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Modulated electrohyperthermia in locally advanced cervical cancer Results of an observational study of 95 patients

Indikáció: Gynecology
Bizonyítás:
Szerző: 
Sun Young Lee Dong Hyun Lee Dong-Hyu Cho
Páciensek száma: 95
Terápia: CCRT + mEHT
Év: 2023

Abstract
Abstract Most federation of gynecology and obstetrics stage II or higher locally advanced cervical cancer (LACC) patients are treated with concurrent chemoradiotherapy (CCRT); however, recurrence is high, and the prognosis is poor. In this observational retrospective study, data from LACC patients treated with CCRT alone or combined with modulated electrohyperthermia (mEHT) were collected from 2011 to 2018. Ninety-five LACC patients, including 53 (%) treated with CCRT alone and 42 (%) treated with CCRT + mEHT, were enrolled. The complete remission rate significantly increased with CCRT + mEHT compared with CCRT alone among LACC cases with lymph node metastasis (45% vs 71%, P = .0377). Additionally, at the last follow-up point, the no-evidence-of-disease rate significantly improved with CCRT + mEHT compared with CCRT (58% vs 82%, P = .0315). Disease-free survival increased in the CCRT + mEHT group with lymph node metastasis (P = .04). The addition of mEHT to CCRT led to a better therapeutic response in LACC with regional lymph node metastasis without severe complications.

Abbreviations
AEs = adverse events, CCRT = concurrent chemoradiotherapy, CR = complete remission, DFS = disease-free survival, HIF-1a = hypoxia-inducible factor-1a, LACC = locally advanced cervical cancer, mEHT = modulated electrohyperthermia, NED = no-evidence-of-disease, OS = overall survival, RF = radio frequency, VEGF = vascular endothelial growth factor.

Meta-Analysis of Modulated Electro-Hyperthermia and Tumor Treating Fields in the Treatment of Glioblastomas

Indikáció: Glioblastoma
Bizonyítás:
Szerző: 
Attila Marcell Szasz Elisabeth Estefanía Arrojo Alvarez Giammaria Fiorentini Magdolna Herold Zoltan Herold Donatella Sarti Magdolna Dank
Páciensek száma: 450
Terápia: mEHT + TTF
Év: 2022

Simple Summary
Glioblastoma is a highly aggressive brain tumor, which has a very poor 5-year survival rate (<5%). In the last decades, the concomitant use of two non-invasive, electromagnetic devices, modulated electro-hyperthermia (mEHT) and Tumor Treating Fields (TTF) has been introduced. Both mEHT and TTF have specific anti-tumor effects, which can help to achieve a more efficient
treatment of patients and a higher rate of therapeutic response. In this meta-analysis we investigated how patient survival rates change if either device is used. The significant difference in the 1-year survival rates between the treated (>60%) and untreated groups (historical data: <40%) confirms the observation that the use of both mEHT and TTF in the treatment of glioblastomas benefits patients. In addition, it is important to emphasize that most studies have proven that the mEHT or TTF-treated patients’ quality of life is much better than that of the untreated patients.

Abstract
Background: Glioblastoma is one of the most difficult to treat and most aggressive brain tumors, having a poor survival rate. The use of non-invasive modulated electro-hyperthermia (mEHT) and Tumor Treating Fields (TTF) devices has been introduced in the last few decades, both of which having proven anti-tumor effects. Methods: A meta-analysis of randomized and observational studies about mEHT and TTF was conducted. Results: A total of seven and fourteen studies about mEHT and TTF were included, with a total number of 450 and 1309 cases, respectively. A 42% [95% confidence interval (95% CI): 25–59%] 1-year survival rate was found for mEHT, which was raised to 61% (95% CI: 32–89%) if only the studies conducted after 2008 were investigated. In the case of TTF, 1-year survival was 67% (95% CI: 53–81%). Subgroup analyses revealed that newly diagnosed patients might get extra benefits from the early introduction of the devices (mEHT all studies: 73% vs. 37%, p = 0.0021; mEHT studies after 2008: 73% vs. 54%, p = 0.4214; TTF studies: 83% vs. 52%, p = 0.0083), compared with recurrent glioblastoma. Conclusions: Our meta-analysis showed that both mEHT and TTF can improve glioblastoma survival, and the most benefit may be achieved in newly diagnosed cases.

Keywords: astrocytoma; glioblastoma; modulated electro-hyperthermia; tumor treating fields

The first experience of application of remote radiotherapy in combination with hyperthermia (oncothermia) in the treatment of patients with primary gliomas of the brain of a high degree of malignancy

Indikáció: Gliomas (advanced)
Bizonyítás:
Szerző: 
Solodkiy VA. Panshin GA. Izmailov TR. Shevchenko TA.
Páciensek száma: 20
Terápia: RT+mEHT
Év: 2021

Abstract

High-grade brain gliomas are characterized by a rapid clinical course and a 2-year survival rate of 8-12%. Despite the improvement of methods of surgery, radiotherapy (RT), and systemic drug therapy, it is still not possible to significantly increase the overall and relapse-free survival in patients withth is neuro-oncological pathology, and the combination of RT and CT with hyperthermic electrotherapy (oncothermy) (OT) looks like a promising method that helps to increase the effectiveness of special treatment. At the same time, oncothermia does not cause brain edema and does not worsen the quality of life of neuro-oncological patients. At the same time, a possible alternative to further progress in improving the results of treatment of primary brain gliomas (WHO Grade III-IV) is not only to optimize the radiotherapy program, but also to combine standard methods of radical treatment with hyperthermic electrotherapy. This article presents preliminary immediate results of treatment of 20 patients who received special treatment in the RSCRR with an assessment of the toxicity and safety of its implementation and with an assessment of the likely resumption of continued tumor growth 1.5 and 3 months after the end of treatment. In General, the data obtained indicate the safety of the developed method of special treatment of this category of neuro-oncological patients, which confirms the results obtained in 28.09.2019 patent for an invention. However, for final conclusions, further clinical studies are required on a larger group of patients with longer follow-up periods, followed by a thorough analysis of the results.

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

Indikáció: Gastrointestinal
Bizonyítás:
Szerző: 
Flora Greta Petenyi Tamas Garay Dorottya Muhl Blanka Izso Adam Karaszi Erika Borbenyi Magdolna Herold Zoltan Herold Attila Marcell Szasz Magdolna Dan
Páciensek száma: 78
Terápia: mEHT
Év: 2021

Abstract: Our present oncological treatment arsenal has limited treatment options for pancreatic ductal adenocarcinoma (PDAC). Extended reviews have shown the benefits of hyperthermia for PDAC, supporting the perspectives with the improvements of the treatment possibilities. METHODS: A retrospective single-center case-control study was conducted with the inclusion of 78 inoperable PDAC patients. Age-, sex-, chemotherapy-, stage-, and ascites formation-matched patients were assigned to two equal groups based on the application of modulated electro-hyperthermia (mEHT). The EHY2030 mEHT device was used. RESULTS: A trend in favor of mEHT was found in overall survival (p = 0.1420). To further evaluate the potential beneficial effects of mEHT, the presence of distant metastasis or ascites in the patients’ oncological history was investigated. Of note, mEHT treatment had a favorable effect on patients’ overall survival in metastatic disease (p = 0.0154), while less abdominal fluid responded to the mEHT treatment in a more efficient way (p 0.0138). CONCLUSION: mEHT treatment was associated with improved overall survival in PDAC in our single-center retrospective case-control study. The outcome measures encourage us to design a randomized prospective clinical study to further confirm the efficiency of mEHT in this patien cohort.

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

Indikáció: Gastrointestinal
Bizonyítás:
Szerző: 
Giammaria Fiorentini Donatella Sarti Girolamo Ranieri Cosmo Damiano Gadaleta Caterina Fiorentini Carlo Milandri Andrea Mambrini Stefano Guadagni
Páciensek száma: 158
Terápia: CRT+mEHT
Év: 2021

Abstract
BACKGROUND
An increasing number of studies report the beneficial effects of regional hyperthermia in association with chemotherapy (CHT) and radiotherapy for the treatment of pancreatic cancer; in particular, the use of modulated electrohyperthermia (mEHT) results in increased survival and tumor response.

AIM
To compare outcomes of CHT alone or in association with mEHT for the treatment of stage III and IV pancreatic cancer. METHODS
This was an observational retrospective study; data were collected for patients with stage III-IV pancreatic cancer that were treated with CHT alone or in combination with mEHT from 2003 to 2019. A total of 158 patients were included in the study out 270 patients screened in four Italian hospitals; 58 (37%) of these received CHT + mEHT and 100 (63%) CHT. CHT was mainly gemcitabine-based
regimens in both groups.

RESULTS
Overall (19.5 mo vs 11.02 mo, P < 0.001) and progression-free (12 mo vs 3 mo, P < 0.001) survival were better for the CHT + mEHT group compared to the CHT group. The association of mEHT resulted also in an improvement of tumor response with disease control rate 95% vs 58% (P < 0.001) at 3 mo. Toxicity was comparable in the two study groups, and mEHT related adverse events were
limited in 8 patients presenting G1-2 skin burns.

CONCLUSION
The addition of mEHT to systemic CHT improved overall and progression-freesurvival and local tumor control with comparable toxicity.

Clinical study of modulated electro‑hyperthermia for advanced metastatic breast cancer

Indikáció: Breast Cancer
Bizonyítás:
Szerző: 
Takuya Nagata Masahiko Kanamori Shinichi Sekine Mie Arai Makoto Moriyama Tsutomu Fujii
Páciensek száma: 10
Terápia: mEHT
Év: 2021

Abstract. Modulated electro‑hyperthermia (mEHT) is a new treatment modality developed to overcome the problems associated with traditional hyperthermia; mEHT uses a precise impedance‑matched system and modulated radiofrequency current flow to malignant tumors. It selects the malignant cells based on their biophysical differences, due to their high metabolic rate, individual (autonomic) behavior and membrane status. The aim of the present study was to report the outcomes of mEHT in the treatment of advanced breast cancer. mEHT was examined in 10 patients with advanced metastatic breast cancer and recurrent disease, who were considered incurable by standard therapy protocols. Of the 10 patients, partial response was achieved in 3, disease stability in 3, and progressive disease in 4; however, their quality of life was improved based on their subjective reports. No adverse effects were observed in any of the 10 patients. The present study demonstrated the feasibility of mEHT as a possible therapy for advanced breast cancer cases when standard therapies fail. Moreover, mEHT had no side effects and may be combined with various treatments for long‑term therapy.

“Oncothermia” (Modulated electro-hyperthermia) ― Present status and future development

Indikáció:
Bizonyítás: Review
Szerző: 
Masahiko Kanamori Tsutomu Sato Tomoko Shima Jun-Ichi Saitoh Gabor Andocs Takashi Kondo
Páciensek száma:
Terápia: mEHT
Év: 2021

Modulated electro-hyperthermia (mEHT) ‒ trade name: Oncothermia ‒ is an emerging curative treatment method in oncological hyperthermia. Although mEHT is similar to other classic hyperthermia methods to utilize temperature rise in tumor, there are several features; i.e. use precise impedance-matched, capacitive-coupled 13.56 MHz radiofrequency (RF) with amplitude modulation, in order to keep the tumor temperature below the cytotoxic range (<42 °C) but induce continuous temperature gradient on the tumor cell membrane. This in homogenous, non-equilibrium heating on the cell membrane induces programmed cancer cell death (apoptosis). mEHT effectiveness has been also proven in clinical studies, and has fewer side effects due to low RF output. Therefore, not only thermal effects but also non-thermal (temperature independent) effects of mEHT are important for considering the biological and clinical significance. Basic, preclinical and clinical reports have been published after “Oncothermia: Principles and Practices” by Szasz A. et al. In this review article these outcomes will be summarized and discuss on the further possibilities and problems of mEHT.

Modulated electro‑hyperthermia with weekly paclitaxel or cisplatin in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: The KGOG 3030 trial

Indikáció: Gynecology
Bizonyítás:
Szerző: 
Kidong Kim Jae‑Hoon Kim Seung Cheol Kim Yong Beom Kim Byung‑Ho Nam Jae Hong No Hanbyoul Cho Woong Ju Dong Hoon Suh Yun Hwan Kim
Páciensek száma: 12
Terápia: mEHT
Év: 2021

The study (KGOG 3030) aimed to evaluate the safety of modulated electro‑hyperthermia (mEHT) therapy with weekly administration of paclitaxel or cisplatin in female patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma. A total of 12 patients were randomized into the paclitaxel or cisplatin arm at a 1:1 ratio. Patients received weekly administration of paclitaxel (70 mg/m2) or cisplatin (40 mg/m2) intravenously on days 1, 8 and 15, and underwent mEHT therapy for 1 h on days 1, 4, 8, 11, 15, 18, 21 and 24 for each 4‑week cycle. The primary endpoint was the occurrence of dose‑limiting toxicity (DLT). The secondary endpoints were treatment‑emergent adverse events (TEAEs), objective response rate, carbohydrate antigen 125 (CA125) response rate, progression‑free survival (PFS) and overall survival (OS). In total, 16 patients were recruited, but four patients dropped out. None of the 12 remaining patients (6 each in the two arms) experienced DLT. Overall, 0 and 4 grade 3 TEAEs (anemia, nausea, neutrophil count decreased and platelet count decreased) occurred in the paclitaxel and cisplatin arm, respectively. Furthermore, one confirmed partial response and two CA125 responses were observed in the cisplatin arm. The median PFS time in the paclitaxel and cisplatin arms was 3.0 months (range, 1.7‑4.6 months) and 6.8 months (range, 3.9‑11.8 months), respectively, while the median OS time was 11.5 months (range, 8.4‑28.8+ months) and not reached (range, 3.9‑38.5+ months), respectively. In conclusion, mEHT therapy with weekly paclitaxel or cisplatin appeared safe and warrants further investigation. The present trial was registered with www.clinicaltrials.gov on January 22, 2015 (trial registration no. NCT02344095).

Marked local and distant response of heavily treated breast cancer with cardiac metastases treated by combined low dose radiotherapy, low dose immunotherapy and hyperthermia: a case report

Indikáció: Breast Cancer
Bizonyítás: Case report
Szerző: 
Mau-Shin Chi Jen-Hong Wu Suzun Shaw Ching-Jung Wu Liang-Kuang Chen Ho-Chi Hsu Kwan-Hwa Chi
Páciensek száma: 1
Terápia: CT+RT+mEHT
Év: 2021

Abstract: Breast cancer (BC) with cardiac metastases (CMs) is often associated with poor prognosis due to late stage of diagnosis. Palliative radiotherapy (RT) for CMs is generally used for symptomatic treatment and to maintain normal cardiac function. Palliative RT with hyperthermia (HT) or immunotherapy have been reported to be effective in prolonging the overall survival and progression-free survival in metastatic patients. In this case report, we present a heavily pretreated 51-year-old lady of metastatic BC presented with recurrent right breast mass with progressive exertional dyspnea caused by symptomatic CM. She received combined palliative low-dose palliative RT [20 Gray (Gy) in 12 fractions], combined with low-dose chemotherapy, biweekly HT treatment course, and low-dose “double blockade” immunotherapy by ipilimumab (0.3 mg/kg) and nivolumab (0.5 mg/kg). The irradiated right chest tumors responded rapidly to treatment. Interestingly, unirradiated metastatic lesions outside the RT and HT treatment field also demonstrated a sustained abscopal response. She continued monthly low-dose immunotherapy in conjunction with HT after RT. The posttreatment cardiac echography disclosed considerably reduced pericardial effusions without cardiac wall motion abnormalities. She remained stable for more than 6 months with no notable treatment-related toxicities. The combination of low-dose RT, low-dose immunotherapy, and HT protocol appears to be a safe method with promising efficacy in metastatic BC patients.

Beneficial effects of modulated electro-hyperthermia during neoadjuvant treatment for locally advanced rectal cancer

Indikáció: Rectal Cancer
Bizonyítás:
Szerző: 
Páciensek száma: 120
Terápia: mEHT
Év: 2021

Purpose: Modulated electro-hyperthermia (mEHT) may enhance the tumor response, although the effectiveness of combined neoadjuvant therapy remains unclear. Therefore, we investigated the role of mEHT with neoadjuvant therapy for locally advanced rectal cancer. Materials and methods: Clinical data were analyzed for 120 patients who received neoadjuvant treatment for locally advanced rectal cancer (T3/4 or Nþ, M0) from May 2012 to December 2017. Capecitabine or 5-fluorouracil was administered along with radiotherapy. Patients were categorized into mEHT group (62 patients) and non-mEHT group (58 patients) depending on whether mEHT was added. Surgery was performed 6–8 weeks after the end of radiotherapy. Results: The median age was 59 years (range, 33–83). The median radiation dose was significantly less for mEHT group (40 Gy) than for non-mEHT group (50.4 Gy). In mEHT group, 80.7% showed down-staging compared with 67.2% in non-mEHT group. For large tumors of more than 65 cm3 (mean), improved tumor regression was observed in 31.6% of mEHT group compared with 0% of non-mEHT group (p¼.024). The gastrointestinal toxicity rate of mEHT group was 64.5%, which was found to be statistically significantly less than 87.9% of non-mEHT group (p¼.010). The 2-year disease-free survival was 96% for mEHT group and 79% for non-mEHT group (p¼.054). Conclusion: The overall mEHT group had a comparable response and survival using less radiation dosing compared with standard care; the subgroup with large tumors showed improved efficacy for tumor regression after mEHT.

Evidence based tools to improve efficiency of currently administered oncotherapies for tumors of the hepatopancreatobiliary system

Indikáció:
Bizonyítás:
Szerző: 
Herold Z. Szasz A. Dank M.
Páciensek száma:
Terápia:
Év: 2021

Hepatopancreatobiliary tumors are challenging to treat, and the advanced or metastatic forms have a very low 5-year survival rate. Several drug combinations have been tested, and new therapeutic approaches have been introduced in the last decades, including radiofrequency and heat based methods. Hyperthermia is the artificial heating of tumors by various biophysical methods that may possess immunostimulant, tumoricidal, and chemoradiotherapy sensitizer effects. Both whole-body and regional hyperthermia studies have been conducted since the 1980s after the introduction of deep-seated tumor hyperthermia techniques. Results of the effects of hyperthermia in hepatocellular and pancreatic cancer are known from several studies. Hyperthermia in biliary cancers is a less investigated area. High local and overall responses to treatment, increased progression-free and overall survival, and improved laboratory and quality-of-life results are associated with hyperthermia in all three tumor types. With the evolution of chemotherapeutic agents and the introduction of newer techniques, the combination of adjuvant hyperthermia with those therapies is advantageous and has not been associated with an increase in alarming adverse effects. However, despite the many positive effects of hyperthermia, its use is still only known at the experimental level, and its concomitant utilization in routine cancer treatment is not certain because of the lack of thorough clinical studies.

