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• W4387207320 abstract "Preclinical studies have shown FLASH radiation therapy (RT) increases the therapeutic index through reduction in normal tissue toxicity but with retained tumor control compared to conventional dose rate (CONV) RT. Dosimetry in FLASH beams is challenging and complex as beam monitoring and proper dosimetry analysis remain uncertain and under investigation. Despite these limitations, clinical translation of FLASH RT has already begun. For translation of FLASH RT from the preclinical stage, it is critical that robust clinical workflows and dosimetry methods be confidently established to ensure patient safety. Here, we present the clinical workflow for the Yorkshire pig, an animal that resembles the body dimension, weight, and biology of a human patient, with the goal to establish standard operating procedures to ensure a safe and robust clinical translation in our upcoming phase I study in cutaneous tumors. The study determines feasibility and safety while finding incidence of dose-limiting toxicities and maximum tolerable dose for future Phase II trials.All procedures were approved by the institutional animal care and use committee. 6 pigs (40-50 kg) were placed under general anesthesia and underwent CT imaging for radiation therapy simulation purposes. The skin was first shaven, and targets on the dorsolateral flanks were marked with tattoos and BBs for CT visualization. Vacloc immobilization was used to allow for reproducible setup on the treatment couch. A treatment planning model was established for treatment planning and dose evaluation purposes. CONV and FLASH single and fractionated dose regimens were prescribed to the 90% isodose line in a 9 MeV beam. Skin collimation and bolus minimized beam penumbra and increased skin dose. Treatment time and pulse repetition frequency were constant between all FLASH fields. Prescription levels were varied via dose per pulse. Calibration and verification of these settings were performed utilizing a multi-dosimeter method for verification in solid water. Output of the beam was verified on the day of the treatment using beam current transformers. This same multi-dosimeter method was used as in-vivo dosimetry on treatment day and compared to the dose verification ensure full dose was received.Variation between the three dosimeter methods was found to be within 5% among all pigs within the study. The maximum percent difference between dose verification and dose delivery was 6%. Consideration must be taken in dosimeter readout error due to the surface of the pig skin. FLASH and CONV toxicity results are currently under evaluation and will be published upon completion of the study.Establishing guidelines and protocols for electron FLASH clinical translation is important to instill confidence in patient safety with this new technique. This study has further optimized and developed dosimetry tools and setup to be used in future clinical trials." @default.
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• W4387207320 date "2023-10-01" @default.
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• W4387207320 title "Feasibility and Clinical Implementation of Electron FLASH Radiation Therapy in the Yorkshire Swine Model" @default.
• W4387207320 doi "https://doi.org/10.1016/j.ijrobp.2023.06.2042" @default.
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