Radiation induced whole & regional lung injury in humans

辐射诱导整体

基本信息

批准号：
6691060
负责人：
LAWRENCE B MARKS
金额：
$ 27.41万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-05-01 至 2005-12-31
项目状态：
已结题

项目摘要

Thoracic irradiation (RT) is a major component of therapy for many patients with tumors of the breast, lung, esophagus, thymus and mediastinal lymphatics. In these patients, RT-induced pulmonary injury is one of the most common treatment-related toxicities. Despite the large number of patients that receive thoracic RT, the biologic and physical determinants of RT-induced lung injury are not fully understood. There are no accepted means of predicting, prior to delivery of RT, what the physiologic consequences of the RT will be. In the prior funding period, we successfully exploited functional lung imaging and three-dimensional (3D) radiation treatment planning tools to address this issue. Using single photon emission computed tomography (SPECT) lung perfusion scans as an assessment of regional function, we defined the dose-response curve for RT-induced regional lung injury, and its temporal nature. Preliminary data suggests that RT- induced changes in whole lung function can be quantitatively related to the sum of regional injuries. We established the importance of understanding the RT dose distribution relative to the functioning (i.e., perfused) regions of the lung in addition to the anatomical CT-defined lung, and the importance of pre-RT whole lung function, in predicting RT-induced whole lung injury. Based on our work, we have developed algorithms that should be predictive for RT-induced changes in lung function. Furthermore, we and others have demonstrated that TGF-beta (transforming growth factor-beta) may be a marker to identify patients who are predisposed to develop RT-induced lung injury. The current proposal builds on our prior work to address persistent/new issues. First, we will prospectively test the ability of our algorithms (based on the dose distribution within the anatomic and functional lung, and pre-RT pulmonary function) to predict which patients are at relatively high vs. low risk of experiencing RT-induced reductions in whole lung function. Second, we will further study the relationship between regional lung injury (assessed with SPECT perfusion scans) and changes in whole lung function. Whole lung function will be assessed, as done previously, by changes in pulmonary function tests and pulmonary symptoms. In addition, we will assess exercise tolerance by monitoring changes m the distance the patient can walk in six minutes. This six minute walk distance is a more clinically and functionally relevant metric since it measures overall exercise capacity. Third, we will prospectively assess the impact of TGF-beta on RT- induced lung dysfunction. This project will increase understanding of the dosimetric, physiologic and biologic determinants of RT-induced lung injury. The development, testing and validation of such predictive algorithms will improve patient care by reducing the incidence of lung injury and facilitate "safe" dose escalation for intrathoracic cancers.

胸腔照射（RT）是许多乳腺癌，肺，食道，胸腺和纵隔淋巴结肿瘤患者治疗的主要组成部分。在这些患者中，RT诱导的肺损伤是最常见的与治疗相关的毒性之一。尽管有大量接受胸腔RT的患者，但尚未完全了解RT诱导的肺损伤的生物学和身体决定因素。在交付RT之前，没有公认的方法可以预测RT的生理后果。在以前的资金期间，我们成功利用了功能性肺成像和三维辐射处理计划工具来解决此问题。我们使用单个光子发射计算机断层扫描（SPECT）肺部灌注扫描作为区域功能的评估，我们定义了RT诱导的区域肺损伤及其时间性质的剂量反应曲线。初步数据表明，RT诱导的整个肺功能变化可能与区域损伤的总和有关。我们确定了理解相对于肺部功能（即灌注）区域的RT剂量分布的重要性，此外，除了解剖学CT定义的肺以及预测RT诱导的整个RT诱导的整个肺部功能的重要性以及预测RT的重要性肺部受伤。根据我们的工作，我们开发了算法，应该可以预测RT诱导的肺功能变化。此外，我们和其他人已经证明，TGF-β（转化生长因子β）可能是确定易于发展RT诱发的肺损伤的患者的标记。当前的提案基于我们先前的工作，以解决持久/新问题。首先，我们将前瞻性地测试算法的能力（基于解剖和功能性肺内的剂量分布以及RT肺部功能），以预测哪些患者处于相对较高的与低风险相对于RT诱导的降低的风险相对较高的风险。整个肺功能。其次，我们将进一步研究区域肺损伤（通过SPECT灌注扫描评估）与整个肺功能变化之间的关系。如前所述，将通过肺功能测试和肺部症状的变化来评估整个肺功能。此外，我们将通过监视变化来评估运动耐受性，而患者可以在六分钟内行走的距离。步行六分钟的距离是临床和功能上相关的度量，因为它可以衡量整体运动能力。第三，我们将前瞻性评估TGF-β对RT诱导的肺功能障碍的影响。该项目将增加对RT诱导的肺损伤的剂量，生理和生物学决定因素的理解。这种预测算法的开发，测试和验证将通过减少肺损伤的发生率并促进胸膜内癌的“安全”剂量升级来改善患者护理。