The objective of this proposal is to answer the question, """"""""Is combined use of low dose rate brachytherapy and hyperthermia superior to low dose rate brachytherapy alone?"""""""". If so, what would be the optimum means to combine heat and brachytherapy? Since cell culture studies of the combined heat and low dose rate irra- diation have yielded important radiobiological clues, in vivo tumor and normal tissue studies are needed to address a number of specific issues relevant to clinical applications. There are four specific aims to achieve the overall objective of the study. They are: (i) an optimum radiation dose rate that would yield the maximum heat radiosensitization, (ii) an optimum temperature and duration of heat treatment, (iii) sequence and timing of heat and radiation, and (iv) the effects of critical normal tissues from the combined heat and radiation. We plan to use two tumor systems: RIF fibrosarcoma growing in the intramuscular site of C3H mice and 9L gliosarcoma growing in the brain of Fischer rats. The end points of ana- lysis for tumors include: (i) clonogenic assays, (ii) tumor growth delays, and (iii) tumor cure rates. The end points for normal tissues include semiquantitative skin scorings and histopathological changes of the tissues. Based on the foregoing end points, a quantitative estimate of thermal enhancement ratio and therapeutic gain will be made. The significance of the study would be two-fold: identification of radiobiological factors that might improve the therapeutic ratio of the combined hyperthermia and low dose rate radiotherapy, and application of the findings to the treatment of radioresistant human tumors, including malignant gliomas of the brain and soft tissue sarcomas.
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