Modulated Electro-Hyperthermia (mEHT) in cancer patients: experiences on 110 patients

Artícle written by Giammaria Fiorentini, Donatella Sarti, Virginia Casadei, Caterina Fiorentini

Onco-Ematology Department, Azienda Ospedaliera “Ospedati Riuniti Marche Nord”, 61122 Pesaro, italy

Department of Medical Biothecnologies, Division of Cardiology, University of Siena, 53100 Siena, Italy,

Presented at 36º ICHS, Budapest, 2018

Background and aims:

There has been a significant improvement in the development and application of hyperthermia treatment and there is a continuous interest and ongoing clinical research in the field of hyperthermia. This study aim to evaluate the efficacy in terms of tumor response, pain reduction and improvement of quality of life due to modulated electro- hyperthermia
(mEHT), for the treatment of cancer.

Methods

This was a retrospective observational clinical study. Patients were included in the study if they had >18 years, informed consent signed, indication for treatment with mEHT.

Hyperthermia was performed with short radiofrequency waves of 13.56 MHz using a capacitive coupling technique keeping the skin surface at 26 C°. The applied power ranged between 40-150 Watts and the calculated average equivalent temperature in the tumors was above 41,5 C° for more than 90% of the treatment duration (20-60 minutes gradually).

Results

Characteristics of patients

110 consecutive patients were enrolled in the study, tumor distribution was: 11 (10%) colon, 11 (10%), ovary, 10 (9%) central nervous system, 10 (9%) breast, 10 (9%) liver (cholangiocarcinoma and HCC), 10 (9%) lung, 9 (8%) pancreas, 8 (7%) prostate, 5 (5%) pseudo mixoma peritoneii, 5 (5%) stomach, 4 (5%) melanoma, 2(2%) mesothelioma, 3(3%) bladder, 3 (3%) liposarcome and 11 (10%) other type of tumor. Other chracteristics of the
sample were: 50% presence of metastasis, 70% received concomitant radio or chemotherapy and median number of mEHT cycles was 8 (range 1-37).

Tumor response analysis three months after mEHT showed 3% complete remission and 41% partial remission, 31 % of stable disease and 25% of progression. Median pain intensity and quality of life improved in 85% of the sample. mEHT toxicity was mostly mild (G1). The small total number of adverse events (5%) in this study supports the strong safety profile of mEHT. No complications were observed during the treatments. Cardiac evaluation was performed for all patients with EKG and echocardiography before and after the last cycle of mEHT. No significant variations were observed.

Figure 1. Tumor response (3 months)

Conclusion

mEHT appears to have promising efficacy in adults with several types of tumor and it can be considered as a highly indicated palliative therapy.

Figure 2. Patient with squamous cellular intraoral tumor
a) baseline, b) one and c) three months after mEHT.
The tumor arises from the gum and perforates the cheek.
Figure 3. Patient, 49yrs with breast cancer and bone metastases.
a) CT scans at baseline showed partial osteolytic metastases (arrow) in thoracic vertebrae.
b) Three months after mEHT, osseous lesions din not change in size, but showed osteoblastic reaction (arrows in B), representing good response, and disappearance of the back pain.

Text extracted from Oncothermia Journal, Volumen 24, October 2018.

www.oncothermia-journal.com/journal/2018/Efficacy_of_Modulated_electro_hyperthermia_(mEHT)_in_cancer_ patients.pdf

New unit of Electro-Hyperthermia modulated (mEHT / Oncothermia) in the University Hospital Marqués de Valdecilla

The Marqués de Valdecilla University Hospital is one of the most prominent public hospitals in Spain. Very soon it will have the first Electro-Hyperthermia modulated equipment (mEHT / Oncothermia) located in a public hospital in Spain.

The medical center works in collaboration with the Center for Medical Simulation de Boston.

This Radiation Oncology unit has designed a clinical study that will be carried out with cancer patients in Phase III, combining Oncothermia with standard chemotherapy and radiotherapy.

The corresponding clinical study proposal is transcribed bellow:

Future position of oncothermia combination with standard chemo and radiotherapy in clinical practice – Highlights of upcoming Phase III clinical studies in Hospital Universitario Marqués de Valdecilla (HUMV)

Elisabeth E. Arrojo

Ratiation Oncologist

University Hospital Marqués de Valdecilla, Santander, Spain.

