Electron beam radiotherapy for the management of squamous cell carcinoma of the anal margin.

PURPOSE AND OBJECTIVE: Squamous cell carcinoma of the anal margin (SCCAM) is an uncommon lesion that comprises one-third to a quarter of all anal squamous cell carcinoma. Treatment involves surgery or exclusive radiotherapy for small tumours, whereas the preferred treatment for larger tumours is chemoradiotherapy. In our department, selected patients with SCCAM are treated with electron beam radiotherapy using one perineal field. The present study evaluates this strategy. MATERIAL AND METHODS: All consecutive patients with SCCAM and treated with electron beam radiotherapy from 2012 to 2022 were included. Data were retrospectively extracted from the medical records and analysed descriptively. Local control (LC) and overall survival (OS) were analysed using Kaplan-Meier statistics. RESULTS: Forty patients were evaluated. Primary radiotherapy was delivered in 35 (87.5%) patients. Five (12.5%) patients had postoperative radiotherapy. Median prescription dose was 60.0 (range 45.0-60.2) Gy in 28 (range 10-30) fractions delivered with 8 (range 4-18) MeV using a standard circular aperture and bolus. At a median follow-up of 73 (range 9-135) months, 7 (17.5%) patients were diagnosed with local recurrences. The 5-year LC rate was 84.3% (95% CI: 71.4%-97.2%). Analysis of LC according to T-stage revealed a 5-year LC of 100% (95% CI: 100%-100%) in T1 tumours compared to 57.0% (95% CI: 27.4%-86.6%) in T2 tumours (p < 0.001). 5-year OS was 91.6% (95% CI: 83.0%-100%). Late grade 3 toxicity included ulceration in the skin and subcutis in 2 (5.0%) patients. INTEPRETATION: Electron beam radiotherapy enables the delivery of 'eye-guided' radiotherapy directly to the tumour. LC is good in patients with T1 tumours. Patients with T2 tumours have less satisfactory LC and should be treated with chemoradiotherapy. Electron beam radiotherapy enables the delivery of "eye-guided" RT directly to the tumour. LC is excellent in patients with T1 tumours. Patients with T2 tumours have less satisfactory LC and should be treated with chemoradiotherapy.

Robust optimization and assessment of dynamic trajectory and mixed-beam arc radiotherapy: a preliminary study.

Objective.Dynamic trajectory radiotherapy (DTRT) and dynamic mixed-beam arc therapy (DYMBARC) exploit non-coplanarity and, for DYMBARC, simultaneously optimized photon and electron beams. Margin concepts to account for set-up uncertainties during delivery are ill-defined for electron fields. We develop robust optimization for DTRT&DYMBARC and compare dosimetric plan quality and robustness for both techniques and both optimization strategies for four cases.Approach.Cases for different treatment sites and clinical target volume (CTV) to planning target volume (PTV) margins,m, were investigated. Dynamic gantry-table-collimator photon paths were optimized to minimize PTV/organ-at-risk (OAR) overlap in beam's-eye-view and minimize potential photon multileaf collimator (MLC) travel. For DYMBARC plans, non-isocentric partial electron arcs or static fields with shortened source-to-surface distance (80 cm) were added. Direct aperture optimization (DAO) was used to simultaneously optimize MLC-based intensity modulation for both photon and electron beams yielding deliverable PTV-based DTRT&DYMBARC plans. Robust-optimized plans used the same paths/arcs/fields. DAO with stochastic programming was used for set-up uncertainties with equal weights in all translational directions and magnitudeδsuch thatm= 0.7δ. Robust analysis considered random errors in all directions with or without an additional systematic error in the worst 3D direction for the adjacent OARs.Main results.Electron contribution was 7%-41% of target dose depending on the case and optimization strategy for DYMBARC. All techniques achieved similar CTV coverage in the nominal (no error) scenario. OAR sparing was overall better in the DYMBARC plans than in the DTRT plans and DYMBARC plans were generally more robust to the considered uncertainties. OAR sparing was better in the PTV-based than in robust-optimized plans for OARs abutting or overlapping with the target volume, but more affected by uncertainties.Significance.Better plan robustness can be achieved with robust optimization than with margins. Combining electron arcs/fields with non-coplanar photon trajectories further improves robustness and OAR sparing.

