Hyperthermia or hyperthermia therapy means the heating of biological tissue to temperatures above the physiological one. The tissue heating, achieved through electromagnetic fields has now a large clinical application (hyperthermia oncology) or rehabilitation (physical therapy).
The electromagnetic waves used are in the range of frequencies ranging from microwave to short wave, long wave up to. Currently it uses the frequency of 13.56 MHz, which allows for a deep heating of tissues treated non-invasively. The power dissipated locally for changes in temperature (41 ° to 45 ° C) of tumor cells, corresponds to SAR values of several hundred W / kg. Arsèned ‘Arsonval (1851-1940), during his studies on high-frequency currents, he discovered that an electric current at a frequency of 10kHz or more, producing a sensation of heat in crossing the tissue (diathermy), without being accompanied by painful muscle contraction, which occurs at low frequencies. It was 1982, the year that marks the official entrance of electromagnetism in medicine.
The tissue heating with electromagnetic fields has some advantages over other forms of heating (conduction, radiation, infrared): you can do it, also located in deep tissues. The main applications we have in clinical hyperthermia are in cancer therapy and physiotherapy.
Hyperthermia in oncology:
Hyperthermia Oncology, with the advent of new higher performance equipment, it is proposed today, selected diseases, as a possible therapeutic option in oncology, no alternative, but in combination with traditional therapies (chemotherapy and radiotherapy).
Through the use of radiofrequency electromagnetic fields, focused by special antennae (on-site regional hyperthermia transcutaneous), the target organ is heated to a temperature near or above 43 ° C for about 60 minutes.
The treatment, that is heating to temperatures above, can be run multiple times, according to the protocols, no more than three times a week, to avoid the phenomenon of thermo tolerance, that is the largest cellular resistance to heat within 48 hours after treatment.
You can also, with different equipment, heat the whole body (total body hyperthermia) or directly to the tumor lesions, introducing special needle, under ultrasound guidance, transcutaneously (interstitial hyperthermia).
The interest in hyperthermia oncology has been increasing in recent years. It has been shown that radiotherapy and chemotherapy, when used in combination with hyperthermia treatments, may have with the same dose, a more effective or maintain the same effectiveness at lower doses.
The heat enhances the effects of radiotherapy and chemotherapy on the tumor without increasing side effects (i.e., the debilitating effects on healthy tissues and organs resulting from cytotoxic chemotherapy and radiotherapy), allowing a significant improvement in the control of tumor growth.
This is made possible by the characteristics of tumor neovascularization. In fact, the tumor vessels, scaffold-free muscle, do not allow for lack of elasticity, the physiological vasodilatation that allows heat dissipation introduced. In other words, the heat is trapped in the tumor lesions causing cell death.
The effect of necrosis is due to inhibition of reproduction of cancer cells, with a mechanism of apoptosis (DNA breakage) on quiescent tumor cells, which are particularly sensitive to high temperatures (7).
Recent molecular biology studies have isolated the protein responsible for inhibition of neo-angiogenesis. Identified as PAI-1 (PAI-ONE) is able to inhibit the formation of new tumor blood vessels typical of tumors giving metastases and is produced by the endothelium of blood vessels under the action of heat (28.29).
The phenomenon is well integrated with the action of conventional therapies (chemotherapy and radiotherapy) to carry out their cytotoxic action on cells in active proliferation. Another significant advantage of hyperthermia is the fact that the immune reactivity of the patient tumor, usually depressed by the disease itself and / or the care taken to control it, which is enhanced by hyperthermia, mimicking the physiological defense mechanism represented by fever, causes the release of immune regulatory substances (cytokines), which have a protective effect for the body of the patient.
The tumor cells under the action of heat producing the protein of dhock heat, HSP (heat shock proteins). The HSP in turn induce the activation of TH1 cells that begin to produce IL-2. Dendritic cells produce IL-12 in turn activates macrophages and production of IL-1, TNF-alpha, IL-6.
Cytokines are involved in activation of the immune function of tumor type. TNF-alpha, IL-6 and IL-1 rather tend to create an inflammatory state and reduction of anti-tumor defenses. At the Institute of Biological Medicine immunotherapy is associated with indulic derivatives of the pineal gland, which modulates and amplifies the activation of antitumor cytokines.
The synergy of the combined therapy of hyperthermia + chemotherapy, radiotherapy or immunotherapy may help you achieve the same result, using conventional therapy, lower doses, thus reducing their often heavy, side effects. Nor must we forget that, preoperatively, the application of hyperthermia can reduce the tumor burden, facilitating the work of the surgeon and allowing interventions at times even in cases where an initial evaluation are deemed inoperable.
The therapeutic properties of heat were already known in the past: the use of hot irons to treat cancer is reported by Hippocrates and Galen, and there are traces of it in 2000 BC. The search for new treatment modalities that have as characteristic the almost total absence of side effects, has revived interest in hyperthermia as a cancer treatment modality, starting from basic research on the mechanisms by which heat is able to kill cancer cells or make them more sensitive to some drugs and radiation.
In the 70 have been published numerous biological studies, which have better defined the cellular effects caused by the heat. These studies have confirmed the effectiveness of hyperthermia and demonstrated the therapeutic benefit derived from association with radiotherapy and chemotherapy.
The clinical trial and the start of the first randomized clinical trials have led to the formation, in Europe the U.S. and Japan companies affiliated organizations hyperthermia for cancer treatment and research. At the international level have been completed many studies on the biological effects of heat, in the temperature range between 42 and 45 ° C, in combination with ionizing radiation.
The integration between hyperthermia and radiation originates from the activation of two different phenomena: heat. A direct cytotoxic effect, due to the particular conditions of tumor cells, characterized by poor nutrition due to vascular deficiency of oxygen and increased acidity, and a radio sensitizing effect that allows the use of hyperthermia as adjuvant therapy to destroy tumor cells radio resistant.
The data derived from laboratory experimental evidence, have shown an increase of efficiency, equal to about one and a half to three times compared to the use of ionizing radiation alone. Interesting data come from the first experimental studies in the eighties with more than 25,000 treated tumors.
The evidence gathered by the Protocols early Americans and Europeans, testified that the combination of heat and radiation in the treatment of squamous cell carcinomas of the neck (25), in melanoma, and breast carcinomas (18), results in an improvement in local control of disease.
The interaction between hyperthermia and chemotherapy is more complex and is based on different mechanisms. One of the major effects of global warming seems to be to increase cell permeability, which allows a greater chance of passage of drugs into the cell. Several studies have confirmed the efficacy of hyperthermia large area of the abdominal and pelvic tumors.