INTERSTITIAL RADIATION AND HYPERTHERMIA IN THE DUNNING R3327 PROSTATETUMOR-MODEL - THERAPEUTIC EFFICACY DEPENDS ON RADIATION DOSE-RATE, SEQUENCE AND FREQUENCY OF HEATING

To determine the most effective means by which to apply the combined t reatments of local tumour hyperthermia (LTH) with interstitial low dos e-rate irradiation (IRT) we examined the significance of such factors as dose-rate of radiation, and the sequence and frequency of hyperther mia applications in the anaplastic Dunning prostate tumour subline R33 27-AT1. IRT was carried out by the insertion of a single Ir-192 seed i nto the center of the tumour. For LTH treatments, the tumour-bearing l eg was positioned in a circulating constant temperature water bath (43 .5 +/- 0.1 degrees C) for 35 min. Neither LTH treatment alone nor the insertion of a dummy seed produced any change in tumour growth compare d with sham-treated controls. With regard to the sequence of heating a nd IRT our results showed that during a 72-h treatment time (30 Gy, 40 cGy/h) a single heat treatment given just before the start of IRT was more efficient (TER = 1.47) in terms of growth delay than LTH given i n the middle or the end of radiation treatment (TER approximate to 1.0 ). The growth delay for both the 20 and 40 cGy/h groups appear to be l inear with increasing dose for the IRT as well as the IRT + LTH groups . The higher dose-rate was more effective especially with respect to l ong-term delay in tumour growth in some of the animals. As TER at 40 c Gy/h decreased subsequently with increasing treatment time from 1.47 t o 1.25 at 60 Gy, we conclude that for treatment times >72 h, one LTH j ust before IRT might not be sufficient. If multiple heat treatments ar e applied during a comparable time course, two LTH treatments one just before the start, the other at the end yielded the greatest local tum our control. In contrast, three LTH given daily were not more effectiv e than the one LTH given just before the start of IRT. These data indi cate a clear thermal enhancement of low dose-rate irradiation, with ma ximal sensitization when hyperthermia was given just before IRT. For m ultiple heatings a better understanding of the underlying mechanisms o f sequencing and timing hopefully provides guidelines how to apply opt imally both modalities in the treatment of cancer.