Thermal isoeffect dose: addressing the problem of thermotolerance

A method of calculating a thermal isoeffect dose by converting thermal exposure into equivalent-minutes at 43 degrees C (EQ43) has been described previously by this investigator and others. Some investigators have suggested variations in the constants of this approach based on evaluations of the available in vivo data. The selection of these constants affect thermal dose calculations most at temperatures below 43 degrees C. Since treatment response appears to be most closely related to the dose in the coolest part of the tumour, the selection of appropriate constants may be quite important. The data suggest that these variations in constants are a consequence of thermotolerance. A more appropriate approach to address this problem is presented. The phenomena of thermotolerance complicates the practical application of this thermal isoeffect dose model. The dose modification caused by chronic thermotolerance which occurs during exposure at mild hyperthermic temperatures can be estimated by calculating the thermotolerance dose ratio (TTDR) between the equivalent-minute dose calculated with and without a transition temperature at 43 degrees C. The data suggest that the TTDR as a function of time can be mathematically described and used to correct for the dose modifying effect of thermotolerance. Using these results in a modification of the thermal isoeffect dose model causes a significant improvement in the fit for in vitro data below 43 degrees C.