Mini-GRID radiotherapy on the CLEAR very-high-energy electron beamline: collimator optimization, film dosimetry, and Monte Carlo simulations.

Objective.Spatially-fractionated radiotherapy (SFRT) delivered with a very-high-energy electron (VHEE) beam and a mini-GRID collimator was investigated to achieve synergistic normal tissue-sparing through spatial fractionation and the FLASH effect.Approach.A tungsten mini-GRID collimator for delivering VHEE SFRT was optimized using Monte Carlo (MC) simulations. Peak-to-valley dose ratios (PVDRs), depths of convergence (DoCs, PVDR ≤ 1.1), and peak and valley doses in a water phantom from a simulated 150 MeV VHEE source were evaluated. Collimator thickness, hole width, and septal width were varied to determine an optimal value for each parameter that maximized PVDR and DoC. The optimized collimator (20 mm thick rectangular prism with a 15 mm × 15 mm face with a 7 × 7 array of 0.5 mm holes separated by 1.1 mm septa) was 3D-printed and used for VHEE irradiations with the CERN linear electron accelerator for research beam. Open beam and mini-GRID irradiations were performed at 140, 175, and 200 MeV and dose was recorded with radiochromic films in a water tank. PVDR, central-axis (CAX) and valley dose rates and DoCs were evaluated.Main results.Films demonstrated peak and valley dose rates on the order of 100 s of MGy/s, which could promote FLASH-sparing effects. Across the three energies, PVDRs of 2-4 at 13 mm depth and DoCs between 39 and 47 mm were achieved. Open beam and mini-GRID MC simulations were run to replicate the film results at 200 MeV. For the mini-GRID irradiations, the film CAX dose was on average 15% higher, the film valley dose was 28% higher, and the film PVDR was 15% lower than calculated by MC.Significance.Ultimately, the PVDRs and DoCs were determined to be too low for a significant potential for SFRT tissue-sparing effects to be present, particularly at depth. Further beam delivery optimization and investigations of new means of spatial fractionation are warranted.

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 (R2= 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.

VHEE FLASH sparing effect measured at CLEAR, CERN with DNA damage of pBR322 plasmid as a biological endpoint.

Ultra-high dose rate (UHDR) irradiation has been shown to have a sparing effect on healthy tissue, an effect known as 'FLASH'. This effect has been studied across several radiation modalities, including photons, protons and clinical energy electrons, however, very little data is available for the effect of FLASH with Very High Energy Electrons (VHEE). pBR322 plasmid DNA was used as a biological model to measure DNA damage in response to Very High Energy Electron (VHEE) irradiation at conventional (0.08 Gy/s), intermediate (96 Gy/s) and ultra-high dose rates (UHDR, (2 × 109 Gy/s) at the CERN Linear Electron Accelerator (CLEAR) user facility. UHDRs were used to determine if the biological FLASH effect could be measured in the plasmid model, within a hydroxyl scavenging environment. Two different concentrations of the hydroxyl radical scavenger Tris were used in the plasmid environment to alter the proportions of indirect damage, and to replicate a cellular scavenging capacity. Indirect damage refers to the interaction of ionising radiation with molecules and species to generate reactive species which can then attack DNA. UHDR irradiated plasmid was shown to have significantly reduced amounts of damage in comparison to conventionally irradiated, where single strand breaks (SSBs) was used as the biological endpoint. This was the case for both hydroxyl scavenging capacities. A reduced electron energy within the VHEE range was also determined to increase the DNA damage to pBR322 plasmid. Results indicate that the pBR322 plasmid model can be successfully used to explore and test the effect of UHDR regimes on DNA damage. This is the first study to report FLASH sparing with VHEE, with induced damage to pBR322 plasmid DNA as the biological endpoint. UHDR irradiated plasmid had reduced amounts of DNA single-strand breaks (SSBs) in comparison with conventional dose rates. The magnitude of the FLASH sparing was a 27% reduction in SSB frequency in a 10 mM Tris environment and a 16% reduction in a 100 mM Tris environment.

A configurable computer simulation model for reducing patient waiting time in oncology departments.

Nowadays, the increase in patient demand and the decline in resources are lengthening patient waiting times in many chemotherapy oncology departments. Therefore, enhancing healthcare services is necessary to reduce patient complaints. Reducing the patient waiting times in the oncology departments represents one of the main goals of healthcare managers. Simulation models are considered an effective tool for identifying potential ways to improve patient flow in oncology departments. This paper presents a new agent-based simulation model designed to be configurable and adaptable to the needs of oncology departments which have to interact with an external pharmacy. When external pharmacies are utilised, a courier service is needed to deliver the individual therapies from the pharmacy to the oncology department. An oncology department located in southern Italy was studied through the simulation model and different scenarios were compared with the aim of selecting the department configuration capable of reducing the patient waiting times.

Enhancing particle bunch-length measurements based on Radio Frequency Deflector by the use of focusing elements.

A method to monitor the length of a particle bunch, based on the combination of a Radio Frequency Deflector (RFD) with magnetic focusing elements, is presented. With respect to state-of-the-art bunch length measurement, the additional focusing element allows to measure also the correlations between the longitudinal and transverse planes in terms of both position and divergence. Furthermore, the quadrupole-based focusing increases the input dynamic range of the measurement system (i.e.  allows for a larger range of beam Twiss parameters at the entrance of the RFD). Thus, measurement resolution and precision are enhanced, by simultaneously preserving the accuracy. In this paper, the method is first introduced analytically, and then validated in simulation, by the reference tool ELEctron Generation ANd Tracking, ELEGANT. Finally, a preliminary experimental validation at CLEAR (CERN Linear Electron Accelerator for Research) is reported.

VHEE beam dosimetry at CERN Linear Electron Accelerator for Research under ultra-high dose rate conditions.

The aim of this work is the dosimetric characterization of a plane parallel ionization chamber under defined beam setups at the CERN Linear Electron Accelerator for Research (CLEAR). A laser driven electron beam with energy of 200 MeV at two different field sizes of approximately 3.5 mm FWHM and approximately 7 mm FWHM were used at different pulse structures. Thereby the dose-per-pulse range varied between approximately 0.2 and 12 Gy per pulse. This range represents approximately conventional dose rate range beam conditions up to ultra-high dose rate (UHDR) beam conditions. The experiment was based on a water phantom which was integrated into the horizontal beamline and radiochromic films and an Advanced Markus ionization chamber was positioned in the water phantom. In addition, the experimental setup were modelled in the Monte Carlo simulation environment FLUKA. In a first step the radiochromic film measurements were used to verify the beamline setup. Depth dose distributions and dose profiles measured by radiochromic film were compared with Monte Carlo simulations to verify the experimental conditions. Second, the radiochromic films were used for reference dosimetry to characterize the ionization chamber. In particular, polarity effects and the ion collection efficiency of the ionization chamber were investigated for both field sizes and the complete dose rate range. As a result of the study, significant polarity effects and recombination loss of the ionization chamber were shown and characterized. However, the work shows that the behavior of the ionization chamber at the laser driven beam line at the CLEAR facility is comparable to classical high dose-per-pulse electron beams. This allows the use of ionization chambers on the CLEAR system and thus enables active dose measurement during the experiment. Compared to passive dose measurement with film, this is an important step forward in the experimental equipment of the facility.