Hyperthermia Treatments for Liver Metastasis from Breast Cancer

John Han-Chih Chang, MD and Kenneth Blank, MD
Last Modified: November 1, 2001

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Question
Dear OncoLink "Ask the Experts,"
I am trying to find information for a friend with breast cancer, which has spread to her liver. She had a bone marrow transplant that kept the disease at bay for six months. She now has a 3cm tumor in her liver. I saw that somewhere they are doing a new procedure which uses direct heat to the affected area. Please guide us on the availability, appropriateness along with effectiveness of this treatment.  
Thank you,
C.S.


Answer
John Han-Chih Chang, MD and Kenneth Blank, MD, Editorial Assistants for Oncolink, respond:

Dear C.S.,  
Thank you for your interest and question.

The use of heat to treat cancer (hyperthermia) is NOT a novel one. Its usage dates back to the 19th century. Dr. W. Coley treated patients with an extracted bacterial toxin from erysipelas, which causes high fevers. This was after observations that some cancers appeared to resolve after prolonged infection with erysipelas. In 1898, a Swedish physician, Dr. Westermark described anecdotal incidences of local hyperthermia causing cervical cancer to regress. Since then the popularity and usage of this modality has waxed and waned. Hyperthermia is still under investigation at a few institutions.

There are different methods of heating: total-body systemic hyperthermia and localized heating. Total-body systemic is usually delivered in an insulated suit or chamber by infared radiation. The blood can be heated in an extracorporeal (outside the body) fashion and reinfused into the body. Localized heating is delivered with short-wave diathermy, radiofrequency-induced currents, microwaves and/or ultrasound. Technical considerations are that microwaves work well at more superficial depths and ultrasound better when there are no bone or air cavities causing inhomogeneity of heating.

The cellular damage by hyperthermia is most dramatic when the temperature is elevated to 43°C or higher in the intended tissue. The cells are most sensitive to heat in the late S phase (DNA synthesis phase) of the cell cycle. This is when a cell is most insensitive to damaging effects of radiation therapy. This is why many have attempted to combine radiation and hyperthermia (both cause cellular damage at different phases in the cell cycle, thus leading to an additive or possibly synergistic affect). By the same token, different chemotherapies that are cell cycle specific or independent have also been combined with hyperthermia to see if there is an additive effect.

The efficacy of hyperthermia alone is not great. In a review of the literature published on the subject, the response rate is less than 50%, while the complete clinical regression rate is just about 10%. The duration of regression is usually short lived. Combining radiation and hyperthermia seems to show promise. Documented response rates of 80% to 90% have been reported with complete clinical responses seen in 50% to 80% patients. Some of the chemotherapeutic agents that have positive interactions against cancer with the addition of hyperthermia are: Melphalan, Cyclophosphamide, BCNU, Cisplatin, Mitomycin C, Bleomycin, Vincristine and Doxirubicin.

Is the right treatment for your friend? Well, it is still controversial whether some of these promising results will translate into truly improved cancer control (or even "cure") or just another temporizing measure. The major problems with hyperthermia are the technical delivery of the heat and measurement of the temperature. Many of the local delivery methods are inconsistent in delivery of the heat to the tumor, such that there are areas that do not receive enough heat. Monitoring systems are not perfected enough for us to truly know the temperature throughout our intended tumor. Whether the treatment is right for your friend's type of cancer is also in question—does it work for all cell types? Please consult you local oncologist to discuss these issues.


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