Hyperthermia, sometimes also called hyperthermia therapy, thermal therapy, or thermotherapy, is the use of therapeutic heat to treat various cancers on and inside the body. The therapy exposes body tissues affected by cancer to high temperatures, generally from 104.9°F (40.5°C) up to 113°F (45°C), although in some types of hyperthermia the temperatures are even higher. These temperatures have been found by medical research to damage or even kill cancerous cells with little or no harm to normal cells. Consequently, such treatments have the potential to provide cancer treatment without many of the adverse side effects present in traditional treatments.
Outside the context of therapy, hyperthermia is defined as an elevated body temperature due to a failure of the body to properly regulate the amount of heat produced, absorbed, or dissipated.
The purpose of hyperthermia is to shrink and destroy cancer without harming noncancerous cells. It can be used to treat cancer in many areas of the body, including the head, neck, and brain; liver; rectum; bladder; esophagus; thyroid; lung; breast; cervix; and prostate. It is thought that high temperatures, up to about 113°F (45°C), though sometimes higher in certain types of hyperthermia, can help shrink cancerous tumors. As of 2017, hyperthermia was becoming more widely used because it does not have side effects like other forms of cancer treatment such as radiation or chemotherapy. In some instances, hyperthermia is used alongside other forms of cancer therapy. Hyperthermia therapy combined with radiation therapy is called thermoradiotherapy.
Through years of research in biology, physics, and engineering as well as clinical medicine, scientists have found that the effectiveness of some forms of radiation therapy and chemotherapy are enhanced when combined with hyperthermia. In addition, the effectiveness of some anticancer drugs is enhanced when combined with hyperthermia therapy. Further refinements in hyperthermia therapy and its use with other cancer therapies and medicines were ongoing as of 2017.
Although the treatment was considered experimental in the late 1980s and early 1990s, its proponents believe that the treatment has been generally accepted by many physicians and that use of hyperthermia will increase as more cancer centers install the equipment necessary for regional and whole body hyperthermia. As of 2017, cancer care centers offering this treatment were limited to those affiliated with university-related medical schools and other large medical centers such as the Cleveland Clinic. The American Cancer Society acknowledges that hyperthermia can make the cancer cells of some cancers more responsive to treatment but still considers the treatment experimental, especially in its whole-body form.
The National Cancer Institute (NCI) sponsored ongoing clinical trials studying hyperthermia. Although hyperthermia was not accepted as standard treatment for cancer as of 2017, clinical trials continue to be performed to determine its effectiveness for cancer treatment, along with research in new techniques for administering it. As of November 2016, there were 235 clinical studies being conducted in the United States of hyperthermia therapy as a treatment for cancer; most of these studies were exploring the benefits of hyperthermia therapy in conjunction with radiation or chemotherapy rather than as monotherapy.
Hyperthermia can be used on very small areas of the body or the entire body. The three main types of hyperthermia are local, regional, and whole-body hyperthermia. In each type, the cancerous cells are heated to high temperatures, which is sufficient to degrade or kill them. Because cancer cells have a disorganized cellular structure, they do not dissipate heat as efficiently as healthy cells. The additional heat provided during hyperthermia therapy is thought to induce apoptosis (programmed cell death) in cancerous cells without harming normal cells. When the cancerous cells undergo apoptosis or are otherwise degraded, other cancer treatments can be implemented and are much more effective because of the weakened state of the harmful cells.
Local hyperthermia, also called thermal ablation, refers to heating just one small area of the body, usually only the region where the tumor is located. The high heat kills the cancer cells and, in some cases, destroys blood vessels or coagulates proteins. Heat can be applied from outside the body using microwaves, radio waves, or ultrasound waves. When ultrasound is used, the technique is called high-intensity focused ultrasound (HIFU). The use of radio waves, called radiofrequency ablation (RFA), is considered the most common type of local hyperthermia. For 10 to 30 minutes, a needle-like probe is inserted into the tumor. Computed tomography (CT) or magnetic resonance imaging (MRI) scans are used to direct the positioning of the probe. Very high heat—122°F–212°F (50°C–100°C)—is used to kill cancerous cells within the localized area. This method is used for tumors up to about 2 in. (5 cm) across and is most common in tumors within the lungs, liver, and kidneys.
