Ultra-high dose rate flash radiotherapy (FLASH-RT) has attracted wide attention in the field of radiotherapy in recent years. For FLASH-RT, radiation is delivered at a very high dose rate [usually thousands of times compared with conventional radiotherapy (CONV-RT)] in an extremely short time. This novel irradiation technique shows a protective effect on normal tissues, also known as the flash effect. At the same time, FLASH-RT is comparable to CONV-RT in terms of tumor-killing efficacy. As basic research dedicates to uncover the mechanisms by which FLASH-RT reduces radiation-induced normal tissue damage, clinical trials of FLASH-RT have been gradually conducted worldwide. This article systematically reviews the evidence of the feasibility and safety of FLASH-RT in clinical practice and offers insights into the future translation of this technology in clinic.

Modern compact proton synchrocyclotrons can achieve ultra-high dose rates ( ≥ $ \ge $ 40 Gy/s) to support ultra-high-dose-rate (UHDR) preclinical experiments utilizing pencil beam scanning (PBS) protons. Unique to synchrocyclotrons is a pulsed proton time structure as compared to the quasi-continuous nature of other proton accelerators like isochronous cyclotrons. Thus, high instantaneous proton currents in the order of several µA must be generated to achieve UHDRs. This will lead to high doses-per-pulse (DPP), which may cause significant charge recombination for ionization chambers, which must be characterized for accurate UHDR dosimetry programs.

In this work, we investigate the suitability of various commercial radiation detectors for accurate proton UHDR dosimetry using PBS proton beams from a compact proton synchrocyclotron (IBA ProteusONE). This is achieved by cross-calibrating them with conventional dose rates, measuring UHDR recombination (Pion) and polarity correction factors (Ppol) for ionization chambers, and determining the absorbed proton UHDR dose delivered for all detectors.

An IBA ProteusONE synchrocyclotron was initially tuned to achieve UHDRs with 228 MeV protons at 0° gantry angle. Various detectors, including Razor Chamber, Razor Nano Chamber, Razor Diode, and microDiamond, were cross-calibrated against a PPC05 plane-parallel ionization chamber (PPIC) that had an ADCL calibration coefficient of 59.23 cGy/nC. Then, all ionization chambers were exposed to UHDR protons with the Ppol and Pion subsequently calculated. Pion was calculated using two methods: TRS-398 methods and Niatel's model. Finally, the absolute UHDR proton doses delivered were determined for all detectors and cross-compared.

Faraday cup measurements were performed for a single spot proton UHDR beam, and the nozzle current at the isocenter was determined to be 129.5 nA during UHDR irradiations at 98.61% of the maximum theoretical dose rate. Repeated Faraday cup measurements of the UHDR beam yielded a percentage standard deviation of 0.8%, which was higher than 0.120% when similar repeated measurements were performed with conventional proton beams. Ppol was found to be relatively dose-rate independent for all ionization chambers investigated. Pion was found to be the lowest for the PPC05 ionization chamber (1.0097) compared to corresponding values of 1.0214 and 1.0294 for the Razor and Razor Nano detectors, respectively, for UHDRs. Pion values calculated using Niatel's model closely matched values from TRS-398 if the VH/VL ratio were kept at 2.5 for the PPC05 and Razor detectors and 2.0 for the Razor Nano detector. Absolute proton UHDR doses determined using cross-calibration factors were generally within ± 1% of PPC05 measurements. However, Razor Diode was found to over-respond by up to 3.79% within UHDR proton beams, rendering them unsuitable for proton UHDR dosimetry.

In this work, we comprehensively evaluated the suitability of various commercial detectors for absolute dosimetry with a pulsed UHDR beam structure from a proton synchrocyclotron. PPC05 had the lowest ionic recombination correction compared to Razor and Razor Nano ion chambers. Other than the diode detector, all other investigated detectors (PPC05, Razor, Razor Nano, microDiamond) were within ± 1% of one another and can be used for accurate absolute proton UHDR dosimetry.

