Electron flash-RT program in clinical setting for human translation.

Abstract

e13596 Background: A FLASH-RT program was established at Dartmouth-Hitchcock Medical Center in minimally-modified clinical setting by joint efforts of biomedical engineering, radiation oncology, radiation biology and medical physics teams. Various projects on dosimetry, chemical sensing, molecular profiling, software/hardware development, and translational studies have been conducted. The aim is to share logistical considerations and experience on running a FLASH-RT program to support institution-wide academic activities with an ultimate goal of treating human patients with FLASH-RT in 2022. Methods: A linac was converted in the clinical setting by qualified engineers to deliver an ultra-high dose rate (UHDR) electron beam. Routine safety and dosimetry checks were done by physicists for every reversible conversion. Long-term record-keeping and retrospective surveys were carried out to demonstrate the feasibility, safety, stability and accuracy of this dual-purpose (FLASH and conventional RT) approach. Comprehensive failure mode and effects analysis (FMEA) has been completed to systematically evaluate safety related considerations. A treatment planning system (TPS) has been developed in Varian Eclipse to facilitated comparative studies. The FLASH-capable linac has been utilized as shared resource to support institution-wide academic activities as well as normal clinical treatments. Results: With its safety (no accident or FLASH-related malfunction), flexibility (> 100 conversions in 2 years), reliability (̃6000 hours in flash mode and ̃5x105 Gy accumulative dose delivered at isocenter) and accuracy (̃5% conversion-to-conversion variations) demonstrated by commissioning, long-term user experience and comprehensive FMEA analysis, the FLASH-RT platform has been actively utilized for researches in six major categories 1) FLASH beam dosimetry; 2) real-time beam delivery monitoring and control; 3) oximetry and chemical sensing; 4) preclinical/translational small/large animal treatment with tumor control and normal tissue complication endpoints, 5) treatment plan and delivery optimization; 6) the design of phase I/II trials. Key findings in each category will be reported. Conclusions: A FLASH-RT program in clinical setting is established at Dartmouth with joint efforts, promoting collaborative projects to advance FLASH-RT to clinical treatment. The system has been reliably utilized for over two years for mechanistic as well as translational studies and support a phase I/II trial treating cutaneous lymphoma with eFLASH-RT.