User:Rrwhite54/Hyperthermia

'Hyperthermia' (also called thermal therapy or thermotherapy) is a type of cancer treatment in which body tissue is exposed to high temperatures (up to 113°F). Research has shown that high temperatures can damage and kill cancer cells, usually with minimal injury to normal tissues (1). By killing cancer cells and damaging proteins and structures within cells (2), hyperthermia may shrink tumors.

How is Hyperthermia used to treat cancer?

Hyperthermia can substantially improve the results from cancer treatments for many types of tumors. In Phase III clinical trials where hyperthermia was combined with radiation, hyperthermia improved 2-year local control of melanoma from 28% to 46%, complete response for recurrent breast cancer from 23% to 68%, the survival rate of patients with glioblastoma (brain cancer) from 15% to 31%, the 3 year survival rate of patients with advanced cervical cancer from 27% to 51% and the 5-year survival rate from 0% to 53% in patients with head and neck cancer, compared to the use of radiation therapy alone. Other, non-randomized trials have demonstrated notable response in prostate cancer, colorectal cancer and other solid tumors.

Vunerability of Cancerous Tumors

Cancerous tumors are growths of mutated cells that often require more energy to survive than do normal cells. As cancer cells multiply unchecked, they can quickly outstrip the capacity of their exisiting blood vessels to supply enough oxygen and nutrients to support them. In response, malignant tumors stimulate growth of additional blood vessels. However, these new blood vessles can be mutated, chaotic structures, as compared to blood vessels of normal tissues-having odd sizes, with loops and even blind ends. Because of this irregular blood vessel structure and rapid tumor growth, there are often large areas in tumors where the blood supply is insufficient.

Cancerous tumors that do not have an adequate blood supply become oxygen starved (hypoxic) because blood is the source of oxygen delivery for cells. They also become acidic because hypoxic tumors cannot adequately expel waste through the blood. These tumors can even experience wide fluctuations in blood flow as their unstable blood vessels periodically collapse, making them acutely oxygen deficient for periods of time. Oxygen starved cancer cells are difficult to kill with ionizing radiation (which creates oxygen radicals that attack tumor DNA) or chemotherapy (where blood transport is required to deliver the drug). Destroying blood/oxygen depleted cancer is a very high priority in cancer therapy because hypoxic cancer cells are especially dangerous and prone to metastasize, or spread the cancer to other parts of the body.

How Hyperthermia Kills Cancer Cells

Hyperthermia destroys cancer cells by raising the tumor termperature to a "high fever" range, similar to the way the body uses fever naturally when combating other forms of disease. Because the body's means of dissipating heat is through cooling from blood circulation, sluggish or irregular blood flow leaves cancerous tumors vulnerable to destruction at elevated temperatures that are safe for surrounding healthy tissues with normal, efficient blood-cooling systems.

Scientists attribute the destruction of cancer cells at hyperthermic temperatures to damage in the plasma membrane, the cytoskeleton and the cell nucleus. Cancer cells are vulnerable to hyperthermia therapy particularly due to their high acidity caused by the inability to properly expel waste created by anaerobic metablolism. Hyperthermia attacks acidic cells, disrupting the stability of cellular proteins and killing them.

How Hyperthermia Increases the Effectiveness of Ionizing Radiation

Hyperthermic temperatures increase blood circulation and perfusion in tumors as the body's response to the stimulus of heat. This increased presence of oxygen-bearing blood in tumor tissues is critical for making inonizing radiation more effective. Ionizing radiation destroys tumor cells substantially through the formation of oxygen radicals that attack tumor cell DNA. Oxygen-starved cells are three times more resistant to ionizing radiation than are normal cells. It has been demonstrated that low oxygen levels in human tumors (hypoxia) are directly linked to failure in achieving local tumor control through ionizing radiation, and the degree of oxygen deficiency in cancerous tumors is a key predictor of the efficacy of ionizing radiation therapy.

While oxygen radicals attack cancer cell DNA, hyperthermia acts further to create an accumulation of proteins in the cell nucleus that bind to nuclear matrix, disrupting the repair of radiation induced DNA damage. Hyperthermia provides additional potentiation of ionizing radiation due to the growth cycle of cancer cells. During the S-phase of cell division, when cancer cells are aggressively resistant to the effects of ionizing radiation, they are susceptible to the destructive effects of hyperthermia.

