Purpose Experimental measurements of two‐dimensional (2D) dose rate distributions in proton pencil beam scanning (PBS) FLASH radiation therapy (RT) are currently lacking. In this study, we characterize a newly designed 2D strip‐segmented ionization chamber array (SICA) with high spatial and temporal resolution and demonstrate its applications in a modern proton PBS delivery system at both conventional and ultrahigh dose rates. Methods A dedicated research beamline of the Varian ProBeam system was employed to deliver a 250‐MeV proton PBS beam with nozzle currents up to 215 nA. In the research and clinical beamlines, the spatial, temporal, and dosimetric performances of the SICA were characterized and compared with measurements using parallel‐plate ion chambers (IBA PPC05 and PTW Advanced Markus chamber), a 2D scintillator camera (IBA Lynx), Gafchromic films (EBT‐XD), and a Faraday cup. A novel reconstruction approach was proposed to enable the measurement of 2D dose and dose rate distributions using such a strip‐type detector. Results The SICA demonstrated a position accuracy of 0.12 ± 0.02 mm at a 20‐kHz sampling rate (50 μs per event) and a linearity of R2 > 0.99 for both dose and dose rate with nozzle beam currents ranging from 1 to 215 nA. The 2D dose comparison to the film measurement resulted in a gamma passing rate of 99.8% (2 mm/2%). A measurement‐based proton PBS 2D FLASH dose rate distribution was compared to simulation results and showed a gamma passing rate of 97.3% (2 mm/2%). Conclusions The newly designed SICA demonstrated excellent spatial, temporal, and dosimetric performances and is well suited for commissioning, quality assurance, and a wide range of clinical applications in proton PBS clinical and FLASH‐RT.
Purpose The transmission proton FLASH technique delivers high doses to the normal tissue distal to the target, which is less conformal compared to the Bragg peak technique. To investigate FLASH radiotherapy (RT) planning using single‐energy Bragg peak beams with a similar beam arrangement as clinical intensity‐modulated proton therapy (IMPT) in a liver stereotactic body radiation therapy (SBRT) and to characterize the plan quality, dose sparing of organs‐at‐risk (OARs), and FLASH dose rate percentage. Materials and methods An in‐house platform was developed to enable inverse IMPT‐FLASH planning using single‐energy Bragg peaks. A universal range shifter and range compensators were utilized to effectively align the Bragg peak to the distal edge of the target. Two different minimum MU settings of 400 and 800 MU/spot (Bragg‐400 MU and Bragg‐800 MU) plans were investigated on 10 consecutive hepatocellular carcinoma patients previously treated by IMPT–SBRT to evaluate the FLASH dose and dose rate coverage for OARs. The IMPT–FLASH using single‐energy Bragg peaks delivered 50 Gy in five fractions with similar or identical beam arrangement to the clinical IMPT–SBRT plans. NRG GI003 dose constraint metrics were used. Three dose rate calculation methods, including average dose rate (ADR), dose threshold dose rate (DTDR), and dose‐ADR (DADR), were all studied. Results The novel spot map optimization can fulfill the inverse planning using single‐energy Bragg peaks. All the Bragg peak FLASH plans achieved similar results for the liver‐gross tumor volume (GTV) Dmean and heart D0.5cnormalm3${D_{0.5\,{\rm{c}}{{\rm{m}}^3}}}$, compared to SBRT–IMPT. The Bragg‐800 MU plans resulted in 18.3% higher clinical target volume (CTV) D2cnormalm3${D_{2\,{\rm{c}}{{\rm{m}}^{\rm{3}}}}}$ compared with SBRT (p < 0.05), and no significant difference was found between Bragg‐400 MU and SBRT plans. For the CTV Dmax, SBRT plans resulted in 10.3% (p < 0.01) less than Bragg‐400 MU plans and 16.6% (p < 0.01) less than Bragg‐800 MU plans. The Bragg‐800 MU plans generally achieved higher ADR, DADR, and DTDR dose rates than Bragg‐400 MU plans, and DADR mostly led to the highest V40 Gy/s compared to other dose rate calculation methods, whereas ADR led to the lowest. The lower dose rate portions in certain OARs are related to the lower dose deposited due to the farther distances from targets, especially in the penumbra of the beams. Conclusion Single‐energy Bragg peak IMPT–FLASH plans eliminate the exit dose in normal tissues, maintaining comparable dose metrics to the conventional IMPT–SBRT plans, while achieving a sufficient FLASH dose rate for liver cancers. This study demonstrates the feasibility of and sufficiently high dose rate when applying the Bragg peak FLASH treatment for a liver cancer hypofractionated FLASH therapy. The advancement of this novel method has the potential to optimize treatment for liver cancer patients.
