Referring to our system for hyperthermia Celsius TCS Thermo Cancer Select we give an active contribution to fighting the battle against cancer and we put all our efforts in continuously realizing and improving this commitment.
Mechanism of Impact
Celsius TCS Hyperthermia-System is supplied with two active and separately controllable electrodes and thus advances itself from previously available offers in the market.
In making use of the different sizes of the electrodes the energy impact can be focused to the tumor's location. An autofocus effect achieved through the different impedance of healthy versus malign tissue further enhances this focus to our benefit.
Celsius TCS can treat as well tumors situated deeper in the body volume. Opposed to microwave applications our carrier frequency of 13,56 MHz in principle can penetrate much deeper regions. Further an increased power supply of up to 600 Watt offers a more than sufficient power base. Much technical effort has been taken to assure a high percentage of effective output to the body dielectricum not being lost in the system. We measured an applied 500 Watts net capacity!
An efficient cooling circuit of regulated water in the water bolus next to the electrodes achieves to dissipate the heat from the surface of the skin. Thus we can induce more power for an effectful penetration in depth avoiding unwell heat sensation in the surface
Application
Celsius TCS Hyperthermia-System is designed for an optimal handling in day to day routine. Movable electrodes can be relocated to match the patients? locations of their tumors. Such readjustments can be set up quickly within less than a minute. This includes possible change of size in electrode on the upper arm and the positioning of the lower electrode to the respective segment in the surface area.
In the planning software size and location of the electrodes are choosen. Celsius TCS automatically detects which electrodes are in fact installed and would indicate to faulty installations to match to the planning status before commencing the treatment. By this safety feature a possibly too high doses originally planned for a larger size electrode can be avoided to be applied to a small size electrode.
Intelligent Mounting of the Electrodes
Using a connective bolus device filled with a specially prepared ionized water allows us to adjust the contact to any given unevenness of body anatomy or skin surface while maintaining the full potential of applied energy. Celsius TCS equalizes movements from respiration and tolerates small changes in position of the patient as they are inevitable in a treatment cycle of up to one hour.
The electrodes will be cooled thus reducing heat sensation at the skin and avoiding moisture which in turn reduced the peril of becoming locally burned drastically.
The membranes of the application electrodes are biocompatible in sensation, easy to clean and robust. Much brain had been used in the overall construction of Membranes and mechanical arm to ensure a universal high adaptability to any given body geometry.
Software and control
All software components for Celsius TCS system have been developed just for this application. A focus had been on an efficient workflow handling and to a reliable ease of use.
You will be able to run the equipment efficiently in high load scenarios. It does not require special trainings to communicate with the machine. Both factors in turn contribute to a safe environment of the treatment.
Celsius TCS entails a comprehensive database. If is not just to query and retrieve patient data and previous treatment plans; it is rather unique that we store all treatment data in detail. Users can indicate characteristics of tumor (TNM-classification; OPS and ICD codes and patient’s state of being: Karnowski index, questionnaire and ex post can match such data to treatment details and possible results. This option does allow you to monitor your treatment planning approach and yields feedback.
Further we do offer you the opportunity to take clinical notes either purely internal for your own purposes or in a different way to have such input become part of an automized report. Such a report along with selected data from the treatment cycle generated by the machine enables you to communicate to your referring colleagues with almost no additional work involved.
As an option we will be able to offer interfacing via HL7 to hospital information systems and electronic patient record systems. DICOM interfacing for image data will be available in the second quart of 2007.
Safety for patient and usersafety
In designing and developing the Celsius TCS device we were driven by the desire to achieve a high level on safety and security. An extensive risk evaluation had been established and in turn marked many decisions in the process.
We measure and control the applied energy permanently and regulate each deviation. As an additional safety device the system suggests regular patient feedback for all phases of high energy absorption. An autostop reacts to any eventual missing positive patient feedback. Regardless of this a patient can stop the treatment at any time with immeaditae effect just by pushing the button on the hand bar.
As an additional measure to prevent eventual mistakes name of patient and all therapy steps are displayed and have to be briefly confirmed before start of any treatment.
Technical data
Couch device with integrated high frequency control unit and separate PC system for planning and controlling treatments as well as clinical documentation. Look attachment.
Indications and working principle of the Celsius TCS
1. Aim and field of application
The aim of the Celsius TCS System is the loco-regional warming of body volume. This is performed in:
- the treatment of tumors
- stimulation of metabolism
- stimulation of the immune system
The Celsius TCS system has been devised as a therapy system for the treatment of tumors. It is mostly used in combination with the chemo and/or the radiotherapy in order to optimize the effect of these therapies.