Feasibility of dose calculation for treatment plans using electron density maps from a novel dual-layer detector spectral CT simulator.

BACKGROUND: Conventional single-energy CT can only provide a raw estimation of electron density (ED) for dose calculation by developing a calibration curve that simply maps the HU values to ED values through their correlations. Spectral CT, also known as dual-energy CT (DECT) or multi-energy CT, can generate a series of quantitative maps, such as ED maps. Using spectral CT for radiotherapy simulations can directly acquire ED information without developing specific calibration curves. The purpose of this study is to assess the feasibility of utilizing electron density (ED) maps generated by a novel dual-layer detector spectral CT simulator for dose calculation in radiotherapy treatment plans. METHODS: 30 patients from head&neck, chest, and pelvic treatment sites were selected retrospectively, and all of them underwent spectral CT simulation. Treatment plans based on conventional CT images were transplanted to ED maps with the same structure set, including planning target volume (PTV) and organs at risk (OARs), and the dose distributions were then recalculated. The differences in dose and volume histogram (DVH) parameters of the PTV and OARs between the two types of plans were analyzed and compared. Besides, gamma analysis between these plans was performed by using MEPHYSTO Navigator software. RESULTS: In terms of PTV, the homogeneity index (HI), gradient index (GI), D2%, D98%, and Dmean showed no significant difference between conventional plans and ED plans. For OARs, statistically significant differences were observed in parotids D50%, brainstem in head&neck plans, spinal cord in chest plans and rectum D50% in pelvic plans, whereas the variance remained minor. For the rest, the DVH parameters exhibited no significant difference between conventional plans and ED plans. All of the mean gamma passing rates (GPRs) of gamma analysis were higher than 90%. CONCLUSION: Compared to conventional treatment plans relying on CT images, plans utilizing ED maps demonstrated similar dosimetric quality. However, the latter approach enables direct utilization in dose calculation without the requirements of establishing and selecting a specific Hounsfield unit (HU) to ED calibration curve, providing an advantage in clinical applications.

A scattering-foil free electron beam to increase dose rate for total skin electron therapy (TSET).

BACKGROUND: Electron beams are used at extended distances ranging between 300 to 700 cm to uniformly cover the entirety of the patient's skin for total skin electron therapy (TSET). Even with electron beams utilizing the high dose rate total skin electron (HDTSe) mode from the Varian 23iX or TrueBeam accelerators, the dose rate is only 2500 cGy/min at source-to-surface distance (SSD) = 100 cm. At extended distances, the decrease in dose rate leads to long beam delivery times that can limit or even prevent the use of the treatment for patients who, in their weakened condition, may be unable to stand on their own for extended periods of time. Previously, to increase dose rate, a customized 6 MeV electron beam was created by removing the x-ray target, flattening filter, beam monitor chamber, and so forth. from the beam path (Chen, et at IJROBP 59, 2004) for TSET. Using this scattering-foil free (SFF) electron beam requires the treatment distance be extended to 700 cm to achieve dose uniformity from the single beam. This room size requirement has limited the widespread use of the 6 MeV-SFF beam. PURPOSE: This study explores an application of a dual-field technique with a 6 MeV-SFF beam to provide broad and uniform electron fields to reduce the treatment distances in order to overcome treatment room size limitations. METHODS: The EGSnrc system was used to generate incident beams. Gantry angles between 6 MeV-SFF dual-fields were optimized to achieve the similar patient skin dose distribution resulting from a standard 6 MeV-HDTSe dual-field configuration. The patient skin dose comparisons were performed based on the patient treatment setup geometries using dose-volume-histograms. RESULTS: Similar dose coverage can be achieved between 6 MeV-SFF and 6 MeV-HDTSe beams by reducing gantry angles between dual-field geometries by 8° and 7° at treatment distances of 400 and 500 cm, respectively. To achieve 95% mean dose to the first 5 mm of skin depth in the torso area, the mean dose to depths of 5-10 mm and 10-15 mm below the skin surface was 74% (74%) and 49% (50%) of the prescribed dose when using 6 MeV-SFF (6 MeV-HDTSe) beam, respectively. CONCLUSIONS: The 6 MeV-SFF electron beam is feasible to provide similar TSET skin dose coverage at SSD ≥ 400 cm using a dual-field technique. The dose rate of the 6 MeV-SFF beam is about 4 times that of current available 6 MeV-HDTSe beams at treatment distances of 400-500 cm, which significantly shortens the treatment beam-on time and makes TSET available to patients in weakened conditions.