Herold Z., Szasz A.M., Dank M., Evidence based tools to improve efficiency of currently administered oncotherapies for tumors of the hepatopancreatobiliary system. World J Gastrointest Oncol 2021; 13(9): 1109-1120 [DOI: 10.4251/wjgo.v13.i9.1109]

Evidence based tools to improve efficiency of currently administered oncotherap…

Suppression of Metastatic Melanoma Growth in Lung by Modulated Electro-Hyperthermia Monitored by a Minimally Invasive Heat Stress Testing Approach in Mice

Indikáció: Lung cancer
Bizonyítás:
Szerző: 
Mbuotidem Jeremiah Thomas Eniko Major Anett Benedek ldikó Horváth Domokos Máthé Ralf Bergmann Attila Marcell Szász Tibor Krenács Zoltán Benyó
Páciensek száma:
Terápia: mEHT
Év: 2020

Simple Summary
The lung is the most frequent site of distant melanoma metastases. Metastases of melanoma in the lungs offer a very poor prognosis, with a 5-year survival rate of below 10%. Hyperthermic therapies including modulated electro-hyperthermia (mEHT) in clinical settings have been used to improve the efficacy of radiotherapy, chemotherapy, and immunotherapy of tumors. In this study, we focused primarily on the optimization of mEHT for targeted lung treatment of mice lungsburdenedwithB16F10melanomapulmonarymetastases,withaparticularfocusonelucidating the mechanism of action of mEHT on treated melanoma cells while investigating any potential treatment-relatedsideeffectsonnormallungtissue. mEHTshowedevidenceofsignificantanti-tumor effects as demonstrated by the reduced number of pulmonary metastatic nodules, DNA damage response, downregulation of Ki67 expression, higher immune cell infiltration, and upregulation of p21waf1 expression in mEHT-treated tumors.

Abstract
Modulated electro-hyperthermia (mEHT) is a novel complementary therapy in oncology which is based on the higher conductivity and permittivity of cancerous tissues due to their enhanced glycolytic activity and ionic content compared to healthy normal tissues. We aimed to evaluate the potential of mEHT, inducing local hyperthermia, in the treatment of pulmonary metastatic melanoma. Our primary objective was the optimization of mEHT for targeted lung treatment as well as to identify the mechanism of its potential anti-tumor effect in the B16F10 mouse melanoma pulmonarymetastasesmodelwhileinvestigatingthepotentialtreatment-relatedsideeffectsofmEHT on normal lung tissue. Repeated treatment of tumor-bearing lungs with mEHT induced significant anti-tumor effects as demonstrated by the lower number of tumor nodules and the downregulation of Ki67 expression in treated tumor cells. mEHT treatment provoked significant DNA double-strand breaks indicated by the increased expression of phosphorylated H2AX protein in treated tumors, although treatment-induced elevation of cleaved/activated caspase-3 expression was insignificant, suggesting the minimal role of apoptosis in this process. The mEHT-related significant increase in p21waf1 positive tumor cells suggested that p21waf1-mediated cell cycle arrest plays an important role in the anti-tumor effect of mEHT on melanoma metastases. Significantly increased CD3+, CD8+ T-lymphocytes, and F4/80+CD11b+ macrophage density in the whole lung and tumor of treated animals emphasizes the mobilizing capability of mEHT on immune cells. In conclusion, mEHT can reduce the growth potential of melanoma, thus offering itself as a complementary therapeutic option to chemo- and/or radiotherapy.

A randomized phase II trial of best supportive care with or without hyperthermia and vitamin C for heavily pretreated, advanced, refractory non-small-cell lung cancer

Indikáció: Lung cancer
Bizonyítás: Phase I.
Szerző: 
Junwen Ou Xinyu Zhu Pengfei Chen Yanping Du Yimin Lu Xiufan Peng Shuang Bao Junhua Wang Xinting Zhang Tao Zhang Clifford L.K. Pang
Páciensek száma: 97
Terápia: IVC + mEHT + BSC
Év: 2020

Abstract

Our previous study indicated that intravenous vitamin C (IVC) treatment concurrent with modulated electrohyperthermia (mEHT) was safe and improved the quality of life (QoL) of non-small-cell lung cancer (NSCLC) patients. The aim of this trial was to further verify the efficacy of the above combination therapy in previously treated patients with refractory advanced (stage IIIb or IV) NSCLC. A total of 97 patients were randomized to receive IVC and mEHT plus best supportive care (BSC) (n = 49 in the active arm, receiving 1 g/kg * d IVC concurrently with mEHT, three times a week for 25 treatments in total) or BSC alone (n = 48 in the control arm). After a median follow-up of 24 months, progression-free survival (PFS) and overall survival (OS) were significantly prolonged by combination therapy compared to BSC alone (PFS: 3 months vs 1.85 months, P < 0.05; OS: 9.4 months vs 5.6 months, P < 0.05). QoL was significantly increased in the active arm despite the advanced stage of disease. The 3-month disease control rate after treatment was 42.9% in the active arm and 16.7% in the control arm (P < 0.05). Overall, IVC and mEHT may have the ability to improve the prognosis of patients with advanced NSCLC.

Analysis of the effects of mEHT on the treatmentrelated toxicity and quality of life of HIV-positive cervical cancer patients

Indikáció: Cervical cancer
Bizonyítás: Phase III
Szerző: 
Carrie Anne Minnaar Jeffrey Allan Kotzen Thanushree Naidoo Mariza Tunmer Vinay Sharma Mboyo-Di-Tamba Vangu Ans Baeyens
Páciensek száma:
Terápia: CRT+mEHT
Év: 2020

ABSTRACT
Introduction: HIV infection is associated with increased treatment-related toxicity and worse outcomes in locally advanced cervical cancer patients (LACC), especially in resource-constrained settings. Local control (LC) in a phase III randomized, controlled trial investigating modulated electro-hyperthermia (mEHT) on LACC patients in South Africa (ethics registration: M120477/M190295), was significantly higher in participants randomized to receive chemoradiotherapy (CRT) with mEHT compared to CRT alone (stratum: HIV status, accounting for age and stage). This analysis investigates whether mEHT adds to the toxicity profile of CRT in HIV-positive LACC participants.
Methods: Inclusion criteria: signed informed consent; International Federation of Gynecology and Obstetrics stages IIB to IIIB squamous cell carcinoma of the cervix; HIV-positive patients: CD4 count >200 cell/mL/on antiretroviral treatment for >6 months; eligible for CRT with radical intent. Recruitment: January 2014 to November 2017 (ClinicalTrials.gov: NCT03332069). Acute toxicity (evaluated using CTCAE v4 criteria) and quality of life (according to EORTC forms) in 206 participants randomized for treatment were evaluated alongside the LC results to determine safety and efficacy in HIV-positive participants.
Results: Compliance to mEHT treatment was high (97% completed 8 treatments) with no significant differences in CRT-related toxicity between treatment groups or between HIV-positive and -negative participants. Adverse events attributed to mEHT were minor, even in obese patients, and did not affect CRT compliance. Participants treated with mEHT reported improved fatigue, pain, emotional and cognitive functioning.
Conclusion: mEHT did not cause unexpected CRT-related toxicities and is a safe treatment modality for HIV-positive patients, with minor limitations regarding body weight, even in a low-resource setting.

Feasibility of Modulated Electro-Hyperthermia in Preoperative Treatment for Locally Advanced Rectal Cancer: Early Phase 2 Clinical Results

Indikáció: Rectal Cancer
Bizonyítás: Phase I
Szerző: 
S H You S Kim
Páciensek száma: 60
Terápia: mEHT
Év: 2020

Abstract: Despite advances in the multimodal approach for rectal cancer, treatment-related side effects remain an important issue. From this perspective, a prospective trial was performed to investigate the feasibility of modulated electro-hyperthermia (mEHT) as a concomitant boost to preoperative chemoradiation in locally advanced rectal cancer. Seventy-six patients with cT3-4 or cT2N+ rectal cancer were enrolled consecutively. Whole pelvic radiotherapy of 40 Gy was delivered with a 2-Gy daily fraction. mEHT with 13.56 MHz frequency was boosted on a twice-weekly schedule concurrently with intravenous 5-fluorouracil or oral capecitabine. Surgical resection was planned 6-8 weeks after radiotherapy. The primary endpoint was the non-inferior treatment response rate assessed by pathologic downstaging and tumor regression. The secondary endpoint was acceptable toxicity during the preoperative treatment period. Sixty patients completed the planned treatment schedule. T- and N-downstaging was demonstrated in 40 patients (66.7%) and 53 patients (88.3%), respectively. Pathologic complete response was noted in 15.0% (9 patients) and 76.7% (46 patients) for T-stage and N-stage, respectively. Total or near total tumor regression was observed in 20 patients (33.3%). Grade ≥3 toxicity occurred only in hematologic assessment; one case (1.7%) of leukopenia and one case (1.7%) of anemia. Sixteen patients (26.7%) developed thermal toxicity, which was mostly Grade 1 (15 patients, 93.8%). The relatively low dose of 40 Gy radiation showed comparable pathologic treatment outcomes and tolerable toxicity profiles with the addition of mEHT, which may potentially replace part of the radiation dose in neoadjuvant treatment for rectal cancer.

Survival Outcomes of Metabolically Supported Chemotherapy Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy in Advanced Gastric Cancer

Indikáció: Gastric Cancer
Bizonyítás:
Szerző: 
MS Iyikesici
Páciensek száma: 22
Terápia: Chemotherapy, Ketogenic Diet, Hyperthermia, Hyperbaric Oxygen Therapy
Év: 2020

Abstract:

Background: Survival outcomes are still far from being satisfactory in patients with advanced gastric cancer, despite availability of novel chemotherapeutic regimens. Aim: This study evaluated the outcomes of patients with advanced gastric cancer who received chemotherapy along with additional treatment modalities targeting multiple tumor cell vulnerabilities. Materials and Methods: A total of 24 patients diagnosed with stage III–IV locally advanced or metastatic gastric adenocarcinoma that received metabolically supported chemotherapy (MSCT) combined with ketogenic diet, local hyperthermia, and hyperbaric oxygen therapy (HBOT) between April 2014 and October 2017 were included in this retrospective study. Survival outcomes were evaluated. Results: In 22 patients (88.0%), complete response was achieved. Mean duration of follow‑up was 23.9 ± 12.7 months. Mean overall survival was 39.5 months (95% confidence interval [CI]: 28.1–51.0) and mean progression free survival was 36.5 months (95% CI: 25.7–47.2). No problems were encountered due to fasting, hypoglycemia, ketogenic diet, hyperthermia or HBOT. Conclusions: The combination treatment used in this study (MSCT together with a ketogenic diet, hyperthermia and HBOT) appears to be promising in the treatment of advanced gastric cancer. Further research and comparative clinical trials are warranted to support and standardize this novel treatment protocol. Keywords: Advanced gastric cancer, hyperbaric oxygen therapy, hyperthermia, ketogenic diet, metabolically supported chemotherapy

Potentiation of the Abscopal Effect by Modulated Electro-Hyperthermia in Locally Advanced Cervical Cancer Patients

Indikáció: Cervical cancer
Bizonyítás: Phase III
Szerző: 
Carrie Anne Minnaar Jeffrey Allan Kotzen Olusegun Akinwale Ayeni Mboyo-Di-Tamba Vangu Ans Baeyens
Páciensek száma: 108
Terápia: mEHT
Év: 2020

ABSTRACT
Background:
 A Phase III randomized controlled trial investigating the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for locally advanced cervical cancer patients is being conducted in South Africa (Human Research Ethics Committee approval: M1704133; ClincialTrials.gov ID: NCT03332069). Two hundred and ten participants were randomized and 202 participants were eligible for six month local disease control evaluation. Screening 18F-FDG PET/CT scans were conducted and repeated at six months post-treatment. Significant improvement in local control was reported in the mEHT group and complete metabolic resolution (CMR) of extra-pelvic disease was noted in some participants. We report on an analysis of the participants with CMR of disease inside and outside the radiation field.
Method: Participants were included in this analysis if nodes outside the treatment field (FDG-uptake SUV>2.5) were visualized on pre-treatment scans and if participants were evaluated by 18F-FDG PET/CT scans at six months post-treatment.
Results: One hundred and eight participants (mEHT: HIV-positive n = 25, HIV-negative n = 29; Control Group: HIV-positive n = 26, HIV-negative n = 28) were eligible for analysis. There was a higher CMR of all disease inside and outside the radiation field in the mEHT Group: n = 13 [24.1%] than the control group: n = 3 [5.6%] (Chi squared, Fisher’s exact: p = 0.013) with no significant difference in the extra-pelvic response to treatment between the HIV-positive and -negative participants of each group.
Conclusion: The CMR of disease outside the radiation field at six months post-treatment provides evidence of an abscopal effect which was significantly associated with the addition of mEHT to treatment protocols. This finding is important as the combined synergistic use of radiotherapy with mEHT could broaden the scope of radiotherapy to include systemic disease.

Putative Abscopal Effect in Three Patients Treated by Combined Radiotherapy and Modulated Electrohyperthermia

Indikáció: Multiple
Bizonyítás:
Szerző: 
Mau-Shin Chi Minesh P. Mehta Kai-Lin Yang Hung-Chih Lai Ying-Chu Lin Hui-Ling Ko Yu-Shan Wang Kuang-Wen Liao Kwan-Hwa Chi
Páciensek száma: 33
Terápia: RT+mEHT
Év: 2020

ABSTRACT
Purpose: 
True abscopal responses from radiation therapy are extremely rare; the combination of immune checkpoint inhibitors with radiation therapy has led to more reports of the abscopal effect, but even in this setting, the genuine magnitude remains unknown and is still considered generally uncommon. We report the occurrence of what appears to be putative, durable abscopal tumor responses with associated auto-immune systemic reactions resulting from the combination of local radiotherapy (RT) and modulated electrohyperthermia (mEHT).

Materials and Methods: Data from advanced cancer patients treated palliatively with RT and mEHT between January and December 2017 were collected as part of a post-marketing safety monitoring program of mEHT therapy. We specified a minimum RT dose of 30Gy and at least four mEHT treatments for reporting toxicities, which was the primary aim of the larger study.

Results: Thirty-three patients treated with RT and mEHT, both applied to the same lesion, were included. The median RT dose was 45.5Gy in 20 fractions (fxs) and the median number of mEHT treatments was 12 (range, 4–20). Most patients had subsequent systemic therapy after one course of RT and mEHT. Three patients (9.1%) developed autoimmune toxicities. Case number 1 received RT and mEHT only; case number 2 had two cycles of concurrent low dose chemotherapy during RT; and case number 3 received concurrent immune checkpoint inhibitors. None of the three patients received any further systemic treatment due to obvious treatment-related autoimmune reactions which occurred rapidly after RT; one had autoimmune hepatitis, one had dermatitis herpetiformis and the third developed severe myasthenia gravis. Interestingly, what we surmise to be long-lasting abscopal responses outside the irradiated area, were noted in all three patients.

Conclusion: RT combined with mEHT could putatively result in enhancing immune responsiveness. These preliminary observational findings lead to the generation of a hypothesis that this combination induces both an in-situ, tumor-specific immune reaction and an anti-self-autoimmune reaction, in at least a small proportion of patients, and of those who experience the auto-immune response, tumor response is a concomitant finding. Mechanisms underlying this phenomenon need to be investigated further.

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy

Indikáció: Immuno-oncology
Bizonyítás:
Szerző: 
Volker Schirrmacher Stefaan van Gool Wilfried Stuecker
Páciensek száma:
Terápia:
Év: 2019

Abstract
Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus(NDV)asabiologicalagentwithpotentialtobreaktherapyresistance. Thisavianviruscombines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11describedimmunestimulatoryproperties. FiftyyearsofclinicalapplicationofNDVgivewitnessto the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the successful production of NDV according to Good Manufacturing Practice (GMP). Based on this, IOZK in Cologne, Germany, obtained a GMP certificate for the production of a dendritic cell vaccine loadedwithtumorantigensfromalysateofpatient-derivedtumorcellstogetherwithimmunological dangersignalsfromNDVforintracutaneousapplication. Thisupdateincludessinglecasereportsand retrospective analyses from patients treated at IOZK. The review also presents future perspectives, including the concept of in situ vaccination and the combination of NDV or other oncolytic viruses with checkpoint inhibitors.
Keywords: NDV; viral oncolysis; immunogenic cell death; type I interferon; dendritic cells; active-specific immunotherapy; bispecific antibodies; gene therapy; checkpoint inhibition; T cell costimulation; RIG-I; IFNAR

Long-Term Survival Outcomes of Metabolically Supported Chemotherapy with Gemcitabine-Based or FOLFIRINOX Regimen Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy in Metastatic Pancreatic Cancer

Indikáció: Pancreas
Bizonyítás:
Szerző: 
Mehmet Salih Iyikesici
Páciensek száma: 25
Terápia:
Év: 2019

Abstract

Background: Despite introduction of new chemotherapeutic agents, outcomes of patients with metastatic pancreatic cancer are still poor. Metabolically supported chemotherapy (MSCT) is a novel approach targeting dysregulated energy mechanism of the tumor cell.
Objectives: This study aimed to examine the efficacy of metabolically supported administration of chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy (HBOT) in patients with metastatic pancreatic cancer.
Method: This retrospective observational study included 25 patients with metastatic pancreatic ductal carcinoma (stage IV) who received MSCT (either gemcitabine-based or FOLFIRINOX regimen administered concomitantly with induced hypoglycemia) plus ketogenic diet, hyperthermia, and HBOT combination. Survival outcomes were evaluated.
Results: During the mean follow-up duration of 25.4 ± 19.3 months, median overall survival and median progression-free survival were 15.8 months (95% CI, 10.5–21.1) and 12.9 months (95% CI, 11.2–14.6), respectively. Age and gender did not have any effect on overall survival (p > 0.05 for all).
Conclusions: MSCT administered together with ketogenic diet, hyperthermia, and HBOT appears to be a viable option with the potential to improve survival outcomes in patients diagnosed with metastatic pancreatic cancer. Further research, particularly with larger comparative clinical trials, is warranted.

Modulated Electro-Hyperthermia as Palliative Treatment for Pancreatic Cancer: A Retrospective Observational Study on 106 Patients

Indikáció: Pancreas
Bizonyítás: Review
Szerző: 
Giammaria Fiorentini Donatella Sarti Virginia Casadei Carlo Milandri Patrizia Dentico Andrea Mambrini Roberto Nani Caterina Fiorentini Stefano Guadagni
Páciensek száma: 106
Terápia: CT+RT+mEHT
Év: 2019

Abstract

Background: Pancreatic adenocarcinoma has a poor prognosis, resulting in a <10% survival rate at 5 years. Modulated electro-hyperthermia (mEHT) has been increasingly used for pancreatic cancer palliative care and therapy. Objective: To monitor the efficacy and safety of mEHT for the treatment of advanced pancreatic cancer. Methods: We collected data retrospectively on 106 patients affected by stage III-IV pancreatic adenocarcinoma. They were divided into 2 groups: patients who did not receive mEHT (no-mEHT) and patients who were treated with mEHT. We performed mEHT applying a power of 60 to 150 W for 40 to 90 minutes. The mEHT treatment was associated with chemotherapy and/or radiotherapy for 33 (84.6%) patients, whereas 6 (15.4%) patients received mEHT alone. The patients of the no-mEHT group received chemotherapy and/or radiotherapy in 55.2% of cases. Results: Median age of the sample was 65.3 years (range = 31-80 years). After 3 months of therapy, the mEHT group had partial response in 22/34 patients (64.7%), stable disease in 10/34 patients (29.4%), and progressive disease in 2/34 patients (8.3%). The no-mEHT group had partial response in 3/36 patients (8.3%), stable disease in 10/36 patients (27.8%), and progressive disease in 23/36 patients (34.3%). The median overall survival of the mEHT group was 18.0 months (range = 1.5-68.0 months) and 10.9 months (range = 0.4-55.4 months) for the non-mEHT group. Conclusions: mEHT may improve tumor response and survival of pancreatic cancer patients.

