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Background: Ultra‐high dose‐rate (UHDR) irradiations (>40 Gy/s) have recently garnered interest in radiotherapy (RT) as they can trigger the so‐called "FLASH" effect, namely a higher tolerance of normal tissues in comparison with conventional dose rates when a sufficiently high dose is delivered to the tissue. To transfer this to clinical RT treatments, adapted methods and practical tools for online dosimetry need to be developed. Ionization chambers remain the gold standards in RT but the charge recombination effects may be very significant at such high dose rates, limiting the use of some of these dosimeters. The reduction of the sensitive volume size can be an interesting characteristic to reduce such effects. Purpose: In that context, we have investigated the charge collection behavior of the recent IBA Razor™ Nano Chamber (RNC) in UHDR pulses to evaluate its potential interest for FLASH RT. Methods: In order to quantify the RNC ion collection efficiency (ICE), simultaneous dose measurements were performed under UHDR electron beams with dose‐rate‐independent Gafchromic™ EBT3 films that were used as the dose reference. A dose‐per‐pulse range from 0.01 to 30 Gy was investigated, varying the source‐to‐surface distance, the pulse duration (1 and 3 μs investigated) and the LINAC gun grid tension as irradiation parameters. In addition, the RNC measurements were corrected from the inherent beam shot‐to‐shot variations using an independent current transformer. An empirical logistic model was used to fit the RNC collection efficiency measurements and the results were compared with the Advanced Markus plane parallel ion chamber. Results: The RNC ICE was found to decrease as the dose‐per‐pulse increases, starting from doses above 0.2 Gy/pulse and down to 40% of efficiency at 30 Gy/pulse. The RNC resulted in a higher ICE for a given dose‐per‐pulse in comparison with the Markus chamber, with a measured efficiency found higher than 85 and 55% for 1 and 10 Gy/pulse, respectively, whereas the Markus ICE was of 60 and 25% for the same doses. However, the RNC shows a higher sensitivity to the pulse duration than the Advanced Markus chamber, with a lower efficiency found at 1 μs than at 3 μs, suggesting that this chamber could be more sensitive to the dose rate within the pulse. Conclusions: The results confirmed that the small sensitive volume of the RNC ensures higher ICE compared with larger chambers. The RNC was thus found to be a promising online dosimetry tool for FLASH RT and we proposed an ion recombination model to correct its response up to extreme dose‐per‐pulses of 30 Gy. [ABSTRACT FROM AUTHOR]

Purpose: The Oriatron eRT6 is a linear accelerator (linac) used in FLASH preclinical studies able to reach dose rates ranging from conventional (CONV) up to ultrahigh (UHDR). This work describes the implementation of commercially available beam current transformers (BCTs) as online monitoring tools compatible with CONV and UHDR irradiations for preclinical FLASH studies. Methods: Two BCTs were used to measure the output of the Oriatron eRT6 linac. First, the correspondence between the set nominal beam parameters and those measured by the BCTs was checked. Then, we established the relationship between the total exit charge (measured by BCTs) and the absorbed dose to water. The influence of the pulse width (PW) and the pulse repetition frequency (PRF) at UHDR was characterized, as well as the short‐ and long‐term stabilities of the relationship between the exit charge and the dose at CONV and UHDR. Results: The BCTs were able to determine consistently the number of pulses, PW, and PRF. For fixed PW and pulse height, the exit charge measured from BCTs was correlated with the dose, and linear relationships were found with uncertainties of 0.5 % and 3 % in CONV and UHDR mode, respectively. Short‐ and long‐term stabilities of the dose‐to‐charge ratio were below 1.6 %. Conclusions: We implemented commercially available BCTs and demonstrated their ability to act as online beam monitoring systems to support FLASH preclinical studies with CONV and UHDR irradiations. The implemented BCTs support dosimetric measurements, highlight variations among multiple measurements in a row, enable monitoring of the physics parameters used for irradiation, and are an important step for the safety of the clinical translation of FLASH radiation therapy. [ABSTRACT FROM AUTHOR]

