CANINE

热疗在肿瘤治疗中发挥着作用，但实施热治疗的最佳方式是 没有被很好地理解。这个项目的目的是量化一个常数的生理效应 热疗总剂量，但使用两种不同的处方进行分割。这次审判是由我们之前的 研究显示了加热总持续时间与肿瘤控制时间之间的反比关系。这 这一发现表明，与高热相关的生理变化对治疗有影响 大的热剂量可能与氧合的有害变化有关。如果 热疗的使用是要优化的，重要的是与热疗相关的生理变化 分数可以理解。本研究将在患有自发性软组织肉瘤的犬中进行。他们 将接受放射治疗和热疗。将犬随机分配至粗略或 精细的高温处方会有灌注，氧合， 在治疗前和治疗期间的多个时间， 治疗，以评估加热的生理效应。将使用坏死和凋亡的测量结果 以获得关于两种分级方案对肿瘤的相对效果的一些信息。是 预计更精细的热疗治疗将与更有利的 生理参数的变化和增加的凋亡和坏死相比，粗 分次方案。从这个标题中获得的信息将有助于优化的方式， 热疗用于治疗人类癌症和设计未来的热疗试验。

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.