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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]

• Comparison of the dosimetric potential of 2 major FLASH-RT candidate modalities. • Differences in beam penumbrae are pivotal for plan quality of VHEE and TP. • VHEE of 100–250 MeV may provide a dosimetric plan quality that is comparable to TP. • VHEE beams ≥ 150 MeV improve plan quality for deep-seated tumours (e.g., pelvis). • VHEE therapy uses a lighter particle beam compared to TP therapy. Clinical translation of FLASH-radiotherapy (RT) to deep-seated tumours is still a technological challenge. One proposed solution consists of using ultra-high dose rate transmission proton (TP) beams of about 200–250 MeV to irradiate the tumour with the flat entrance of the proton depth-dose profile. This work evaluates the dosimetric performance of very high-energy electron (VHEE)-based RT (50–250 MeV) as a potential alternative to TP-based RT for the clinical transfer of the FLASH effect. Basic physics characteristics of VHEE and TP beams were compared utilizing Monte Carlo simulations in water. A VHEE-enabled research treatment planning system was used to evaluate the plan quality achievable with VHEE beams of different energies, compared to 250 MeV TP beams for a glioblastoma, an oesophagus, and a prostate cancer case. Like TP, VHEE above 100 MeV can treat targets with roughly flat (within ± 20 %) depth-dose distributions. The achievable dosimetric target conformity and adjacent organs-at-risk (OAR) sparing is consequently driven for both modalities by their lateral beam penumbrae. Electron beams of 400[500] MeV match the penumbra of 200[250] MeV TP beams and penumbra is increased for lower electron energies. For the investigated patient cases, VHEE plans with energies of 150 MeV and above achieved a dosimetric plan quality comparable to that of 250 MeV TP plans. For the glioblastoma and the oesophagus case, although having a decreased conformity, even 100 MeV VHEE plans provided a similar target coverage and OAR sparing compared to TP. VHEE-based FLASH-RT using sufficiently high beam energies may provide a lighter-particle alternative to TP-based FLASH-RT with comparable dosimetric plan quality. [ABSTRACT FROM AUTHOR]

Purpose: Driven by advances in accelerator technology and the potential of exploiting the FLASH effect for the treatment of deep‐seated targets (>5 cm), there is an active interest in the construction of devices to deliver very high‐energy electron (VHEE) beams for radiation therapy. The application of novel VHEE devices, however, requires an assessment of the tradeoffs between the different beam parameter choices including beam energies, beam divergences, and maximal field sizes. This study systematically examines the dosimetric beam properties of VHEE beams, determining their clinical usefulness while marking their limits of applications for different beam configurations. Methods: We performed Monte Carlo simulations of the dose distributions of electron beams for different energies (25–250 MeV), source‐to‐surface distances (SSD) (50 cm, 100 cm, parallel), and field sizes (2 cm2 × 2 cm2 to 15 cm2 × 15 cm2) in water using a research version of the RayStation treatment planning system (RaySearch Labs 9A IONPG). The beam was simulated using a monoenergetic point source and perfect collimation. Central axis percentage depth dose (PDD) and transverse dose profiles at multiple depths were evaluated and compared to those of MV photon beams. Profile characteristics including therapeutic range (TR) at 90%, proximal fall‐off (PFO) at 90%, lateral penumbra (LP) at 90%–10%, and field width (FW) at 90% were obtained. Results: Very high‐energy electrons beams with SSD 100 cm and parallel beams (infinite SSD) exhibit a linear to near‐linear increase of TR as a function of energy in the simulated energy range and reach values well beyond the typical depths of lesions encountered in clinics (<20 cm). Their TR show a marked field size dependence only for field sizes <10 cm2 × 10 cm2. For VHEE beams with SSD 50 cm, TR are largely reduced (4–8 cm). For beam energies >150 MeV with large SSD (>100 cm), for many configurations, there is no substantial difference in PDD when adding an opposed beam. This may potentially reduce the number of VHEE beams needed for treatment by a factor of two compared to a treatment using lower energies and lower SSD. In order to cover deep‐seated targets homogeneously, VHEE devices with a parallel beam must provide a maximum field size up to several centimeters larger than the tumor size. For the investigated diverging beams, there is not such a significant field width reduction with depth for larger fields as it is compensated by divergence. Penumbrae of VHEE beams are smaller than those of clinical MV photon beams for lower depths (<5 cm) but increase quickly for larger depths. There is only a relatively small dependence of penumbra on the SSD of the beam. Conclusions: The findings presented in this study assess the performance of VHEE beams and offer a first estimate of treatment indications and tradeoffs for a given design of a VHEE device. SSD >100 cm results in clinically more favorable PDD. Beam energies of 100 MeV and above are needed to cover common tumors (5–15 cm in‐depth) conformally. Higher energies provide an additional benefit specifically for small and deep‐seated lesions due to their reduced lateral penumbrae. [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]

