Abstract
Most patients treated with hyperthermia have tumors which are refractory advanced and/or recurrent tumors which cannot be controlled by conventional treatments, and their performance status is often poor. Thus, it is very difficult for these patients to maintain a physical position suitable for heating tumors whose temperatures can be maintained at more than 42°C for nearly an hour (in order to induce direct toxicity in tumor cells). Furthermore, we sometimes cannot help interrupting the heating due to acute adverse reactions such as severe pain. In addition, it is also very difficult to heat tumors homogeneously to temperatures over 42°C, using currently available heating devices. In many clinical studies in which hyperthermia was used to enhance the efficacy of radiotherapy, tumor temperatures could be increased only to the 40-41.5°C range. Under these conditions, heat-induced cell death, increased cellular radiosensitivity, and vascular damage are likely to be insignificant in spite of the increased response of tumors to radiotherapy. Recently, mild temperature hyperthermia (MTH)-induced physiological effects on tumors have been shown to lead to an increased blood flow and a resulting increase in tumor oxygenation, and this could lead to increased radiosensitivity if radiotherapy was used after MTH, and to an increase in chemosensitivity via an increased transport of drugs into tumors. Therefore, if the clinician's goal is to keep the tumor temperature in the 40-41°C range, it is possible to reduce a patient's burden, make it easier to maintain a patient in a suitable position for heating, and avoid interrupting the heating session. In thermoradiotherapy, when heating at temperatures higher than 42-43°C can be warranted, hyperthermia should be performed after radiotherapy. However, when heating over 42°C is difficult, an alternative useful approach may be to reverse the order of radiotherapy and hyperthermia : specifically apply radiotherapy subsequent to tumor oxygenation-inducing MTH.
