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

摘要/摘要 FLASH放射治疗（FLASH-RT）是一种新型的放射治疗形式，它保证了大量的正常- 组织中的癌症治疗，同时显示没有肿瘤保留。在FLASH-RT中，辐射剂量被输送到 肿瘤组织和正常组织之间的时间间隔为毫秒而不是分钟。FLASH-RT仅在给予大 在1-3次治疗中递送的每部分剂量。这将把标准的30天治疗缩短为1- 3天， 从而大大降低了对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年成功接受治疗。第一个临床试验有十（10）名患者开始在美国， 2020年11月计划于2021年在美国和欧洲进行额外的临床试验，至少有100名患者。 FLASH-RT的一个主要限制是缺乏能够快速转换为临床应用的检测器， 满足真实的实时监测和终止FLASH-RT治疗所需的要求。我们提出 开发和演示用于FLASH-RT的大面积、超快和精确的外部束流监测器， 适用于电子、质子、光子和离子，可在患者接受治疗时在≤1 ms内终止射束 治疗。对于本提案，我们将主要关注电子系统的开发和演示 使用直线加速器的FLASH-RT和使用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，拟议的系统基于我们的专利（2020年1月 和2020年11月）电离辐射束监测系统技术，该技术可以提供超快读出， 在真实的时间内以≥10的速率对辐射束位置、轮廓和通量/剂量测定进行同步分析 kHz（即，光束分析≤100 µs）。所提出的系统提供实时剂量测定、射束控制和 验证FLASH-RT。它提供了一个准确的2D位置和快速扫描光束的光束轮廓， 在26 cm x 30 cm的有效射束监测区域上具有几微米的空间分辨率。光束监视器 响应是线性的，没有饱和，所有的FLASH-RT光束光度。质子束测试将主要 在密歇根大学离子束实验室，和电子束测试在圣母院辐射 实验室拟议的计划是3年，将从制造和测试的四分之一规模 从第1年的光束监测器到第3年的具有自校准能力的全尺寸系统。我们的主要合作伙伴 参加这个项目的有密歇根大学物理系和洛马琳达大学物理学院。 药拟议的束流监测器构成了所有类型FLASH-RT的关键使能技术。 将确保FLASH放射治疗的安全性、质量和效率，让癌症患者 成功地治疗了高得多的剂量，副作用少，肿瘤控制出色。它也适用 用于空间分割放射治疗技术，例如GRID、LATTICE、微束RT（MRT），以及 质子微束RT（pMBRT）。拟议的光束监测器也正在设计成一种新颖的（专利申请中） 超快射频消融系统，消除了治疗心律失常（AFib）的运动问题。 OMB编号0925-0001/0002（2018年1月批准至2020年3月31日修订版）页码续页格式页码

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