20 fraction (3 hr between fractions) irradiations. These data demonstrate an RBE in the SOBP and the proton valley of 1.23 and 1.17 respectively for the 20 fraction experiment, and 1.19 and 1.13 for the single fraction experiment. These RBE values are only minimally dependent on the endpoint used for the analysis. The second assay was the acute skin reaction in the mouse thigh after 20 fractions of irradiation. Analyzing the average response from 11 to 30 days after irradiation the RBE was 1.13, and analyzing the dose for 50% of the animals to reach a score of 2.5 indicated an RBE of 1.14. Analysis of late effects by measurement of thigh epilation indicated an RBE of 1.14 while analysis of contraction was inadequate for an RBE estimate. These experiments indicate an RBE of approximately 1.20 for protons (compared to 60Co) when analyzing mouse jejunum and approximately 1.13 when analyzing acute and late skin reaction. They also indicate that the RBE is relatively independent of fraction size in the range studied, and independent of whether the irradiation is performed in the center of a 10 cm wide SOBP or in the valley of the proton beam.