Search

Background: Pre‐clinical ultra‐high dose rate (UHDR) electron irradiations on time scales of 100 ms have demonstrated a remarkable sparing of brain and lung tissues while retaining tumor efficacy when compared to conventional dose rate irradiations. While clinically‐used gantries and intensity modulation techniques are too slow to match such time scales, novel very‐high energy electron (VHEE, 50–250 MeV) radiotherapy (RT) devices using 3D‐conformed broad VHEE beams are designed to deliver UHDR treatments that fulfill these timing requirements. Purpose: To assess the dosimetric plan quality obtained using VHEE‐based 3D‐conformal RT (3D‐CRT) for treatments of glioblastoma and lung cancer patients and compare the resulting treatment plans to those delivered by standard‐of‐care intensity modulated photon RT (IMRT) techniques. Methods: Seven glioblastoma patients and seven lung cancer patients were planned with VHEE‐based 3D‐CRT using 3 to 16 coplanar beams with equidistant angular spacing and energies of 100 and 200 MeV using a forward planning approach. Dose distributions, dose‐volume histograms, coverage (V95%) and homogeneity (HI98%) for the planning target volume (PTV), as well as near‐maximum doses (D2%) and mean doses (Dmean) for organs‐at‐risk (OAR) were evaluated and compared to clinical IMRT plans. Results: Mean differences of V95% and HI98% of all VHEE plans were within 2% or better of the IMRT reference plans. Glioblastoma plan dose metrics obtained with VHEE configurations of 200 MeV and 3–16 beams were either not significantly different or were significantly improved compared to the clinical IMRT reference plans. All OAR plan dose metrics evaluated for VHEE plans created using 5 beams of 100 MeV were either not significantly different or within 3% on average, except for Dmean for the body, Dmean for the brain, D2% for the brain stem, and D2% for the chiasm, which were significantly increased by 1, 2, 6, and 8 Gy, respectively (however below clinical constraints). Similarly, the dose metrics for lung cancer patients were also either not significantly different or were significantly improved compared to the reference plans for VHEE configurations with 200 MeV and 5 to 16 beams with the exception of D2% and Dmean to the spinal canal (however below clinical constraints). For the lung cancer cases, the VHEE configurations using 100 MeV or only 3 beams resulted in significantly worse dose metrics for some OAR. Differences in dose metrics were, however, strongly patient‐specific and similar for some patient cases. Conclusions: VHEE‐based 3D‐CRT may deliver conformal treatments to simple, mostly convex target shapes in the brain and the thorax with a limited number of critical adjacent OAR using a limited number of beams (as low as 3 to 7). Using such treatment techniques, a dosimetric plan quality comparable to that of standard‐of‐care IMRT can be achieved. Hence, from a treatment planning perspective, 3D‐conformal UHDR VHEE treatments delivered on time scales of 100 ms represent a promising candidate technique for the clinical transfer of the FLASH effect. [ABSTRACT FROM AUTHOR]

Purpose: Normal tissue (NT) sparing by ultra‐high dose rate (UHDR) irradiations compared to conventional dose rate (CONV) irradiations while being isotoxic to the tumor has been termed "FLASH effect" and has been observed when large doses per fraction (d ≳ 5 Gy) have been delivered. Since hypofractionated treatment schedules are known to increase toxicities of late‐reacting tissues compared to normofractionated schedules for many clinical scenarios at CONV dose rates, we developed a formalism based on the biologically effective dose (BED) to assess the minimum magnitude of the FLASH effect needed to compensate the loss of late‐reacting NT sparing when reducing the number of fractions compared to a normofractionated CONV treatment schedule while remaining isoeffective to the tumor. Methods: By requiring the same BED for the tumor, we derived the "break‐even NT sparing weighting factor" WBE for the linear‐quadratic (LQ) and LQ‐linear (LQ‐L) models for an NT region irradiated at a relative dose r (relative to the prescribed dose per fraction d to the tumor). WBE was evaluated numerically for multiple values of d and r, and for different tumor and NT α/β‐ratios. WBE was compared against currently available experimental data on the magnitude of the NT sparing provided by the FLASH effect for single fraction doses. Results: For many clinically relevant scenarios, WBE decreases steeply initially for d > 2 Gy for late‐reacting tissues with (α/β)NT ≈ 3 Gy, implying that a significant NT sparing by the FLASH effect (between 15% and 30%) is required to counteract the increased radiobiological damage experienced by late‐reacting NT for hypofractionated treatments with d < 10 Gy compared to normofractionated treatments that are equieffective to the tumor. When using the LQ model with generic α/β‐ratios for tumor and late‐reacting NT of (α/β)T = 10 Gy and (α/β)NT = 3 Gy, respectively, most currently available experimental evidence about the magnitude of NT sparing by the FLASH effect suggests no net NT sparing benefit for hypofractionated FLASH radiotherapy (RT) in the high‐dose region when compared