Background:The potential reduction of normal tissue toxicities during FLASH radiotherapy (FLASH-RT) has inspired many efforts to investigate its underlying mechanism and to translate it into the clinic. Such investigations require experimental platforms of FLASH-RT capabilities. Purpose: To commission and characterize a 250 MeV proton research beamline with a saturated nozzle monitor ionization chamber for proton FLASH-RT small animal experiments. Methods: A 2D strip ionization chamber array (SICA) with high spatiotemporal resolution was used to measure spot dwell times under various beam currents and to quantify dose rates for various field sizes. An Advanced Markus chamber and a Faraday cup were irradiated with spot-scanned uniform fields and nozzle currents from 50 to 215 nA to investigate dose scaling relations. The SICA detector was set up upstream to establish a correlation between SICA signal and delivered dose at isocenter to serve as an in vivo dosimeter and monitor the delivered dose rate. Two off -the-shelf brass blocks were used as apertures to shape the dose laterally. Dose profiles in 2D were measured with an amorphous silicon detector array at a low current of 2 nA and validated with Gafchromic films EBT-XD at high currents of up to 215 nA. Results: Spot dwell times become asymptotically constant as a function of the requested beam current at the nozzle of greater than 30 nA due to the saturation of monitor ionization chamber (MIC). With a saturated nozzle MIC, the delivered dose is always greater than the planned dose,but the desired dose can be achieved by scaling the MU of the field. The delivered doses exhibit excellent linearity with R 2 > 0.99 with respect to MU, beam current, and the product of MU and beam current. If the total number of spots is less than 100 at a nozzle current of 215 nA, a field-averaged dose rate greater than 40 Gy/s can be achieved. The SICA-based in vivo dosimetry system achieved excellent estimates of the delivered dose with an average (maximum) deviation of 0.02 Gy (0.05 Gy) over a range of delivered doses from 3 to 44 Gy. Using brass aperture blocks reduced the 80%-20% penumbra by 64% from 7.55 to 2.75 mm. The 2D dose profiles measured by the Phoenix detector at 2 nA and the EBT-XD film at 215 nA showed great agreement, with a gamma passing rate of 95.99% using 1 mm/2% criterion.
Objective: To investigate the effects of respiratory motion on the delivered dose in the context of proton pencil beam scanning (PBS) transmission FLASH-RT by simulation and phantom measurements. 
Approach: An in-house simulation code was employed to perform in silico simulation of 2D dose distributions for clinically relevant proton PBS transmission FLASH-RT treatments. A moving simulation grid was introduced to investigate the impacts of various respiratory motion and treatment delivery parameters on the dynamic PBS dose delivery. A strip-ionization chamber array detector and an IROC motion platform were employed to perform phantom measurements of the 2D dose distribution for treatment fields similar to those used for simulation. 
Main results: Clinically relevant respiratory motion and treatment delivery parameters resulted in degradation of the delivered dose compared to the static delivery as translation and distortion. Simulation showed that the gamma passing rates (2 mm/2% criterion) and target coverage (V100%) could drop below 50% and 80%, respectively, for certain scenarios if no mitigation strategy was used. The gamma passing rates and target coverage could be restored to more than 95% and 98%, respectively, for short beams delivered at the maximal inhalation or exhalation phase. The simulation results were qualitatively confirmed in phantom measurements with the motion platform. 
Significance: Respiratory motion could cause dose quality degradation in a clinically relevant proton PBS transmission FLASH-RT treatment if no mitigation strategy is employed, or if an adequate margin is not given to the target. Besides breath-hold, gated delivery can be an alternative motion management strategy to ensure high consistency of the delivered dose while maintaining minimal dose to the surrounding normal tissues. To the best of our knowledge, this is the first study on motion impacts in the context of proton transmission FLASH radiotherapy.
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