The use of ultra-high dose rate beams (UHDR) (> 40 Gy/s) for radiotherapy, despite its advantage of exhibiting the FLASH effect that improves the sparing of healthy tissues, faces challenges in dosimetry and beam monitoring since standard dosimeters like the ionization chamber experience saturation effects at such high dose rates. Silicon carbide (SiC) detectors have recently been demonstrated to be dose-rate independent with low-energy pulsed electron beams up to an instantaneous dose rate of 5.5 MGy/s, and has emerged as a reliable alternative technology for dosimetry in FLASH-RT. This study explored the suitability of using the SiC detector for measuring intra-pulse instantaneous dose rates, which are necessary for monitoring fluctuations within the pulse of UHDR pulsed electron beams. The experiments reported were conducted using UHDR electron beams accelerated at 9 MeV by an ElectronFlash linac and using varying different beam parameters, such as the beam current (i.e., different dose per pulse) and pulse width settings. The temporal single pulse shape signals were measured with a 10 µm thick, 4.5 mm2 area SiC detector for different configurations and compared with a well-characterized AC current transformer (ACCT) (which served as the standard monitoring system of the accelerator), and with a second ACCT placed at the same location as the SiC detector (i.e., after the applicator at the irradiation point). The results show a high level of agreement between the signals of the SiC detector and ACCT placed after the applicator at around the irradiation point. This underscores the potential of the SiC detector and the ACCT to be used for monitoring instantaneous dose rates within a pulse. Furthermore, since use of the SiC detector and ACCT are based on different physical principles, they can provide complementary beam information. A combination of the two has the potential to provide insight about a variety of variables of interest for UHDR beams. However, some discrepancies were observed when comparing the SiC signals with the ACCT installed in the LINAC, which increased linearly with decreasing dose per pulse. Further studies are required to better understand these observations.

FLASH radiotherapy is an emerging treatment modality using ultra-high dose rate beams. Much effort has been made to develop suitable dosimeters for reference dosimetry, yet the spatial beam characteristics must also be characterized to enable computerized treatment planning, as well as quality control and service of a treatment delivery device. In conventional radiation therapy, this is commonly achieved by beam profile scans in a water phantom using a point detector. In ultra-high dose rate beams, the delivered dose needed for a set of beam profile scans may exceed the regulatory dose limit specified for a typical treatment room, or degrade components of the scanning system and scanning detector. Point detector scans also cannot quantify the pulse-to-pulse stability of a beam profile. Detector arrays can overcome these challenges, but to date, no detector arrays suitable for ultra-high dose rate beams are commercially available.

The study presents the development and characterization of a two-dimensional detector array for measuring pulse-resolved spatial fluence distributions in real-time and temporal structure of intra-pulse dose rate of ultra-high pulsed dose rate (UHPDR) electron beams used in FLASH radiotherapy.

The performance of the SunPoint 1 diode was evaluated by measuring the response of the EDGE Detector in a 20 MeV UHPDR electron beam with a dose per pulse of 0.04 Gy - 6 Gy at a pulse duration of 1 µs or 1.9 µs, and instantaneous dose rates of 0.040 - 3.2 MGy·s-1. Based on the findings regarding a suitable signal acquisition technique, a PROFILER 2 detector array made of SunPoint 1 diodes was then modified by minimizing trace resistance, applying a reverse bias, and implementing an RC component to each diode to optimize the transfer of the collected charge during a pulse. The resultant "FLASH Profiler" was then tested in the same UHPDR electron beam.

The FLASH Profiler exhibited a linear response within ± 3% deviation over the investigated dose per pulse range. The FLASH Profiler array showed good agreement with the absolute dose measured using a flashDiamond point detector and an integrating current transformer for dose-per-pulse values of up to 6 Gy. The FLASH Profiler was able to measure lateral beam profiles in real-time and on a single-pulse basis. The ability to capture and display the profiles during steering of UHPDR beams was demonstrated. The SunPoint 1 diode was able to measure the pulse duration and the intra-pulse dose rate with a time resolution of 4 ns.

The FLASH Profiler could be used for characterizing UHPDR electron beams and facilitating quality control and beam steering service of electron FLASH irradiators.

Ultra-high dose-rate (FLASH) radiotherapy serves as an ideal procedure to treat tumors efficiently without harming normal tissues and has demonstrated satisfactory antitumor effects in multiple animal tumor models. However, the biological mechanisms of FLASH radiotherapy have not yet been fully elucidated, and the small number of devices delivering FLASH dose rate has limited its wide application. This review summarizes the possible biological mechanisms and antitumor effects of FLASH radiotherapy, its application in nanotherapeutic strategy, as well as its challenges and future development. Furthermore, some valuable guidance for promoting the progress of FLASH radiotherapy in nanotherapeutic strategies are provided.

