Oncothermia Journal Volume 1

„In der Onkologie, besonders in der Medikamentösen Tumortherapie wären gegenwärtiger Standard, innovative Therapien und künftige Entwicklungen ohne Studien nicht mehr denkbar. Der empirische Erkenntnisgewinn verliert an Bedeutung, damit auch das individuelle ärztliche Urteil („Erfahrung heißt gar nichts. Man kann eine Sache auch 35 Jahre schlecht machen“ Kurt Tucholsky).

“Background: Hyperthermia was the very first oncotherapy in human medical history. It was virtually forgotten till the discovery of the electromagnetic radiations. Form that time hyperthermia has a rapid development in the modern oncotherapy, [1], [2]. This relatively simple, physical-physiological method has a phoenix-like history with some bright successes and many deep disappointments. The reason is simple: the technique to deliver the appropriate energy and selectively target the deep-seated tumor, was not available. Oncothermia solved this long time open problem.

„The author travels around the world looking for promising cancer treatments for clients of his report and mconsultation service. He reports here on his site visits to complementary and alternative medicine (CAM) clinics that treat cancer in the United States, Caribbean, Europe, Near East and Asia. What are some of the methods that are commonly found in these clinics? What are the “signature” methods that are unique to each particular venue?

“Dr. Dr. Dipl.-Phys. E. D. Hager ist in der Nacht des 13. Dezember 2009 im Alter von nur 62 Jahren, für uns alle dramatisch und erschütternd auf der Höhe seiner geistigen Schaffenskraft und Reife, in der von ihm gegründeten BioMed-Klinik verstorben. Er war uns ein Freund, ein Gefährte, ein Helfer, ein hilfsbereiter Arztkollege, ein Familienmensch für Mitarbeiter und Verwandte und eine Eindrucksvolle, visionäre Persönlichkeit in Einem, mit allen Widersprüchen die einen individuellen Pionier charakterisieren. Der Name von Dr.

“The purpose of this study was to evaluate the activity and toxicity of electro-hyperthermia (ET) on relapsed malignant glioma patients. Twenty four patients with histologically diagnosed malignant glioma entered the study. Sixteen patients had glioblastoma multiforme, four had anaplastic astrocytoma grade III and four 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 degrees C….”

„Die transurethrale Thermotherapie ist eine schonende und nicht invasive Methode, die die Prostata selektiv vom Prostatakarzinomgewebe befreien kann. Durch eine gleichzeitig eingeleitete komplette Androgenblockade kann dieser Prozess dauerhaft positiv unterstütz werden. In unserer Anwendungsstudie, die vor 10 Jahren begonnen wurde, wurden 123 Patienten mit bioptisch gesichertem und auf die Prostata begrenztem Prostatakarzinom eingeschlossen. Die Patienten erhielten nach Einleitung einer kompletten Androgenblockade eine zweimalige transurethrale Thermotherapie mit dem PCT der Fa.

„Background: The results in the therapy of pancreas carcinoma remain disappointing. In nearly all cases the disease progresses, response rates of cytotoxic therapy are low and the 5-year survival rate amounts to 1%. The purpose of our treatment was to enhance the effectiveness of a cytostatic treatment with mitomycin c by combination with regional hyperthermia. Patients and Methods: In a retrospective analysis 30 patients with advanced pancreatic carcinoma treated with a combined treatment with hyperthermia and chemotherapy were included.

„Auf der Basis der Datenlage der ERSPC Studie werden die Hintergründe und Argumentationsgrundlagen beleuchtet. Die Statistiken hinter der Statistik werden mit einbezogen und erläutert. Die Datenlage rückt die Prostatahyperthermie in eine wichtige Position im allgemeinen Therapieschema der gutartigen und bösartigen Erkrankungen. Vor dem Hintergrund der neu erstellten Leitlinien zur activ surveillance findet sich die Prostatahyperthermie in einer Schlüsselposition zur Behandlung der Patienten gerade mit bösartigen Erkrankungen….“

„Gerade in vermeintlich palliativer onkologischer Behandlungssituation ist man gehalten, nur noch Krankheitsrisiken und Symptome zu verhindern oder zu mindern, aber nicht mehr mit minimalen Erfolgsaussichten und maximalen Nebenwirkungsrisiken Heilungen zu erzielen. Das Optimum solch einer Behandlungsstrategie wird anscheinend dann erreicht, wenn man hierfür die Elektrohyper thermie/ Oncothermie in ein relativ anspruchsvolles, teilweise Fachdisziplin-übergrei fen des Gesamtkonzept einbettet.