with WBE. Instead, clinical indications with more similar α/β‐ratios of the tumor and dose‐limiting NT toxicities [i.e., (α/β)T ≈ (α/β)NT], such as prostate treatments, are generally less penalized by hypofractionated treatments and need consequently smaller magnitudes of NT sparing by the FLASH effect to achieve a net benefit. For strongly hypofractionated treatments (>10–15 Gy/fraction), the LQ‐L model predicts, unlike the LQ model, a larger WBE suggesting a possible benefit of strongly hypofractionated FLASH RT, even for generic α/β‐ratios of (α/β)T = 10 Gy and (α/β)NT = 3 Gy. However, knowledge on the isoeffect scaling for high doses per fraction (≳10 Gy/fraction) and its modeling is currently limited and impedes accurate and reliable predictions for such strongly hypofractionated treatments. Conclusions: We developed a formalism that quantifies the minimal NT sparing by the FLASH effect needed to compensate for hypofractionation, based on the LQ and LQ‐L models. For a given hypofractionated UHDR treatment scenario and magnitude of the FLASH effect, the formalism predicts if a net NT sparing benefit is expected compared to a respective normofractionated CONV treatment. [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 derive the isodose line R relative to the prescription dose below which irradiated normal tissue (NT) regions benefit from a hypofractionated schedule with an isoeffective dose to the tumor. To apply the formalism to clinical case examples. Methods: From the standard biologically effective dose (BED) equation based on the linear‐quadratic (LQ) model, the BED of an NT that receives a relative proportion r of the prescribed dose per fraction for a given α/β‐ratio of the tumor, (α/β)T, and NT, (α/β)NT, is derived for different treatment schedules while keeping the BED to the tumor constant. Based on this, the "break‐even" isodose line R is then derived. The BED of NT regions that receive doses below R decreases for more hypofractionated treatment schedules, and hence a lower risk for NT injury is predicted in these regions. To assess the impact of a linear behavior of BED for high doses per fraction (>6 Gy), we evaluated BED also using the LQ‐linear (LQ‐L) model. Results: The formalism provides the equations to derive the BED of an NT as function of dose per fraction for an isoeffective dose to the tumor and the corresponding break‐even isodose line R. For generic α/β‐ratios of (α/β)T = 10 Gy and (α/β)NT = 3 Gy and homogeneous dose in the target, R is 30%. R is doubling for stereotactic treatments for which tumor control correlates with the maximum dose of 100% instead of the encompassing isodose line of 50%. When using the LQ‐L model, the notion of a break‐even dose level R remains valid up to about 20 Gy per fraction for generic α/β‐ratios and DT=2(α/β). Conclusions: The formalism may be used to estimate below which relative isodose line R there will be a differential sparing of NT when increasing hypofractionation. More generally, it allows to assess changes of the therapeutic index for sets of isoeffective treatment schedules at different relative dose levels compared to a reference schedule in a compact manner. [ABSTRACT FROM AUTHOR]

Purpose: To implement and validate a beam current transformer as a passive monitoring device on a pulsed electron beam medical linear accelerator (LINAC) for ultra‐high dose rate (UHDR) irradiations in the operational range of at least 3 Gy to improve dosimetric procedures currently in use for FLASH radiotherapy (FLASH‐RT) studies. Methods: Two beam current transformers (BCTs) were placed at the exit of a medical LINAC capable of UHDR irradiations. The BCTs were validated as monitoring devices by verifying beam parameters consistency between nominal values and measured values, determining the relationship between the charge measured and the absorbed dose, and checking the short‐ and long‐term stability of the charge‐absorbed dose ratio. Results: The beam parameters measured by the BCTs coincide with the nominal values. The charge‐dose relationship was found to be linear and independent of pulse width and frequency. Short‐ and long‐term stabilities were measured to be within acceptable limits. Conclusions: The BCTs were implemented and validated on a pulsed electron beam medical LINAC, thus improving current dosimetric procedures and allowing for a more complete analysis of beam characteristics. BCTs were shown to be a valid method for beam monitoring for UHDR (and therefore FLASH) experiments. [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: To investigate the impact of respiratory motion in the treatment margins for lung SBRT frameless treatments and to validate our treatment margins using 4D CBCT data analysis. Methods: Two hundred and twenty nine fractions with early stage NSCLC were retrospectively analyzed. All patients were treated in frameless and free breathing conditions. The treatment margins were calculated according to van Herk equation in Mid‐Ventilation. For each fraction, three 4D CBCT scans, pre‐ and postcorrection, and posttreatment, were acquired to assess target baseline shift, target localization accuracy and intra‐fraction motion errors. A bootstrap analysis was performed to assess the minimum number of patients required to define treatment margins. Results: The retrospectively calculated target‐baseline shift, target localization accuracy and intra‐fraction motion errors agreed with the literature. The best tailored margins to our cohort of patients were retrospectively computed and resulted in agreement with already published data. The bootstrap analysis showed that fifteen patients were enough to assess treatment margins. Conclusions: The treatment margins applied to our patient's cohort resulted in good agreement with the retrospectively calculated margins based on 4D CBCT data. Moreover, the bootstrap analysis revealed to be a promising method to verify the reliability of the applied treatment margins for safe lung SBRT delivery. