The analysis of growth delay data of a rat
rhabdomyosarcoma tumor system with and without
misonidazole and irradiated with spread-peak heavy-ion radiation yields two conclusions that bear on the relative efficacy of the two modes of treatment and imply a complementary role of the two modes which enhances the effects of either given separately. 1. For both
carbon and neon ion peak radiation given in four fractions, RBE values for
tumor growth delay are significantly greater than the enhancement ratio for an X ray plus
misonidazole fractionation scheme [2.0-2.3 (
carbon) and 2.6-2.8 (neon) vs. 1.2-1.5 (X rays plus
misonidazole)]. This implies that high LET killing is considerably more effective in this
tumor system (hypoxic fraction of about 35%) than the hypoxic cell sensitization caused by
misonidazole. 2. When
misonidazole is given in conjunction with the heavy ion beam irradiations, an increased growth delay is seen, greater than when either heavy ions or
misonidazole plus X rays are given separately. The product of the sensitizer enhancement ratio for heavy ions and the RBE for no sensitizer yields a measure of the overall enhancement of effect relative to an X ray treatment. The values of this product for the
carbon beam (2.4-2.5) and neon beam (3.4) show high effectiveness for either beam plus
misonidazole. The interpretation is that heavy ion beams reach and kill hypoxic cells not penetrated by the
misonidazole, and some hypoxic cells not killed by the high LET component receive low LET damage which is made lethal by the
drug. Thus, the net hypoxic cell killing is enhanced by the high LET beams and in a complementary way by the combination of the
drug and the low LET portion of the radiation.