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The aim of the NEPTUNE (Nuclear process-driven Enhancement of Proton Therapy UNravEled) project is to investigate in detail both the physical and radiobiological phenomena that could justify an increase of the proton-induced cytogenetic effects in cells irradiated in presence of an agent containing natural boron. In this work, a double-stage silicon telescope coupled to different boron converters was irradiated at the CATANA proton therapy facility (INFN-LNS) for studying the proton boron fusion and the neutron boron capture reactions by discriminating secondary particles from primary protons. Different boron targets were developed by depositing boric acid, enriched with a higher than 99% content of 10B or 11B, on a 50 µm thick PolyMethilMetacrylate (PMMA) substrate. The 10B target allows to evaluate the contribution of lithium and alpha particles produced by the boron neutron capture reaction triggered by secondary thermal neutrons, while the 11B target is exploited for studying the effect of the p + 11B → 3α nuclear reaction directly triggered by primary protons. Experimental results clearly show the presence of alpha particles from both the reactions. The silicon telescope is capable of discriminating, by means of the so-called “scatter plots”, the contribution of alpha particles originated by thermal neutrons on 10B with respect to the ones produced by protons impinging on 11B. Although a reliable quantitative study of the alpha production rate has not been achieved yet, this work demonstrates that low energy and, therefore, high-LET particles from both the reactions can be measured.

Purpose A 5 and 10 μm thin silicon on insulator (SOI) 3D mushroom microdosimeter was used to characterise both the in-field and out-of-field of a 62 MeV proton beam. Methods The SOI mushroom microdosimeter consisted of an array of cylindrical sensitive volumes (SVs), developed by the Centre for Medical Radiation Physics, University of Wollongong, was irradiated with 62 MeV protons at the CATANA (Centro di AdroTerapia Applicazioni Nucleari Avanzate) facility in Catania, Italy, a facility dedicated to the radiation treatment of ocular melanomas. Dose mean lineal energy, ( y D ¯ ), values were obtained at various depths in PMMA along a pristine and spread out Bragg peak (SOBP). The measured microdosimetric spectra at each position were then used as inputs into the modified Microdosimetric Kinetic Model (MKM) to derive the RBE for absorbed dose in a middle of the SOBP 2Gy (RBED ). Microdosimetric spectra were obtained with both the 5 and 10 μm 3D SOI microdosimeters, with a focus on the distal part of the BP. The in-field and out-of-field measurement configurations along the Bragg curve were modelled in Geant4 for comparison with experimental results. Lateral out-of-field measurements were performed to study secondary particles' contribution to normal tissue's dose, up to 12 mm from the edge of the beam field, and quality factor and dose equivalent results were obtained. Results Comparison between experimental and simulation results showed good agreement between one another for both the pristine and SOBP beams in terms of y D ¯ and RBED . Though a small discrepancy between experiment and simulation was seen at the entrance of the Bragg curve, where experimental results were slightly lower than Geant4. The dose equivalent value measured 12 mm from the edge of the target volume was 1.27 ± 0.15 mSv/Gy with a Q ¯ value of 2.52 ± 0.30, both of which agree within uncertainty with Geant4 simulation. Conclusions These results demonstrate that SOI microdosimeters are an effective tool to predict RBED in-field as well as dose equivalent monitoring out-of-field to provide insight to probability of second cancer generation.

Aim:Conjunctival squamous cell carcinoma (SCC) is a rare tumour of the ocular region and microscopic radical surgical is difficult. There are no single guidelines for therapeutic management and the role of radiation therapy is not clearly defined although conventionally photon or electron beams are used. Proton beam radiotherapy (PBRT) is a new option for a conservative approach and allows good sparing of the organs at risk.Materials and methods:After surgical resection, we collected 15 cases treated at our institution with PBRT. The dose delivered was between 48 and 60 Gy relative biological effectiveness (RBE), with fractions of 12–15 Gy RBE.Results:After an average period of 48 months, the patients achieved excellent disease control (overall survival and disease-free survival: 86·6%), with minimal acute and late toxicity.Findings:In this work, we present our experience on the use of PBRT technique in SCC treatment. A larger sample of patients is needed to draw conclusions about the impact of this treatment on disease recurrence and overall survival.

Hydrogenated Amorphous Silicon (a-Si:H) is a material well known for its intrinsic radiation hardness and is primarily utilized in solar cells as well as for particle detection and dosimetry. Planar p-i-n diode detectors are fabricated entirely by means of intrinsic and doped PECVD of a mixture of Silane (SiH4) and molecular Hydrogen. In order to develop 3D detector geometries using a-Si:H, two options for the junction fabrication have been considered: ion implantation and charge selective contacts through atomic layer deposition. In order to test the functionality of the charge selective contact electrodes, planar detectors have been fabricated utilizing this technique. In this paper, we provide a general overview of the 3D fabrication project followed by the results of leakage current measurements and x-ray dosimetric tests performed on planar diodes containing charge selective contacts to investigate the feasibility of the charge selective contact methodology for integration with the proposed 3D detector architectures., Submitted to JINST

The acceleration processes based on the coherent interaction of high-power lasers with matter are, by now, one of the most interesting topics in the field of particle acceleration, becoming day by day a real alternative to conventional approaches. Some of the extraordinary peculiarities of laser–matter interaction, such as the production of multi-species (gamma, X-rays, electrons, protons and ions), short-pulsed and intense beams are particularly attracting for many applications as well as for fundamental physics. In particular, laser-accelerated protons, if well controlled in terms of final energy spread, divergence and dose rate, could lead to investigate new research regimes in the field of medical physics, as well as in radiobiological applications. Many approaches are currently being developed aiming at optimizing the laser–target interaction mechanism and at collecting and selecting through dedicated transport beamlines the laser-accelerated proton beams in a future perspective to use them for the medical and radiobiological applications with a reduced uncertainty. An overview of the main parameters characterizing the laser-accelerated protons and of the transport, diagnostics and dosimetry solutions, currently adopted from the laser community, will be provided in this contribution.