(1) Background: Ultra-high dose rate (UHDR) radiation therapy needs a reliable dosimetry solution and scintillation detectors are promising candidates. In this study, we characterized an inorganic powder-based scintillation detector under a 9 MeV UHDR electron beam. (2) Methods: A mixture of ZnS:Ag powder and optic glue was coupled to an 8 m Eska GH-4001-P polymethyl methacrylate (PMMA) optical fiber. We evaluated the dependence of the detector on dose per pulse (DPP), pulse repetition frequency (PRF), and pulse width (PW). Additionally, we determined the stability and the reproducibility of the detector. (3) Results: The signal ratio between the PMMA clear optical fiber and the ZnS:Ag scintillator was around 210. ZnS:Ag produced a signal yield 54 times greater than that of a BCF-12 plastic scintillator. Signal variation with PRF changes was under 0.5%. The signal was linear to the integrated dose up to the maximum deliverable dose, 180 Gy. The variation in signal was linear to the change in both PW and DPP. Regarding stability, the standard deviation of 10 consecutive irradiations was 0.83%. For the reproducibility, all daily measurements varied within ±1.5%. (4) Conclusions: These findings show that the ZnS:Ag detector can be used for accurate dosimetry with UHDR beams.

Reference dosimetry in ultra-high dose rate (UHDR) beamlines is significantly hindered by limitations in conventional ionization chamber design. In particular, conventional chambers suffer from severe charge collection efficiency (CCE) degradation in high dose per pulse (DPP) beams.

The aim of this study was to optimize the design and performance of parallel plate ion chambers for use in UHDR dosimetry applications, and evaluate their potential as reference class chambers for calibration purposes. Three chamber designs were produced to determine the influence of the ion chamber response on electrode separation, field strength, and collection volume on the ion chamber response under UHDR and ultra-high dose per pulse (UHDPP) conditions.

Three chambers were designed and produced: the A11-VAR (0.2-1.0 mm electrode gap, 20 mm diameter collector), the A11-TPP (0.3 mm electrode gap, 20 mm diameter collector), and the A30 (0.3 mm electrode gap, 5.4 mm diameter collector). The chambers underwent full characterization using an UHDR 9 MeV electron beam with individually varied beam parameters of pulse repetition frequency (PRF, 10-120 Hz), pulse width (PW, 0.5-4 µs), and pulse amplitude (0.01-9 Gy/pulse). The response of the ion chambers was evaluated as a function of the DPP, PRF, PW, dose rate, electric field strength, and electrode gap.

The chamber response was found to be dependent on DPP and PW, and these dependencies were mitigated with larger electric field strengths and smaller electrode spacing. At a constant electric field strength, we measured a larger CCE as a function of DPP for ion chambers with a smaller electrode gap in the A11-VAR. For ion chambers with identical electrode gap (A11-TPP and A30), higher electric field strengths were found to yield better CCE at higher DPP. A PW dependence was observed at low electric field strengths (500 V/mm) for DPP values ranging from 1 to 5 Gy at PWs ranging from 0.5 to 4 µs, but at electric field strengths of 1000 V/mm and higher, these effects become negligible.

This study confirmed that the CCE of ion chambers depends strongly on the electrode spacing and the electric field strength, and also on the DPP and the PW of the UHDR beam. A significant finding of this study is that although chamber performance does depend on PW, the effect on the CCE becomes negligible with reduced electrode spacing and increased electric field. A CCE of ≥95% was achieved for DPPs of up to 5 Gy with no observable dependence on PW using the A30 chamber, while still achieving an acceptable performance in conventional dose rate beams, opening up the possibility for this type of chamber to be used as a reference class chamber for calibration purposes of electron FLASH beamlines.

This review article synthesizes key findings from studies on the use of diamond dosimeters in advanced radiotherapy techniques, showcasing their applications, challenges, and contributions to enhancing dosimetric accuracy. The article explores various dosimeters, highlighting synthetic diamond dosimeters as potential candidates especially due to their high spatial resolution and negligible ion recombination effect. The clinically validated commercial dosimeter, PTW microDiamond (mD), faces limitations in small fields, proton and hadron therapy and ultra-high dose per pulse (UHDPP) conditions. Variability in reported values for field sizes < $<$ 2 × $\times$ 2cm 2 ${\rm cm}^2$ is noted, reflecting the competition between volume averaging and density perturbation effects. PTW's introduction of flashDiamond (fD) holds promise for dosimetric measurements in UHDPP conditions and is reliable for commissioning ultra-high dose rate (UHDR) electron beam systems, pending the clinical validation of the device. Other advancements in diamond detectors, such as in 3D configurations and real-time dose per pulse x-ray detectors, are considered valuable in overcoming challenges posed by modern radiotherapy techniques, alongside relative dosimetry and pre-treatment verifications. The studies discussed collectively provide a comprehensive overview of the evolving landscape of diamond dosimetry in the field of radiotherapy, and offer insights into future directions for research and development in the field.