Introdution

Aggressive malignant tumors are known to be usually hypoxic. It´s well known that hypoxia decreases tumors’ response to radiotherapy (radiosensitivity). At least 2 or 3 times more radiation dose is needed to kill hypoxic cells compared with well oxygenated cells.

Several studies have shown that modulated electro hyperthermia (mEHT) is able to increase tumor oxygenation, and thus alleviate the hypoxia that would lead to greater radioresistance, establishing itself as an optical moment to apply radiotherapy, about 30 minutes after the treatment of mEHT.

There are also several studies showing the efficacy of mEHT in killing cancer cells when used alone without any other cancer treatments.

These are some of the reasons why the combination of these treatments (mEHT + Radiochemotherapy) could result on an improvement in tumor control and survival for cancer patients. Despite several studies about mEHT treatment in cancer patients alone or combined with standard radio-chemotherapy have been published with wonderful results, we still do
not have enough phase III trials to clarify the role of mEHT on cancer treatment.

Purpose

To perform three different phase III clinical studies to test whether the combination of radiochemotherapy treatment with mEHT in the 30 minutes prior to the radiotherapy session, or the treatment in monotherapy with mEHT in those cases not susceptible to another oncological treatment, will improve local control (primary objective) and/or survival (secondary objective) in patients with high-grade brain tumors, pancreatic cancer or rectal cancer, without increasing side effects from the standard treatments.

Material and methods

Patients diagnosed with high grade glioma, pancreatic cancer, or rectal cancer will be included in three different phase III clinical studies. These studies will include newly diagnosed cancer patients or patients with recurrent malignant tumors after treatment with standard therapies. The study for patients diagnosed with high grade brain glioma (stages III and IV) will include patients who will receive treatment in an adjuvant setting after surgery combining mEHT with standard chemo-radiotherapy or with mEHT as the only treatment in those cases not candidates to surgery, chemo and/or radiotherapy. The clinical study about pancreatic cancer, will include patients with locally advanced cancer and again, mEHT treatment will be combined with the standard chemo-radiotherapy treatment in a neoadjuvant, radical, palliative or adjuvant setting, or will be the unique treatment in those cases not amenable to be treated with standard therapies. The third study, is for patients diagnosed with rectal cancer who meet the criteria to receive standard treatment with neoadjuvant chemo and radiotherapy, in whom mEHT will be combined with these neoadjuvant treatments. In all the studies, when mEHT is combined with radiotherapy, it will be always delivered around 30 minutes before each radiotherapy session. Patients with history of other cancer in the past 10 years will be excluded.

Results

Three different phase III clinical studies have been already designed to be performed at the radiation oncology department of Valdecilla University Hospital in Santander, Spain. We have already received the approval of the University Hospital Marqués de Valdecilla and the “Idival” research institute, which will be also a collaborator, to begin with the studies, and we also have the necessary insurances to run them. We have also appointed a coordinator to control and check the proper development of these studies.

Conclusion

Modulated electro hyperthermia combined with standard radio and chemotherapy or as a unique treatment in cancer patients not candidate to standard treatment, looks very promising to improve local control and survival in cancer patients. These clinical studies will give us very valuable information about the role of mEHT in cancer treatment, and its contribution as a radiotherapy and chemotherapy sensitizer.

More information:

Arrojo E. (2018): Future position of oncothermia combination with standard chemo and radiotherapy in clinical practice – Highlights of upcoming Phase III clinical studies in Hospital Universitario Marqués de Valdecilla (HUMV); Oncothermia Journal 24:59-90 www.oncothermia-journal.com/journal/2018/Future_position_of_oncothermia .pdf

New unit of Electro-Hyperthermia modulated (mEHT / Oncothermia) in the University Hospital Marqués de Valdecilla

The Marqués de Valdecilla University Hospital is one of the most prominent public hospitals in Spain. Very soon it will have the first Electro-Hyperthermia modulated equipment (mEHT / Oncothermia) located in a public hospital in Spain.

