Electron Radiotherapy Research Articles

Monte Carlo dose calculation for photon and electron radiotherapy on dynamically deforming anatomy.

Dose calculation in radiotherapy aims to accurately estimate and assess the dose distribution of a treatment plan. Monte Carlo (MC) dose calculation is considered the gold standard owing to its ability to accurately simulate particle transport in inhomogeneous media. However, uncertainties such as the patient's dynamically deforming anatomy can still lead to differences between the delivered and planned dose distribution. Development and validation of a deformable voxel geometry for MC dose calculations (DefVoxMC) to account for dynamic deformation in the dose calculation process of photon- and electron-based radiotherapy treatment plans for clinically motivated cases. DefVoxMC relies on the subdivision of a regular voxel geometry into dodecahedrons. It allows shifting the dodecahedrons' corner points according to the deformation in the patient's anatomy using deformation vector fields (DVF). DefVoxMC is integrated into the Swiss Monte Carlo Plan (SMCP) to allow the MC dose calculation of photon- and electron-based treatment plans on the deformable voxel geometry. DefVoxMC is validated in two steps. A compression test and a Fano test are performed in silico. Delta4 (for photon beams) and EBT4 film measurements in a cubic PMMA phantom (for electron beams) are performed on a TrueBeam in Developer Mode for clinically motivated treatment plans. During these measurements, table motion is used to mimic rigid dynamic patient motion. The measured and calculated dose distributions are compared using gamma passing rate (GPR) (3% / 2mm (global), 10% threshold). DefVoxMC is used to study the impact of patient-recorded breathing motion on the dose distribution for clinically motivated lung and breast cases, each prescribed 50Gy to 50% of the target volume. A volumetric modulated arc therapy (VMAT) and an arc mixed-beam radiotherapy (Arc-MBRT) plan are created for the lung and breast case, respectively. For the dose calculation, the dynamic deformation of the patient's anatomy is described by DVFs obtained from deformable image registration of the different phases of 4DCTs. The resulting dose distributions are compared to the ones of the static situation using dose-volume histograms and dose differences. DefVoxMC is successfully integrated into the SMCP to enable the MC dose calculation of photon- and electron-based treatments on a dynamically deforming patient anatomy. The compression and the Fano test agree within 1.0% and 0.1% with the expected result, respectively. Delta4 and EBT4 film measurements agree with the calculated dose by a GPR>95%. For the clinically motivated cases, breathing motion resulted in areas with a dose increase of up to 26.9Gy (lung) and up to 7.6Gy (breast) compared to the static situation. The largest dose differences are observed in high-dose-gradient regions perpendicular to the beam plane, consequently decreasing the planning target volume coverage (V95%) by 4.2% for the lung case and 2.0% for the breast case. A novel method for MC dose calculation for photon- and electron-based treatments on dynamically deforming anatomy is successfully developed and validated. Applying DefVoxMC to clinically motivated cases, we found that breathing motion has non-negligible impact on the dosimetric plan quality.

Comprehensive analysis of peripheral dose in electron beam therapy with a Varian TrueBeam Linac

