Potential for Hyperthermia and Radiation Therapy¹

The field of clinical application of hyperthermia to treatment of the cancer patient is developing rapidly both with respect to basic thermal biology, dose-effect relationships, technology for heating and monitoring temperature, efficacy of combination of heat plus radiation, and early clinical studies. The major attraction at this time in studies of hyperthermia is the convincing rationale that there is likely to be a differential cytotoxic effect of hyperthermia between tumor and normal tissue systems. This is based on the increased effectiveness of hyperthermia to kill mammalian cells which are existing under conditions of reduced pH or metabolically deprived circumstances. Also, the temperature level in the tumor being treated by local or regional hyperthermia is expected to reach higher levels than that of the adjacent normal tissues. Combinations of hyperthermia and radiation are attractive because thermal killing is most effective against S-phase cells and the oxygen enhancement ratio (hyperthermia) is ≃1. That is, hyperthermia is effective against those cells which are least sensitive to radiation. The principal problems facing clinical application of hyperthermia are: only partially developed techniques for monitoring temperature in tissue, determining isothermal lines of surfaces in tissue, methodologies for achieving uniform heating of local regions of the human body, and information as to the frequency of distant metastasis after hyperthermia. In addition, further studies are needed to determine the influence of the tumor and normal tissue microenvironment on thermal sensitivity, kinetics for repair of sublethal heat damage, and induction and decay of thermal tolerance.