Laboratory and clinical studies have documented multiple mechanisms of action for hyperthermia. Hyperthermia kills cells in solid tumors, without damaging normal tissues, because higher temperatures selectively destroy cells that are hypoxic and have low pH, a condition of tumor cells and not a condition of normal cells. The low pH and hypoxic condition of tumor cells also makes them radiation resistant, which makes hyperthermia and radiation complementary treatments. In addition, the elevated temperatures that would not be fatal to normal cells can destroy cancerous tissue, which lacks the normal vascular supply that dissipates heat and supplies oxygen.ii,v,vi,vii Recent physiological data show that hyperthermia substantially increases perfusion in solid tumors, by 50-100%, and moderately increases perfusion in surrounding normal tissue, leading to higher oxygen concentration.vi These effects on blood flow and tumor oxygenation make the cancer cells more susceptible to radiation therapy.viii Hyperthermia has also been shown to inhibit cellular repair mechanisms, induce heat-shock proteins, denature proteins, induce apoptosis, and inhibit angiogenesis.i,ii,iii,vi
The complementary interaction of hyperthermia combined with radiation is due to the independent cytotoxic effects of hyperthermia combined with its radiosensitizing effects. Laboratory studies have shown that hyperthermia potentiates radiotherapy.ii Hyperthermia and radiation therapy kill cancer cells at different stages of growth. Hyperthermia increases blood flow, resulting in improved tissue oxygenation and thus increased radiosensitivity.ix Hyperthermia also interferes with cellular repair of the DNA damage caused by radiation.i The basis for the additive effect of hyperthermia on radiotherapy comes from the ability of hyperthermia to kill cells that are hypoxic, have a low pH, and are in the S-phase of division, which are all conditions that make cells radioresistant.viii Randomized studies have not shown an increase in either acute or late toxicity of radiotherapy from the addition of hyperthermia.ii
i Dahl O, Dalene R, Schem BC, Mella O. Status of clinical hyperthermia. Acta Oncol. 1999;38(7):863-73.
ii Van der Zee J. Heating the patient: a promising approach? Annals of Oncology 2002;13:1173-1184.
iii Falk MH and Issels RD. Hyperthermia in oncology. Int J Hyperthermia 2001;17 (1):1-18.
iv Kapp DS. Hyperthermia: rationale and clinical applications. Syllabus: Refresher Course 310, Presented at 38th Annual ASTRO Meeting. Los Angeles, CA. October 29, 1996.
v Jones EL, Oleson JR, Posnitz LR, et al. A randomized trial of hyperthermia and radiation for superficial tumors. J of Clin Oncol 2005;23(13): 3079-85.
vi Wust P, Hildebrandt B, Sreenivasa G, Rau B, et al. Hyperthermia in combined treatment of cancer. Lancet 2002;3:487-497.
vii Hehr T, Wust P, Bamberg M, Budach W. Current and potential role of thermoradiotherapy for solid tumours. Oncologie 2003;26:295-302.
viii Raaphorst GP. Fundamental aspects of hyperthermic biology. In Field SB, Hand JW (EDS): An Introduction to the Practical Aspects of Clinical Hyperthermia. London: Taylor and Francis 1990; 10-54.
ix Song CWM, Shakil A, Griffin RF, Okajima K. Improvement of tumor oxygenation status by mild temperature hyperthermia alone or in combination with carbogen. Semin Oncol 1997; 24: 626-632.