Warm Up to Hyperthermia
by Dr. Jeff Lin
Hyperthermia therapy (also known as thermal therapy or thermotherapy) is a type of cancer treatment in which body tissues are exposed to higher-than-normal temperatures and is often combined with other cancer treatment modalities (e.g., HIPEC with surgery, thermoradiotherapy with radiation).1,2 Hyperthermia can be achieved by internal (e.g., radiofrequency ablation) or external means (e.g., radiant thermal chambers) and applied either loco-regionally (e.g., HIPEC) or to the whole body (e.g., blood-based hyperthermia). There are no limitations on the cell type or disease site where hyperthermia can be applied, and there have been clinical trials in sarcoma, melanoma, and cancers of the head and neck, brain, lung, esophagus, breast, bladder, rectum, liver, appendix, cervix, and peritoneal lining, among others. 1,2,3,4,5,6
Hyperthermia has been found to preferentially kill7 as well as sensitize1 cancer cells to other cancer treatment modalities (such as surgery, chemotherapy, radiation or immunotherapy) compared to normal cells. This can lead to: 1. Primary therapeutic benefit, 2. Potentiation of other cancer treatment, and/or 3. Increase in therapeutic window of chemotherapy and/or radiotherapy.
Historically, treatment of tumors with heat has been tried in ancient Greece, Rome, Egypt, and India8 and in the past century interest was rekindled when it was noted that systemic hyperthermia due to fevers associated with acute bacterial infections resulted in tumor regression in patients with inoperable sarcomas9 and localized hyperthermia produced tumor regression, with10 and without11 radiation therapy. Prospective, controlled trials began in the 1970s12 and many are ongoing today. Please see the clinical trials section for details on up-to-date investigations and future directions.
While cellular mechanisms of hyperthermia are still being elucidated, it appears that normal and cancer cells respond to hyperthermia differentially, both in intracellular response as well as on the tissue level. Intracellularly, a balance of apoptosis (cell death) with cellular recovery, mediated by heat shock proteins, is seen when cells are exposed to hyperthermia. This balance is perturbed in cancer cells where heat shock proteins, while abundant, are sequestered, leading to increased likelihood of apoptosis. Tumors also have aberrant blood supply that do not distribute heat well. Many basic science studies are also ongoing; please see scientific background section for details.
The advent of modern hyperthermia therapy is ushered in by technological advances in both the delivery and monitoring of heat delivery to target tissue(s). The effectiveness of hyperthermia treatment is thought to be related to the achieved therapeutic temperature, duration of hyperthermia, as well as target and normal tissue characteristics. Some hyperthermia approaches require sedation or general anesthesia to prevent patient discomfort. Myriad systems have been developed to target various diseases, with some (e.g., local hyperthermia in superficial tumors) applicable only to specific disease conditions. Please see the hyperthermia modalities section for details on different types and delivery methods of hyperthermia.
While most normal tissues are not damaged during hyperthermia, there is a dose-dependent toxicity effect that is noted, especially with techniques where “hot spots” where temperatures that exceed the monitored temperature are frequent or extreme, which can result in burns, blisters, discomfort, pain, swelling, or blood clots1,5,6. Whole-body, systemic hyperthermia has been associated with cardiovascular dysfunction in some reports and is more commonly associated with nausea, vomiting and diarrhea.1,2,6
Hyperthermia is under study in multiple clinical trials and is not widely available. Many ongoing trials are being conducted to evaluate the optimum delivery methods and techniques as well as effectiveness of hyperthermia. Because it is not widely available, it is important that patients should be referred to centers with teams experienced in the delivery of hyperthermia.
For general patient information, please refer to National Cancer Institute and American Cancer Society web pages. To learn more about clinical trials such as those conducted through the National Cancer Institute, please visit NCI’s Clinical Trials Home Page.