Proton RBE for early intestinal tolerance in mice after fractionated irradiation

Background and purpose: To determine the influence of the number of fractio ns (or the dose per fraction) on the proton relative biological effectivene ss (RBE). Materials and methods: Intestinal crypt regeneration in mice was used as th e biological endpoint. RBE was determined relative to cobalt-60 gamma rays for irradiations in one, three and ten fractions separated by a time interv al of 3.5 h. Proton irradiations were performed at the middle of a 7-cm Spr ead Out Bragg Peak (SOBP). Results: Proton RBEs (and corresponding gamma dose per fraction) at the lev el of 20 regenerated crypts per circumference were found equal to 1.15 +/- 0.04 (10.0 Gy), 1.15 +/- 0.05 (4.8 Gy) and 1.14 +/- 0.07 (1.7 Gy) for irrad iations in one, three and ten fractions, respectively. Alpha/beta ratios as derived from direct analysis of the 'quantal radiation response data' were -found to be 7.6 Gy for gamma rays and 8.2 Gy for protons. Additional proto n irradiations in ten fractions at the end of the SOBP were found to be mor e effective than at the middle of the SOBP by a factor of 1.14 (1.05-1.23). Conclusion: Proton RBE for crypt regeneration was found to be independent o f fractionation up to ten fractions. One can expect that it remains unchang ed for higher number of fractions as the lethalities for doses smaller than 3 Gy are exclusively due to direct lethal events. As a tendency for increa sed effectiveness at the end of the SOBP is reported in the majority of the studies, for clinical applications it would be advisable to allow for by a rranging a sloping depth dose curve in the deeper part of the target volume . Finally, it must be noticed that most of in vitro and in vivo RBE values for protons are larger than the current clinical RBE (RBE = 1.10). (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.