„Abstrakt: Seit mehr als 100 Jahren wird auf dem Gebiet der Hyperthermie geforscht. Zahlreiche Wirkungsmechanismen der Hyperthermie auf Krebszellen konnten mittlerweile aufgeklärt werden. Voruntersuchungen auf zellulärem Niveau und in Tierversuchen konnten eine günstige Wirkung der Hyperthermie bei Krebserkrankungen belegen. Auch bei Menschen konnte in Studien mit der Hyperthermiebehandlung eine Wirkungsverstärkung anderer Krebstherapien wie Chemotherapie oder Bestrahlung gezeigt werden….“

„Zusammenfassung: Das intrahepatische cholangiocelluläre Carcinom gehört in Mitteleuropa zu den seltenen malignen Erkrankungen. Die Diagnose wird häufig erst in einem fortgeschrittenen Stadium gestellt. Die Behandlungsansätze sind unterschiedlich, eine Heilung kann nur selten erreicht werden. Beschrieben wird die Behandlung einer 61-jährigen Patientin mit einem intrahepatischen CCC. Es konnte gezeigt werden, dass mit der Kombination von extremer Ganzkörperhyperthermie und Regionaler Tiefenhyperthermie ein dreijähriges symptomfreies Überleben möglich ist.

“Summary: Тhe article is devoted to the problem of primary operable rectal cancer. The research purpose was to study and to assess the use of local electrohyperthermia in combination with radiaotherapy in primaryoperable rectal cancer and the role of neoangiogenesis in the relapses development. The data of 90 patients with primary operable rectal cancer over a period between December 2005 and September 2006 were analyzed. Depending on the treatment method patients were divided into 2 groups.

“Local-regional hyperthermia devices are using round treatment electrodes with different sizes up to 30 cm in diameter. Unfortunately in many patients 30 cm diameter electrodes do not cover all tumors areas in the body. Trying to overcome this problem, many patients are treated with 2 or even 3 fields at any session doubling the treatment time by a factor of 2 or 3. In addition, the round electrodes do not allow a complete cover of the treatment field. With the new EHY-3000 device by Oncotherm this problem was completely disappeared.

“Purpose: On the basis of the definition of high-risk soft tissue sarcomas and prognostic factors, the most recent developments with spezial emphasis on regional hyperthermia combined chemotherapy are reviewed. Findings: The most important prognostic factors (e.g.

“Background: Neutrophil granulocytes are presented in blood stream in greatest strength among white blood cells in mammalians, having crucial role in the immune system. Neutrophils are one of the first responders on inflammations or bacteria infections, and their role is essential in the defense mechanisms of the organism [1]. Various chemical signals activate the migration of neutrophils toward to the site of inflammation [2] and it could effect even in the cancer cases [3]….”

“Material und Methodik: In den Jahren 1999 bis 2009 wurden 10 Patientinnen im Rahmen der Dolphin-0- Studie (Carboplatin AUC6/ Paclitaxel 175mg/m2 kombiniert mit Ganzkörperhyperthermie (GKHT) bei primärem oder rezidiviertem Ovarialkarzinom) und 29 Patientinnen im Rahmen der Dolphin-1-Studie (Carboplatin AUC5/ Ifosfamid 3g/m2 kombiniert mit GKHT bei rezidiviertem Ovarialkarzinom) behandelt. Nach Abschluss der Dolphin-1-Studie wurden weitere 13 Patientinnen nach dem Studienprotokoll außerhalb der Studie behandelt.