Feasibility study of metabolically supported chemotherapy with weekly carboplatin/paclitaxel combined with ketogenic diet, hyperthermia and hyperbaric oxygen therapy in metastatic nonsmall cell lung cancer

Indikáció: Lung
Bizonyítás:
Szerző: 
Mehmet Salih Iyikesici
Páciensek száma: 44
Terápia:
Év: 2019

ABSTRACT
Background: Previous evidence suggests that metabolically supported chemotherapy (MSCT), ketogenic diet, hyperthermia and hyperbaric oxygen therapy (HBOT) could all target vulnerabilities of cancer cells. This study aimed to evaluate the efficacy and the tolerability of this combination therapy in the treatment of stage IV non-small cell lung cancer (NSCLC).
Methods: Forty-four NSCLC patients with distant metastasis that received MSCT (administration of chemotherapy regimen following induced hypoglycemia) plus ketogenic diet, hyperthermia and HBOT combination were included in this retrospective study. Survival and treatment response rates as well as toxicities were evaluated.
Results: Overall response rate (ORR, complete response plus partial response) was 61.4%; whereas, 15.9% and 22.7% of patients had stable disease (SD) and progressive disease (PD), respectively. Mean overall survival (OS) and progression-free survival (PFS) was 42.9months (95% CI: 34.0–51.8) and 41.0months (95% CI: 31.1–50.9), respectively. A higher Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 2) was associated with worse OS and PFS. Patients received chemotherapy cycles with acceptable toxicity and adverse events. No problems were encountered due to fasting, hypoglycemia, ketogenic diet, hyperthermia or hyperbaric oxygen therapy.
Conclusions: Findings of this study suggest that MSCT combined with other modalities targeting multiple pathways and cellular vulnerabilities may bring about remarkable improvements in survival outcomes and treatment response rates in metastatic NSCLC, without additional safety concerns. Large comparative studies are warranted to draw robust conclusions.

Defining Characteristics of Nodal Disease on PET/CT Scans in Patients With HIV-Positive and-Negative Locally Advanced Cervical Cancer in South Africa

Indikáció: Cervical cancer
Bizonyítás:
Szerző: 
Carrie Anne Minaar Ans Baeyens Olusegun Akinwale Ayeni Jeffrey Allan Kotzen Mboyo-Di-Tamba Vangu
Páciensek száma:
Terápia:
Év: 2019

Abstract 
Literature reports increased FDG nodal uptake in HIV-positive patients. Our aim is to identify differences in presentation and characteristics of FDG-avid lymph nodes between HIV-positive and HIV-negative locally advanced cervical cancer (LACC) patients in our clinical setting. We evaluated 250 pre-treatment 18F-FDG PET/CT imaging studies from women screened for a phase III randomised controlled trial investigating modulated electro-hyperthermia as a radiosensitiser (Ethics approval: M120477). The number of nodes; size; maximum standardised uptake value (SUVmax); symmetry; and relationship between nodal size and SUVmax uptake, were assessed by region and by HIV status. In total, 1314 nodes with a SUVmax ≥ 2.5 were visualised. Of 128(51%) HIV-positive participants, 82% were on antiretroviral therapy (ART) and 10 had a CD4 count <200 cells/mL. Overall pattern of presentation and nodal characteristics were similar between HIV-positive and -negative groups and the uniformity in presentation of the nodes draining the cervix strongly suggests these nodes may be attributed to malignancy rather than HIV infection. Novel findings: HIV infection is associated with: >four nodes visualised in the neck, symmetrical inguinal lymph nodes, increased rates of supraclavicular node visualisation; FDG-avid axillary nodes were more common, but not exclusive, in HIV-positive participants. 18F-FDG PET/CT is a reliable staging method for LACC in HIV-positive patients who are not in acute stages of HIV infection, have a CD4 count >200 cells/mL, and/or are on ART and there is a potential risk of underestimating metastatic spread by attributing increased nodal metabolic activity to HIV infection in these patients.

Fluctuations hypothesize the new explanation of meridians in living systems

Indikáció: Non-oncology
Bizonyítás:
Szerző: 
Szigeti Gy Szasz A
Páciensek száma:
Terápia:
Év: 2019

Abstract 

Biosystems are complex. Their physiology is well-controlled with various negative feedback signals and processes, it describes by opposite interfering effects which are characterized in the Eastern philosophy by Yin-Yang (Y-Y) pairs. Y-Y pairs could be described by the promoter-suppressor pairs in a wide range of physiologic signals creating the homeostasis of the complex system. This type of control appears as fluctuations from the average (mean) value of the signal. The mean carries an ineluctable fluctuation (called pink-noise or 1/f noise). All signals in homeostasis have equal entropy (SE = 1.8), which is the character of the complex equilibrium. The various controlling opposite signals (Y-Y) have different time-scales which change by aging. The processes with smaller time-scale are degraded by aging, but the pink-noise ensures that the deviations of the signals of the healthy homeostatic system remain constant. Meridians are connected to the general transport systems that combined the material and the information transport with the considerable transport networks, like blood, lymph, nerve, cell-junctions, mesenchymal “ground substance” cytoskeletons. The meridians in this meaning only virtual line averaged from multiple realized paths to connect two acupuncture points by the material, energy and information transport processes. The meridian network is designed by various coupling points (acupoints), which could be perturbed by actuating stimulus. Our objective is to describe the meridian system from complexity point of view.

Thermal and Nonthermal Effects of Radiofrequency on Living State and Applications as an Adjuvant with Radiation Therapy

Indikáció: Non-oncology
Bizonyítás: Review
Szerző: 
Andras Szasz
Páciensek száma:
Terápia:
Év: 2019

Abstract

One of the most frequently applied bioelectromagnetic effects is the deep heating of living species with electromotive force energy. Despite its long history, hyperthermia is a rarely applied oncotherapy because of controversial results and complicated control. The challenge in clinical studies of oncological hyperthermia is the disharmony of the local response and local control with overall survival. Both whole‑body (complete isothermia for the body) and local (isothermia for the chosen target) heating show excellent local effects; however, this is not followed with the expected elongation of survival time. A possible solution could be nonisothermal heating to the heterogeneity of the malignancy itself. The distinguishing parameters to select the target are the electromagnetic properties of the malignant tissue together with the physiological differences between malignant cells and their healthy counterparts. Selection could allow for cellular targeting, generating
natural reactions, such as programmed cell death (apoptosis) followed by immunogenic cell death involving extended immune reactions. This complex method is a new kind of hyperthermia, named modulated electrohyperthermia (tradename oncothermia). The selective, nonequilibrium energy absorption is well synergized with modern radiation therapies, presenting a solution of an active and controllable tumor‑specific immune reaction and subsequent abscopal effects.

Phase I/II clinical trial of modulated electro-hyperthermia treatment in patients with relapsed, refractory or progressive heavily treated ovarian cancer

Indikáció: Gynecology
Bizonyítás: Phase I/II
Szerző: 
Heon Jong Yoo Myong Cheol Lim Sang-Soo Seo Sokbom Kang Jungnam Joo Sang-Yoon Park
Páciensek száma: 19
Terápia: mEHT
Év: 2019

Abstract

Objective: To determine the maximal tolerated dose (MTD) of modulated electro-hyperthermia (mEHT) treatment and to reveal whether mEHT treatment is feasible and effective as second-line therapy in recurrent and progressive ovarian cancer.

Methods: Patients were treated with mEHT with dose escalation during the first cycle (two sessions each week for three weeks) to determine the MTD. Additional cycles were carried out with the determined dose. Dose limiting toxicity (DLT) was defined grade ≥ 2: skin burns and inability to endure the hyperthermic state of the study. The Fact-O quality of life scale was used to assess health-related well-being.

Results: Nineteen patients with recurrent and progressive ovarian cancer were enrolled. In the first cycle of mEHT treatment, no patient developed DLT with applied power up to 110 W, 130 W, and 150 W/day; the 150W was the maximal applied power. Stable disease was observed in only one patient (12.5%). With median progression of 4.0 months (range, 2–17 months), 18 patients (95%) demonstrated disease progression. With median overall survival of 8.0 months (range, 2–32 months), 18 patients (95%) had died. Physical well-being scores were significantly decreased over the study period, although social, emotional, and functional well-being scores did not significantly change.

Conclusions: The mEHT treatment was feasible in patients with recurrent or progressive ovarian cancer without any complication and optimal dose of mEHT treatment was up to 150W for 1 hour/ day.

Integrative Therapeutic Options for Treating Stage Four Breast Cancer

Indikáció: Breast Cancer
Bizonyítás:
Szerző: 
Magda Havas
Páciensek száma:
Terápia: Integrative Therapeutic Options
Év: 2019

Abstract
Traditional Western medicine treats breast cancer – the most commonly occurring cancer in women with some combination of surgery, chemotherapy and/or radiation therapy. Few doctors’ council their patients to use complementary modalities and some forbid their use. However, complementary therapies in the form of agents or activities that minimize exposure to toxins, detoxify the body, strengthen the immune system, increase cellular energy, promote circulation, reduce inflammation, alleviate pain and create a hostile internal environment for the growth of cancerous cells without damage to normal healthy cells have been shown to enhance survival and reduce morbidity of cancer patients. Some of these complementary modalities are presented here as options for both oncologists and patients to consider.

The effect of modulated electro-hyperthermia on local disease control in HIV-positive and -negative cervical cancer women in South Africa: Early results from a phase III randomised controlled trial

Indikáció: Cervical cancer
Bizonyítás: Phase III
Szerző: 
Carrie Anne Minnaar Jeffrey Allan Kotzen Olusegun Akinwale Ayeni Thanushree Naidoo Mariza Tunmer Vinay Sharma Mboyo-Di-Tamba Vangu Ans Baeyens
Páciensek száma: 271
Terápia: CT+mEHT
Év: 2019

Background
The global burden of cervical cancer remains high with the highest morbidity and mortality rates reported in developing countries. Hyperthermia as a chemo- and radiosensitiser has shown to improve treatment outcomes. This is an analysis of the local control results at six months post-treatment of patients enrolled in an ongoing study investigating the effects of the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for the treatment of HIV-positive and -negative cervical cancer patients in a low-resource setting.

Methods
This ongoing Phase III randomised controlled trial, conducted at a state hospital in Johannesburg, South Africa, was registered with the appropriate ethics committee. After signing an informed consent, participants with FIGO stages IIB to IIIB squamous cell carcinoma of the cervix were randomised to receive chemoradiotherapy with/without mEHT using a secure online random-sampling tool (stratum: HIV status) accounting for age and stage. Reporting physicians were blind to treatment allocation. HIV-positive participants on antiretroviral treatment, or with a CD4 count >200cell/μL were included. mEHT was administered 2/weekly immediately before external beam radiation. The primary end point is local disease control (LDC) and secondary endpoints are toxicity; quality of life analysis; and two year survival. We report on six month LDC, including nodes visualised in the radiation field on 18FFDG PET/CT (censored for six month survival), and six month local disease free survival (LDFS) (based on intention to treat). Trial status: Recruitment closed (ClinicalTrials.gov: NCT03332069).

Results
271 participants were recruited between January 2014 and November 2017, of which 210 were randomised for trial and 202 were available for analysis at six months post-treatment (mEHT: n = 101; Control: n = 101). Six month LDFS was higher in the mEHT Group (n = 39[38.6%]), than in the Control Group (n = 20[19.8%]); p = 0.003). LDC was also higher in the mEHT Group (n = 40[45.5%]) than the Control Group (n = 20[24.1%]); (p = 0.003).

Conclusion
Our results show that mEHT is effective as a chemo-radiosensitiser for cervical cancer, even in high risk a patients and resource-constrained settings.

Nanoparticles and nanothermia for malignant brain tumors, a suggestion of treatment for further investigations

Indikáció: Gliomas (advanced)
Bizonyítás:
Szerző: 
Prieto C Linares I
Páciensek száma:
Terápia: TSL+mEHT
Év: 2018

Abstract

The current treatment for brain tumors, such as glioblastoma multiforme (GBM), has not been developed enough yet in order to fully heal them. The main causes are the lack of specificity of the treatments, the difficulty of passage of drugs through the blood-brain barrier, heterogeneity and tumor aggressiveness, and widespread dissemination in the brain. The application of nanoparticles (Nps) have been a breakthrough for both diagnostic imaging and targeted therapies. There have been numerous studies with different types of Nps in brain tumors, but we have focused on thermosensitive liposomes, which are characterized by releasing the chemotherapeutic agent included within its lipophilic membranes through heat. Furthermore, increasing the temperature in brain tumors through hyperthermia has been proven therapeutically beneficial. Nanothermia or modulated-electro-hyperthermia (MEHT) is an improved technique that allows to create hot spots in nanorange at the membrane rafts, specifically in tumor cells, theoretically increasing the selectivity of the damage. In scientific records, experiments that combine both techniques (thermosensitive liposomes and nanothermia) have never been conducted. We propose a hypothesis for further research.

KEYWORDS:

GBM; Liposomes; MEHT; Nanoparticles; Termosensitive

Combined treatment with modulated electro-hyperthermia and an autophagy inhibitor effectively inhibit ovarian and cervical cancer growth

Indikáció: Gynecology
Bizonyítás:
Szerző: 
Wookyeom Yang Gwan Hee Han Ha-Yeon Shin Eun-Ju Lee Hanbyoul Cho Doo Byung Chay & Jae-Hoon Kim
Páciensek száma:
Terápia: Autophagy Inhibitor+mEHT
Év: 2018

Abstract

Purpose: Modulated electro-hyperthermia (mEHT), known as oncothermia, is an anticancer therapy that induces radiofrequency thermal damage to the cancer tissues. This study aimed to evaluate the potential effectiveness of mEHT as a therapeutic tool in ovarian and cervical cancer.

Materials and methods: We used both tumor-bearing mice and ovarian and cervical OVCAR-3, SK-OV-3, HeLa and SNU-17 cancer cell lines to investigate the effects of mEHT in vivo and in vitro, respectively, and determine whether it was enhanced by cotreatment with an autophagy inhibitor.

Results: We discovered that phosphorylation of p38, a stress-dependent kinase, was induced at the Thr180/Tyr182 residue in cancer cells exposed to mEHT. Apoptotic markers such as cleaved caspase-3 and poly-ADP ribose polymerase (PARP) were increased in OVCAR-3 and SNU-17 cells. Fluorescence-activated cell sorting (FACS) analysis showed a significant increase in the population of sub-G1 mEHT-exposed cells, which are dying and apoptotic cells. mEHT also reduced both weight and volume of xenograft tumors in mice transplanted with ovarian and cervical cancer cells and patient-derived cancer tissues. We determined that mEHT-induced cellular damage recovery was mediated by autophagy and, therefore, expectedly, cotreatment with mEHT and 3-methyladenine (3-MA), an autophagy inhibitor, more effectively inhibited cancer cell growth than individual treatment did.

Conclusions: mEHT treatment alone was sufficient to inhibit cancer growth, while a combined treatment with mEHT and an autophagy inhibitor amplified this inhibition effect.

Keywords: Modulated electro-hyperthermia, ovarian cancer, cervical cancer, autophagy inhibitor, anti-cancer effects

The effect of modulated electro-hyperthermia on temperature and blood flow in human cervical carcinoma

Indikáció: Temperature
Bizonyítás: Phase I
Szerző: 
Lee S-Y Kim J-H Han Y-H Cho D-H
Páciensek száma: 20
Terápia: mEHT
Év: 2018

Abstract

Introduction: Mild hyperthermia has been known to enhance the response of tumours to radiotherapy or chemotherapy by increasing tumour blood flow, thereby increasing tumour oxygenation or drug delivery. The purpose of this study was to assess the changes in temperature and blood flow in human cervical cancer in response to regional heating with modulated electro-hyperthermia (mEHT).

Methods: The pelvic area of 20 patients with cervical carcinoma was heated with mEHT. The peri-tumour temperature was measured using an internal organ temperature probe. The tumour blood flow was measured using 3D colour Doppler ultrasound by determining the peak systolic velocity/end-diastolic velocity ratio (S/D ratio) and the resistance index (RI) within blood vessels.

Results: The mean peri-tumour temperature was 36.7 ± 0.2 °C before heating and increased to 38.5 ± 0.8 °C at the end of heating for 60 min. The marked declines in RI and S/D values strongly demonstrated that heating significantly increased tumour blood perfusion.

Conclusions: Regional heating of the pelvic area with mEHT significantly increased the peri-tumour temperature and improved the blood flow in cervical cancer. This is the first demonstration that the blood flow in cervical cancer is increased by regional hyperthermia. Such increases in temperature and blood flow may account for the clinical observations that hyperthermia improves the response of cervical cancer to radiotherapy or chemotherapy.

The Induction of Immunogenic Cell Death (ICD) During Maintenance Chemotherapy and Subsequent Multimodal Immunotherapy for Glioblastoma (GBM)

Indikáció: Gliomas (advanced)
Bizonyítás: Retrospective study
Szerző: 
Van Gool SW Makalowski J Feyen O Prix L Schirrmacher V Stuecker W1
Páciensek száma: 115
Terápia: IMT+mEHT
Év: 2018

Abstract

The prognosis of Glioblastoma multiforme remains poor. Immunotherapy improved survival in a small fraction of patients. We studied the efficiency of multimodal immunotherapy as part of first line treatment for patients with GBM. Immunogenic Cell Death (ICD) was induced with Newcastle Disease Virus (NDV) and Modulated Electrohyperthermia (mEHT), and Dendritic Cell (DC) vaccinations loaded with autologous tumor proteins were performed. In a retrospective analysis of 60 adults, we detected 15 adults in whom NDV/mEHT were added at days 8/9/10 during Temozolomide Maintenance (TMZm) cycles, multimodal immunotherapy with NDV/mEHT/DC vaccinations were administered after TMZm, and further 3-day NDV/mEHT maintenance immunotherapy treatments were given thereafter. Median age was 60 years. Median Karnofsky was 90. There was no added toxicity due to immunotherapy. Median progression-free survival was 13 months (m). With a median follow up of 17m (ranging 4-30m), median overall survival was not reached, and estimated overall survival at 30m was 58% (95%CI: +27, -42). The detection of Apo10 protein epitope (Apo10) and Transketolase-like 1 (TKTL1) in monocytes, the mRNA expression level for PDL1 on circulating tumor cells, and the Th1/Th2 balance in CD4+ T cells showed a dynamic interaction between tumor cells and immune reactivity. The data suggest that the additional induction of ICD via NDV/mEHT during TMZm is beneficial in improving overall survival. While TMZm only targets dividing tumor cells, ICD targets dividing and non-dividing tumor cells. DC vaccination induces an antitumoral and anti-viral immune response which is maintained by the 3-day NDV/mEHT maintenance immunotherapy treatments.

Keywords: Newcastle disease virus; Modulated electrohyperthermia;
Glioblastoma; Immunogenic cell death; chemotherapy

Modulated Electrohyperthermia in Integrative Cancer Treatment for Relapsed Malignant Glioblastoma and Astrocytoma: Retrospective Multicenter Controlled Study

Indikáció: Gliomas (advanced)
Bizonyítás: Retrospective study
Szerző: 
Fiorentini G Sarti D Milandri C Dentico P Mambrini A Fiorentini C Mattioli G Casadei Guadagni S
Páciensek száma: 149
Terápia: mEHT
Év: 2018

Abstract

BACKGROUND:

There are interesting studies on glioma therapy with modulated electrohyperthermia (mEHT), which combines heat therapy with an electric field. Clinical researchers not only found the mEHT method feasible for palliation but also reported evidence of therapeutic response.

PURPOSE:

To study the efficacy and safety of mEHT for the treatment of relapsed malignant glioma and astrocytoma versus best supportive care (BSC).

METHODS:

We collected data retrospectively on 149 patients affected by malignant glioma and astrocytoma. Inclusion criteria were informed consent signed; >18 years old; histological diagnosis of malignant glioma or astrocytoma; relapsed after surgery, adjuvant temozolomide-based chemotherapy, and radiotherapy; and indication for treatment with mEHT in palliative setting. mEHT was performed with capacitive coupling technique keeping the skin surface at 26°C and the tumor temperature at 40°C to 42.5°C for > 90% of treatment duration (20-60 minutes). The applied power was 40 to 150 W using a step-up heating protocol. Results from patients treated with mEHT were compared with those treated with BSC.

