Studies relevant to a means of quantifying the effects of hyperthermia

There is as yet no fully satisfactory method of defining 'thermal dose'. However, in order to relate different hyperthermal treatments it has been suggested that the relationship between heating time and temperature be used to derive an isoeffect parameter which might be useful in this context. The equation t2/t1 = RT1-T2, where t is the treatment time, T the temperature, R = 2 for T greater than 42.5 degrees C and R = approximately 6 for T less than 42.5 degrees C, has been shown to fit the isoeffect data from many studies both in vivo and in vitro. Whether or not this relationship is applicable when the temperature is varying has been tested using an animal model system, i.e. the response of the baby rat tail. It has shown that the relationship between time and temperature is indeed characterized by the above equation, and the phenomena of thermotolerance and step-down sensitization were clearly demonstrated. Tails were then alternated between waterbaths at different temperatures in order to simulate varying temperature. The measured effects were, in general, in good agreement with those derived from the formula. The maximum difference between the observed and predicted effect, obtained under rather extreme conditions unlikely to be experienced clinically, amounted to an under-estimate of the effective temperature by approximately 0.3 degrees C, i.e. a net small effect of thermotolerance. It is therefore suggested that the above formula for 'heat dose' provides a reasonable interim method for comparing clinical hyperthermic treatments. The formula does not, however, account for differing absolute sensitivities between tissues nor for effects of fractionating heat treatments.