RADIATION REPAIR OF NORMAL MAMMALIAN TISSUES

这项研究的目的是评估剂量-体积关系 正常肺的放射性损伤。长期目标是允许更多 积极使用放射治疗通过最小化来控制肿瘤 对正常组织的有害影响。一个尚未解决的重大问题 很好地解决了体积对辐射耐受性的影响。更好的 了解剂量-体积关系对于 阿龙。肺癌是导致男性和女性癌症死亡的主要原因 每年新增病例15万例。放射治疗有一个 在许多这类癌症的治疗中起着重要作用。不能手术的卵巢肿瘤 纵隔是最有可能受到辐射的，因此 在本研究中使用的包括纵隔。改进的本地控制 与肺癌存活率的增加有关。就地控制 有限的小细胞肺癌可以通过放射治疗来实现。一个 更好地理解容量对肺耐受性的影响可能 允许更积极地使用放射治疗这些和其他 胸癌。之前的研究由于缺乏 完整的三维解剖和剂量学数据。在建议的 基于CT扫描的三维规划研究将使 剂量体积直方图的计算。肺耐量的参数 治疗时除全肺外均未确诊。 从人类临床数据中积累的这类信息是 困难，因为生存时间短，同时治疗，很差 尸检依从性，肿瘤负担的未知影响，以及 其他疾病的情况。狗是这些研究的理想选择，因为它们是 大到足以处理一系列定义明确的体积，并具有足够的 寿命，以允许评估后期影响。我们将寻找相关信息 照射肺体积与全肺和局部肺变化的关系 功能。这些研究将包括在以下方面的通风灌流评估 辐射区域和非辐射区域。病理生理变化将是 与定量组织病理学数据相关。生理终点 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。所有的狗都将被持续监测 呼吸窘迫和体重减轻。组织形态计量学终点包括 大血管病变、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.