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Background: This manuscript describes modifications to a pencil beam scanning (PBS) proton gantry that enables ultra-high dose rates (UHDR) irradiation, including treatment planning and validation. Methods: Beamline modifications consisted of opening the energy slits and setting the degrader to pass-through mode to maximize the dose rate. A range shifter was inserted upstream from the isocenter to enlarge the spot size and make it rotationally symmetric. We measured the beamline transport efficiency and investigated the variation in output due to the recombination of charge in the dose monitoring chamber. The output calibration was performed through a parallel plate chamber (PPC05), and an intercomparison was performed for various detectors. The pre-clinical field for mice irradiation consisted of different dose levels to deliver uniform doses in transmission mode. The field dose rates were determined through log files while scripting in TPS was used to estimate PBS dose rates. The survival experiments consisted of irradiating the full pelvis of the mice at UHDR and conventional dose rates. Results: The spot size was constant with beam current and had a sigma of 8.5 mm at the isocenter. The beam output increased by 35% at 720 nA compared to 5.6 nA, primarily due to recombination in the dose-monitoring ion chambers. The Faraday Cup and PPC05 agreed within 2%, while other detectors were within 3% of FC for dose rates <60 Gy/s. The pre-clinical fields' PBS dose rate is above 45 Gy/sec for all voxels within the target volume. The average and PBS dose rates decrease as field size increases and approaches 40 Gy/s for a field size of 7x7 cm2. All UHDR arms showed better survival than the corresponding conventional dose rate arms. Conclusions: We successfully modified a clinical system to perform UHDR pre-clinical experiments. As part of our pre-clinical experiments, we observed the FLASH effect concerning mice survival. [ABSTRACT FROM AUTHOR]

Objective. Ionization chambers, mostly used for beam calibration and for reference dosimetry, can show high recombination effects in pulsed high dose rate proton beams. The aims of this paper are: first, to characterize the linearity response of newly designed asymmetrical beam monitor chambers (ABMC) in a 100–226 MeV pulsed high dose rate per pulse scanned proton beam; and secondly, to calibrate the ABMC with a PPC05 (IBA Dosimetry) plane parallel ionization chamber and compare to calibration with a home-made Faraday cup (FC). Approach. The ABMC response linearity was evaluated with both the FC and a PTW 60019 microDiamond detector. Regarding ionometry-based ABMC calibration, recombination factors were evaluated theoretically, then numerically, and finally experimentally measured in water for a plane parallel ionization chamber PPC05 (IBA Dosimetry) through k s saturation curves. Finally, ABMC calibration was also achieved with FC and compared to the ionometry method for 7 energies. Main results. Linearity measurements showed that recombination losses in the new ABMC design were well taken into account for the whole range of the machine dose rates. The two-voltage-method was not suitable for recombination correction, but Jaffé's plots analysis was needed, emphasizing the current IAEA TRS-398 reference protocol limitations. Concerning ABMC calibration, FC based absorbed dose estimation and PPC05-based absorbed dose estimation differ by less than 6.3% for the investigated energies. Significance. So far, no update on reference dosimetry protocols is available to estimate the absorbed dose in ionization chambers for clinical high dose rate per pulse pulsed scanned proton beams. This work proposes a validation of the new ABMC design, a method to take into account the recombination effect for ionometry-based ABMC calibration and a comparison with FC dose estimation in this type of proton beams. [ABSTRACT FROM AUTHOR]

• Investigated the flat-panel detector for quenching effect and range accuracy. • PBS daily QA test performance of x-ray/proton coincidence and spot characteristics. • Low, mid, high proton energy checks and its detection sensitivities. • Transformed profiles of proton spread-out Bragg peaks. To evaluate the flat-panel detector quenching effect and clinical usability of a flat-panel based compact QA device for PBS daily constancy measurements. The QA device, named Sphinx Compact, is composed of a 20x20 cm2 flat-panel imager mounted on a portable frame with removable plastic modules for constancy checks of proton energy (100 MeV, 150 MeV, 200 MeV), Spread-Out-Bragg-Peak (SOBP) profile, and machine output. The potential quenching effect of the flat-panel detector was evaluated. Daily PBS QA tests of X-ray/proton isocenter coincidence, the constancy of proton spot position and sigma as well as the energy of pristine proton beam, and the flatness of SOBP proton beam through the 'transformed' profile were performed and analyzed. Furthermore, the sensitivity of detecting energy changes of pristine proton beam was also evaluated. The quenching effect was observed at depths near the pristine peak regions. The flat-panel measured range of the distal 80% is within 0.9 mm to the defined ranges of the delivered proton beams. X-ray/proton isocenter coincidence tests demonstrated maximum mismatch of 0.3 mm between the two isocenters. The device can detect 0.1 mm change of spot position and 0.1 MeV energy changes of pristine proton beams. The measured transformed SOBP beam profile through the wedge module rendered as flat. Even though the flat-panel detector exhibited quenching effect at the Bragg peak region, the proton range can still be accurately measured. The device can fulfill the requirements of the daily QA tests recommended by the AAPM TG224 Report. [ABSTRACT FROM AUTHOR]

• Daily QA is of utmost importance in particle therapy due to the workflow complexity. • The Sphinx Compact can fasten the daily QA procedures in particle therapy. • Quenching effect is an issue for the Sphinx Compact, 3D measurements are discouraged. • The Sphinx Compact can be a useful and time-saving tool for constancy checks. To fully characterize the flat panel detector of the new Sphinx Compact device with scanned proton and carbon ion beams. The Sphinx Compact is designed for daily QA in particle therapy. We tested its repeatability and dose rate dependence as well as its proportionality with an increasing number of particles and potential quenching effect. Potential radiation damage was evaluated. Finally, we compared the spot characterization (position and profile FWHM) with our radiochromic EBT3 film baseline. The detector showed a repeatability of 1.7% and 0.9% for single spots of protons and carbon ions, respectively, while for small scanned fields it was inferior to 0.2% for both particles. The response was independent from the dose rate (difference from nominal value < 1.5%). We observed an under-response due to quenching effect for both particles, mostly for carbon ions. No radiation damage effects were observed after two months of weekly use and approximately 1350 Gy delivered to the detector. Good agreement was found between the Sphinx and EBT3 films for the spot position (central-axis deviation within 1 mm). The spot size measured with the Sphinx was larger compared to films. For protons, the average and maximum differences over different energies were 0.4 mm (3%) and 1 mm (7%); for carbon ions they were 0.2 mm (4%) and 0.4 mm (6%). Despite the quenching effect the Sphinx Compact fulfills the requirements needed for constancy checks and could represent a time-saving tool for daily QA in scanned particle beams. [ABSTRACT FROM AUTHOR]