The objective of this research is to evaluate dose-volume relationships of radiation injury to normal lung. the long term goal is to permit more aggressive use of radiation therapy for tumor control by minimizing detrimental effects on normal tissue. A major question which has not been addressed well is the influence of volume on radiation tolerance. A better understanding of dose-volume relationships is of particular importance for lung. Lung cancer is the leading cause of cancer death in men and women with an annual occurrence of 150,000 new cases. Radiation therapy has a role in treatment of many of these cancers. Inoperable tumors of the mediastinum are the most likely to be irradiated, therefore the fields to be used in this study include the mediastinum. Improved local control correlates with increased survival for carcinomas of lung. Local control of limited small cell lung cancer can be achieved by radiotherapy. An improved understanding of the influence of volume on tolerance of lung may allow more aggressive use of radiation for treatment of these and other thoracic cancers. Previous studies have been hampered by the lack of complete three dimensional anatomic and dosimetric data. In the proposed studies three dimensional planning based on CT scans will allow accurate computation of dose-volume histograms. The parameters for lung tolerance have not been established when treating other than whole lung. Accumulation of this type of information from human clinical data is difficult because of short survival times, concurrent treatments, poor compliance for autopsy, unknown influence of tumor burden, and the presence of other disease conditions. Dogs are ideal for these studies as they are large enough to treat a range of well defined volumes and have a sufficient life span to allow evaluation of late effects. Correlations will be sought between irradiated lung volume and change in overall and regional lung function. These studies will include ventilation perfusion evaluations in irradiated and nonirradiated areas. Pathophysiologic changes will be correlated with quantitative histopathologic data. Physiologic end points for lung injury include arterial pO2, functional residual capacity, lung compliance, extra vascular lung water, endothelial cell function and pulmonary artery pressures. All dogs will be continually monitored for respiratory distress and weight loss. Histomorphometric end points include presence and severity of large vessel lesions, interstitial fibrosis, pleural fibrosis and consolidation of alveolar space.
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