First in vitro measurement of VHEE relative biological effectiveness (RBE) in lung and prostate cancer cells using the ARES linac at DESY.

Very high energy electrons (VHEE) are a potential candidate for radiotherapy applications. This includes tumours in inhomogeneous regions such as lung and prostate cancers, due to the insensitivity of VHEE to inhomogeneities. This study explores how electrons in the VHEE range can be used to perform successful in vitro radiobiological studies. The ARES (accelerator research experiment at SINBAD) facility at DESY, Hamburg, Germany was used to deliver 154 MeV electrons to both prostate (PC3) and lung (A549) cancer cells in suspension. Dose was delivered to samples with repeatability and uniformity, quantified with Gafchromic film. Cell survival in response to VHEE was measured using the clonogenic assay to determine the biological effectiveness of VHEE in cancer cells for the first time using this method. Equivalent experiments were performed using 300 kVp X-rays, to enable VHEE irradiated cells to be compared with conventional photons. VHEE irradiated cancer cell survival was fitted to the linear quadratic (LQ) model (R2 = 0.96-0.97). The damage from VHEE and X-ray irradiated cells at doses between 1.41 and 6.33 Gy are comparable, suggesting similar relative biological effectiveness (RBE) between the two modalities. This suggests VHEE is as damaging as photon radiotherapy and therefore could be used to successfully damage cancer cells during radiotherapy. The RBE of VHEE was quantified as the relative doses required for 50% (D0.5) and 10% (D0.1) cell survival. Using these values, VHEE RBE was measured as 0.93 (D0.5) and 0.99 (D0.1) for A549 and 0.74 (D0.5) and 0.93 (D0.1) for PC3 cell lines respectively. For the first time, this study has shown that 154 MeV electrons can be used to effectively kill lung and prostate cancer cells, suggesting that VHEE would be a viable radiotherapy modality. Several studies have shown that VHEE has characteristics that would offer significant improvements over conventional photon radiotherapy for example, electrons are relatively easy to steer and can be used to deliver dose rapidly and with high efficiency. Studies have shown improved dose distribution with VHEE in treatment plans, in comparison to VMAT, indicating that VHEE can offer improved and safer treatment plans with reduced side effects. The biological response of cancer cells to VHEE has not been sufficiently studied as of yet, however this initial study provides some initial insights into cell damage. VHEE offers significant benefits over photon radiotherapy and therefore more studies are required to fully understand the biological effectiveness of VHEE.

Plastic scintillator-based dosimeters for ultra-high dose rate (UHDR) electron radiotherapy.

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.

A quantitative assessment of Geant4 for predicting the yield and distribution of positron-emitting fragments in ion beam therapy.

Objective.To compare the accuracy with which different hadronic inelastic physics models across ten Geant4 Monte Carlo simulation toolkit versions can predict positron-emitting fragments produced along the beam path during carbon and oxygen ion therapy.Approach.Phantoms of polyethylene, gelatin, or poly(methyl methacrylate) were irradiated with monoenergetic carbon and oxygen ion beams. Post-irradiation, 4D PET images were acquired and parent11C,10C and15O radionuclides contributions in each voxel were determined from the extracted time activity curves. Next, the experimental configurations were simulated in Geant4 Monte Carlo versions 10.0 to 11.1, with three different fragmentation models-binary ion cascade (BIC), quantum molecular dynamics (QMD) and the Liege intranuclear cascade (INCL++) - 30 model-version combinations. Total positron annihilation and parent isotope production yields predicted by each simulation were compared between simulations and experiments using normalised mean squared error and Pearson cross-correlation coefficient. Finally, we compared the depth of the maximum positron annihilation yield and the distal point at which the positron yield decreases to 50% of peak between each model and the experimental results.Main results.Performance varied considerably across versions and models, with no one version/model combination providing the best prediction of all positron-emitting fragments in all evaluated target materials and irradiation conditions. BIC in Geant4 10.2 provided the best overall agreement with experimental results in the largest number of test cases. QMD consistently provided the best estimates of both the depth of peak positron yield (10.4 and 10.6) and the distal 50%-of-peak point (10.2), while BIC also performed well and INCL generally performed the worst across most Geant4 versions.Significance.The best predictions of the spatial distribution of positron annihilations and positron-emitting fragment production along the beam path during carbon and oxygen ion therapy was obtained using Geant4 10.2.p03 with BIC or QMD. These version/model combinations are recommended for future heavy ion therapy research.

