Modulated Electrohyperthermia: A New Hope for Cancer Patients

Abstract

According to the World Health Organization, the prevalence of cancer has increased worldwide. Oncological hyperthermia is a group of methods that overheat the malignant tissues locally or systematically. Nevertheless, hyperthermia is not widely accepted, primarily because of the lack of selectivity for cancer cells and because the temperature-triggered higher blood flow increases the nutrient supply to the tumor, raising the risk of metastases. These problems with classical hyperthermia led to the development of modulated electrohyperthermia (mEHT). The biophysical differences of the cancer cells and their healthy hosts allow for selective energy absorption on the membrane rafts of the plasma membrane of the tumor cells, triggering immunogenic cell death. Currently, this method is used in only 34 countries. The effectiveness of conventional oncotherapies increases when it is applied in combination with mEHT. In silico, in vitro, and in vivo preclinical research studies have all shown the extraordinary ability of mEHT to kill malignant cells. Clinical applications have improved the quality of life and the survival of patients. For these reasons, many other research studies are presently in progress worldwide. Thus, the objective of this review is to highlight the capabilities and advantages of mEHT and provide new hopes for cancer patients worldwide.

Modulated electro-hyperthermia in stage III and IV pancreatic cancer: Results of an observational study on 158 patients

“…Improvements were reported also in tumor response for locally advanced pancreatic carcinoma a consequence of the association of CHT to mEHT with a DCR of 95% that were in agreement with previous data: DCR of 71%-96%[ 8 - 11 ] and resulted higher than that reported by CHT associated with local hyperthermia, showing a DCR of 50%-61%[ 17 - 19 ]. The level of hyperthermia related toxicity was 5% as reported by other studies, showing G2 pain and a skin rash and 5% grade III–IV toxicity[ 15 , 18 ].…”

“…Hyperthermia has been used as cancer therapy for decades, especially for its benefits in enhancing chemotherapy and radiotherapy efficacy[ 6 , 14 - 22 ]. mEHT has been more recently introduced among hyperthermia methods, targeting malignant cell membranes and the extracellular matrix and overcoming the issue of homogenous tissue heating[ 7 , 8 ]. The efficacy of mEHT was shown for several types of tumors, including pancreatic cancer, increasing tumor response and survival[ 5 , 9 , 15 - 21 ].…”

“…A new method of RHT has been recently developed: The modulated electro-hyperthermia (mEHT) that is performed with a 13.56 MHz capacitive coupled device. It targets malignant cell membranes and extracellular matrix, allowing to overcome the issue of reaching deep tumors and achieving homogenous heating[ 7 , 8 ]. The mEHT has comparable benefits to other RHT methods and improves survival and local tumor control for several tumors, including pancreatic cancer[ 9 - 11 ].…”

Oligometastatic Disease in Prostate Cancer. Evolving paradigm: current knowledge, diagnostic techniques and treatment strategies

“…An extrinsic effect (abscopal) is a process in which local tumour treatment leads to the antitumour impacts observed outside the radiation field at a considerable distance from it [76]. Based on the existing literature, abscopal effects are observed in patients treated with RT [77], oncothermia [78] or a combination of them. Local irradiation of a tumour at one site induces the entry of tumour antigens or inflammatory response factors into the circulatory system, which may cause an increased defence response directed against non-irradiated tumour lesions displaying similar tumour antigens [79].This is supported by the potential benefits of immunotherapy and the evidence of the activity of immune checkpoint inhibitors in mCRPC [80], [81].…”

Modulated Electro-Hyperthermic (mEHT) Treatment in the Therapy of Inoperable Pancreatic Cancer Patients—A Single-Center Case-Control Study

“…The functional and bioelectric features of the malignant cells drive the selective process, which, together with the dynamic interactions and thermal exchanges, kills the cancer cells in an apoptotic way. Without going into details, mEHT exploits the biophysical differences of cancer cells that their energy absorption on the membrane rafts is different than those of healthy host cells, furthermore, damage-associated molecular patterns (DAMPS) will occur and all of these eventually lead to programmed or immunogenic tumor cell death [ 25 , 26 ]. The mEHT method re-sensitizes the refractory cases, can act as monotherapy as preclinical results and case studies suggested [ 25 , 27 , 28 , 29 ], and increases the survival time and QoL in parallel.…”