PULSED LOW-DOSE RATE BRACHYTHERAPY IN A RAT MODEL - DEPENDENCE OF LATE RECTAL INJURY ON RADIATION PULSE SIZE

Purpose: Clinical protocols utilizing pulsed low dose rate brachythera py (PDR) to replace traditional continuous low dose rate brachytherapy (CLDR) employ irradiation in individual pulses given at intervals of a few hours. A critical factor in determining whether PDR will produce equivalent or greater late-occurring normal tissue toxicity is the do se per pulse. A rat rectal model was used to determine the role of pul se size in modifying dose effectiveness in producing late-occurring to xicity. Methods and Materials: A rat model in which the rectum is irra diated with Ir-192 sources was used in conjunction with an intracavita ry applicator. A section of rectum 1.3 cm in length was irradiated wit h either 0.75 Gy/h CLDR or one of five schemes of PDR. The schemes app lied 0.375, 0.75, 1.5, 3.0, or 6.0 Gy pulses at 0.5, 1.0, 2.0, 4.0, or 8.0 h intervals, respectively. Rats were observed for up to 300 days after completion of irradiation for rectal obstruction. Rectal specime ns were taken at the time of sacrifice for obstruction or at the end o f follow-up and analyzed histologically for injury. Results: Effective ness of irradiation was analyzed by calculating the ED50 for incidence of obstruction and severe histological injury. The ED50 for obstructi on after treatment with CLDR and pulse sizes of 0.375, 0.75, and 1.5 G y were 70.5, 68.0, 68.6, and 68.8 Gy, respectively. These values were not significantly different. Compared to CLDR, the ED50 for obstructio n after pulse sizes of 3.0 and 6.0 Gy were significantly different at 60.9 and 46.3 Gy, respectively. The relative changes in ED50 for the d ifferent radiation schemes in producing ulceration, fibrosis, and vasc ular sclerosis injury were similar to that observed for obstruction. T he endpoints of colitis cystica profunda and atypical epithelial regen eration varied less with increasing pulse size. Conclusions: We have d emonstrated that for late rat rectal injury, dose responses to PDR pul se sizes up to 1.5 Gy at 2-h intervals are not distinguishable from th at seen with CLDR at a dose rate of 0.75 Gy/h. (C) 1997 Elsevier Scien ce Inc.