This invention relates to systems and methods for treatment of cancer, and particularly to the use of hyperthermia in cancer treatment.
Present modalities for treatment of malignant tumors include surgery, radiation therapy, chemotherapy, and immunotherapy which apply a physical or chemical force to alter the biological function of a tumor in order to affect its viability. Despite the medical advances that these modalities represent, most solid cancerous tumors carry with them a very poor prognosis for survival. Quality of life during and after treatment for survivors is often poor. The dismal prognosis for malignant solid tumors has led to continuing research for more effective treatment modalities with a lesser degree of disability and fewer side effects. In vitro and in vivo evidence indicates hyperthermia produces a significant anti-cancer activity through alteration of the physical environment of the tumor caused by increasing the temperature. Hyperthermia is more cytotoxic to tumor cells than normal cells because cancer cells are oxygen deprived, nutritionally deficient, and low in pH making them incapable of tolerating the stress imposed by elevated temperature. Tumor vasculature is immature, lacking the smooth muscle and vasoactivity which allows mature vessels to dilate, increasing blood flow to carry away heat, therefore intratumor temperatures exceed those in normal tissue. The mechanisms of selective cancer cell eradication by hyperthermia is not completely understood. However, four cellular effects of hyperthermia on cancerous tissue have been proposed: 1) changes in cell or nuclear membrane permeability or fluidity, 2) cytoplasmic lysomal disintegration, causing release of digestive enzymes, 3) protein thermal damage affecting cell respiration and the synthesis of DNA and RNA and 4) potential excitation of immunologic systems.
The major forms of energy for generating hyperthermia to date include microwaves, radio frequency induction, radio frequency localized current, and ultrasound. Most of the techniques used to dispense these are non-invasive, i.e,. the heat generating source is external to the body and does not invade the body. Consequently, the energy must pass through the skin surface and substantial power absorption by normal peripheral body tissue is unavoidable. Currently available external heating sources result in nonuniform temperature profiles throughout the tumor and increased temperatures in normal tissue. It is desirable to selectively heat tissues deep in a patient's body, i.e., to heat the tumor mass without heating cutaneous and normal tissue.
Others have attempted the use of interstitial techniques to obtain local hyperthermia, with limited success. Interstitial heating of brain tumors through an implantable microwave antenna has been investigated. However, microwave probes are ineffective in producing precisely controlled heating of tumors. Temperatures may deviate as much as 10 degrees Celcius from the desired target temperature. Besides, microwave activity adversely affects cellular structures and their integration, regardless of other thermal effects. The result is nonuniform temperatures throughout the tumor. Studies indicate that tumor mass reduction by hyperthermia is related to the thermal dose. Thermal dose is the minimum effective temperature applied throughout the tumor mass for a defined period of time. Hot spots and cold spots which occur with microwave hyperthermia may cause increased cell death at the hot spot, but ineffective treatment at cold spots resulting in future tumor growth. Such variations are a result of the microwave antenna's inability to evenly deposit energy throughout the tissue.
Since efferent blood flow is the major mechanism of heat loss for tumors being heated and blood flow varies throughout the tumor, more even heating of tumor tissue is needed to ensure more effective treatment.
To be effective, the application and deposition of thermal energy to the tumor must be precisely controlled to compensate for the variations in blood flow. In addition, the therapy itself will perturb the tumor's vascular system during treatment causing variations in local perfusion around the probe. Thus, heat loss from a tumor will be time dependent and affected by the hyperthermia treatment. This demonstrates the need to both monitor and control the temperature of the tumor throughout treatment.