The conditions that enhance the effects of hyperthermia are typcially those that reduce the effects of ionizing radiation. Low blood-flow tumor tissues, resistant to ionizing radiation, are sensitive to hyperthermia, while tumor tissues with high blood flow are sensitive to inonizing radiation. This highly complementary interaction is a compelling reason for combining hyperthermia and ionizing radiation. In vivo studies have demonstrated that the effects of ionizing radiation can be enhanced by a factor between 1.2 and 5, making hyperthermia the most potent sensitizer to ionizing radiation therapy known.

How Hyperthermia May Increase the Effectiveness of Chemotherapy

For chemotherapy drugs that depend on blood transport for delivery, hyperthermia used in combination with chemotherpay to enhance blood flow in tumor tissues, may increase the uptake of chemotherapy drugs in tumor membranes. Hyperthermia also induces disassembly of the cytoskeleton, which can enlarge the tumor pores for easier drug entry. Hyperthermic temperatures can also be used as a drug activator, accelerating chemical reactions through heat and drawing essential oxygen molecules to tumor tissue for chemical reaction with the drug. Studies have been published regarding the interactions of hyperthermia with a range of chemotherapy drugs, including doxorubicin, mitomycin C, mitoxantrone, bleomycin, cisplatin, nitrosoureas and cyclophosphamide. Hyperthermia has deomonstrated the ability to enhance drug toxicity in cells that are resistant to many drugs used in chemotherapy.

Hyperthermia may have a role as a valuable companion therapy when chemotherapy drugs are injected into the blood encapsulations called "liposomes". Research has shown that when a liposome-encapsulated drug is used in combination with hyperthermia therapy directed on a tumor, drug penetration can dramatically increase. Research is also being conducted on heat-activated liposomes that use hyperthermic temperatures as the release mechanism for the encapsulated drug when they reach the tumor.

Hyperthermia has also been employed synergistically with chemotherapy in strategies to treat bulky tumors. The cores and other regions of these tumors are often difficult to penetrate with drugs because of low blood flow in up to a third of the mass of the tumor. In addition, chemotherapeutic drugs act best on rapidly dividing cells. As blood-starved cells are growth retarded, chemotherapy has limited efficacy against them. Hyperthermia is able to attack cancer cells in blood-deficient regions of the tumor while the drug permeates tissues with higher blood flow nearer the surface, providing potentiation of drug uptake.

Hyperthermia and Surgery

Tumors tend to shrink when treated with hyperthermia, due to the collapse of dead cancer cells. This can make tumor removal through surgery easier or even possible. Hyperthermia may have preoperative value when tumor removal is dangerous or not possible because or proximity to vulnerable adjacent tissue. Additional benefits of hyperthermia include the potential for reduced disfiguration resulting from surgical removal of tumors of the head and neck or other conspicuous parts of the body by shrinking the tumor prior to surgery.

Hyperthermia and Biological Therapies

Increased blood flow and perfusion also results in the increase of the presence of the body's own antibodies in the tumor. In addition, gene therapy research is showing hyperthermia to be an activator to turn on new biological therapies, speeding gene production by thousands of times (heat mediated gene therapy). Hyperthermia plays an essential role in the development of anti-tumor vaccines that are based on heat shock proteins. Research has shown hyperthermia to be an angiogenesis inhibitor, preventing cancer from inducing growth of new blood vessels to expand its blood supply. Hyperthermia has also been studied as a companion therapy of depleted cancer cells that survive blood starved conditions. Some scientists have noted that hyperthermia stimulates the immune system, which may have the potential to assist patients in recovery from toxic cancer therapies such as chemotherapy and ionizing radiation.

Hyperthermia and Quality of Life

A study by the National Academy of Sciences has pointed out the shortcomings of the single-minded search for cancer cure while ignoring existing patients who need treatment for pain and other conditions associated with cancer. A substantial improvement in both palliation and durability of palliation has been observed when hyperthermia is added to ionizing radiation treatments. Even in situations where there is no hope for survival, hyperthermia may provide benefit through alleviation of such effects.