Breast conserving surgery with intraoperative electron beam radiation therapy for low-risk breast cancer: Five-year follow-up of 306 patients.

Recent studies have reported a higher than expected risk of ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) and a single dose of electron beam intra-operative radiotherapy (IORT). This finding was the rationale to perform a retrospective single center cohort study evaluating the oncologic results of consecutive patients treated with BCS and IORT. Women were eligible if they had clinical low-risk (N0, ≤2 cm unifocal, Bloom and Richardson grade 1-2), estrogen receptor-positive and human-epidermal-growth-factor-receptor-2-negative breast cancer. Prior to BCS, pN0 status was determined by sentinel lymph node biopsy. Data on oncologic follow-up were analyzed. Between 2012 and 2019, 306 consecutive patients were treated and analyzed, with a median age of 67 (50-86) years at diagnosis. Median follow-up was 60 (8-120) months. Five-year cumulative risk of IBTR was 13.4% (95% confidence interval [CI] 9.4-17.4). True in field recurrence was present in 3.9% of the patients. In 4.6% of the patients, the IBRT was classified as a local recurrence due to seeding of tumor cells in the cutis or subcutis most likely related to percutaneous biopsy. In 2.9% of the patients, the IBRT was a new outfield primary tumor. Three patients had a regional lymph node recurrence and two had distant metastases as first event. One breast cancer-related death was observed. Estimated 5-year overall survival was 89.8% (95% CI 86.0-93.6). In conclusion, although some of IBTR cases could have been prevented by adaptations in biopsy techniques and patient selection, BCS followed by IORT was associated with a substantial risk of IBTR.

The effect of electron backscatter and charge build up in media on beam current transformer signal for ultra-high dose rate (FLASH) electron beam monitoring.

Objective.Beam current transformers (BCT) are promising detectors for real-time beam monitoring in ultra-high dose rate (UHDR) electron radiotherapy. However, previous studies have reported a significant sensitivity of the BCT signal to changes in source-to-surface distance (SSD), field size, and phantom material which have until now been attributed to the fluctuating levels of electrons backscattered within the BCT. The purpose of this study is to evaluate this hypothesis, with the goal of understanding and mitigating the variations in BCT signal due to changes in irradiation conditions.Approach.Monte Carlo simulations and experimental measurements were conducted with a UHDR-capable intra-operative electron linear accelerator to analyze the impact of backscattered electrons on BCT signal. The potential influence of charge accumulation in media as a mechanism affecting BCT signal perturbation was further investigated by examining the effects of phantom conductivity and electrical grounding. Finally, the effectiveness of Faraday shielding to mitigate BCT signal variations is evaluated.Main Results.Monte Carlo simulations indicated that the fraction of electrons backscattered in water and on the collimator plastic at 6 and 9 MeV is lower than 1%, suggesting that backscattered electrons alone cannot account for the observed BCT signal variations. However, our experimental measurements confirmed previous findings of BCT response variation up to 15% for different field diameters. A significant impact of phantom type on BCT response was also observed, with variations in BCT signal as high as 14.1% when comparing measurements in water and solid water. The introduction of a Faraday shield to our applicators effectively mitigated the dependencies of BCT signal on SSD, field size, and phantom material.Significance.Our results indicate that variations in BCT signal as a function of SSD, field size, and phantom material are likely driven by an electric field originating in dielectric materials exposed to the UHDR electron beam. Strategies such as Faraday shielding were shown to effectively prevent these electric fields from affecting BCT signal, enabling reliable BCT-based electron UHDR beam monitoring.

