RADIATION INDUCED WHOLE & REGIONAL LUNG INJURY IN HUMANS

辐射诱导整体

• 批准号: 2414439
• 负责人: LAWRENCE B MARKS
• 金额: $ 10.36万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2414439
• 关键词: clinical research; computer data analysis; disease /disorder proneness /risk; human subject; human therapy evaluation; longitudinal human study; lung injury; lung neoplasms; mathematical model; model design /development; neoplasm /cancer radiation therapy; perfusion; prognosis; pulmonary circulation; radiation therapy dosage; respiratory function; respiratory toxin; sign /symptom; single photon emission computed tomography; statistics /biometry

Thoracic irradiation is a major component of therapy for many patients with tumors of the breast, lung, esophagus, thymus and mediastinal lymphatics. In these patients, radiation-induced pulmonary injury is one of the most common treatment-related toxicities. Despite the large number of patients that receive thoracic irradiation, the biologic and physical determinants of radiation-induced lung injury are not understood fully. There are currently no means of predicting, prior to delivery of radiotherapy, what the physiologic consequences of the radiation will be. Previous studies in this area have been hampered by uncertainties regarding the three-dimensional (3-D) radiation dose distribution, lack of understanding of the mechanisms underlying the pathophysiology, use of inconsistent assessments of pulmonary injury, and confusion relating regional versus whole lung injury. While regional injury within the irradiated lung is almost universally seen, whole organ dysfunction is less common. This study will address the physical factors related to the development of radiation-induced lung dysfunction. The long-term goal of this project is to develop algorithms to predict, prior to radiotherapy, the patient's risk of developing symptomatic lung injury and the reduction in pulmonary function that the patient will experience. Advances in functional lung imaging and 3-D radiation treatment planning will be exploited to better understand the physical determinants of radiation- induced lung injury. Regional lung function will be assessed by single photon emission computed tomography (SPECT) lung perfusion scans. Changes in regional lung function will be correlated with regional radiation dose. Whole lung function will be assessed with pulmonary function tests and clinical symptoms. We believe that it is possible to directly relate changes in whole lung function to the following physical parameters: I.) the full 3-D dose distribution; 2.) the summation of regional lung injuries; 3.) baseline whole lung function; and 4.) preradiation functional heterogeneity within the lung. We hypothesize that changes in whole lung function result from the summation of dose-dependent regional injuries and the compensatory capacity of the functioning lung. We postulate that patients with good pulmonary reserve have greater compensatory abilities and are therefore less likely to develop whole lung dysfunction. This relationship between baseline pulmonary function, regional and whole lung injury will be explicitly addressed. An improved understanding of the physical determinants of radiation-induced lung injury and the development of predictive algorithms will improve patient care by reducing the incidence of clinically significant lung injury and facilitate "safe" dose escalation for intrathoracic tumors. While not part of this study, patients enrolled onto this protocol will be included in parallel biological studies designed to consider the molecular biological mechanisms of radiation-induced lung injury.

胸腔照射是许多患者治疗的主要组成部分 乳房，肺，食道，胸腺和纵隔的肿瘤 淋巴管。在这些患者中，辐射引起的肺损伤是一个 最常见的与治疗有关的毒性。尽管有很多 接受胸腔照射的患者，生物学和物理 辐射引起的肺损伤的决定因素尚不完全理解。 目前，在交付之前，目前尚无预测 放射疗法，辐射的生理后果是什么。 该领域的先前研究受到不确定性的阻碍 关于三维（3-D）辐射剂量分布 了解病理生理学基础的机制，使用 对肺损伤的评估不一致，与之混乱有关 区域性与整个肺损伤。而区域伤害 辐照肺几乎是普遍看的，整个器官功能障碍是 不太常见。这项研究将解决与 辐射引起的肺功能障碍的发展。长期目标 该项目将开发算法，以预测放疗之前 患者患有症状性肺损伤和减少的风险 在患者会经历的肺功能中。进步 功能性肺成像和3D辐射治疗计划将是 被利用以更好地了解辐射的物理决定因素 - 诱发肺损伤。区域肺功能将通过单一评估 光子发射计算机断层扫描（SPECT）肺部灌注扫描。更改 在区域肺功能中，肺功能将与区域辐射剂量相关。 将通过肺功能测试评估整个肺功能 临床症状。我们认为有可能直接联系 将整个肺功能变为以下物理参数：I。） 完整的3-D剂量分布； 2.）区域肺的总和 受伤； 3.）基线整个肺功能；和4.）预先鉴定 肺部功能异质性。我们假设变化 剂量依赖性区域的总和导致了整个肺功能 功能肺的伤害和补偿能力。我们 假设具有良好肺部储备的患者具有更大的 补偿能力，因此不太可能发展整个肺 功能障碍。基线肺功能之间的这种关系， 区域和整个肺部受伤将明确解决。改进 了解辐射诱导的肺的物理决定因素 伤害和预测算法的发展将改善患者 通过降低临床意义肺损伤的发生率和 促进胸前肿瘤的“安全”剂量升级。虽然不是一部分 在这项研究中，参加此方案的患者将包括 平行生物学研究旨在考虑分子生物学 辐射引起的肺损伤的机制。