The medical center works in collaboration with the Center for Medical Simulation de Boston.

This Radiation Oncology unit has designed a clinical study that will be carried out with cancer patients in Phase III, combining Oncothermia with standard chemotherapy and radiotherapy.

The corresponding clinical study proposal is transcribed bellow:

Future position of oncothermia combination with standard chemo and radiotherapy in clinical practice – Highlights of upcoming Phase III clinical studies in Hospital Universitario Marqués de Valdecilla (HUMV)

Elisabeth E. Arrojo

Ratiation Oncologist

University Hospital Marqués de Valdecilla, Santander, Spain.

Introdution

Aggressive malignant tumors are known to be usually hypoxic. It´s well known that hypoxia decreases tumors’ response to radiotherapy (radiosensitivity). At least 2 or 3 times more radiation dose is needed to kill hypoxic cells compared with well oxygenated cells.

Several studies have shown that modulated electro hyperthermia (mEHT) is able to increase tumor oxygenation, and thus alleviate the hypoxia that would lead to greater radioresistance, establishing itself as an optical moment to apply radiotherapy, about 30 minutes after the treatment of mEHT.

There are also several studies showing the efficacy of mEHT in killing cancer cells when used alone without any other cancer treatments.

These are some of the reasons why the combination of these treatments (mEHT + Radiochemotherapy) could result on an improvement in tumor control and survival for cancer patients. Despite several studies about mEHT treatment in cancer patients alone or combined with standard radio-chemotherapy have been published with wonderful results, we still do
not have enough phase III trials to clarify the role of mEHT on cancer treatment.

Purpose

To perform three different phase III clinical studies to test whether the combination of radiochemotherapy treatment with mEHT in the 30 minutes prior to the radiotherapy session, or the treatment in monotherapy with mEHT in those cases not susceptible to another oncological treatment, will improve local control (primary objective) and/or survival (secondary objective) in patients with high-grade brain tumors, pancreatic cancer or rectal cancer, without increasing side effects from the standard treatments.

Material and methods

Patients diagnosed with high grade glioma, pancreatic cancer, or rectal cancer will be included in three different phase III clinical studies. These studies will include newly diagnosed cancer patients or patients with recurrent malignant tumors after treatment with standard therapies. The study for patients diagnosed with high grade brain glioma (stages III and IV) will include patients who will receive treatment in an adjuvant setting after surgery combining mEHT with standard chemo-radiotherapy or with mEHT as the only treatment in those cases not candidates to surgery, chemo and/or radiotherapy. The clinical study about pancreatic cancer, will include patients with locally advanced cancer and again, mEHT treatment will be combined with the standard chemo-radiotherapy treatment in a neoadjuvant, radical, palliative or adjuvant setting, or will be the unique treatment in those cases not amenable to be treated with standard therapies. The third study, is for patients diagnosed with rectal cancer who meet the criteria to receive standard treatment with neoadjuvant chemo and radiotherapy, in whom mEHT will be combined with these neoadjuvant treatments. In all the studies, when mEHT is combined with radiotherapy, it will be always delivered around 30 minutes before each radiotherapy session. Patients with history of other cancer in the past 10 years will be excluded.

Results

Three different phase III clinical studies have been already designed to be performed at the radiation oncology department of Valdecilla University Hospital in Santander, Spain. We have already received the approval of the University Hospital Marqués de Valdecilla and the “Idival” research institute, which will be also a collaborator, to begin with the studies, and we also have the necessary insurances to run them. We have also appointed a coordinator to control and check the proper development of these studies.

Conclusion

Modulated electro hyperthermia combined with standard radio and chemotherapy or as a unique treatment in cancer patients not candidate to standard treatment, looks very promising to improve local control and survival in cancer patients. These clinical studies will give us very valuable information about the role of mEHT in cancer treatment, and its contribution as a radiotherapy and chemotherapy sensitizer.

