How valid is the assumption of equal effect per fraction?

The validity of the assumption of equal biological effect with dose per fraction in fractionated radiotherapy has been examined for the acute skin reaction in a rat foot model using a variable number of 2-Gy daily fractions followed by graded top-up doses.

Mature female rats were used. Both hind feet of each rat were irradiated with a range of fractionated and top-up doses of 60Co gamma-rays. The dose-related incidence of moist desquamation was used as an end-point. Quantal data for the incidence of moist desquamation were analysed using probit analysis and ED50 (+/-SE) values were obtained. The results were also compared with predicted values obtained from the application LQ-model.

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 +/- 0.13 Gy was 1.16 Gy less than the ED50 of 20.94 +/- 0.15 Gy for large single dose exposure alone. This implied that only approximately 58% of the initial 2-Gy fraction was effective, and the rest was repaired within a 24-h interval between the 2 Gy and top-up doses. However, after two or three 2-Gy daily fractions the dose effect curves for the subsequent top-up doses moved to the higher doses again and the ED50 for top-up dose increased to 20.33 +/- 0.21 and 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 lower doses and ED50 values for the top-up doses decreased progressively.

The findings were not in keeping with values predicted based on 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.