Biological rationale and clinical experience with hyperthermia

Hyperthermia (HT) as an adjunct to radiation therapy (RT) has been a focus of interest in cancer management. In recent years there have been numerous randomized and nonrandomized studies conducted to assess the efficacy of HT combined with either RT or chemotherapy especially in the treatment of superficially seated malignant tumors. The major impact of HT is currently on locoregional control of tumor. Heat may be directly cytotoxic to tumor cells or inhibit repair of both sublethal and potentially lethal damage after radiation. These effects are augmented by the physiological conditions in tumor that lead to states of acidosis and hypoxia. Blood flow is often impaired in tumor relative to normal tissues, and HT may lead to a further decrease in blood flow and augment heat sensitivity. Three major areas of clinical investigation have borne the greatest fruit for HT as adjunctive therapy to RT. These include recurrent and primary breast lesions, melanoma, and head and neck neoplasms. Thermal enhancement ratio was increased in all cases and is approximately 1.4 for neck nodes, 1.5 for breast, and 2 for malignant melanoma. In general, the most important prognostic factors for complete response (CR) are RT dose, tumor size and minimal thermal parameters [minimal thermal dose (t(43min)), mean minimal temperature (T-min) or T-90 i.e, temperature exceeded by 90% of thermal sensors]. The number of HT fractions administered per week appears to have no bearing on the overall response, which may be indicative of the effects of thermotolerance. The total number of HT fractions delivered also appears irrelevant provided adequate HT is delivered in one or two sessions. The major prognostic factors for the duration of local control were tumor histology, concurrent RT dose, tumor depth and T-min. Although numerous single institution studies showed increased CR rates and improved local control, the efficacy of HT as an adjunct to RT should be assessed with well-designed multi-institutional randomized clinical trials. Such clinical trials are underway.