ObjectiveTo investigate the characteristics of peripheral doses outside electron-beam applicators in Varian TrueBeam linacs. MethodPeripheral doses outside the electron applicator were measured for 6-, 9- and 12-MeV beams at the maximum dose depth (Dmax) for each energy source and at a source-to-surface distance of 100 cm. Measurements were performed using EBT3 films in solid water phantoms. The impact of field size on the penumbra width and peripheral doses was studied using various cutouts, including 3 cm × 3 cm, 6 cm × 6 cm, and 10 cm × 10 cm in a 10 cm × 10 cm applicator with the gantry and collimator at 0°. The influence of the applicator size was investigated using a circular cutout of 5 cm in diameter for various applicator sizes, including 6 cm × 6 cm, 10 cm × 10 cm, 15 cm × 15 cm, 20 × 20 cm, and 25 cm × 25 cm, at Dmax for each energy, while keeping the gantry and collimator angle at 0°. The measured dose profiles were compared with the Eclipse treatment planning system (TPS) predicted dose profiles. The effect of varying gantry angles (0°, 90°, and 270°) for a 3 cm × 3 cm cutout in a 10 cm × 10 cm applicator for each energy source and varying collimator angles (0°, 90°, and 270°) for a 10 cm × 10 cm field were investigated to determine their effects on the penumbra widths and peripheral doses. ResultsBoth the penumbra width and peripheral dose values increased with energy across different field sizes, gantry angles, collimator angles, and applicator sizes. Root Mean Square Deviation (RMSD) analysis indicated minimal differences between the measured profiles and TPS data. Peripheral doses remained below 5% of the maximum dose approximately 10–15 mm away from the field edges, suggesting the potential for implementing additional shielding where required. ConclusionsThis study highlights the importance of considering peripheral doses in electron radiotherapy. It is important to note the impact on healthy tissues beyond the treatment area to ensure patient safety and prevent the long-term side effects of treatment. These findings emphasize the necessity of implementing appropriate measures to minimize peripheral doses.

Hybrid ultra-high and conventional dose rate treatments with electrons and photons for the clinical transfer of FLASH-RT to deep-seated targets: A treatment planning study

PurposeThis study explores the dosimetric feasibility and plan quality of hybrid ultra-high dose rate (UHDR) electron and conventional dose rate (CDR) photon (HUC) radiotherapy for treating deep-seated tumours with FLASH-RT. MethodsHUC treatment planning was conducted optimizing a broad UHDR electron beam (between 20–250 MeV) combined with a CDR VMAT for a glioblastoma, a pancreatic cancer, and a prostate cancer case. HUC plans were based on clinical prescription and fractionation schemes and compared against clinically delivered plans. Considering a HUC boost treatment for the glioblastoma consisting of a 15-Gy-single-fraction UHDR electron boost supplemented with VMAT, two scenarios for FLASH sparing were assessed using FLASH-modifying-factor-weighted doses. ResultsFor all three patient cases, HUC treatment plans demonstrated comparable dosimetric quality to clinical plans, with similar PTV coverage (V95% within 0.5 %), homogeneity, and critical OAR-sparing. At the same time, HUC plans delivered a substantial portion of the dose to the PTV (Dmedian of 50–69 %) and surrounding tissues at UHDR. For the HUC boost treatment of the glioblastoma, the first FLASH sparing scenario showed a moderate FLASH sparing magnitude (10 % for D2%,PTV) for the 15-Gy UHDR electron boost, while the second scenario indicated a more substantial sparing of brain tissues inside and outside the PTV (32 % for D2%,PTV, 31 % for D2%,Brain). ConclusionsFrom a planning perspective, HUC treatments represent a feasible approach for delivering dosimetrically conformal UHDR treatments, potentially mitigating technical challenges associated with delivering conformal FLASH-RT for deep-seated tumours. While further research is needed to optimize HUC fractionation and delivery schemes for specific patient cohorts, HUC treatments offer a promising avenue for the clinical transfer of FLASH-RT.

Performance of a BeO-based dosimetry system for proton and electron beam dose measurements

This study aims to evaluate the performance of the BeO-based myOSLchip system (RadPro International GmbH, Remscheid, Germany) for dosimetry of proton and electron radiotherapy beams. Although beryllium oxide (BeO) has been recognised as a promising material for luminescence dosimetry in radiotherapy, this research extends beyond material properties and examines the entire BeO-based dosimetry system, including the detector, holder, and readout components.Packages of myOSLchip detectors were irradiated either in a (70−230) MeV proton beam or in a 16 MeV electron beam. The readouts were carried out using the portable myOSLchip reader. In the electron beam, tests on the precision, dose response up to 100 Gy and dose-rate effects of the system were carried out. In the proton beam, the system was tested for its dose response (up to 10 Gy), fading, and linear energy transfer (LET) response.For proton irradiations, the myOSLchip BeO OSLDs exhibited stability within 2 % over 135 days, as well as a linear dose response in the tested range, (0.1−10) Gy. The efficiency showed a reduction for proton beams with LET values (for water) above 0.6 keV/μm, with up to 40 % loss in efficiency at 4 keV/μm. For the electron irradiations, they showed a linear dose–response up to 20 Gy and dose-rate independence, with a constant response at least up to 2.99×105 Gy s−1. Using individual chip sensitivity correction, the precision for a single chip was around 3.5% (standard deviation of the data of all chips) and for a package comprising four chips was 1.7% (standard deviation of the mean of the four chips).These findings suggest the myOSLchip system’s potential as a reliable alternative to existing dosimetry systems in clinical applications.