Dosimetric validation of intensity-modulated bolus electron conformal therapy planning and delivery using an anthropomorphic cylindrical head phantom.

PURPOSE: This work investigated the dosimetric accuracy of the intensity-modulated bolus electron conformal therapy (IM-BECT) planning and delivery process using the decimal ElectronRT (eRT) treatment planning system. METHODS: An IM-BECT treatment plan was designed using eRT for a cylindrical, anthropomorphic retromolar trigone phantom. Treatment planning involved specification of beam parameters and design of a variable thickness wax bolus and Passive Radiotherapy Intensity Modulator for Electrons (PRIME) device, which was comprised of 33 tungsten island blocks of discrete diameters from 0.158 to 0.223 cm (Intensity Reduction Factors from 0.937 to 0.875, respectively) inside a 10.1 × 6.7 cm2 copper cutout. For comparison of calculation accuracy, a BECT plan was generated by copying the IM-BECT plan and removing the intensity modulation. For both plans, a 16 MeV electron beam was used with 104.7 cm source-to-surface distance to bolus. In-phantom TLD-100 measurements (N = 47) were compared with both eRT planned dose distributions, which used the pencil beam redefinition algorithm with modifications for passive electron intensity modulation (IM-PBRA). Dose difference and distance to agreement (DTA) metrics were computed for each measurement point. RESULTS: Comparison of measured dose distributions with planned dose distributions yielded dose differences (calculated minus measured) characterized by a mean and standard deviation of -0.36% ± 1.64% for the IM-BECT plan, which was similar to -0.36% ± 1.90% for the BECT plan. All dose measurements were within 5% of the planned dose distribution, with both the BECT and IM-BECT measurement sets having 46/47 (97.8%) points within 3% or within 3 mm of the respective treatment plans. CONCLUSIONS: It was found that the IM-BECT treatment plan generated using eRT was sufficiently accurate for clinical use when compared to TLD measurements in a cylindrical, anthropomorphic phantom, and was similarly accurate to the BECT treatment plan in the same phantom.

Technical note: A comparison of in-house 3D-printed and commercially available patient-specific skin collimators for use with electron beam therapy.

PURPOSE: Skin collimation is a useful tool in electron beam therapy (EBT) to decrease the penumbra at the field edge and minimize dose to nearby superficial organs at risk (OARs), but manually fabricating these collimation devices in the clinic to conform to the patient's anatomy can be a difficult and time intensive process. This work compares two types of patient-specific skin collimation (in-house 3D printed and vendor-provided machined brass) using clinically relevant metrics. METHODS: Attenuation measurements were performed to determine the thickness of each material needed to adequately shield both 6 and 9 MeV electron beams. Relative and absolute dose planes at various depths were measured using radiochromic film to compare the surface dose, flatness, and penumbra of the different skin collimation materials. RESULTS: Clinically acceptable thicknesses of each material were determined for both 6 and 9 MeV electron beams. Field width, flatness, and penumbra results between the two systems were very similar and significantly improved compared to measurements performed with no surface collimation. CONCLUSION: Both skin collimation methods investigated in this work generate sharp penumbras at the field edge and can minimize dose to superficial OARs compared to treatment fields with no surface collimation. The benefits of skin collimation are greatest for lower energy electron beams, and the benefits decrease as the measurement depth increases. Using bolus with skin collimation is recommended to avoid surface dose enhancement seen with collimators placed on the skin surface. Ultimately, the appropriate choice of material will depend on the desire to create these devices in-house or outsource the fabrication to a vendor.

Planar dose calculation of electron therapy.

