An Introduction to Hyperthermia
The idea of using heat to treat cancer has long been considered, but the efforts of recent years have led to the operation of this idea. The main reason for this delay is to achieve the ability to raise the temperature appropriately in the appropriate place so that it does not damage the cells and body tissues of the body. Today this is somewhat achievable with new devices and methods.
Typically, hyperthermia, along with other cancer treatments such as chemotherapy and radiation therapy, is used. Hyperthermia seems to cause more cancer cells to become susceptible to radiation and chemotherapy drugs. Many clinical trials have been conducted on the combination of hyperthermia, radiation therapy or chemotherapy on various types of cancers such as sarcoma, melanoma, head and neck cancer, rectum, liver, cervix, mesothelioma, breast, bladder, lung, brain, and so on. Many of these studies show the effect of hyperthermia on reducing tumor size as a treatment.
How to raise the temperature of a specific area of the body from above the system temperature is a technical challenge and is under investigation. Generally, the flow of blood prevents the temperature from rising, and the blood flow rate in the tumor tissue is about 100 grams per minute. Therefore, in order to reach a temperature higher than 42 degrees, in some areas of the tumor, the minimum density of 40-40 W / kg should be used in the target area.
At present, the optimal temperature distribution for hyperthermia clinical applications is unknown. The distribution of the temperature obtained in various hyperthermia methods has low homogeneity and the total amount of heat produced is also limited. This is due to the physiological and physical characteristics of the electrical tissue binderies, the varying speed and order of blood flow in different areas and other factors (minimum temperatures for hyperthermia treatments typically range from about 4.40 to 3.39 ° C.) With the advances made in hyperthermia tools and methods, today, about fifty percent of deep tumors can be heated up to 42 degrees at specific points. However, the reach of a specific temperature in tumors with clinical applications is still uncertain. Therefore, the need for high and homogeneous temperature in the tumor remains as far as possible.
Hyperthermia is used in general for cancer treatment. In the first method, a very high temperature is used to remove a small part of the cells or tissues such as the tumor. This type of hyperthermia is usually called local hyperthermia. In the second method, the temperature of a part of the body or even the whole body is raised a few degrees higher than the normal body temperature, this type of treatment improves the performance of other cancer treatments such as radiotherapy and chemotherapy. This form of hyperthermia, regional hyperthermia, or whole-body hyperthermia is called. Both general methods are commonly used as a combination therapy. Of course, in some hyperthermia modes such as radiofrequency degradation, it may also be used as a primary treatment.
In topical hyperthermia (or thermal degradation), heat is used to destroy small areas, such as the tumor. Typically, the very high temperatures used can damage the proteins of the cancer cells and destroy the adjacent vessels. To create such heat, radio frequency, microwave, ultrasound and other types of energy are commonly used, and the method used is named, depending on the wave used. For example, when the ultrasound is used, a technique known as high-intensity focused ultrasound (HIFU) is called a technique called "HIFU" that is used in conjunction with an application (such as an antenna converter or any other device used to generate electromagnetic or ultrasound energy, field Electric, diamter, or laser is called an applicator) electromagnetism is less important. Each of these waves somehow heats up a region that is irradiated. Microwave electromagnetic radiation, radio wave and infrared Red, with the movement of bonds in water and other molecules The polarized polarized tissues produce heat, and microwave waves have very little penetration depth, near infrared radiation and radiomoday have a higher penetration depth and absorption, depending on the frequency. It should be noted, however, that the energy absorption in different tissues is different A large amount of the effect of these waves depends on the power of these waves penetrating into the body, which varies in different frequencies.
The mechanical energy generated by ultrasound is usually converted into thermal energy by the effect of friction and rubbing. Sonic energy has a high penetration depth, but the mechanical pressure used usually results in severe damage to healthy cells and tissues. The specific absorption rate (SAR) is the quantity that indicates the energy absorption of waves in the body and can directly indicate the intensity of their thermal effects. In other words, the higher the SAR, the greater the thermal effects of electromagnetic waves. SAR unit watt per kilogram.
