Though historically impossible for most large tumors, hyperthermia has been shown effective for small cancers when sufficiently high thermal doses are delivered in close association with radiation or drug therapies. Phase III clinical trials have investigated 1 hour heat treatments delivered within an hour of approximately 10-20% of the radiation fractions. While showing promise for small tumors, most trials failed to demonstrate sufficient interaction between sequentially applied treatments at the cumulative thermal doses possible in large tumors with a maximum of 8 heat treatments using the best available equipment. The objective of the proposed research is to complete the development of a large, flexible, and easily expandable microwave heat applicator that will facilitate new treatment protocols for maximizing interaction of modalities by delivering well-controlled superficial heat simultaneously with external beam radiation for longer duration treatments up to 4 hours each. To accomplish this goal, applicator design parameters will be optimized theoretically with systematic parametric studies of realistic applicator and tissue load configurations using existing electromagnetic and thermal modeling programs. The applicator will be designed so that it can be secured comfortably to the body surface under a lightweight elastic jacket for heating large area superficial disease such as chestwall recurrence of breast carcinoma. Using optimized applicator designs, very thin conformal microwave array applicators (3-6 mm including water bolus) will be constructed in several useful sizes. Heating patterns will be characterized with detailed radiated field measurements in chestwall tissue phantoms and in vivo temperature distribution measurements in a small number of animals. Finally, applicator functionality in the clinic will be evaluated with feasibility studies intended to provide feedback for final applicator design modifications and to assess the uniformity of heating, feasibility of heating simultaneously with external beam radiation, and patient tolerance and toxicity to the new heat protocols intended to deliver higher cumulative thermal doses simultaneously with radiation. This research should produce a fully tested hyperthermia applicator design that is ready to distribute at relatively low cost to other investigational centers by the end of the grant, in order to initiate a multi-institutional Phase III clinical trial of simultaneous heat with external beam radiation for treatment of diffuse superficial disease. The anticipated long term benefits are a significant increase in efficacy of current treatments for this devasting disease, as measured by improved complete response rates, duration of response, and quality of life, due to the addition of relatively high cumulative thermal doses delivered simultaneously with radiation for maximum synergism of modalities.
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