„Background: Disulfiram is an old drug used to treat alcholism. Recently some authors has demonstrated antineoplastic activity in preclinical settings on various cancer types. The mechanisms of action is not fully understood but seems to rely mainly on the inhibition of proteasome, comparable to that of other specific drugs like bortezomib. Previous complexation of disulfiram with heavy metal ions, mainly Cu and Zn, is mandatory for disulfiram activity. Hyperthermia on the other hand proved to be sinergistic with proteasome inhibition in cancer cell lines.

“Objective: Study and research of the therapeutic efficacy and adverse reactions of integrative treatment of colon carcinoma with Oncothermia and Clifford TCM (Traditional Chinese Medicine) Immune Booster.

“Background: Learning from the widely published literature we started to treat our gynecology patients who were eligible for oncothermia to treat in harmony with brachy- chemo- and external radio-therapies. Our aim was in this article to report our observations and results. Method: We had offered for the eligible patients receiving complementary oncothermia to their standard treatment protocols. In the actual circumstances and financial conditions, we were able to recruit 80 patients for this study.

“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.

“Astrocytomas and glioblastomas are a class of aggressive neoplasms that are resistant to convectional therapies. Recent studies have demonstrated that Temozolomide (TMZ) is a well tolerated chemotherapy for brain tumors and is active as single agent or in combination with radiotherapy. Several studies in vitro have demonstrated that hyperthermia plus chemotherapy has a higher cytotoxic effect than chemotherapy alone. We have studied 29 patients with aggressive brain tumors [11 glioblastomas (GBM), 6 Astrocytomas IV , 8 Astro II, 1 Oligoastrocytomas) 2 ependymomas and 1 medulloblastomas].

“Purpose: Oncothermia has been started in South Korea since 2007 and its treatment is getting gradually expanded in Korean cancer patients. Though this device is widely accepted that it is safe and beneficial, Korean experience of oncothermia was not known until now. Thus this study was underwent retrospectively to determine the safety and complications of oncothermia Methods: From June to November in 2009, 127 cancer patients were received oncothermia alone or combined with other cancer treatment at SAM general hospital.

“Background: Treatment of intramuscular vascular malformations (IVMs) poses a major clinical challenge for the contemporary medicine. Surgical resection is difficult and frequently unsuccessful, radiological intervention with embolization has an ill-defined role, and conventional sclerotherapy has little to offer for a large scale disease. Objective: To evaluate the efficacy and safety of electrochemotherapy (EChT) in treating intramuscular vascular malformations….”

„Im Konzept der biologischen Krebstherapie spielt die Ganzkörperhyperthermie eine wichtige Rolle, meist jedoch in palliativer Situation. In der adjuvanten Situation gibt es bisher nur kasuistische Daten. Im Vortrag wird die Immunologie bei/nach Chemotherapie beleuchtet und ein Überblick zur immunologischen Bedeutung von Fieber gegeben, welches Krebspatienten meist langjährig vor der Erkrankung nicht mehr erlebt haben. Seit Praxisniederlassung Anfang 2002 wird ein Kollektiv von  zwischenzeitlich 47 Patienten (überwiegend Mamma-Ca.) beobachtet, dass adjuvant mit mind.

“Background: Oncothermia method (OTM) uses well controlled modulated radiofrequency (RF) current-flow through the target tumor. It is an emerging technique for oncology [1]. OTM is based on solid scientific roots [2], and its experimental support connects the in-silico, in-vitro and in-vivo experiments in a synergic harmony with the permanent development of its clinical success [3].

“Introduction: During the last decade, there has been an amazing progress in cancer research and treatment in the world and also in Korea. Nevertheless, the overall 5-year survival rate of lung cancer patients in 2001 - 2005 period was still 15.6% in South Korea. This type of cancer is usually diagnosed in advanced stage, consequently the overall survival did not show noticeable improvement. Poor performance status and/or multiple co-morbidities limit the treatment options for elderly patients.

“Introduction: Oncothermia method is more than twenty years serves the cancer treatments demands. It is successfully applied both in monotherapy and as complementary therapy with other oncotherapeutic modalities, irrespective their specialties. The experimental preclinical research started five years ago to investigate the theoretically predicted mechanisms by rigorous basic science approvals. The complexity and interdisciplinary of the in vivo experimental series requested a wide cooperative scheme of various respected and honored research institutes and university laboratories.