Purpose: To present the acceptance and the commissioning, to define the reference dose, and to prepare the reference data for a quality assessment (QA) program of an ultra‐high dose rate (UHDR) electron device in order to validate it for preclinical animal FLASH radiotherapy (FLASH RT) experiments and for FLASH RT clinical human protocols. Methods: The Mobetron® device was evaluated with electron beams of 9 MeV in conventional (CONV) mode and of 6 and 9 MeV in UHDR mode (nominal energy). The acceptance was performed according to the acceptance protocol of the company. The commissioning consisted of determining the short‐ and long‐term stability of the device, the measurement of percent depth dose curves (PDDs) and profiles at two different positions (with two different dose per pulse regimen) and for different collimator sizes, and the evaluation of the variability of these parameters when changing the pulse width and pulse repetition frequency. Measurements were performed using a redundant and validated dosimetric strategy with alanine and radiochromic films, as well as Advanced Markus ionization chamber for some measurements. Results: The acceptance tests were all within the tolerances of the company's acceptance protocol. The linearity with pulse width was within 1.5% in all cases. The pulse repetition frequency did not affect the delivered dose more than 2% in all cases but 90 Hz, for which the larger difference was 3.8%. The reference dosimetry showed a good agreement within the alanine and films with variations of 2.2% or less. The short‐term (resp. long‐term) stability was less than 1.0% (resp. 1.8%) and was the same in both CONV and UHDR modes. PDDs, profiles, and reference dosimetry were measured at two positions, providing data for two specific dose rates (about 9 Gy/pulse and 3 Gy/pulse). Maximal beam size was 4 and 6 cm at 90% isodose in the two positions tested. There was no difference between CONV and UHDR mode in the beam characteristics tested. Conclusions: The device is commissioned for FLASH RT preclinical biological experiments as well as FLASH RT clinical human protocols. [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]

• FLASH-RT a paradigm-shifting method of delivering doses within an extremely short irradiation time. • FLASH-RT is a promising new tool to enhance the differential effect between tumors and normal tissues. • The consistency of the preclinical data clinical justifies transfer of FLASH-RT. • The most relevant parameters for FLASH are the combination of dose, dose-rate within the pulse, and overall time of irradiation. • A first proof of concept could be done with low-energy electrons and further tested with VHEE, protons and X-rays. Over the past decades, technological advances have transformed radiation therapy (RT) into a precise and powerful treatment for cancer patients. Nevertheless, the treatment of radiation-resistant tumors is still restricted by the dose-limiting normal tissue complications. In this context, FLASH-RT is emerging in the field. Consisting of delivering doses within an extremely short irradiation time, FLASH-RT has been identified as a promising new tool to enhance the differential effect between tumors and normal tissues. Indeed, preclinical studies on various animal models and a veterinarian clinical trial have recently shown that compared to conventional dose-rate RT, FLASH-RT could control tumors while minimizing normal tissue toxicity. In the present review, we summarize the main data supporting the clinical translation of FLASH-RT and explore its feasibility, the key irradiation parameters and the potential technologies needed for a successful clinical translation. [ABSTRACT FROM AUTHOR]

Simple Summary: The ability of ultra-high dose rate FLASH radiation therapy (RT) to reduce normal tissue toxicity without affecting tumor response relative to conventional dose rate radiation therapy could fundamentally change the way we treat cancer. However, this field is still in its early stages, and the magnitude of the sparing effect between treatment centers differs greatly for reasons as yet unknown, which has put the robustness of the effect into question. In this study, we show that when similar irradiation beam parameter settings are used, the induced sparing effect is robust and reproducible across institutions. These settings should serve as a reference for further optimization of the FLASH effect. FLASH radiation therapy (RT) is a promising new paradigm in radiation oncology. However, a major question that remains is the robustness and reproducibility of the FLASH effect when different irradiators are used on animals or patients with different genetic backgrounds, diets, and microbiomes, all of which can influence the effects of radiation on normal tissues. To address questions of rigor and reproducibility across different centers, we analyzed independent data sets from The University of Texas MD Anderson Cancer Center and from Lausanne University (CHUV). Both centers investigated acute effects after total abdominal irradiation to C57BL/6 animals delivered by the FLASH Mobetron system. The two centers used similar beam parameters but otherwise conducted the studies independently. The FLASH-enabled animal survival and intestinal crypt regeneration after irradiation were comparable between the two centers. These findings, together with previously published data using a converted linear accelerator, show that a robust and reproducible FLASH effect can be induced as long as the same set of irradiation parameters are used. [ABSTRACT FROM AUTHOR]

A patient with a cutaneous lymphoma was treated on the same day for 2 distinct tumors using a 15 Gy single electron dose given in a dose rate of 0.08 Gy/second versus 166 Gy/second. Comparing the two treatments, there was no difference for acute reactions, late effects at 2 years and tumor control. [ABSTRACT FROM AUTHOR]