Simulation and commissioning of a Faraday cup for absolute charge measurements of very high-energy electrons in-air at PEER

The Pulsed Energetic Electrons for Research (PEER) beamline at the ANSTO Australian Synchrotron comprises a 100 MeV linac injector that is currently being developed for ultra-high dose-rate, very high-energy electron radiotherapy research. Previously, dosimetry studies discovered a lack of reliable charge measurement to the in-air end station, though no change in response was recorded in fast current transformer measurements, the only available diagnostic device for measuring charge. This work describes the process of simulating and then commissioning a purpose-built Faraday cup to ascertain absolute in-air charge measurements at PEER. By combining simulation data with experimental results, the PEER Faraday cup is shown to possess a primary electron capture efficiency of (99.22 ± 0.10)%, with a net capture efficiency due to secondary electron emission of (97.87 ± 0.24)%. These results show the PEER Faraday cup performs as intended and, when scaled against simulations, will be suitable for measuring absolute charge at PEER.

MR-PVHEE: A novel magnetic resonance-guided parallel-beam very high-energy electron radiotherapy system

PurposeMR-guided very high-energy electron (VHEE) radiotherapy can combine the imaging advantages of MR with the dosimetry advantages of VHEE radiotherapy, which is of significant clinical value. However, VHEEs are highly susceptible to the Lorentz force generated by the MR magnetic field, and coupling MR and VHEEs is challenging. Here, we present a novel MR-guided parallel-beam VHEE (MR-PVHEE) radiotherapy system and confirm its feasibility and effectiveness. MethodThe proposed MR-PVHEE radiotherapy system includes an ingenious coupling model of MR and VHEEs and an electromagnetic steering parameters commissioning (ESP-COM) method for accurate delivery. First, by generating parallel VHEE (PVHEE) beamlets that point in the same direction as the MR main magnetic field, the coupling model based on triple-stage electromagnetic steering can significantly lessen the twisting and deflecting of the VHEE beamlets' delivery trajectory caused by the MR magnetic field. The dosimetric advantage of VHEEs will be enhanced by delicately utilizing the MR magnetic field to constrain lateral scatter. Then, the ESP-COM method based on Bayesian black-box optimization for the PVHEE beamlets is designed by constructing a cost function using the position and direction information of particles in phase space and optimizing the parameters to deliver the beamlets accurately to the target spots. Finite element electromagnetic modeling and Monte Carlo particle transport simulation are used to validate the MR-PVHEE. ResultsMR-PVHEE can generate the PVHEE beamlets in the same direction as the MR magnetic field and accurately deliver them to the target spots. The average position error is within 0.5 mm, and the average direction error is about 0.5°, which can meet the requirements of clinical treatment accuracy. MR-PVHEE can reduce the VHEE lateral penumbra and increase the dose drop gradient. ConclusionFor the first time, MR and VHEE radiotherapy are successfully coupled in this study, and the innovative MR-PVHEE radiotherapy system can elicit new modalities for MR-guided charged particle radiotherapy and spatially fractionated radiotherapy.

Evaluation of cutout factors with small and narrow fields using various dosimetry detectors in electron beam keloid radiotherapy.

