Local and Systemic Hyperthermia for Cancer Treatment

Laboratory observations have shown that overheating can damage and even kill both healthy and cancerous cells. In healthy cells, thermal damage repair mechanisms are more efficient than in malignant cells, and therefore a larger proportion of them are able to survive thermal damage.

Hyperthermia therapy is currently only given in selected and specific cases, as an adjunct to conventional cancer treatments such as radiation and chemotherapy. There is no advantage or justification for administering hyperthermia therapy as a stand-alone treatment, without combining it with these conventional oncological treatments.

In certain malignant diseases, such as advanced cervical cancer and sarcoma, there is an advantage to combining chemotherapy with hyperthermia, which has been demonstrated in Phase III studies, with the advantage being expressed in a higher rate of stages 1 and 2. However, in most other malignant diseases, this is an experimental treatment whose benefit is still questionable.

Hyperthermia treatment is performed using one of the following three methods:

Local hyperthermia

Local hyperthermia is performed in combination with radiation and/or chemotherapy, in cases of superficial and near-skin recurrences, such as breast cancer recurrence, malignant melanoma, etc. Equipment for heat treatment of superficial tumors has been available for many years in many hospitals around the world. In Israel, standard equipment for superficial hyperthermia is available at the Tel Aviv Medical Center. The treatment is given using an applicator, which is held close to or inside the tumor. There are several ways to deliver local hyperthermia: using an external applicator, inside a cavity, or using an interstitial applicator, depending on the location of the tumor. The heat can be delivered by several energy sources: microwave radiation, radio frequency radiation, and ultrasound. Temperature sensors are placed around the tumor area and a plastic catheter is inserted into it, with temperature monitoring equipment inside. A single treatment can last up to an hour and a half.

Regional (deep) hyperthermia

The effectiveness of this method (in combination with chemotherapy or radiation) has been proven in cases of recurrent cervical cancer and locally advanced sarcoma. Deep regional hyperthermia treatments are currently mostly given as part of clinical trials. Another method is to administer chemotherapy by intra-arterial or intraperitoneal injection in a heated solution. This method is used in certain surgical departments in Israel.

Whole-body (deep) hyperthermia

Experimental treatment, for metastatic systemic malignancies. Whole-body hyperthermia treatments are currently only given as part of clinical trials. That is, these are treatments that are still in the research phase and have not yet been approved by the competent authorities. Their initial results have not yet shown unequivocal efficacy.

How does hyperthermia Therapy Work?

In principle, there is no difference in the sensitivity of healthy cells to hyperthermia compared to the sensitivity of malignant cells. However, most healthy tissues are not damaged by heating to 40-44°C for about an hour, and more selective killing of malignant cells is achieved. The selective destruction of malignant cells results from changes in cell proteins at temperatures higher than 40°C, which causes irreversible damage to the repair mechanisms of the malignant cell. In contrast, healthy cells manage to repair the heat damage and recover over time.

When normal body tissue with a healthy vascular system is heated, the blood vessels in the area dilate to allow faster and easier blood flow, which helps cool the area by spreading the heat to other areas of the body. In this way, damage to healthy tissue is prevented.

In contrast, the blood supply to a malignant tumor is different. In tumor tissue, the blood vessels are tortuous and inflexible. Under the influence of heat, not only do they not expand, but they even contract. This prevents heat from draining from the tumor area, so the heat remains there for a longer time and causes damage to the tumor cells. In addition, the contraction of the blood vessels in the tumor tissue prevents nutrients and oxygen, which the cells need to live and develop, from reaching them.

In contrast to the theory based on the constriction of blood vessels in the tumor, others believe that in most malignant tumors, there is increased blood flow during, and for hours after, the hyperthermia treatment. Hyperthermia treatment causes faster blood flow, which corrects the lack of oxygen and allows for optimal effects of concomitant treatments such as radiation and chemotherapy.

Additionally, in response to heat, tumor cells produce special proteins designed to protect themselves from the next heat stroke. These proteins are called Heat Shock Proteins and are located on the cell membrane. These proteins are “foreign” to the body and the immune system recognizes them as foreign and sends immune system cells to attack and destroy them.

The high heat inside the cell also causes the destruction of proteins, such as enzymes and other components of the cell.

Normal tissues have an efficient and rapid damage repair system, and by the time of the next hyperthermic treatment, any damage caused to the cell is completely repaired. In contrast, in tumor cells, the heat damage repair system is slow and inefficient and is unable to repair all the damage caused in the time interval between two treatments. Therefore, each heat treatment causes additional damage to the tumor cells, in addition to the damage from radiation and/or chemotherapy, and as a result, the tumor may shrink.