The benefits of hyperthermia as an adjunct to radiation in cancer therapy are due to two biological mechanisms: hyperthermic cell kill and thermal radiosensitization. Hyperthermic cell kill is most effective in radioresistant areas of a tumor and is significant when temperatures exceeding 42 degrees C are maintained for 45 minutes or more. However, adequate time-temperature distributions are very difficult to achieve due to the inability of most heating devices to shape power patterns to overcome both physical and physiological heat removal processes. Thermal radiosensitization is a synergistic effect that reaches a maximum when hyperthermia is delivered simultaneously with radiation and decreases rapidly as the time between therapies increases. Since hyperthermia and radiation treatments have traditionally been given sequentially, thermal radiosensitization has not played an important role in clinical outcome. The delivery of simultaneous thermoradiotherapy has been discouraged both due to logistical problems and the lack of appropriate hyperthermia systems for this purpose. The lone term goal of this proposal is to maximize the therapeutic benefits of hyperthermia by developing a system capable of inducing adequate time-temperature distributions in entire tumor volumes (to maximize hyperthermic cell kill) and that allows the simultaneous delivery of ionizing radiation (to maximize thermal radiosensitization). This system's applicators will be specifically designed for concurrent operation with linear accelerators to permit the treatment of superficial tumors (up to 600 cm2 of surface area and 5 cm deep) with simultaneous hyperthermia and external photon and electron beams. To achieve this goal, a novel applicator design that combines a dual-frequency ultrasound array (Aim l) with a mechanically scanned acoustic reflector (Aim 2), is proposed. The array will be out of the radiation field directing the ultrasound waves towards the scanning reflector which in turn will deflect the waves towards the tumor. This design removes heterogeneous densities from the radiation beam path. Independent element control, scanning motion of the reflector and measured temperatures will be used to implement a temperature controller (Aim 3). Three applicators are proposed to target different tumor sizes and depths. Finally, the proposed system will be thoroughly characterized for clinical use (Aim 4) in terms of both hyperthermia parameters and radiation dosimetry. The proposed system will represent a significant improvement over existing commercial superficial hyperthermia devices as it will induce controlled tumor heating when it is most biologically effective, that is, simultaneously with radiation. This will lead to phase I/II clinical research trials to assess the benefits/complications of this treatment approach, thus making new and important contributions in the field of cancer therapy with radiation and hyperthermia.