Background There is currently significant interest in assessing the role of oxygen in the radiobiological effects at ultra-high dose rates. Oxygen modulation is postulated to play a role in the enhanced sparing effect observed in FLASH radiotherapy, where particles are delivered at 40–1000 Gy/s. Furthermore, the development of laser-driven accelerators now enables radiobiology experiments in extreme regimes where dose rates can exceed 109 Gy/s, and predicted oxygen depletion effects on cellular response can be tested. Access to appropriate experimental enviroments, allowing measurements under controlled oxygenation conditions, is a key requirement for these studies. We report on the development and application of a bespoke portable hypoxia chamber specifically designed for experiments employing laser-driven sources, but also suitable for comparator studies under FLASH and conventional irradiation conditions. Materials and methods We used oxygen concentration measurements to test the induction of hypoxia and the maintenance capacity of the chambers. Cellular hypoxia induction was verified using hypoxia inducible factor-1α immunostaining. Calibrated radiochromic films and GEANT-4 simulations verified the dosimetry variations inside and outside the chambers. We irradiated hypoxic human skin fibroblasts (AG01522B) cells with laser-driven protons, conventional protons and reference 225 kVp X-rays to quantify DNA DSB damage and repair under hypoxia. We further measured the oxygen enhancement ratio for cell survival after X-ray exposure in normal fibroblast and radioresistant patient- derived GBM stem cells. Results Oxygen measurements showed that our chambers maintained a radiobiological hypoxic environment for at least 45 min and pathological hypoxia for up to 24 h after disconnecting the chambers from the gas supply. We observed a significant reduction in the 53BP1 foci induced by laser-driven protons, conventional protons and X-rays in the hypoxic cells compared to normoxic cells at 30 min post-irradiation. Under hypoxic irradiations, the Laser-driven protons induced significant residual DNA DSB damage in hypoxic AG01522B cells compared to the conventional dose rate protons suggesting an important impact of these extremely high dose-rate exposures. We obtained an oxygen enhancement ratio (OER) of 2.1 ± 0.1 and 2.5 ± 0.1 respectively for the AG01522B and patient-derived GBM stem cells for X-ray irradiation using our hypoxia chambers. Conclusion We demonstrated the design and application of portable hypoxia chambers for studying cellular radiobiological endpoints after exposure to laser-driven protons at ultra-high dose, conventional protons and X-rays. Suitable levels of reduced oxygen concentration could be maintained in the absence of external gassing to quantify hypoxic effects. The data obtained provided indication of an enhanced residual DNA DSB damage under hypoxic conditions at ultra-high dose rate compared to the conventional protons or X-rays.

Purpose Monte Carlo (MC) simulations are widely used for medical applications and nuclear reaction models are fundamental for the simulation of the particle interactions with patients in ion therapy. Therefore, it is of utmost importance to have reliable models in MC simulations for such interactions. Geant4 is one of the most used toolkits for MC simulation. However, its models showed severe limitations in reproducing the yields measured in the interaction of ion beams below 100 MeV/u with thin targets. For this reason, we interfaced two models, SMF (“Stochastic Mean Field”) and BLOB (“Boltzmann-Langevin One Body”), dedicated to simulate such reactions, with Geant4. Methods Both SMF and BLOB are semi-classical, one-body approaches to solve the Boltzmann-Langevin equation. They include an identical treatment of the mean-field propagation, on the basis of the same effective interaction, but they differ in the way fluctuations are included. Furthermore, we tested a correction to the excitation energy calculated for the light fragments emerging from the simulations and a simple coalescence model. Results While both SMF and BLOB have been developed to simulate heavy ion interactions, they show very good results in reproducing the experimental yields of light fragments, up to alpha particles, obtained in the interaction of 12C with a thin carbon target at 62 MeV/u. Conclusions BLOB in particular gives promising results and this stresses the importance of integrating it into the Geant4 toolkit.

A new mini-TEPC with cylindrical sensitive volume of 0.9 mm in diameter and height, and with external diameter of 2.7 mm, has been developed to work without gas flow. With such a mini counter we have measured the physical quality of the 62 MeV therapeutic proton beam of CATANA (Catania, Italy). Measurements were performed at six precise positions along the Spread-Out Bragg Peak (SOBP): 1.4, 19.4, 24.6, 29.0, 29.7 and 30.8 mm, corresponding to positions of clinical relevance (entrance, proximal, central, and distal-edge of the SOBP) or of high lineal energy transfer (LET) increment (distal-dose drop off). Without refilling the microdosimeter with new gas, the measurements were repeated at the same positions 4 months later, in order to study the stability of the response in sealed-mode operation. From the microdosimetric spectra the frequency-mean lineal energy y

The main direction proposed by the community of experts in the field of laser-driven ion acceleration is to improve particle beam features (maximum energy, charge, emittance, divergence, monochromaticity, shot-to-shot stability) in order to demonstrate reliable and compact approaches to be used for multidisciplinary applications, thus, in principle, reducing the overall cost of a laser-based facility compared to a conventional accelerator one and, at the same time, demonstrating innovative and more effective sample irradiation geometries. The mission of the laser-driven ion target area at ELI-Beamlines (Extreme Light Infrastructure) in Dolni Břežany, Czech Republic, called ELI Multidisciplinary Applications of laser-Ion Acceleration (ELIMAIA) [1], is to provide stable, fully characterized and tunable beams of particles accelerated by Petawatt-class lasers and to offer them to the user community for multidisciplinary applications. The ELIMAIA beamline has been designed and developed at the Institute of Physics of the Academy of Science of the Czech Republic (IoP-ASCR) in Prague and at the National Laboratories of Southern Italy of the National Institute for Nuclear Physics (LNS-INFN) in Catania (Italy). The key section of the beamline, which includes the beam focusing, the energy selection, the beam transport, the dosimetric and sample irradiation elements, is called ELIMED (ELI MEDical and multidisciplinary applications) [2] portion. At ELIMED, controlled proton and light ion (included carbon) beams up to 300 MeV and 70 AMeV, respectively, can be transported down to the in-air section where absolute dosimetry can be carried out with dose-rate independent devices. A transmission, dual-gap air ionisation chamber provides an on-line measurement of the ion beam dose at the irradiation point, simultaneously allowing for corrections related to ion recombination effects. The maximum expected uncertainty in the final dose released into the user sample is less then 5%. The ELIMED pilot experiment on sample irradiation with laser-accelerated protons is scheduled in 2021. A radiobiological campaign for in-vitro irradiation is planned. In this presentation the status of the ELIMED-ELIMAIA beamline will be reported along with a complete description of its dosimetry systems and their preliminary calibration. The expected final beam characteristics, in terms of dose per pulse, dose-rate and beam spot size (numerically calculated by Monte Carlo simulations) will also be reported. Moreover, an innovative detector based on Silicon Carbide technology capable to reconstruct proton range, energy spectrum, and online released dose will be also discussed. [1] D. Margarone, G.A.P.Cirrone et al., “ELIMAIA: A Laser-Driven Ion Accelerator for Multidisciplinary Applications”, Quantum Beam. Sci., 2, 8 (2018) [2] G.A.P Cirrone, M. Carpinelli et al., “ELIMED, future hadrontherapy applications of laser-accelerated beams”, Nucl. Inst. Meth. 730:174–177 (2013)

