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Background: Normal tissue sparing from radiation damage upon ultra-high dose rate irradiation, known as the FLASH effect with an equivalent tumor response, has been widely reported in murine skin models, and translation of this type of radiotherapy to humans has already begun, with skin sparing being a primary outcome expected. Methods: This study reviews the status of the field, focusing on the proposed mechanisms and skin response assays, outlining what has become known in terms of input parameters that might control the magnitude of the FLASH effect. Results: Murine studies have largely focused on acute damage responses, developing over 3–8 weeks, to single doses of FLASH versus conventional dose rate (CDR), suggesting that at dose rates above tens of Gray per second, with a total dose of more than 20 Gy, the FLASH effect is induced. Fractionated delivery appears to be possible, although fraction sizes >17 Gy appear to be needed for sparing efficacy. The interplay between the dose rate and total dose per fraction remains to be fully elucidated. Oxygen is a modulator of efficacy, with both hypoxia and hyperoxia diminishing the effect of FLASH. Measurement of transient changes in oxygen levels is possible and may be a marker of treatment efficacy. Conclusion: Taken together, murine skin data provide important information for translational studies, despite the associated limitations. Studies of later-term sparing effects, as well as studies on pig skin, are needed to take the next step in assessing translational FLASH efficacy. The control of biological factors, such as tissue oxygenation, may be required to understand and control the response. [ABSTRACT FROM AUTHOR]

Background: The extremely fast delivery of doses with ultra high dose rate (UHDR) beams necessitates the investigation of novel approaches for real‐time dosimetry and beam monitoring. This aspect is fundamental in the perspective of the clinical application of FLASH radiotherapy (FLASH‐RT), as conventional dosimeters tend to saturate at such extreme dose rates. Purpose: This study aims to experimentally characterize newly developed silicon carbide (SiC) detectors of various active volumes at UHDRs and systematically assesses their response to establish their suitability for dosimetry in FLASH‐RT. Methods: SiC PiN junction detectors, recently realized and provided by STLab company, with different active areas (ranging from 4.5 to 10 mm2) and thicknesses (10–20 µm), were irradiated using 9 MeV UHDR pulsed electron beams accelerated by the ElectronFLASH linac at the Centro Pisano for FLASH Radiotherapy (CPFR). The linearity of the SiC response as a function of the delivered dose per pulse (DPP), which in turn corresponds to a specific instantaneous dose rate, was studied under various experimental conditions by measuring the produced charge within the SiC active layer with an electrometer. Due to the extremely high peak currents, an external customized electronic RC circuit was built and used in conjunction with the electrometer to avoid saturation. Results: The study revealed a linear response for the different SiC detectors employed up to 21 Gy/pulse for SiC detectors with 4.5 mm2/10 µm active area and thickness. These values correspond to a maximum instantaneous dose rate of 5.5 MGy/s and are indicative of the maximum achievable monitored DPP and instantaneous dose rate of the linac used during the measurements. Conclusions: The results clearly demonstrate that the developed devices exhibit a dose‐rate independent response even under extreme instantaneous dose rates and dose per pulse values. A systematic study of the SiC response was also performed as a function of the applied voltage bias, demonstrating the reliability of these dosimeters with UHDR also without any applied voltage. This demonstrates the great potential of SiC detectors for accurate dosimetry in the context of FLASH‐RT. [ABSTRACT FROM AUTHOR]

Irradiations at Ultra-High Dose Rate (UHDR) regimes, exceeding 40 Gy/s in single fractions lasting less than 200 ms, have shown an equivalent antitumor effect compared to conventional radiotherapy with reduced harm to normal tissues. This work details the hardware and software modifications implemented to deliver 10 MeV UHDR electron beams with a linear accelerator Elekta SL 18 MV and the beam characteristics obtained. GafChromic EBT XD films and an Advanced Markus chamber were used for dosimetry characterization, while a silicon sensor assessed the machine's beam pulses stability and repeatability. The dose per pulse, average dose rate and instantaneous dose rate in the pulse were evaluated for four experimental settings, varying the source-to-surface distance and the beam collimation, i.e., with and without the use of a cylindrical applicator. The results showed a dose per pulse from 0.6 Gy to a few tens of Gy and an average dose rate up to 300 Gy/s. The obtained results demonstrate the possibility to perform in vitro radiobiology experiments and test new technologies for beam monitoring and dosimetry at the upgraded LINAC, thus contributing to the electron UHDR research field. [ABSTRACT FROM AUTHOR]

