RADIATION REPAIR OF NORMAL MAMMALIAN TISSUES

本研究的目的是评估剂量-体积关系， 对正常肺的辐射损伤。 长期目标是允许更多的 积极使用放射治疗来控制肿瘤， 对正常组织的有害影响。 一个主要的问题， 很好地解决了体积对辐射耐受性的影响。 更好的 理解剂量-体积关系对于以下方面特别重要： 肺。 肺癌是男性和女性癌症死亡的主要原因 每年有150，000个新病例。 放射治疗有一个 在治疗许多癌症中的作用。 不能手术的肿瘤 纵膈是最有可能被照射的，因此， 包括纵隔。 改进本地控制 与肺癌存活率的增加相关。 本地控制 局限性小细胞肺癌可以通过放射治疗来实现。 一个 提高对肺容量对肺耐受性影响的认识， 允许更积极地使用放射治疗这些和其他 胸部癌症 以前的研究由于缺乏 完整的三维解剖和剂量数据。 拟议 基于CT扫描的研究三维规划将允许准确的 剂量-体积直方图的计算。 肺耐受性参数 在治疗全肺以外的疾病时尚未确立。 从人类临床数据中积累这种类型的信息是必要的。 由于生存时间短，并发治疗， 尸检依从性，肿瘤负荷的未知影响， 其他疾病的症状。 狗是理想的这些研究，因为他们是 大到足以治疗一系列明确定义的体积， 寿命，以评估后期影响。 将寻求相关性 照射肺体积与整体和局部肺变化之间的关系 功能 这些研究将包括通气灌注评价， 辐射区和非辐射区。 病理生理变化将是 与定量组织病理学数据相关。 生理学终点 肺损伤包括动脉血氧分压、功能残气量、肺 顺应性、血管外肺水、内皮细胞功能和 肺动脉压 所有犬将持续监测 呼吸窘迫和体重减轻 组织形态学终点包括 大血管病变的存在和严重程度，间质纤维化， 胸膜纤维化和肺泡腔实变。

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.