Hyperthermia for Chest Wall Recurrence

Current recommendations for treatment of local breast cancer recurrence include surgery, chemotherapy, hormone therapy, radiation alone, or radiation with hyperthermia. Tumor-directed hyperthermia (also called thermal therapy) is when the body or cancer tissue is heated to high temperatures, ranging from 40 to 43 C. When combined with radiation, hyperthermia plays a pivotal role in improving local control for breast patients with breast or chest wall recurrences that are chemo-refractory, not surgically resectable, and have had prior radiation. Hyperthermia helps to enhance the effects of radiation-induced, DNA damage by blocking DNA repair in cancer cells and by increasing oxygenation of tumors, needed for RT-induced free radical production to damage cancer cells. The considerable advantage of hyperthermia is the ability to combine it with lower doses of radiation therapy, leading to more effective outcomes with fewer side effects . Hyperthermia is a specialized treatment that is only offered at select centers throughout the United States and around the world, so it is important for doctors to know more about this therapy so that they can help their patients get access. The purpose of this article is to review treatment options for local breast cancer recurrences, with a special focus on the role of hyperthermia.

Hyperthermia Mechanisms of Action

The applicability of hyperthermia in cancer treatment stems from the cytotoxic effects of elevated temperatures on tumor cells. Studies have shown temperatures between 41 to 44 C to be non-toxic to normal cells, but show toxicity in tumor cells . Several cellular alterations induced by extreme temperatures include

1. Increased cellular permeability increasing the influx of Ca2+, an ion involved in the apoptotic signaling cascade, and increasing cellular permeability to drug delivery

2. Disassembly of the cytoskeleton, enlarged tumor pores, enabling easier drug delivery

3. Alteration of the mitotic spindles, centrosome organization, and protein denaturation which results in the formation of multinucleated non-clonogenic cells

4. Alterations of the integrin-cytoskeleton network with concomitant cell shape change, anoikis, and programmed cell death

5. Induction of DNA double-strand breaks due to the denaturation and dysfunction of heat-labile repair proteins such as DNA polymerases

6. Precipitation of denatured proteins onto nuclear chromatin structures, generating a barrier which prevents repair enzymes from reaching damage sites

7. Induction of apoptosis through generation of reactive oxygen species and increased expression of the pro-apoptotic BAX gene

Different Hyperthermia Modalities

Energies used to heat tumors include microwaves (wavelengths ranging from 433 to 2450 MHz), radiofrequency (ranging from 100 KHz to 150 MHz), ultrasound, hot water perfusion (tubes, blankets), resistive wire implants, ferromagnetic seeds, nanoparticles, and infrared radiators. Hyperthermia is more commonly administered with electromagnetic applicators since they appear to yield better power disposition and temperature distribution . The superficial applicators include a waveguide, spiral, and current sheet, and are positioned on tumor surfaces with a bolus.