Improved therapeutic response by distinct timing of multiple heat treatments during interstitial radiation in the Dunning R3327 prostate tumor model

Abstract

Purpose: As a continuation of a previous study showing the efficacy of a single local tumor heat treatment (LTH) in combination with interstitial radiation (IR) in the Dunning tumor system R3327 (subline AT1), we evaluated higher doses and/or lower dose rates with an extended time course of IR treatment, which allowed greater flexibility for LTH applications. Methods; IR was carried out by the insertion of one removable ¹⁹²Ir seed into the center of a R3327-AT1 tumor, transplanted s.c. into the distal thigh of Copenhagen rats. LTH (43.5°C, for 35 min) varied from one treatment just before IR to multiple applications beginning at 0 h and repeated every 48 h or 72 h. Results: The Dunning subline R3327-AT1 is a very thermoresistant tumor, which did not reveal any thermal response when heated up to 44.5°C for 35 min. IR alone produced a delay in tumor growth, related to dose and dose rates of 18–53 cGy/h. During longer treatment times, a single LTH just before the IR was no more effective than IR alone. Thermoradiotherapy with multiple LTH treatments given at intervals of between 48 h and 72 h resulted in a clear increase in growth delay. Radiosensitization was highest in all dose-rate groups where LTH was applied every 72 h during a complete course of IR. Conclusions; These results demonstrate the importance of administering a sequence of multiple applications of LTH during continuous low-dose-rate irradiation and they substantiate our earlier findings, with shorter exposure times, where one LTH given every 72 h appeared to be most efficient in the combined treatment of the Dunning rat prostate tumor R3327-AT1.