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to calculate dose distributions from CyberKnife image‐guided radiation therapy (IGRT) for brain, H&N, lung, and pelvis treatment regions and use them to extract the corresponding effective dose and estimate‐related risk. Methods: We developed a CyberKnife IGRT kV beam model in a standard treatment planning system and validated it against measurements in heterogeneous phantoms. Five brain, five head and neck, five thorax, and 10 (five male and five female) pelvis patient computed tomographies (CTs) were contoured. The dose distribution resulting from different CyberKnife IGRT protocols was calculated. From them, the effective dose was calculated according to ICRP publication Nr 103, using the average dose to contoured organs. The corresponding risk factors were calculated. Entrance surface dose (ESD) was also calculated and compared with existing data. Results: The maximum effective dose produced by CyberKnife IGRT protocols was 0.8 mSv (brain), 1.9 mSv (H&N), 20.2 (pelvis), and 42.4 mSv (thorax) per fraction for a risk estimate of 0.004% (brain), 0.01% (H&N), 0.1% (pelvis), and 0.2% (thorax). Calculated ESD were compatible with existing data. Conclusions: Dose calculation models for CyberKnife IGRT kV beams were implemented in a clinical treatment planning system and validated in water and heterogeneous phantoms. We determined the effective dose and the related risk estimate resulting from CyberKnife IGRT protocols for brain, head and neck, thorax, and pelvis cases. The effective doses calculated for CyberKnife IGRT protocols were similar to those obtained for cone beam CT protocols on conventional C‐arm linear accelerators, except for extreme irradiation conditions for thorax cases (140 kV X‐ray tube tension). [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to calculate dose distributions from CyberKnife image‐guided radiation therapy (IGRT) for brain, H&N, lung, and pelvis treatment regions and use them to extract the corresponding effective dose and estimate‐related risk. Methods: We developed a CyberKnife IGRT kV beam model in a standard treatment planning system and validated it against measurements in heterogeneous phantoms. Five brain, five head and neck, five thorax, and 10 (five male and five female) pelvis patient computed tomographies (CTs) were contoured. The dose distribution resulting from different CyberKnife IGRT protocols was calculated. From them, the effective dose was calculated according to ICRP publication Nr 103, using the average dose to contoured organs. The corresponding risk factors were calculated. Entrance surface dose (ESD) was also calculated and compared with existing data. Results: The maximum effective dose produced by CyberKnife IGRT protocols was 0.8 mSv (brain), 1.9 mSv (H&N), 20.2 (pelvis), and 42.4 mSv (thorax) per fraction for a risk estimate of 0.004% (brain), 0.01% (H&N), 0.1% (pelvis), and 0.2% (thorax). Calculated ESD were compatible with existing data. Conclusions: Dose calculation models for CyberKnife IGRT kV beams were implemented in a clinical treatment planning system and validated in water and heterogeneous phantoms. We determined the effective dose and the related risk estimate resulting from CyberKnife IGRT protocols for brain, head and neck, thorax, and pelvis cases. The effective doses calculated for CyberKnife IGRT protocols were similar to those obtained for cone beam CT protocols on conventional C‐arm linear accelerators, except for extreme irradiation conditions for thorax cases (140 kV X‐ray tube tension). [ABSTRACT FROM AUTHOR]

Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy·s-1). Compared with conventional dose-rate (CONV; 0.07-0.1 Gy·s-1) modalities, we showed that FLASH did not cause radiation-induced deficits in learning and memory in mice. Moreover, 6 months after exposure, CONV caused permanent alterations in neurocognitive end points, whereas FLASH did not induce behaviors characteristic of anxiety and depression and did not impair extinction memory. Mechanistic investigations showed that increasing the oxygen tension in the brain through carbogen breathing reversed the neuroprotective effects of FLASH, while radiochemical studies confirmed that FLASH produced lower levels of the toxic reactive oxygen species hydrogen peroxide. In addition, FLASH did not induce neuroinflammation, a process described as oxidative stress-dependent, and was also associated with a marked preservation of neuronal