RESULTS:

A total of 149 consecutive patients were enrolled in the study, 111 (74%) had glioblastoma multiforme (GBM), and 38 (26%) had astrocytoma (AST). mEHT was performed for 28 (25%) of GBM and 24 (63%) of AST patients. Tumor response at the 3-month follow-up was observed in 29% and 48% of GBM and AST patients after mEHT, and in 4% and 10% of GBM and AST patients after BSC, respectively. The survival rate at first and second year in the mEHT group was 77.3% and 40.9% for AST, and 61% and 29% for GBM, respectively. The 5-year overall survival of AST was 83% after mEHT versus 25% after BSC and 3.5% after mEHT versus 1.2% after BSC for GBM. The median overall survival of mEHT was 14 months (range 2-108 months) for GBM and 16.5 months (range 3-156 months) for the AST group. We observed 4 long-term survivors in the AST and 2 in the GBM group. Two of the long survivors in AST and 1 in GBM group were treated by mEHT.

CONCLUSIONS:

mEHT in integrative therapy may have a promising role in the treatment and palliation of relapsed GBM and AST.

KEYWORDS:

astrocytoma; modulated electrohyperthermia; relapsed malignant glioma; survival; tumor response

Comparing the Effectiveness of Pain Therapy (PT) and Modulated Electro-Hyperthermia (mEHT) Versus Pain Therapy Alone in Treating Patients With Painful Bony Metastases: an observational trial

Indikáció: Non-oncology
Bizonyítás:
Szerző: 
Virginia Casade Donatella Sarti Carlo Milandri Patrizia Dentico Stefano Guadagni Giammaria Fiorentini
Páciensek száma: 19
Terápia: PT + mEHT
Év: 2018

Overview

The aim of the trial is to compare the response, duration of pain relief and time to achieve pain relief after pain therapy (PT) with or without hyperthermia (mEHT) in patients with painful bony metastases. Cancer patients with bony metastases and a VAS score of ≥5 on a 0– 10 scale were treated with fentanyl patches (100 μg every three days) and zoledronic acid (4mg every 28 days) combined with mEHT (PT + mEHT)  versus PT alone. Hyperthermia was performed using the Oncotherm EHY2000 plus device with the maintenance of the target temperature for 60 minutes twice a week for 2 weeks. The primary endpoint was VAS = 0–2 after treatment and an ECOG performance status reduction of at least one point from baseline evaluation.  The study included 19 patients: 10 in the PT + mEHT group and 9 patients in the PT-alone group. The average age of the patients was 57 years (range 40–86). The median VAS for the PT + mEHT group was 8 at baseline and had decreased to 3, 1 and 2 at 1, 3 and 6 months after the start of mEHT respectively. The median VAS for the PT-alone group was 8 at baseline and was unchanged at the subsequent time points. The median ECOG of the PT + mEHT group was 2 at baseline and had decreased to 1, 1 and 0 at 1, 3 and 6 months after the start of mEHT respectively. The median ECOG for the PT-alone group was 2 at baseline and was unchanged at the subsequent time points. The addition of mEHT to PT significantly increases the pain control rate and ECOG compared to RT alone for painful bony metastases.

PD-1, PD-L1 and CTLA-4 in pregnancy-related – and in early-onset breast cancer: A comparative study

Indikáció:
Bizonyítás: Comparative study
Szerző: 
Ács B Madaras L Tőkés AM Kovács AK Kovács E
Páciensek száma: 42
Terápia: mEHT
Év: 2017

Abstract

PURPOSE:

We aimed to compare the immunohistochemical expression of PD-1, PD-L1 and CTLA-4 of pregnancy-related breast cancer (PRBC) and early onset non-PRBC (YWBC), and their prognosis prediction potential was correlated to that of conventional clinicopathological factors.

METHODS:

Twenty-one PRBC cases were paired with 21 YWBC in this matched case-control study. Immune-checkpoint markers (ICM) were evaluated with immunohistochemistry (IHC) on whole slides using the following antibodies: PD-1 (NAT-105), PD-L1 (28-8) and CTLA-4 (F-8). IHC score was defined as the percentage of positive cells, assessed separately among tumor cells, intratumoral lymphocytes and peritumoral lymphocytes.

RESULTS:

The optimal threshold of PD-L1 expression of tumor cells occurred at 10% for overall survival (OS, AUC = 0.847, p = 0.009), and at 1% for disease-free survival (DFS, AUC = 0.795, p = 0.010). For PD-L1 expression on intratumoral lymphocytes, the optimal cut-off was 1% (AUC = 0.763, p = 0.048). Considering PD-1, PD-L1 and CTLA-4 expression, no significant difference occurred between PRBC and YWBC (p > 0.05 for all comparisons). PD-1, PD-L1 expressed on peritumoral lymphocytes and CTLA-4 failed, but PD-L1 expressed on tumor cells and on intratumoral lymphocytes was suitable to distinguish patient cohorts with different OS and DFS (p ≤ 0.011 for all comparisons). Higher PD-L1 expression was associated with poor prognosis. PD-L1 expressed on tumor cells represented an independent association with OS (p = 0.023) and DFS (p = 0.032).

CONCLUSIONS:

Our results suggest that PRBC and YWBC do not differ in the expression of PD-1, PD-L1 and CTLA-4. However, our findings emphasize the relevance of PD-L1 expression in early-onset breast cancer, as an independent negative predictor of prognosis.

Oncothermia-Booster (Targeted Radiofrequency) Treatment – in Some Non-Oncological Diseases as Special Physiotherapy

Indikáció: Non-oncology
Bizonyítás: Review
Szerző: 
Mate M Molnar I Petrovits G et al.
Páciensek száma: 155
Terápia: mEHT+TCM
Év: 2017

Abstract
Introduction: Oncothermia (OTM) is based on electromagnetic interactions with the living organism. Its nano-targeting approach [established a newer paradigm, which could be applied not only in case of malignancies but in any other diseases, when the non-selective conditions are existing. This technique by now is well proven from the simple laboratory level to the several different clinical applications. Oncothermia method ignites the natural processes to rescue them from the system, re-establishing the better communication harmony between the cells of organism. This method will lead us to the treatment of some non-malignant diseases too to try delaying their development or offering earlier recovery. Our aim was to use OTM on the common basis of equilibrium demand; and use the recognition of the deviations from the complex harmony of the organism or its part for selection to act properly.

Study protocol and Method:
Oncothermia was successfully applied for non malignant conditions like Lyme disease, for non-specific low-back pain, for Peyronie disease, and for Dupuytren’s contracture, too. We made more extended study, proving in details the applicability of the OTM in these diseases, especially in the situations when traditional Chinese Medicine (TCM) is also applicable (acupuncture, permanent needle techniques). Our special permanent acupuncture method was proven previously and well fits to the complementary applications.Results & Discussion: The synergy of the ancient knowledge – application of heat energy – and the high-tech state-of-art of the medical knowledge could be established with our research. Recognition of the distortions in the healthy tissue have some common principles and possibilities in TCM and OTM: the left complexity of the living organization is recognized by both the methods.OTM application is a useful, harmless additional complementary treatment for management of selected diseases. Our topic is giving western trained physicians clinical applications of modern (Oncothermia-Booster) as a physiotherapeutic – equipment to accommodate accelerating interests in modern complex treatment of chronic low back pain and Dupuytren’s contracture.

Conclusion:
In recent study data verified the relevant end-points of the study: the safety, the quality of life (QoL), the shortened rest time, duration of painless state, cost/benefit ratio.

Keywords: Physiotherapy; Oncothermia; Dupuytran’s contracture; Non-specific low back pain

Abbreviations: OTH: Oncothermy; LBP: Low Back Pain; TCM: Traditional Chinese Medicine; VAS: Visual Analog Scale; QoL: Quality of Life

Local modulated electro-hyperthermia in combination with traditional Chinese medicine vs. intraperitoneal chemoinfusion for treatment of peritoneal carcinomatosis with malignant ascites: a phase II randomized trial

Indikáció:
Bizonyítás: Phase II
Szerző: 
Pang CLK Xinting Z Zhen W Junwen O Yimin L Roussakow R
Páciensek száma: 260
Terápia: mEHT
Év: 2017

Abstract

The purpose of this study was to develop a safe and non-toxic alternative to the conventional conservative treatment of peritoneal carcinomatosis with malignant ascites (PCMA) by investigating the efficacy and safety of local modulated electro-hyperthermia (mEHT) combined with the traditional Chinese medicine (TCM) ‘Shi Pi’ herbal decoction, compared with standard intraperitoneal chemoinfusion (IPCI). A randomized, controlled, single-center, open-label clinical trial (phase II) with two parallel groups (allocation ratio, 1:1) was conducted to investigate the efficacy and safety of mEHT+TCM (study group, SG) vs. standard IPCI (control group, CG) in patients with PCMA by intention-to-treat analysis. A total of 260 patients with PCMA were randomly allocated into the two groups (130/130); mEHT was applied for 60 min per session every second day for 4 weeks, for a total of 14 sessions. The TCM decoction was administered orally, at 400 ml daily. In CG, occlusive IPCI with cisplatin (30-60 mg) and fluorouracil (500-600 mg/m2) was applied twice, biweekly. The objective response rate (ORR), quality of life (QoL) and adverse event rate (AER) in the two groups were evaluated 1 month after treatment, analyzed and compared. The present study is registered on ClinicalTrials.gov (NCT02638051). No case was lost or excluded (0/260). The ORR in SG was 77.69% (101/130) vs. 63.85% (73/130) in CG (P<0.05). The QoL in SG was 49.23% vs. 32.3% in CG (P<0.05). The AER in SG was 2.3% (3/130) vs. 12.3% (16/130) in CG (P<0.05). All the adverse events were grade I. In conclusion, the combination of mEHT with TCM achieves better control of PCMA compared with standard IPCI, with less toxicity. Both components of the combination are non-toxic treatments easily tolerated by patients. Thus, this combined treatment may be preferred due to the better benefit-harm balance.

Retrospective observational Clinical Study on Relapsed Malignant Gliomas Treated with Electro-Hyperthermia

Indikáció: Gliomas
Bizonyítás:
Szerző: 
Giammaria Fiorentini Donatella Sarti Carlo Milandr Patrizia Dentico Andrea Mambrini Stefano Guadagni
Páciensek száma: 24
Terápia: mEHT
Év: 2017

ABSTRACT

Aim: to evaluate the effi cacy and tolerability of electro-hyperthermia (ET) for the treatment of relapsed malignant glioma. Methods: this was a retrospective observational clinical study. Patients were included in the study if they had >18 years, informed consent signed, histological diagnosis of malignant glioma, failure of previous temozolamide-based chemotherapy and radiotherapy, indication for treatment with ET. 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 40 C° for more than 90% of the treatment duration (20-60 minutes gradually). Results: 24 consecutive patients were enrolled in the study, 19 (79%) had glioblastoma multiforme (GBM) 13 were of grade 1-3 and 6 of grade 4, 5 (21%) astrocitoma. Tumor response analysis two months after ET showed 2 (8%) complete remission (astrocytomas) and 5 (21%) partial remission (2 astrocitoma, and 3 glioblastomas), with a response rate of 29%. The median duration of response was 16 months (range 6-120). The median survival of whole study population was 19.5 months (range 2-156), 55% survival rate at 1 year, and 15 % at two years. We observed 3 long survivors at 156, 60, 62 months in atrocitomas. Conclusions: ET appears to have promising effi cacy in adults with relapsed malignant glioma. Keywords: Relapsed Malignant Glioma; Electro-Hyperthermia; Survival; Tumor Response

Clinical and economic evaluation of modulated electrohyperthermia concurrent to dose-dense temozolomide 21/28 days regimen in the treatment of recurrent glioblastoma: a retrospective analysis of a 2-centre German cohort trial with systematic comparison

Indikáció: Gliomas (advanced)
Bizonyítás: Retrospective study
Szerző: 
Roussakow S.
Páciensek száma: 168
Terápia: CT+mEHT
Év: 2017

Abstract

OBJECTIVE: To assess the efficacy and cost-effectiveness of modulated electrohyperthermia (mEHT) concurrent to dose-dense temozolomide (ddTMZ) 21/28 days regimen versus ddTMZ 21/28 days alone in patients with recurrent glioblastoma (GBM).

DESIGN: A cohort of 54 patients with recurrent GBM treated with ddTMZ+mEHT in 2000-2005 was systematically retrospectively compared with five pooled ddTMZ 21/28 days cohorts (114 patients) enrolled in 2008-2013.

RESULTS: The ddTMZ+mEHT cohort had a not significantly improved mean survival time (mST) versus the comparator (p=0.531) after a significantly less mean number of cycles (1.56 vs 3.98, p<0.001). Effect-to-treatment analysis (ETA) suggests that mEHT significantly enhances the efficacy of the ddTMZ 21/28 days regimen (p=0.011), with significantly less toxicity (no grade III-IV toxicity vs 45%-92%, p<0.0001). An estimated maximal attainable median survival time is 10.10 months (9.10-11.10). Cost-effectiveness analysis suggests that, unlike ddTMZ 21/28 days alone, ddTMZ+mEHT is cost-effective versus the applicable cost-effectiveness thresholds €US$25 000-50 000/quality-adjusted life year (QALY). Budget impact analysis suggests a significant saving of €8 577 947/$11 201 761 with 29.1-38.5 QALY gained per 1000 patients per year. Cost-benefit analysis suggests that mEHT is profitable and will generate revenues between €3 124 574 and $6 458 400, with a total economic effect (saving+revenues) of €5 700 034 to $8 237 432 per mEHT device over an 8-year period.

CONCLUSIONS: Our ETA suggests that mEHT significantly improves survival of patients receiving the ddTMZ 21/28 days regimen. Economic evaluation suggests that ddTMZ+mEHT is cost-effective, budget-saving and profitable. After confirmation of the results, mEHT could be recommended for the treatment of recurrent GBM as a cost-effective enhancer of ddTMZ regimens, and, probably, of the regular 5/28 days regimen. mEHT is applicable also as a single treatment if chemotherapy is impossible, and as a salvage treatment after the failure of chemotherapy.

Rescue Therapy in Patient with Glioblastoma Multiforme Combining Chemotherapy, Hyperthermia, Phytotherapy

Indikáció: Glioblastoma
Bizonyítás: Case report
Szerző: 
Carlo Pastore Massimo Fioranelli Maria Grazia Roccia
Páciensek száma:
Terápia: Chemotherapy, Hyperthermia, Phytotherapy
Év: 2017

Abstract
Glioblastoma multiforme is a pathology that is poorly treatable and tends towards recurrence. If surgically unresectable, at least without macroscopically visible residue, the prognosis is severe. Here is the case of a 60-yearold woman suffering from recurrent glioblastoma who comes to my observation with no therapeutic options and treated with a combination of antiangiogenic drug, RF capacitive hyperthermia and herbal medicine, earns an acceptable quality of life and survival prolongation of six months.

Newer application of oncothermia to non-malignant diseases such as Dupuytren’s contracture of the hand and chronic lower back pain lasting more than 4 weeks

Indikáció: Non-oncology
Bizonyítás:
Szerző: 
Mate A Molnar I Szoke H Hegyi G.
Páciensek száma: 231
Terápia: mEHT
Év: 2017

ABSTRACT

Oncothermia (OTM) is based on electromagnetic interactions with the living matter. Its nano-targeting approach establishes a new paradigm. OTM could be applied not only to treat malignancies but it is feasible to apply for other diseases too. OTH is well proven method from the laboratory level to the clinical applications, promoting the natural processes, re-establishing of the synchronization between the cells. This approach allows therapy of some non-malignant diseases too. Our objective is to use OTM for the irregularities of tissue-growth and for pain syndromes as well. OTM uses precisely tuned radiofrequency (RF) current flowing through the treated part of the body. We made extensive study, proving in details the applicability of the OTM for Dupuytren’s contracture and chronic low back pain, in conjunction with permanent acupuncture method, a modified process of traditional Chinese Medicine (TCM). The synergy of the ancient and the state-of-art medical knowledges is the basic method of the present research. Our results with application of OTM for chronic low back pain and Dupuytren’s contracture shows definite improvements of the patients involved in the study. We measured the success with the Visual Analog Scale (VAS), with anecdotic quality of life (QoL), and the shortening of the of-work period due to the disease. We measured that VAS decreased significantly, the hand contracture became less rigid and less contracted. The QoL of patients improved and their complaints which blocked their regular activity has significantly reduced. OTM method was safe & no adverse effects were observed. Recognition of the distortions in the healthy tissue have some common principles and possibilities in TCM and OTM: both the methods recognize the loss of complexity of the living organization. Data of our recent study verified the relevant end-points of our present study: the safety, the quality of life (QoL), the prolonged painless status of the patient.

Bevacizumab-Based Chemotherapy Combined with Regional Deep Capacitive Hyperthermia in Metastatic Cancer Patients: A Pilot Study

Indikáció: Multiple
Bizonyítás:
Szerző: 
Ranieri G Ferrari C Di Palo A
Páciensek száma: 23
Terápia: CT+mEHT
Év: 2017

Abstract

As an angiogenesis inhibitor, bevacizumab has been investigated in combination with different chemotherapeutic agents, achieving an established role for metastatic cancer treatment. However, potential synergic anti-angiogenic effects of hyperthermia have not tested to date in literature. The aim of our study was to analyze efficacy, safety, and survival of anti-angiogenic-based chemotherapy associated to regional deep capacitive hyperthermia (HT) in metastatic cancer patients. Twenty-three patients with metastatic colorectal (n = 16), ovarian (n = 5), and breast (n = 2) cancer were treated with HT in addition to a standard bevacizumab-based chemotherapy regimen. Treatment response assessment was performed, according to the modified Response Evaluation Criteria for Solid Tumors (mRECIST), at 80 days (timepoint-1) and at 160 days (timepoint-2) after therapy. Disease Response Rate (DRR), considered as the proportion of patients who had the best response rating (complete response (CR), partial response (PR), or stable disease (SD)), was assessed at timepoint-1 and timepoint-2. Chi-squared for linear trend test was performed to evaluated the association between response groups (R/NR) and the number of previous treatment (none, 1, 2, 3), number of chemotherapy cycles (<6, 6, 12, >12), number of hyperthermia sessions (<12, 12, 24, >24), and lines of chemotherapy (I, II). Survival curves were estimated by Kaplan-Meier method. DRR was 85.7% and 72.2% at timepoint-1 and timepoint-2, respectively. HT was well tolerated without additional adverse effects on chemotherapy-related toxicity. Chi-squared for linear trend test demonstrated that the percentage of responders grew in relation to the number of chemotherapy cycles (p = 0.015) and to number of HT sessions (p < 0.001) performed. Both overall survival (OS) and time to progression (TTP) were influenced by the number of chemotherapy cycles (p < 0.001) and HT sessions (p < 0.001) performed. Our preliminary data, that need to be confirmed in larger studies, suggest that the combined treatment of bevacizumab-based chemotherapy with HT has a favorable tumor response, is feasible and well tolerated, and offers a potentially promising option for metastatic cancer patients.