Surface tumors are easily warmed up with microwaves or radiomodium applicators. How to use such systems is shown in Figure 1. In order to ensure the electromagnetic coupling of the applicator to the tissue, a water chamber is used. The tumor temperature is typically controlled through the power output of the generator or the applicator placement. The distribution of the final SAR is only uniform in the first few centimeters and is lower in areas of the body with a non-uniform surface, such as head and neck, or under the armpit.
Figure 1: Schematic representation of the application of topical hyperthermia, applicator location and output power can be used as a variable to obtain suitable conditions. Temperature control is carried out through a thermistor placed in the tissue.
In this method, which is in fact a type of topical hyperthermia, the applicator is placed inside the tumor tissue and is typically used in combination with brachytherapy (a radiotherapy treatment method in which small amounts of radionuclide in the tumor area are placed) Gets This technique is commonly used for tumors less than 5 cm in diameter, but it is possible for any available tumor (such as head, neck, and prostate tumors). Microwave hyperthermia antennas, radio frequency ablation electrodes, ultrasound transducers (HIFUs) and even photo thermal therapies can be used as an antenna or heat source. For physical reasons, the gradient gradient around the antenna is very high, so there are a lot of heat changes. For this reason, there is a need to place multiple antennas at 1 to 1.5 centimeters apart in tumor tissue, which is also highly invasive, and it may be difficult due to the sensitivity of microwave antennas to wave interference, which requires precision Is high. Unfortunately, even with the application of a large number of applicators, the distribution of homogeneous temperature throughout the entire tumor tissue is almost inaccessible.
In this method, natural cavities or body entries such as the urethra (prostate treatment), rectum, vagina, cervix and esophagus are used. This method has the same basic physical principles as the intra-texture method, but uses an electrodes of centimeters (which also results in greater penetration depths).
Regional hypertrophy or partial hyperthermia of the body
Deep tumors, for example, in the pelvis or in the abdominal cavity can be heated by an array of antennas. The Sigma 60 applicator (Figure 3), which consists of four pairs of antennas and loops to the patient, is a system. Distribution of Temperature and Density The power of this system can be changed depending on different treatments. There are, of course, restrictions on the distribution of SAR production. Modeling calculations have shown that with increasing the number of antennas, power distribution is more controllable.
Figure 3: Sigma-60 applicator with BSD-2000 system treatment table used to treat hyperthermia
Frequency can also be used as another variable for controlling distributed SAR (150-100 MHz). Advanced generations have the ability to connect to MRI devices and simultaneously examine MRI tomography (Fig. 4). Localized hyperthermia can cause nausea, diarrhea, vomiting and, in severe cases, it rarely leads to damage to the arteries, kidneys, heart and other organs, depending on the area under treatment.
Figure 4: U.S. hybrid system Tomography (MRT)
Whole body hyperthermia
In cancers with metastases, a steady-state temperature of 42 degrees can be used for 1 hour. Complications caused by this treatment are acceptable, but such treatment should be treated with accommodation, sedation or even general anesthesia. Methods such as the use of Pyrogen and Contact Heating have been excluded due to toxic effects and functional limitations, and today only radiation systems (Figures 5 and 6), with radiation treatment periods of 60 and 90 A minute is used in the bedside. Aquatherm (Fig. 5) is a moisture saturation chamber with tubes containing hot water (60-50 ºC) which is placed in the patient's inner compartment. In this system, the IR wave is coupled with a high wavelength, which is accompanied by an increase in the velocity of the subcutaneous blood stream, which leads to heat transfer to the systemic circulation and the entire body.
Figure 5: Schematic view of the aqua term system for whole-body hyperthermia. The patient is placed in a humidity saturation chamber with circulating water tubes at 60 ° C.
