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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

基本信息

批准号：
10675046
负责人：
Dimitre Hristov Hristov
金额：
$ 39.25万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
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/10675046
关键词：
3-Dimensional Address Affect Age related macular degeneration Animal Experimentation Animal Model Animals Apoptotic Area Behavior Blindness Blood Vessels Brain Characteristics Charge Chronic Clinical Clinical Research Code Collimator Computer Simulation Conformal Radiotherapy Custom Data Developed Countries Development Devices Diameter Dose Dose Rate Educational process of instructing 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 Paint Pathway interactions Patients Pharmaceutical Preparations Photons Play Radiation Radiation Dose Unit Radiation Toxicity Radiation induced damage Radiation therapy Radiobiology Radiosurgery Rattus Regional Disease Research Research Design Retina Risk Rodent Roentgen Rays Role Rotation 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 Writing animal imaging anticancer research 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

项目摘要

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/摘要放射治疗机递送需要被准直以治疗放射性疾病的固有发散的X射线辐射。病区。半影和功率效率限制了辐射场的最小尺寸，约5 对于光子和带电粒子束来说是毫米。因此，许多医疗条件，对局部辐射敏感的肿瘤由于体积小和不能耐受的附带损伤而不能得到有效治疗对周围重要器官的损害。为了克服准直辐射的基本问题，该提案旨在开发基于多毛细管X射线透镜的新用途的聚焦kV X射线系统。的所提出的技术可以将X射线束聚焦到直径小于0.2mm。光束可以共形扫描将辐射剂量输送到小而浅的目标，同时最大限度地减少对周围健康的辐射损伤组织中我们的目标是建立和充分表征一个功能原型聚焦千伏X射线平台的幻影和临床前治疗计划研究。强有力的证据表明放射治疗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）的方法国际吧它攻击的AMD途径与主流的血管内皮生长因子（VEGF）不同用于AMD治疗抑制剂。抗VEGF治疗需要每隔几周重复注射，手术伤害和费用超过30，000美元/年。使用一个通用的4 mm直径kV辐射进行辐射治疗正在试验与抗VEGF药物协同联合收割机。目前的结果是有希望的在减少所需的抗VEGF注射次数方面，但表明剂量覆盖不足大于4 mm的病变和偶尔的辐射毒性。我们假设，使用拟议的重点根据病变形态进行个性化适形放射的X射线技术可以通过以下方式改善结局：增强靶点覆盖率并将对健康视网膜的毒性降至最低，黄斑同时还研究与讨论此外，我们认为，该技术提供了一种高度空间调制的网格治疗的新的剂量递送策略，显示相对于正常血管优先损伤异常新生血管。所提出的技术也可以治疗啮齿类动物的超小靶点（与人类的相对大小相当），用于临床前研究这不能使用准直的发散光束来执行未受影响的组织。具体目标：设计并建立一个原型临床前系统，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，用于聚焦x- 射线治疗研究设计：将编写统一的MC代码以模拟多毛细管中的X射线传输透镜和患者体内进行剂量计算。将进行广泛的体模剂量测定测量， MC模型治疗计划优化和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疗未满足的需求基于病变形状和关键结构保留，向小的mm尺寸的目标递送。