The superior dose distributions which can be achieved by proton beams will be evaluated for their efficacy in clinical radiation therapy. The basis for interest is that for some anatomic sites, the proton treatment volumes will be smaller and conform more closely to the target volumes than is possible with photon beams. As a consequence, the dose to the target can be increased and hence also the tumor control probability. Since there will be less non-target normal tissues being irradiated, we anticipate that the frequency and severity of normal tissue damage will be reduced. In project 1 we employ Phase III and Phase II trials to test these dose distributions against diseases at several sites. In project 2 we will use the patient database acquired in project 1 to analyze the dose response relationships for normal tissues and tumors. Project 3 makes the other two projects possible; new treatment planning, delivery, and quality control measures will be developed and implemented to allow more efficient and even more precise treatments to be delivered. Clinical Trials (project 1) Existing clinical trials of proton beams will be continued and new trials begun. Existing trials are for treatment of 1) chordomas and chondrosarcomas of the base of skull and cervical spine and 2) stage T3-T4 carcinoma of the prostate. Phase II and III trials will be undertaken for: 1) glioblastoma multiform (90 CGE; 1.8 CGE bid) 2) T3 glottis (80 CGE, 1.6 CGE bid), 3) sarcomas involving S1-S2 (about 75 CGE qd), 4) uveal melanoma (70 vs 50 CGE) 5) benign recurrent meningioma (59.4 CGE vs 50.4 Gy), and 6) early rectal cancer (66.6 CGE vs 59.4 Gy). Other sites are under consideration. Clinical Investigations (project 2) Evaluations and analyses will be performed on the patient data from project 1 yielding quantitative information on: the dose-response of fully or partially irradiated normal tissues; and the tumor control under conditions of non-uniform irradiation of the target volume. In addition, comparative treatment planning studies will be performed which will suggest techniques for, and the benefit from, proton beam therapy at several sites and provide comparisons of various technologies for improving dose distributions. Physics (project 3) This project has two goals: 1) to develop techniques for better proton beam treatments through improvements in beam quality, treatment planning, treatment techniques and 2) to increase the speed and efficiency of proton beam therapy. When these goals are realized, tumor/sites will have been identified for which improved proton therapy leads to higher frequencies of tumor control and/or reduced morbidity.