The inherent problems in the existence of electron equilibrium and steep dose fall-off pose difficulties for small- and narrow-field dosimetry. To investigate the cutout factors for keloid electron radiotherapy using various dosimetry detectors for small and narrow fields. The measurements were performed in a solid water phantom with nine different cutout shapes. Five dosimetry detectors were used in the study: pinpoint 3D ionization chamber, Farmer chamber, semiflex chamber, Classic Markus parallel plate chamber, and EBT3 film. The results demonstrated good agreement between the semiflex and pinpoint chambers. Furthermore, there was no difference between the Farmer and pinpoint chambers for large cutouts. For the EBT3 film, half of the cases had differences greater than 1%, and the maximum discrepancy compared with the reference chamber was greater than 2% for the narrow field. The parallel plate, semiflex chamber and EBT3 film are suitable dosimeters that are comparable with pinpoint 3D chambers in small and narrow electron fields. Notably, a semiflex chamber could be an alternative option to a pinpoint 3D chamber for cutout widths≥3 cm. It is very important to perform patient-specific cutout factor calibration with an appropriate dosimeter for keloid radiotherapy.

4D in vivo dosimetry for a FLASH electron beam using radiation-induced acoustic imaging

Objective. The primary goal of this research is to demonstrate the feasibility of radiation-induced acoustic imaging (RAI) as a volumetric dosimetry tool for ultra-high dose rate FLASH electron radiotherapy (FLASH-RT) in real time. This technology aims to improve patient outcomes by accurate measurements of in vivo dose delivery to target tumor volumes. Approach. The study utilized the FLASH-capable eRT6 LINAC to deliver electron beams under various doses (1.2 Gy pulse−1 to 4.95 Gy pulse−1) and instantaneous dose rates (1.55 × 105 Gy s−1 to 2.75 × 106 Gy s−1), for imaging the beam in water and in a rabbit cadaver with RAI. A custom 256-element matrix ultrasound array was employed for real-time, volumetric (4D) imaging of individual pulses. This allowed for the exploration of dose linearity by varying the dose per pulse and analyzing the results through signal processing and image reconstruction in RAI. Main Results. By varying the dose per pulse through changes in source-to-surface distance, a direct correlation was established between the peak-to-peak amplitudes of pressure waves captured by the RAI system and the radiochromic film dose measurements. This correlation demonstrated dose rate linearity, including in the FLASH regime, without any saturation even at an instantaneous dose rate up to 2.75 × 106 Gy s−1. Further, the use of the 2D matrix array enabled 4D tracking of FLASH electron beam dose distributions on animal tissue for the first time. Significance. This research successfully shows that 4D in vivo dosimetry is feasible during FLASH-RT using a RAI system. It allows for precise spatial (∼mm) and temporal (25 frames s−1) monitoring of individual FLASH beamlets during delivery. This advancement is crucial for the clinical translation of FLASH-RT as enhancing the accuracy of dose delivery to the target volume the safety and efficacy of radiotherapeutic procedures will be improved.

Toward a multi-layer micro-structured detector for high-energy electron radiotherapy.

The use of electron beams has been rekindled by the advent of ultra-high-dose rate radiotherapy (FLASH) and very high energy electrons (VHEE). The need for development of novel technology for beam monitoring and dosimetry of such beams is of paramount importance prior to their clinical translation. In this work we explore the potential of a multi-layer nanoporous aerogel High-Energy-Current (HEC) detector as a dosimeter for electron beam. The detector does not suffer from radiation damage or signal saturation, making it suitable for very-high-dose-rate applications. Standard dose rates and energies are used to establish reference for FLASH and VHEE. We explore detector response to electron energy and residual range both experimentally and computationally. Multilayer HEC detectors were constructed using 1×-10× basic modules of Aluminum(Al)_aerogel(A)_Tantalum(Ta) with 10-70 µm layer thicknesses. Signals are collected from all electrodes (3-21, depending on module multiplicity) with zero external voltage bias. Measurements are acquired as a function of depth(z) in water equivalent plastic using Varian TrueBeam for energies E=6,9,12,15 MeV (SAD=105cm, 6×6 cone, 1000 MU/min). Computational simulations of identical detector geometries are performed using the 1D deterministic code CEPXS/ONEDANT. Additionally, percent-depth-doses PDD(z), measured with diode in water, are used to explore the response of HEC for various energies and residual ranges. The current measured from Ta electrodes resembles the shape of deposited charges in water and it is proportional to the derivative of the clinical PDD corrected for contribution from photon contamination. The signal is positive on the surface, and it decreases with depth reaching a negative local minimum at z=R50, before increasing again, reaching zero at about the practical range z=Rp. In contrast, the signal from Al electrodes is shaped like the electron PDD(z) shape but with lower signal at the surface and higher bremsstrahlung tail. By subtracting the signal from Ta and Al electrodes we obtained a curve resembling PDD(z,E) after Bremsstrahlung contamination correction. Multi-layer HEC sensors exhibit characteristic responses to electron beams that are unlike responses of ion chambers or diodes. Since the sensor structures are sensitive to electronic disequilibrium, high-Z electrodes give a signal proportional to the charge deposition pattern and can be modeled using the derivative of PDD(z).

