The objective of this research is to evaluate the factors of dose fractionation and treatment volume which influence late complications following radiation therapy. Increased knowledge of the pathogenesis of late effects including better definition of dose limiting cells will provide a better understanding of the effects of altered fractionation schemes and treatment volume. Isoeffect curves for response of canine heart and mediastinal structures including the esophagus and trachea will be generated by exposing those tissues to a range of total doses given a range of doses per fraction. Sequential studies will be done using noninvasive endoscopic, radiographic, electrocardiographic and echocardiographic techniques. Histologic analyses will be done two years after irradiation for comparison with functional studies and provide information on the pathogenesis of late effects. The volume effect will be evaluated by irradiating variable lengths of spinal cords of dogs. Electrophysiologic measurements will be made sequentially and histologic analyses done two years following irradiation. If a volume effect is found, additional studies will be done with smaller doses per fraction to determine the influence of fractionation on volume effect. These studies will show quantitatively how tissues respond to the different methods of irradiation and the histologic analyses will contribute to the description of pathogenesis of late effects. The isoeffect curves generated may provide directions for adjusting fraction size and dose delivery and indicate how those alterations may be additionally influenced by volume irradiated.
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