Chronic radiation damage in the rat rectum: an analysis of the influences of fractionation, time and volume.

Abstract

Analysis of four different sets of experiments performed by the G.S.F. group in Munich investigating the late tolerance of the rat rectum to external or intracavitary irradiation. The endpoint was late rectal stenosis in female Wistar rats. The raw data were fitted to the linear-quadratic model by means of a likelihood maximization method (Direct Analysis). The model was altered to allow for repopulation, incomplete repair, and varying irradiated lengths of the rectum. Fractionation sensitivity was high or intermediate (alpha/beta ratio values [95% confidence limits] ranging from 2.67 [0.86, 4.80] to 6.65 [2.21, 11.73] Gy). Significant repopulation occurred when treatments were longer than 5 days (Dprolif equal to 0.61 [0.20, 1.47] and 1.08 [0.58, 1.90] Gy/day, in fractions of 4 Gy). Another interpretation is that radiosensitivity changed during treatment. Repair half-time estimates ranged between 1.84 [1.52, 2.34] and 5.02 [2.83, 21.7] h. Finally, the present analysis indicated that the smallest surviving compartment capable of tissue rescue was about 1/50 to 1/100 of a 1 cm high cylinder of the rectum wall. The radiobiological features of late stenosis in the rats are consistent with combined injuries of early and late responding components of the rectal wall. This raises some concerns about the possible danger of hyperfractionated treatments, where the beneficial impact of fraction size reduction may be obviated for interfraction intervals that are too short. Also, accelerated irradiation may result in more late complications because of increased early reactions.