Heat can be applied from inside the body or even inside the tumor itself by the use of thin heated wires, small tubes filled with hot water, or implanted microwave antennae. Interstitial techniques, as they are called, are used to treat tumors deep within the body such as those in the brain. Intraluminal methods, also called endocavitary approaches, are used to treat tumors in or around such body cavities as the rectum or esophagus. For tumors near or on the skin, external application of hyperthermia is used. A device aims high-energy waves at the tumor, which heats the area and kills the cancerous cells. Recent advances in local hyperthermia therapy include the use of nanomaterials to provide more precise targeting of cancer cells.
If heat is used to treat an entire organ, body cavity, or limb, it is referred to as regional hyperthermia. High-energy magnets or other devices that produce heat are placed over the larger areas to be heated. This approach is called deep-tissue treatment and is used to treat cancers of the cervix and bladder.
Another method of regional hyperthermia is the use of perfusion. Hyperthermia regional perfusion, sometimes also called isolation perfusion, uses the patient's own blood. The blood is removed, heated outside the body (usually from 104°F to 113°F [40°C to 45°C]), then pumped (perfused) back into the area that contains the cancer. Usually, only a portion of the blood within the body is perfused. Cancers within the arms and legs, such as melanomas or sarcomas, are often treated with perfusion. Chemotherapy drugs can be included within the blood at the same time.
Another regional technique is called continuous hyperthermic peritoneal perfusion (CHPP). It is used to treat cancers within the peritoneal cavity (the body cavity that contains the intestines, liver, and stomach). Heated anticancer drugs are sent through the peritoneal cavity, usually at temperatures of 106°F to 108°F (41.1°C to 42.2°C).
Deep-tissue hyperthermia is another regional technique. It uses a device placed on the surface of an organ, body cavity, or limb that produces highenergy waves (usually radio or microwave radiation) directed at a specific cancerous area.
Patients who have extensive metastatic cancer (spreading of the cancer throughout their body) may not be good candidates for hyperthermia. Patients must be free of major infections and able to tolerate the high temperatures of the treatment. Caution must be used when areas of the body are heated with such external heat sources as heating pads to avoid potentially dangerous burns. Normally, the process does not harm healthy tissues. However, due to differences in tissues within the body, temperatures that are higher than anticipated can result in some areas. If the temperature of hyperthermia remains below 111°F (43.9°C), then normal tissues are safe. If normal tissues are harmed, it is usually in the form of discomfort or pain, blisters, or burns.
There are generally no advance preparations needed for a patient considering the use of hyperthermia other than an explanation of the specific form of hyperthermia that will be used. The patient should be reassured that a physician, nurse, or therapist will be present in the treatment room with them at all times.
After (or during) hyperthermia other types of anticancer treatments are sometimes performed, usually within an hour of administering hyperthermia therapy. Hyperthermia seems to help these treatments work better, especially the regional and whole-body types, because cancer cells are weakened by the process and are much more easily treated by radiation or the various drugs used in chemotherapy. Patients undergoing hyperthermia need little aftercare, unless such medical problems result as blistering, burning, or similar concerns. For the most part, hyperthermia therapy appears to avoid many of the serious side effects found in such traditional cancer treatments as chemotherapy and radiation therapy.
The major complications of hyperthermia are pain and external burns. Heat applied directly to the skin can cause minor discomfort to significant pain, especially when high temperatures are used. Blistering and actual burning of the skin can occur at higher temperatures, although with careful application of the hyperthermia, these side effects are rare. Other problems include blood clots; swelling; and damage to the skin, muscles, or nerves near the treatment site. For the most part, such side effects are short term but can be serious if the hyperthermia process is not controlled properly.
In some circumstances, perfusion techniques can cause such moderate problems as blood clots, bleeding, tissue swelling, and other damage to the normal tissues. However, for the most part, these problems are temporary. Serious problems can be caused by whole-body hyperthermia. Such problems include vascular (blood vessels) and cardiac (heart) disorders, along with problems with other major organs. Minor after effects include diarrhea, nausea, or vomiting.
There are typically no abnormal results seen with the use of hyperthermia. Such side effects as pain and burning from external heat sources can be minimized with careful application of the heat. However, control of the exact temperature used for hyperthermia is still difficult. For instance, an accurate way to measure temperature inside a tumor had not been devised as of 2017. In addition, different body tissues respond differently to heat. For instance, the brain is very sensitive to heat. As scientists continue to learn more about hyperthermia therapy, such as better control of temperatures and delivery of heat, hyperthermia becomes a more effective method of cancer treatment.
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Edward R. Rosick, DO, MPH
Revised by William A. Atkins, BB, BS, MBA
Revised by Rebecca J. Frey, PhD