Figure 6 illustrates the Isotherm 2000 system (Isotherm 2000), which uses infrared light sources (NIR, Near Infera Red). This kind of radiation is more intrusive, but like other systems, it increases the temperature of the body surface and, in some cases, causes burn injuries. Therefore, it's a safe way to control the skin's temporal control and the power output of the device.
Figure 6: The schematic view of the 2000 isotherm system for hyperthermia of the entire body, the patient is exposed from the high and low under IR radiation.
Both of these systems have the ability to create a temperature of 41.5 to 42 degrees in the body with acceptable side effects. Systemic toxicity, including cardiac dysfunction, abnormal blood coagulation and increased capillary endothelial penetration, can be cited as the complications of these two systems.
The mechanism of hyperthrimes in eliminating tumors and the limitations of current hyperthermia methods
New clinical reviews have created a new look at the mechanism of hyperthermia in cancer treatment. It seems that the sensitivity of the tumor is greater due to factors such as pH and oxygen pressure. One of the major hypotheses in the effectiveness of hyperthermia treatment is that the deep-hypoxia regions of the tumor, which are usually resistant to the drug, are more likely to disappear in this treatment, because these areas are poorly circulating, which can remove heat. . Of course, this assumption is questionable because chronic hypoxia leads to tumor resistance, and the actual distribution of temperature at the level of the tissue cells due to the lack of regular vessels in these areas is unclear.
In contrast to this theory, studies have shown that areas of better tumor-bearing tumors not only entail more lethal drugs into tumor cells, but are also more susceptible to chronic oxidation (increased oxygen pressures in the tumor tissue). It seems that at temperatures above 40 ° C this process occurs better in tumor cells, and as a result, we can see the improvement of chemotherapy performance by simultaneously using hyperthermia.
In the whole body hyperthermia, the system temperature remains at 42 ° C for one hour. In addition to having systemic and topical complications and its efficacy is not completely clear, it should be noted that all healthy cells also have the same treatment and may receive more fatal chemotherapy drugs, resulting in inefficiency To be treated.
Regional hypertrophy and regional hypertrophy with better performance than hyperthermia of the whole body and more acceptable side effects. In some indications, such as head and neck cancers, a radiotherapy program with high-level regional and high-level hyperthermia is used. Multiple studies have also shown that this type of treatment is only applicable to small tumors and ulcers.
However, the lack of heat distribution in all of the tumor cells, as well as the irresponsible heat treatment of healthy cells, is a challenge that a variety of regional and regional hyperthermia methods are faced with. In addition, the need for accurate control of the temperature and physiological conditions of the patient in hyperthermia treatments is a major obstacle to further development of these methods.
With the introduction of nanostructures in recent years and their ability to produce concentrated heat in the special area of local hyperthermia and their ability to accumulate in cancer cells, these problems seem to be solvable. One of the leading methods in nanotechnology for hyperthermia can be referred to photothermal therapies (neurogarmotherapy) with gold nanostructures and magnetic hyperthermia with magnetic nanostructures, which will be discussed later in these discussions.
Hyperthermia now provides acceptable benefits for treating cancer patients, better understanding of appellants' arrangement in therapeutic procedures, designing better applicators and newer technologies for heavier tumors seems necessary. Correct insights into molecular mechanisms can also lead to the design of hyperthermia-related therapies, such as those with temperature-sensitive nanomaterials or drug delivery with temperature-sensitive nanomaterials and the combination of different therapies.
Obviously, with the advent of nanotechnology and overcoming the current limitations of this method, such as temperature de-concentration in particular areas, lack of proper temperature control, lack of access to deep tumors and side effects due to warming of cells and healthy tissues, this type of cancer treatment has much more contribution In the future, there are ways to treat cancer.
- February 28, 2012
- Author : Alireza Ghasemlouy
- Design, Simulation, Anten, Hyperthermia