Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Number of anticipated awards: 2-3 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Page 74 Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary An important development in the field of radiation oncology is demonstration that ultra-fast dose rate (also known as FLASH) radiation therapy at the same delivered dose has fewer side effects than regular radiation therapy. This finding is under intense investigation globally and a race is underway to understand and subsequently implement this methodology in the clinic. The current devices that measure radiation dose lack response times sufficient to adequately address ultra-fast dose rates of 40-120 Gy/second. This is especially problematic when the total prescribed dose may be only 8-20 Gy. Current medical practice dictates that radiation dose must be given within 20% of the prescription, or else be subject to a formal reportable medical event, as regulated by the United States Nuclear Regulatory Commission. In order to safely utilize FLASH radiobiology effects in the clinic, detectors need to be developed that can affordably extend dose rate capacities from 2-10 Gy/minute to 40-120 Gy/second. Additionally, the physical structure of the pulse must meet FLASH specifications. Project Goals The goal of this concept is to solicit proposals to advance the development and/or application of devices, to allow FLASH radiation therapy to be properly evaluated and ultimately translated into the clinic. In particular, ultra-fast radiation dose rate detectors, and related components are the focus of this topic solicitation. By prompting the development of new, commercialized, ultra-fast detectors and safety systems, this solicitation has the potential to facilitate validated translation of laboratory findings to patients in this new and exciting domain – that of FLASH radiation therapy. The supported projects will focus on various devices and technologies to allow for measurement and evaluation of FLASH radiation delivery. The examples of the products are: • Development of devices to measure and validate the time and pulse structure, fluence and other characteristics of the FLASH irradiation beam in both laboratory and clinic. • Systems to record delivery rapidly and precisely enough to measure over or under dose delivery, and stop dose delivery if needed quickly enough to prevent delivery of dose causing a medical event. Activities not responsive to announcement: Tools that don’t measure FLASH dose rate reproducibly; tools that cannot measure the time structure of flash radiation therapy; design approaches that don’t account for scalability, interoperability or the need to be tested for daily validation in a non-destructive fashion; approaches that don’t plan for using tools in diverse medical centers and IT systems; tools or devices unable to be validated and traced to NIST sources/dose definitions. For applications designing safety system, systems that cannot stop the beam fast enough to prevent more than 5% dose over/under the goal (prescribed) dose. Phase I Activities and Deliverables: • Project team: Establish a project team, including proven expertise in: sensor development, user-centered design, team communication and clinical workflows, ultra-high speed electronic safety systems, radiation hardening electronics engineering and testing, measurement and display of beam time structure in a FLASH environment for at least one and ideally multiple modalities (electron beam, proton beam, photon beam, and other hadron beams potentially), clinical radiation oncology and medical physics. Knowledge and design of medical electronic safety systems architecture, health IT interoperability, NIST traceability and related processes will be required. • Design and build proof-of-principle prototype system to measure the time structure of FLASH beam delivery than can both sum dose and collect time structure data and allow the analysis of such data to confirm if it is with 5% of planned beam delivery immediately after treatment (within seconds but ideally much faster to allow use in a safety feedback system that could stop a beam during treatment). Appropriate controls with poor beam structure and inadequate dose rate should be implemented in the testing process. If a system is designed to shut off a delivery device that capability must be designed and tested in the prototype system. • Demonstrate that the prototype has a high probability of development into a clinically-relevant radiation measurement tool and/or safety device component that has is able to work in the FLASH regime (40-120 Gy/s). • Provide a report on the results of the first round of usability testing and any resultant modifications of the platform based on this user feedback. • Present phase I findings and demonstrate the functional prototype system to an NCI evaluation panel via webinar to be summarized in a formal report. Phase II Activities and Deliverables: • Enhance, beta test, and finalize system, data standards and protocols for a platform that can measure FLASH beam deliveries with less than 1% variance between at least 5 prototype measurement devices by the end of year Page 75 1 of the Phase II contract. • Enhance, beta test, and finalize system for clinical implementation. • Provide a report that synthesizes feedback from all relevant categories of end-users (such as physicians, physicists, OEM engineers, and radiobiologists) and summarizes the modifications made to the platform after each round of usability testing. • Provide a report specifying lessons learned and recommended next steps to implement the components in a commercial capacity. • Provide a report detailing plans for implementation of technical assistance and delivery of the complete system including needed software and related API data, platform compatibility standards employed if any, and measures developed, including standard operating procedures for use, validation of measurements, and checking device performance. • Develop systems documentation and user guides to facilitate commercialization. • Present phase II findings and demonstrate the system via a webinar at a time convenient to the offeror and NCI program staff. • In the first year of the contract (Phase II), provide the program and contract officers with a letter(s) of commercial interest. • In the first year of the contract (Phase II), conduct a call with the FDA. • In the second year of the contract, provide the program and contract officers with a letter(s) of commercial commitment. Where cooperation with other equipment manufacturers is critical for implementation of proposed technology, company should provide evidence of such cooperation (through partnering arrangement, collaboration, or letters of intent) as part of the Phase II proposal.