Journal of Personalized Medicine 11(4), 308 (2021). doi:10.3390/jpm11040308, Published by MDPI, Basel

CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) was the first Italian protontherapy facility dedicated to the treatment of ocular neoplastic pathologies. It is in operation at the LNS Laboratories of the Italian Institute for Nuclear Physics (INFN-LNS) and to date, 500 patients have been successfully treated. Even though proton therapy has demonstrated success in clinical settings, there is still a need for more accurate models because they are crucial for the estimation of clinically relevant RBE values. Since RBE can vary depending on several physical and biological parameters, there is a clear need for more experimental data to generate predictions. Establishing a database of cell survival experiments is therefore useful to accurately predict the effects of irradiations on both cancerous and normal tissue. The main aim of this work was to compare RBE values obtained from in-vitro experimental data with predictions made by the LEM II (Local Effect Model), Monte Carlo approaches, and semi-empirical models based on LET experimental measurements. For this purpose, the 92.1 uveal melanoma and ARPE-19 cells derived from normal retinal pigmented epithelium were selected and irradiated in the middle of clinical SOBP of the CATANA proton therapy facility. The remarkable results show the potentiality of using microdosimetric spectrum, Monte Carlo simulations and LEM model to predict not only the RBE but also the survival curves.

The main effort of the laser-driven ion acceleration community is aimed to improve particle beam features (energy, charge, divergence, monochromaticity) and to demonstrate reliable approaches to be used for multidisciplinary applications. An ion acceleration target area based on unique laser capabilities is available at ELI-Beamlines (Extreme Light Infrastructure) in the Czech Republic; it is called ELIMAIA (ELI Multidisciplinary Applications of laser-Ion Acceleration) and aims to provide stable, fully characterized and tuneable beams of particles accelerated by multi-Petawatt-class lasers and to offer them to the user community for multidisciplinary applications. The ELIMAIA section dedicated to ion focusing, selection, characterization and irradiation is named ELIMED (ELI MEDical and multidisciplinary applications). Thanks to ELIMED, very high-dose-rate (around Gy/min) controlled proton and ion beams, with energy ranging from 5 to 250 MeV, will be transported up to an in-air section dedicated to absolute and relative dosimetry of the laser-generated ions. A transmission, dual-gap air ionisation chamber will allow an on-line, non-destructive characterization of the ion dose at the user sample irradiation point. The uncertainty in the final dose released onto the sample is expected to be well below 5$\%$. An ELIMED radiobiology pilot experiment is scheduled in 2021, during which in-vitro cell irradiations will be carried out with well-controlled proton beams. In this work, the status of the ELIMED/ELIMAIA beamline will be reported along with a complete description of the main dosimetric systems and of their calibrations carried out at conventional accelerators.

Significant challenges in the detection of laser-accelerated ions result from the high flux (1010-1012 ions/pulse) and the short bunch duration which are intrinsic to laser-driven sources. The development of diagnostic techniques able to operate in real-time and on a high-rep basis is a key step towards multidisciplinary applications of such non-conventional beams. Real time diagnosis of the main beam parameters for high-energy protons accelerated by the Vulcan Petawatt (VULCAN-PW) laser system has been performed using an on line diagnostics based on the Time of Flight (TOF) technique and the use of diamond detectors. Proton energy spectra have been measured for energies exceeding 30 MeV. The results show that the TOF method employing state-of-the-art detectors is a robust real-time diagnostics, able to operate efficiently under the harsh conditions occurring with kJ-class, PW laser systems, and offering the possibility to monitor on a shot-by-shot basis the main beam parameters of high intensity proton bunches for energies up to the 100 MeV level.

We present preliminary results on generation of energetic α-particles driven by lasers. The experiment was performed at the Institute of Laser Engineering in Osaka using the short-pulse, high-intensity, high-energy, PW-class laser. The laser pulse was focused onto a thin plastic foil (pitcher) to generate a proton beam by the well-known TNSA mechanism which, in turn, was impinging onto a boron-nitride (BN) target (catcher) to generated alpha-particles as a result of proton-boron nuclear fusion events. Our results demonstrate generation of α-particles with energies in the range 8–10 MeV and with a flux around 5 × 10^9 sr^−1.

Specific breast cancer (BC) subtypes are associated with bad prognoses due to the absence of successful treatment plans. The triple-negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptor status, is a clinical challenge for oncologists, because of its aggressiveness and the absence of effective therapies. In addition, proton therapy (PT) represents an effective treatment against both inaccessible area located or conventional radiotherapy (RT)-resistant cancers, becoming a promising therapeutic choice for TNBC. Our study aimed to analyze the in vivo molecular response to PT and its efficacy in a MDA-MB-231 TNBC xenograft model. TNBC xenograft models were irradiated with 2, 6 and 9 Gy of PT. Gene expression profile (GEP) analyses and immunohistochemical assay (IHC) were performed to highlight specific pathways and key molecules involved in cell response to the radiation. GEP analysis revealed in depth the molecular response to PT, showing a considerable immune response, cell cycle and stem cell process regulation. Only the dose of 9 Gy shifted the balance toward pro-death signaling as a dose escalation which can be easily performed using proton beams, which permit targeting tumors while avoiding damage to the surrounding healthy tissue.

A microdosimetric characterization of the 62 MeV proton beam line of CATANA has been performed all along the Spread Out Bragg Peak with three different detectors. Two silicon detectors and a Tissue Equivalent Proportional Counter measured at approximately the same depths of the SOBP. The TEPC is a new miniaturized gas counter developed at the Legnaro National Laboratories of INFN, modified to work without gas flow. The first silicon detector has been developed at the Politecnico of Milano and it is a monolithic telescope composed by a matrix of 2 µm thick cylindrical diodes with a diameter 9 µm. that compose the ΔE layer. The E and ΔE layers are fabricated on a single substrate of silicon. The third detector is the MicroPlus probe developed at the CMRP - University of Wollongong, it is an array of 3D sensitive volumes each with dimension 30x30 µm and 10 µm thick fabricated on SOI. Measurements performed with the three detectors are presented and discussed. This work was supported by the 5th Scientific Commission of the Italian Institute for Nuclear Physics (INFN), the Belgian Nuclear Research Centre SCK•CEN and Hasselt University. This work has been partially supported by the ENEN+ project that has received funding from the EURATOM research and training Work Programme 2016 – 2017 – 1 #755576.