BackgroundNormal tissue sparing from radiation damage upon ultra-high dose rate irradiation, known as the FLASH effect with an equivalent tumor response, has been widely reported in murine skin models, and translation of this type of radiotherapy to humans has already begun, with skin sparing being a primary outcome expected.MethodsThis study reviews the status of the field, focusing on the proposed mechanisms and skin response assays, outlining what has become known in terms of input parameters that might control the magnitude of the FLASH effect.ResultsMurine studies have largely focused on acute damage responses, developing over 3–8 weeks, to single doses of FLASH versus conventional dose rate (CDR), suggesting that at dose rates above tens of Gray per second, with a total dose of more than 20 Gy, the FLASH effect is induced. Fractionated delivery appears to be possible, although fraction sizes >17 Gy appear to be needed for sparing efficacy. The interplay between the dose rate and total dose per fraction remains to be fully elucidated. Oxygen is a modulator of efficacy, with both hypoxia and hyperoxia diminishing the effect of FLASH. Measurement of transient changes in oxygen levels is possible and may be a marker of treatment efficacy.ConclusionTaken together, murine skin data provide important information for translational studies, despite the associated limitations. Studies of later-term sparing effects, as well as studies on pig skin, are needed to take the next step in assessing translational FLASH efficacy. The control of biological factors, such as tissue oxygenation, may be required to understand and control the response.

The article discusses the potential benefits of ultra-high dose rate irradiation, known as FLASH radiotherapy, in cancer treatment. FLASH-RT has been shown to reduce radiation-induced toxicity on normal tissues while maintaining similar antitumor effects as conventional radiotherapy. However, there are technological challenges in designing stable radiation sources and developing accurate dosimetric protocols for FLASH-RT. Additionally, the biological mechanisms underlying the FLASH effect are not yet fully understood. The article presents a multidisciplinary approach involving technological advancements, dosimetry, radiobiological experiments, and in silico simulations to further investigate and optimize FLASH-RT for clinical implementation. [Extracted from the article]

Purpose: Most current research toward ultra‐high dose rate (FLASH) radiation is conducted with advanced proton and electron accelerators, which are of limited accessibility to basic laboratory research. An economical alternative to charged particle accelerators is to employ high‐capacity rotating anode x‐ray tubes to produce kilovoltage x‐rays at FLASH dose rates at short source‐to‐surface distances (SSD). This work describes a comprehensive dosimetric evaluation of a rotating anode x‐ray tube for potential application in laboratory FLASH study. Methods and materials: A commercially available high‐capacity fluoroscopy x‐ray tube with 75 kW input power was implemented as a potential FLASH irradiator. Radiochromic EBT3 film and thermoluminescent dosimeters (TLDs) were used to investigate the effects of SSD and field size on dose rates and depth‐dose characteristics in kV‐compatible solid water phantoms. Custom 3D printed accessories were developed to enable reproducible phantom setup at very short SSD. Open and collimated radiation fields were assessed. Results: Despite the lower x‐ray energy and short SSD used, FLASH dose rates above 40 Gy/s were achieved for targets up to 10‐mm depth in solid water. Maximum surface dose rates of 96 Gy/s were measured in the open field at 47 mm SSD. A non‐uniform high‐to‐low dose gradient was observed in the planar dose distribution, characteristic of anode heel effects. With added collimation, beams up to 10‐mm diameter with reasonable uniformity can be produced. Typical 80%–20% penumbra in the collimated x‐ray FLASH beams were less than 1 mm at 5‐mm depth in phantom. Ramp‐up times at the maximum input current were less than 1 ms. Conclusion: Our dosimetric characterization demonstrates that rotating anode x‐ray tube technology is capable of producing radiation beams in support of preclinical FLASH radiobiology research. [ABSTRACT FROM AUTHOR]

Irradiations at Ultra-High Dose Rate (UHDR) regimes, exceeding 40 Gy/s in single fractions lasting less than 200 ms, have shown an equivalent antitumor effect compared to conventional radiotherapy with reduced harm to normal tissues. This work details the hardware and software modifications implemented to deliver 10 MeV UHDR electron beams with a linear accelerator Elekta SL 18 MV and the beam characteristics obtained. GafChromic EBT XD films and an Advanced Markus chamber were used for dosimetry characterization, while a silicon sensor assessed the machine’s beam pulses stability and repeatability. The dose per pulse, average dose rate and instantaneous dose rate in the pulse were evaluated for four experimental settings, varying the source-to-surface distance and the beam collimation, i.e., with and without the use of a cylindrical applicator. The results showed a dose per pulse from 0.6 Gy to a few tens of Gy and an average dose rate up to 300 Gy/s. The obtained results demonstrate the possibility to perform in vitro radiobiology experiments and test new technologies for beam monitoring and dosimetry at the upgraded LINAC, thus contributing to the electron UHDR research field.

