Review of the Clinical Evidences of Modulated Electro-Hyperthermia (mEHT) Method: An Update for the Practicing Oncologist

Abstract

Background: Modulated electro-hyperthermia (mEHT) is a variation of the conventional hyperthermia which selectively targets the malignant cell membranes in order to heat the malignant tissue and sensitize the tissue to oncology treatments. Although widely applied, the formulation of guidelines for the use thereof is still in progress for many tumors.Aim: In this paper we review the literature on the effects of mEHT in cancer patients on local disease control and survival.Methodology: Our review on data presents the collected experience with capacitive hyperthermia treatments with the EHY-2000+ device (OncoTherm Ltd., Germany). A literature search was conducted in Pubmed and articles were grouped and discussed according to: trial type, animal studies, in vitro studies, and reviews. Search results from Conference Abstracts; Trial Registries; Thesis and Dissertations and the Oncothermia Journal were included in the discussions.Results: Modulated electro-hyperthermia is a safe form of hyperthermia which has shown to effectively sensitizes deep tumors, regardless of the thickness of the adipose layers. The technology has demonstrated equal benefits compared to other forms of hyperthermia for a variety of tumors. Given the effective heating ability to moderate temperatures, the improved tumor perfusion, and ability to increase drug absorption, mEHT is a safe and effective heating technology which can be easily applied to sensitize tumors which have demonstrated benefits with the addition of hyperthermia. Modulated electro-hyperthermia also appears to improve local control and survival rates and appears to induce an abscopal (systemic) response to ionizing radiation.Conclusion: Based on clinical studies, the method mEHT is a feasible hyperthermia technology for oncological applications. Concomitant utilization of mEHT is supported by the preclinical and clinical data.

Bevacizumab Plus FOLFOX-4 Combined With Deep Electro-Hyperthermia as First-line Therapy in Metastatic Colon Cancer: A Pilot Study

“…In fact, the electric field tends to move through the pathways with the lowest impedance, i.e. through the malignant tissue (71,(74)(75)(76)(77).…”

Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models

“…The 13.56 MHz radiofrequency has been endorsed and widely used for medical applications with safety, under the conditions described, or when using EHY 2000+ for human treatment between 110–130 W with large electrodes, and no risk of damaging normal tissues or interfering with the action potentials of nerves, cardiac muscle, or with any telecommunication instrument has been found [ 10 , 15 ]. Human mEHT therapy (Oncothermia), which is mirrored in preclinical studies, applies nearly an order of magnitude less of energy for comparable effect when compared with other similar techniques.…”

“…This loco-regionally delivered deep hyperthermia generated by mEMT has been an efficient and safe chemo- and radiosensitizer in human oncotherapy by improving both the local tumor control and survival rates, along with contributing to the systemic (abscopal) effect of ionizing radiation [ 10 , 95 ]. Besides many positive case studies being published in a wide range of tumors, several clinical papers analyzing the statistically relevant number of patients have come out recently confirming the added benefits of mEHT treatment to conventional oncotherapy.…”

“…Randomized clinical trials have recently been running for testing the benefits of mEHT combined with folfirinox or gemcitabine chemotherapy in metastatic pancreatic cancers, weekly paclitaxel or cisplatin use in recurrent or persistent ovarian cancer, chemo-irradiation in locally advanced cervical cancer, and for improving quality of life in unresectable pancreatic cancer patients [ 10 ].…”

“…The modulated electro-hyperthermia generated by 13.56 MHz amplitude-modulated radio-frequency (mEHT; trade name: Oncothermia) has lately been an emerging way of delivering loco-regional clinical hyperthermia with favorable safety and tolerance profiles [ 10 ]. Though mEHT has also been used in combination with chemo-, radiation-, or more recently immunotherapy, a growing number of preclinical studies have demonstrated that it can also induce significant tumor damage in monotherapy, primarily through provoking cell stress and regulated cell death response [ 11 , 12 ].…”