The safety and pharmacokinetics of high dose intravenous ascorbic acid synergy with modulated electrohyperthermia in Chinese patients with stage III-IV non-small cell lung cancer

Indikáció: Lung
Bizonyítás: Phase I
Szerző: 
Ou J Zhu X Lu Y Zhao C Zhang H Wang X Gui X Wang J Zhang X Zhang T Pang C
Páciensek száma: 35
Terápia: mEHT
Év: 2017

Abstract

Ascorbic acid (AA) infusion and modulated electrohyperthermia (mEHT) are widely used by integrative cancer practitioners for many years. However, there are no safety and pharmacokinetics data in Chinese cancer patients. We carried out a clinical trial to evaluate the safety and pharmacokinetics of those methods in patients with stage III-IV non-small cell lung cancer (NSCLC). Blood ascorbic acid in the fasting state was obtained from 35 NSCLC patients; selecting from them 15 patients with stage III-IV entered the phase I study. 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. Pharmacokinetic profiles were obtained when they received solely IVAA and when IVAA in combination 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. IVAA synergy with simultaneous mEHT is safe and the concomitant application significantly increases the plasma AA level for NSCLC patients.

Graphical abstract

Pharmacokinetic plots of each treatment in the six groups by increasing dosage. Junwen Ou, Xinyu Zhu, et al.

Efficacy of metabolically supported chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy for stage IV triple-negative breast cancer

Indikáció: Gynecology
Bizonyítás: Case report
Szerző: 
Iyikesici MS Slocum AK Slocum A
Páciensek száma: 1
Terápia: CT+mEHT
Év: 2017

Abstract

Triple-negative breast cancer (TNBC) is more aggressive and metastatic than other breast cancer types. Cytotoxic chemotherapy is presently the predominant systemic therapy for TNBC patients. This case report highlights the influence of metabolically supported chemotherapy (MSCT), ketogenic diet (KD), hyperthermia (HT), and hyperbaric oxygen therapy (HBOT) in an overweight 29-year-old woman with stage IV (T4N3M1) triple-negative invasive ductal carcinoma of the breast. The patient presented with an observable mass in her left breast detected during a physical examination in December 2015. Magnetic resonance imaging revealed a Breast Imaging Reporting and Data System Category 5 tumor and multiple lymphadenomegaly in the left axilla. A Tru-Cut biopsy led to the diagnosis of a triple-negative nuclear grade 2 invasive ductal carcinoma. The patient was admitted to ChemoThermia Oncology Center, Istanbul, Turkey in October 2016, and a whole body (18F)-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET-CT) scan revealed a 77 mm x 55 mm primary tumor in her left breast, multiple left pectoral and axillary lymph nodes, multiple widespread liver masses, and an upper left nodular abdominal lesion. The patient received a treatment protocol consisting of MSCT, KD, HT, and HBOT. A follow-up whole body 18F-FDG PET-CT scan in February 2017 showed a complete therapeutic response with no evidence of abnormal FDG uptake. The patient continued to receive this treatment protocol and in April 2017 underwent a mastectomy, which revealed a complete pathological response consistent with the response indicated by her PET-CT imaging. This single case study presents evidence of a complete clinical, radiological, and pathological response following a six-month treatment period using a combination of MSCT and a novel metabolic therapy in a patient with stage IV TNBC.

Keywords: metabolically supported chemotherapy, ketogenic diet, hyperthermia, hyperbaric oxygen therapy, pathological complete response, triple negative breast cancer

A new strategy of cancer immunotherapy combining hyperthermia/oncolytic virus pretreatment with specific autologous anti-tumor vaccination – a review

Indikáció: Immuno-oncology
Bizonyítás: Review
Szerző: 
Schirrmacher V Lorenzen D Van Gool SW Stuecker W
Páciensek száma: 206
Terápia: IMT+mEHT
Év: 2017

Abstract

This review describes and explains a specific immunotherapy strategy that has been developed at the Immunological and Oncological Center Cologne in Germany. The strategy is based on many years of basic and translational research. It is a highly individualized approach to activate and target the patient’s immune system against the patient’s own tumor. In a first step, the patient’s immune system is conditioned by pretreatment with oncolytic virus in combination with hyperthermia. The second step consists of active-specific autologous anti-tumor vaccination. The vaccine, VOL-DC, consists of autologous Dendritic Cells (DCs) which are loaded with Viral Oncolysate (VOL) from the patient’s tumor cells. VOL transfers to the DCs information about tumor-associated antigens from the patient’s tumor and Pathogen-Associated Molecular Patterns (PAMPs, danger signals) from the virus. The product VOL-DC, which involves Newcastle Disease Virus, has been approved in Germany as an Advanced Therapeutic Medicinal Product for individual treatment by the institution which received this permit. This review includes promising results from case-series studies of glioblastoma patients. It also discusses future strategies for treatment of late-stage disease including combination of this immunotherapy with immune checkpoint blocking antibodies and/or with costimulatory bispecific antibodies.

Role of HIF-1α in response of tumors to a combination of hyperthermia and radiation in vivo

Indikáció: Immuno-oncology
Bizonyítás: Review
Szerző: 
Kim W Kim MS Kim HJ Lee E Jeong JH Park I Jeong YK Jang WI
Páciensek száma:
Terápia: RT+mEHT
Év: 2017

Abstract

PURPOSE:

Mild temperature hyperthermia (MTH) increases blood flow and oxygenation in tumours. On the other hand, high-dose-per-fraction irradiation damages blood vessels, decreases blood flow and increases hypoxia in tumours. The radiation-induced hypoxia in tumours activates hypoxia-inducible factor-1α (HIF-1α) and its target genes, such as vascular endothelial growth factor (VEGF), promoting revascularization and recurrence. In the present study, we examined the hypothesis that MTH inhibits radiation-induced upregulation of HIF-1α and its target genes by increasing tumour oxygenation.

MATERIALS AND METHODS:

FSaII fibrosarcoma tumours grown subcutaneously in the legs of C3H mice were used. Tumours were irradiated with 15 Gy using a 60Co irradiator or heated at 41 °C for 30 min using an Oncothermia heating unit. Blood perfusion and hypoxia in tumours were assessed with Hoechst 33342 and pimonidazole staining, respectively. Expression levels of HIF-1α and VEGF were determined using immunohistochemical techniques. Apoptosis of tumour cells was quantitated via TUNEL staining and the effects of treatments on tumour growth rate were assessed by measuring tumour diameters.

RESULTS:

Irradiation of FSaII tumours with a single dose of 15 Gy led to significantly decreased blood perfusion, increased hypoxia and upregulation of HIF-1α and VEGF. On the other hand, MTH at 41 °C for 30 min increased blood perfusion and tumour oxygenation, thereby suppressing radiation-induced HIF-1α and VEGF in tumours, leading to enhanced apoptosis of tumour cells and tumour growth delay.

CONCLUSION:

MTH enhances the anti-tumour effect of high-dose irradiation, at least partly by inhibiting radiation-induced upregulation of HIF-1α.

Treatment outcome analysis of chemotherapy combined with modulated electro-hyperthermia compared with chemotherapy alone for recurrent cervical cancer, following irradiation

Indikáció: Gynecology
Bizonyítás:
Szerző: 
Sun Young Lee Na Ri Lee Dong Hyu Cho
Páciensek száma: 20
Terápia: CT+mEHT
Év: 2017

The survival of patients with recurrent cervical cancer following irradiation remains poor. Chemotherapy combined with hyperthermia has been demonstrated to improve the response rate. The present study was performed to evaluate the effect of modulated electro‑hyperthermia combined with conventional chemotherapy compared with chemotherapy alone on recurrent cervical cancer previously treated with irradiation. A total of 20 patients were treated with chemotherapy alone, and 18 were treated with chemotherapy combined with modulated electro‑hyperthermia. A single patient was treated with chemo‑radiotherapy as primary treatment and then relapsed; the tumor was inoperable and radio‑refractory upon recurrence. Local metastases, including metastasis of the para‑aortic lymph nodes and adjacent pelvic lymph nodes were included, but distant metastases were excluded. Modulated electro‑hyperthermia was performed three times per week beginning at chemotherapy initiation, and patients underwent a total of 36 sessions. The overall response (complete remission + partial remission + stable disease/progressive disease) to treatment was significantly greater in the group of patients who underwent chemotherapy combined with modulated electro‑hyperthermia (P=0.0461), and at the evaluation conducted at the last follow‑up visit, the response rate was significantly higher (P=0.0218). Additionally, severe complications were not reported. In the present study, of patients with recurrent cervical cancer previously treated with irradiation, the overall response rate for patients treated with chemotherapy combined with modulated electro-hyperthermia was significantly greater than that for those treated with chemotherapy alone.

Update on phase III randomized clinical trial investigating the effects of the addition of electro-hyperthermia to chemora-diotherapy for cervical cancer patients in South Africa

Indikáció: Gynecology
Bizonyítás: Phase III
Szerző: 
C Minnaar A Baeyens J Kotzen
Páciensek száma: 100
Terápia: CT+mEHT
Év: 2016

Introduction

The Electro-Hyperthermia trial an ongoing phase III randomised clinical trial being conducted at the Charlotte Maxeke Johannesburg Academic Hospital. The general aim is to determine the clinical effects of the addition of modulated electro-hyperthermia (EHT) to the standard treatment protocols for locally advanced cervical cancer patients in state healthcare in South Africa. The objectives are to assess the effects of the addition of EHT on local disease control, quality of life, acute and late toxicity and overall survival.

Materials and methods

The study aims to enrol 236 female participants with FIGO stage IIB distal to IIIB cervical cancer. Participants are being randomised into a “Hyperthermia” group (EHT plus chemoradiation) and a “Control” group (chemoradiation alone), randomisation stratums: HIV status; age; stage of disease. All participants are receiving 50 Gy external beam radiation, 3 doses of high dose rate brachytherapy (8 Gy) and cisplatin. The Hyperthermia group is receiving two 55 minute local EHT treatments per week during radiation therapy. Local disease control is being assessed by Positron Emission Tomography (PET) scans. Adverse events, quality of life and overall survival are being recorded and the data is being analysed.

Results

We report preliminary data of the first 100 participants to reach 6 months post treatment. We see a positive trend in survival and local disease control in the group receiving hyperthermia. There are no significant differences in acute adverse events or quality of life between the groups.

Conclusion

The preliminary results on the addition of EHT are positive with no impact on adverse events, however this must be confirmed with more patients on completion of the study.

Stage IV Wilms tumor treated by Korean medicine, hyperthermia and thymosin-α1: A case report

Indikáció: Immuno-oncology
Bizonyítás: Case report
Szerző: 
Donghyun Lee Sung Su Kim Shin Seong Wonjun Cho Hyejin Yu
Páciensek száma: 1
Terápia: CT+mEHT
Év: 2016

Abstract

Introduction

Wilms tumor is one of general solid cancers that occur in children, which carries a death rate of 7–8 in a million. The cure rate of Wilms tumor in the recent 30 years has dramatically been improved, but a proper remedy is still not prepared enough in terms of application in tumor therapy upon recurrence after radiotherapy, surgery and chemotherapy. We present an integrative medical remedy – hyperthermia and thymosin-α1 treatment focused on herbal remedy – since there have been cases in which this remedy contributed to remission in the liver-transferred part in the 4th phase of Wilms tumor and stable maintenance of metastatic lung lesion.

Case Presentation

Our patient, a female Korean mongoloid outpatient, was treated from October 25, 2014, to July 22, 2015. The herbal remedy consisted of 8 ml inhalation of Soram nebulizer solution q.d., Soramdan S 8 g p.o., Hangamdan S 1 g p.o., t.i.d., Cheongjangtang 10–30 ml, and Spiam HC 8 g p.o. The integrative medical therapy was done with hyperthermia therapy (oncothermia) and 1.6 mg of thymosin-α1 treatment (Zadaxin) i.m. According to the CT result on July 15th, 2015, the liver metastasis was not seen anymore, while the lung metastasis was maintained stably without tumor progress.

Conclusions

Accompanying integrative medical therapy with herbal remedy in the treatment of Wilms tumor showing progress patterns after surgery and chemotherapy can be meaningful as a new remedy.

Key Words: Wilms tumor, Korean medicine therapy, Hangamdan S, Soramdan S, Spiam HC, Hyperthermia, Thymosin-α1

Positive response of a primary leiomyosarcoma of the breast following salvage hyperthermia and pazopanib

Indikáció: Gynecology
Bizonyítás: Case report
Szerző: 
Sun Young Lee Na-Ri Lee
Páciensek száma: 1
Terápia: CT+mEHT
Év: 2016

Primary sarcomas of the breast are rare tumors, accounting for less than 1% of all breast neoplasms. Leiomyosarcoma is an extremely rare subtype of breast sarcoma [1]. Prognoses for primary breast sarcoma are poor and treatment modalities are limited. Pazopanib is an oral, multitargeted tyrosine kinase inhibitor, with activity against vascular endothelial growth factors (VEGFs) 1, 2, and 3, and platelet-derived growth factors (PDGFs) [2]. Pazopanib has been approved for the treatment of advanced renal cell carcinoma and metastatic soft tissue sarcoma (STS) [2]. Hyperthermia inhibits sub-lethal cellular damage repair and improves oxygenation; thus, making it an attractive therapy for combining with radiation and/or chemotherapy to generate a potentially synergistic response. Hyperthermia has a proven benefit for treating STS [3]. Herein, we report a case of primary breast leiomyosarcoma treated with regional hyperthermia and pazopanib.

Complete Response of Locally Advanced (stage III) Rectal Cancer to Metabolically Supported Chemoradiotherapy with Hyperthermia

Indikáció: Rectal Cancer
Bizonyítás:
Szerző: 
Iyikesici MS. Slocum A. Turkmen E. Akdemir O. Slocum AK. Berkarda FB.
Páciensek száma: 1
Terápia:
Év: 2016

Abstract
Background: Locally advanced rectal cancer is defined as a rectal mass that cannot be resected without a high probability of leaving residual disease at the tumor site. While the standard treatment for locally advanced rectal cancer is chemoradiotherapy followed by surgery, this study reports a locally invasive rectal adenocarcinoma patient who achieved complete pathological and clinical remission after receiving a combination of metabolically supported chemotherapy (MSCT), radiotherapy (RT) and hyperthermia (HT). Case presentation: An 81-year-old female underwent a rectosigmoidoscopy at a referring hospital following a complaint of bloody stools for a period of 20 days. The rectosigmoidoscopy revealed an ulcerated tumor beginning at the level of the anal sphincter. A pathological examination of biopsy material revealed moderately differentiated invasive adenocarcinoma and the patient received a diagnosis of stage III (T3N2M0) lowlying rectal cancer. When further follow-up revealed colonic obstruction, the patient was recommended an abdominoperineal resection (APR) and was referred after refusing surgical treatment. The patient received a metabolically supported combination of oxaliplatin, 5-florouracil (5-FU) and calcium folinate (FOLFOX6) concomitant to RT and local HT and, ultimately, never underwent surgery. 27 months since her disease-free PET-CT scan, the patient remains with no sign of disease recurrence. Conclusion: According to the findings of the present study, the non-surgical treatment and achievement of complete clinical and pathological remission of locally advanced rectal adenocarcinoma may be possible by means of a combination of MSCT, RT and HT. Keywords: Pathological complete response; Locally advanced rectal cancer; Metabolically supported chemotherapy; Hyperthermia

Effect of modulated electrohyperthermia on the pharmacokinetics of oral transmucosal fentanyl citrate in healthy volunteers

Indikáció: Temperature
Bizonyítás: Open-label study
Szerző: 
Lee SY Kim M-G
Páciensek száma: 12
Terápia: mEHT
Év: 2016

Abstract

PURPOSE:

This study aimed to determine whether changes occur in fentanyl absorption and disposition when administered in conjunction with modulated electrohyperthermia (mEHT) treatment.

METHODS:

A randomized, single-dose, crossover, open-label study was used to investigate the effect of mEHT on the pharmacokinetic properties of fentanyl in 12 healthy volunteers. The 12 healthy volunteers were each administered a single dose of oral transmucosal fentanyl citrate (OTFC) or a single dose of OTFC with mEHT. mEHT was performed on the abdomen for 1 hour. Blood samples were collected for 24 hours after dosing. The temperature of the abdominal skin surface was assessed before dosing and at 10, 20, and 60 minutes after dosing.

FINDINGS:

Geometric mean ratios (ratio of fentanyl with mEHT to fentanyl alone) for the Cmax and AUC0-last were 1.20 (90% CI, 1.09-1.32) and 1.15 (90% CI, 0.99-1.33), respectively. The mean temperature of the abdominal skin surface increased by approximately 4°C.

IMPLICATIONS:

There was an increase in the overall exposure to the drug without implications of any clinical significance. OTFC can be administered without limitations in combination with mEHT, and it is not necessary to modify the dosing regimen. cris.nih.go,kr Identifier: KCT0001286.

Definitive radiotherapy with concurrent oncothermia for stage IIIB non‑small‑cell lung cancer: A case report

Indikáció: Lung
Bizonyítás: Case report
Szerző: 
Seung-Gu Yeo
Páciensek száma: 1
Terápia: RT+mEHT
Év: 2015

Abstract

Hyperthermia enhances the susceptibility of tumors to radiotherapy (RT) and chemotherapy. Oncothermia, also known as electro-hyperthermia, is a new treatment modality developed to overcome the problems of traditional hyperthermia by selectively delivering energy to the malignant tissues. The present study reports the outcome of combined oncothermia and RT in a 75-year-old patient with stage IIIB non-small-cell lung cancer (NSCLC). Due to the advanced age and the performance status of the patient, the combination of systemic chemotherapy and RT was deemed infeasible; therefore, the patient instead decided to undergo oncothermia concurrently with definitive RT. The RT was administered at a dose of 64.8 Gy in 36 fractions using a three-dimensional conformal plan technique. Oncothermia was started concomitantly with RT and was performed for 60 min per session, two sessions per week, for a total of 12 sessions. No severe toxicities developed, with the exception of mild odynophagia, which resolved soon after the treatments. Follow-up computed tomography showed complete tumor response, and the patient was alive with no evidence of the disease 18 months after the completion of the treatment. In conclusion, the present case report suggests that oncothermia combined with RT, with the former possessing radiosensitizing potential and no additional toxicities, may be a promising alternative for advanced-age and/or frail patients with locally advanced NSCLC.

The Outcome of the Chemotherapy and Oncothermia for Far Advanced Adenocarcinoma of the Lung: Case reports of four patients

Indikáció: Lung
Bizonyítás: Case report
Szerző: 
Doo Yun Lee Joon Seok Park Hae Chul Jung Eun Seol Byun Seok Jin Haam Sung Soo Lee
Páciensek száma: 4
Terápia: CT+mEHT
Év: 2015

ABSTRACT

Lung cancer is one of the most aggressive and lethal form of cancers. Patients with far advanced lung cancer are treated by chemotherapy with or without radiotherapy. However, median survival of these patients is less than 6 months. To increase survival and quality of life for these patients, various forms of complementary treatments have been tried in clinical practices, and oncothermia is supposed to be one of the promising candidates. From May 2008 to November 2013, 4 patients with far advanced lung adenocarcinoma (stages IIIB and IV) were treated with oncothermia in addition to conventional chemotherapy at Gangnam Severance Hospital and Bundang CHA Hospital. All these patients have survived for more than 2 years.

Oncolytic Newcastle disease virus as a prospective anti-cancer therapy. A biologic agent with potential to break therapy resistance

Indikáció: Immuno-oncology
Bizonyítás:
Szerző: 
Schirrmacher V
Páciensek száma:
Terápia: IMT+mEHT
Év: 2015

Abstract

INTRODUCTION:

Oncolytic viruses (OVs) selectively replicate in tumor cells and cause cancer cell death. Most OVs in clinical studies are genetically engineered. In contrast, the avian Newcastle disease virus (NDV) is a naturally oncolytic RNA virus. While anti-viral immunity is considered a major problem in achieving maximal tumor cell killing by OVs, this review discusses the importance of NDV immunogenic cell death (ICD) and how anti-viral immune responses can be integrated to induce maximal post-oncolytic T-cell-mediated anti-tumor immunity. Since replication of NDV is independent of host cell DNA replication (which is the target of many cytostatic drugs and radiotherapy) and because of other findings, oncolytic NDV is a candidate agent to break therapy resistance of tumor cells.