Simple Summary: FLASH radiotherapy (RT) delivering ultra-high dose rate radiation can reduce normal tissue toxicity while effectively treating tumors. However, implementing FLASH RT in clinical settings faces challenges like limited depth penetration and complex treatment planning. Monte Carlo simulation is a valuable tool to optimize FLASH RT. Radiation detectors, including diamond detectors like microDiamond and ionization chambers, play a crucial role in accurately measuring dose delivery. Moreover, optically stimulated luminescence dosimeters and radiochromic films are used for validation. Advancements are being made to improve detector accuracy in FLASH RT. Further research is needed to refine treatment planning and detector performance for widespread FLASH RT implementation, which can potentially revolutionize cancer treatment. Radiotherapy (RT) using ultra-high dose rate (UHDR) radiation, known as FLASH RT, has shown promising results in reducing normal tissue toxicity while maintaining tumor control. However, implementing FLASH RT in clinical settings presents technical challenges, including limited depth penetration and complex treatment planning. Monte Carlo (MC) simulation is a valuable tool for dose calculation in RT and has been investigated for optimizing FLASH RT. Various MC codes, such as EGSnrc, DOSXYZnrc, and Geant4, have been used to simulate dose distributions and optimize treatment plans. Accurate dosimetry is essential for FLASH RT, and radiation detectors play a crucial role in measuring dose delivery. Solid-state detectors, including diamond detectors such as microDiamond, have demonstrated linear responses and good agreement with reference detectors in UHDR and ultra-high dose per pulse (UHDPP) ranges. Ionization chambers are commonly used for dose measurement, and advancements have been made to address their response nonlinearities at UHDPP. Studies have proposed new calculation methods and empirical models for ion recombination in ionization chambers to improve their accuracy in FLASH RT. Additionally, strip-segmented ionization chamber arrays have shown potential for the experimental measurement of dose rate distribution in proton pencil beam scanning. Radiochromic films, such as GafchromicTM EBT3, have been used for absolute dose measurement and to validate MC simulation results in high-energy X-rays, triggering the FLASH effect. These films have been utilized to characterize ionization chambers and measure off-axis and depth dose distributions in FLASH RT. In conclusion, MC simulation provides accurate dose calculation and optimization for FLASH RT, while radiation detectors, including diamond detectors, ionization chambers, and radiochromic films, offer valuable tools for dosimetry in UHDR environments. Further research is needed to refine treatment planning techniques and improve detector performance to facilitate the widespread implementation of FLASH RT, potentially revolutionizing cancer treatment. [ABSTRACT FROM AUTHOR]

Ultra-high dose rate (UHDR) beams for FLASH radiotherapy present significant dosimetric challenges. Although novel approaches for decreasing or correcting ion recombination in ionization chambers are being proposed, applicability of ionimetric dosimetry to UHDR beams is still under investigation. Solid-state sensors have been recently investigated as a valuable alternative for real-time measurements, especially for relative dosimetry and beam monitoring. Among them, Silicon Carbide (SiC) represents a very promising candidate, compromising between the maturity of Silicon and the robustness of diamond. Its features allow for large area sensors and high electric fields, required to avoid ion recombination in UHDR beams. In this study, we present simulations and experimental measurements with the low energy UHDR electron beams accelerated with the ElectronFLASH machine developed by the SIT Sordina company (IT). The response of a newly developed 1 × 1 cm2 SiC sensor in charge as a function of the dose-per-pulse and its radiation hardness up to a total delivered dose of 90 kGy, was investigated during a dedicated experimental campaign, which is, to our knowledge, the first characterization ever done of SiC with UHDR-pulsed beams accelerated by a dedicated ElectronFLASH LINAC. Results are encouraging and show a linear response of the SiC detector up to 2 Gy/pulse and a variation in the charge per pulse measured for a cumulative delivered dose of 90 kGy, within ±0.75%. [ABSTRACT FROM AUTHOR]