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.

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.

Development of a novel fibre optic beam profile and dose monitor for very high energy electron radiotherapy at ultrahigh dose rates

Objective. Very high energy electrons (VHEE) in the range of 50–250 MeV are of interest for treating deep-seated tumours with FLASH radiotherapy (RT). This approach offers favourable dose distributions and the ability to deliver ultra-high dose rates (UHDR) efficiently. To make VHEE-based FLASH treatment clinically viable, a novel beam monitoring technology is explored as an alternative to transmission ionisation monitor chambers, which have non-linear responses at UHDR. This study introduces the fibre optic flash monitor (FOFM), which consists of an array of silica optical fibre-based Cherenkov sensors with a photodetector for signal readout. Approach. Experiments were conducted at the CLEAR facility at CERN using 200 MeV and 160 MeV electrons to assess the FOFM’s response linearity to UHDR (characterised with radiochromic films) required for FLASH radiotherapy. Beam profile measurements made on the FOFM were compared to those using radiochromic film and scintillating yttrium aluminium garnet (YAG) screens. Main results. A range of photodetectors were evaluated, with a complementary-metal-oxide-semiconductor (CMOS) camera being the most suitable choice for this monitor. The FOFM demonstrated excellent response linearity from 0.9 Gy/pulse to 57.4 Gy/pulse (R 2 = 0.999). Furthermore, it did not exhibit any significant dependence on the energy between 160 MeV and 200 MeV nor the instantaneous dose rate. Gaussian fits applied to vertical beam profile measurements indicated that the FOFM could accurately provide pulse-by-pulse beam size measurements, agreeing within the error range of radiochromic film and YAG screen measurements, respectively. Significance. The FOFM proves to be a promising solution for real-time beam profile and dose monitoring for UHDR VHEE beams, with a linear response in the UHDR regime. Additionally it can perform pulse-by-pulse beam size measurements, a feature currently lacking in transmission ionisation monitor chambers, which may become crucial for implementing FLASH radiotherapy and its associated quality assurance requirements.

Preliminary study on the correlation between accelerated current and dose in water for an electron-based LINAC

Purpose: Intraoperative electron radiotherapy (IOeRT) is considered the first clinical translation of FLASH with electrons. A crucial aspect is represented by the precise dose monitoring and measurement; to this aim, we propose a method fully based on Monte Carlo (MC) simulation that uses as input the beam current measurement and the beam optics simulation. To validate this approach, we chose the NOVAC11 (produced by Sordina IORT Technologies SpA) accelerator, which provides a well-studied model.Methods: We used FLUKA and FRED MC software to simulate in detail the geometry of the NOVAC11 and the coupled applicator usually adopted in clinical practice to deliver the dose in the surgical bed. The simulation results of the longitudinal and off-axis profiles and dose per pulse obtained in a water phantom with different applicators are compared to the experimental data.Results: A very good agreement not only for the relative dosimetry in both the longitudinal and off-axis profiles, with a gamma index pass rate of 100% with 3%/3 mm acceptance criteria, but also for the absolute dosimetry was obtained.Conclusion: The results completely validate the MC description of the system and provide a reliable evaluation of the dose per pulse and output factor with an accuracy of the order of few % for different sets of applicator diameters and lengths.

