The effect of hyperthermia on normal and tumor tissue was studied following water bath heating of a methylcholanthrene-induced fibrosarcoma (FSal) 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° showed a log linear relationship which followed a biphasically modified Arrhenius plot. At temperatures above 43°, there was a 50% reduction in heating time to obtain the 50% tumor control dose for each 1° increase in temperature, corresponding to an activation energy of 140 kcal/mol. At temperatures below 43°, the curve was steeper, with a tendency to double the treatment time for each 0.5° reduction in temperature (activation energy, approximately 230 kcal/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 FSal fibrosarcoma is supported by other studies and points to a general time-temperature relationship for hyperthermic tumor destruction.
Supported in part by Department of Health, Education and Welfare Grant CA13311 and the Danish Cancer Society.