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Background: Dosimetry in ultra‐high dose rate (UHDR) beamlines is significantly challenged by limitations in real‐time monitoring and accurate measurement of beam output, beam parameters, and delivered doses using conventional radiation detectors, which exhibit dependencies in ultra‐high dose‐rate (UHDR) and high dose‐per‐pulse (DPP) beamline conditions. Purpose: In this study, we characterized the response of the Exradin W2 plastic scintillator (Standard Imaging, Inc.), a water‐equivalent detector that provides measurements with a time resolution of 100 Hz, to determine its feasibility for use in UHDR electron beamlines. Methods: The W2 scintillator was exposed to an UHDR electron beam with different beam parameters by varying the pulse repetition frequency (PRF), pulse width (PW), and pulse amplitude settings of an electron UHDR linear accelerator system. The response of the W2 scintillator was evaluated as a function of the total integrated dose delivered, DPP, and mean and instantaneous dose rate. To account for detector radiation damage, the signal sensitivity (pC/Gy) of the W2 scintillator was measured and tracked as a function of dose history. Results: The W2 scintillator demonstrated mean dose rate independence and linearity as a function of integrated dose and DPP for DPP ≤ 1.5 Gy (R2 > 0.99) and PRF ≤ 90 Hz. At DPP > 1.5 Gy, nonlinear behavior and signal saturation in the blue and green signals as a function of DPP, PRF, and integrated dose became apparent. In the absence of Cerenkov correction, the W2 scintillator exhibited PW dependence, even at DPP values <1.5 Gy, with a difference of up to 31% and 54% in the measured blue and green signal for PWs ranging from 0.5 to 3.6 µs. The change in signal sensitivity of the W2 scintillator as a function of accumulated dose was approximately 4%/kGy and 0.3%/kGy for the measured blue and green signal responses, respectively, as a function of integrated dose history. Conclusion: The Exradin W2 scintillator can provide output measurements that are both dose rate independent and linear in response if the DPP is kept ≤1.5 Gy (corresponding to a mean dose rate up to 290 Gy/s in the used system), as long as proper calibration is performed to account for PW and changes in signal sensitivity as a function of accumulated dose. For DPP > 1.5 Gy, the W2 scintillator's response becomes nonlinear, likely due to limitations in the electrometer related to the high signal intensity. [ABSTRACT FROM AUTHOR]

Background: Dosimetry in ultra‐high dose rate (UHDR) electron beamlines poses a significant challenge owing to the limited usability of standard dosimeters in high dose and high dose‐per‐pulse (DPP) applications. Purpose: In this study, Al2O3:C nanoDot optically stimulated luminescent dosimeters (OSLDs), single‐use powder‐based LiF:Mg,Ti thermoluminescent dosimeters (TLDs), and Gafchromic EBT3 film were evaluated at extended dose ranges (up to 40 Gy) in conventional dose rate (CONV) and UHDR beamlines to determine their usability for calibration and dose verification in the setting of FLASH radiation therapy. Methods: OSLDs and TLDs were evaluated against established dose‐rate–independent Gafchromic EBT3 film with regard to the potential influence of mean dose rate, instantaneous dose rate, and DPP on signal response. The dosimeters were irradiated at CONV or UHDR conditions on a 9‐MeV electron beam. Under UHDR conditions, different settings of pulse repetition frequency (PRF), pulse width (PW), and pulse amplitude were used to characterize the individual dosimeters' response in order to isolate their potential dependencies on dose, dose rate, and DPP. Results: The OSLDs, TLDs, and Gafchromic EBT3 film were found to be suitable at a dose range of up to 40 Gy without any indication of saturation in signal. The response of OSLDs and TLDs in UHDR conditions were found to be independent of mean dose rate (up to 1440 Gy/s), instantaneous dose rate (up to 2 MGy/s), and DPP (up to 7 Gy), with uncertainties on par with nominal values established in CONV beamlines (± 4%). In cross‐comparing the response of OSLDs, TLDs and Gafchromic film at dose rates of 0.18–245 Gy/s, the coefficient of variation or relative standard deviation in the measured dose between the three dosimeters (inter‐dosimeter comparison) was found to be within 2%. Conclusions: We demonstrated the dynamic range of OSLDs, TLDs, and Gafchromic film to be suitable up to 40 Gy, and we developed a protocol that can be used to accurately translate the measured signal in each respective dosimeter to dose. OSLDs and powdered TLDs were shown to be viable for dosimetric measurement in UHDR beamlines, providing dose measurements with accuracies on par with Gafchromic EBT3 film and their concurrent use demonstrating a means for redundant dosimetry in UHDR conditions. [ABSTRACT FROM AUTHOR]