On the need of in vivo verifications as quality control for intraoperative electron radiotherapy in breast cancer.

Intraoperative electron radiotherapy (IOERT) is a technique aiming to deliver radiotherapy during oncological surgery. In breast IOERT, the applicator and shielding disc placement are correlated with organs at risk (OAR) irradiation, in vivo verification of these parameters is scarcely reported. The aim of our study is to report and analyze possible causes of the misalignment using radiochromic films and compare our results to others reported in the bibliography. From November 2019 to April 2023, in vivo verifications were performed for 33 patients. IOERT was performed using a LIAC 10MeV (Sordina, Italy) electron accelerator. We attached a radiochromic film to the upper side of the polytetrafluoroethylene cover of the shielding disc. The percentage of the irradiation area outside the disc was recorded and various parameters (applicator angulations, prescription depth, tumor location and breast size) were analyzed to find possible correlations. For 29 patients, 20Gy were prescribed while 10Gy were prescribed to 4 patients. The average irradiated area outside the disc was 19% (0-56%) corresponding to a surface of 4.5 cm2 (0-17.4 cm2). The applicator of 5cm was used for most of the patients. The mean prescription depth was 1.4cm (0.5-2.5cm). We found no correlation between the analyzed parameters and misalignment. This study confirms the presence and magnitude of the misalignments. We strongly recommend in vivo verifications as a quality check during IOERT procedures. The misalignment has no correlation with tumor localization parameters, so the solution could be based on technical improvements of the applicator.

Near infrared low-level laser effect on electron radiation therapy of non-melanoma human squamous cell cancer: An in-vitro study

PurposeThe aim is to assess the efficacy of combined electron-laser radiation therapy on non-melanoma Squamous cell carcinoma (SCC) cancer cells in an in-vitro model. Material and methodsThe human SCC cancer line (TSCC-1) was purchased from the Iranian Biological Resources Center (IBRC) and cultured according to the standard protocol. The groups of this study were control; only electron radiation; only Low-Level Laser Therapy (LLLT); and combined laser-electron radiation. Irradiation with a 980 nm 50 mW laser was performed in a single session with energy doses of 1 and 1.5 J/cm2. Electron radiation was carried out using a Varian accelerator with a radiation dose of 2 and 4 Gy. 24 h after laser treatment of cancer cells, combined electron irradiation was performed. MTT and flow cytometry bioassays were performed and analyzed to check their effectiveness. ResultsThe cell viability assay for irradiation with 980 nm 50 mW NIR laser in a single session with an irradiation time of 20 and 30 s in combination with 2 and 4 Gy electrons showed a significant difference (P-value <0.01). Flow cytometry test of the electron-radiated samples showed that the sum of early and late apoptosis was the highest. However, for the combination of electron-laser radiation of 30 s with 2 and 4 Gy electrons, the maximum percentage of apoptosis and necrosis was obtained close to the electron alone. Except for the control group, the quantitative interval of induced necrosis of all the groups evaluated by electron alone, laser alone, and combined electron laser was almost equivalent. ConclusionsThis study showed that the physical parameters of a 980 nm NIR LLLT might not have a synergy effect on treatment response in combination with an electron ionizing beam on SCC cancer cells. It is critical to consider the effect of light irradiation parameters for combination therapy in more extensive studies.

Intra-operative radiation for pancreatic cancer: Initial experience at the Hadassah Medical Center.