AREAS COVERED:

Properties of this avian paramyxovirus are summarized with special emphasis to its anti-neoplastic and immune-stimulatory properties. The review then discusses prospective anti-cancer therapies, including treatments with NDV alone, and combinations with an autologous NDV-modified tumor cell vaccine or with a viral oncolysate pulsed dendritic cell vaccine. Various combinatorial approaches between these and with other modalities are also reviewed.

EXPERT OPINION:

Post-oncolytic anti-tumor immunity based on ICD is in the expert’s opinion of greater importance for long-term therapeutic effects than maximal tumor cell killing. Of the various combinatorial approaches discussed, the most promising and feasible for clinical practice appears to be the combination of systemic NDV pre-treatment with anti-tumor vaccination.

Results of Oncothermia Combined with Operation, Chemotherapy and Radiation Therapy for Primary, Recurrent and Metastatic Sarcoma

Indikáció: Sarcoma
Bizonyítás:
Szerző: 
Tae Sig Jeung Sun Young Ma JiHoon Choi Jeasang Yu Su Yong Lee Sangwook Lim
Páciensek száma: 13
Terápia: SRG+CT+mEHT
Év: 2015

ABSTRACT

Sarcomas are relatively rare malignancies; however, their huge variety and shortage of the effective therapies make this disease face huge challenge for oncology. It is recently shown that hyperthermia could be successfully applied even in high-risk cases in combination with the available gold-standard regiments. Our aim is to present various advanced cases treated with a new hyperthermia method, oncothermia, showing its advantages and feasibility to successfully treat highly advanced sarcomas with curative intent.

The effect of modulated electro-hyperthermia on the pharmacokinetic properties of nefopam in healthy volunteers: A randomised, single-dose, crossover open-label study

Indikáció: Temperature
Bizonyítás: Open-label study
Szerző: 
Lee SY Kim M-G
Páciensek száma: 12
Terápia: mEHT
Év: 2015

Abstract

PURPOSE:

Nefopam is a widely available analgesic for the management of pain. The aim of this study was to reveal the effect of regional hyperthermia of the abdominal area on the pharmacokinetics of nefopam.

MATERIALS AND METHODS:

A randomised, single-dose, crossover, open-label study was conducted to reveal the effect of hyperthermia using modulated electro-hyperthermia on the pharmacokinetics of nefopam. The pharmacokinetics of orally administered nefopam without hyperthermia was studied in 12 healthy volunteers and then 7 days later they were treated with nefopam plus modulated electro-hyperthermia to the abdominal area for 1 h. Blood samples were collected up to 24 h after the drug administration. From the blood concentration-time curve, the maxinum plasma concentration (C(max)), time to C(max) (T(max)) and the area under the curve (AUC) were obtained. The safety and tolerability of these treatments were also assessed.

RESULTS:

The geometric mean ratios (GMRs) ((nefopam + modulated electro-hyperthermia)/nefopam) and the associated 90% confidence intervals (CIs) for C(max), AUC(last) and AUC(inf) were 1.2804 (1.1155∼1.4696), 1.0512 (0.9555∼1.1566) and 1.0612 (0.9528∼1.1819), respectively. The increase in C(max) was statistically significant, and T(max) was significantly shortened.

CONCLUSIONS:

The significant increase in C(max) and decrease in T(max) indicated that modulated electro-hyperthermia increased the absorption of the orally administered nefopam, thereby transitionally increasing the blood concentration of the drug. The AUC is an important parameter that contributes to the therapeutic effect of drugs. The lack of significant change in AUC suggests that modulated electro-hyperthermia may increases the absorption of orally administered drugs without increasing the systemic adverse effect of the drugs.

Conventional cancer treatment alone or with regional hyperthermia for pain relief in lung cancer: A case–control study

Indikáció: Lung cancer
Bizonyítás: Case report
Szerző: 
Yeon-PyoKim YuriChoi SunKim Yoon-SungPark In-JaeOh Kyu-SikKim Young-ChulKim
Páciensek száma: 115
Terápia: Conventional treatment, Hyperthermia
Év: 2015

Objective: To investigate the effect of combining conventional treatment with regional hyperthermia on cancer pain in lung cancer patients.
Design: Case–control study.
Setting: One Korean university hospital and three complementary cancer clinics.
Main outcomes and measures: Main outcome was effective analgesic score (EAS, PI[1 + (M/10)], 1: anti-inflammatory drug consumption at a regular dosage, M: weekly dose (mg) of oral morphine equivalent and PI: pain intensity) at four time points (baseline (days −30 to 0), time 1 (days 1–60), time 2 (days 61–120), and time 3 (days 121–180)). Propensity score matching between the hyperthermia and control groups was performed using a 1:5 ratio. A linear mixed effects model was employed to measure EAS changes over time in the two groups.
Results: At baseline, there were 83 subjects in the control group and 32 subjects in the hyperthermia group. At time 3, there were 49 subjects in the control group and 16 subjects in the hyperthermia group. Analyses showed rate of change of EAS, treatment × time was significant (p = 0.038). This significant difference was mainly observed for time 1 (mean difference: 101.76 points, 95% confidence interval: 10.20–193.32 points, p = 0.030).
Conclusions: Our results indicate an increase in cancer pain in lung cancer patients administered regional hyperthermia, particularly during the early stage of hyperthermia treatment.

Second-line chemotherapy with gemcitabine and oxaliplatin in combination with loco-regional hyperthermia (EHY-2000) in patients with refractory metastatic pancreatic cancer – preliminary results of a prospective trial

Indikáció: Pancreas
Bizonyítás: Clinical study
Szerző: 
Volovat C Volovat SR Scripcaru V Miron L
Páciensek száma: 26
Terápia: CT+mEHT
Év: 2014
Abstract
There is no standard treatment for second-line in patients with metastatic pancreatic cancer. The treatment with local hyperthermia (41–42°C) in order to enhance the activity gemcitabine-oxaliplatin on liver metastasis and primary advanced tumor was added as standard treatment. The primary objective was the response rate while the secondary objective were the safety of chemotherapy associated with hyperthermia and overall survival. There were 26 patients included, diagnosed with metastatic pancreatic cancer with progressive disease after gemcitabine treatment. The patients were enrolled in the period January 2005 – May 2011. The patients received gemcitabine 1000 mg/msq IV and oxaliplatin 100 mg/msq IV day 1(GEMOX) combined with locoregional hyperthermia days1, 3 and 5 all repeated at 14 days. From 26 patients included, 19 patients had an evaluable response at the treatment. The toxicity of chemotherapy for these patients was related with chemotherapy (neutropeniagrade III – 24%; anemia grade III – 8%, thrombopenia grade III– 6%; neurologic toxicity grade III – 22%. Toxicity related to hyperthermia was:discomfort because of bolus pressure (2%), pain related with position (12%), power related pain (2%). Rate of response was stable disease 53%, partial response 18% and progression disease 29%. Progression-free-survival was 3.9 months. Overall survival was 8.9 months.

Long‑term remission of prostate cancer with extensive bone metastases upon immuno‑ and virotherapy: A case report

Indikáció: Prostate
Bizonyítás: Case report
Szerző: 
Volker Schirrmacher Akos-Sigmund Bihari Wilfried Stücker Tobias Sprenger
Páciensek száma: 1
Terápia: SRG+CT+mEHT
Év: 2014

Abstract

The present study reports the case of a patient with hormone-refractory metastatic prostate cancer who had failed standard therapy, but then achieved complete remission following combined treatment with local hyperthermia (LHT), Newcastle disease virus and dendritic cell (DC) vaccination, which was an unusual combination. In August 2005, the patient underwent a radical prostatectomy. Despite standard treatment, the patient developed progressive bone metastases and stopped conventional therapy in June 2007. Starting in October 2007, the patient was treated with LHT, oncolytic virotherapy and DC vaccination. Prostate‑specific antigen (PSA)-levels, with the highest level of 233.8 ng/ml in January 2008, decreased to 0.8 ng/ml in late February 2008. In March 2008, a reduction in bone metastases could be detected by positron emission tomography/computed tomography. Since then, the PSA levels have remained low and the patient is doing well. The treatment induced a long-lasting antitumor memory T-cell response. This possibly explains the long-term effectiveness of this novel experimental combined treatment approach.

Synergy between Oncothermia and Traditional Chinese Medicine

Indikáció: Non-oncology
Bizonyítás:
Szerző: 
Hegyi G
Páciensek száma:
Terápia: mEHT+TCM
Év: 2014

Abstract

Aim of this article is to show the possibility and great advantage of the synergy of oncothermia with traditional Chinese medicine for treatment of malignant diseases based on the common basis of equilibrium demand. We use the re cognit io n of thedeviat ions fr om the com plex har monyof the org anismor its part for se lectionto actproperly.

Current Status of Oncothermia Therapy for Lung Cancer

Indikáció: Lung
Bizonyítás:
Szerző: 
Andras Szasz Ph.D
Páciensek száma:
Terápia: CT+RT+mEHT
Év: 2014

Abstract

Lung cancer is one of the most common malignant tumors, and it has the highest death rate. Oncothermia is a feasible and successful treatment for lung cancer. Results show a remarkable survival benefit for patients, with a good quality of life. The treatment has no, or in some cases mild, side-effects and could decrease the adverse effects of the complementary treatment. Applying oncothermia together with other treatment methods could increase the effects and result in better performance. A comparison of studies demonstrates a good correspondence in the data, which strengthens the reliability of the studies, and clearly shows the feasibility of the application of oncothermia to treating all kinds of pulmonary malignancies including non-small-cell and small-cell primary tumors, and all of the metastatic diseases of the pulmonary system.

The results of combination of ifosfamid and locoregional hyperthermia (EHY 2000) in patients with advanced abdominal soft-tissue sarcoma after relapse of first line chemotherapy

Indikáció: Sarcoma
Bizonyítás:
Szerző: 
Volovat C Volovat SR Scripcaru V Miron L Lupascu C
Páciensek száma: 24
Terápia: CT+mEHT
Év: 2014

Abstract

From 2003 to 2011, 24 patients with advanced soft-tissue sarcoma with high-risk pretreated using first line chemotherapy with doxorubicin and recurrence disease were treated with chemotherapy (ifosfamide 3000mg/sqm, day 1–3) and locoregional hyperthermia (1 hour application with temperature between 41.5°C and 42°C, 3 days/week). The purpose was to evaluate the efficacy and safety of chemotherapy combined with locoregional non-invasive hyperthermia for local tumor control in patients with retroperitoneal or visceral advanced soft tissue sarcomas. From 24 patients, 18 patients have had an evaluable response on CT scan using RECIST 1.0 (stable disease 8 patients for 4 months and 1 patients for 1 month, partial response 8 patients for 4 months, progression disease for 1 patient). The response was mainly on local tumor site. The side effects were correlated only with chemotherapy (neutropenia grade III 40%, grade 4 20%, trombocytopenia 2%, anemia grade III 10%, neurologic toxicity 9%). No toxicity was correlated with hyperthermia treatment.

Sorafenib and locoregional deep electro‑hyperthermia in advanced hepatocellular carcinoma: A phase II study

Indikáció: Gastrointestinal
Bizonyítás: Phase II
Szerző: 
Gennaro Gadaleta-Caldarola Stefania Infusino Ida Galise Girolamo Ranier Gianluca Vinciarelli Vito Fazio Rosa Divella Antonella Daniele Gianfranco Filippelli
Páciensek száma: 21
Terápia: CT+mEHT
Év: 2014

Abstract.

The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55-73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2-6.2) and 10.4 (95% CI, 10-11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC.

Long-term remission of prostate cancer with extensive bone metastases upon immuno- and virotherapy: A case report

Indikáció: Prostate
Bizonyítás: Case report
Szerző: 
Schirrmacher V Bihari A-S Stücker W
Páciensek száma: 1
Terápia: mEHT+OV therapy+DC
Év: 2014

Abstract

The present study reports the case of a patient with hormone-refractory metastatic prostate cancer who had failed standard therapy, but then achieved complete remission following combined treatment with local hyperthermia (LHT), Newcastle disease virus and dendritic cell (DC) vaccination, which was an unusual combination. In August 2005, the patient underwent a radical prostatectomy. Despite standard treatment, the patient developed progressive bone metastases and stopped conventional therapy in June 2007. Starting in October 2007, the patient was treated with LHT, oncolytic virotherapy and DC vaccination. Prostate-specific antigen (PSA)-levels, with the highest level of 233.8 ng/ml in January 2008, decreased to 0.8 ng/ml in late February 2008. In March 2008, a reduction in bone metastases could be detected by positron emission tomography/computed tomography. Since then, the PSA levels have remained low and the patient is doing well. The treatment induced a long-lasting antitumor memory T-cell response. This possibly explains the long-term effectiveness of this novel experimental combined treatment approach.

Electrochemical Therapy of Tumors

Indikáció: Hemangioma
Bizonyítás:
Szerző: 
Li Jing-Hong Xin Yu Ling
Páciensek száma:
Terápia: ECT
Év: 2013

ABSTRACT

Application of electric current for the tumor destruction has a long time history. The theory of the direct galvanic current (galvanotherapy, GT) is worked out by B. Nordenstrom in the frame of biologically closed electric circuits (BCECs). Later, GT was extended by chemical considerations (EChT), and, starting with pioneering work of Professor Xin Yu Ling, a wide, intensive application had been developed in China. My objective is showing the principles and practice of the EChT treatment modality for multiple advanced lesions.

Androtherm application for the Peyronie’s Disease

Indikáció: Prostate
Bizonyítás:
Szerző: 
Ballerini M Baronzio G F Capito G Szasz O Cassutti V
Páciensek száma: 30
Terápia: mEHT
Év: 2013

Abstract

Peyronie’s disease is characterized by a scarring fibrosis within the tunica albuginea of the penis that could lead to penile length loss, narrowing, curvature, erectile dysfunction, or pain with erection. This problem has recently no appropriate treatment. Our objective is to treat this kind of disease by a new kind of hyperthermia method.

Low back pain – complex approach of treatment by different CAM modalities (Acupuncture and other type of dry-needling, “Targeted RF non invasive physiotherapy” for low back pain).

Indikáció: Non-oncology
Bizonyítás: Phase I/II
Szerző: 
Hegyi G Jian Li
Páciensek száma: 2861
Terápia: mEHT
Év: 2013

Abstract

For at least 2,500 years, acupuncture has been an integral part of the traditional Chinese medicine. Recently, more people are diagnosed with chronic disease, and many of them are poorly treated with conventional therapies. Those frequently prefer other forms of complementary medical treatments. Based on the theory of homeostatic equilibrium being the basis of health, acupuncture focuses on restoring the homeostasis by manipulation of the complementary and opposing elements of yin and yang. It is possible that by affecting afferent nerve signaling, acupuncture may influence the release of endogenous opioids to promote pain relief. Our objective is giving western trained physicians clinical applications together with acupuncture and modern physiotherapeutic equipment (booster) to accommodate accelerating interests in acupuncture and related techniques in modern complex treatment of chronic low back pain. In recent prospective phase I/II study, statistical data verified the relevant end points of the study: the safety, the quality of life (QoL), the rest time, duration of painless state, and cost/benefit ratio.

Oncothermia with chemotherapy in the patients with Small Cell Lung Cancer

Indikáció: Lung
Bizonyítás: Phase I
Szerző: 
Doo Yun Lee Seok Jin Haam Tae Hoon Kim Jae Yoon Lim Eun Jung Kim Na Young Kim
Páciensek száma: 31
Terápia: CT+mEHT
Év: 2013

Abstract

Small-cell lung cancer (SCLC) is one of the most aggressive and lethal forms of lung cancers. Chemotherapy and radiotherapy would be standard modality for SCLC with median survival being less than 4 months only. Complementary treatment to chemotherapy is desired. Oncothermia will be one of the candidates to this addition. We have made a study of 31 SCLC patients from April 2006 to March 2012. 23 cases were treated with combined chemotherapy and oncothermia, and 8 cases were treated with chemotherapy alone. Three patients from 14 patients (14/31) died in the study period; there were equal numbers in the two arms, including one long survival case of 28 months and one of 26 months, in the combination and chemo-group, respectively .16 patients (16/31) are alive: 4 patients with chemotherapy only, including one long survival case of 28.7 months, and 11 cases with combined therapy including three long survival cases of more than 3 years. We conclude that the combined use of chemotherapy and oncothermia has significantly enhanced the survival rate in comparison with the use of chemotherapy alone (log-rank test: P value < 0.02).

Hypoxia Immunity, Metabolism and Hyperthermia

Indikáció: Immuno-oncology
Bizonyítás: Review
Szerző: 
Baronzio G Kiselevsky M Ballerini M Cassuti V
Páciensek száma:
Terápia: mEHT
Év: 2013

Abstract

Hypoxia is common in solid tumors and in many other disease states such as myocardial infarction, stroke, bone fracture, and pneumonitis. Once hypoxia has developed, the undernourished and hypoxic cells trigger signals in order to obtain new blood vessels to satisfy their increasing demands and to resolve hypoxia. The principal signal activated is an ancestral oxygen sensor, the hypoxia inducible factor (HIF). After its nuclear translocation, HIF triggers a series of mediators that recruit, into the hypoxic milieu, several immature myeloid, mesenchymal, and endothelial progenitors cells. Resident and recruited cells participate in the processes of neoangiogenesis, for resolving the hypoxia, while at the same time trigger an inflammatory reaction. The inflammatory reaction has as primary end point, the repair of the damaged area, but if an insufficient production of resolvins is produced, the inflammatory reaction becomes chronic and is unable to repair the damaged tissue. In this brief overview, we will show the differences and the similar events present in cancer, myocardial infarction, and stroke. Furthermore, the metabolic alterations produced in the tumor by hypoxia/HIF axis and the consequences on hyperthermic treatment are also discussed.

Lyme Disease and Oncothermia

Indikáció: Lyme-disease
Bizonyítás: Phase III
Szerző: 
Zais O
Páciensek száma: 12
Terápia: mEHT+Vitamins
Év: 2013

Abstract

Lyme disease is a tick-borne disease with multiple organ failures, and systemic disorders. Dramatic change becomes apparent in the chronic phase of the disease. Chronic fatigue syndrome, lapse of concentration, depression, joint pain, and muscle pain are a few, but major clinical symptoms characterizing the disease. The human immune system is defenseless. Borrelia uses various mechanisms to escape from immunoattacks or antibiotic therapies. This “stealth phenomenon” needs new therapeutic principles to be interrupted. Our objective in this paper is to study the effect of oncothermia, which is a well-established oncological therapy, on Lyme disease. First, in our present work, we definitely concentrate on the quality of life of the patients.

Oncothermia Application for Various Malignant Diseases

Indikáció: Multiple
Bizonyítás: Retrospective study
Szerző: 
Youngsuk Lee
Páciensek száma: 277
Terápia: CT+RT+mEHT
Év: 2013
ABSTRACT

Oncothermia was introduced to our hospital in 2010. Our objective is to report results of 277 patients treated by oncothermia during 20 months. We present some characteristic cases and statistical study of the overall results. We concluded by stating the feasibility of oncothermia to treat high variety of malignant diseases also in their very advanced (T4N3M1) stages.