Ultra-high dose rate external beam radiotherapy (UHDR-RT) uses dose rates of several tens to thousands of Gy/s, compared with the dose rate of the order of a few Gy/min for conventional radiotherapy techniques, currently used in clinical practice. The use of such dose rate is likely to improve the therapeutic index by obtaining a radiobiological effect, known as the "FLASH" effect. This would maintain tumor control while enhancing tissues protection. To date, this effect has been achieved using beams of electrons, photons, protons, and heavy ions. However, the conditions required to achieve this "FLASH" effect are not well defined, and raise several questions, particularly with regard to the definition of the prescription, including dose fractionation, irradiated volume and the temporal structure of the pulsed beam. In addition, the dose delivered over a very short period induces technical challenges, particularly in terms of detectors, which must be mastered to guarantee safe clinical implementation. IRSN has carried out an in-depth literature review of the UHDR-RT technique, covering various aspects relating to patient radiation protection: the radiobiological mechanisms associated with the FLASH effect, the used temporal structure of the UHDR beams, accelerators and dose control, the properties of detectors to be used with UHDR beams, planning, clinical implementation, and clinical studies already carried out or in progress.

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.

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.

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.

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.

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.

Dosimetry of ultra-high dose rate beams is one of the critical components which is required for safe implementation of FLASH radiotherapy (RT) into clinical practice. In the past years several national and international programmes have emerged with the aim to address some of the needs that are required for translation of this modality to clinics. These involve the establishment of dosimetry standards as well as the validation of protocols and dosimetry procedures. This review provides an overview of recent developments in the field of dosimetry for FLASH RT, with particular focus on primary and secondary standard instruments, and provides a brief outlook on the future work which is required to enable clinical implementation of FLASH RT.

Ultra-high dose-rate 'FLASH' radiotherapy may be a pivotal step forward for cancer treatment, widening the therapeutic window between radiation tumour killing and damage to neighbouring normal tissues. The extent of normal tissue sparing reported in pre-clinical FLASH studies typically corresponds to an increase in isotoxic dose-levels of 5-20%, though gains are larger at higher doses. Conditions currently thought necessary for FLASH normal tissue sparing are a dose-rate ≥40 Gy s-1, dose-per-fraction ≥5-10 Gy and irradiation duration ≤0.2-0.5 s. Cyclotron proton accelerators are the first clinical systems to be adapted to irradiate deep-seated tumours at FLASH dose-rates, but even using these machines it is challenging to meet the FLASH conditions. In this review we describe the challenges for delivering FLASH proton beam therapy, the compromises that ensue if these challenges are not addressed, and resulting dosimetric losses. Some of these losses are on the same scale as the gains from FLASH found pre-clinically. We therefore conclude that for FLASH to succeed clinically the challenges must be systematically overcome rather than accommodated, and we survey physical and pre-clinical routes for achieving this.

FLASH-radiotherapy delivers a radiation beam a thousand times faster compared to conventional radiotherapy, reducing radiation damage in healthy tissues with an equivalent tumor response. Although not completely understood, this radiobiological phenomenon has been proved in several animal models with a spectrum of all kinds of particles currently used in contemporary radiotherapy, especially electrons. However, all the research teams have performed FLASH preclinical studies using industrial linear accelerator or LINAC commonly employed in conventional radiotherapy and modified for the delivery of ultra-high-dose-rate (UHDRs). Unfortunately, the delivering and measuring of UHDR beams have been proved not to be completely reliable with such devices. Concerns arise regarding the accuracy of beam monitoring and dosimetry systems. Additionally, this LINAC totally lacks an integrated and dedicated Treatment Planning System (TPS) able to evaluate the internal dose distribution in the case of in vivo experiments. Finally, these devices cannot modify dose-time parameters of the beam relevant to the flash effect, such as average dose rate; dose per pulse; and instantaneous dose rate. This aspect also precludes the exploration of the quantitative relationship with biological phenomena. The dependence on these parameters need to be further investigated. A promising advancement is represented by a new generation of electron LINAC that has successfully overcome some of these technological challenges. In this review, we aim to provide a comprehensive summary of the existing literature on in vivo experiments using electron FLASH radiotherapy and explore the promising clinical perspectives associated with this technology.