Purpose: A reliable model to simulate nuclear interactions is fundamental for Ion-therapy. We already showed how BLOB ("Boltzmann-Langevin One Body"), a model developed to simulate heavy ion interactions up to few hundreds of MeV/u, could simulate also $^{12}$C reactions in the same energy domain. However, its computation time is too long for any medical application. For this reason we present the possibility of emulating it with a Deep Learning algorithm. Methods: The BLOB final state is a Probability Density Function (PDF) of finding a nucleon in a position of the phase space. We discretised this PDF and trained a Variational Auto-Encoder (VAE) to reproduce such a discrete PDF. As a proof of concept, we developed and trained a VAE to emulate BLOB in simulating the interactions of $^{12}$C with $^{12}$C at 62 MeV/u. To have more control on the generation, we forced the VAE latent space to be organised with respect to the impact parameter ($b$) training a classifier of $b$ jointly with the VAE. Results: The distributions obtained from the VAE are similar to the input ones and the computation time needed to use the VAE as a generator is negligible. Conclusions: We show that it is possible to use a Deep Learning approach to emulate a model developed to simulate nuclear reactions in the energy range of interest for Ion-therapy. We foresee the implementation of the generation part in C++ and to interface it with the most used Monte Carlo toolkit: Geant4., Comment: 8 pages, 9 figures, Accepted by Physica Medica

The ELIMAIA beamline, recently installed at ELI-Beamlines, aims at offering short ion bunches accelerated by high repetition-rate, PW-class lasers to users from multidisciplinary fields by using innovative and compact ion beam transport and dosimetry approaches.

PURPOSE The purpose of this study was to investigate for the first time the performance of a synthetic single crystal diamond detector for the microdosimetric characterization of clinical 62 MeV ocular therapy proton beams. METHODS A novel diamond microdosimeter with a well-defined sensitive volume was fabricated and tested with a monoenergetic and spread-out Bragg peak (SOBP) of the CATANA therapeutic proton beam in Catania, Italy. The whole sensitive volume of the detector has an active planar-sectional area of 100 µm × 100 µm and a thickness of approximately 6.3 um. Microdosimetric measurements were performed at several water equivalent depths, corresponding to positions of clinical relevance. From the measured spectra, microdosimetric quantities such as the frequency mean lineal energy ( y¯F ), dose mean lineal energy ( y¯D ) as well as microdosimetric relative biological effectiveness (RBEµ ) values were derived for each depth along both a pristine Bragg curve and SOBP. Finally, Geant4 Monte Carlo simulations were performed modeling the detector geometry and CATANA beamline in order to calculate the average linear energy transfer (LET) values in the diamond active layer and water. RESULTS The microdosimetric spectra acquired by the diamond microdosimeter show different shapes as a function of the water equivalent depths. No spectral distortion, due to pile-up events and polarization effects, was observed. The experimental spectra have a very low detection threshold due to the electronic noise during the irradiation of about 1 keV/μm. The y¯F and y¯D values were in agreement with expected trends, showing a sharp increase in mean lineal energy at the distal edge of the Bragg peak. In addition, a good agreement between the mean lineal energy values and the calculated average LET ones was also observed. Finally, the RBE values evaluated with the diamond microdosimeter were in excellent agreement with those obtained with a mini tissue equivalent proportional counter as well as with radiobiological measurements in the same proton beam field. CONCLUSIONS The microdosimetric performance of the tested synthetic single crystal diamond microdosimeter clearly indicates its suitability for quality assurance in clinical proton therapy beam.

Purpose The main purpose of this work is the inter-comparison between different devices devoted to the transversal dose profile recostruction for daily QA tests in proton therapy. Methods The results obtained with the EBT3 radiochromic films, used as a reference, and other common quality control devices, have been compared with those obtained with a beam profiling system developed at the “Laboratori Nazionali del Sud” of Italian Institute for Nuclear Physics (INFN-LNS, Catania, Italy). It consists of a plastic scintillator screen (thickness 1 mm), mounted perpendicularly to the beam axis and coupled with a highly sensitive CCD detector in a light-tight box. Results and conclusion The tests, carried out both at the INFN-LNS and Trento Proton Therapy Center facilities, show, in general, a good agreement between the different detectors. The beam profiling system, in particular, appears to be a promising quality control device for 2-D relative dosimetry, because of its linear response in a dose rate range useful for proton therapy treatments, its high spatial resolution and its short acquisition and processing time.

Conjunctival melanoma is a rare neoplasia, whose therapeutic management is generally of ophthalmological relevance, through radical surgical resection. The high incidence of local relapses after surgery, has made it necessary to combine various types of adjuvant treatments, which in some cases take on the role of radical treatments. Among these non-surgical treatments, those involving the application of ionizing radiation are becoming particularly important. In this review, we discuss the role of episcleral brachytherapy, external photon-beam radiotherapy, also made through stereotactic or radiosurgical modality, and of proton-beam radiotherapy. We try also to take stock of the benefits of the different irradiation modalities and the application difficulties of each.

The main purpose of this paper is to quantitatively study the possibility of delivering dose distributions of clinical relevance with laser-driven proton beams. A Monte Carlo application has been developed with the Geant4 toolkit, simulating the ELIMED (MEDical and multidisciplinary application at ELI-Beamlines) transport and dosimetry beam line which is being currently installed at the ELI-Beamlines in Prague (CZ). The beam line will be used to perform irradiations for multidisciplinary studies, with the purpose of demonstrating the possible use of optically accelerated ion beams for therapeutic purposes. The ELIMED Geant4-based application, already validated against reference transport codes, accurately simulates each single element of the beam line, necessary to collect the accelerated beams and to select them in energy. Transversal dose distributions at the irradiation point have been studied and optimized to try to quantitatively answer the question if such kind of beam lines, and specifically the systems developed for ELIMED in Prague, will be actually able to transport ion beams not only for multidisciplinary applications, such as pitcher-catcher nuclear reactions (e.g. neutrons), PIXE analysis for cultural heritage and space radiation, but also for delivering dose patterns of clinical relevance in a future perspective of possible medical applications.

