Significance of the beta term in biological gain of carbon-ion radiotherapy

High LET radiation minimizes any difference in the radiosensitivity of different types of cells to which photon irradiation produces large variation. It is anticipated that side effects of high LET particle radiotherapy would not bring a biological therapeutic gain. The purpose of this paper is to answer a question whether high LET radiation could discriminate tumor and normal tissues so that biological advantage could be achieved. We here selected and measured the growth delay of an experimental tumor and the skin reaction in C3H mice, as a model for biological gain. The tumor was a syngeneic NFSa fibrosarcoma, and were transplanted intramuscularly into the right hind legs of male mice 7 days before the first irradiation. Hairs on the right hind leg of female mice were removed by applying a depilatory agent 7 to 8 days before the first irradiation. Carbon-12 ions were accelerated by the HIMAC synchrotron up to 290 MeV/u. Cs-137 gamma-rays were used as a reference beam for determining the RBE. Daily fractionation was given with equal daily doses using an interfractional interval of 24 hours. Several graded doses were used to determine an isoeffect dose, and animals assigned to a given dose group received equal daily doses. The tumor growth (TG) time obtained for all animals were averaged per each dose group. Irradiated legs were observed for skin reaction scoring every other day up to 5 weeks. The skin scores in an individual mouse were averaged, and was used for obtaining dose-response. Carbon ions of LET 42 and 77 keV/micro.m, but not 14 or 20 keV/ micro.m, showed larger RBE values in retarding tumor growth than causing skin reaction after daily-fractionated irradiation. Using Fe-plot, we analyzed the isoeffect dose to evaluate dependence of intra-track damages (alpha term) and of inter-track damages (beta terms) on LET. The alpha term of tumor growth delay and skin reaction equally increased with an increase in LET, and no difference was observed between the two tissues. Beta term was, however, different between the two tissues such that the beta term of skin reaction apparently increased with LET while that of tumor growth delay was independent of LET. It is clear that beta term is a determinant of tissue specific response to high LET radiation, while alpha term solely depends on LET. It is implied that high-LET radiotherapy could achieve a large therapeutic gain when a large dose per fraction is used.9th workshop on Heavy Charged Particles in Biology and Medicine and 3rd ENLIGHT co-ordination meetin