This application is designed to prepare the applicant for a research-oriented academic career in Radiation Oncology. A comprehensive interstitial hyperthermia program is planned, including in vitro experiments, canine brain hyperthermia experiments, and clinical trials in brain and other sites. In vitro experiments will study the effects of different sequencing of heat and low-dose rate irradiation in both rapidly and slowly-cycling cells. Canine brain hyperthermia experiments will study the acute and late toxicity in normal brain of heat alone and of heat combined with iodine-125 implants, and will also be used to compare 3 different interstitial hyperthermia methods: microwave, radiofrequency local current field (LCF), and induction heating of ferromagnetic seeds. In patients with advanced, malignant disease, non-randomized clinical trials will be undertaken utilizing interstitial microwave or radiofrequency hyperthermia in combination with interstitial irradiation in various sites, including brain. After interstitial implantation of the tumor region, it will be attempted to maintain a minimum tumor temperature of 43 degrees C for 60 min (or 60 """"""""equivalent-minutes at 43 degrees C""""""""). Within 1 hr after the heat treatment, radiation sources will be loaded into the catheters. The total radiation dose to be delivered will depend upon prior treatment, clinical situation, and physician discretion. A second hyperthermia treatment will be delivered after unloading the radioactive sources. The validity of the concept of thermal dose will be evaluated in patients and in normal canine brain. Data from all patients' hyperthermia treatments will be analyzed to search for parameters affecting patient tolerance of treatment, temperature uniformity, difficulty in achieving minimum tumor temperature of 43 degrees C, difficulty in limiting temperature in normal tissue, degree and duration of tumor response, and the occurrence of acute and late side effects and complications. Microwave and LCF hyperthermia methods will be compared for each site heated. Technical and physiologic difficulties in delivering hyperthermia will be addressed in an attempt to improve interstitial hyperthermia techniques. Experience gained will also be used to lay a foundation for the implementation of randomized trials to evaluate the efficacy of interstitial hyperthermia plus interstitial irradiation versus interstitial irradiation alone in the initial treatment of advanced head and neck and pelvic malignancies.
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