Purpose.The aim of this study is to determine the planar dose distribution of irregularly-shaped electron beams at their maximum dose depth (zmax) using the modied lateral build-up ratio (LBR) and curve-fitting methods.Methods.Circular and irregular cutouts were created using Cerrobend alloy for a 14 × 14 cm2applicator. Percentage depth dose (PDD) at the standard source-surface-distance (SSD = 100 cm) and point dose at different SSD were measured for each cutout. Orthogonal profiles of the cutouts were measured atzmax. Data were collected for 6, 9, 12, and 15 MeV electron beam energies on a VERSA HDTMLINAC using the IBA Blue Phantom23D water phantom system. The planar dose distributions of the cutouts were also measured atzmaxin solid water using EDR2 films.Results.The measured PDD curves were normalized to a normalization depth (d0) of 1 mm. The lateral-buildup-ratio (LBR), lateral spread parameter (σR(z)), and effective SSD (SSDeff) for each cutout were calculated using the PDD of the open applicator as the reference field. The modified LBR method was then employed to calculate the planar dose distribution of the irregular cutouts within the field at least 5 mm from the edge. A simple curve-fitting model was developed based on the profile shapes of the circular cutouts around the field edge. This model was used to calculate the planar dose distribution of the irregular cutouts in the region from 3 mm outside to 5 mm inside the field edge. Finally, the calculated planar dose distribution was compared with the film measurement.Conclusions.The planar dose distribution of electron therapy for irregular cutouts atzmaxwas calculated using the improved LBR method and a simple curve-fitting model. The calculated profiles were within 3% of the measured values. The gamma passing rate with a 3%/3 mm and 10% dose threshold was more than 96%.

IOeRT conventional and FLASH treatment planning system implementation exploiting fast GPU Monte Carlo: The case of breast cancer.

Partial breast irradiation for the treatment of early-stage breast cancer patients can be performed by means of Intra Operative electron Radiation Therapy (IOeRT). One of the main limitations of this technique is the absence of a treatment planning system (TPS) that could greatly help in ensuring a proper coverage of the target volume during irradiation. An IOeRT TPS has been developed using a fast Monte Carlo (MC) and an ultrasound imaging system to provide the best irradiation strategy (electron beam energy, applicator position and bevel angle) and to facilitate the optimisation of dose prescription and delivery to the target volume while maximising the organs at risk sparing. The study has been performed in silico, exploiting MC simulations of a breast cancer treatment. Ultrasound-based input has been used to compute the absorbed dose maps in different irradiation strategies and a quantitative comparison between the different options was carried out using Dose Volume Histograms. The system was capable of exploring different beam energies and applicator positions in few minutes, identifying the best strategy with an overall computation time that was found to be completely compatible with clinical implementation. The systematic uncertainty related to tissue deformation during treatment delivery with respect to imaging acquisition was taken into account. The potential and feasibility of a GPU based full MC TPS implementation of IOeRT breast cancer treatments has been demonstrated in-silico. This long awaited tool will greatly improve the treatment safety and efficacy, overcoming the limits identified within the clinical trials carried out so far.

Automated determination of the ion-recombination correction factor (ksat) in ultra-high dose rate electron radiation therapy.

BACKGROUND: Plane-parallel ionization chambers are the recommended secondary standard systems for clinical reference dosimetry of electrons. Dosimetry in high dose rate and dose-per-pulse (DPP) is challenging as ionization chambers are subject to ion recombination, especially when dose rate and/or DPP is increased beyond the range of conventional radiotherapy. The lack of universally accepted models for correction of ion recombination in UDHR is still an issue as it is, especially in FLASH-RT research, which is crucial in order to be able to accurately measure the dose for a wide range of dose rates and DPPs. PURPOSE: The objective of this study was to show the feasibility of developing an Artificial Intelligence model to predict the ion-recombination factor-ksat for a plane-parallel Advanced Markus ionization chamber for conventional and ultra-high dose rate electron beams based on machine parameters. In addition, the predicted ksat of the AI model was compared with the current applied analytical models for this correction factor. METHODS: A total number of 425 measurements was collected with a balanced variety in machine parameter settings. The specific ksat values were determined by dividing the output of the reference dosimeter (optically stimulated luminescence [OSL]) by the output of the AM chamber. Subsequently, a XGBoost regression model was trained, which used the different machine parameters as input features and the corresponding ksat value as output. The prediction accuracy of this regression model was characterized by R2-coefficient of determination, mean absolute error and root mean squared error. In addition, the model was compared with the Two-Voltage (TVA) method and empirical Petersson model for 19 different dose-per-pulse values ranging from conventional to UDHR regimes. The Akiake Information criterion (AIC) was calculated for the three different models. RESULTS: The XGBoost regression model reached a R2-score of 0.94 on the independent test set with a MAE of 0.067 and RMSE of 0.106. For the additional 19 random data points, the ksat values predicted by the XGBoost model showed to be in agreement, within the uncertainties, with the ones determined by the Petersson model and better than the TVA method for doses per pulse >3.5 Gy with a maximum deviation from the ground truth of 14.2%, 16.7%, and -36.0%, respectively, for DPP >4 Gy. CONCLUSION: The proposed method of using AI for ksat determination displays efficiency. For the investigated DPPs, the ksat values obtained with the XGBoost model were in concurrence with the ones obtained with the current available analytical models within the boundaries of uncertainty, certainly for the DPP characterizing UDHR. But the overall performance of the AI model, taking the number of free parameters into account, lacked efficiency. Future research should optimize the determination of the experimental ksat, and investigate the determination the ksat for DPPs higher than the ones investigated in this study, while also evaluating the prediction of the proposed XGBoost model for UDHR machines of different centers.

