THE EFFECT OF HYPERTHERMIA ON REOXYGENATION DURING THE FRACTIONATED RADIOTHERAPY OF 2 MURINE TUMORS, FSA-II AND MCA

Purpose: To investigate the effect of hyperthermia on the tumor reoxyg enation during fractionated irradiations. It has been shown that hyper thermia increases the size of hypoxic cell fraction in some murine tum ors and reoxygenation is critical for successful radiotherapy. Methods and Materials: Tumors were early generation isotransplants of spontan eous murine fibrosarcoma (FSa-II) and mammary carcinoma (MCa) in C3Hf/ Sed mice. Treatments were initiated when they reached an average diame ter of 4 mm. A local heat treatment at 43.5 degrees C for 45 min was g iven in a constant temperature water bath 24 h before irradiation(s). This interval was selected to avoid heat-radiation interaction and to simply investigate the heat effect on the reoxygenation process. Tumor s were irradiated under hypoxic conditions or in air and observed for recurrences for 120 days. The foot reaction of animals with controlled -tumors was scored on the last day of experiments. The TCD50 (50% tumo r control dose) and RD(50) (dose to induce partial foot atrophy in 50% of treated animals) were calculated. Results: The TCD(50)s following a various number of fractions were obtained for FSa-II and MCa with or without hyperthermia. The difference between the TCD50 (hypoxia) and TCD50 (in air) without hyperthermia increased with an increasing numbe r of fractions, suggesting that significant reoxygenation occured duri ng the fractionated irradiation. The TCD(50)s (with heat, in air) were smaller than the TCD(50)s (radiation alone, in air) following fractio nated irradiations, indicating that hyperthermia did not affect tumor reoxygenation. The difference between these TCD50 values was greater f or heat-sensitive MCa than for heat-resistant FSa-II, suggesting that this difference was due to additive heat cytotoxicity. An unexpected o bservation was that heat significantly enhanced the foot reaction with no resultant therapeutic gain for both MCa and FSa-II tumors. Conclus ion: Hyperthermia given independently prior to fractionated irradiatio n did not affect tumor reoxygenation, nor was there a therapeutic gain for the two murine tumors. These results suggest that selective tumor heating is essential in clinical thermoradiotherapy.