The clinical efficacy of localized hyperthermia

Abstract

Localized hyperthermia alone can induce regressions in human neoplasms, but superior results can be obtained by integrating hyperthermia with even low doses of radiotherapy. Several clinical trials demonstrate that hyperthermia plus irradiation can produce higher tumor response rates than the same irradiation alone. While minimal enhancement of irradiation effects on normal tissues is reported, this may be due in part to the physical localization of the heating preferentially in tumors, often assisted by normal tissue cooling or shielding. These advantages may exist only in special circumstances in the treatment of deep tumor volumes. A variety of hyperthermia and irradiation fractionation schemes has been used; the optimal one(s) is yet to be clearly established. To date, no tumor histology has been shown to be more sensitive than another, although the relative radioresistance of melanomas, especially to smaller fraction sizes, is substantially offset by the addition of hyperthermia. Larger tumor volumes are more difficult to heat and achieve lower response rates, but may be relatively less problematic for combined hyperthermia and irradiation than for irradiation alone. Currently used microwave and unfocused ultrasound applicators, when used singly, usually achieve potentially therapeutic temperatures to only about 2- to 4-cm depth, although site-specific tissue characteristics may greatly alter this in individual circumstances. Anatomical factors limit the number of sites which can be usefully treated because of inflexibilities of the currently available equipment. Single-point temperature measurements during treatment correlate poorly with tumor response, while minimum mean tumor temperatures may correlate more strongly. Local and radicular pain occurs commonly during treatment, superficial burns occur occasionally, but major tissue complications have been reported rarely. While the efficacy of localized hyperthermia in augmenting tumor responses to irradiation with acceptable toxicity is established, much important clinical work remains to be done in carefully defined treatment protocols.