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发散的X射线辐射，需要对其进行准直才能治疗 病区。半影和功率效率将辐射场的最小尺寸限制为 大约5个 毫米的光子和带电粒子束。 因此，一系列可能是 对局部辐射的反应不能有效地治疗，因为它们的体积小，无法忍受侧枝 对周围关键器官的损害。为了克服准直辐射的根本问题，这 该提案旨在开发一种基于多毛细管X射线透镜的新用途的聚焦千伏X射线系统。这个 所提出的技术可以将X射线束聚焦到直径小于0.2 mm。光束可以扫描成共形 向小而浅的目标提供辐射剂量，同时将对周围健康的辐射损害降至最低 纸巾。我们的目标是建立并充分表征一个用于体模的聚焦kv x射线平台的功能原型。 和临床前治疗计划研究。强有力的证据表明，辐射可能是一种可行的治疗方法。 影响数千万患者的新生血管性老年性黄斑变性(AMD)的治疗方法 全世界。它攻击的AMD途径与主要的血管内皮生长因子(VEGF)不同 治疗AMD的抑制剂。抗血管内皮生长因子治疗需要每隔几周重复注射一次，有可能导致 手术伤害，每年花费超过30,000美元。一种通用的4 mm直径千伏辐射治疗 正在进行与抗血管内皮生长因子药物协同结合的试验。目前的结果是有希望的。 在减少所需的抗血管内皮生长因子注射次数方面，但表明剂量学覆盖不足 适用于大于4毫米的皮损和偶尔的辐射毒性。我们假设使用提议的焦点 根据病变形态个性化适形放射的X射线技术可以通过以下方式改善结果 提高目标覆盖率并将对健康视网膜的毒性降至最低/ 黄斑 在同一时间。再说了， 这项技术提供了一种高度空间调制的栅格疗法的新剂量传递策略，已被 显示优先损害异常新生血管而不是正常血管。建议的技术 还可以治疗啮齿类动物的超小靶标(与人类的相对大小相当)，用于临床前研究 这不可能在不照射相对较大体积的情况下使用准直发散光束来实现 未受影响的组织。具体目标：设计和构建临床前系统的原型，执行剂量测量 系统调试，并开发了基于蒙特卡罗(MC)的聚焦X-射线治疗计划系统。 射线治疗。研究设计：将编写统一的MC程序来模拟X射线在毛细血管中的传输 镜片和住院患者用于剂量计算。将进行广泛的体模剂量测量以调整 MC模型。治疗计划优化及影响靶向和剂量学不确定性的因素 将会被研究。与健康相关：本提案旨在解决未得到满足的适形放射治疗需求 根据病变形状和关键结构的保留，向小的毫米大小的目标投放。