Lung Functional Avoidance Radiotherapy Using Hyperpolarized Xenon MRI

使用超极化氙 MRI 进行肺功能性回避放射治疗

• 批准号: 10299299
• 负责人: STEPHEN J KADLECEK
• 金额: $ 66.24万
• 依托单位: XEMED, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10299299
• 关键词: 3-Dimensional; Acute; Address; Affinity; Aftercare; Alveolar wall; Authorization documentation; Biological Markers; Blood; Blood Circulation; Breathing; Cancer Patient; Characteristics; Chronic; Climacteric; Communication; Consensus; Consequentialism; Control Groups; Custom; Development Plans; Dose; Dose-Rate; Enrollment; Erythrocytes; Esophagus; Exhibits; Fibrosis; Functional Imaging; Gases; Heart; Hemoglobin; Heterogeneity; Incidence; Industrialization; Infrastructure; Institutional Review Boards; Insurance Carriers; Intensity-Modulated Radiotherapy; Investments; Kinetics; Location; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of lung; Maps; Measures; Methods; Organ; Outcome; Patients; Performance; Perfusion; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Positron-Emission Tomography; Procedures; Protocols documentation; Public Health; Pulmonary Emphysema; Pulmonary Inflammation; Pulmonary function tests; Quality of life; Radiation; Radiation Dosage; Radiation Dose Unit; Radiation Fibrosis; Radiation Pneumonitis; Radiation therapy; Randomized; Research Personnel; Resolution; Risk; Series; Services; Severities; Signal Transduction; Site; Solubility; Spirometry; Structure; Structure of parenchyma of lung; Techniques; Technology; Tissues; Tracer; Translating; Treatment Protocols; United States National Institutes of Health; Vertebral column; Xenon; base; cancer radiation therapy; chemotherapy; cohort; comorbidity; cost; dosage; follow-up; functional decline; high resolution imaging; imaging modality; improved; improved outcome; individualized medicine; industry partner; loss of function; meetings; novel; open label; patient stratification; preservation; primary endpoint; pulmonary function; recruit; research and development; secondary endpoint; single photon emission computed tomography; standard of care; translational study; treatment planning; tumor; ventilation

SUMMARY Customized 3D planning of radiation therapy for lung cancer delivers a lethal dose to the tumor region while avoiding important structures (spine) and organs (esophagus, heart, lungs) Since radiation dose to functioning lung is associated with acute radiation pneumonitis and chronic radiation fibrosis, researchers seek to shift dosage preferentially away from lung regions with highest function. Several lung functional imaging modalities have been investigated (ventilation- perfusion SPECT and PET, 4DCT, hyperpolarized 3He). These studies indicate that regional ventilation is not the optimal biomarker. What is needed is a high-resolution imaging modality, tolerable to patients who have difficulty holding their breath, that delineates regions of full lung function warranting preservation, and also identifies regions whose function is irrevocably gone. Hyperpolarized xenon-129 (HXe) MRI provides highly detailed maps of several lung functional characteristics. Its solubility in tissues and affinity for hemoglobin allow it to be used as a tracer for gas exchange kinetics, a so-called “regional DLCO”. Up until now, HXe imaging modalities required long breath holds, which are not well tolerated by lung-compromised patients. We developed an HXe assessment technique that probes several lung function characteristics, including gas exchange to/from red blood cells, with a natural tidal-breathing protocol. Our industrial team developed an automated xenon hyperpolarizer that delivers the required multi-liter volumes at polarizations that approach 50%, enabling this protocol to become routine. We propose a translational study applying HXe MRI to functional avoidance plan optimization to minimize fibrosis in lung cancer patients. To maximize statistical significance, we stratify the patient cohort selecting patients with significant heterogeneity: half with de novo lung cancer with GOLD stage 3+ emphysema comorbidity and half receiving RT for their second (primary) lung cancer. Maps will delineate three functional regions: full function with both ventilation and gas exchange to RBCs (extra importance for avoidance), regions where function is irrevocably absent (reduced avoidance), and other regions where function may be present or recoverable (normal avoidance). In year 1 we conduct an open-label trial to optimize the functional imaging protocols with upgraded hardware. With IRB and DSMB approval, our Phase 2 clinical trial will enroll 70 patients: half receiving standard-of-care treatment and half undergoing RT guided by HXe MRI. Six-month post-treatment assessments include changes in HXe MRI, for regional correlation with local dose. Primary endpoint will be change in DLCO, with secondary endpoints of breathing- related quality of life change from baseline, spirometry/DLCO relative to predicted, incidence/severity of pneumonitis, and change in HXe-MRI.

概括 定制的3D肺癌放射治疗计划为肿瘤提供致命剂量 区域同时避免重要结构（脊柱）和器官（食道，心脏，肺），因为 肺部辐射剂量与急性辐射肺炎和慢性有关 辐射纤维化，研究人员试图更容易地从肺区域转移剂量 最高功能。已经研究了几种肺功能成像方式（通风 - 灌注SPECT和PET，4DCT，超极化3HE）。这些研究表明区域 通风不是最佳的生物标志物。需要的是高分辨率成像方式， 难以忍受呼吸的患者可以忍受，这描绘了全肺的区域 功能警告准备，还标识了功能不可撤销的区域。 超极化XENON-129（HXE）MRI提供了几个肺功能的高度详细地图 特征。它在组织中的溶解度和对血红蛋白的亲和力允许将其用作示踪剂 对于天然气交换动力学，所谓的“区域DLCO”。到目前为止，HXE成像方式 所需的长呼吸持有，肺部受损患者无法很好地容忍。我们 开发了一种HXE评估技术，该技术探究了几个肺功能特征， 包括与红细胞的气体交换，具有天然的潮汐呼吸方案。我们的 工业团队开发了一个自动氙气超极化器，可提供所需的多升 极化接近50％的极化，使该方案成为常规。 我们提出了一项翻译研究，将HXE MRI应用于功能避免计划优化到 最小化肺癌患者的纤维化。为了最大化统计意义，我们将 患者队列选择具有显着异质性的患者：一半患有从头肺癌的患者 金阶段3+肺气肿合并症，第二（主要）肺的RT一半接收RT 癌症。地图将描述三个功能区域：通风和气体的完整功能 交换与RBC（对于回避的额外重要性），功能不可撤销的区域 （减少回避）以及可能存在功能或可恢复功能的其他区域（正常 避免）。在第1年中，我们进行了开放标签试验以优化功能成像协议 通过IRB和DSMB批准，我们的2阶段临床试验将注册70 患者：一半接受护理标准治疗，一半接受HXE MRI指导的RT。 治疗后六个月的评估包括HXE MRI的变化，与区域相关 局部剂量。主要终点将是DLCO的变化，呼吸的次要终点 相关的生活质量从基线，肺活量测定法/DLCO相对于预测而变化， 肺炎的发生率/严重程度，HXE-MRI的变化。