Dosimetry, Physics & Modeling Core

项目总结：剂量学、物理和建模核心 我们建议建立一个研究项目，名为“提高脑瘤的治疗指数”。 通过创新的闪光放射治疗(闪光-RT)，重点是转化一种新的照射 医疗模式迅速进入临床。要检验的总体假设是，辐射是否在超高辐射下传递 剂量率(与目前临床实践中使用的低得多的剂量率相比)可以显著改善 正常的组织并发症，同时保持可接受的，如果不是改善的肿瘤控制。为了检验这一假设， 该计划将部署一系列全面的临床前研究，对肿瘤控制进行关键评估， 闪光照射和常规剂量照射后的神经认知结果和由此导致的脑辐射损伤 率照射。总的来说，这些研究将产生快速翻译所需的必要数据集 将新型闪光照射平台应用于临床。小鼠评估原位移植的临床前研究 肿瘤控制、认知、神经和血管结构可塑性、免疫调节和氧依赖 辐射损伤的机制与对GBM犬患者的临床试验相结合，以告知肿瘤学家 这项潜在的范式转换技术的潜在好处。该计划项目的目标是 由剂量测定、物理和建模核心(核心2)和 神经行为核心(核心3)。 Core 2将开发三项关键创新，使Flash-RT能够快速转化到临床。 首先，我们将开发和表征剂量学工具，以准确测量超高剂量率束流。这 将使我们能够交叉验证电子和光子闪光辐射束之间的剂量学 参与机构(洛桑大学医院、斯坦福大学和印第安纳大学)。第二，我们将建设 并委托第一个小动物共形光子闪光照射平台，使我们能够 描述闪光现象具有更大的临床相关性。第三，我们将制定和实施 临床医用直线加速器转换为实验闪光灯的“交钥匙”技术 辐照器(印第安纳大学)。 这一创新计划项目赠款的成功得到了无与伦比的广度和深度的支持 我们在加州大学欧文分校、斯坦福大学、SLAC国家加速器的多学科调查团队 实验室、CHUV和印第安纳大学率先开发了最初的实验 进行闪存RT研究的基础设施，并提供了强有力的临床前证据 治疗指数，包括放射肿瘤学、放射生物学、医学物理学和临床前的专业知识 成像和加速器科学。 总而言之，Core2将开发必要的剂量测量工具来支持所有项目，启用交叉验证 所有参与站点之间和束流质量之间的剂量测量，从而确保实验 斯坦福大学洛桑大学医院和印第安纳州洛桑大学医院照射系统之间的重复性 大学。

PROJECT SUMMARY: DOSIMETRY, PHYSICS & MODELING CORE We are proposing the creation of a research program entitled, “Increasing the therapeutic index of brain tumor treatment through innovative FLASH radiotherapy (FLASH-RT), focused on translating a novel irradiation modality rapidly into the clinic. The overall hypothesis to be tested is whether radiation delivered at ultra high dose rates (compared to the much lower dose rates used in current clinical practice) can significantly ameliorate normal tissue complications while maintaining acceptable if not improved tumor control. To test this hypothesis, the program will deploy a comprehensive series of preclinical studies that will critically evaluate tumor control, neurocognitive outcomes and resultant radiation injury to the brain following FLASH-RT and conventional dose rate irradiation. Collectively, these studies will generate the requisite data sets required for the rapid translation of the novel FLASH irradiation platform to the clinical scenario. Preclinical studies in mice assessing orthotopic tumor control, cognition, neuronal and vascular structural plasticity, immune-modulation and oxygen dependent mechanisms of radiation injury are coupled with a clinical trial in GBM dog patients to inform the oncologists of the potential benefits of this potentially paradigm shifting technology. The objectives of this program project will be facilitated by the activities conducted by the Dosimetry, Physics & Modeling Core (Core 2) and the Neurobehavioral Core (Core 3). The Core 2 will develop three key innovations that will enable the rapid translation of FLASH-RT in to the clinic. First, we will develop and characterize dosimetric tools to accurately measure ultra-high dose rate beams. This will allow us to cross-validate the dosimetry between electron and photon FLASH radiation beams at each participating institution (Lausanne University Hospital, Stanford and Indiana Universities). Second, we will build and commission the first small animal conformal photon FLASH irradiation platform that will allow us to characterize the FLASH phenomenon with greater clinical relevance. Third, we will develop and implement the “turn-key” technology for the conversion of a clinical medical linear accelerator to an experimental FLASH irradiator (Indiana University). The success of this innovative program project grant is bolstered by the unparalleled breadth and depth of our multi-disciplinary investigative team at UC Irvine, Stanford University, SLAC National Accelerator Laboratory, CHUV and Indiana University that has pioneered the development of the initial experimental infrastructure for conducting FLASH RT research and produced strong preclinical evidence of increased therapeutic index, comprising expertise in radiation oncology, radiobiology, medical physics, and preclinical imaging and accelerator science. In summary, Core 2 will develop the necessary dosimetric tools to support all projects, enable the cross validation of the dosimetry between all participating sites and between beam qualities, and thus ensuring experimental reproducibility between the irradiations systems at Lausanne University Hospital, Stanford and Indiana Universities.