IMPROVED THERAPEUTIC RESPONSE BY DISTINCT TIMING OF MULTIPLE HEAT-TREATMENTS DURING INTERSTITIAL RADIATION IN THE DUNNING R3327 PROSTATE TUMOR-MODEL

Purpose: As a continuation of a previous study showing the efficacy of a single local tumor heat treatment (LTH) in combination with interst itial radiation (IR) in the Dunning tumor system R3327 (subline AT1), we evaluated higher doses and/or lower dose rates with an extended tim e course of IR treatment, which allowed greater flexibility for LTH ap plications. Methods; IR was carried out by the insertion of one remova ble Ir-192 seed into the center of a R3327-AT1 tumor, transplanted s.c . into the distal thigh of Copenhagen rats. LTH (43.5 degrees C, for 3 5 min) varied from one treatment just before IR to multiple applicatio ns beginning at 0 h and repeated every 48 h or 72 h. Results: The Dunn ing subline R3327-AT1 is a very thermoresistant tumor, which did not r eveal any thermal response when heated up to 44.5 degrees 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 7 2 h resulted in a clear increase in growth delay. Radiosensitization w as highest in all dose-rate groups where LTH was applied every 72 h du ring a complete course of IR. Conclusions; These results demonstrate t he 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.