Chemotherapy and Oncothermia association

Chemotherapy and Oncothermia association

Lower and less toxic doses of chemotherapy by combining it with Oncothermia and complementary treatments.

Modelo EHY-2000 de Oncothermia

Professor Dr. med. Alexander Herzog, Chief-physician, Fachklinik Dr. Herzog, Germany has published a recent clinical study in the Oncothermia journal. He also presented it at the 35th ICHS, Guangzhou, China, 2017. The study explains the results in the use of lower and less toxic doses of chemotherapy when combined with hyperthermia and complementary treatments.

Electro-hyperthermia (Oncothermia) is an important tool for improving the efficacy of chemotherapy and radiation in cancer.

Numerous studies have been published on Oncothermia treatment in cell cultures, in animal experiments, but also in patients. Furthermore, these studies include randomised studies, phase 2 studies, but also many successful case reports that provide evidence for the benefit of Oncothermia.

Methods:

Oncothermy means heating the cancerous tissue up to 42°C (107.6°F). In several experiments, it has been shown that chemotherapy works more efficiently if the temperature of the cancer tissue is increased. There can be a linear or even exponential increase in the activity of cytostatic drugs.

The Oncotherm device with 13.56 MHz and energies up to 150 watts was used. The local treatment takes 1 hour for each session. In addition, such treatment can be repeated frequently (the interval between 2 treatments should be at least 48 hours to avoid thermal tolerance).

Chemotherapy is administered simultaneously with a local Oncothermia session.

Results for a selection of different cancers:

♦ ENT-Cancers:

The standard chemotherapy in these cases would be a rather toxic 5-day programme of cisplatin together with 5-FU as a continuous infusion. Together with oncothermia, a 4-day programme would be sufficient.

♦ Non-small cell lung cancer:

The dosing regimen would follow platinum-based chemotherapy, but the doses of Carboplatin and Gemcitabine or Vinorelbine could be reduced by approximately 20%, if applied together with Oncothermia.

♦ Colorectal cancer:

Chemotherapy protocols in colorectal cancer are mainly the FOLFOX protocol and the Folfiri protocol, which can be combined with Bevacizumab or Cetuximab antibodies. Together with Oncothermia, the dose of Oxaliplatin would be kept at the standard level. Irinotecan could be reduced. 5-FU administered as a chronomodulated treatment at night with 50% of the dose between 2 a.m. and 6 a.m. could also be significantly reduced. In addition, Capecitabine can be used together with Oncothermia at a reduced dose.

♦ Ovarian and cervical cancers:

In ovarian and cervical cancer, the standard chemotherapy is Carboplatin and the neurotoxic drug Paclitaxel. Together with Oncothermia, Carboplatin could be combined with a less toxic dose of Cyclophosphamide, which is a drug with potentiation of its activity under hyperthermic conditions.

♦ Breast cancer:

In one study, it has been shown that 70-80% of breast cancer patients respond to a treatment programme with local oncothermia together with moderate doses of chemotherapy.

Reduces toxicity

In conjunction with oncothermia, it is possible to use chemotherapy in more moderate doses. This reduces toxicity. Above all, it helps patients in particular in the palliative situation to preserve quality of life. It also allows for more regular treatments and for a longer period of time which is possibly very important to improve survival times.

Sources:

Herzog A. (2018): Lower and less toxic doses of chemotherapy by combining it with hyperthermia and complementary treatments; Oncothermia Journal 22:46-56

Ascending colon cancer treated with Oncothermia and Chemotherapy

Ascending colon cancer treated with Oncothermia and Chemotherapy

The following is the clinical case of a 63-year-old male patient. The diagnosis is ascending colon cancer with liver metastases. He was treated with chemotherapy, combined with oncothermia.

Diagnosis

In November 2016, he presented with an ascending colon neoplasm. Consequently, he underwent a right hemicolectomy. As a result, the biopsy showed infiltrating adenocarcinoma.

Subsequently, in January 2017, she presented with elevated CEA. A CT scan revealed mesenteric and retroperitoneal lymphadenopathy. Multiple liver metastases were also observed, the largest measuring 35 mm.

Treatment

Immediately, in February 2017, he started treatment with chemotherapy (FOLFOX) and 4 sessions of 90-minute oncothermia.

The CT scan of April 2017 showed resolution of the mesenteric and retroperitoneal adenopathies. There was also a significant decrease in the multiple liver metastases, the largest being 14 mm.

Result

Finally a normalisation of tumour markers is detected.

If you wish, you can find more information about colon cancer treated with Oncothermia on our website at this link.

Breast Cancer treated with Chemotherapy and Oncothermia

Breast Cancer treated with Chemotherapy and Oncothermia

The following is the clinical case of a 51 year old female patient. The diagnosis is infiltrating ductal carcinoma of the left breast. She was treated with chemotherapy, combined with oncothermia.

Diagnosis

She presented in May 2016 with breast cancer, infiltrating ductal carcinoma of the left breast. Consequently, the MRI shows multiple and extensive irregular confluent foci. In addition, the cancer forms a mass measuring 79 mm x 52 mm x 58 mm extending to the nipple-areola complex with infiltration of the dermis.