“Background: Long-time living ancient paradigm is eliminating the tumor cells by drastic, artificial effects (resection and necrosis) in the actual lesions. Original idea of the very first interventions in oncology had favored the necrosis by elevated temperatures in the local area. The original hyperthermia (HT) concept used the consequences of the definite high temperature in the tissue and in the physiology reactions. Oncothermia method (OTM) is a modern heir of this ancient thinking.

“Objective: One of the problematic point of the medication its targeting. The systemically administered drugs are distributed in the whole body by the blood, irrespective its origin by i.v. infusion, orally taken or getting by muscular injection, rectal suppository, skin-addicted, inhalations etc. However the delivery and the in-situ effect of the given drug to the target is a crucial point of the treatment.

“Objective: None of the established state-of-the-art treatments in malignant primary brain tumors, especially in glioblastoma multiform (GBM), could show effective or commonly accepted curative potential until today. The editorial question of JAMA [1] in 2005 is actual even now: “Where to go from here?” Our objective to show a feasible way to go, summarizing the results obtained till now made by modulated electrohyperthermia (oncothermia) in various clinics in EU….”

“Background: Hyperthermia is an ancient treatment modality, but more than two millennia were not enough for its wide acceptance. Modulated RF-conductive heating (oncothermia [1]) introduces a new controllable, successful paradigm. It has twenty years experience in the clinical practices. During this long time, a huge number of patients were treated with the method in their advanced states, in combination with conventional therapies, or sometimes, when those were fall, applied as monotherapy.

“Clifford Hospital is the first JCI (Joint Comission International) accredited Chinese hospital, a National Grade ”Triple-A” Hospital and a ”Famous Traditional Chinese Medicine Hospital” of China. It is a large modern general hospital, has been accredited by JCI three times. (The JCI accreditation surveys are carried out once every 3 years.)…”

“The backbone of therapy in non-operable non-small cell lung cancer (NSCLC) is systemic treatment. The principle goal is to prolong survival with the least toxicity keeping in mind the importance of patients’ quality of life. Bevacizumab (bev) has been accepted as first line and maintenance therapy in NSCLC. Bev can be added safely to several chemotherapeutic agent and radiation therapy, however there is no data on coadministration with thermotherapy.

“Objective: The modern development and design is based on the harmony of the integrated parts, and also their updates with the state-of art of the science and other professional knowledge. Oncotherm is devoted to the highest available efficacy and safety, which requests a real interdisciplinary thinking and wide range knowledge in both the scientific and technical fields. Our objective is to show how Oncotherm follows this interdisciplinary trend and develops its devices….”

„Die Elektrophysiologie ist noch weitgehend von Denkweisen und Ansichten aus der Elektrophysik und Elektrotechnik geprägt. Da international eingeführte Meßgrößen, Normen und Meßverfahren sowie Bezeichnungen übernommen werden mußten, ist das verständlich. Der elektrische Leitfähigkeitsmechanismus im Körper weicht aber von demjenigen in der üblichen Elektrotechnik gravierend ab. So erwächst das Problem, die physikalisch-technischen Meßwerte humanbiologisch richtig zu interpretieren….”

“Background: Observation and explanation of rouleaux phenomenon induce permanent debate started from its discovery. The aggregation of erythrocytes is a prominent feature in humans and other species “athletic” species [1]. In vitro studies have shown that aggregation of blood increases as shear rate decreases. Aggregation also depends on hematocrit and the concentration of macromolecules in the plasma or suspending medium [2], and in the presence of high molecular weight polymers, such as plasma proteins or dextrans, aggregate to form rouleaux and rouleaux networks [3].

“Introduction: One of the very first treatment “technologies” for oncology is the regional heating of the tissues and bodyparts, (hyperthermia, HT). This long history was not enough to be accepted as conventional treatment, facing mostly skeptic opinions among the oncology experts. The main reason is its controversial results and poor control, the missing of appropriate selective, controllable safe deep heat-delivery. Constrained balance of physiological feedback and the sophisticated transport network with very heterogenic tissue structures block applying the simple heating practices.