• Deeper understanding of the charge collection efficiency of ionization chambers. • Simulation of the charge collection efficiency including charge multiplication. • Application of ionization chambers under ultra-high dose rate electron beams. • Promising tool for real-time dosimetry in FLASH radiotherapy. Investigating and understanding of the underlying mechanisms affecting the charge collection efficiency (CCE) of vented ionization chambers under ultra-high dose rate pulsed electron radiation. This is an important step towards real-time dosimetry with ionization chambers in FLASH radiotherapy. Parallel-plate ionization chambers (PPIC) with three different electrode distances were build and investigated with electron beams with ultra-high dose-per-pulse (DPP) up to 5.4 Gy. The measurements were compared with simulations. The experimental determination of the CCE was done by comparison against the reference dose based on alanine dosimetry. The numerical solution of a system of partial differential equations taking into account charge creations by the radiation, their transport and reaction in an applied electric field was used for the simulations of the CCE and the underlying effects. A good agreement between the experimental results and the simulated CCE could be achieved. The recombination losses found under ultra-high DPP could be attributed to a temporal and spatial charge carrier imbalance and the associated electric field distortion. With ultra-thin electrode distances down to 0.25 mm and a suitable chamber voltage, a CCE greater than 99 % could be achieved under the ultra-high DPP conditions investigated. Well-guarded ultra-thin PPIC are suited for real-time dosimetry under ultra-high DPP conditions. This allows dosimetry also for FLASH RT according to common codes of practice, traceable to primary standards. The numerical approach used allows the determination of appropriate correction factors beyond the DPP ranges where established theories are applicable to account for remaining recombination losses. [ABSTRACT FROM AUTHOR]

Air-vented ionization chambers have been the secondary standard for radiation dosimetry since the origins of radiation metrology. However, the feasibility of their use in ultra-high dose rate pulsed beams has been a matter of discussion, as large losses are caused by ion recombinations and no suitable theoretical model is available for their correction. The theories developed by Boag and his contemporaries since the 1950s, which have provided the standard ion recombination correction factor in clinical dosimetry, do not provide an accurate description when used under the limit conditions of ultra-high dose rates (UHDRs). Moreover, the high-ion recombination effects of ionization chambers under extreme dose-rate applications are an obstacle to the development of adequate dosimetry standards. In this article, the charge carrier transport equations within a parallel plate ionization chamber (PPIC) have been solved numerically with a double aim. First, this numerical model provides a more accurate tool that can be used to evaluate ion recombination correction for established PPICs in pulsed ultra-high dose rate regimes. Second, studying the chamber behavior in detail allow as to explore the limits of new chamber designs in order to improve their performance under UHDRs. The model presented here has been tested by measuring the instantaneous current of one unit of a Roos chamber (i.e., the time-resolved current during and after the irradiation pulse under UHDR conditions) and comparing these results with the absolute value of the simulated current. The experimental data show consistent agreement with the results obtained using the numerical model. The experimental instantaneous current reveals effects such as the variation of the free electron fraction with the dose per pulse that are supported by the numerical model but cannot be explained in the framework of Boag's theory. Numerical solutions of the charge carrier released and transport in ionization chambers are able to estimate the effects observed when PPICs are irradiated with ultra-high dose rate beams and to provide new insight into processes related to recombination losses at UHDRs. These models can be reliably extended to include regions where current analytical solutions are not valid. An agreement of better than 5 % between the experimental and simulated effective free electron fraction is found. We were able to reproduce the instantaneous current from a Roos chamber. The discrepancies observed between the experimental data and the numerical simulations can be attributed to the uncertainty about the transport parameters involved in the calculation. • Numerical method to describe air ionization chambers at UHDR. • Free electron fraction as a function of dose per pulse and electrode distance. • Instantaneous current, ion collection time, free electron fraction for Roos chamber. • Comparative study of numerical and analytical models. • Effect of the time pulse structure on charge collection efficiency. [ABSTRACT FROM AUTHOR]