More information:

Arrojo E. (2018): Future position of oncothermia combination with standard chemo and radiotherapy in clinical practice – Highlights of upcoming Phase III clinical studies in Hospital Universitario Marqués de Valdecilla (HUMV); Oncothermia Journal 24:59-90 www.oncothermia-journal.com/journal/2018/Future_position_of_oncothermia .pdf

Modulated Electro-Hyperthermia (mEHT) in cancer patients: experiences on 110 patients

Artícle written by Giammaria Fiorentini, Donatella Sarti, Virginia Casadei, Caterina Fiorentini

Onco-Ematology Department, Azienda Ospedaliera “Ospedati Riuniti Marche Nord”, 61122 Pesaro, italy

Department of Medical Biothecnologies, Division of Cardiology, University of Siena, 53100 Siena, Italy,

Presented at 36º ICHS, Budapest, 2018

Background and aims:

There has been a significant improvement in the development and application of hyperthermia treatment and there is a continuous interest and ongoing clinical research in the field of hyperthermia. This study aim to evaluate the efficacy in terms of tumor response, pain reduction and improvement of quality of life due to modulated electro- hyperthermia
(mEHT), for the treatment of cancer.

Methods

This was a retrospective observational clinical study. Patients were included in the study if they had >18 years, informed consent signed, indication for treatment with mEHT.

Hyperthermia was performed with short radiofrequency waves of 13.56 MHz using a capacitive coupling technique keeping the skin surface at 26 C°. The applied power ranged between 40-150 Watts and the calculated average equivalent temperature in the tumors was above 41,5 C° for more than 90% of the treatment duration (20-60 minutes gradually).

Results

Characteristics of patients

110 consecutive patients were enrolled in the study, tumor distribution was: 11 (10%) colon, 11 (10%), ovary, 10 (9%) central nervous system, 10 (9%) breast, 10 (9%) liver (cholangiocarcinoma and HCC), 10 (9%) lung, 9 (8%) pancreas, 8 (7%) prostate, 5 (5%) pseudo mixoma peritoneii, 5 (5%) stomach, 4 (5%) melanoma, 2(2%) mesothelioma, 3(3%) bladder, 3 (3%) liposarcome and 11 (10%) other type of tumor. Other chracteristics of the
sample were: 50% presence of metastasis, 70% received concomitant radio or chemotherapy and median number of mEHT cycles was 8 (range 1-37).

Tumor response analysis three months after mEHT showed 3% complete remission and 41% partial remission, 31 % of stable disease and 25% of progression. Median pain intensity and quality of life improved in 85% of the sample. mEHT toxicity was mostly mild (G1). The small total number of adverse events (5%) in this study supports the strong safety profile of mEHT. No complications were observed during the treatments. Cardiac evaluation was performed for all patients with EKG and echocardiography before and after the last cycle of mEHT. No significant variations were observed.

Figure 1. Tumor response (3 months)

Conclusion

mEHT appears to have promising efficacy in adults with several types of tumor and it can be considered as a highly indicated palliative therapy.

Figure 2. Patient with squamous cellular intraoral tumor
a) baseline, b) one and c) three months after mEHT.
The tumor arises from the gum and perforates the cheek.
Figure 3. Patient, 49yrs with breast cancer and bone metastases.
a) CT scans at baseline showed partial osteolytic metastases (arrow) in thoracic vertebrae.
b) Three months after mEHT, osseous lesions din not change in size, but showed osteoblastic reaction (arrows in B), representing good response, and disappearance of the back pain.

Text extracted from Oncothermia Journal, Volumen 24, October 2018.

www.oncothermia-journal.com/journal/2018/Efficacy_of_Modulated_electro_hyperthermia_(mEHT)_in_cancer_ patients.pdf

Effects of the addition of electro-hyperthermia (Oncothermia) to chemoradiotherapy in cancer of the cervix. Randomized clinical trial – Phase III.

Dr. Minara CA of the University of Witwatersrand, Johannesburg, South Africa has published in the journal Oncothermia journal 21:56 57, 2017 an update on the phase III randomized clinical trial investigating the effects of the addition of electrons hyperthermia to chemoradiotherapy for patients with cancer of the cervix in South Africa.