Oncothermia in HIV positive and negative locally advanced cervical cancer patients in South Africa

Indikáció: Gynecology
Bizonyítás: Phase III
Szerző: 
Carrie Strauss Jeffrey Kotzen Ans Baeyens Irma Maré
Páciensek száma: 236
Terápia: CT+RT+mEHT
Év: 2013

Abstract

Aim. Investigate the clinical, economic, and cellular effects of the addition of oncothermia to standard treatment for HIV-positive and -negative locally advanced cervical cancer patients in public healthcare in South Africa. Objectives. Evaluate the effect that the addition of oncothermia has on local disease control, progression-free survival, overall survival at 2 years, treatment toxicity, quality of life, economic impact, and HIV status of participants. Radiobiology investigations will evaluate thermoradiosensitivity and the molecular markers for thermoradiosensitivity. Methodology. Phase III randomised clinical trial involving 236 HIV-negative and -positive stage IIb-III locally advanced cervical cancer patients. Treatment includes cisplatin, external beam radiation, and brachytherapy. The study group will receive oncothermia treatments. Participants will be monitored for two years after completion of treatment. Hypothesis. The addition of oncothermia to standard treatment protocols will result in improved clinical response without increasing treatment toxicity in HIV-positive patients or raising healthcare costs.

Treatment of advanced cervical cancer with complex chemoradio – hyperthermia

Indikáció: Gynecology
Bizonyítás: Retrospective study
Szerző: 
Lajos Pesti Zsófia Dankovics Péter Lorencz András Csejtei
Páciensek száma: 72
Terápia: CT+mEHT
Év: 2013

Abstract

This single arm, retrospective, single institution study investigated intention to treat patients (n=72) with advanced cancer of cervix of uterus. The study was performed in 2001–2010, providing 331 sessions. All patients had radiotherapies as fractional radiotherapy and intracavital brachytherapy. Some patients (n=34) received chemotherapy (Cisplatin 40 mg/m2/week; concomitantly with tele-radiotherapy) as well. Complementary to the teleradiotherapy, oncothermia was used two times a week, targeting the pelvis. Applied energy dose was 45 W, 60 min. Oncothermia was applied immediately after the infusion, when chemotherapy was also administered. Complete and partial remission were achieved in trimodal therapies for 73.5% of the patients, while we could stabilize the disease for 14.7% of the patients.

Successful Treatment of Advanced Ovarian Cancer with Thermochemotherapy and Adjuvant Immune Therapy

Indikáció: Gynecology
Bizonyítás: Case report
Szerző: 
R. Kleef S. Kekic N. Ludwig
Páciensek száma: 1
Terápia: CT+mEHT
Év: 2012

Abstract
We report on a 4-year progression-free survival of a 54-year-old female first diagnosed in December 2007 with advanced bilateral ovarian cancer FIGO IIIc, disseminated peritoneal carcinosis and malignant diaphragm invasion. Treatment started in January 2008 with 6 cycles of Taxol 175 mg/m2/carboplatin AUC 5 in 3-week intervals. Twenty-four hours following each chemotherapy session, fever-range long-duration whole-body hyperthermia (WBH) was performed at the temperature plateau of 40°C body core temperature for 6 h. Three months after completion of chemotherapy, 4 more long-duration WBH procedures were performed in monthly intervals. Importantly, long-duration WBH was paralleled with intradermal vaccination of autologous dendritic cells. No other treatment was given to the patient. Four years following the first diagnosis, the patient is still in complete remission with no evidence of disease.

Für und Wider des Prostata-Karzinom-Screenings

Indikáció: Prostate
Bizonyítás:
Szerző: 
Douwes FR
Páciensek száma:
Terápia:
Év: 2011

Adjuvante Radiotherapie: Welcher Patient mit Prostatakarzinom profitiert?

Indikáció: Prostate
Bizonyítás:
Szerző: 
Douwes FR
Páciensek száma:
Terápia:
Év: 2011

Successful Treatment of Solitary Bone Metastasis of Non-Small Cell Lung Cancer with Bevacizumab and Hyperthermia

Indikáció: Bone
Bizonyítás: Case report
Szerző: 
Gábor Rubovszky Tünde Nagy Mária Gődény András Szász István Láng
Páciensek száma: 1
Terápia: CT+mEHT
Év: 2011

Abstract

Non-small cell lung cancer (NSCLC) represents 85 % of all malignant lung cancers. In metastatic disease the principle goal of palliative therapy is to prolong survival with least toxicity and best patients’ quality of life. Bevacizumab (BEV) has been approved as first line treatment in combination with platinum based chemotherapy and maintenance therapy in NSCLC. BEV can be added safely to several chemotherapeutic agents, however there is no data on coadministration with thermotherapy. Even in localized disease no robust evidence exists about the beneficial effect of loco-regional thermotherapy on overall survival, but it might be used successfully in symptom palliation. In this article a successful co-administration of BEV and hyperthermia is reported in a patient with monolocalized bone metastasis from previously operated NSCLC. This case suggests that electrohyperthermia can probably be incorporated in palliative therapy added not only to radiotherapy or chemotherapy but also to anti-angiogenic BEV treatment.

Neue Studie heizt Diskussion über den Wert von PSA-Tests an

Indikáció: Prostate
Bizonyítás:
Szerző: 
Douwes FR
Páciensek száma:
Terápia:
Év: 2011

Oncothermia: Emerging Therapy in Oncology

Indikáció: Multiple
Bizonyítás: Review
Szerző: 
Marwan Akasheh
Páciensek száma:
Terápia:
Év: 2010

Abstract

The healing effect of heat was already mentioned in the advanced cultures of the old Egypt (2400 B.C.), but only the medical professionals of the Greek Antique used this therapeutic approach consistently, acknowledged it and called it over-warming (in Greek: Hyperthermia). Oncothermia is a new paradigm which entails the generation of temperature gradient by self-selection absorption of electric field energy based on the bio-impedance selection and modulated radiofrequency electric current to produce lethal heat flow between the extra- and intracellular matrix of the tumor cell membrane. It provides synergies with other traditional treatment modalities. The spread of this technology worldwide is a strong evidence to support it, based on palliative pain control and prolongation of survival in many solid tumors e.g. liver, pancreas, brain, prostate and lung when other therapies fail.

Keywords:
Oncothermia, Cancer, Deep Electro-Hyperthermia, Conductive Hyperthermia, Modulated Radiofrequency Electric Field.

Transcranial electro-hyperthermia combined with alkylating chemotherapy in patients with relapsed high-grade gliomas: phase I clinical results

Indikáció: Gliomas (advanced)
Bizonyítás: Phase I
Szerző: 
Wismeth C Dudel C Pascher C Ramm P Pietsch T Hirschmann Reinert C Proescholdt M Rümmele P Schuierer G Bogdahn U Hau P
Páciensek száma: 15
Terápia: CT+mEHT
Év: 2009

Abstract

Non-invasive loco-regional electro-hyperthermia (EHT) plus alkylating chemotherapy is occasionally used as salvage treatment in the relapse of patients with high-grade gliomas. Experimental data and retrospective studies suggest potential effects. However, no prospective clinical results are available. We performed a single-center prospective non-controlled single-arm Phase I trial. Main inclusion criteria were recurrent high-grade glioma WHO Grade III or IV, age 18-70, and Karnofsky performance score > or = 70. Primary endpoints were dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) with the combined regimen. Groups of 3 or 4 patients were treated 2-5 times a week in a dose-escalation scheme with EHT. Alkylating chemotherapy (ACNU, nimustin) was administered at a dose of 90 mg/m(2) on day 1 of 42 days for up to six cycles or until tumor progression (PD) or DLT occurred. Fifteen patients with high-grade gliomas were included. Relevant toxicities were local pain and increased focal neurological signs or intracranial pressure. No DLT occurred. In some patients, the administration of mannitol during EHT or long-term use of corticosteroids was necessary to resolve symptoms. Although some patients showed responses in their primarily treated sites, the pattern of response was not well defined. EHT plus alkylating chemotherapy is tolerable in patients with relapse of high-grade gliomas. Episodes of intracranial pressure were, at least, possibly attributed to EHT but did not cause DLTs. A Phase II trial targeting treatment effects is warranted on the basis of the results raised in this trial.

Clinical study for advanced non-small-cell lung-cancer treated by oncothermia

Indikáció: Lung
Bizonyítás: Open-label study
Szerző: 
Dani A Varkonyi A Magyar T Szasz A
Páciensek száma: 258
Terápia: CT+RT+mEHT
Év: 2009

Abstract

The non-small-cell-lung-cancer (NSCLC) is a common malignant tumor, and generally not best candidates for hyperthermia due to the cooling effect of the breathing. We present two retrospective clinical studies for NSCLC done by two medical centers (HTT-MED Day-clinic and Peterfy Hospital) made by special modulated field electro-hyperthermia, called oncothermia. Both of the centers made the treatments by oncothermia in combination with the conventional tumor-therapies. We present the data from both of the centers and make a metaanalysis as well. Results show a remarkable survival benefit for the patients compared to the historical data. The comparison of the studies demonstrates a good correspondence in the data, which strengthens the reliability of the studies, and greatly points out the feasibility of the oncothermia application on the NSCLC.

Clinical study for advanced pancreas cancer treated by oncothermia

Indikáció: Pancreas
Bizonyítás: Clinical study
Szerző: 
Dani A Varkonyi A Magyar T Szasz A
Páciensek száma: 99
Terápia: CT+RT+mEHT
Év: 2008

Abstract

Pancreas cancer (PCA) is an aggressive, common malignant tumor. We present two retrospective clinical studies of PCA done in two medical centers (HTT-MED Day-clinic and Peterfy Hospital). Both of the centers made the treatments by oncothermia in combination with the conventional tumor-therapies. We present the data from both centers and make a metaanalysis of the data as well. Results show a remarkable survival benefit for the patients compared to the historical data. The comparison of the studies shows a good correspondence in the data, which strengthens the reliability of the studies, and points out the feasibility of the oncothermia application on PCA.

Prostatakarzinom: Neue Aspekte für Diagnostik und Therapie

Indikáció: Prostate
Bizonyítás:
Szerző: 
Douwes FR
Páciensek száma:
Terápia:
Év: 2008

Prospective phase II trial for recurrent high-grade malignant gliomas with capacitive coupled low radiofrequency (LRF) deep hyperthermia

Indikáció: Gliomas (advanced)
Bizonyítás: Phase II
Szerző: 
Hager ED Sahinbas H Groenemeyer DH Migeod F
Páciensek száma: 179
Terápia: CT+RT+mEHT
Év: 2008

Abstract

Treatment of malignant gliomas is in spite of many new approaches still disappointing. Median survival time (MST) of pts. with glioblastoma multiforme (GM) after diagnosis is 6 to 12 months. Surgery is treatment of first choice, but in most cases healing is not possible. The aims of surgery are tumor debulking or decompression of the brain. Radiation will double MST after surgery but high grade gliomas are not very radiosensitivesurvival. Concomitant radiation with temozollamide could increase median survival time of pts with GM from 12.1 to 14.6 months.

Sanfte Hilfen für die Prostata

Indikáció: Prostate
Bizonyítás:
Szerző: 
Douwes FR
Páciensek száma:
Terápia:
Év: 2008

Deep electro-hyperthermia (EHY) with or without thermo-active agents in patients with advanced hepatic cell carcinoma: phase II study

Indikáció: Liver
Bizonyítás: Phase II
Szerző: 
Ferrari VD De Ponti S Valcamonico F Amoroso V Grisanti S Rangoni G Marpicati P Vassalli L Simoncini E Marini G
Páciensek száma: 22
Terápia: SRG+CT+mEHT
Év: 2007

Background: Advanced HCC has no standard chemotherapy , all pts would be valuabled in clinical trials. We evaluated effectiveness and toxicity of capacitatively coupled low-frequency 13.56 MHz deep hyperthermia (Oncotherm-EHY 2000) treatment on chemo- refractory malignant primary liver cancer which underwent all other possible treatment. Methods: From February 2005 to July 2006, we enrolled 22 pts with advanced HCC. ECOG PS was 1 or O. Viral hepatic infection status was 7 HBV+, 8 HCV+, 1 HCV/HBV+. Median age was 67,5 y (range 63 -78), male/female 20/2 . 15 pts were uneligible for liver surgery, 3 pts received TACE, 1 PEI, 1 a lot of therapy. 7 pts were pre-treated with surgery, 2 also received TACE, 1 PEI and 1 a lot of therapy. 75% of pts were in stage C of BCLC classification. 2 pts had also distant metastases, 70% of pts had portal vein thromboses. 8 pts underwent only to EHY without CT. Schedule: EHY was achieved by arrangements of capacitative electrodes with a radiofrequency field of 13.56 Mhz (RF-DHT) at 80- 130 W equivalent to 41 °- 47° C for 60 minutes, 2 times/w for 5 weeks in combination with thermo-active agents . EHY was applied over 2 time a week over 1 hour as mono – combined therapy . Concomitant chemotherapy was oxaliplatin 50 mgr at fixed dose on D 1and D 15. One cycle is 10 treatments of EHY ; 4 pts underwent 2 cycles and 2 pts to 3 cycles and 1 pt to 4 cycles . Median number of cycles was 1,5 (range 1–4), total EHY applications were 365. Results: EHY plus thermo-active drug is beneficial on clinical conditions off treated pts with an excellent compliance on out- patients. We observed 1 CR ( pt has only one bone metastases after 6 months without liver relapse), no PR, 25% of SD. Median survival time was 20’5 weeks (5 – 81+) We noted that 11 pts (50%) presented evidence of increasing well-being. Toxicity : 4 pts had skin reaction after application of EHY. In 3 pts we observed cutaneous hyperemia on the area of treatment and mild burn on the skin ; all symptoms disappeared after local steroid therapy , treatment was interrupted until resolution. Conclusions: Low toxicity and clinical benefit will be confirmed in further clinical studies. Capacitively coupled low-frequency 13.56 deep-hyperthermia is feasible for chemo-refractory HCC.

Retrospective clinical study of adjuvant electro-hyperthermia treatment for advanced brain-gliomas

Indikáció: Gliomas (advanced)
Bizonyítás: Retrospective study
Szerző: 
Sahinbas H Groenemeyer DHW Boecher E Szasz A
Páciensek száma: 140
Terápia: mEHT
Év: 2007

Summary

Malignant gliomas represent about 70 % of all brain tumors. Despite advances in standard therapy consisting of surgery, radiation therapy and chemotherapy, gliomas remain an essentially fatal disease, with a median survival time of 10 to 12 months and a 2-year survival rate of 8 % to 12 %. Electro-hyperthermia applied either alone or in combination with chemo- and/or radio-therapy is an advanced hyperthermia technique that has been used as adjuvant treatment for patients with malignant glioma. We present the results of a retrospective study of 140 patients with different stages of malignant glioma, which were treated/followed from January 2000 to February 2005. The endpoint was the overall survival and the survival from the 1st electro-hyperthermia treatment. The overall median survival time for patients with mostly advanced malignant glioma who received adjuvant electro-hyperthermia in this study was 20.4 months. The median survival time from the first electro-hyperthermia treatment was 6.6 months. Electro-hyperthermia was safe and well tolerated. The presented results show the feasibility of the treatment and suggest a benefit of the electro-hyperthermia treatment for patients with advanced malignant glioma.

A Phase II Clinical Study on Relapsed Malignant Gliomas Treated with Electro-hyperthermia

Indikáció: Gliomas (advanced)
Bizonyítás: Phase II
Szerző: 
Giammaria Fiorentini Petros Giovanis Susanna Rossi Patrizia Dentico Raffaele Paola Gina Turrisi Paolo Bernardeschi
Páciensek száma: 12
Terápia: CT+RT+mEHT
Év: 2006

Abstract

The purpose of this study was to evaluate the activity and toxicity of electro-hyperthermia (ET) on relapsed malignant glioma patients. Twelve patients with histologically diagnosed malignant glioma entered the study. Eight patients had glioblastoma multiforme, two had anaplastic astrocytoma grade III and two had anaplastic oligodendroglioma. All patients were pre-treated with temozolamide-based chemotherapy and radiotherapy. Hyperthermia with short radiofrequency waves of 13.56 MHz was applied using a capacitive coupling technique keeping the skin surface at 20°C. The applied power ranged between 40-150 Watts and the calculated average equivalent temperature in the tumours was above 40°C for more than 90% of the treatment duration. One complete remission and 2 partial remission were achieved, with a response rate of 25%. The median duration of response was 10 months (range 4-32). The median survival of the entire patient population was 9 months, with 25% survival rate at 1 year. ET appears to have some effectiveness in adults with relapsed malignant glioma.

Glioblastoma multiforme Grad IV: Regionale Tiefenhyperthermie, Antiangiogenese mit Thalidomid, Hochdosis-Ascorbinsäureinfusionen und komplementäre Therapie

Indikáció: Gliomas (advanced)
Bizonyítás:
Szerző: 
Hager ED Birkenmeier J
Páciensek száma:
Terápia:
Év: 2006

Einleitung

Epidemiologisch werden primäre Hirntumoren in Deutschland mit einer Inzidenz von etwa 10/100 000 Einwohner und Jahr beobachtet. Im Erwachsenenalter sind hierbei bis zu 50 % aller Gehirntumoren den Gliomen zuzuordnen mit deutlichem Anstieg ab dem 65. Lebensjahr auf ca. 18/100 000 Einwohner [1], [2]. Männer erkranken statistisch gesehen häufiger als Frauen (m/w: 1,2-1,9/1).

Die histologische Klassifikation, die nach dem überwiegendem Zelltyp vorgenommen wird, stellt eine wesentliche Grundlage für die Behandlung von malignen Gliomen dar, da die verschiedenen, feingeweblichen Entitäten ein unterschiedliches biologisches Verhalten und somit auch eine unterschiedliche Malignität aufweisen [15].

Nach Kernohan (1949) und Russel (1977) werden die einzelnen Tumoren in bis zu 4 Malignitätsgraden, entsprechend dem histologischen Grad der Entdifferenzierung und des Wachstumsverhaltens, unterteilt. Für Grad-I- und -II-Tumoren wird eine mittlere Überlebensdauer von 3 bis 5 Jahren angegeben. Bereits Gehirntumore vom Grad III mit malignem, infiltrativem Tumorwachstum verzeichnen eine Überlebensdauer von 2 bis 3 Jahren, während die Prognose für Patienten mit einem hochmalignem Glioblastoma multiforme Grad IV mit einer mittleren Überlebenszeit von 10 bis 12 Monaten als ganz schlecht anzusehen ist [1], [5].

Je nach histologischer Klassifikation kommen als leitlinienorientierte Behandlungsmaßnahmen von Hirntumoren die operative Entfernung [1], [2], [14] – zumindest eines Großteils des Tumors – und eine postoperative Bestrahlung mit einer empfohlenen Dosis von 60 Gy [1], [2], [13], [14] sowie ggf. die Chemotherapie (z.B. Temozolomid) in Frage [3], [9].

Die Radiatio erfuhr in den letzten Jahren einen stärkergradigen positiven Effekt mit Verlängerung der Überlebenszeit um etwa 4 bis 5 Monate, bedingt dadurch, dass eine höhere Strahlendosis hierbei exakter auf den Tumor gerichtet werden kann [8].

Der Nutzen einer Chemotherapie ist allerdings nach wie vor äußerst umstritten und wird unter Experten kontrovers diskutiert, so insbesondere beim Grad-IV-Glioblastom, wo kein wesentlicher Effekt evaluierbar ist [1]. Nach einer aktuellen randomisierten EORTC-Studie [12] bei Glioblastomen aus dem Jahr 2005 konnte die mediane Überlebenszeit von Patienten in gutem AZ durch eine Radiochemotherapie mit Temozolomid von 12 auf 15 Monate gesteigert werden, während bei Patienten in schlechtem AZ die adjuvante Chemotherapie nicht sicher wirksam war [5], [13]. Literaturangaben zufolge lassen weder eine Polychemotherapie inkl. des PCV-Schemas [1], [2], [7] noch eine Monotherapie mit BCNU oder ACNU nennenswert wirksame und lebensverlängernde Ansprechraten erkennen, wobei die individuelle Lebensqualität der Patienten unter dem Therapieregime entsprechende Berücksichtigung finden sollte [5], [11].

