The effect of hyperthermia on reoxygenation during the fractionated radiotherapy of two murine tumors, FSa-II and MCa.
OBJECTIVE
To investigate the effect of hyperthermia on the tumor reoxygenation during fractionated irradiations. It has been shown that hyperthermia increases the size of hypoxic cell fraction in some murine tumors and reoxygenation is critical for successful radiotherapy.


METHODS
Tumors were early generation isotransplants of spontaneous murine fibrosarcoma (FSa-II) and mammary carcinoma (MCa) in C3Hf/Sed mice. Treatments were initiated when they reached an average diameter of 4 mm. A local heat treatment at 43.5 degrees C for 45 min was given 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. Tumors 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% tumor control dose) and RD50 (dose to induce partial foot atrophy in 50% of treated animals) were calculated.


RESULTS
The TCD50s 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 number of fractions, suggesting that significant reoxygenation occurred during the fractionated irradiation. The TCD50s (with heat, in air) were smaller than the TCD50s (radiation alone, in air) following fractionated irradiations, indicating that hyperthermia did not affect tumor reoxygenation. The difference between these TCD50 values was greater for heat-sensitive MCa than for heat-resistant FSa-II, suggesting that this difference was due to additive heat cytotoxicity. An unexpected observation was that heat significantly enhanced the foot reaction with no resultant therapeutic gain for both MCa and FSa-II tumors.


CONCLUSIONS
Hyperthermia given independently prior to fractionated irradiation 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.
Nishimura
Y
Y
Department of Radiation Medicine, University of Kentucky, Chandler Medical Center, Lexington 40536-0084.
Urano
M
M
D000818:Animals; D006979:Hyperthermia, Induced; D051379:Mice; D008809:Mice, Inbred C3H; D010100:Oxygen / Q000378:metabolism*; D011879:Radiotherapy Dosage; D012513:Sarcoma, Experimental / Q000378:metabolism / Q000532:radiotherapy
D010100:Oxygen