Purpose: A diamond detector prototype was recently proposed by Marinelli et al. (Medical Physics 2022, https://doi.org/10.1002/mp.15473) for applications in ultrahigh‐dose‐per‐pulse (UH‐DPP) and ultrahigh‐dose‐rate (UH‐DR) beams, as used in FLASH radiotherapy (FLASH‐RT). In the present study, such so‐called flashDiamond (fD) was investigated from the dosimetric point of view, under pulsed electron beam irradiation. It was then used for the commissioning of an ElectronFlash linac (SIT S.p.A., Italy) both in conventional and UH‐DPP modalities. Methods: Detector calibration was performed in reference conditions, under 60Co and electron beam irradiation. Its response linearity was investigated in UH‐DPP conditions. For this purpose, the DPP was varied in the 1.2–11.9 Gy range, by changing either the beam applicator or the pulse duration from 1 to 4 μs. Dosimetric validation of the fD detector prototype was then performed in conventional modality, by measuring percentage depth dose (PDD) curves, beam profiles, and output factors (OFs). All such measurements were carried out in a motorized water phantom. The obtained results were compared with the ones from commercially available dosimeters, namely, a microDiamond, an Advanced Markus ionization chamber, a silicon diode detector, and EBT‐XD GAFchromic films. Finally, the fD detector was used to fully characterize the 7 and 9 MeV UH‐DPP electron beams delivered by the ElectronFlash linac. In particular, PDDs, beam profiles, and OFs were measured, for both energies and all the applicators, and compared with the ones from EBT‐XD films irradiated in the same experimental conditions. Results: The fD calibration coefficient resulted to be independent from the investigated beam qualities. The detector response was found to be linear in the whole investigated DPP range. A very good agreement was observed among PDDs, beam profiles, and OFs measured by the fD prototype and reference detectors, both in conventional and UH‐DPP irradiation modalities. Conclusions: The fD detector prototype was validated from the dosimetric point of view against several commercial dosimeters in conventional beams. It was proved to be suitable in UH‐DPP and UH‐DR conditions, for which no other commercial real‐time active detector is available to date. It was shown to be a very useful tool to perform fast and reproducible beam characterizations in standard clinical motorized water phantom setups. All of the previously mentioned demonstrate the suitability of the proposed detector for the commissioning of UH‐DR linac beams for preclinical FLASH‐RT applications. [ABSTRACT FROM AUTHOR]

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]

The challenge of saturation at the high dose rate employed in FLASH radiotherapy and the lack of real-time 2D and 3D dosimeters create an opportunity for the use of plastic scintillators. This study presents the development of an online dosimetric system designed for electron FLASH radiotherapy applications: an array of dosimeters, made by plastic scintillating fibers, each one coupled to an optical fiber, was evaluated as a proof-of-concept using a LINAC providing 9 MeV electrons, at the Centro Pisano Flash Radiotherapy. Signal linearity was established up to 10 Gy/pulse, with a pulse duration of 4 μ s. We also measured the signal variation across the beam profile using different applicators (30 mm, 50 mm and 100 mm in diameters) and we developed a geometrical model that accounts for the different amount of dose absorbed by the plastic scintillating fibers and the optical fibers. By fitting this model to the data, we estimated both the inter-calibration factors of the dosimeters, as well as the intrinsic ratio (i.e. for equal irradiated volumes) of spurious light in the optical fiber respect to the scintillation, which is equal to (4.7 ± 0. 1 s t a t. ± 1. 0 s y s t. ) %. • Dosimeters made by an array of plastic scintillating fibers tested with a FLASH beam. • Beam profile measured with an array of five dosimeters. • New calibration method to equalize response and subtract spurious signal. [ABSTRACT FROM AUTHOR]

Purpose: FLASH radiotherapy (RT) is an emerging technique in which beams with ultra‐high dose rates (UH‐DR) and dose per pulse (UH‐DPP) are used. Commercially available active real‐time dosimeters have been shown to be unsuitable in such conditions, due to severe response nonlinearities. In the present study, a novel diamond‐based Schottky diode detector was specifically designed and realized to match the stringent requirements of FLASH‐RT. Methods: A systematic investigation of the main features affecting the diamond response in UH‐DPP conditions was carried out. Several diamond Schottky diode detector prototypes with different layouts were produced at Rome Tor Vergata University in cooperation with PTW‐Freiburg. Such devices were tested under electron UH‐DPP beams. The linearity of the prototypes was investigated up to DPPs of about 26 Gy/pulse and dose rates of approximately 1 kGy/s. In addition, percentage depth dose (PDD) measurements were performed in different irradiation conditions. Radiochromic films were used for reference dosimetry. Results: The response linearity of the diamond prototypes was shown to be strongly affected by the size of their active volume as well as by their series resistance. By properly tuning the design layout, the detector response was found to be linear up to at least 20 Gy/pulse, well into the UH‐DPP range conditions. PDD measurements were performed by three different linac applicators, characterized by DPP values at the point of maximum dose of 3.5, 17.2, and 20.6 Gy/pulse, respectively. The very good superimposition of three curves confirmed the diamond response linearity. It is worth mentioning that UH‐DPP irradiation conditions may lead to instantaneous detector currents as high as several mA, thus possibly exceeding the electrometer specifications. This issue was properly addressed in the case of the PTW UNIDOS electrometers. Conclusions: The results of the present study clearly demonstrate the feasibility of a diamond detector for FLASH‐RT applications. [ABSTRACT FROM AUTHOR]

