Dosimetry, Physics & Modeling Core

项目概要：剂量学、物理学和建模核心 我们建议创建一个研究项目，题为“提高脑肿瘤的治疗指数 通过创新的FLASH放射治疗（FLASH-RT），专注于将一种新的放射疗法 快速进入临床。要检验的总体假设是， 剂量率（与当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，如果没有改善的肿瘤控制。为了验证这个假设， 该计划将部署一系列全面的临床前研究，将严格评估肿瘤控制， FLASH-RT和常规剂量后的神经认知结局和由此产生的脑辐射损伤 速率辐照总的来说，这些研究将产生快速翻译所需的必要数据集。 新型FLASH辐照平台的临床应用。小鼠临床前研究，评估原位 肿瘤控制、认知、神经元和血管结构可塑性、免疫调节和氧依赖性 辐射损伤的机制与GBM狗患者的临床试验相结合，以告知肿瘤学家 这种潜在的范式转变技术的潜在好处。该项目的目标将 由剂量学、物理学和建模核心（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能够快速应用于临床。 首先，我们将开发和表征剂量测定工具，以准确测量超高剂量率束。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测定， 参与机构（洛桑大学医院、斯坦福大学和印第安纳州大学）。第二，我们将建立 并委托第一个小动物适形光子FLASH照射平台，这将使我们能够 描述具有更大临床相关性的FLASH现象。第三，我们会制订和推行 将临床医用直线加速器转换为实验用FLASH的“交钥匙”技术 辐照器（印第安纳州大学）。 这项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和印第安纳州大学，率先开发了最初的实验 进行FLASH RT研究的基础设施，并产生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 成像和加速器科学。 总之，核心2将开发必要的剂量测定工具，以支持所有项目，实现交叉验证 所有参与站点之间和射束质量之间的剂量测定，从而确保实验 洛桑大学医院、斯坦福大学和印第安纳州辐照系统之间的再现性 高校

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.