Hyperthermia therapy
Hyperthermia therapy is a type of medical treatment in which body tissue is exposed to temperatures above body temperature, in the region of. Hyperthermia is usually applied as an adjuvant to radiotherapy or chemotherapy, to which it works as a sensitizer, in an effort to treat cancer.
Hyperthermia uses higher temperatures than diathermy and lower temperatures than ablation. When combined with radiation therapy, it can be called thermoradiotherapy.
Definition
Hyperthermia is defined as supra-normal body temperatures. There is no consensus as to what is the safest or most effective target temperature for the whole body. During treatment the body temperature reaches a level between. However, other researchers define hyperthermia between to near .Types
- Local hyperthermia heats a very small area and is typically used for cancers near or on the skin or near natural openings in the body. In some instances, the goal is to kill the tumor by heating it, without damaging anything else. The heat may be created with microwave, radiofrequency, ultrasound energy or using magnetic hyperthermia ). Depending on the location of the tumor, the heat may be applied to the surface of the body ', inside normal body cavities ', or deep in tissue through the use of needles or probes . It should not be confused with ablation of small tumors, where higher temperatures are applied with an aim to kill the tumor cells.
- Regional hyperthermia heats a larger part of the body, such as an entire organ or limb. Usually, the goal is to weaken cancer cells so that they are more likely to be killed by radiation and chemotherapeutic medications. This may use the same techniques as local hyperthermia treatment, or it may rely on blood perfusion. In blood perfusion, the patient's blood is removed from the body, heated up, and returned to blood vessels that lead directly through the desired body part. Normally, chemotherapy drugs are infused at the same time. One specialized type of this approach is continuous hyperthermic peritoneal perfusion, which is used to treat difficult cancers within the peritoneal cavity, including primary peritoneal mesothelioma and stomach cancer. Hot chemotherapy drugs are pumped directly into the peritoneal cavity to kill the cancer cells.
- Whole-body hyperthermia heats the entire body to temperatures of about, with some advocating even higher temperatures. It is typically used to treat metastatic cancer. Techniques include infrared hyperthermia domes which include the whole body or the body apart from the head, putting the patient in a very hot room/chamber, or wrapping the patient in hot, wet blankets or a water tubing suit.
Treatment
Localized hyperthermia treatment is a well-established cancer treatment method with a simple basic principle: If a temperature elevation to can be maintained for one hour within a cancer tumor, the cancer cells will be destroyed.
The schedule for treatments has varied between study centers. After being heated, cells develop resistance to heat, which persists for about three days and reduces the likelihood that they will die from direct effects of the heat. Some even suggest maximum treatment schedule of twice a week. Japanese researchers treated people with "cycles" up to four times a week apart. Radiosensitivity may be achieved with hyperthermia, and using heat with every radiation treatment may drive the treatment schedule. Moderate hyperthermia treatments usually maintain the temperature for approximately an hour.
Before the advent of modern antiretroviral therapy extracorporeal whole body hyperthermia was tried as a treatment for HIV/AIDS, with some positive outcomes.