Dose and dose rate dependence of the tissue sparing effect at ultra-high dose rate studied for proton and electron beams using the zebrafish embryo model.

PURPOSE: A better characterization of the dependence of the tissue sparing effect at ultra-high dose rate (UHDR) on physical beam parameters (dose, dose rate, radiation quality) would be helpful towards a mechanistic understanding of the FLASH effect and for its broader clinical translation. To address this, a comprehensive study on the normal tissue sparing at UHDR using the zebrafish embryo (ZFE) model was conducted. METHODS: One-day-old ZFE were irradiated over a wide dose range (15-95 Gy) in three different beams (proton entrance channel, proton spread out Bragg peak and 30 MeV electrons) at UHDR and reference dose rate. After irradiation the ZFE were incubated for 4 days and then analyzed for four different biological endpoints (pericardial edema, curved spine, embryo length and eye diameter). RESULTS: Dose-effect curves were obtained and a sparing effect at UHDR was observed for all three beams. It was demonstrated that proton relative biological effectiveness and UHDR sparing are both relevant to predict the resulting dose response. Dose dependent FLASH modifying factors (FMF) for ZFE were found to be compatible with rodent data from the literature. It was found that the UHDR sparing effect saturates at doses above âˆ¼ 50 Gy with an FMF of âˆ¼ 0.7-0.8. A strong dose rate dependence of the tissue sparing effect in ZFE was observed. The magnitude of the maximum sparing effect was comparable for all studied biological endpoints. CONCLUSION: The ZFE model was shown to be a suitable pre-clinical high-throughput model for radiobiological studies on FLASH radiotherapy, providing results comparable to rodent models. This underlines the relevance of ZFE studies for FLASH radiotherapy research.

Rapid Switching of a C-Series Linear Accelerator Between Conventional and Ultrahigh-Dose-Rate Research Mode With Beamline Modifications and Output Stabilization.

PURPOSE: In this study, a C-series linear accelerator was configured to enable rapid and reliable conversion between the production of conventional electron beams and an ultrahigh-dose-rate (UHDR) electron beamline to the treatment room isocenter for FLASH radiation therapy. Efforts to tune the beam resulted in a consistent, stable UHDR beamline. METHODS AND MATERIALS: The linear accelerator was configured to allow for efficient switching between conventional and modified electron output modes within 2 minutes. Additions to the air system allow for retraction of the x-ray target from the beamline when the 10 MV photon mode is selected. With the carousel set to an empty port, this grants access to the higher current pristine electron beam normally used to produce clinical photon fields. Monitoring signals related to the automatic frequency control system allows for tuning of the waveguide while the machine is in a hold state so a stable beam is produced from the initial pulse. A pulse counting system implemented on an field-programmable gate array-based controller platform controls the delivery to a desired number of pulses. Beam profiles were measured with Gafchromic film. Pulse-by-pulse dosimetry was measured using a custom electrometer designed around the EDGE diode. RESULTS: This method reliably produces a stable UHDR electron beam. Open-field measurements of the 16-cm full-width, half-maximum gaussian beam saw average dose rates of 432 Gy/s at treatment isocenter. Pulse overshoots were limited and ramp up was eliminated. Over the last year, there have been no recorded incidents that resulted in machine downtime due to the UHDR conversions. CONCLUSIONS: Stable 10 MeV UHDR beams were generated to produce an average dose rate of 432 Gy/s at the treatment room isocenter. With a reliable pulse-counting beam control system, consistent doses can be delivered for FLASH experiments with the ability to accommodate a wide range of field sizes, source-to-surface distances, and other experimental apparatus that may be relevant for future clinical translation.