morphology and dendritic spine density. The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: The Oriatron eRT6 is an experimental high dose‐per‐pulse linear accelerator (linac) which was designed to deliver an electron beam with variable dose‐rates, ranging from a few Gy/min up to hundreds of Gy/s. It was built to study the radiobiological effects of high dose‐per‐pulse/dose‐rate electron beam irradiation, in the context of preclinical and cognitive studies. In this work, we report on the commissioning and beam monitoring of the Oriatron eRT6 prototype linac. Materials and Methods: The beam was characterized in different steps. The output stability was studied by performing repeated measurements over a period of 20 months. The relative output variations caused by changing beam parameters, such as the temporal electron pulse width, the pulse repetition frequency and the pulse amplitude were also analyzed. Finally, depth dose curves and field sizes were measured for two different beam settings, resulting in one beam with a conventional radiotherapy dose‐rate and one with a much higher dose‐rate. Measurements were performed with Gafchromic EBT3 films and with a PTW Advanced Markus ionization chamber. In addition, we developed a beam current monitoring system based on the signals from an induction torus positioned at the beam exit of the waveguide and from a graphite beam collimator. Results: The stability of the output over repeated measurements was found to be good, with a standard deviation smaller than 1%. However, non‐negligible day‐to‐day variations of the beam output were observed. Those output variations showed different trends depending on the dose‐rate. The analysis of the relative output variation as a function of various beam parameters showed that in a given configuration, the dose‐rate could be reliably varied over three orders of magnitude. Interdependence effects on the output variation between the parameters were also observed. The beam energy and field size were found to be slightly dose‐rate‐dependent and suitable mainly for small animal irradiation. The beam monitoring system was able to measure in a reproducible way the total charge of electrons that exit the machine, as long as the electron pulse amplitude remains above a given threshold. Furthermore, we were able to relate the charge measured with the monitoring system to the absorbed dose in a solid water phantom. Conclusion: The Oriatron eRT6 was successfully commissioned for preclinical use and is currently in full operation, with studies being performed on the radiobiological effects of high dose‐per‐pulse irradiation. [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]

Purpose The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose-per-pulse linear accelerator (linac), capable of delivering electron beams with a mean dose-rate ( Ḋ m) ranging from 0.07 to 3000 Gy/s and a dose-rate in pulse ( Ḋ p) of up to 8 × 106 Gy/s. To do this, we evaluated the overall uncertainties in EBT3 film dosimetry as well as the energy and dose-rate dependence of their response. Material and methods Our dosimetric system was composed of EBT3 Gafchromic films in combination with a flatbed scanner and was calibrated against an ionization chamber traceable to primary standard. All sources of uncertainties in EBT3 dosimetry were carefully analyzed using irradiations at a clinical radiotherapy linac. Energy dependence was investigated with the same machine by acquiring and comparing calibration curves for three different beam energies (4, 8 and 12 MeV), for doses between 0.25 and 30 Gy. Ḋ m dependence was studied at the clinical linac by changing the pulse repetition frequency ( f) of the beam in order to vary Ḋ m between 0.55 and 4.40 Gy/min, while Ḋ p dependence was probed at the prototype machine for Ḋ p ranging from 7 × 103 to 8 × 106 Gy/s. Ḋ p dependence was first determined by studying the correlation between the dose measured by films and the charge of electrons measured at the exit of the machine by an induction torus. Furthermore, we compared doses from the films to independently calibrated thermo-luminescent dosimeters (TLD) that have been reported as being dose-rate independent up to such high dose-rates. Results We report that uncertainty below 4% ( k = 2) can be achieved in the dose range between 3 and 17 Gy. Results also demonstrated that EBT3 films did not display any detectable energy dependence for electron beam energies between 4 and 12 MeV. No Ḋ m dependence was found either. In addition, we obtained excellent consistency between films and TLDs over the entire Ḋ p range attainable at the prototype linac confirming the absence of any dose-rate dependence within the investigated range (7 × 103 to 8 × 106 Gy/s). This aspect was further corroborated by the linear relationship between the dose-per-pulse ( D p ) measured by films and the charge per pulse ( C p) measured at the prototype linac exit. Conclusion Our study shows that the use of EBT3 Gafchromic films can be extended to reference dosimetry in pulsed electron beams with a very high dose rate. The measurement results are associated with an overall uncertainty below 4% ( k = 2) and are dose-rate and energy independent. [ABSTRACT FROM AUTHOR]