This Program Project is a first step in a long range plan to develop new radiation therapy techniques to increase local control of human primary tumors, and to test the hypothesis that enhancement of local control results in decreased metastatic spread and increased survival. We hypothesize that improving target coverage and increasing tumor dose may increase local control, decrease metastatic spread and improve cancer cure. That dose escalation may increase local control is based on the fundamental tenet of radiotherapy, i.e., the concept of dose response. The hypothesis that enhanced local control will decrease metastasis is based on experimental and clinical data which suggest that in many instances metastases form secondarily to the re-growth of the tumor after unsuccessful local treatment. For such patients increased local control would translate to cure. To test the above hypothesis it will be necessary to apply therapeutic methods capable of increasing local tumor control over that achievable with current techniques. We suggest that 3D conformal radiotherapy is an appropriate tool. Others have expended efforts on this, but they were ahead of their time because the technology were not available. In the 1990's, the key components either have been or are being developed, such that with a concerted effort we can bring the idea into reality. We currently have a functional 3D treatment planning system, and are in the process of implementing a computer-controlled 3D treatment delivery system. This Program Project proposes research projects to provide scientific foundation for 3D conformal radiotherapy, to enhance its precision, to improve its implementation, so as to enable significant increases in tumor dose without concomitant increase in normal tissue sequelae. These projects include numerical evaluation of treatment plans, computer-aided optimization of conformal treatments, radiation dosimetry for multileaf collimated fields, and consideration of treatment error. Whereas it is postulated that improved target coverage and increased tumor doses are likely to enhance local tumor control, it is not known to what extent tumor doses can be increased, and by how much local control will be improved. Investigations of dose response of tumor control will entail large numbers of patients and many years of follow-up. We propose to take the first step in this direction, and perform Phase I dose escalation studies to establish the maximum tolerable doses to patients with three types of tumors, and to obtain preliminary data on dose response, and to establish a data base of normal tissue response with complete dose volume information.
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