Preclinical studies represent an important step towards a deep understanding of the biological response to ionizing radiations. The effectiveness of proton therapy is higher than photons and, for clinical purposes, a fixed value of 1.1 is used for the relative biological effectiveness (RBE) of protons considered 1.1. Recent in vitro studies have reported that the RBE along the spread-out Bragg peak (SOBP) is not constant and, in particular, the RBE value increases on the distal part of SOBP. The present work has been carried-out in the perspective of a preclinical hadrontherapy facility at LNS-INFN and was focused on the experimental preparation of an in vivo study concerning the RBE variation along the SOBP. The main purpose of this work was to determine, using GEANT4-based Monte Carlo simulations, the best configuration for small animal treatments. The developed GEANT4 application simulates the proton-therapy beam line of LNS-INFN (CATANA facility) and allows to import the DICOM-CT images as targets. The RBE will be evaluated using a deterministic radiation damage like myelopathy as end-point. In fact, the dose at which the 50% of animals will show the myelopathy is supposed to be LET-dependent. In this work, we studied different treatment configurations in order to choose the best two that maximize the LET difference reducing as much as possible the dose released to healthy tissue. The results will be useful to plan hadrontherapy treatments for preclinical in vivo studies and, in particular, for the future in vivo RBE studies.

ELIMED has been developed and installed at ELI beamlines as a part of the ELIMAIA beamline to transport, monitor, and use laser-driven ion beams suitable for multidisciplinary applications, including biomedical ones. This paper aims to investigate the feasibility to perform radiobiological experiments using laser-accelerated proton beams with intermediate energies (up to 30 MeV). To reach this goal, we simulate a proton source based on experimental data like the ones expected to be available in the first phase of ELIMED commissioning by using the G4-ELIMED application (an application based on the Geant4 toolkit that simulates the full ELIMED beamline). This allows the study of transmission efficiency and the final characteristics of the proton beam at the sample irradiation point. The Energy Selector System is used as an active energy modulator to obtain the desired beam features in a relatively short irradiation time (around 6 min). Furthermore, we demonstrate the capability of the beamline to filter out other ion contaminants, typically co-accelerated in a laser-plasma environment. These results can be considered as a detailed feasibility study for the use of ELIMED for various user applications such as radiobiological experiments with ultrahigh dose rate proton beams.

Simple Summary Proton therapy is now an established external radiotherapy modality for cancer treatment. Clinical routine currently neglects the radiobiological impact of nuclear target fragments even if experimental evidences show a significant enhancement in cell-killing effect due to secondary particles. This paper quantifies the contribution of proton target fragments of different charge in different irradiation scenarios and compares the computationally predicted corrections to the overall biological dose with experimental data. Abstract Clinical routine in proton therapy currently neglects the radiobiological impact of nuclear target fragments generated by proton beams. This is partially due to the difficult characterization of the irradiation field. The detection of low energetic fragments, secondary protons and fragments, is in fact challenging due to their very short range. However, considering their low residual energy and therefore high LET, the possible contribution of such heavy particles to the overall biological effect could be not negligible. In this context, we performed a systematic analysis aimed at an explicit assessment of the RBE (relative biological effectiveness, i.e., the ratio of photon to proton physical dose needed to achieve the same biological effect) contribution of target fragments in the biological dose calculations of proton fields. The TOPAS Monte Carlo code has been used to characterize the radiation field, i.e., for the scoring of primary protons and fragments in an exemplary water target. TRiP98, in combination with LEM IV RBE tables, was then employed to evaluate the RBE with a mixed field approach accounting for fragments’ contributions. The results were compared with that obtained by considering only primary protons for the pristine beam and spread out Bragg peak (SOBP) irradiations, in order to estimate the relative weight of target fragments to the overall RBE. A sensitivity analysis of the secondary particles production cross-sections to the biological dose has been also carried out in this study. Finally, our modeling approach was applied to the analysis of a selection of cell survival and RBE data extracted from published in vitro studies. Our results indicate that, for high energy proton beams, the main contribution to the biological effect due to the secondary particles can be attributed to secondary protons, while the contribution of heavier fragments is mainly due to helium. The impact of target fragments on the biological dose is maximized in the entrance channels and for small α/β values. When applied to the description of survival data, model predictions including all fragments allowed better agreement to experimental data at high energies, while a minor effect was observed in the peak region. An improved description was also obtained when including the fragments’ contribution to describe RBE data. Overall, this analysis indicates that a minor contribution can be expected to the overall RBE resulting from target fragments. However, considering the fragmentation effects can improve the agreement with experimental data for high energy proton beams.

The characterisation of a novel multi-strip silicon detector, the serial Dose Magnifying Glass, to incident 60 MeV mono-energetic proton beams, typical for ocular melanoma treatment, was performed by means of Geant4 simulations and experimental methods. Geant4 simulations were performed to determine the applicability and potential of the detector for proton beam range verification with high spatial resolution. Experimental characterisation was performed using the CATANA beam line to confirm the Monte Carlo feasibility study and determine the detector response to incident proton beams of 5 mm, 13 mm, 25 mm and 36 mm diameter, in addition to the detector response when PMMA slabs are positioned between the detector and the beam nozzle. Results indicate the suitability of the detector for proton beam range verification in proton therapy Quality Assurance.

The Bragg Peak is a unique characteristic of ion beams which makes their use beneficial in cancer treatment as it allows the majority of dose deposition to be localised in a precise volume. The use of a laser system for particle acceleration is currently investigated as a potential alternative to the conventional RF accelerators currently used for hadrontherapy. The biological response of cells irradiated by high dose-rate laser-driven ions is currently being explored in this context. The experiment reported here was carried out as part of the A-SAIL project, a UK-wide collaboration aiming to develop innovative techniques for accelerating ions for future clinical applications. In this contest, a radiobiological experiment was carried out on the pico2000 laser beamline at LULI-aEcole Polytechnique using an energetically spread, laser-accelerated proton beam. This paper will discuss the arrangement used in the experiment, and the techniques employed for an accurate estimation of the dose deposited, supported by Monte Carlo simulations of the particle propagation through the irradiation system.