Ion chambers are required for calibration and reference dosimetry applications in radiation therapy (RT). However, exposure of ion chambers in ultra‐high dose rate (UHDR) conditions pertinent to FLASH‐RT leads to severe saturation and ion recombination, which limits their performance and usability. The purpose of this study was to comprehensively evaluate a set of commonly used commercially available ion chambers in RT, all with different design characteristics, and use this information to produce a prototype ion chamber with improved performance in UHDR conditions as a first step toward ion chambers specific for FLASH‐RT. The Advanced Markus and Exradin A10, A26, and A20 ion chambers were evaluated. The chambers were placed in a water tank, at a depth of 2 cm, and exposed to an UHDR electron beam at different pulse repetition frequency (PRF), pulse width (PW), and pulse amplitude settings on an IntraOp Mobetron. Ion chamber responses were investigated for the various beam parameter settings to isolate their dependence on integrated dose, mean dose rate and instantaneous dose rate, dose‐per‐pulse (DPP), and their design features such as chamber type, bias voltage, and collection volume. Furthermore, a thin parallel‐plate (TPP) prototype ion chamber with reduced collector plate separation and volume was constructed and equally evaluated as the other chambers. The charge collection efficiency of the investigated ion chambers decreased with increasing DPP, whereas the mean dose rate did not affect the response of the chambers (± 1%). The dependence of the chamber response on DPP was found to be solely related to the total dose within the pulse, and not on mean dose rate, PW, or instantaneous dose rate within the ranges investigated. The polarity correction factor (Ppol) values of the TPP prototype, A10, and Advanced Markus chambers were found to be independent of DPP and dose rate (± 2%), while the A20 and A26 chambers yielded significantly larger variations and dependencies under the same conditions. Ion chamber performance evaluated under different irradiation conditions of an UHDR electron beam revealed a strong dependence on DPP and a negligible dependence on the mean and instantaneous dose rates. These results suggest that modifications to ion chambers design to improve their usability in UHDR beamlines should focus on minimizing DPP effects, with emphasis on optimizing the electric field strength, through the construction of smaller electrode separation and larger bias voltages. This was confirmed through the production and evaluation of a prototype ion chamber specifically designed with these characteristics. [ABSTRACT FROM AUTHOR]

Background: Gafchromic film's unique properties of tissue‐equivalence, dose‐rate independence, and high spatial resolution make it an attractive choice for many dosimetric applications. However, complicated calibration processes and film handling limits its routine use. Purpose: We evaluated the performance of Gafchromic EBT3 film after irradiation under a variety of measurement conditions to identify aspects of film handling and analysis for simplified but robust film dosimetry. Methods: The short‐ (from 5 min to 100 h) and long‐term (months) film response was evaluated for clinically relevant doses of up to 50 Gy for accuracy in dose determination and relative dose distributions. The dependence of film response on film‐read delay, film batch, scanner type, and beam energy was determined. Results: Scanning the film within a 4‐h window and using a standard 24‐h calibration curve introduced a maximum error of 2% over a dose range of 1–40 Gy, with lower doses showing higher uncertainty in dose determination. Relative dose measurements demonstrated <1 mm difference in electron beam parameters such as depth of 50% of the maximum dose value (R50), independent of when the film was scanned after irradiation or the type of calibration curve used (batch‐specific or time‐specific calibration curve) if the same default scanner was used. Analysis of films exposed over a 5‐year period showed that using the red channel led to the lowest variation in the measured net optical density values for different film batches, with doses >10 Gy having the lowest coefficient of variation (<1.7%). Using scanners of similar design produced netOD values within 3% after exposure to doses of 1–40 Gy. Conclusions: This is the first comprehensive evaluation of the temporal and batch dependence of Gafchromic EBT3 film evaluated on consolidated data over 8 years. The relative dosimetric measurements were insensitive to the type of calibration applied (batch‐ or time‐specific) and in‐depth time‐dependent dosimetric signal behaviors can be established for film scanned outside of the recommended 16–24 h post‐irradiation window. We generated guidelines based on our findings to simplify film handling and analysis and provide tabulated dose‐ and time‐dependent correction factors to achieve this without reducing the accuracy of dose determination. [ABSTRACT FROM AUTHOR]

