The History of Hyperthermia Rise and Decline

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Related collections

Most cited references 179

Record: found
Abstract: found
Article: not found

Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors.

Eilon Kirson, Vladimír Dbalý, František Tovaryš … (2007)

We have recently shown that low intensity, intermediate frequency, electric fields inhibit by an anti-microtubule mechanism of action, cancerous cell growth in vitro. Using implanted electrodes, these fields were also shown to inhibit the growth of dermal tumors in mice. The present study extends these findings to additional cell lines [human breast carcinoma; MDA-MB-231, and human non-small-cell lung carcinoma (H1299)] and to animal tumor models (intradermal B16F1 melanoma and intracranial F-98 glioma) using external insulated electrodes. These findings led to the initiation of a pilot clinical trial of the effects of TTFields in 10 patients with recurrent glioblastoma (GBM). Median time to disease progression in these patients was 26.1 weeks and median overall survival was 62.2 weeks. These time to disease progression and OS values are more than double the reported medians of historical control patients. No device-related serious adverse events were seen after >70 months of cumulative treatment in all of the patients. The only device-related side effect seen was a mild to moderate contact dermatitis beneath the field delivering electrodes. We conclude that TTFields are a safe and effective new treatment modality which effectively slows down tumor growth in vitro, in vivo and, as demonstrated here, in human cancer patients.

0 comments Cited 266 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Disruption of cancer cell replication by alternating electric fields.

Eilon Kirson, Zoya Gurvich, Rosa Sara Schneiderman … (2004)

Low-intensity, intermediate-frequency (100-300 kHz), alternating electric fields, delivered by means of insulated electrodes, were found to have a profound inhibitory effect on the growth rate of a variety of human and rodent tumor cell lines (Patricia C, U-118, U-87, H-1299, MDA231, PC3, B16F1, F-98, C-6, RG2, and CT-26) and malignant tumors in animals. This effect, shown to be nonthermal, selectively affects dividing cells while quiescent cells are left intact. These fields act in two modes: arrest of cell proliferation and destruction of cells while undergoing division. Both effects are demonstrated when such fields are applied for 24 h to cells undergoing mitosis that is oriented roughly along the field direction. The first mode of action is manifested by interference with the proper formation of the mitotic spindle, whereas the second results in rapid disintegration of the dividing cells. Both effects, which are frequency dependent, are consistent with the computed directional forces exerted by these specific fields on charges and dipoles within the dividing cells. In vivo treatment of tumors in C57BL/6 and BALB/c mice (B16F1 and CT-26 syngeneic tumor models, respectively), resulted in significant slowing of tumor growth and extensive destruction of tumor cells within 3-6 days. These findings demonstrate the potential applicability of the described electric fields as a novel therapeutic modality for malignant tumors.