The influence of the number of fractions on tumor and skin response to fractionated irradiation was studied. R1H rhabdomyosarcomas of the rat (volume doubling time 3 days) were irradiated with 6, 18, 30, or 42 fractions in 6 weeks. Total doses of 45, 60, or 75 Gy were applied in each fractionation scheme, that is, the dose per fraction ranged from 1.07 to 12.5 Gy. Tumor response was assessed by tumor control probability and tumor net growth delay. A clearcut reduction of skin damage was observed with increasing number of fractions, whereas the tumor response was found to be the same whether the dose was given in 6, 18, 30, or 42 fractions. Thus, the fractionation regimens were more effective than expected from calculations based on single-dose in situ survival curves. This result can be explained by assuming that the clonogenic tumor cells become less hypoxic with increasing number of fractions. Since normal tissue damage decreases with increasing number of fractions, the therapeutic gain may be improved by applying a greater number of fractions.