Ultra-high dose rate (UHDR) beams for FLASH radiotherapy present significant dosimetric challenges. Although novel approaches for decreasing or correcting ion recombination in ionization chambers are being proposed, applicability of ionimetric dosimetry to UHDR beams is still under investigation. Solid-state sensors have been recently investigated as a valuable alternative for real-time measurements, especially for relative dosimetry and beam monitoring. Among them, Silicon Carbide (SiC) represents a very promising candidate, compromising between the maturity of Silicon and the robustness of diamond. Its features allow for large area sensors and high electric fields, required to avoid ion recombination in UHDR beams. In this study, we present simulations and experimental measurements with the low energy UHDR electron beams accelerated with the ElectronFLASH machine developed by the SIT Sordina company (IT). The response of a newly developed 1 × 1 cm2 SiC sensor in charge as a function of the dose-per-pulse and its radiation hardness up to a total delivered dose of 90 kGy, was investigated during a dedicated experimental campaign, which is, to our knowledge, the first characterization ever done of SiC with UHDR-pulsed beams accelerated by a dedicated ElectronFLASH LINAC. Results are encouraging and show a linear response of the SiC detector up to 2 Gy/pulse and a variation in the charge per pulse measured for a cumulative delivered dose of 90 kGy, within ±0.75%.

This paper reports the development of dosimeters based on plastic scintillating fibers imaged by a charge-coupled device camera, and their performance evaluation through irradiations with the electron Flash research accelerator located at the Centro Pisano Flash Radiotherapy. The dosimeter prototypes were composed of a piece of plastic scintillating fiber optically coupled to a clear optical fiber which transported the scintillation signal to the readout systems (an imaging system and a photodiode). The following properties were tested: linearity, capability to reconstruct the percentage depth dose curve in solid water and to sample in time the single beam pulse. The stem effect contribution was evaluated with three methods, and a proof-of-concept one-dimensional array was developed and tested for online beam profiling. Results show linearity up to 10 Gy per pulse, and good capability to reconstruct both the timing and spatial profiles of the beam, thus suggesting that plastic scintillating fibers may be good candidates for low-energy electron Flash dosimetry. • Flash radiotherapy may be groundbreaking for improving cancer treatment. • Conventional dosimeters do not function properly in the Flash regime. • Dosimeters based on plastic scintillating fibers were developed and characterized. • No quenching or energy dependence was observed in the Flash regime. • The beam time structure could be properly sampled. [ABSTRACT FROM AUTHOR]

• Conformal and targeted irradiation of mice can be performed without image guidance. • The end-to-end validation of methodology has been performed on a dead mouse. • Respiration's impact was studied 65 MeV protons lateral and posterior irradiations. • OC-1 radiochromic films can be used to check treatment planning. As part of translational research projects, mice may be irradiated on radiobiology platforms such as the one at the ARRONAX cyclotron. Generally, these platforms do not feature an integrated imaging system. Moreover, in the context of ultra-high dose-rate radiotherapy (FLASH-RT), treatment planning should consider potential changes in the beam characteristics and internal movements in the animal. A patient-like set-up and methodology has been implemented to ensure target coverage during conformal irradiations of the brain, lungs and intestines. In addition, respiratory cycle amplitudes were quantified by fluoroscopic acquisitions on a mouse, to ensure organ coverage and to assess the impact of respiration during FLASH-RT using the 4D digital phantom MOBY. Furthermore, beam incidence direction was studied from mice µCBCT and Monte Carlo simulations. Finally, in vivo dosimetry with dose-rate independent radiochromic films (OC-1) and their LET dependency were investigated. The immobilization system ensures that the animal is held in a safe and suitable position. The geometrical evaluation of organ coverage, after the addition of the margins around the organs, was satisfactory. Moreover, no measured differences were found between CONV and FLASH beams enabling a single model of the beamline for all planning studies. Finally, the LET-dependency of the OC-1 film was determined and experimentally verified with phantoms, as well as the feasibility of using these films in vivo to validate the targeting. The methodology developed ensures accurate and reproducible preclinical irradiations in CONV and FLASH-RT without in-room image guidance in terms of positioning, dose calculation and in vivo dosimetry. [ABSTRACT FROM AUTHOR]