The type of application depends on the current generally accepted medical guidelines and recommendations of the respective expert medical institutions.
2. Range of applications
- Primary tumors or those occurring as a metastasis in organs (e.g.: liver, spleen, kidneys, lung, etc.)]
- Tumors of the intestinal tract
- Tumors in the pelvic region
- Tumors in head or throat
- Cerebral tumors or cerebral metastases
- Mammary carcinoma / local recidivist mammary carcinoma
- Cancer of the prostate
- Melanomas and
- superficial tumors
3. Appropriate use of the equipment
The Celsius TCS is a medical product of the class II b which may only be used by competent medical personnel trained regularly in the use of the product. Instruction by the manufacturer in accordance with the provisions of the Article 5 MPBetreibV is mandatory.
4. Contraindications
- metallic implants or similar objects in the area of the treatment
- electrical (cardiac) pacemaker in the area of the treatment
- patients with bone marrow transplantation
- previously damaged dermal condition in the area of the treatment since this may result in burns
- patients who are epileptic require special clinical monitoring
- patients with decreased perception of temperature (e.g. subsequent to a stroke) must be monitored specifically during the therapy.
5. Technology
In the hyperthermia therapy system Celsius TCS (Thermo - Cancer - Select) the aim is to specifically destroy the tumor cells by means of a radio frequency of 13.56 MHz. The Celsius TCS allows also any desired upward modulation of the targeted individual frequencies later.
In this method of therapy, the patient is the dielectric between both the active application electrodes and is, therefore, part of a resonant oscillating circuit. Due to the capacitive thermodynamic effects in the tissue electromagnetic current and heat are generated. With this arrangement the treatment can be customized to the patient's needs and to the location of the tumor as well as its biology (resonance frequencies = modulation frequency).
6. Working principles
Based on the characteristics of tumor cells mentioned in the following section the operating principles of electrical hyperthermia are as follows:
- it auto-focuses on the cancer cells
- it destroys tumor cells considering their obvious intolerance to heat
- it destroys the positive chemical back coupling process for the growth stimulation
- it brings the cell membrane of the tumor cell into an unstable state
- it increases the anaerobic metabolism in the cells
- through electromagnetic induction it destroys the intermediary cell structure and the cell communication
- it blocks the pain receptors
- it re-polarizes (or over-polarizes) the cancer cell membrane to enable access to immune cells.
- by influencing the electromagnetic field in the extra-cellular fluid it causes an indirect flow of ions at the cell membrane (Ca+ / Na+) and changes the pH value of the carcinogenic cells
- by constantly changing the pH value it leads to an intra-cellular acidosis (over-acidification).
6.1 Selectivity
Between healthy and carcinogenic cells there are several identified and measurable differences.
The primary difference between the cells is their electrical charge. The healthy cell is charged positive mainly inside and negative outside. This charge gives rise to a certain voltage within and outside the cell. The voltage in the healthy cell can be up to +70 mV and in the modified (diseased cell) up to –30 mV (Nordenström).
This differential voltage leads to a variable electromagnetic field around the cells. Similarly, the ion distribution (Na, H, K, Ca, Cl) within and outside the cells varies according to their charge. That is to say, the composition of the extra-cellular fluids (ECF) differs from each other. This in turn results in the ECF reacting very differently to various external stimuli. An important characteristic is the absorption of certain frequencies. The ECF around the healthy cell mainly absorbs frequencies around 100 MHz and oscillates (resonates) simultaneously with this frequency. On the other hand, the ECF of the modified diseased cells absorbs frequencies between 10 and 15 MHz. Now, if such a frequency (in the case of TCS 13.56 MHz) is transmitted into the body between the application's electrodes, it will have, as a result, a selective effect on the ECF of the tumor cells. In other words, the ECF around the tumor cell goes into oscillation at 13.56 MHz (13.56 million per second). This high oscillation frequency induces a selective heating in the tumor in the extra-cellular space (ECS). This generated heat gets transferred by the ECS, bound to the ions, into the intra-cellular space (ICS). On exceeding the "equalization capacity“ of the cell, the heat gradient (ΔT) increases steadily. A temperature difference of 0.01 ºC (ΔT) within and outside the cell membrane is sufficient to influence the process of metabolism or to block it or even to denature the proteins.
