Focused kV X-ray Modulated Conformal Radiotherapy for Small Targets

针对小目标的聚焦 kV X 射线调制适形放射治疗

• 批准号: 10490908
• 负责人: Wu Liu
• 金额: $ 39.86万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10490908
• 关键词: 3-Dimensional; Address; Affect; Age related macular degeneration; Animal Experimentation; Animal Model; Animals; Apoptotic; Area; Behavior; Blindness; Blood Vessels; Brain; Caliber; Characteristics; Charge; Chronic; Clinical; Clinical Research; Code; Collimator; Computer Simulation; Conformal Radiotherapy; Custom; Data; Developed Countries; Development; Devices; Disease; Dose; Dose-Rate; Exudative age-related macular degeneration; Film; Fractionation; Geometry; Goals; Health; Human; Infection; Injections; Injury; Laboratory Research; Learning; Lesion; Lesion by Morphology; Life; Measurement; Medical; Medicine; Methods; Modeling; Monte Carlo Method; Necrosis; Nerve; Neurons; Optics; Organ; Outcome; Output; Pathway interactions; Patients; Pharmaceutical Preparations; Photons; Play; Radiation; Radiation Dose Unit; Radiation Toxicity; Radiation induced damage; Radiation therapy; Radiobiology; Radiosurgery; Rattus; Research; Research Design; Retinal macula; Risk; Rodent; Roentgen Rays; Role; Scanning; Shapes; Source; Spottings; Structure; Surgical Injuries; System; Techniques; Technology; Testing; Time; Tissues; Toxic effect; Translating; Translational Research; Uncertainty; Uveal Melanoma; Vascular Endothelial Growth Factors; animal imaging; anticancer research; base; clinical application; cost; design; dosimetry; experimental study; follow-up; improved; improved outcome; inhibitor; intravitreal injection; irradiation; lens; macula; millimeter; neovascular; neovasculature; neuroregulation; novel; particle beam; personalized medicine; pre-clinical; pre-clinical research; prototype; public health relevance; radiation delivery; retinal damage; simulation; spectral energy; surgical risk; targeted treatment; treatment planning

Project summary / Abstract Radiation therapy machines deliver intrinsically divergent x-ray radiation that needs to be collimated to treat a diseased region. The penumbra and power efficiency limit the minimal size of a radiation field to about 5 millimeters for photon and charged particle beams. Therefore, a host of medical conditions that may be responsive to local radiation cannot be effectively treated because of their small size and intolerable collateral damages to surrounding critical organs. To overcome the fundamental issues of collimated radiation, this proposal aims to develop a focused kV x-ray system based on novel usage of polycapillary x-ray lens. The proposed technique can focus x-ray beams to less than 0.2 mm in diameter. The beam can scan to conformally delivery radiation dose to small, shallow targets while minimizing the radiation damage to surrounding healthy tissues. Our goal is to build and fully characterize a functional prototype focused kV x-ray platform for phantom and preclinical treatment planning research. Strong evidence has shown that radiation may be a viable treatment approach for neovascular age-related macular degeneration (AMD), which affects tens of millions of patients worldwide. It attacks a different AMD pathway than the mainstay vascular endothelial growth factor (VEGF) inhibitor for AMD treatment. Anti-VEGF therapy requires repeated injection every few weeks with a risk of surgical injury and costs over $30,000/year. Radiation treatment using one universal 4 mm diameter kV radiation for all patients is being trialed to synergistically combine with anti-VEGF drugs. The current results are promising in terms of reducing the number of required anti-VEGF injections, but indicate insufficient dosimetric coverage for lesions larger than 4 mm and occasional radiation toxicity. We hypothesize that using the proposed focused x-ray technique to personalize conformal radiation according to lesion morphology can improve outcomes by enhancing the target coverage and minimizing the toxicity to healthy retina/ macula at the same time. Besides, this technique offers a novel dose delivery strategy of highly spatially-modulated grid therapy, which has been shown to preferentially damage abnormal neovasculature vs normal blood vessels. The proposed technique can also treat ultrasmall targets in rodents (comparable to the relative size in humans) for preclinical research that cannot be performed using collimated divergent beams without inevitably irradiating a relatively large volume of uninvolved tissues. Specific aims: Design and build a prototype pre-clinical system, perform dosimetric commissioning of the system and develop a Monte Carlo (MC)-based treatment planning system for focused x- ray treatment. Study design: A unified MC code will be written to simulate the x-ray transport in polycapillary lens and in patient for dose calculation. Extensive phantom dosimetry measurements will be performed to tune the MC model. Treatment planning optimization and factors affecting the targeting and dosimetric uncertainties will be studied. Health relatedness: This proposal aims to address the unmet need of conformal radiotherapy delivery to small, mm-sized targets based on the lesion shape and critical structure sparing.

项目概要/摘要 放射治疗机提供本质上发散的 X 射线辐射，需要进行准直才能治疗 患病区域。半影和功率效率将辐射场的最小尺寸限制为 约5 光子和带电粒子束为毫米。 因此，可能会出现一系列的医疗状况 由于其体积小且附带不良，对局部辐射敏感，无法有效治疗 周围重要器官受损。为了克服准直辐射的基本问题，这 该提案旨在开发一种基于多毛细管 X 射线透镜的新颖用途的聚焦 kV X 射线系统。这 所提出的技术可以将 X 射线束聚焦到直径小于 0.2 毫米。光束可以共形扫描 向小而浅的目标输送辐射剂量，同时最大限度地减少对周围健康的辐射损害 组织。我们的目标是构建并全面表征用于体模的功能原型聚焦 kV X 射线平台 和临床前治疗计划研究。强有力的证据表明放射可能是一种可行的治疗方法 治疗影响数千万患者的新生血管性年龄相关性黄斑变性 (AMD) 的方法 全世界。它攻击与主要血管内皮生长因子 (VEGF) 不同的 AMD 通路 AMD 治疗抑制剂。抗 VEGF 治疗需要每隔几周重复注射一次，存在以下风险： 手术损伤和费用超过 30,000 美元/年。使用一种通用 4 毫米直径 kV 辐射进行放射治疗 正在尝试与所有患者联合使用抗 VEGF 药物产生协同作用。目前的结果是有希望的 就减少所需的抗 VEGF 注射次数而言，但表明剂量测定覆盖范围不足 适用于大于 4 毫米的病灶和偶发的放射毒性。我们假设使用拟议的重点 根据病变形态进行个性化适形辐射的 X 射线技术可以通过以下方式改善结果： 提高目标覆盖范围并最大限度地减少对健康视网膜的毒性/ 黄斑 同时。除了， 该技术提供了一种新型的高度空间调制网格疗法的剂量输送策略，该策略已被 与正常血管相比，它会优先损害异常的新血管系统。所提出的技术 还可以治疗啮齿动物的超小目标（与人类的相对大小相当）用于临床前研究 如果不不可避免地照射相对较大的体积，则无法使用准直发散光束来执行 未受累组织。具体目标：设计和构建原型临床前系统，进行剂量测定 调试系统并开发基于蒙特卡罗 (MC) 的治疗计划系统，用于重点治疗 射线治疗。研究设计：将编写统一的MC代码来模拟多毛细管中的X射线传输 镜片和患者体内进行剂量计算。将进行广泛的体模剂量测量以调整 MC 模型。治疗计划优化以及影响靶向和剂量测定不确定性的因素 将被研究。健康相关性：该提案旨在解决适形放射治疗未得到满足的需求 根据病变形状和关键结构保留，输送到毫米级的小目标。