Thermal dose and time-temperature factors for biological responses to heat shock

The application of hyperthermia in human cancer therapy, especially by radiotherapists who are accustomed to prescribing ionizing radiation treatments in physical dose units, has stimulated workers in this area to consider the possibility and utility of defining a unit of 'thermal dose'. Previous thermal dose definitions have, primarily, been based on biological isoeffect response relationships, which attempt to relate exposure times that elicit a given biological response at one temperature to exposure times at another temperature that elicit the same biological response. This 'equivalent time' method is shown to have certain limitations. For both 42.4 and 45 degrees C hyperthermia, these relationships accurately describe cell survival responses only when the heating rate is rapid (greater than 0.5 degrees C min-1 from ambient to hyperthermic temperature). Further, the form of these isoeffect relationships appears to be temperature range and cell/tissue-type dependent, and it is suggested that these relationships be referred to as a 'time-temperature factor' (TTF) to help distinguish them from possible physical thermal dose definitions. Two physical dose definitions are discussed, one being simply exposure time at some temperature and the other being a more fundamental definition, the free energy change which is a temperature-dependent driving force for chemical reactions.