“Background: Oncothermia survival studies are problematic due to the missing control arm. This is a problem is general, when the treatment targets advanced, mostly refractory, relapsed malignancies in high treatment lines, when the only way is the sequential treatment. The sequential trial [1], [2], [3], is well known, and applied frequently in the case of small trials [4]. The sequential trial (like the oncothermia) is applied for the same patient in sequences, In this approach the development of the patient is measured and documented.

“Background: We provide oncothermia treatment to our patienst from 2001. Approximately 700 patients received oncothermia in this time, with more than 3500 sessions. Our aim in this article is to show what causality condition could be established between the curative rate and the time of care….”

“Introduction: Hyperthermia was one of the very first treatments in human medicine, having 5 thousand years history. Of course it had a sacral meaning at the beginning, and Hippocrates was convinced about its overall efficacy, telling when hyperthermia (fire) does not help, than the disease has to be declared as incurable. Our objective is to follow the development of the heat-therapies by selection important moment from its history….”

“Objective: Oncothermia concept was found when the company was established, however the way of realization is a long process, having various steps forward and sometimes dead-ends. Our objective to show the history of oncothermia through its devices, giving a picture how stable development was achieved by the years, and conclude with a lesson how to go further….”

„Trotz beeindruckender Therapieerfolge ist die Hyperthermie noch keine allgemein anerkannte Behandlungsmethode. Hyperthermische Behandlungen werden deshalb bislang nur eingeschränkt erstattet. In einem grundlegenden Urteil des Bundesverfassungsgerichtes aus dem Jahre 2007 wurde die therapeutische Bedeutung der Hyperthermie erstmals höchstrichterlich anerkannt….“

“Introduction: The most important aspect for the Oncotherm Group is that our medical devices are prepared according to the concerning international standards and fulfill the inquiries of our customers. These standards are the followings: • ISO 9001:2008 Quality Management Systems. Requirements • ISO 13485: 2003 Medical Devices. Quality Management Systems. Requirements for regulatory purposes • 93/42/EEC MDD (Medical Device Directive) …”

“Background: New treatments are being investigated in patients with multiple or unresectable liver metastases, usually characterized by poor prognosis. Based on the predominant arterial blood supply of hepatic neoplasms, liver trans-arterial chemotherapy administers Mitomycin-C is characterized by a high liver extraction rate. Low-frequency 13.56 MHz deep hyperthermia (Oncotherm-EHY 2000) treatment of liver cancer is another possible treatment for liver metastases.

“Hyperthermia is a leading edge, proven treatment option for cancer patients which can be integrated approach. Oncothermia, was founded in Germany twenty years ago. Since that time, oncothermia has been accepted by many oncological practitioners and institutions as a viable and successful treatment option. Presently oncothermia is used in many countries around the world, and by more than 180 institutions. More than 100,000 oncothermia treatments are conducted yearly and have delivered remarkable survival elongation with good quality of life….”

“LRF-DHT is feasible in treating patients with brain tumours without any severe side effects. LRF-DHT may induce complete impartial remissions. Overall median survival time (MST) could be increased by 13 and 7 months from onset of LRF-DHT after progression or recurrence in grade III and grade IV gliomas (astrocytoma WHO III, Glioblastoma muliforme WHO IV). Quality of life and overall survival could be improved by this method compared to historical control groups. Further trials are urgently warranted. …”

“Objective: Advantageous thermal and induced non-thermal effects of electromagnetic hypertermia (EHT, Oncothermia®) in human medicine is in use for decades. Surprisingly there are much less references about the veterinary utilities….”

“Background: Acupuncture and their connective pathways the meridians are ancient Chinese knowledge but it is not understood yet in details [1]. Request of the stable homeostasis of the complex organisms is demanding interdisciplinary approach and new paradigm for the topic. The detecting and reconstructing the deviation from the normal balance of the homeostasis is the basic principle of TCM.