FLASH is an emerging treatment paradigm in radiotherapy (RT) that utilizes ultra-high dose rates (UHDR; >40 Gy)/s) of radiation delivery. Developing advances in technology support the delivery of UHDR using electron and proton systems, as well as some ion beam units (eg, carbon ions), while methods to achieve UHDR with photons are under investigation. The major advantage of FLASH RT is its ability to increase the therapeutic index for RT by shifting the dose response curve for normal tissue toxicity to higher doses. Numerous preclinical studies have been conducted to date on FLASH RT for murine sarcomas, alongside the investigation of its effects on relevant normal tissues of skin, muscle, and bone. The tumor control achieved by FLASH RT of sarcoma models is indistinguishable from that attained by treatment with standard RT to the same total dose. FLASH's high dose rates are able to mitigate the severity or incidence of RT side effects on normal tissues as evaluated by endpoints ranging from functional sparing to histological damage. Large animal studies and clinical trials of canine patients show evidence of skin sparing by FLASH vs. standard RT, but also caution against delivery of high single doses with FLASH that exceed those safely applied with standard RT. Also, a human clinical trial has shown that FLASH RT can be delivered safely to bone metastasis. Thus, data to date support continued investigations of clinical translation of FLASH RT for the treatment of patients with sarcoma. Toward this purpose, hypofractionated irradiation schemes are being investigated for FLASH effects on sarcoma and relevant normal tissues.

We have previously adapted a clinical linear accelerator (Elekta Precise, Elekta AB) for ultra-high dose rate (UHDR) electron delivery. To enhance reliability in future clinical FLASH radiotherapy trials, the aim of this study was to introduce and evaluate an upgraded beam control system and beam tuning process for safe and precise UHDR delivery.

The beam control system is designed to interrupt the beam based on 1) a preset number of monitor units (MUs) measured by a monitor detector, 2) a preset number of pulses measured by a pulse-counting diode, or 3) a preset delivery time. For UHDR delivery, an optocoupler facilitates external control of the accelerator's thyratron trigger pulses. A beam tuning process was established to maximize the output. We assessed the stability of the delivery, and the independent interruption capabilities of the three systems (monitor detector, pulse counter, and timer). Additionally, we explored a novel approach to enhance dosimetric precision in the delivery by synchronizing the trigger pulse with the charging cycle of the pulse forming network (PFN).

Improved beam tuning of gun current and magnetron frequency resulted in average dose rates at the dose maximum at isocenter distance of >160 Gy/s or >200 Gy/s, with or without an external monitor chamber in the beam path, respectively. The delivery showed a good repeatability (standard deviation (SD) in total film dose of 2.2%) and reproducibility (SD in film dose of 2.6%). The estimated variation in DPP resulted in an SD of 1.7%. The output in the initial pulse depended on the PFN delay time. Over the course of 50 measurements employing PFN synchronization, the absolute percentage error between the delivered number of MUs calculated by the monitor detector and the preset MUs was 0.8 ± 0.6% (mean ± SD).

We present an upgraded beam control system and beam tuning process for safe and stable UHDR electron delivery of hundreds of Gy/s at isocenter distance at a clinical linac. The system can interrupt the beam based on monitor units and utilize PFN synchronization for improved dosimetric precision in the dose delivery, representing an important advancement toward reliable clinical FLASH trials.

Accurate dosimetry in Ultra-High Dose Rate (UHDR) beams is challenging because high levels of ion recombination occur within ionisation chambers used as reference dosimeters. A Small-body Portable Graphite Calorimeter (SPGC) exhibiting a dose-rate independent response was built to offer reduced uncertainty on secondary standard dosimetry in UHDR regimes. The aim of this study was to quantify the effect of the geometry and material properties of the device on the dose measurement.

A detailed model of the SPGC was built in the Monte Carlo code TOPAS (v3.6.1) to derive the impurity and gap correction factors, k i m p and k g a p . A dose conversion factor, D w MC / D g MC , was also calculated using FLUKA (v2021.2.0). These factors convert the average dose to its graphite core to the dose-to-water for a 249.7 MeV mono-energetic spot-scanned clinical proton beam. The effect of the surrounding Styrofoam on the dose measurement was examined in the simulations by substituting it for graphite.

The k i m p and k g a p correction factors were 0.9993 ± 0.0002 and 1.0000 ± 0.0001, respectively when the Styrofoam was not substituted, and 1.0037 ± 0.0002 and 0.9999 ± 0.0001, respectively when substituted for graphite. The dose conversion factor was calculated to be 1.0806 ± 0.0001. All uncertainties are Type A.

Impurity and gap correction factors, and the dose conversion factor were calculated for the SPGC in a FLASH proton beam. Separating out the effect of scatter from Styrofoam insulation showed this as the dominating correction factor, amounting to 1.0043 ± 0.0002.

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.