The History of Hyperthermia Rise and Decline

Abstract

Electromagnetic hyperthermia remains experimental treatment after 40 years of research and application in view of its “temperature concept” based on the belief that temperature is the only parameter of the efficacy. Initial “extreme hyperthermia” concept was based on the wrong premise of much higher thermal susceptibility of malignant cells and broad therapeutic range of hyperthermia, allowing to kill tumor cells by above-threshold (>43°C) temperature without damaging healthy tissues. Indeed, this therapeutic gap is minor or absent which makes the extreme hyperthermia impossible. The next concept of “thermal dose” was based on the ungrounded extrapolation of the biochemical Arrhenius relationship onto the living matter and formed the basis of “moderate hyperthermia” concept, believing that it could enhance tumor oxygenation and radio- and chemosensitivity, ignoring the special features of tumor blood flow. Both concepts have not been confirmed; “thermal dose” is currently proven to be not connected with any clinical outcome. Analysis of randomized trials with respect to biases has not confirmed hyperthermia efficacy. The growing evidence of athermal effects and their broad application has caused development of some athermal cancer treatments. Hyperthermia concept should be cardinally reevaluated now with respect to obvious bankruptcy of the temperature concept and development of the athermal concept.