INTERSTITIAL HYPERTHERMIA AND INTERSTITIAL RADIOTHERAPY OF A RAT RHABDOMYOSARCOMA - EFFECTS OF SEQUENTIAL TREATMENT AND CONSEQUENCES FOR CLONOGENIC REPOPULATION

Animal tumour experiments have been performed to elucidate the interac tions between interstitial hyperthermia (IHT) and interstitial radioth erapy (IRT), and to obtain information about the most effective sequen ce of these treatment modalities. Experimental tumours, transplanted i n the flank of Wag/Rij rats, were treated with IHT for 0.5 h at 44 deg rees C, and with IRT using low dose-rate (LDR) iridium-192 sources. Bo th tumour cure probability and the fraction of clonogenic cells in vit ro after different IHT and IRT treatments in vivo, were used as endpoi nts. The sequence of a short (0.5 h) IHT treatment followed by an exte nded LDR-IRT treatment lasting up to 10 days appeared to be very effec tive, and resulted in a significant thermal enhancement ratio of 1.34 at the 50% tumour cure probability level. A not significantly increase d thermal enhancement of 1.06 was found when the same IHT treatment fo llowed IRT. The level of clonogenic cell survival after IHT alone is h igh (0.24 +/- 0.08) compared with that after an IRT dose of 20 Gy (0.0 17 +/- 0.004). Clonogenic cell repopulation started 2-4 days after the in vivo treatment irrespective of the type of treatment. The in vivo combination of IHT and LDR-IRT resulted in lower surviving fractions c ompared with IRT alone, regardless of the time interval between the en d of treatment and in vitro clonogenic assay. IHT followed by LDR-IRT appeared to be the most effective treatment in terms of tumour cure. T he in vivo/in vitro studies indicated that the effect of hyperthermia is mainly attributed to radiosensitization, possibly by partial inhibi tion of sublethal damage repair processes during the subsequent irradi ation. The hyperthermia-induced cytotoxicity was of minor importance a s estimated from the surviving clonogenic fraction.