International audience; The Time-of-Flight (TOF) technique coupled with semiconductorlike detectors, as silicon carbide and diamond, is one of the most promising diagnostic methods for high-energy, high repetition rate, laser-accelerated ions allowing a full on-line beam spectral characterization. A new analysis method for reconstructing the energy spectrum of high-energy laser-driven ion beams from TOF signals is hereby presented and discussed. The proposed method takes into account the detector’s working principle, through the accurate calculation of the energy loss in the detector active layer, using Monte Carlo simulations. The analysis method was validated against well-established diagnostics, such as the Thomson parabola spectrometer, during an experimental campaign carried out at the Rutherford Appleton Laboratory (UK) with the high-energy laser-driven protons accelerated by the VULCAN Petawatt laser.

A new practical method to determine the ion recombination correction factor (alt;iagt;kalt;subagt;salt;/subagt;alt;/iagt;) for plane-parallel and Farmer-type cylindrical chambers in particle beams is investigated. a#13; Experimental data were acquired in passively scattered and scanned particle beams and compared with theoretical models developed by Boag and/or Jaffe. The new method, named the three-voltage linear method(3VL-method), is simple and consists of determining the saturation current using the current measured at three voltages in a linear region and dividing it by the current at the operating voltage(alt;iagt;Valt;/iagt;) (even if it is not in the linear region) to obtain alt;iagt;kalt;subagt;salt;/subagt;alt;/iagt;.a#13; For plane-parallel chambers, comparing alt;iagt;kalt;subagt;salt;/subagt;alt;/iagt;-values obtained by model fits to values obtained using the 3VL-method, an excellent agreement is found. For cylindrical chambers, recombination is due to volume recombination only. At low voltages, volume recombination is too large and Boag's models are not applicable. However, for Farmer-type chambers (NE2571), using a smaller voltage range, limited down to 100 V, we observe a linear variation of alt;iagt;kalt;subagt;salt;/subagt;alt;/iagt; with 1/alt;iagt;Valt;/iagt;² or 1/alt;iagt;Valt;/iagt; for continuous or pulsed beams, respectively. This linearity trend allows applying the 3VL-method to determine alt;iagt;kalt;subagt;salt;/subagt;alt;/iagt; at any polarizing voltage. a#13; For the particle beams used, the 3VL-method gives an accurate determination of alt;iagt;kalt;subagt;salt;/subagt;alt;/iagt; at any polarizing voltage. The choice of the three voltages must to be done with care to ensure to be in a linear region. For Roos-type or Markus-type chambers (alt;iagt;i.e.alt;/iagt; chambers with an electrode spacing of 2 mm) and NE2571 chambers, the use of the 3VL-method with 300 V, 200 V and 150 V is adequate. A difference with the 2V-method and some 3V-methods in the literature is that in the 3VL-method the operational voltage does not have to be one of the three voltages. An advantage over a 2V-method is that the 3VL-method can inherently verify if the linearity condition is fulfilled.

Purpose To perform the first dosimetric intercomparison for proton beams in Italy using ionization chambers, according to the IAEA TRS-398 code of practice. Methods Measurement sites included: National Center for Oncological Hadron Therapy (CNAO, Pavia), Center for Proton Therapy (CTP, Trento) and Center for Hadron Therapy and for advanced Nuclear Applications (CATANA, Catania). For comparison we also included a 6 MV photon beam produced at Istituti Clinici Scientifici Maugeri (ICSM, Pavia). For proton beams, both single pseudo-monoenergetic layers (in order to obtain a planned dose of 2 Gy at the reference depth of 2 cm in a water phantom) and Spread-out Bragg peaks (SOBP) have been delivered. Measurements were performed with a PTW Farmer 30010-1 and a PTW Advanced Markus type 34,045 ionization chamber. Results Data obtained at CATANA, CNAO and CPT in terms of absorbed dose to water depth show good consistency within the experimental uncertainties, with a weighted mean of 1.99 ± 0.01 Gy and a standard error of 0.003 Gy, with reference to a nominal dose of 2 Gy as designed by the treatment planning system. Conclusions The results showed a standard deviation of less than 1% for single layer and SOBP beams, for all chambers and a percent deviation less than 1.5% for single layer measurements. The weighted means of the absorbed doses for clinical proton beams (118.19 MeV and 173.61 MeV) are consistent within less than 1%. These results agree within the 1.5% difference considered acceptable for national dose intercomparison.

A TEPC capable of simulating site sizes down to 25 nm was designed and constructed in order to fill the gap between nanodosimetry and experimental microdosimetry. In this paper, this device was proposed for assessing the quality of the therapeutic CATANA (INFN-LNS) proton beam. The detector was irradiated with a modulated 62 MeV proton beam and was placed at different depths across the spread-out of Bragg peak. For each position, several microdosimetric distributions for different simulated site size from 0.5 μm to 35 nm were acquired. The 0.5 μm spectra are in good agreement with spectra measured employing a reference TEPC in the same experimental conditions. The results show that, for bigger sites, microdosimetric distributions follow the slowing down of the primary particles, while, for smaller sites, they exhibit a bimodal shape, in particular at smaller depths in PMMA. The comparison between different simulated volumes shows an increment of the dose-averaged lineal energy with the reduction of the site. Moreover, a comparison between a ratio of the dose-averaged lineal energy for different simulates site sizes and the microdosimetric R B E shows that the smaller is the simulated volume, the better is the resembling of the microdosimetric R B E even if, the agreement is not yet fully reached for any site size. Finally, Monte Carlo simulations show that the electron energy threshold in FLUKA is too high for reproducing microdosimetric distributions for nanometric sites for proton beams.

Purpose The Geant4 Monte Carlo simulation toolkit was used to reproduce radiobiological parameters measured by irradiating three different cancerous cell lines with monochromatic and clinical proton beams. Methods The experimental set-up adopted for irradiations was fully simulated with a dedicated open-source Geant4 application. Cells survival fractions was calculated coupling the Geant4 simulations with two analytical radiobiological models: one based on the LEM (Local Effect Model) approach and the other on a semi-empirical parameterisation. Results was evaluated and compared with experimental data. Results and conclusions The results demonstrated the Geant4 ability to reproduce radiobiological quantities for different cell lines.