Behandlung des fortgeschrittenen Pankreaskarzinoms mit regionaler Hyperthermie und einer Zytostase mit Mitomycin- C und 5-Fluorouracil/ Folinsäure

Indikáció: Pancreas
Bizonyítás:
Szerző: 
Douwes F Migeod F Grote C
Páciensek száma: 30
Terápia: CT+mEHT
Év: 2006

Zusammenfassung

Hintergrund

Das Pankreaskarzinom stellt für die onkologische Therapie nach wie vor eine große Herausforderung dar. Bisher lässt sich der fortschreitende Verlauf der Erkrankung kaum aufhalten, so dass die 5- Jahres- Überlebensrate unter 1% liegt. Aufgrund der niedrigen Ansprechraten einer zytostatischen Therapie soll die Wirksamkeit einer Chemotherapie mit Mitomycin C/ 5-Fluorouracil/ Folinsäure durch den Einsatz der regionalen Hyperthermie verstärkt werden.

Methoden

Die Behandlungsergebnisse von 30 Patienten mit einem fortgeschrittenen Pankreaskarzinom wurden ausgewertet. Die Therapie bestand in einer Zytostase mit Mitomycin C (8 mg/m2), Tag 1 sowie 5-Fluorouracil (500 mg/m2) und Folinsäure (200 mg/m2) am Tag 1-5 und einer regionalen kapazitiven Hyperthermie (13,56 MHz), welche am Tag 1, 3, 5 und 10 für jeweils 60 min. angewendet wurde. Während der Hyperthermie wurden dabei im Tumorgewebe Temperaturen von 420C bis 440C erreicht. Der Behandlungszyklus wurde alle 4 Wochen, bis zum Auftreten einer Progression, wiederholt.

Ergebnisse

Die 30 Patienten erhielten insgesamt 94 Behandlungszyklen. Als Resultat der Kombinationstherapie kam es bei einem Patienten zu einer kompletten Remission, 10 (33,3%) weitere zeigte eine partielle Remission. Bei 12 (40%) konnte eine Stabilisierung der Erkrankung erreicht werden, 7 Patienten (23,3%) sprachen nicht auf die Therapie an. Die mediane Überlebenszeit betrug 8 Monate (2-53), die mediane Zeit bis zur Progression (1-40 Monate). Schluss Die Kombination von regionaler Hyperthermie und Chemotherapie stellt eine sinnvolle Erweiterung in der palliativen Behandlung von Pankreaskarzinomen dar. Die in unserer Klinik gemachten Erfahrungen zeigen eine erhöhte Effektivität der eingesetzten Zytostatika bei guter Verträglichkeit.

Thermo-chemotherapy of the advanced pancreas carcinoma

Indikáció: Pancreas
Bizonyítás:
Szerző: 
Douwes FR
Páciensek száma: 18
Terápia: CT+mEHT
Év: 2006
Abstract
The results of chemotherapy of pancreas carcinoma are still disappointing. In nearly all cases the disease progresses, response rates to cytotoxic therapy are low and the 5-year survival rate amounts to 1%. The purpose of the present study was to evaluate whether response rate, time to progression and survival time can be improved by the combination of cytostatic treatment and loco-regional hyperthermia (thermo-chemotherapy). Results: According to the standard criteria, 1 patient had a complete remission, 10 patients had a partial remission; 7 patients did not respond to the therapy and showed progressive disease. Thermo-chemotherapy as applied in this clinical study shows a remarkable clinical outcome in advanced pancreas cancer and is well tolerated. The results suggest further evaluation in randomized trials.

Malignes Melanom Stadium IV: Anwendung von regionaler Tiefenhyperthermie, Tamoxifen, Interferon-α und komplementären Therapien

Indikáció: Melanoma
Bizonyítás:
Szerző: 
Hager ED Birkenmeier J
Páciensek száma:
Terápia:
Év: 2006

Einleitung

Die Prognose von Patienten mit metastasiertem Melanom ist schlecht. Alle bisherigen Behandlungskonzepte sind unbefriedigend. Die mediane Überlebenszeit liegt in den meisten Studien zwischen 6 und 9 Monaten und das 5-Jahresüberleben bei nur 1 bis 2 %.

Zytostatika ermöglichen Ansprechraten zwischen 10 und 20 % mit einem Anteil von kompletten Ansprechraten von bis zu 5 %. Am besten sprechen Haut-, Lymphknoten- und Lungenmetastasen an. Obwohl ein Viertel der kompletten Remissionen länger anhalten, überleben weniger als 2 % der Patienten 5-6 Jahre. Dacarbazin ist das einzige für diese Indikation zugelassene Zytostatikum, aber es gibt keine Phase-III-Studien, die einen Überlebensvorteil im Vergleich zu anderen Behandlungen oder selbst Nicht-Behandlungen zeigen. Temozolomid, als aktiver Metabolit von Dacarbazin, kann ebenfalls angewendet werden. Platinderivate weisen eine mäßige Aktivität bei Melanomen auf; ebenso Vinblastin und Taxane. Nach Phase-II-Untersuchungen scheint die Kombination mit Tamoxifen die antineoplastische Wirkung von Zytostatika zu verstärken (von 10 % auf über 40 % mit Œ CR); aber in Phase-III-Studien wurden diese Resultate bisher nicht bestätigt.

Obwohl die Immuntherapie nur bei einem kleinen Prozentsatz der Patienten effektiv ist, können die Resultate in Einzelfällen dramatisch sein. Die bisher am meisten untersuchten Substanzen sind Interferon-α (IFN-α) und Interleukin-2 (IL-2), weshalb sie in die Therapie einbezogen werden. Das Tumoransprechen liegt bei 15 %, ist aber meist auf kleinvolumige kutane oder Weichteiltumore beschränkt. Allerdings kann die progressionsfreie Zeit von Patienten mit einer kompletten Remission (ca. 5 %) nach einer Immuntherapie sehr lang sein. Monoklonale Antikörper gegen Ganglioside, meist GD2 und GD3, zeigten antitumorale Aktivitäten in Phase-I/II-Studien. Durch Konjugation mit Antikörpern und Fusion mit Proteinen kann die Wirkung noch gesteigert werden. Die adoptive Immuntherapie mit ‚IL-2-aktivierten peripheren Blut-Lymphozyten’ (LAK-Zellen) führte zu keinem therapeutischen Vorteil. Dagegen konnte mit ‚Tumor-infiltrierenden Lymphozyten’ (TILs) in Phase-I/II-Studien ein Ansprechen in bis zu 34 % erreicht werden. Vakzinationsstrategien mit verschiedenen Melanom-Zellpräparationen erwiesen sich potenziell effektiv, aber die optimalen Bedingungen für diese Therapien müssen noch gefunden werden. Dies gilt auch für die Therapie mit dendritischen Zellen. Das Hauptproblem der Immuntherapie liegt wohl in der Überwindung der tumorassoziierten Immunsuppressionen.

Hyperthermia in combination with ACNU chemotherapy in the treatment of recurrent glioblastoma

Indikáció: Gliomas (advanced)
Bizonyítás:
Szerző: 
Douwes F Douwes O Migeod F Grote C Bogovic J
Páciensek száma: 19
Terápia: SRG+CT+RT+mEHT
Év: 2006

Bestrahlung der Prostata erhöht Rektum-Ca-Risiko

Indikáció: Prostate
Bizonyítás:
Szerző: 
Douwes FR
Páciensek száma:
Terápia:
Év: 2005

Whole body hyperthermia combined with carboplatin/paclitaxel in patients with ovarian carcinoma – Phase-II-study

Indikáció: Gynecology
Bizonyítás: Phase II
Szerző: 
Strobl B Rjosk D Janni W et al.
Páciensek száma: 9
Terápia: CT+WBH
Év: 2004

Rebell gegen den Krebs. Biologische Intersivtherapie – Neue Hoffnung für Patienten?

Indikáció: Prostate
Bizonyítás:
Szerző: 
Maar K
Páciensek száma:
Terápia:
Év: 2004

Whole-body hyperthermia in combination with platinum containing drugs in patients with recurrent ovarian cancer

Indikáció: Gynecology
Bizonyítás:
Szerző: 
Douwes F BogoviC J Douwes O et al.
Páciensek száma: 21
Terápia: CT+WBH
Év: 2004

Abstract

BACKGROUND:

Patients with advanced ovarian cancer have an enormous risk of relapse after primary therapy, and the prognosis for these patients remains bleak. Primary and acquired resistance of tumor cells to antineoplastic drugs is a major cause of the limited effectiveness of chemotherapy. The effect of whole-body hyperthermia (WBH) combined with platinum-containing chemotherapy in the treatment of recurrent ovarian cancer was examined in this study.

Lebermetastasen bei kolorektalen Karzinomen

Indikáció: Liver
Bizonyítás:
Szerző: 
Hager ED
Páciensek száma:
Terápia:
Év: 2004

Thermo-Chemotherapie des fortgeschrittenen Pankreaskarzinoms. Ergebnisseeiner klinischen Anwendungsstudie

Indikáció: Pancreas
Bizonyítás: Clinical study
Szerző: 
Douwes FR
Páciensek száma: 30
Terápia: CT+mEHT
Év: 2004

ABSTRACT: Oncothermia is a method of hyperthermia in oncology, controlling the locally applied deep heat by selectively targeting the cellular membrane of the malignant cells. The selection of the method is based on various biophysical and biochemical achievements. There are various differences between the malignant and healthy cells, which could be used for their selection by heat targeting. The primary selection factor is a different metabolic activity which creates distinguishable environments of the malignant cells. The other factor is the clear difference of dielectric properties of the membrane and near-membrane extracellular electrolytes, marking off the malignancies. There is also a structural factor, which is clear in the different pathological patterns of the malignancy from their healthy counterparts. This last is described by fractal pattern evaluation technique, in which dynamic time-fractal transformation is used for further discernment of the malignancy. My objective is to show a new heating method, which makes oncological hyperthermia controllable and effective. 1. Introduction Oncological hyperthermia is the overheating of the malignant tissues locally or systemically. The method is deduced from the ancient medical practices, where the heat therapies had a central role in medicine. The local hyperthermia by the radiation of red-hot iron was the first known oncological treatment applied by Hypocrites, who described the method [1]. The main idea was originated from sacral considerations formulating the overall force of the “fire.” However, physiological consideration was also behind that together with beliefs: the local heat accelerates the metabolic activity without extra supply of this action from the unheated neighboring volumes. This physiological mechanism is accompanied by severe hypoxia, and it finally kills the target by acidosis. The working idea has recently been shown, proving the impoverishment of ATP and enrichment of lactate in the locally heated tumor tissue [2]. Due to the primitive heating techniques, the ancient radiative heat is only rarely applied in real cases. The central point of the locally applied oncological hyperthermia is the selective heat delivery into the deep-seated tumors. The discovery of the electromagnetic heating gave new perspectives for deep heating, and hyperthermia started its first “golden era” in oncology. It was among the first modern curative applications of modern techniques in oncology [3] and was followed by a controlled clinical study involving 100 patients as early as 1912. It showed remarkable.

Malignus és benignus prosztatadaganatok hyperthermiája

Indikáció: Prostate
Bizonyítás:
Szerző: 
Szasz A
Páciensek száma: 252
Terápia: mEHT
Év: 2003

The treatment of patients with high-grade malignant gliomas with RF-hyperthermia

Indikáció:
Bizonyítás:
Szerző: 
Hager ED Dziambor H App EM Popa C Popa O Hertlein M
Páciensek száma: 36
Terápia: CT+RT+mEHT
Év: 2003

Tolerability of external electro-hyperthermia in the treatment of solid tumors

Indikáció: Toxicity
Bizonyítás:
Szerző: 
Cremona F Pignata A Izzo F Ruffolo F Delrio P
Páciensek száma:
Terápia:
Év: 2003

Whole-body hyperthermia in combination with platinum-containing drugs in patients with recurrent ovarian cancer

Indikáció:
Bizonyítás:
Szerző: 
Friedrich Douwes Juri Bogovic Ortrun Douwes Friedrich Migeod Christoph Grote
Páciensek száma: 21
Terápia: CT+mEHT
Év: 2003

Abstract

Background. Patients with advanced ovarian cancer have an enormous risk of relapse after primary therapy, and the prognosis for these patients remains bleak. Primary and acquired resistance of tumor cells to antineoplastic drugs is a major cause of the limited effectiveness of chemotherapy. The effect of whole-body hyperthermia (WBH) combined with platinum-containing chemotherapy in the treatment of recurrent ovarian cancer was examined in this study. Methods. Patients studied were those with pathologically verified epithelial ovarian cancer after operation who had had first-line chemotherapy with cisplatin or carboplatin, and relapsed. All 21 patients were treated with WBH and platinum-based chemotherapy. During the WBH, a core temperature of 41.5°C–42°C was attained in the rectum. We combined the WBH with 300–400mg/dl artificial hyperglycemia. The plateau temperature was held over a period of, on average, 90 30min, and the artificial hyperglycemia, on average, 240 30min. WBH was repeated at the beginning of each new chemotherapy cycle. Results. One patient (4.8%) had a complete remission, 7 patients (33.3%) had a partial remission, stable disease was noted in 10 patients (47.6%), and 3 (14.3%) patients did not respond and had progressive disease. Median time to progression was 6.5 months, and median survival time, 16.5 months. Conclusion. Our results validate the efficacy of WBH in the treatment of patients with recurrent platinum-resistant ovarian cancer. The overall tolerance of this treatment was good. The priority for all patients was an improvement in life quality; this was seen 3–4 days after WBH. The encouraging results should be confirmed in randomized studies.

Radiofrequency Transurethral Hyperthermia and complete Androgen Blockade. A Nonsurgical Approach to Treating Prostate Cancer

Indikáció: Prostate
Bizonyítás:
Szerző: 
Douwes FR Lieberman S
Páciensek száma: 184
Terápia: mEHT
Év: 2002

Transurethral hyperthermia in early stage prostate cancer

Indikáció: Prostate
Bizonyítás:
Szerző: 
Douwes FR
Páciensek száma: 34
Terápia: mEHT
Év: 2001

Objective

A treatment only has value if it can be demonstrated to be more effective than doing nothing. The major treatment for early prostate cancer (PC) is surgery or radiation. Unfortunately, none of these has been clearly shown to have a positive effect on long-term survival. In a study published in JAMA in 1997 a prospective, population-based study in Sweden showed that 223 patients that did not have a radical prostatectomy had the same long-term survival rate (81%) as those that did. Several statistics show that prostatectomy in early-stage cancer cannot affect the natural course of the disease. Several investigations have shown the efficiency of hyperthermia in different malignant tumours. We now have more than 10 years of experience with hyperthermia for the treatment of PC and the results are promising. The strategy of modern anticancer therapy is directed towards the control of local tumour growth with the maximum possible elimination of the neoplastic cell load. Hyperthermia offers support for both direct cell killing and sensitising neoplastic cells to hormone-, radio- and chemo-therapy.

Posttreatment Histology and Microcirculation Status of Osteogenic Sarcoma after a Neoadjuvant Chemo- and Radiotherapy in Combination with Local Electromagnetic Hyperthermia

Indikáció: Bone
Bizonyítás: Retrospective study
Szerző: 
Bogovic J Douwes F Muravjov G Istomin J
Páciensek száma: 62
Terápia: CT+RT+mEHT
Év: 2001

Abstract

BACKGROUND:

Many biological attributes of tumors (including regional blood flow and microcirculation) can deteriorate the homogeneity of heat distribution and temperature elevation during hyperthermia. We analyzed the connection between the microcirculation status of osteogenic sarcomas and the posttreatment histology after neoadjuvant chemotherapy, irradiation and local hyperthermia.

PATIENTS AND METHODS:

62 patients with histologically verified osteosarcoma (35 men, 27 women, age 9-53, average 21 years) were enrolled in the retrospective pathohistological study. 61 patients were evaluable. In 72.6% of cases the tumor was localized in bones forming knee joints. All patients received neoadjuvant treatment [6 hyperthermias (60 min, 42-45 degrees C), daunorubicin 30-50 mg/m(2), 6 infusions, adriamycin or cisplatin 30 mg/m(2) for 3 days or once 90 mg/m(2) monochemotherapy before the hyperthermic procedure; subsequently gamma-therapy, 20-36 Gy] followed by surgery. From archives, a control group was formed of 20 therapy-naive tumors. Resected tumors were histologically examined for assessment of spontaneous and therapeutically induced alterations. For analysis of the functionality status of microcirculation on histological cuts, 40 tumors (without selection) were investigated: 10 controls and 10 cases each with minimal, subtotal and total posttreatment alterations.

RESULTS:

Chemotherapy and radiotherapy in combination with local hyperthermia induced a distinct damage to osteosarcoma. In 39.3 and 35.7% of cases there was subtotal and total devitalization of tumor parenchyma, respectively. Thrombosis of magistral and middle vessels, stasis in the microcirculation tree (collapse), damage to intimal vessels and endothelial cells, and necrotic alterations of the vessel walls appeared predominantly in central areas of tumors. Tumors with minimal devitalization of the parenchyma had a share of nonfunctional vessels ranging from 10.6 to 61.7%, mean 29.7%. In tumors with subtotal necrosis, between 34.5 and 72.0% (mean 49.46%) of vessels were nonfunctional (stasis, thrombosis). In 10 cases with 100% necrosis of the osteosarcoma parenchyma, a mean of 56.05% of nonfunctional vessels was registered (12.3-83.0%). In the control group, between 2.85 and 73.4% (mean 21.69%) of vessels showed damage to the microcirculation.

CONCLUSION:

There is a direct correlation between deterioration of the microcirculation in osteosarcoma and thermo-radiochemotherapy- induced tissue alteration; the devitalization grade is directly proportional to the number of nonfunctional vessels in the tumor.

Deep hyperthermia with radiofrequencies in patients with liver metastases from colorectal cancer

Indikáció: Gastrointestinal
Bizonyítás: Clinical study
Szerző: 
Hager ED Dziambor H Höhmann D Gallenbeck D Stephan M Popa C.
Páciensek száma: 80
Terápia: CT+mEHT
Év: 1999

Abstract

Patients at advanced stage of colorectal cancer with liver metastases have been treated with deep hyperthermia alone or in combination with chemotherapy (5-FU + FA + MMC). Hyperthermia was achieved by arrangements of capacitive electrodes with a radiofrequency field of 13.56 MHz (RF-DHT). This prospective open single-arm clinical study with 80 patients suffering from liver metastases from colorectal cancer gives some first hints, that deep RF-hyperthermia alone may have a substantial beneficial effect on overall survival time of patients with liver metastases from colorectal cancer. Long lasting no-change, partial and even some complete remissions could be observed. The overall median survival time from progression of metastases or relapse was 24.5 months and survival rates at 1, 2 or 3 years from first diagnosis of metastases or progression were twice as high as expected from patients treated with chemotherapy. The combination of hyperthermia with delayed chemotherapy did not change overall survival time. These encouraging results deserve to be confirmed in randomized clinical studies.

Hoffnung bei Prostata-Beschwerden. Die neue Therapie ohne Messer

Indikáció: Prostate
Bizonyítás:
Szerző: 
Douwes F Sillner L Köhnlechner M
Páciensek száma:
Terápia:
Év: 1999

Complex therapy of the not in sano respectable carcinoma of the pancreas – a pilot study

Indikáció: Pancreas
Bizonyítás:
Szerző: 
Hager ED Süsse B Popa C Schritttwieser G Heise A Kleef R
Páciensek száma:
Terápia:
Év: 1994
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