Physiological mechanisms underlying heat-induced radiosensitization.

The objective of this review is to evaluate hyperthermia related changes in tumor physiologic parameters and their relevance for tumor radiosensitization with particular emphases on tumor oxygenation. Elevation of temperature above the physiological level causes changes in blood flow, vascular permeability, metabolism, and tumor oxygenation. These changes in addition to the cellular effects such as direct cytotoxicity, inhibition of potentially lethal damage and sublethal damage repair, have an important influence on the efficacy of radiotherapy. There is now clear evidence that in a variety of rodent and canine, as well as human tumors, the changes in tumor oxygenation status caused by hyperthermia are temperature dependent and this relationship may greatly influence the response of tumors to thermoradiotherapy. The improvement of tumor oxygenation after mild hyperthermia, which often lasts for as long as 24-48 h after heating, may increase the likelihood of a positive response of tumors to radiation therapy. Furthermore, the activity of some chemotherapy drugs is also oxygen dependent, therefore, the heat-induced increase in tumor oxygenation may significantly increase the effectiveness of thermoradiotherapy in combination with certain chemotherapy drugs. Further investigations remain to be conducted to obtain clearer insights into the relationship between thermal parameters, oxygenation and response of human tumors to hyperthermia in combination with radiotherapy and/or chemotherapy.