Monte Carlo simulation represents nowadays one of the powerful approach for the simulation of very complex environments like those typical of medical physics where, in general, an accurate simulation of the involved radiation beams and of the patients are required to fully reproduce a clinical case. It since from 1963, when Berger introduced the condensed approach for the simulation of electron interaction with matter grew being today one of the most important tools used to verify the dose distribution in patients, design radiotherapy facility, study the radioisotopesproton/ion beams and their application (Berger. Monte Carlo calculation of the penetration and diffusion of fast charged particles, vol. I. Academic Press, New York, pp. 135–215, 1963 [1]),(Berger and Hubbell. XCOM: photon cross sections on a personal computer, Technical Report NBSIR 87–3597. National Institute of Standards and Technology, Gaithersburg, MD, 1987. [2]). Monte Carlo is also often used to evaluate important parameters related with the quality of a radiation treatment [3]. Evaluation of radiobiological damage from charged particles represents a complex calculation where a simple analytical approach is not sufficient for a precise and complete description of involved phenomena. In this work we will present, after a brief introduction on Monte Carlo method, the use of the open-source Geant4 toolkit for the simulation of a typical hadrontherapy passive beamline and how it can be efficiently used to retrieve critical parameters like LET and RBE.

In this work we present the response of a new large volume 4H Silicon Carbide (SiC) detector to 14 MeV neutrons. The device has an active thickness of 100 μ m (obtained by epitaxial growing) and an active area of 25 mm2. Tests were conducted at the ENEA-Frascati Neutron Generator facility by using 14.1 MeV neutrons. The SiC detector performance was compared to that of Single-Crystal Diamond (SCD) detectors. The SiC response function was successfully measured and revealed a very complex structure due to the presence in the detector of both Silicon and Carbon atoms. Nevertheless, the flexibility in the SiC manufacturing and the new achievements in terms of relatively large areas (up 1x1 cm2) and a wide range of thicknesses makes them an interesting alternative to diamond detectors in environments where limited space and high neutron fluxes are an issue, i.e. modern neutron cameras or in-vessel tokamak measurements for the new generation fusion machines such as ITER. The absence of instabilities during neutron irradiation and the capability to withstand high neutron fluences and to follow the neutron yield suggest a straightforward use of these detectors as a neutron diagnostics.

Since 2017, the Laboratori Nazionali del Sud (LNS) – INFN Catania is involved into the ASI Supported Irradiation Facilties (ASIF) Project. This program is formulated by the Italian Space Agency (ASI) aims to establish an interactive coordinated set of the irradiation facilities, throughout the national territory, serving the national and international space communities. All the facilities involved must follow the recommendations provided by the ESA in order to obtain the standardization of the space testing procedures. Two beamlines at LNS have been appropriately adapted for Integrated Dose Test and Single Event Effect measurement. The paper will present the upgrade measures implemented to fulfill the European Space Agency (ESA) recommendations and the latest results of beam diagnostic system.

A first prototype of transport beam-line for laser-driven ion beams to be used for the handling of particles accelerated by high-power laser interacting with solid targets has been realized at INFN. The goal is the production of a controlled and stable beam in terms of energy and angular spread. The beam-line consists of two elements: an Energy Selection System (ESS), already realized and characterized with both conventional and laser-accelerated beams, and a Permanent Magnet Quadrupole system (PMQ) designed, in collaboration with SIGMAPHI (Fr), to improve the ESS performances. In this work a description of the ESS system and some results of its characterization with conventional beams are reported, in order to provide a complete explanation of the acceptance calculation. Then, the matching with the PMQ system is presented and, finally, the results of preliminary simulations with a realistic laser-driven energy spectrum are discussed demonstrating the possibility to provide a good quality beam downstream the systems.

In proton beam therapy, a Spread-Out Bragg peak (SOBP) is used to establish a uniform dose distribution in the target volume. In order to create a SOBP, several Bragg peaks of different ranges, corresponding to different entrance energies, with certain intensities (weights) should be combined each other. In a passive beam scattering system, the beam is usually extracted from a cyclotron at a constant energy throughout a treatment. Therefore, a SOBP is produced by a range modulator wheel, which is basically a rotating wheel with steps of variable thicknesses, or by using the ridge filters. In this study, we used the Geant4 toolkit to simulate a typical passive scattering beam line. In particular, the CATANA transport beam line of INFN Laboratori Nazionali del Sud (LNS) in Catania has been reproduced in this work. Some initial properties of the entrance beam have been checked by benchmarking simulations with experimental data. A class dedicated to the simulation of the wheel modulators has been implemented. It has been designed in order to be easily modified for simulating any desired modulator wheel and, hence, any suitable beam modulation. By using some auxiliary range-shifters, a set of pristine Bragg peaks was obtained from the simulations. A mathematical algorithm was developed, using the simulated pristine dose profiles as its input, to calculate the weight of each pristine peak, reproduce the SOBP, and finally generate a flat dose distribution. Therefore, once the designed modulator has been realized, it has been tested at CATANA facility, comparing the experimental data with the simulation results.

A sealed mini-TEPC able to work in gas-steady modality, a monolithic silicon device composed by a matrix of micrometric cylindrical diodes and a residual energy measurement stage and the silicon MicroPlus Bridge detector were used to perform microdosimetric measurements at the 62 MeV proton clinical SOBP of CATANA at the Southern National Laboratories of INFN (LNS – INFN, Catania, Italy). Measurements were taken at the same different positions in a PMMA phantom, in order to analyse the detector response differences. Finally, a weighting function was applied to the spectra to see if the microdosimetric detectors are able to monitor RBE data for glioma cells (U87) irradiated at six positions along the same modulated 62-MeV proton beam. The results obtained with the three microdosimeters are compared and discussed.

In the last decades Silicon Carbide (SiC) received special attentions, in particular as semiconductor material, because is considered as alternative to Silicon for the future high-power, low consumption, radiation-hard microelectronics devices. This ambitious goal is particularly interesting also for the physics of the detectors. In this work are discussed some of the recent results obtained by SiCILIA collaboration, a joint research activity between INFN and IMM institutions to increase the level of technological development in the field of SiC detectors.

A sealed miniaturized Tissue Equivalent Proportional Counter (mini-TEPC) able to work in gas-steady modality was developed at the Legnaro National Laboratories of the Italian National Institute of Nuclear Physics (LNL – INFN, Legnaro, Italy). The aim of the present work is to compare the response of this mini-TEPC with that of a silicon microdosimeter based on a monolithic telescope. Pairwise measurements were performed at the 62 MeV proton clinical Spread Out Bragg Peak (SOBP) of CATANA at the Southern National Laboratories of INFN (LNS – INFN, Catania, Italy). The dose mean lineal energy values were derived from the spectra measured with the two detectors and compared with the total dose-averaged LET calculated by means of Geant4 Monte Carlo simulations. Finally, the possibility to apply the Microdosimetric Kinetic Model (MKM) to reproduce RBE variations with depth along the Spread Out Bragg Peak was investigated.

