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

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