634 Background: Prognosis following surgery for pancreatic cancer (PC) remains poor. Local recurrence is common and negatively impacts survival rate. In an effort to improve local control and potentially improve survival, we have adopted a strategy of adding intra-operative electron radiation therapy (IOeRT) to selected patients undergoing pancreatic resection (PR) for PC. Here we report our initial experience with this treatment modality. Methods: 14 patients (10 male, 4 female), age between 44 - 81 years (mean 66.17), who underwent PR (Head 7, Body7) between 1/2021-1/2023 were included in this analysis. Patients selected for IOeRT included patients that according to surgeon assessment were at risk not to achieve satisfactory resection margins by surgery alone. All had resectable or borderline resectable disease according to standard criteria. 8 patients underwent pre-op chemotherapy followed by stereotactic body radiotherapy (SBRT) to a dose of 25-40 Gy in 5 fractions to the tumor and regional lymphatics followed by PR (5 Whipple, 3 distal pancreatectomy) and IOeRT, 3 patients received preop SBRT followed by PR (3 distal pancreatectomy) + IOeRT, 2 patients underwent PR (whipple 1, distal pancreatectomy 1) + IoeRT, and 1 received neoadjuvant chemotherapy followed by SBRT only and did not undergo surgery due to tumor progression. Immediately following resection, mobile IOeRT accelerator using a 40-80mm applicator with a level of 0-15 degrees was directed at the tumor bed deemed at high risk for recurrence. 10-20 Gy was delivered using 6-8 MeV electrons to the 90% isodose line at the discretion of the treating radiation oncologist. Data including serial imaging, genomic analysis, radiation protocol, complications, pathological results and outcome was collected for analysis. Results: Mean follow up was 9.7 months (2-21). 8 patients are alive: 7 pts with no evidence of disease and 1 pt with liver metastases. 6 patients died: 4 with distant metastatic disease, 1 from disease progression prior to surgery and 1 from early post-op sepsis. Negative surgical margins were achieved in 10 patients of which 2 mutated BRCA gene carriers showed complete pathological response (both who received combined neoadjuvant chemotherapy followed by SBRT). Post-operative complications possibly attributed to RT included hepatic artery occlusion (1 pt), portal vein stenosis (1 pt) and prolonged GI tract dysfunction (1pt). Conclusions: Combining RT with resection appears feasible and safe. Our data possibly show a reduction in local recurrence following resection of PC, however, longer follow up is necessary. Refinements in patient selection and treatment protocol may further improve outcomes. Larger scale studies are required to determine the benefit of this modality.

Post-operative complications following dose adaptation of intra-operative electron beam radiation therapy in locally advanced or recurrent rectal cancer.

The benefit of intra-operative radiotherapy (IORT) in the treatment of locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC) lie in its ability to provide high-dose of radiation to limited at-risk volume, thereby eliminating microscopic disease and decreasing toxicity. A comparative study between high-dose-rate (HDR) brachytherapy, named intra-operative brachytherapy (IOBT), and intra-operative electron radiotherapy (IOERT) was performed showing favorable LRFS after IOBT, possibly due to a higher surface dose that is inherent in IOBT technique. The IOERT technique in Catharina Hospital Eindhoven was adapted to increase the surface dose, aiming to improve local control. Post-operative complications due to an increased radiation dose remain the matter of concern. This retrospective study was performed to compare complication rates before and after adapted IOERT dose. All patients undergoing surgery with IOERT for LARC or LRRC from September 2019 until July 2023, were considered. Patients selected until August 31, 2021 were included in control cohort (n = 108), and those chosen from September 1, 2021 onwards were included in intervention cohort (n = 92). Perioperative and (major) post-operative complications were classified retrospectively, during admission, at 30 days, and at 90 days. In LARC patients, a decrease in post-operative complications was observed (p = 0.009). 19% of LARC patients experienced major post-operative surgical complications, i.e., Clavien-Dindo grade 3b-5, regardless of treatment group. No difference in major 90-day complications was noted (p = 0.142). In LRRC patients, the use of induction chemotherapy decreased from 78% to 29% (p < 0.001), which complicated comparison. However, no difference in major post-operative complications was observed at 30 days (p = 0.222) or 90 days (p = 0.977) after surgery. Increased surface dose of IOERT does not seem to lead to an increase in post-operative complications. Further research is needed to evaluate the efficacy of dose adaptation in IOERT to improve local oncological control rates. Routine evaluation of CTCAE scores in follow-up will help uncover possible long-term radiation-induced toxicity.

Design and performance validation of a novel 3d printed thin-walled and transparent electron beam applicators for intraoperative radiation therapy with beam energy up to 12 MeV.