“Background: Hyperthermia is an ancient oncology method. It is the very first treatment modality for this type of disease, having 5000 year history [1], based on the Sun as the overall curative force in ancient Egypt. Later Hippocratic paradigm described it using physiological process (acidosis) to eliminate the malignant tissue. This natural approach is in well correlation with the far-away developed medical concept in the same ancient time: the Traditional Chinese Medicine (TCM) [2]. This medical philosophy was also based on natural harmony inside and outside the human organism.

“Background: Oncothermia became a widely used and popular method in over 15 countries of the world. It is not a “gold standard” yet, but it is on the way to reach its stable and important position as a “fourth column” among the main oncotherapy modalities. It has wide-range applicability for every solid tumor in all possible localization, irrespective its primary or metastatic form. It could be applied together with all the known oncotherapy methods, and it is applicable in higher lines of the therapy protocols, even in the refractory and multirelapsed cases as well.

“Introduction: Our hospital intensively uses oncothermia for gynecological malignancies. The time for the application of the new technology is not enough to present statistically evaluable number of patients in cohorts, so our objective is reporting a few interesting cases from our practice. Method: We apply for the treatment the EHY-2000 oncothermia device with variable electrode sizes. A treatment cycle contains 10 sessions in average, made 2-3 times a week, having at least a day between the treatments….”

“Introduction: Advanced lung carcinomas were studied combined with various chemotherapies. Our objective was to obtain reliable data of lung-cancer treatment with oncothermia. Method: The study was started in August 2008, and was sequentially evaluated in December 2009 (n=66) and September 2010 (n=118), retrospectively. In first period 54.5% in the second one 64.4% was in advanced stages, and additionally 21.2% and 33 % had recurrence or metastases, respectively. The other stages were only 24.2% and 9% in the investigation sequences respectively….”

“Introduction: Small cell lung carcinomas (SCLC) were studied combined with various chemotherapies. This is a running study, we present only interim results. Our objective was to obtain reliable data of SCLC treatment with oncothermia. Method: The treatments were provided with device EHY-2000, 60 min in all sessions, using the electrode of 30 cm diameter. Data of the patients (n=14) are registered and evaluated retrospectively. The average age of patients is 64.4 y (50-77, St.Err.: 1.94), having 12/2 male/female ratio….”

“Objective: Dosing of oncothermia is based on the energy delivery to the targeted tumor [1]. This energy is well focused on cellular level [2], and makes the dose of energy optimal for cell destruction [3]. The personal feedback of the patient is the important control of the process; the patient became the primary sensor of the treatment protocol. This gives good safety records and low toxicity and side effects for the patients, however the objective dose is not equal for them. We know it well, that the dose is an important factor, the too low is ineffective, the too high is toxic.

“The aim of all scientific experiment and measurement is to collect information about the measured object or incident. On the field of research it’s especially important to acquire all of measurable information during the experiments, because often we don’t know exactly, which of the parameters will give us new and useful information. But in a lot of cases the data acquisition could be quite difficult, because: • If during the measurement more instruments are used, the simultaneous and continuous observation all of them is not possible.

“Background: Oncotherm has started its life in the Universities. The ideas were formulated as a part of the surface science in Glasgow (Scottish Surface Centre, Strathclyde University), followed by a spin-off form the Eotvos University Budapest in 1988. The first contacts with Germany were established almost immediately. Dr. Douwes (St.Georg Klinik, Bad Aibling), asked the human medical applications of the till that time only theoretically formulated ideas. The actual requests of the clinical use formulated by Dr.

“Introduction: Advertising, distribution and selling are words often identified with marketing. But this is not all. Of course they are part of every marketing concept. Oncotherm however sees something else in the centre of the work: the customer. Oncotherm sells for them not devices only, but a complete method and permanent help to use it. Method: Marketing of Oncotherm is the process of identifying, anticipating and satisfying the customers’ needs.

“Russian Scientific Centre of Roetgenology and Radiology carries out hyperthermia of oncologic patients, predominantly with gynecologic cancer, for a relatively long time. In particular, we used combination of radiotherapy with modern laser-induced hyperthermia. At the same time, about a half-year ago we started clinical research of application of local electrohyperthermia (oncothermia) in combination with radiotherapy and chemotherapy using still the only in Russia oncothermia unit "EHY2000" (Oncotherm, Hungary).