Treatment

In June 2016 she started chemotherapy with Paclitaxel and Trastuzumab. Subsequently, in August 2016, oncothermia treatment was started, with 60-minute sessions.

Result

In October 2016 a breast MRI is performed for control, after the administration of 9 sessions of chemotherapy and 6 sessions of 60-minute oncothermia.

The result of the MRI shows disappearance of the tumour mass indicating a complete response to treatment.

Consequently, the patient refuses surgical treatment as there is no tumour mass and continues with radiological controls. In October 2018 the patient has shown no signs of recurrence.

If you wish, you can find more information about breast cancer treated with Oncothermia on our website at this link.

Clinical case: breast cancer treated with Oncothermia and surgery

CLINICAL CASE 3:

• BREAST CANCER
• ONCOTHERMIA+ SURGERY

A 41-year-old woman presented in June 2015 a palpable mass in the right breast of 9.3 mm. The biopsy in November 2015 shows infiltrating carcinoma. The patient, due to physical deterioration secondary to intermittent diarrhea of ​​8 years of evolution and phobia of aggressive medical treatments, decides not to do anything and returns to control it in October 2016 by magnetic resonance, whose result shows compatible image with neoformative infiltrating lobular process with nodular component of 16 mm x 9 mm and possible extension in the shape of the dough, reaching about 5 cm in diameter. The patient decides to treat with oncothermia and begins treatment in November 2016: 15 sessions of oncothermia of 1 hour. In February 2017, magnetic resonance was performed, showing a complete disappearance of the mass enhancement and a slight decrease in the nodular component: 15 mm x 8 mm. The patient decides to do nothing and check if there is growth by magnetic resonance every 6 months. Last resonance of July 2018, shows radiological stability and finally decides to undergo surgery to remove the tumor.

Pancreatic Cancer treated with Oncothermia, Chemotherapy and Radiotherapy

Pancreatic Cancer treated with Oncothermia, Chemotherapy and Radiotherapy

The following is a case report of a 72 year old female patient. The diagnosis is pancreatic cancer. She was treated with chemotherapy and radiotherapy, combined with oncothermia.

Diagnosis

She presented in March 2017 with a 4 cm tumour in the neck of the pancreas. In particular, the biopsy shows adenocarcinoma.

Treatment

He could not be resected surgically and started chemotherapy with Folfirinox together with 10 sessions of 90 minutes of Oncothermia.

Subsequently, in July 2017, a control CT scan was performed, showing a tumour reduction of 50%. He then started treatment with radiotherapy plus 10 sessions of 90-minute oncothermia.

Result

A new CT scan in June 2018 showed tumour stability with Ca 19-9 CEA tumour markers within normal limits.

If you wish, you can find more information about pancreatic cancer treated with Oncothermia on our website at this link.

Clinical case: brain tumor, glioblastoma

CLINICAL CASE 5:

• BRAIN TUMOR (GLIOBLASTOMA)
• CHEMOTHERAPY + ONCOTHERMIA

A 60-year-old male presented a brain tumor in the left hemisphere in April 2016, showing the biopsy a high-grade glioblastoma multiforme inoperable by size. In July 2016 begins radiotherapy and chemotherapy with temozolamide coinciding with significant clinical worsening, tumor progression and increase in the number of epileptic seizures with more than 7 episodes a day. The patient had a significant decrease in the state of consciousness, total aphasia and right hemiparesis. Given the significant deterioration suffered by the treatment and tumor progression, evicted and without therapeutic options, the family rejects palliative treatment of chemotherapy and decide to perform treatment with oncothermia. In September 2016, she started treatment with oncothermia 60 minutes, 2-3 times / week continuously with some rest periods until March 2018. Throughout the treatment he has shown clinical improvement with improvement of aphasia and coordination. Until March 2018 without tumor progression.

Rectal cancer treated with oncothermia and surgery

Rectal Cancer treated with Oncothermia and Surgery

The following is a case report of a 67 year old male patient. The diagnosis is rectal cancer. He was treated with oncothermia and surgery.

Diagnosis

He presented with rectal adenocarcinoma in February 2018. In particular, it is a tumour 6 cm from the anal margin occupying one third of the intestinal lumen. In addition, the ultrasound scan showed serosal involvement, and it was classified as stage III.

Treatment

Preoperative chemotherapy and radiotherapy are recommended to reduce the tumour volume and perform surgical resection.

In this case, the patient categorically rejects chemotherapy and radiotherapy. On the contrary, he decided to start treatment with Oncothermia, with the aim of reducing the tumour volume and undergoing surgery.

He underwent 20 sessions of 90-minute oncothermia for 2 months, with a frequency of 3 sessions per week.

Result

Ultrasound endoscopy in May 2018 showed a T1 polypoid lesion. In September 2018 he underwent endoanal resection of the polypoid lesion with all the margins of the piece free of tumour.

If you wish, you can find more information about rectal cancer treated with Oncothermia on our website at this link.

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.

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