The general objectives of this research are to esblish quantitative criteria for evaluating the potential effectiveness of altered fractionation schemes in radiotherapy by developing models of tissue responses to fractionated doses and the development of more effective experimental designs and methods of analysis. More specifically, these studies are aimed at determining the influence of particular fractionation regimens on the rate of recovery during interfraction intervals and on the severity of the accompanying acute responses. Emphasis is placed on the application of applied mathematics to problems in experimental design and analysis, in which the emphasis is on determining the differential responses of normal tissues and tumors to various fractionation regimens. In particular, techniques are sought for obtaining quantitative, dose-response and repair kinetics parameters from qualitative assays of early and late normal tissue responses, as well as estimates of the response of human tumors to small fractional doses in order to predict radioresponsiveness. finally, the techniques of design and analysis will be made availabel to the experimental community through the development of exportable computer code. These studies might ultimately provide guidelines for the use of accelerated fractionation and hyperfractionation in radiotherapy, by determining the sites where it might be most beneficial and by establishing of the limits imposed on the number of daily treatments, both by the necessity for complete Elkind repair and by the level of acute response accompany these fractionation regimens.
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