Peripheral Doses Beyond Electron Applicators in Conventional C-Arm Linear Accelerators: A Systematic Literature Review.

Background: This review investigates peripheral dose levels in electron beam treatments, comparing different manufacturers including Varian, Elekta, and Siemens. Accurate measurement of peripheral dose is vital for patient safety and precise radiation delivery in radiation therapy. Methods: This review followed PRISMA standards, conducting a comprehensive literature search from 1978 to July 2023. Emphasis was on identifying studies analyzing peripheral doses related to various electron beam energies, beam angle, field sizes, cutouts, and applicator combinations. Three major databases including PubMed, Web of Science, and Scopus were searched. Results: A total of 7 articles were included in this review. Strategies such as bolus materials, personalized cutouts, and optimal treatment procedures have all been developed to reduce peripheral radiation exposure and enhance patient safety. Ongoing research in this field is focused on further minimizing the risks associated with out-of-field radiation by improving dose delivery systems. Conclusion: The literature emphasizes importance of precision in electron beam radiation therapy, highlighting the critical need for managing peripheral doses and optimizing hardware to ensure patient safety. It advocates for the use of advanced tools and protocols to maintain a balance between effective treatment while protecting healthy tissues. Continuous research, careful treatment planning, and effective management of peripheral doses are essential.

First Monte Carlo beam model for ultra-high dose rate radiotherapy with a compact electron LINAC.

BACKGROUND: FLASH radiotherapy based on ultra-high dose rate (UHDR) is actively being studied by the radiotherapy community. Dedicated UHDR electron devices are currently a mainstay for FLASH studies. PURPOSE: To present the first Monte Carlo (MC) electron beam model for the UHDR capable Mobetron (FLASH-IQ) as a dose calculation and treatment planning platform for preclinical research and FLASH-radiotherapy (RT) clinical trials. METHODS: The initial beamline geometry of the Mobetron was provided by the manufacturer, with the first-principal implementation realized in the Geant4-based GAMOS MC toolkit. The geometry and electron source characteristics, such as energy spectrum and beamline parameters, were tuned to match the central-axis percentage depth dose (PDD) and lateral profiles for the pristine beam measured during machine commissioning. The thickness of the small foil in secondary scatter affected the beam model dominantly and was fine tuned to achieve the best agreement with commissioning data. Validation of the MC beam modeling was performed by comparing the calculated PDDs and profiles with EBT-XD radiochromic film measurements for various combinations of applicators and inserts. RESULTS: The nominal 9 MeV electron FLASH beams were best represented by a Gaussian energy spectrum with mean energy of 9.9 MeV and variance (σ) of 0.2 MeV. Good agreement between the MC beam model and commissioning data were demonstrated with maximal discrepancy < 3% for PDDs and profiles. Hundred percent gamma pass rate was achieved for all PDDs and profiles with the criteria of 2 mm/3%. With the criteria of 2 mm/2%, maximum, minimum and mean gamma pass rates were (100.0%, 93.8%, 98.7%) for PDDs and (100.0%, 96.7%, 99.4%) for profiles, respectively. CONCLUSIONS: A validated MC beam model for the UHDR capable Mobetron is presented for the first time. The MC model can be utilized for direct dose calculation or to generate beam modeling input required for treatment planning systems for FLASH-RT planning. The beam model presented in this work should facilitate translational and clinical FLASH-RT for trials conducted on the Mobetron FLASH-IQ platform.

Very high-energy electron therapy as light-particle alternative to transmission proton FLASH therapy - An evaluation of dosimetric performances.

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