Interstitial Microwave Thermal Therapy

Definition

Interstitial microwave thermal therapy is a type of hyperthermia treatment for cancer, in which heat produced by microwaves (which are a non-ionizing form of radiation) is used in conjunction with other cancer treatments, such as radiation or chemotherapy, to kill cancer cells associated with tumors located deep with the body.

Purpose

The purpose of interstitial microwave thermal therapy is to damage and kill cancer cells associated with tumors that are deep within the body. Interstitial microwave therapy is a type of hyperthermia cancer treatment procedure (also called thermal therapy or thermotherapy) in which body tissue and the cancerous tumor are exposed to high temperatures (up to 113°F). Hyperthermia kills cancer cells with usually only minimal injury to normal tissues by damaging proteins and structures within the cells. Thermal therapy is usually used with other forms of cancer therapy, such as radiation and chemotherapy. The increased temperatures may make some cancer cells more sensitive to radiation or may harm some cancer cells that radiation cannot damage.

Precautions

If a patient has become insensitive to pain due to disease, radiation, surgery, anesthetics, or other conditions, hyperthermia treatment cannot be used to treat tumors. Also the excessive heating of normal surrounding tissue is prevented by normal blood perfusion, so hyperthermia should not be used in patients with known circulatory problems in the heated areas or in patients who are taking vasoconstrictive drugs.

Description

Interstitial microwave thermal therapy is used to treat tumors that are deep within the body, such as brain, cervical, breast, prostate, and neck tumors. This technique allows the tumor to be heated to higher temperatures than external thermal therapy techniques allow. Probes or needles are inserted into the tumor, guided by the use of imaging techniques, such as ultrasound, to make sure that the probe is properly located within the tumor. A new type of microwave generator includes electronic phase control that allows the operator to electronically direct and shape the pattern of hyperthermia treatments based on the positioning the microwave antennae array that is used in treating the tumor. The treatment pattern can be electronically targeted on the tumor position, shape, and size.

Tissues are heated as the electromagnetic energy produced by the microwave treatment results in heating through molecular excitation. This energy is dissipated in normal living tissue by the blood that perfuses through the tissue. However, since large solid malignant tumors have less blood perfusion than the surrounding normal tissue, for a given absorbed thermal dose, the tumor reaches a higher temperature than the normal tissue. Tumors present within normal tissue will therefore be preferentially heated and will reach higher temperatures than the surrounding tissue.

As cancerous tumors grow rapidly, their need for blood quickly begins to exceed the available blood supply, and major portions of the tumors become blood-starved. These blood-starved tumors are resistant to both radiation and chemotherapy. Chemotherapy drugs carried through the blood cannot effectively penetrate tumors that have poor blood flow. Poor blood flow also means that the tumors are oxygen-starved (hypoxic), making it difficult for radiation therapy to make the oxygen radicals that are needed to destroy the DNA of cancer cells. Hypoxic cancer cells, which are an especially dangerous type of cancer, for they have a tendency to metastasize and spread the cancer to other parts of the body, are three times more resistant to ionizing radiation than are normal cells.

When the tumor is heated to fever levels through the use of microwave thermal therapy, its blood vessels expand so that more blood can flow into the tumor in order to carry away the excess heat. With the increased blood flow, more blood-borne chemotherapy drugs can be carried into the tumor. Blood is also the source of oxygen for tumors, so with increased blood flow due to the thermal therapy, radiation therapy can form the necessary oxygen radicals to kill the cancer cells. The increased temperature also acts as a drug activator, accelerating chemical reactions and pulling increased oxygen molecules into the tumor tissue for chemical reactions with the chemotherapy drug. Hypothermia also enhances the effectiveness of chemotherapy drugs encapsulated in liposomes, increasing the penetration of the drug into the tumor.

When tumors are heated to higher temperatures for at least an hour, the tumors in some cases have been shown to decrease in size and to exhibit necrosis (death of the tumor cells). Therefore, hyperthermia by itself also tends to shrink tumors, often dramatically, due to the collapse of dead cancer cells, making it easier to remove the tumor by surgical techniques. For tumors of the head and neck, a smaller tumor due to hyperthermia treatment may reduce the disfiguration associated with surgical removal of the tumor.

Hyperthermia is being studied as a means of enhancing gene therapy by acting as an activator to turn on new biological therapies, by speeding up gene production by thousands of times. In addition, hyperthermia is used as an essential tool to turn on anti-tumor vaccines that are based on heat shock proteins. Hyperthermia has been shown to prevent a cancererous tumor from growing new blood vessels to expand its blood supply. With regards to quality of life, hyperthermia lessens pain and stimulates the immune system, thus helping patients recover from toxic cancer therapies such as ionizing radiation and chemotherapy. Even in patients with terminal cancer, hyperthermia can provide benefits through the alleviation of bleeding, pain, and infection.

