How valid is the assumption of equal effect per fraction?

Background and purpose: The validity of the assumption of equal biological effect with dose per fraction in fractionated radiotherapy has been examine d for the acute skin reaction in a rat foot model using a variable number o f 2-Gy daily fractions followed by graded top-up doses. Material and methods: Mature female rats were used. Both hind feet of each rat were irradiated with a range of fractionated and top-up doses of Co-60 gamma-rays. The dose-related incidence of moist desquamation was used as an end-point. Quantal data for the incidence of moist desquamation were analy sed using probit analysis and ED50 (+/-SE) values were obtained. The result s were also compared with predicted values obtained from the application LQ -model. Results: After a single 2-Gy fraction followed by top-up doses 24 h later, the dose effect curve for the top-up doses used was shifted to lower doses as expected and the ED50 for moist desquamation of 19.78 +/- 0.0.13 Gy was 1.16 Gy less than the ED50 of 20.94 +/- 0.15 Gy for large single dose expos ure alone. This implied that only approximately 58% of the initial 2-Gy fra ction was effective, and the rest was repaired within a 24-h interval betwe en the 2 Gy and top-up doses. However, after two or three 2-Gy daily fracti ons the dose effect curves for the subsequent top-up doses moved to the hig her doses again and the ED50 for top-up dose increased to 20.33 +/- 0.21 an d 20.75 +/- 0.11 Gy, respectively. A further increase in the number of 2-Gy daily fractions shifted the dose effect curves for the top-up doses to low er doses and ED50 values for the top-up doses decreased progressively. Conclusions: The findings were not in keeping with values predicted based o n the assumption of equal effect per fraction and could not be explained by the use of a single alpha/beta ratio in the LQ-model. (C) 1999 Elsevier Sc ience Ireland Ltd. Al rights reserved.