Radiation-Induced Cardiopulmonary Injury in Humans

辐射引起的人类心肺损伤

• 批准号: 8085824
• 负责人: LAWRENCE B MARKS
• 金额: $ 22.89万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 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 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8085824
• 关键词: 3-Dimensional; Address; Algorithms; Cardiopulmonary; Chest; Clinical; Clinical Research; Conformal Radiotherapy; Congenital Heart Defects; Data; Defect; Dependence; Diffusion; Discipline of Nuclear Medicine; Dose; EFRAC; Exercise stress test; Forced expiratory volume function; Functional disorder; Funding; Gases; Goals; Heart; Heart Injuries; Human; IL8 gene; Image; Injury; Institutes; Intensity-Modulated Radiotherapy; Interleukin-8; Investigation; Lead; Lung; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Methods; Modeling; Monitor; Morbidity - disease rate; Motion; Myocardial; Myocardial perfusion; Netherlands; Normal tissue morphology; Organ; Oxygen Consumption; Pathogenesis; Patient Care; Patients; Perfusion; Photons; Physiological; Positron-Emission Tomography; Principal Investigator; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary function tests; Quality of life; Radiation; Radiation therapy; Radiosurgery; Regional Perfusion; Relative (related person); Research; Respiratory physiology; Risk; Scanning; Severities; Shortness of Breath; Source; Symptoms; Techniques; Testing; Thick; Thoracic Neoplasms; Time; Transforming Growth Factor beta; Walking; Work; animal data; base; chemotherapy; clinical practice; clinically significant; design; effective intervention; functional outcomes; heart function; heart imaging; human data; improved; lung basal segment; lung injury; lung volume; programs; ranpirnase; response; single photon emission computed tomography; tomography; tool; treatment planning

DESCRIPTION (provided by applicant): Radiation therapy (RT)-induced cardiopulmonary injury, usually manifest as shortness of breath, is a major source of morbidity, and limits the delivery of RT for thoracic tumors. The physiologic determinants of RT-induced cardiopulmonary injury are not fully understood. In prior funding periods, we defined the relationship between changes in regional lung perfusion and changes in pulmonary function tests and symptoms. However, we also demonstrated that current methods to predict such RT-induced injury are suboptimal. In separate clinical studies, we have shown that RT causes reductions in regional myocardial perfusion that are correlated with abnormalities in heart wall motion and ejection fraction. The present proposal aims to simultaneously study RT-induced changes in lung and heart function and quantify their impact on global cardiopulmonary function. Animal and human data suggest that RT-induced heart and lung injury act together to cause cardiopulmonary dysfunction. Further, new conformal RT methods (e.g., intensity modulated RT, radiosurgery), often expose large portions of the lung and heart to diverse RT doses and fraction sizes. The impact of dose and fraction size on the pathogenesis of clinically significant lung and heart injury is not fully known. The current proposal builds on our prior work in the context of evolving clinical practice. We will simultaneously study RT-induced heart and lung injury in patients receiving modern conformal RT for lung cancer. We will prospectively determine the time, dose, and fraction-size dependence of RT-induced changes in regional lung perfusion (Aim 1), and regional heart perfusion/function (Aim 2). Heart and lung perfusion/function will be assessed with nuclear medicine and magnetic resonance imaging. We will quantify the relationship between RT-induced changes in regional lung perfusion, regional heart perfusion/function, and associated changes in global cardiopulmonary function (e.g. exercise testing) (Aim 3). This project is first to comprehensively evaluate both the lung-based and heart-based dosimetric and physiologic determinants of RT-induced cardiopulmonary injury. This information will lead to algorithms that accurately predict the risk of cardiopulmonary injury, facilitate the design of "safer" 3D dose distributions, and thus improve patient care.

描述（由申请人提供）：放射治疗（RT）引起的心肺损伤通常表现为呼吸短促，是发病的主要来源，并限制了胸部肿瘤的放射治疗。放疗引起的心肺损伤的生理决定因素尚不完全清楚。在之前的资助期间，我们定义了局部肺灌注变化与肺功能测试和症状变化之间的关系。然而，我们还证明，目前预测此类放疗引起的损伤的方法并不理想。在单独的临床研究中，我们表明放疗会导致局部心肌灌注减少，这与心壁运动和射血分数异常相关。本提案旨在同时研究放疗引起的肺和心功能变化，并量化其对整体心肺功能的影响。动物和人类数据表明，放疗引起的心脏和肺损伤共同作用，导致心肺功能障碍。此外，新的适形放疗方法（例如调强放疗、放射外科）通常使大部分肺和心脏暴露于不同的放疗剂量和分次大小。剂量和分次大小对有临床意义的肺和心脏损伤发病机制的影响尚不完全清楚。当前的提案建立在我们之前在不断发展的临床实践背景下的工作的基础上。我们将同时研究接受现代适形放疗治疗肺癌的患者放疗引起的心脏和肺损伤。我们将前瞻性地确定放疗引起的区域肺灌注（目标 1）和区域心脏灌注/功能（目标 2）变化的时间、剂量和分数大小依赖性。将通过核医学和磁共振成像评估心脏和肺的灌注/功能。我们将量化放疗引起的局部肺灌注、局部心脏灌注/功能变化与整体心肺功能（例如运动测试）的相关变化之间的关系（目标 3）。该项目首次全面评估放疗引起的心肺损伤的基于肺和基于心脏的剂量学和生理决定因素。这些信息将催生出准确预测心肺损伤风险的算法，有助于设计“更安全”的 3D 剂量分布，从而改善患者护理。