Silicon Carbide (SiC) has been recently proposed and patented as a material for the realization of radiation dosimetry detectors. SiC properties, including its high sensitivity, radiation damage resistance and its extremely small sensitivity region, make it an amazing device susceptible to radiation dosimetric applications of direct ionizing radiations. In this work, a dosimetric characterization of a 10 μm thick SiC detector, irradiated with 62 MeV monochromatic and clinical SOBP proton beams, is reported. Short term reproducibility and linearity with the absorbed dose demonstrate that SiC can be profitably used as radiation dosimetry in proton therapy applications.

The tissue-equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a particle beam but, since the lower operation limit of common TEPCs is ~0.3 μm, no detailed information on the track structure of the impinging particles can be obtained. The pattern of particle interactions at the nanometric level is measured directly by only three different nanodosimeters worldwide: practical instruments are not yet available. In order to partially fill the gap between microdosimetry and track-nanodosimetry, a low-pressure avalanche-confinement TEPC was designed and constructed for simulating tissue-equivalent sites down to the nanometric region. The present paper aims at describing the response of this TEPC in the range 0.3 μm-25 nm to a 62 MeV/n 4He ion beam. The experimental results, for depths near the Bragg peak, show good agreement with FLUKA simulations and suggest that, for smaller depths, the distribution is highly influenced by secondary electrons.

Reliable nuclear fragmentation models are of utmost importance in hadron therapy, where Monte Carlo (MC) simulations are used to compute the input parameters of the treatment planning software, to validate the deposited dose calculation, to evaluate the biological effectiveness of the radiation, to correlate the \( \beta + \) emitters production in the patient body with the delivered dose, and to allow a non-invasive treatment verification. Despite of its large use, the models implemented in Geant4 have shown severe limitations in reproducing the measured secondaries yields in ions interaction below 100 MeV/A, in term of production rates, angular and energy distributions. We present a benchmark of the Geant4 models with double-differential cross section of the secondary fragments produced in the \( ^{12} {\text{C}} \) fragmentation at 62 MeV/A on thin carbon target. Such a benchmark includes the recently implemented model “Liege Intranuclear Cascade’’. Moreover, we present the preliminary results, obtained in simulating the same interaction, with the “Boltzmann-Langevin One Body’’ model (BLOB). BLOB is a semiclassical one-body approaches to solve the Boltzmann-Langevin equation. It includes a mean-field propagation term, on the basis of an effective interaction. In addition to the mean field term, BLOB introduces fluctuations in full phase space through a modified collision term where nucleon-nucleon correlations are explicitly involved. It has been developed to simulate the heavy ion interactions in the Fermi-energy regime. In this work, we show the BLOB capabilities in describing \( ^{12} {\text{C}} \) fragmentation, in the perspective of a direct implementation in Geant4. Monte Carlo simulation, nuclear interaction, nuclear fragmentation, hadron therapy.

Purpose The aim of this paper is to investigate the limits of LET monitoring of therapeutic carbon ion beams with miniaturized microdosimetric detectors. Methods Four different miniaturized microdosimeters have been used at the 62 MeV/u 12C beam of INFN Southern National Laboratory (LNS) of Catania for this purpose, i.e. a mini-TEPC and a GEM-microdosimeter, both filled with propane gas, and a silicon and a diamond microdosimeter. The y - D (dose-mean lineal energy) values, measured at different depths in a PMMA phantom, have been compared with LET ¯ D (dose-mean LET) values in water, calculated at the same water-equivalent depth with a Monte Carlo simulation setup based on the GEANT4 toolkit. Results In these first measurements, no detector was found to be significantly better than the others as a LET monitor. The y - D relative standard deviation has been assessed to be 13% for all the detectors. On average, the ratio between y - D and LET ¯ D values is 0.9 ± 0.3, spanning from 0.73 ± 0.08 (in the proximal edge and Bragg peak region) to 1.1 ± 0.3 at the distal edge. Conclusions All the four microdosimeters are able to monitor the dose-mean LET with the 11% precision up to the distal edge. In the distal edge region, the ratio of y - D to LET ¯ D changes. Such variability is possibly due to a dependence of the detector response on depth, since the particle mean-path length inside the detectors can vary, especially in the distal edge region.

Silicon carbide (SiC) is a compound semiconductor, which is considered as a possible alternative to silicon for particles and photons detection. Its characteristics make it very promising for the next generation of nuclear and particle physics experiments at high beam luminosity. Silicon Carbide detectors for Intense Luminosity Investigations and Applications (SiCILIA) is a project starting as a collaboration between the Italian National Institute of Nuclear Physics (INFN) and IMM-CNR, aiming at the realization of innovative detection systems based on SiC. In this paper, we discuss the main features of silicon carbide as a material and its potential application in the field of particles and photons detectors, the project structure and the strategies used for the prototype realization, and the first results concerning prototype production and their performance.

Silicon carbide is a very promising material for next generation nuclear physics experiments at high beam luminosity. Such activities require devices able to sustain high fluxes of particles (up to 1014 ions/cm2) in order to determine the cross sections of very rare nuclear phenomena. One of these activities is the NUMEN project, which aims, through the double charge exchange reactions, to impact in the determination of nuclear matrix elements entering in the expression of half-life of the neutrino-less double beta decay. Due to the very low cross sections, these features can just be explored at fluences which exceed by far those tolerated in state of the art solid state detectors, typically used in this kind of experiments. The SiC technology offers today an ideal response to such challenges, giving the opportunity to cope the excellent properties of silicon detectors with the radiation hardness, thermal stability and visible blindness of SiC material.

On the wake of the results obtained so far at the SPARC_LAB test-facility at the Laboratori Nazionali di Frascati (Italy), we are currently investigating the possibility to design and build a new multi-disciplinary user-facility, equipped with a soft X-ray Free Electron Laser (FEL) driven by a ∼ 1 GeV high brightness linac based on plasma accelerator modules. This design study is performed in synergy with the EuPRAXIA design study. In this paper we report about the recent progresses in the on going design study of the new facility. On the wake of the results obtained so far at the SPARC\_LAB test-facility at the Laboratori Nazionali di Frascati (Italy), we are currently investigating the possibility to design and build a new multi-disciplinary user-facility, equipped with a soft X-ray Free Electron Laser (FEL) driven by a $\sim$1 GeV high brightness linac based on plasma accelerator modules. This design study is performed in synergy with the EuPRAXIA design study. In this paper we report about the recent progresses in the on going design study of the new facility.