Whole-body hyperthermia: a review of theory, design and application

Abstract

The intentional induction of elevated body temperature to treat malignant lesions has its origins in the 18th century. The mechanism of heat-induced cell death is not clear; however, heat induces a variety of cellular changes. For heat to exert a therapeutic effect, pathogens (bacteria, viruses, or neoplastic tissues) need to be susceptible within temperature ranges that do not exert deleterious effects on normal tissues. Hyperthermia has been used successfully to treat isolated neoplastic lesions of the head and neck, regional tumors such as melanoma of the limb, and is under investigation as either an adjunct to, or therapy for, locally disseminated and systemic diseases. The clinical utility of perfusion hyperthermia has evolved into three approaches - isolated organ or limb, tumorous invasion of a cavity, and systemic or metastatic spread. When whole-body hyperthermic treatment has been tried, it has been induced in the patient by submersion in hot wax or liquid, wrapping in plastic, encasement in a high-flow water perfusion suit, or by extracorporeal perfusion. Our group has developed an extracorporeal method, veno-venous perfusion-induced systemic hyperthermia, that was used first to safely heat swine homogenously to an average body temperature of 43 degrees C for 2 h. More recently, a Phase I clinical trial has been completed in which all patients were safely heated to 42 or 42.5 degrees C for 2 h and survived the 30-day study period. We have been sufficiently encouraged by these results and are continuing to develop this technology.

Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model

“…Unfortunately, "extreme" whole body hyperthermia (.41.5°C), which elevates core temperatures to the level where direct thermal toxicity is observed, can cause severe side effects, which may limit its usefulness. [4][5][6][7][8] Fever-level whole body hyperthermia (∼39°C-41°C) can mitigate many of these side effects and has potential to be an effective cancer treatment, but this lower heat level is thought, primarily, to stimulate the immune system and the benefits of direct thermal toxicity are reduced. 9,10 Generating localized hyperthermia at the cancer site could alleviate many of the side effects associated with whole body hyperthermia while still taking advantage of the thermal susceptibility of tumors.…”

Current devices for high-performance whole-body hyperthermia therapy

“…After the introduction of blood circulation into the heat exchanger, it is easy to control and monitor the temperature [87]. The ongoing Phase I study in advanced non-small-cell lung cancer patients approved by the US FDA has shown its safety and effectiveness [88][89][90][91][92][93]. Several therapeutic effective strategies of heat in combination with other antineoplastics have been developed in this platform as shown in Figure 7a.…”

Evaluation on the capacity of selectively heating vessel-rich-skin to realize noninvasive whole body hyperthermia

“…Actually, the rich network of vessels absorbs bigger proportion of heat than compartment average if the equal amount of heat is imposed from outside. The unexpected systemic thermal responses reported during clinical practice in a regional hyperthermia [27,28] indicate the need of both description of remote temperature responses and the utilization of these effects. Given that 20 W heat is irradiated from skin surface, the heat absorbed by blood will be 6 W for systemic [15], the same as the compartment calculation.…”