CANINE

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Hyperthermia has a role in the treatment of tumors but the optinal manner in which to apply heat treatment is not well understood. The purpose of this project is to quantify the physiologic effects of a constant hyperthermia total dose but fractionated using two different prescriptions. This trial arose from our previous work showing an inverse relationship between total duration of heating and length of tumor control. This finding suggests that physiologic changes associated with hypertermia have an influence on treatment outcome and that large thermal doses may be associated with deleterious changes in oxygenation. If hyperthermia use is to be optimized it is important that the physiologic changes associated with hyperthermia frationation be understood. This study will be performed in dogs with spontaneous soft tisue sarcoma. They will receive radiation therapy in addition to hyperthermia. Dogs will be randomized to either a coarsely or finely fractionated hyperthermia prescription. There will be measurements of perfusion, oxygenation, angiogenesis, interstitial pressure and gene expression before treatment and at multiple times during treatment to assess the physiologic effects of heating. Measurements of necrosis and apoptosis will be used to obtain some information on the relative effect of the two fractionation schemes on the tumor. It is anticipated that the more finely fractionated hyperthermia treatment will be associated with more favorable changes in physiologic parameters and increased apoptosis and necrosis compaed to the coarsely fractionated protocol. The information gained from this tiral will be helpful in optimizing the manner in which hyperthermia is used for the treatment of human cancer and for design of future hyperthemria trials.