• The first high-energy X-ray FLASH radiotherapy platform (PARTER) has been upgraded. • 6–8 MVs X-ray is available for FLASH irradiation at dose rate of 40–1000 Gy/s. • Treatment system and dosimetry were improved to provide verified high-performance FLASH X-rays. • The FLASH effect was demonstrated by numerous experiments using PARTER's MV X-rays. • The accelerator is being upgraded for FLASH irradiation at 80-cm SSD at the end of 2025. Recent studies indicated that ultrahigh dose rate (FLASH) radiation can reduce damage to normal tissue while maintaining anti-tumour activity compared to conventional dose rate (CONV) radiation. This paper provides a comprehensive description of the current status of the Platform for Advanced Radiotherapy Research (PARTER), which serves as the first experimental FLASH platform utilizing megavoltage X-rays and has facilitated numerous experiments. PARTER was established in 2019 based on a superconducting linac to support experimental FLASH studies using megavoltage X-rays. Continuous upgrades have been made to the accelerator, collimators, flattening filters, monitors, other auxiliary devices, and irradiation process in order to achieve optimal results. Passive and active dosimeters are employed for measuring dose distribution and to ensure traceability of radiation doses. The dose monitors and dosimeters demonstrate reliable performance with acceptable stability. At PARTER, the maximum mean dose rate is approximately 400 Gy/s at a surface-source distance of 20 cm (over 1000 Gy/s at smaller distances), with an instantaneous dose rate of approximately 8E5 Gy/s. Both passive and active dosimeters exhibit good linearity and agreement during FLASH X-ray irradiation. The monitors show good linearity to dose rate, with short-term fluctuations within 1.5 % for the diamond monitor. The discrepancy between measured absorbed dose and dose protocol is typically less than 4 %. The X-ray energy spectra on PARTER are comparable to those for megavoltage CONV linacs operating in flattening filter-free mode. The maximum field size of the FLASH beam is 4.5 cm × 4.5 cm. The FLASH dose profile demonstrates satisfactory flatness (1.04) and similar penumbra compared to clinical CONV linac, while the percentage depth dose curve of FLASH X-rays is steeper than that of the clinical megavoltage CONV X-ray. PARTER represents a pioneering platform for conducting megavolts FLASH X-ray irradiation in biological experiments. It effectively fulfills the requirements of preclinical research on megavoltage X-ray FLASH and undergoes continuous upgrades to meet increasingly demanding performance criteria. [ABSTRACT FROM AUTHOR]

Recently, as the biological effects of ultrahigh-dose-rate radiation therapy (flash RT) have been verified, many kinds of research on the clinical application of high-dose-rate radiation therapy have been performed. Moreover, various studies are being performed to determine the absorbed dose in the volume of cancers. In this study, to evaluate the absorbed dose of the human body during high-dose-rate radiation therapy, a dosimeter system was developed using a tissue equivalent plastic scintillator having the same geometric structure as the Farmer-type ionization chamber, and its characteristics were evaluated. The plastic scintillator was based on PMMA, and PPO was used as the primary scintillator and POPOP as the wavelength shifter. An Irgacure 819 photo-initiator and a Hg lamp were used to polymerize of PMMA plastic scintillator. The fabricated plastic scintillator was characterized for conventional LINAC X-ray and 45 MeV proton beams. The results of this study combined with 3D printing technology are planned to be used as dosimeters for volumetric dosimetry of normal and cancerous tissues during radiation therapy. • A PMMA scintillator can be used for dosimetry because of tissue-equivalent. • The PMMA-based plastic scintillators could be applied 3d DLP printing. • An integral mode of the DAQ system can measure a very high dose rate. [ABSTRACT FROM AUTHOR]