Adaptation of a Clinical Proton Pencil Beam Scanning System for FLASH Experiments

Abstract

To characterize a proton pencil beam scanning system for ultra-high dose rate (UHDR) irradiations and validate it with FLASH preclinical experiments. After modifications to the beamline to maximize the beam current at isocenter in our gantry room, we characterized the UHDR beam in terms of: 1) Size and shape of the beam spot in three configurations; pristine beam, 75 mm water-equivalent-thickness (WET) range shifter (RS), and custom-built 135 mm WET RS mounted 310 mm upstream of the aperture in the snout housing. These configurations were analyzed to determine which one achieved the highest dose rate; 2) Beam transport efficiency and beam output. We compared the signal in the monitor chambers of the proton system with a Faraday cup and plane parallel ionization chamber (PPC05, IBA dosimetry) for beam current at the cyclotron from 7.5 nA to 800 nA; 3) Dose homogeneity, beam penumbra, and dose rate for the fields to be used in preclinical irradiations. All measurements were performed at isocenter, in air or at 1 cm depth in solid water, using the highest energy (about 230 MeV), which corresponded to a nominal range of 32.9 cm in water. We modeled the UHDR beam in our treatment planning system (TPS) to optimize the dose homogeneity and lateral penumbra of the irradiation fields. We performed the preclinical experiments in single fractions of 19 Gy (RBE), 21 Gy (RBE) and 23 Gy (RBE) (RBE = 1.1), targeting the pelvis of C57BL/6 mice and using survival as the endpoint. Each arm included 6-10 mice. The proton beam was used in transmission mode, positioning the center of the mouse pelvis at isocenter, and irradiating the pelvis with a 2x6 cm^2 field. Apertures were placed at 9cm from the isocenter to sharpen the lateral penumbra. The range measurements with a multi-layer ionization chamber were consistent within 1 mm with the nominal range. In UHDR mode, the spot size at the isocenter varied from 4.5 mm for the pristine beam to 9.2 mm for the 135 mm RS. The spot size at isocenter remained constant when the beam intensity varied from 7.5 nA to 800 nA at the cyclotron exit. By employing the configuration with the 135 mm RS and optimizing the fields in the TPS, we achieved a dose rate of 1 Gy (RBE)/s for the conventional regime and 75(RBE) Gy/s for the UHDR regime. The monitor chambers of the proton system were affected by recombination at high dose rates: we observed about 35% higher output for the same number of monitor units delivered at 800 nA vs 7.5 nA. The delivered dose was determined with the PPC05 for each field, as this detector did not show recombination effects. When preclinical irradiations were independently monitored, the delivered dose was typically within 1% of the intended value. In three independent experiments, a dose of 21 Gy (RBE) or higher was associated with an increased survival in the UHDR arm compared to the conventional arm. We adapted a clinical proton system for preclinical irradiations at UHDR. Our results confirm the presence of the FLASH effect.