Purpose The purpose of this work was to establish an empirical model of the ion recombination in the Advanced Markus ionization chamber for measurements in high dose rate/dose-per-pulse electron beams. In addition, we compared the observed ion recombination to calculations using the standard Boag two-voltage-analysis method, the more general theoretical Boag models, and the semiempirical general equation presented by Burns and McEwen. Methods Two independent methods were used to investigate the ion recombination: (a) Varying the grid tension of the linear accelerator (linac) gun (controls the linac output) and measuring the relative effect the grid tension has on the chamber response at different source-to-surface distances (SSD). (b) Performing simultaneous dose measurements and comparing the dose-response, in beams with varying dose rate/dose-per-pulse, with the chamber together with dose rate/dose-per-pulse independent Gafchromic™ EBT3 film. Three individual Advanced Markus chambers were used for the measurements with both methods. All measurements were performed in electron beams with varying mean dose rate, dose rate within pulse, and dose-per-pulse (10−2 ≤ mean dose rate ≤ 103 Gy/s, 102 ≤ mean dose rate within pulse ≤ 107 Gy/s, 10−4 ≤ dose-per-pulse ≤ 101 Gy), which was achieved by independently varying the linac gun grid tension, and the SSD. Results The results demonstrate how the ion collection efficiency of the chamber decreased as the dose-per-pulse increased, and that the ion recombination was dependent on the dose-per-pulse rather than the dose rate, a behavior predicted by Boag theory. The general theoretical Boag models agreed well with the data over the entire investigated dose-per-pulse range, but only for a low polarizing chamber voltage (50 V). However, the two-voltage-analysis method and the Burns & McEwen equation only agreed with the data at low dose-per-pulse values (≤ 10−2 and ≤ 10−1 Gy, respectively). An empirical model of the ion recombination in the chamber was found by fitting a logistic function to the data. Conclusions The ion collection efficiency of the Advanced Markus ionization chamber decreases for measurements in electron beams with increasingly higher dose-per-pulse. However, this chamber is still functional for dose measurements in beams with dose-per-pulse values up toward and above 10 Gy, if the ion recombination is taken into account. Our results show that existing models give a less-than-accurate description of the observed ion recombination. This motivates the use of the presented empirical model for measurements with the Advanced Markus chamber in high dose-per-pulse electron beams, as it enables accurate absorbed dose measurements (uncertainty estimation: 2.8-4.0%, k = 1). The model depends on the dose-per-pulse in the beam, and it is also influenced by the polarizing chamber voltage, with increasing ion recombination with a lowering of the voltage. [ABSTRACT FROM AUTHOR]