As of 2005, the use of hyperthermia alone and in conjunction with radiation therapy has been approved by the United States Food and Drug Administration for the treatment of advanced, recurrent, and persistent tumors, upon authorization of a licensed practitioner. When used with radiation, the treatment regimen usually consists of 10 hyperthermia treatments delivered twice a week, at 72 hour intervals. The prescribed radiation is administered within 30 minutes of the hyperthermia treatment. During each heat treatment, the temperature within the tumor is usually maintained at 42.5 degrees centigrade for 60 minutes. The use of hyperthermia in conjunction with chemotherapy is presently investigational in the United States as of 2005.

The effectiveness of treatment is related to the temperature achieved during the treatment process, the length of the treatment, and cell and tissue characteristics. The temperature within the tumor must be monitored to ensure that the appropriate temperature is achieved, but not exceeded, in the treatment area. Monitoring is accomplished by inserting small needles or tubes with small thermometers into the treatment area. Imaging techniques such as computed tomography (CT) are used to make sure that the temperature probes are positioned appropriately.

Preparation

The safety and effectiveness of hyperthermia treatment is dependent on careful placement of the temperature probes and careful monitoring of tissue temperatures during treatment.

Aftercare

During the treatment period, which may last for weeks, the patient must be instructed in proper care of implanted catheters and temperature probe sites to avoid the risk of infection.

Risks

Excessive heating of normal tissues may result in areas of thermal aseptic necrosis that will require medical care. The electromagnetic radiation from the microwave equipment can interfere with electronic devices such as cardiac pacemakers or other implanted electronic devices. Thermal treatment of tumors in the neck or head may result in inadvertent heating of thermoregulatory centers in the brain stem, thus resulting in overheating of the body, beyond levels that the patient can tolerate. Metallic implants, such as joint protheses or dental braces may become excessively and preferentially overheated and adversely affect the patient.

Normal results

The effectiveness of interstitial microwave thermal therapy varies among cancer patients. For example, studies have shown in Phase III clinical trials, when hyperthermia was used with ionizing radiation treatment, that the following treatment improvements were seen, as compared to the use of ionizing radiation therapy alone:

• complete response for recurrent breast cancer increased from 38% to 60%
• 2-year survival for globlastoma (brain cancer) increased from 15% to 31%
• complete response for advanced cervical cancer increased from 57% to 83%

Known side effects of hypothermia are associated with direct effects of heat on tissues and indirect effects of tumor necrosis. These side effects, as determined in various medical studies, include:

• surface burns and blistering in the area of application of heat by the microwave applicators; experienced in about 10% of the tumor sites studied.
• localized and temporary pain in the area of and during the delivery of the heat by the microwave applicators; experienced in about 8% of the tumor sites studied.

• ulceration from rapid tumor necrosis following successful hyperthermia treatment, resulting in fever from toxemia and patient discomfort through drainage and bleeding; experienced in about 4% of the tumor sites studied.
• local and systematic (rarely) infections from placement of the temperature probes and from ulceration related to tumor necrosis; experienced in about 2% of the tumor sites studied.

Abnormal results

Hyperthermia has the potential for producing the following adverse reactions as a result of exposure to electromagnetic radiation:

• cataracts
• permanent or temporary male sterility
• exacerbation of existing diseases due to additional systemic stress
• enhanced drug activity
• thermal stress

Resources

BOOKS

Rosenbaum, Ernest, Dollinger, Malin, Tempero, Margaret, and Mulvihill, Sean. Everyone's Guide to Cancer Therapy. 4th Edition. Kansas City, KS: Andrews McMeel Publishing, 2002

PERIODICALS

Falk, M.H., and Issels, R.D. "Hyperthermia in Oncology." International Journal of Hyperthermia. 2001, (17) 1-18.

van der Zee, J. "Heating the Patient: A Promising Approach?" Annals of Oncology 2002, (13) 1173-1184.

Wust, P., Hildebrandt, B., Sreenivasa, G. et al. "Hyperthermia in Combined Treatment of Cancer." The Lancet Oncology 2002, (3) 487-497.

ORGANIZATION

Hyperthermia in Cancer Treatment. National Cancer Institute. 〈www.cis.nci.gov/fact/7_3.htm〉

Society for Thermal Medicine. 〈www.thermaltherapy.org〉.

KEY TERMS

Blood perfusion— A physiological term that refers to the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue.

Hyperthermia therapy— A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs.

Non-ionizing radiation— Rays of energy that move in long, slow wave patterns and do not penetrate cells.t

Ionizing radiation— Any electromagnetic or particulate radiation capable of producing ions, directly or indirectly, in its passage through matter.