Time-temperature relationship th hyperthermic treatment of malignant and normal tissue in vivo.
The effect of hyperthermia on normal and tumor tissue was studied following water bath heating of a methylcholanthrene-induced fibrosarcoma (FSaI) isotransplanted into the feet of C3H mice. The time-temperature relation for the 50% tumor control dose over the temperature range of 41.5--45.5 degrees showed a log linear relationship which followed a biphasically modified Arrhenius plot. At temperatures above 43 degrees, there was a 50% reduction in heating time to obtain the 50% tumor control dose for each 1 degree increase in temperature, corresponding to an activation energy of 140 kcal/mol. At temperatures below 43 degrees, the curve was steeper, with a tendency to double the treatment time for each 0.5 degree reduction in temperature (activation energy, approximately 230kcal/mol). Normal tissue damage in the tumor-bearing foot was estimated at two levels with a 50% response dose assay. Severe normal tissue damage showed a time-temperature relationship similar to the tumor response, thus indicating no variation in therapeutic ratio at different temperatures. However, for slight tissue damage, the therapeutic ratio increased with decreasing temperatures, yielding a better therapeutic ratio at lower temperatures. The time-temperature relationship obtained in the FSaI fibrosarcoma is supported by other studies and points to a general time-temperature relationship for hyperthermic tumor destruction.
D000818:Animals; D004487:Edema / Q000209:etiology; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009336:Necrosis / Q000209:etiology; D012513:Sarcoma, Experimental / Q000628:therapy*; D013696:Temperature; D013997:Time Factors