Electro-osmotic effects during the therapy increase the water psressure in the cytoplasm and cause a thermo-dynamic pressure on the cell wall. Furthermore, the pressure is increased due to the intracellular ion migration which again is sufficient to destabilize and to destroy the cell membrane. Hence, the delivered frequency of 13.56 MHz brings about a cascade of consequences which can ultimately result in the destruction of the tumor cell.
6.2 Effect of the electrical field
Another difference between the tumor cells and normal cells are their electrical characteristics. Tumor cells have relatively lower electrical resistance, higher dielectric constant and higher negative polarization. The electro-hyperthermia system Celsius TCS builds up a high, homogeneous electrical field between the application's electrodes. Since tumor cells have a low electrical resistance, the electrical current flows, as a result, intensely over the tumor cells and influences their charge and functional state. Thermo-electrical current causes a drastic decrease in the membrane potential and destabilizes thereby the cell membrane.
6.3 Capillary changes
Heating the tumorous tissue also affects partly the adjacent healthy tissue. But a healthy tissue can dissipate the heat easily by increasing its blood circulation, an ability which the tumorous tissue does not possess due to its inability to regulate the thermal energy consequent to a non-existent muscular layer of the capillary tumor vessels. Since the heat dissipation is less in the tumor, the heat generated by hyperthermia is contained primarily in the tumorous tissue and causes thus a selective temperature increase.
This so-called "heat trap“ leads to undernourishment of the tumor cells due to less oxygen and nutrients, resulting in a breakdown of important metabolic processes in the cell division and the cell conservation.
In addition, after repeated sessions of hyperthermia treatment it results in endothelial swelling and micro-thrombosis which acts additively on the decreased blood flow ("angiogenetic block“).
6.4 ATP - impoverishment
Due to absence of supply of 02 and nutrients the energy generation through oxygenation is reduced in the tumorous tissue.
6.5 Acidosis
The tumor cell further relies on anaerobic (without oxygen) generation of energy. The hyperthermia increases the speed of the biochemical reactions and, therefore, also the metabolism so that it results in hypoxia and, due to increased demand in an anaerobic metabolism in which the final product is lactate. The tumor cell is over-acidified intracellularly and this leads to intensified cell destruction.
6.6 Synergetic effects
Another important point is the synergetic effect of the hyperthermia in combination with radiotherapy and/or chemotherapy. In this, hyperthermia prepares the tumorous tissue by sensitizing it for the radiotherapy or chemotherapy.
Certain chemotherapeutics are partly potentiated in their effect. Preclinical and clinical works show, especially also in a number of cytostatic agents, a prominent synergetic effect in combination with hyperthermia. The pharmacological kinetic acceleration of the rate of reaction due to the temperature and the complementing range of action induce the synergy of these methods.
Besides, the dormant cells are brought out of the GO phase into the G1 phase or S phase due to the effect of heat as a result of which they become vulnerable to chemo and radiation therapies.
Synergetic effect with radiotherapy:
modified after Seegenschmied
Synergetic effect with chemo-therapy (example):
Cell Control Biomedical Laboratories 1996
6.7 Strengthening the immune reaction
On the cellular molecular level, hyperthermia causes a curtailment of cellular repair processes (DNA reparation enzymes), the inhibition of enzymes and damage to the cell membrane and to the cytoskeleton.
Further to be discussed are the induction of cytokines, unspecific immune stimulation and specific immunization against heat shock proteins (HSP) with formation of tumor-associated and tumor-specific antigens.
According to recent molecular-biological investigations, hyperthermia induces the macrophage activation, natural killer cells, cytokine HSP interfered immune effects; HSP interfered thermo-tolerance (=> HSP27) and HSP interfered immune suppression (= HSP90 => Corticoids). In the application of capacitive hyperthermia, the heat penetrates over the thermal diffusion from the extra-cellular fluid into the cell's interior and destroys the malign cells before the HSP expression is triggered.
7. Main effects of hyperthermia with the Celsius TCS System
- Direct tumor necrosis due to the effect of heat
- Increased blood circulation in the healthy tissue
- Reactive lowered blood circulation and impoverishment of nutrients in the tumorous tissue
- Apoptosis due to anaerobic metabolic induction
- Sensitization to radiotherapy and chemotherapy (synergetic effect)
- Breaching the resistance to chemo and radiation
- Expression of stress proteins (HSP)
- (Enhancement of immunogenicity) with intensified surface presentation
- Micro-thrombosis of cancerous capillaries (angiogenetic block)
- Amelioration of pain
- Improvement of the quality of life (Karnofsky index)
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