The electrohyperthermia (EHT) trial is an ongoing phase III randomized clinical trial that is conducted at the Charlotte Maxeke Johannesburg Academic Hospital. The overall objective is to determine the clinical effects of the addition of modulated electrohyperthermia (EHT) to standard treatment protocols for locally advanced cervical cancer patients in state health care in South Africa. The objectives are to evaluate the effects of the addition of EHT on local control of the disease, quality of life, acute and late toxicity and overall survival.

Methods:

The purpose of the study is to treat 236 women with a FIGO IIB to IIIB stage of cervical cancer. Participants are randomly assigned to a group of “Hyperthermia” (EHT plus chemoradiation) and a group of “Control” (chemoradiation alone), strata of randomization: HIV status; years; stage of the disease. All participants receive external radiation of 50 Gy, 3 doses of brachytherapy with a high dose rate of 8 Gy and cisplatin. The “Oncothermia” group receives two local EHT treatments of 55 minutes per week during radiation therapy. Local control of the disease is evaluated by positron emission tomography (PET) scans. Adverse events, quality of life and overall survival are recorded and the data analyzed.

Results:

The first 100 participants are evaluated until they reach 6 months after treatment.

There has been a positive trend in the survival and local control of the disease in the group receiving OT.

There are no significant differences in acute adverse events or quality of life between the two groups.

The preliminary results of the addition of EHT are positive without impact on adverse events, however, this should be confirmed with more patients at the end of the study.

Oncothermia in brain tumors

Prof. Giammaria Fiorentini of the Department of Onco-Hematology of Azienda Ospedaliera Marche Nord, Pesaro, Italy, presented at the 35th Annual Conference of the International Clinical Hyperthermia Society (ICHS) in Guangzhou, the results of their work in the treatment with Hyperthermia (Oncothermia) in patients with brain tumors.

The study was carried out with an Oncotherm EHY-2000 PLUS device, on 24 patients: 19 with glioblastoma multiforme and 5 with astrocytoma. All of them were previously treated with surgery, TMZ chemotherapy and radiotherapy.

Through the article Prof. Giammaria Fiorentini describes the characteristics of brain tumors, their incidence and mortality, survival and conventional therapies that are used, with an emphasis on the case of Glioblastoma and the benefits obtained by applying Electro-hyperthermia.

According to his observations Oncothermia (Electro-hyperthermia) is a non-invasive treatment, without toxicity and feasible to treat recurrent malignant gliomas, which allows to increase the response to the tumor and the survival of the patient.

The full article can be accessed by visiting this link.

Hypothesis: Studies that observe the effectiveness of Hyperthermia in HG Gliomas.

Oncothermia (Electro – Hyperthermia) traslational studies.

Oncothermia application in malignant gliomas.

Study on the activity and toxicity of Oncothermia in recurrent malignant gliomas.

Description of the equipment used: Oncotherm EHY-2000 PLUS, non-ionizing therapy that elevates the temperature of the tumor macro and micro-enviroments, to a range of 40-45ºC, generating a 40-150 Watt radiofrequency, at 13.56 MHz.

24 patients, 19 with glioblastoma multiforme and 5 with astrocytoma. All patient were pre-treated with surgery, chemotherapy and radiotherapy.

Oncothermia treatment: 3 sessions/week for 4 weeks, 20 a 60 minutes each session.

Results: 2 complete remissions and 5 partial remissions were observed. The medial OS was 14 months for gliomas and 61 months for astrocitomas.

Conclussions:

– Oncothermia applicated in patients with relapsed malignant gliomas is feasible and may increase tumor response and survival.

– EHT is a non-invasive method to treat malignant gliomas without toxicity.

– EHT appears to have effectiveness and further studies are warranted.

– EHT can be considered a landmark stone of integrative oncology.

Source:

Fiorentini G. (2018): Oncothermia in brain tumours; Oncothermia Journal 22: 151-177

www.oncothermia- journal.com/journal/2018/Oncothermia_in_brain_tumours.pdf

Oncothermia Barcelona unit: latest generation model EHY-2000 plus

Oncothermia is a method of non-invasive modulated electromagnetic hyperthermia, complementary in the treatment against cancer, which promotes a natural regulatory process of the body. The brand Oncotherm® was founded in 1988 by Professor Dr. András Szász, as an initiative for the development and research of the electro-hyperthermia method in the treatment of cancer.

