Improvement of tumor oxygenation by mild hyperthermia

There is now abundant evidence that oxygenation in rodent, canine and human tumors is improved during and for up to 1-2 days after heating at mild tem peratures. An increase in tumor blood perfusion along with a decline in the oxygen consumption rate appears to account for the improvement of tumor ox ygenation by mild hyperthermia. The magnitude of the increase in tumor pO(2 ), determined with oxygen-sensitive microelectrodes, caused by mild hyperth ermia is less than that caused by carbogen breathing. However, mild hyperth ermia is far more effective than carbogen breathing in increasing the radia tion response of experimental tumors, probably because mild hyperthermia ox ygenates both (diffusion-limited) chronically hypoxic and (perfusion-limite d) acutely hypoxic cells, whereas carbogen breathing oxygenates only the ch ronically hypoxic cells. Mild hyperthermia is also more effective than nico tinamide, which is known to oxygenate acutely hypoxic cells, in enhancing t he radiation response of experimental tumors. The combination of mild hyper thermia with carbogen or nicotinamide is highly effective in reducing the h ypoxic cell fraction in tumors and increasing the radiation response of exp erimental tumors. A primary rationale for the use of hyperthermia in combin ation with radiotherapy has been that hyperthermia is equally cytotoxic tow ard fully oxygenated and hypoxic cells and that it directly sensitizes both fully oxygenated and hypoxic cells to radiation. Such cytotoxicity and suc h a radiosensitizing effect may be expected to be significant when the tumo r temperature is elevated to at least 42-43 degreesC. Unfortunately, it is often impossible to uniformly raise the temperature of human tumors to this level using the hyperthermia devices currently available. However, it is r elatively easy to raise the temperature of human tumors into the range of 3 9-42 degreesC, which is a temperature that cars improve tumor oxygenation f or up to 1-2 days. The potential usefulness of mild hyperthermia to enhance the response of human tumors to radiotherapy by improving tumor oxygenatio n merits continued investigation, (C) 2001 Radiation Research society.