In their seminal paper from 2014, Fauvadon et al. coined the term FLASH irradiation to describe ultra‐high‐dose rate irradiation with dose rates greater than 40 Gy/s, which results in delivery times of fractions of a second. The experiments presented in that paper were performed with a high‐dose‐per‐pulse 4.5 MeV electron beam, and the results served as the basis for the modern‐day field of FLASH radiation therapy (RT). In this article, we review the studies that have been published after those early experiments, demonstrating the robust effects of FLASH RT on normal tissue sparing in preclinical models. We also outline the various irradiation parameters that have been used. Although the robustness of the biological response has been established, the mechanisms behind the FLASH effect are currently under investigation in a number of laboratories. However, differences in the magnitude of the FLASH effect between experiments in different labs have been reported. Reasons for these differences even within the same animal model are currently unknown, but likely has to do with the marked differences in irradiation parameter settings used. Here, we show that these parameters are often not reported, which complicates large multistudy comparisons. For this reason, we propose a new standard for beam parameter reporting and discuss a systematic path to the clinical translation of FLASH RT. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusion FLASH or ultra‐high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an example of commissioning.A protocol for acceptance, commissioning, and QA of UHDR linear accelerators was established by combining and adapting standards and professional recommendations for standard linear accelerators based on the experience with UHDR at four clinical centers that use different UHDR devices. Non‐standard dosimetric beam parameters considered included pulse width, pulse repetition frequency, dose per pulse, and instantaneous dose rate, together with recommendations on how to acquire these measurements.The 6‐ and 9‐MeV beams of an UHDR electron device were commissioned by using this developed protocol. Measurements were acquired with a combination of ion chambers, beam current transformers (BCTs), and dose‐rate–independent passive dosimeters. The unit was calibrated according to the concept of redundant dosimetry using a reference setup.This study provides detailed recommendations for the acceptance testing, commissioning, and routine QA of low‐energy electron UHDR linear accelerators. The proposed framework is not limited to any specific unit, making it applicable to all existing eFLASH units in the market. Through practical insights and theoretical discourse, this document establishes a benchmark for the commissioning of UHDR devices for clinical use. [ABSTRACT FROM AUTHOR]

Ultrahigh-dose-rate (UHDR) radiation therapy (RT) has produced the FLASH effect in preclinical models: reduced toxicity with comparable tumor control compared with conventional-dose-rate RT. Early clinical trials focused on UHDR RT feasibility using specialized devices. We explore the technical feasibility of practical electron UHDR RT on a standard clinical linear accelerator (LINAC). We tuned the program board of a decommissioned electron energy for UHDR electron delivery on a clinical LINAC without hardware modification. Pulse delivery was controlled using the respiratory gating interface. A short source-to-surface distance (SSD) electron setup with a standard scattering foil was configured and tested on an anthropomorphic phantom using circular blocks with 3- to 20-cm field sizes. Dosimetry was evaluated using radiochromic film and an ion chamber profiler. UHDR open-field mean dose rates at 100, 80, 70, and 59 cm SSD were 36.82, 59.52, 82.01, and 112.83 Gy/s, respectively. At 80 cm SSD, mean dose rate was ∼60 Gy/s for all collimated field sizes, with an R80 depth of 6.1 cm corresponding to an energy of 17.5 MeV. Heterogeneity was <5.0% with asymmetry of 2.2% to 6.2%. The short SSD setup was feasible under realistic treatment conditions simulating broad clinical indications on an anthropomorphic phantom. Short SSD and tuning for high electron beam current on a standard clinical LINAC can deliver flat, homogenous UHDR electrons over a broad, clinically relevant range of field sizes and depths with practical working distances in a configuration easily reversible to standard clinical use. [ABSTRACT FROM AUTHOR]

• We established and validated scheme for UHDR intercomparisons. • We bring bring dosimetry consensus across participating institutions. • The method was tested and validated with high-energy electron beams between two centers and three different devices with CONV and UHDR. • The compatibility between the measured and expected doses show good agreement. • A first step towards dosimetric consensus for FLASH-RT. We describe a multicenter cross validation of ultra-high dose rate (UHDR) (>= 40 Gy/s) irradiation in order to bring a dosimetric consensus in absorbed dose to water. UHDR refers to dose rates over 100–1000 times those of conventional clinical beams. UHDR irradiations have been a topic of intense investigation as they have been reported to induce the FLASH effect in which normal tissues exhibit reduced toxicity relative to conventional dose rates. The need to establish optimal beam parameters capable of achieving the in vivo FLASH effect has become paramount. It is therefore necessary to validate and replicate dosimetry across multiple sites conducting UHDR studies with distinct beam configurations and experimental set-ups. Using a custom cuboid phantom with a cylindrical cavity (5 mm diameter by 10.4 mm length) designed to contain three type of dosimeters (thermoluminescent dosimeters (TLDs), alanine pellets, and Gafchromic films), irradiations were conducted at expected doses of 7.5 to 16 Gy delivered at UHDR or conventional dose rates using various electron beams at the Radiation Oncology Departments of the CHUV in Lausanne, Switzerland and Stanford University, CA. Data obtained between replicate experiments for all dosimeters were in excellent agreement (±3%). In general, films and TLDs were in closer agreement with each other, while alanine provided the closest match between the expected and measured dose, with certain caveats related to absolute reference dose. In conclusion, successful cross-validation of different electron beams operating under different energies and configurations lays the foundation for establishing dosimetric consensus for UHDR irradiation studies, and, if widely implemented, decrease uncertainty between different sites investigating the mechanistic basis of the FLASH effect. [ABSTRACT FROM AUTHOR]