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.

项目摘要 /摘要 放射治疗机提供本质上不同的X射线辐射，需要准确治疗 患病地区。半身和功率效率将辐射场的最小尺寸限制为 大约5 光子和带电颗粒梁的毫米。 因此，可能是许多医疗状况 由于其尺寸很小和无法忍受的抵押品，无法有效治疗对局部辐射的响应 损坏周围的器官。为了克服准直辐射的基本问题， 提案旨在基于多毛细管X射线镜头的新颖使用来开发集中的KV X射线系统。这 提出的技术可以将X射线梁聚焦到直径小于0.2 mm。光束可以扫描以形式 递送辐射剂量针对小的浅目标，同时最大程度地减少对周围健康的辐射损害 组织。我们的目标是为Phantom构建并充分表征功能原型的KV X射线平台 和临床前治疗计划研究。有力的证据表明，辐射可能是可行的治疗 新生血管相关的黄斑变性（AMD）的方法，影响数千万患者 全世界。它攻击了与中流血管内皮生长因子（VEGF）不同的AMD途径 AMD治疗的抑制剂。抗VEGF疗法需要每隔几周重复注射一次 手术损伤和每年30,000美元以上的费用。使用一个通用4 mm直径KV辐射的辐射处理 对于所有患者，正在试用与抗VEGF药物协同作用。当前的结果是有希望的 在减少所需抗VEGF注射的数量方面，但表示剂量覆盖不足 对于大于4 mm的病变和偶尔的辐射毒性。我们假设使用拟议的聚焦 根据病变形态来个性化保形辐射的X射线技术可以通过 增强目标覆盖范围并最大程度地减少对健康的视网膜的毒性/ 黄斑 同时。除了， 该技术提供了一种新型的剂量输送策略，以高度空间调制的网格疗法，这是 显示出优先损害异常的神经系统与正常血管。提出的技术 临床前研究还可以治疗啮齿动物中的超质靶标（与人类的相对大小相当） 在不可避免地辐射相对较大的体积的情况下，无法使用准直发束执行。 未参与的组织。具体目的：设计和构建原型前临床系统，执行剂量计 调试系统并开发蒙特卡洛（MC）的基于重点的治疗计划系统 射线处理。研究设计：将编写统一的MC代码，以模拟X射线运输。 镜头和患者进行剂量计算。将进行广泛的幻影剂量测量以调整 MC模型。治疗计划的优化以及影响靶向和剂量不确定性的因素 将被研究。健康相关性：该提案旨在满足未满足的保形放射疗法的需求 基于病变形状和临界结构保留的小型MM大小目标。