A high-energy electron accelerator is used in the treatment of patients in the so-called intraoperative electron radiotherapy (IOERT). The work aimed to present the results of the validation of a new design of an electron beam applicator for use in IOERT. A novel solution was described along with the design optimization method based on Monte Carlo simulations. In this solution, the applicator consists of two parts. The lower exchangeable part collimates the therapeutic field. Measurements were made based on the International Electrotechnical Commission (IEC) standard recommendations. The measurement described in the standard has been adapted to the specificity of the intraoperative accelerator Source to Skin Distance - of 60 cm and applicators with a circular cross-sectional area. Measurements were performed for nominal beam energies of 6, 10, and 12 MeV and two therapeutic field diameters of 6 and 10 cm. The dose due to stray X-ray radiation in all energies is less than 0.3% and increases for energies from 6 to 12 MeV by 2.9 times from 0.1 for 6MeV to 0.29 for 12 MeV. The average dose due to leakage radiation also shows an increasing trend and is higher for a 6 cm diameter applicator. Validation confirmed the usefulness of the novel applicator design for clinical applications. Thanks to the use of 3D printing, it was possible to make applicators that are transparent, biocompatible and, at the same time, light and form a beam field with therapeutically useful accuracy, and the leakage radiation does not exceed normative recommendations.

Matrix metal collimators studies for the spatially fractionated radiation therapy

Traditional radiation therapy is hindered by limitations in dose delivery and the risk of over-irradiation, which can harm healthy tissues surrounding tumors. Spatially fractionated and intensity-modulated radiation therapies have emerged as promising techniques to mitigate these issues by reducing damage to healthy tissues. This study explores the potential of enhancing radiation therapy's therapeutic efficacy through spatial fractionation of X-ray beams, a technique that can significantly increase radiation efficiency by reducing the dose load on healthy tissues. This research hypothesizes that microscopic lesions within the paths of micro/mini-beams can be repaired by minimally irradiated cells adjacent to the irradiated tissue slices, based on observations with high-energy (MV) photons. Spatial fractionation is particularly valuable for X-ray and electron radiation therapy, which is more widespread and cost-effective than proton therapy. The study introduces a new type of cost-effective metal matrix collimators designed for beam fractionation. These collimators are constructed using lead plates for thickness variation implementation and employ a 5x5 hole matrix with 1 mm diameter and 3 mm pitch, covering an area of 14x14 mm². To visualize beam distribution, a Timepix detector, capable of providing real-time 2D beam profiles, was employed. Experiments were conducted using a medical LINAC with typical therapeutic energy ranging from 6 to 18 MeV. Results indicate that spatial fractionation can be achieved for X-ray radiation, with a PVDR of approximately 3 for a 3 cm lead collimator. However, issues with hole uniformity and blurring in the peak area prompted a shift to using copper collimators due to their superior manufacturing properties. This study presents a novel matrix collimator design made from various materials for shaping mini beams, aimed at improving the efficiency of spatial dose fractionation for different ionizing radiation types. Geant4 simulations have been instrumental in optimizing collimator features. The findings suggest that high levels of dose fractionization can be achieved for X-rays, electrons, and proton beams. These results warrant further biological studies to evaluate the effects of fractionation on normal and tumoral tissues, supporting the practical implementation of collimation in radiation therapy.

KiT-RT: An Extendable Framework for Radiative Transfer and Therapy

In this article, we present Kinetic Transport Solver for Radiation Therapy (KiT-RT), an open source C++-based framework for solving kinetic equations in therapy applications available at https://github.com/CSMMLab/KiT-RT . This software framework aims to provide a collection of classical deterministic solvers for unstructured meshes that allow for easy extendability. Therefore, KiT-RT is a convenient base to test new numerical methods in various applications and compare them against conventional solvers. The implementation includes spherical harmonics, minimal entropy, neural minimal entropy, and discrete ordinates methods. Solution characteristics and efficiency are presented through several test cases ranging from radiation transport to electron radiation therapy. Due to the variety of included numerical methods and easy extendability, the presented open source code is attractive for both developers, who want a basis to build their numerical solvers, and users or application engineers, who want to gain experimental insights without directly interfering with the codebase.