Ultrafast and Precise External Beam Monitor for FLASH and Other Advanced Radiation Therapy Modalities

摘要/摘要 闪光放射治疗(Flash-RT)是一种新的放射治疗形式，有望大大节省正常- 组织在癌症治疗的同时没有表现出肿瘤的保留性。在闪光放射治疗中，辐射剂量被传递到 肿瘤和正常组织只需几毫秒，而不是几分钟。Flash-RT仅在使用大型 在1-3次治疗过程中提供的每部分剂量。它将把标准的30天治疗缩短到1-3天， 从而大大降低了患者和社会的副作用和放射治疗成本。第一个人类 患者于2018年成功救治。第一次有十(10)名患者参加的临床试验于#年在美国开始 2020年11月。计划于2021年在美国和欧洲进行更多的临床试验，至少有100名患者。 Flash-RT的一个主要限制是缺乏能够 满足实时监测和终止闪光RT治疗所需的要求。我们建议 开发和演示大面积、超快、高精度的闪光RT外束监视器 适用于电子、质子、光子和离子，当患者正在接受治疗时，可以在≤1ms内终止光束 治疗过了。对于这个方案，我们将主要集中在开发和演示电子产品系统。 配备直线加速器的Flash-RT和配备现有回旋加速器的质子Flash-RT，但也将展示性能 使用X光。与条状或线状电离室不同，建议的系统基于我们的专利(2020年1月 和2020年11月)的电离辐射束监测系统技术，该技术可以为超高速读数提供 以≥10的速率实时同时分析辐射束位置、轮廓和通量/剂量学 KHZ(即束流分析≤100微米S)。建议的系统提供实时剂量测量、束流控制和 验证闪存-RT。它为快速扫描的光束提供了准确的2D位置和光束轮廓 在26厘米×30厘米的有源射束监测区域上的几微米的空间分辨率。束流监测器 对于所有闪光RT光束亮度，响应都是线性的，没有饱和。质子束测试将主要是 密歇根大学离子束实验室和巴黎圣母院辐射的电子束测试 实验室。拟议的计划为期3年，将从四分之一规模的制造和测试演变为 从第一年的束流监视器到第三年具有自校准能力的全尺寸系统。我们的主要合作者 该项目包括密歇根大学物理系和洛玛琳达大学，学院 医学。拟议的束流监测器构成了所有类型闪光RT的关键使能技术。它 将确保闪光放射治疗的安全、质量和效率，让癌症患者 治疗成功，剂量大得多，副作用少，肿瘤控制出色。它也适用于 用于空间分割放射治疗技术，例如网格、晶格、微束RT(MRT)和 质子-微束RT(PMBRT)。拟议中的光束监测器也被设计成一种新型的(正在申请专利) 超快放射消融系统，消除了治疗心律失常(AFib)的运动问题。 OMB编号0925-0001/0002(01/18修订版批准至2020年3月31日)页面续格式页面

Summary/Abstract FLASH radiotherapy (FLASH-RT) is a novel form of radiation therapy that promises large sparing of normal- tissues in cancer treatment while showing no tumor sparing. In FLASH-RT, the radiation dose is delivered to the tumor and normal tissues in milliseconds rather than minutes. FLASH-RT is only effective when given with large doses per fraction delivered in 1-3 treatment sessions. It would shorten a standard 30-day treatment to 1- 3 days, thus greatly reducing side-effects and radiation therapy costs to both the patient and society. The first human patient was successfully treated in 2018. The first clinical trial with ten (10) patients started in the U.S. in November 2020. Additional clinical trials are planned for 2021 in the U.S. and in Europe with at least 100 patients. A major limitation of FLASH-RT, preventing a fast translation to clinical use, is the lack of detectors capable of meeting the requirements needed to monitor and terminate the FLASH-RT treatment in real time. We propose to develop and demonstrate a large area, ultrafast and precise external beam monitor for FLASH-RT, universally suitable for electrons, protons, photons, and ions, that can terminate the beam in ≤1 ms while the patient is being treated. For this proposal, we will primarily focus on developing and demonstrating the system for electron FLASH-RT with linacs and proton FLASH-RT with existing cyclotrons, but will also demonstrate performance using X-rays. Unlike strip or wire ionization chambers, the proposed system is based on our patented (Jan 2020 and Nov 2020) ionizing-radiation beam monitoring system technology, which can provide ultrafast readout with concurrent analysis of the radiation beam position, profile, and fluence/dosimetry in real time at a rate of ≥10 kHz (i.e., beam analysis ≤100 µs). The proposed system provides real-time dosimetry, beam control, and verification for FLASH-RT. It provides an accurate 2D position and beam profile of rapidly scanned beams with a spatial resolution of a few microns over an active beam monitoring area of 26 cm x 30 cm. The beam monitor response is linear, without saturation, for all FLASH-RT beam luminosities. Proton beam testing will be primarily at the University of Michigan Ion Beam Laboratory, and electron beam testing at the Notre Dame Radiation Laboratory. The proposed program is for 3-years and will evolve from fabrication and testing of a quarter-scale beam monitor in Year 1 to a full-size system with self-calibration capability in Year 3. Our principal collaborators on this program include the University of Michigan, Physics Department, and Loma Linda University, School of Medicine. The proposed beam monitor constitutes a critical enabling technology for all types of FLASH-RT. It will ensure the safety, quality, and efficiency of FLASH radiation therapy, allowing cancer patients to be successfully treated with much higher doses, fewer side-effects, and excellent tumor control. It is also suitable for spatially fractionated radiation therapy techniques such as GRID, LATTICE, microbeam RT (MRT), and proton-minibeam RT (pMBRT). The proposed beam monitor is also being designed into a novel (patent pending) ultrafast radioablation system that eliminates the motion problem for treating cardiac arrhythmia (AFib). OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page