Glioblastomas are the most common form of brain tumors, but despite aggressive treatment protocols involving surgery, radiation therapy, and chemotherapy, the mean life time of these patients after diagnosis is 10 months. The long term objective is to investigate the efficacy of interstitial hyperthermia and radiation therapy as a treatment for this type of tumor. Interstitial hyperthermia involves implanting a set of 2 mm catheters in the tumor and then inserting a set of 1 mm microwave antennas into each catheter, along with a thermometry probe. The electromagnetic energy radiated from these antennas heats the tumor volume to the temperature range of 43-50 degrees C. The specific objectives of this research are to 1) continue a phase I clinical trial for the treatment of glioblastoma multiforme (Grade III and IV) in humans, 2) develop 3-dimensional computer-based thermal and radiation treatment planning models, 3) investigate the phenomenon of thermotolerance in normal and tumor tissue, 4) assess long term toxicity of combined heat and radiation in normal brain, 5) study time/temperature dose escalation effects in normal brain, 6) develop a new 2450 MHz interstitial microwave system for clinical and animal studies, and 7) measure the power deposition and thermal dosmetry for new antenna designs. The phase I clinical trial will study the efficacy of treatment of brain tumors using an interstitial microwave antenna array hyperthermia system and brachytherapy. The ability of this system to effectively heat brain tumors will be evaluated as well as the effects of increasing the heated region around the CT defined tumor margin. Fundamental studies will be conducted on questions of thermotolerance, both in normal dog brain and in an avian sarcoma virally induced tumor model. This information could lead to a better treatment protocol for the clinical trials. Thermotolerance will be assessed by neurohistological and heat shock protein analysis. The long term toxicity of combined heat and radiation will be studied for hyperthermia applied with the interstitial system and with low dose irradiation using iridium-192 seeds, again using a dog model. Various heat/radiation combinations will be assessed, i.e. heat-radiation-heat, heat-radiation, radiation-heat, and heat-radiation-heat-radiation. The time/temperature escalation study will be performed using a 915 MHz spiral surface applicator in normal dog brain and the analysis will be based on histological and neuroradiological evaluation 7 days after treatment.
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