Investigating Radiation-Induced Injury to Airways and Pulmonary Vasculature in Lung SABR

研究 Lung SABR 中辐射引起的气道和肺血管损伤

• 批准号: 9106613
• 负责人: Amit Sawant
• 金额: $ 60.89万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-19 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9106613
• 关键词: Accounting; Address; Algorithms; Anatomy; Atelectasis; Beryllium; Bronchi; Bronchial Tree; Bronchoscopy; Caliber; Cancer Patient; Clinical; Clinical Protocols; Clinical Research; Clinical Treatment; Collaborations; Computer software; Data; Disease; Dose; Dose-Limiting; Education; Elements; Environmental air flow; Evaluation; Fibrosis; Goals; Guidelines; High Resolution Computed Tomography; Image; Impairment; Individual; Injury; Investigation; Knowledge; Lesion; Lobar; Lobar bronchus structure; Lung; Malignant neoplasm of lung; Maps; Medical; Medical center; Minor; Minority; Modeling; Multicenter Studies; Non-Small-Cell Lung Carcinoma; Organ; Patients; Perfusion; Peripheral; Physicians; Population; Practice Guidelines; Primary Neoplasm; Process; Public Health; Pulmonary vessels; Quality of life; Radiation; Radiation Injuries; Radiation Pneumonitis; Radiation Tolerance; Radiation therapy; Research; Residual state; Respiration; Respiratory physiology; Risk; Site; Staging; Stenosis; Structure; System; Techniques; Technology; Testing; Toxic effect; Translating; Translations; Work; X-Ray Computed Tomography; base; cancer therapy; clinical practice; follow-up; functional loss; image guided; industry partner; novel; patient population; pre-clinical; prospective; prototype; public health relevance; pulmonary function; quality assurance; radiation effect; radiation-induced injury; response; single photon emission computed tomography; treatment planning; tumor; virtual

 DESCRIPTION (provided by applicant): We form an academic-industrial collaboration to investigate and create a clinically translatable solution that accounts for a poorly-understood aspect of pulmonary toxicity in lung stereotactic ablative radiotherapy (SAbR) - radiation injury to branching serial structures (BSS), i.e., airways and pulmonary vessels. Lung SAbR involves the precise administration of very high, biologically potent doses (54-70 Gy) in relatively few fractions. While this highly successful technique has been demonstrated to achieve excellent 5-year local control (>90%), the use of such potent doses puts patients at risk for collateral toxiciy including radiation pneumonitis and radiation injury to airways, causing stenosis, atelectasis and ultimately fibrosis. A common limitation of current treatment planning strategies is that they use a relatively crude model of the lung as a uniform, solely parallel organ. There is compelling clinical evidence to show that this simplistic approach has limited power to predict and/or avoid toxicity. In order to address this gap in current knowledge, we propose the integration of virtual bronchoscopy technology into the radiation treatment planning process to map BSS segments, quantify their radiosensitivity and create treatment plans that limit dose to these structures. We hypothesize that anatomically variable radiation injury to the elements of the bronchial tree and pulmonary vasculature is an important determinant of post-SAbR toxicity and residual pulmonary function. We test this hypothesis through Aims 1-3 and develop a clinical translation framework for end-user evaluation of a prototype system in Aim 4. In Aim 1, we will perform a prospective clinical study with 40 lung cancer patients to assess the relationship between dose and radiation injury to BSS segments. Broncus will adapt their virtual bronchoscopy algorithms to create LungPointRT. This software will enable BSS autosegmentation and DICOMRT export. We will compute the dose to each segment and compare pre-SAbR and 8-12 months post-SAbR CT scans to assess radiation-induced segmental collapse. In Aim 2, we will acquire pre- and post-SAbR ventilation/perfusion (V/Q) SPECT-CT scans to spatially map the localized loss of pulmonary function, and determine the association between segmental collapse (Aim 1) and localized functional loss (Aim 2). These data will be used to estimate dose thresholds for each segment type. In Aim 3, we will develop novel treatment planning strategies that account for BSS radiosensitivity. In order to account for the increased complexity of the optimization problem, we will investigate parallelized global optimization implemented on graphic processor unit (GPU) platform. The optimization algorithms will be integrated into a research version of a clinical treatment planning system (TPS), Eclipse. In Aim 4, we will create a pre-clinical prototype system for end-user evaluation. The TPS and the LungpointRT will be installed on a GPU workstation. We will form an end-user evaluation team consisting of a physician, physicist and dosimetrist. The team will work with developers to iteratively refine user interfaces and clinical workflow, and to develop practice guidelines and education frameworks to facilitate clinical translation.

 描述（由申请人提供）：我们形成了一个学术-工业合作，以研究和创建一个临床上可翻译的解决方案，该解决方案解释了肺立体定向消融放射治疗（SAbR）中肺毒性的一个知之甚少的方面-对分支序列结构（BSS）的辐射损伤，即，气道和肺血管。肺SAbR涉及以相对较少的分数精确施用非常高的生物学有效剂量（54-70戈伊）。虽然这种非常成功的技术已被证明可以实现良好的5年局部控制（>90%），但使用这种强效剂量会使患者面临附带毒性的风险，包括放射性肺炎和气道放射性损伤，导致狭窄、肺不张和最终纤维化。当前治疗计划策略的一个常见局限性是，它们使用相对粗糙的肺模型作为统一的、完全平行的器官。有令人信服的临床证据表明，这种简单化的方法预测和/或避免毒性的能力有限。为了解决目前知识中的这一差距，我们建议将虚拟支气管镜技术整合到放射治疗计划过程中，以映射BSS段，量化其放射敏感性并创建限制这些结构剂量的治疗计划。我们假设，解剖学上可变的辐射损伤的支气管树和肺血管的元素是一个重要的决定因素后SAbR毒性和残余肺功能。我们通过目标1-3测试这一假设，并在目标4中为原型系统的最终用户评估开发了一个临床翻译框架。在目标1中，我们将对40例肺癌患者进行前瞻性临床研究，以评估剂量与BSS节段辐射损伤之间的关系。Broncus将调整其虚拟支气管镜检查算法以创建LungPointRT。该软件将启用BSS自动分段和DICOMRT导出。我们将计算每个节段的剂量，并比较SAbR前和SAbR后8-12个月的CT扫描，以评估辐射诱导的节段性塌陷。在目标2中，我们将采集SAbR通气/灌注（V/Q）前后SPECT-CT扫描，以空间映射肺功能的局部丧失，并确定节段性塌陷（目标1）和局部功能丧失（目标2）之间的关联。这些数据将用于估计每种节段类型的剂量阈值。在目标3中，我们将开发新的治疗计划策略，说明BSS放射敏感性。为了考虑到优化问题的复杂性增加，我们将研究在图形处理器单元（GPU）平台上实现的并行化全局优化。优化算法将被集成到临床治疗计划系统（TPS）的研究版本Eclipse中。在目标4中，我们将创建一个用于最终用户评估的临床前原型系统。TPS和LungpointRT将安装在GPU工作站上。我们将组建一个由医生、物理学家和剂量学家组成的最终用户评估小组。该团队将与开发人员合作，反复完善用户界面和临床工作流程，并制定实践指南和教育框架，以促进临床翻译。