Fractionated split-course treatments were given with gaps of different length and the effects on tumor response was studied using the rhabdomyosarcoma R1H of the rat. Total doses of 68, 75 and 82 Gy were applied in 30 fractions (five fractions per week). After four weeks, that is after 20 fractions, treatment was interrupted for one or two weeks followed by another ten fractions. The results were compared to those of continuous treatment given in six consecutive weeks. Tumor response was quantified by TCD37% and net growth delay. The TCD37% increased with increasing duration of the gap. A mean repopulated dose of 0.72 Gy per day was obtained. This corresponds to a doubling time of tumor clonogens of 4.2 days during the gap, which is somewhat slower than the volume doubling time of unperturbed tumors (2.5 days) of the same size. The results obtained for the net growth delay support the results of the TCD37% data. It is concluded that a gap during fractionated radiotherapy leads to poorer results since the dose required for tumor control is enhanced and sparing of normal tissue can only be expected for early but not for late reacting tissues.