• HUC RT combines UHDR electrons (20–250 MeV) with CDR IMRT for deep-seated tumours. • HUC plans matched clinical quality, with similar PTV coverage and OAR sparing. • "HUC boost" treatments may deliver large fraction doses to optimize FLASH sparing. • HUC treatments are dosimetrically feasible for delivering conformal FLASH-RT. • HUC RT may improve accessibility to FLASH-RT by reducing technical burdens. This study explores the dosimetric feasibility and plan quality of hybrid ultra-high dose rate (UHDR) electron and conventional dose rate (CDR) photon (HUC) radiotherapy for treating deep-seated tumours with FLASH-RT. HUC treatment planning was conducted optimizing a broad UHDR electron beam (between 20–250 MeV) combined with a CDR VMAT for a glioblastoma, a pancreatic cancer, and a prostate cancer case. HUC plans were based on clinical prescription and fractionation schemes and compared against clinically delivered plans. Considering a HUC boost treatment for the glioblastoma consisting of a 15-Gy-single-fraction UHDR electron boost supplemented with VMAT, two scenarios for FLASH sparing were assessed using FLASH-modifying-factor-weighted doses. For all three patient cases, HUC treatment plans demonstrated comparable dosimetric quality to clinical plans, with similar PTV coverage (V 95% within 0.5 %), homogeneity, and critical OAR-sparing. At the same time, HUC plans delivered a substantial portion of the dose to the PTV (D median of 50–69 %) and surrounding tissues at UHDR. For the HUC boost treatment of the glioblastoma, the first FLASH sparing scenario showed a moderate FLASH sparing magnitude (10 % for D 2%,PTV) for the 15-Gy UHDR electron boost, while the second scenario indicated a more substantial sparing of brain tissues inside and outside the PTV (32 % for D 2%,PTV , 31 % for D 2%,Brain). From a planning perspective, HUC treatments represent a feasible approach for delivering dosimetrically conformal UHDR treatments, potentially mitigating technical challenges associated with delivering conformal FLASH-RT for deep-seated tumours. While further research is needed to optimize HUC fractionation and delivery schemes for specific patient cohorts, HUC treatments offer a promising avenue for the clinical transfer of FLASH-RT. [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]

• At conventional dose-rates (few Gy/min), the alanine, the Gafchromic films, the TLD and the ionization chamber agree within 2%. • For dose-rates up to 1050 Gy/s, the alanine, the Gafchromic films and the TLD agree within 3%, showing no dose-rate dependency. • Thanks to the dosimetric procedure, the uncertainty in the delivered dose for the biological experiments is estimated to be about 3%. • Without this dosimetric procedure, deviations between the delivered dose and the prescription dose can reach 15%. Preclinical studies using a new treatment modality called FLASH Radiotherapy (FLASH-RT) need a two-phase procedure to ensure minimal uncertainties in the delivered dose. The first phase requires a new investigation of the reference dosimetry lying outside the conventional metrology framework from national metrology institutes but necessary to obtain traceability, repeatability, and stability of irradiations. The second consists of performing special quality assurance procedure prior to irradiation. The Oriatron eRT6 (PMB-Alcen, France) is an experimental high dose-per-pulse linear accelerator, delivering a 6 MeV pulsed electron beam with mean dose-rates, ranging from a few Gy/min up to thousands of Gy/s. Absolute dosimetry is investigated with alanine, thermo-luminescent dosimeters (TLD) and radiochromic films as well as an ionization chamber for relative stability. The beam characteristic and dosimetry are prepared for three different setups. A cross-check between alanine, films and TLD revealed a dose agreement within 3% for dose-rates between 0.078 Gy/s and 1050 Gy/s, showing that these dosimeters are suitable for absolute dosimetry for FLASH-RT. In absence of appropriate setup dependent corrections, active dosimetry can reveal dose deviations up to 15% of the prescribed dose. These differences reduce to less than 3% when our dosimetric procedure is applied. We developed procedures to accurately irradiate biological models. Our method is based on validated absolute dosimeters and extends their use to routine FLASH irradiations. We reached an agreement of 3% between the delivered and prescribed dose and developed the requirements needed for workflows of preclinical and clinical studies. [ABSTRACT FROM AUTHOR]