Effect of Changing Weekly Dose on Accelerated Repopulation during Fractionated Irradiation of Mouse Tongue Mucosa

Abstract

The effect on accelerated repopulation of fractionated radiotherapy with changing weekly dose was studied in mouse oral mucosa. The basic conventional treatment protocol comprised five daily fractions per week, 3 Gy per fraction, given over 3 weeks. In dynamic treatment schedules the same total dose was delivered by giving 5 × 2, 5 × 3 and 5 × 4 Gy, or the reverse sequence. In concomitant boost experiments five additional daily doses of 1 or 2 Gy respectively were applied either during the first or last week of the conventional treatment. Graded terminating test doses were given in order to establish dose-effect curves for complete mucosal denudation. Higher initial doses consistently resulted in longer latent times between top-up irradiation and complete epithelial denudation, corresponding to significantly higher cell densities at the time of test irradiation. The top-up ED₅₀'s served as a measure of repopulation efficacy. The difference in repopulated dose between schedules with initial or terminal dose concentration was 10% for dynamic fractionation (p = 0·02) and about 7% in the 2-Gy boost protocol (p = 0·13), and no difference was observed with boost doses of 5 × 1 Gy. In conclusion, a clear though moderate increase in both cell density and residual tissue tolerance can be achieved by protocols with substantially higher doses in the first treatment week.