Adverse effects
External application of heat may cause surface burns. Tissue damage to a target organ with a regional treatment will vary with what tissue is heated. Whole body hyperthermia can cause swelling, blood clots, and bleeding. Systemic shock, may result, but is highly dependent upon method difference in achieving it. It may also cause cardiovascular toxicity. All techniques are often combined with radiation or chemotherapy, muddying how much toxicity is the result of those treatments versus the temperature elevation achieved.Technique
Heat sources
There are many techniques by which heat may be delivered. Some of the most common involve the use of focused ultrasound, RF sources, infrared sauna, microwave heating, induction heating, magnetic hyperthermia, infusion of warmed liquids, or direct application of heat such as through sitting in a hot room or wrapping a patient in hot blankets.Controlling temperature
One of the challenges in thermal therapy is delivering the appropriate amount of heat to the correct part of the patient's body. For this technique to be effective, the temperatures must be high enough, and the temperatures must be sustained long enough, to damage or kill the cancer cells. However, if the temperatures are too high, or if they are kept elevated for too long, then serious side effects, including death, can result. The smaller the place that is heated, and the shorter the treatment time, the lower the side effects. Conversely, tumor treated too slowly or at too low a temperature will not achieve therapeutic goals. The human body is a collection of tissues with differing heat capacities, all connected by a dynamic circulatory system with variable relationship to skin or lung surfaces designed to shed heat energy. All methods of inducing higher temperature in the body are countered by the thermo-regulatory mechanisms of the body. The body as a whole relies mostly on simple radiation of energy to the surrounding air from the skin which is augmented by convection and vaporization through sweat and respiration. Regional methods of heating may be more or less difficult based on the anatomic relationships, and tissue components of the particular body part being treated. Measuring temperatures in various parts of the body may be very difficult, and temperatures may locally vary even within a region of the body.To minimize damage to healthy tissue and other adverse effects, attempts are made to monitor temperatures. The goal is to keep local temperatures in tumor bearing tissue under to avoid damage to surrounding tissues. These temperatures have been derived from cell culture and animal studies. The body keeps itself normal human body temperature, near. Unless a needle probe can be placed with accuracy in every tumor site amenable to measurement, there is an inherent technical difficulty in how to actually reach whatever a treating center defines as an "adequate" thermal dose. Since there is also no consensus as to what parts of the body need to be monitored. Clinicians have advocated various combinations for these measurements. These issues complicate the ability of comparing different studies and coming up with a definition of exactly what a thermal dose actually should be for tumor, and what dose is toxic to what tissues in human beings. Clinicians may be able to apply advanced imaging techniques, instead of probes, to monitor heat treatments in real time; heat-induced changes in tissue are sometimes perceptible using these imaging instruments.
There is the further difficulty inherent in the devices delivering energy. Regional devices may not uniformly heat a target area, even without taking into account compensatory mechanisms of the body. A great deal of current research focuses on how one might precisely position heat-delivery devices using ultrasound or magnetic resonance imaging, as well as developing new types of nanoparticles that can more evenly distribute heat within a target tissue.
Among hyperthermia therapy methods, magnetic hyperthermia is well known as the one that produce a controllable heat inside the body. Because of using magnetic fluid in this method, temperature distribution can be controlled by the velocity, size of nanoparticles and distribution of them inside the body. These materials upon application of external, alternating magnetic field convert electromagnetic energy into thermal energy and induce temperature rises.
Mechanism
Hyperthermia can kill cells directly, but its more important use is in combination with other treatments for cancer. Hyperthermia increases blood flow to the warmed area, perhaps doubling perfusion in tumors, while increasing perfusion in normal tissue by ten times or even more. This enhances the delivery of medications. Hyperthermia also increases oxygen delivery to the area, which may make radiation more likely to damage and kill cells, as well as preventing cells from repairing the damage induced during the radiation session.Cancerous cells are not inherently more susceptible to the effects of heat. When compared in in vitro studies, normal cells and cancer cells show the same responses to heat. However, the vascular disorganization of a solid tumor results in an unfavorable microenvironment inside tumors. Consequently, the tumor cells are already stressed by low oxygen, higher than normal acid concentrations, and insufficient nutrients, and are thus significantly less able to tolerate the added stress of heat than a healthy cell in normal tissue.
Mild hyperthermia, which provides temperatures equal to that of a naturally high fever, may stimulate natural immunological attacks against the tumor. However, it is also induces a natural physiological response called thermotolerance, which tends to protect the treated tumor.
Moderate hyperthermia, which heats cells in the range of, damages cells directly, in addition to making the cells radiosensitive and increasing the pore size to improve delivery of large-molecule chemotherapeutic and immunotherapeutic agents, such as monoclonal antibodies and liposome-encapsulated drugs. Cellular uptake of certain small molecule drugs is also increased.
Very high temperatures, above, are used for ablation of some tumors. This generally involves inserting a metal tube directly into the tumor, and heating the tip until the tissue next to the tube has been killed.