Critical Analysis of Electromagnetic Hyperthermia Randomized Trials: Dubious Effect and Multiple Biases

Abstract

Hyperthermia in oncology still remains an experimental treatment with no realistic future in clinical cancer therapy, though declaration of the undisputed efficacy of hyperthermia is a common place in every hyperthermia paper. We have studied the available randomized trials on hyperthermia from the position of “null hypothesis” to confirm or refuse the efficacy and safety of clinical hyperthermia, taking into account also the possible biases. Unfortunately, careful analysis of 14 randomized clinical trials has not confirmed a clinical benefit of hyperthermia independently of its type: superficial, deep or whole-body. We have not found any positive trial not affected with biases. With correction to the distortions, there is no trial with obvious long-term positive effect of hyperthermia. Effect of hyperthermia could be shown in experimentally designed clinical trial or versus inadequate comparator. In clinical setting and provided that study design is correct, hyperthermia is not effective at all or not effective enough to justify its obvious disadvantages: toxicity and labor intensity. Thermal concept of hyperthermia seems to be irrelevant. Nevertheless, multiple publications of positive trials, reviews, and meta-analyses create an impression of hyperthermia renaissance.