Treatment with Oncothermia started in Germany 25 years ago, and is currently used in more than 25 countries. Only in Germany is it in 4 hospitals and in more than 50 clinics functioning effectively. Every year more than 100,000 annual treatments are carried out worldwide

At the Oncothermia Barcelona Unit is the latest generation model: EHY-2000 plus, the latest technology to offer the best results

Modelo EHY-2000 de Oncothermia

About Oncothermia:

  • Oncothermia is active in all solid tumors.
  • No side effects, rare contraindications.
  • Energy absorption combined with modulated electric field.
  • Tumor tissue is treated selectively by destroying only the malignant tissue
  • Healthy tissue is not affected.
  • The effectiveness of chemotherapy and radiotherapy improves with treatment.
  • Restores intercellular junctions, suppresses dissemination (metastasis).
  • Oncothermia induces immunogenic cell death.
  • It improves the quality of life, reduces the side effects of other treatments.
  • A proven method for 30 years with more than 100,000 treatments per year.

Synergy of Oncothermia with Vitamin C in the treatment of lung cancer

Dr Ou’s team, from Cancer Center, Clifford Hospital, Guangzhou, University of Medicine, China, published in the journal Eur J Pharm Sci. 2017 Nov 15; 109: 412-418, results on the synergy of intravenous Vitamin C and Oncothermia.

Vitamin C intravenously (VitC) and Oncothermia (electrohyperthermia modulated (mEHT)) have been used in medical centers for integrative medicine for the treatment of cancer, for many years. However, no pharmacokinetic study had been planned to assess Chinese cancer patients.

A clinical trial was conducted to evaluate safety and pharmacokinetics in patients with stage III-IV non-small cell lung cancer (NSCLC). A total of 35 patients with lung cancer (NSCLC) were included. A total of 15 patients with stage III-IV who entered the phase I study were selected. They were randomized allocated into 3 groups, and received doses 1.0, 1.2, 1.5 g/kg AA infusions. Participants in the first group received intravenous AA (IVAA) when mEHT was finished, in the second group IVAA was administered simultaneously with mEHT and in the third group IVAA was applied first, and followed with mEHT. The process was applied 3 times a week (every other day, weekend days off) for 4 weeks. We found that fasting plasma AA levels were significantly correlated with stage of the disease. Peak concentration of AA was significantly higher in the simultaneous treatments than in other combinations with mEHT or in solely IVAA-managed groups. 

Results:

IVAA synergy with simultaneous mEHT is safe. The concomitant application significantly increases the plasma AA level for NSCLC patients wiht non-small cell lung cancer (NSCLC).

Retrospective study of Oncothermia combined with chemotherapy for the treatment of Glioblastoma. Efficiency and cost-effectiveness analysis

Retrospective study of Oncothermia combined with chemotherapy for the treatment of Glioblastoma. Efficiency and cost-effectiveness analysis

Dr. Roussakow`s Team, Department Galenic Research Institute, Moscow, Russia, recently published in the Biomedical Journal Open (BMJ Open, 2017 Nov 3; 7 (11)) the results on the complementary use of Oncothermia in Glioblastoma multiform.

Researchers compared the efficacy and cost-effectiveness of Oncothermia (electrohyperthermia mEHT) with chemotherapy (temozolomide, ddTMZ) versus chemotherapy alone in a patient with recurrent Glioblastoma multiforme (GBM).

This is a retrospective study of a population of 54 patients diagnosed with recurrent Glioblastoma multiforme treated with chemotherapy and Oncothermia (ddTMZ + mEHT) during the period 2000-2005. The comparison was made with a population of 114 patients, diagnosed with GBM, treated with chemotherapy alone (ddTMZ) during the period 2008-2013.

Results:

The treatment effect analysis (ETA) suggests that Oncothermia significantly improves the survival of patients receiving oral chemotherapy (ddTMZ). Economic evaluation suggests that ddTMZ+Oncothermia is cost-effective, budget-saving and profitable. It is derived from the results that Oncothermia can be recommended for the treatment of recurrent Glioblastoma multiforme. Oncothermia can even be assessed as monotherapy as a rescue treatment when chemotherapy fails.