Oliver Szasz

Oncothermia treatment of cancer: from the laboratory to clinic.

Oncothermia is a long-time applied method (since 1989) in oncology. Its clinical results excellently show its advantages, however the details of its mechanism are under investigation even today. The method is based on a self-selective process of energy concentration and targets the membrane of the malignant cell, using the temperature gradient and the beta-dispersion of the membrane proteins. To prove the theory we show the experimental evidences in vitro experiments where we showed the definite difference between the conventional heating and the oncothermia at the same temperature. In the next step, we studied some xenograft nude-mice models, verifying the temperature-dependent and non temperature dependent factors. In addition, the synergic effect with some chemotherapies were studied, having more efficacy of the oncothermia with drugs than the conventional heating. These experiments show the definite advantages of the oncothermia compared to its classical counterpart, acting on the same temperature. We have also proved the beneficial effect of oncothermia treatment in the veterinary practice Oncothermia is applied in numerous clinics and hospitals, and we would like to show some characteristic case-reports and also the clinical benefit on the survival time elongation of liver-, pancreas-, brain-, and lung-tumor-lesions.

An Energy Analysis of Extracellular Hyperthermia

The classical hyperthermia effect is based on well‐focused energy absorption targeting the malignant tissue. The treatment temperature has been considered as the main technical parameter. There are discussions about the mechanism and control of the process because of some doubts about the micro‐mechanisms. The main idea of the extracellular hyperthermia is to heat up the targeted tissue by means of electric field, keeping the energy absorption in the extracellular liquid. This produces a temperature gradient and connected heat flow through the cell membrane, which initializes numerous nonequilibrium thermal microprocesses to destroy the cell membrane. Furthermore, before the heat shock activates the intracellular heat shock protein (HSP) mechanisms, thecell membrane has been already compromised, therefore the HSP synthesis in the cells starts secondarily only after the membrane damage. The process could explain why the nonuniform and basically unsatisfactorily high temperature locoregional hyperthermia could be effective.

Physical Background and Technical Realizations of Hyperthermia

Hyperthermia is a medical heat-treatment, widely used in various medical fields and has a well-recognized effect in oncology. It is an ancient treatment. However, when making hyperthermia we are limited by numerous biological, physical/technical and physiological problems. The word hyperthermia means increased temperature by heating of tumors. This relatively simple, physical-physiological method has a phoenix-like history with some bright successes and many deep disappointments. Why is this enigma? What do we have in hand? Answers lie in the applied techniques.

Oncothermia-Nano-heating paradigm

To face the challenges in hyperthermic oncology we have made research on nano-heating the malignant and healthy cells and this review paper shows our results which were presented at the largest OMICS Group Conference in the United States in 2013. We introduced nano-heating technology which means selecting and heating the membrane of the malignant cells purely by the electromagnetic effects without any extra nano-particle applications. The technology (called modulated electrothermia or oncothermia) is impedance controlled capacitive coupling; no plane-wave radiation is dominating as in other capacitive (radiative) solutions. The nano-selection is based on the metabolic, on the adherent and on the organizing deviations of the malignant cells from their healthy hosts. The cell-killing mechanism is connected to the intensive, but very local, nano-range heating. These effects are proven in silico, in vitro and in vivo experiments, as well as in pre-clinical and veterinarian applications. Based on the controllable and safe methodology the treatment is applied in human clinical practice. My objective is to summarize the results which are connected with oncothermia method.

Bystander Effect of Oncothermia

Metastatic form of malignant tumor diseases is the most serious problem in oncology and the greatest challenge in tumor therapy. Conventional therapeutical approaches (surgery, irradiation, and chemotherapy) cannot manage this challenge in oncological practice. According to our theory, oncothermia treatment-induced immunogenic tumor cell death can be a very good basis for immunotherapy combination to make systemic tumor control from a local tumor destruction effect. We summarize the molecular basis of the oncothermia treatment-induced immunogenic cell death as a necessary basic condition to achieve the bystander effect.

Modulation Effect in Oncothermia

Conventional hyperthermia is based on the local or systemic heating, which is measured by the realized temperature in the process. Oncothermia applies nanoheating, which means high energy absorption in the nanoscopic range of the malignant cell membrane selectively. This high temperature and its consequent stress create special effects: it evolves the possibility for chaperone proteins to be expressed on the outer membrane by softening the membrane and starts various excitations for programmed cell death of the targeted malignant cell. The process needs special delivery of the energy which selects as desired. A strict 13.56 MHz sinusoidal carrier frequency is amplitude modulated by time-fractal signals. The modulation is far from any sinus or other periodic patterns; it is a 1/f spectrum having definite templates for its construction. In some personalized cases, a definite template is used for the fractal pattern, which is copied from the actual character of the tumor pathology or any other specialty of the target.

Do field-free electromagnetic potentials play a role in biology?

All bio-systems are imperfect dielectrics. Their general properties however cannot be described by conventional simple electrodynamics; the system is more complex. A central question in our present paper is centered on a controversial debate of the possible effect of the zero fields (only potentials exist). We show that the identical use of the “field-free,” “curl-free,” and “force-free” terminologies is incorrect, there have definitely different meanings. It is shown that the effective electro-dynamical parameters that describe and modify living systems are the potentials and not the fields. We discuss how the potentials have a role in biological processes even in field-free cases.

Deep Temperature Measurements in Oncothermia Processes

Temperature in depth of various model systems was measured, starting with muscle and other phantoms. It was shown that the temperature can be selectively increased in the target. In water-protein phantom, the protein coagulation (>60°C) was observed selectively while the water temperature around it was a little higher than room temperature.

Hyperthermia versus Oncothermia: Cellular Effects in Cancer Therapy

Hyperthermia means overheating of the living object completely or partly. Hyperthermia, the procedure of raising the temperature of a part of or the whole body above the normal for a defined period of time, is applied alone or as an adjunctive with various established cancer treatment modalities such as radiotherapy and chemotherapy. The fact that is the hyperthermia is not generally accepted as conventional therapy. The problem is its controversial performance. The controversy is originated from the complications of the deep heating and the focusing of the heat effect. The idea of oncothermia solves the selective deep action on nearly cellular resolution. We would like to demonstrate the force and perspectives of oncothermia as a highly specialized hyperthermia in clinical oncology. Our aim is to prove the ability of oncothermia to be a candidate to become a widely accepted modality of the standard cancer care. We would like to show the proofs and the challenges of the hyperthermia and oncothermia applications to provide the presently available data and summarize the knowledge in the topic. Like many early-stage therapies, oncothermia lacks adequate treatment experience and long-range, comprehensive statistics that can help us optimize its use for all indications.

Oncothermia as personalized treatment option

Oncothermia is a nanoheating technology personalized for individual status depending on the state, stage, grade, and other personal factors. The guiding line of the treatment keeps the homeostatic control as much effective as possible. One of the crucial points is the surface heat regulation, which has to be carefully done by the electrode systems. The applied stepup heating supports the physiological selection. Recognizing the hysteresis type of SAR-temperature, development of the protocol could be well conducted. Using the Weibull distribution function of the transport processes as well as considering the typical physiological relaxation time of the tissues, special protocols can be developed. It has wide-range applicability for every solid tumor, irrespective of its primary or metastatic form. It could be applied complementary to all the known oncotherapy methods. It is applicable in higher lines of the therapy protocols, even in the refractory and relapsed cases as well.