Radiation induced whole & regional lung injury in humans

辐射诱导整体

基本信息

批准号：
6436323
负责人：
LAWRENCE B MARKS
金额：
$ 26.21万
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 2004-12-31
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.

胸部放疗 (RT) 是许多患有乳腺、肺、食道、胸腺和纵隔淋巴管肿瘤患者治疗的主要组成部分。在这些患者中，放疗引起的肺损伤是最常见的治疗相关毒性之一。尽管有大量患者接受胸部放疗，但放疗引起的肺损伤的生物学和物理决定因素尚不完全清楚。在进行 RT 之前，没有公认的方法可以预测 RT 的生理后果。在之前的资助期间，我们成功地利用功能性肺部成像和三维（3D）放射治疗计划工具来解决这个问题。使用单光子发射计算机断层扫描 (SPECT) 肺灌注扫描作为区域功能的评估，我们定义了放疗引起的区域性肺损伤的剂量反应曲线及其时间性质。初步数据表明，放疗引起的整个肺功能的变化可以与区域损伤的总和定量相关。我们确定了除了解剖学 CT 定义的肺之外，了解相对于肺功能（即灌注）区域的放疗剂量分布的重要性，以及放疗前整个肺功能在预测放疗诱导的整体肺功能方面的重要性。肺损伤。根据我们的工作，我们开发了可以预测放疗引起的肺功能变化的算法。此外，我们和其他人已经证明，TGF-β（转化生长因子-β）可能是识别易于发生放疗引起的肺损伤的患者的标志物。当前的提案建立在我们之前解决持续存在/新问题的工作的基础上。首先，我们将前瞻性地测试我们的算法（基于解剖和功能性肺内的剂量分布以及放疗前肺功能）的能力，以预测哪些患者经历放疗引起的肺功能降低的风险相对较高和较低。整个肺功能。其次，我们将进一步研究局部肺损伤（通过 SPECT 灌注扫描评估）与整个肺功能变化之间的关系。如之前所做的那样，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，我们将通过监测患者六分钟内步行距离的变化来评估运动耐力。这六分钟的步行距离是一个更具临床和功能相关性的指标，因为它衡量的是整体运动能力。第三，我们将前瞻性评估 TGF-β 对放疗引起的肺功能障碍的影响。该项目将增进对放疗引起的肺损伤的剂量学、生理学和生物学决定因素的了解。此类预测算法的开发、测试和验证将通过降低肺损伤的发生率来改善患者护理，并促进胸腔内癌症的“安全”剂量递增。