Welcome & Opening

• Cesar Domingo-Pardo (IFIC (CSIC-University of Valencia))
• Bernardo Valdivieso Andres (Secretario autonómico de Planificación, Información y Transformación Digital)
• Juan Antonio Fuster Verdu (IFIC (Instituto de Fisica Corpuscular))

The protontherapy project in Spain and in the Comunitat Valenciana

• José Perez Calatayud (Hospital La Fe, Valencia)

Research opportunities in protontherapy centers

• Juan Antonio Vera (Quironsalud)

Clinical aspects and challenges in protontherapy

• Diego Azcona

Clinical results in proton therapy 2024: evidence available and work-in-progress

• Felipe Calvo

Clinical experience and perspective at CPT

• Stephanie Bolle

Clinical aspects and challenges in protontherapy

• Marie Vidal

Recent advances and research at the Heidelberg Ion-beam Therapy Center

• Julia Bauer

Overview of instrumental developments for PT @ CV

• Fernando Hueso Gonzalez (IFIC (CSIC - UV))

I will give an overview of the instrumental developments for proton therapy at different research groups of Comunitat Valenciana.

Overview of the protontherapy program in Portugal

• Patricia Gonçalves

Preliminary results of neutron spectrometry in the treatment room during proton and heavy ion therapy from measurements performed in the framework of the EURADOS WG9 activities.

• Carles Domingo (Universitat Autònoma de Barcelona)

One of the currant tasks of Working Group 9 (WG9: Radiation dosimetry in Radiotherapy) of EURADOS (The European Radiation Dosimetry Group) is to characterize the spectrum of the neutron parasitic field originated as a consequence of radiotherapy. This neutron field may affect patient organs outside the treatment volume, leading to unwanted doses which potentially produce unwanted radiation effects, but do not have any therapeutical benefit. This task has been already running for several years, and activities of WG9 in the past included measurements in photon therapy facilities. Nowadays, its main activity has concentrated in characterizing radiation fields in proton therapy facilities, including measurements of neutron spectra in the treatment room and in-patient dosimetry. In this work, we will present preliminary results of neutron spectra measured in the HIT (Heidelberg, Germany) facility, when irradiating phantoms to proton, Helium, Carbon and Oxygen beams of energies appropriate to mimic treatment of a brain tumour in an anthropomorphic paediatric phantom. Measurements were performed in the forward beam direction, after the phantom, where the primary ions were stopped. Neutron spectra were determined from adequate unfolding of measurements performed with a set of Bonner Spheres, containing a He-3 detector at their centre. The main features of the spectra obtained will be discussed and compared to former proton irradiations.

New b+ production cross sections and their impact on offline and online PET range verification in proton therapy

• Carlos Guerrero (Universidad de Sevilla / CNA)

PET range verification in proton therapy relies in the comparison of the measured and expected b+ annihilation profiles following the patient irradiation with protons of up to 200 MeV. The very different half-lives of the b+ emitters produced by the beam allows to study the b+ profiles both online or offline, by detecting either short- or long-lived isotopes, respectively. In order to contribute to a reliable implementation of PET range verification, we have conducted a comprehensive experimental campaign at several irradiation facilities (CNA, WPE and HIT) to measure accurately all the cross sections for proton energies up to 200 MeV that result in a significant production of b+ emitters with both short- (12N, 38mK and 29P) and long- (11C, 13N and 15O) half-lives. The new data, containing some cross section never measured before, have been used on Monte Carlo simulations with heterogenous phantoms that not only illustrate their impact but also show some interesting features to be considered when discussing the viability, capabilities, and limitations of online PET range verification.

FLASH Irradiation of A549 Lung Cancer Cells and IMR90 Healthy Fibroblasts in the Synchocyclotron Room of a Clinical PT System

• Daniel Sanchez Parcerisa (Universidad Complutense de Madrid)

Background and Aims The discovery of the FLASH effect has spurred the development of clinical proton therapy (PT) facilities to include Ultra-High Dose Rate (UHDR) capabilities for in-vitro, pre-clinical, and clinical studies. Here, we present a cost-effective passive irradiation system for small samples that can be installed and commissioned within minutes in a clinical PT facility. Methods An irradiation system, comprising a lead scatterer and a 3D-printed positioning system, was placed in the synchrocyclotron room of a clinical PT facility. Dosimetry was performed with radiochromic films. Healthy lung fibroblasts (IMR90) and lung adenocarcinoma cells (A549), cultured under standard conditions, were pelleted in Eppendorf vials and irradiated under normoxic conditions at FLASH (>800 Gy/s) and conventional (<0.2 Gy/s) dose rates. Biological assays were conducted on the irradiated samples, including clonogenic and viability studies, irradiation-induced cell cycle arrest via flow cytometry, and dose-dependent expression of the p21 protein via immunofluorescence. Results The irradiation system produced a usable irradiation field of 3x12 mm² with a positioning accuracy of 0.5 mm and a dose homogeneity better than 10%. Clonogenic (A549) and viability (IMR90) assays showed no differential dose-rate effect on the biological response. Cell cycle analysis revealed a decreased rate of cells in arrest at the G2/M phase at FLASH rate for both cell lines, while A549 cells exhibited a lower rate of p21-positive cells when irradiated at FLASH rates. Conclusions The in-house designed and fabricated irradiation system enabled FLASH irradiation of biological samples in a clinical proton therapy center without any hardware or software system modifications. While no significant dose-rate effects were measured in cell survival for either healthy or cancerous cells, observed differences in cell cycle arrest rates might point to differential (FLASH vs. conventional) cell cycle arrest and cell death mechanisms, which should be further investigated in future experiments.

Development of a DOI mini PET/SPECT prototype based on scintillation detectors in phoswich configuration

• Alicia Reija

Positron Emission Tomography (PET) scanners possess the capability to both delineate three-dimensional images of organs affected by different diseases and investigate the metabolic behavior of tumoral structures. This is accomplished by detecting the two 511 keV photons produced in positron annihilation emitted by a β+ radionuclide. On the other hand, Single Photon Emission Computed Tomography (SPECT) systems employ γ-emitting radionuclides to identify single-photon events and reconstruct three-dimensional images in a similar fashion to PET imaging. In practical terms, the reconstruction of images in PET detection assumes that the two annihilation photons are emitted along a certain Line Of Response (LOR). However, uncertainties arising from the actual size of the detectors transform this LOR into a volume of response. Hence, it becomes imperative to introduce a third dimension, namely the Depth Of Interaction (DOI), to enhance sensitivity and spatial resolution. To address this issue, as an alternative to the typical single-crystal configuration in PET scanners, this study proposes the use of two scintillation crystals in phoswich configuration. This configuration relies on the utilization of two scintillators with different decay times, optically coupled and integrated into a single readout and acquisition system. These differences in the decay time of each crystal enable for a better discrimination of the depth of interaction within the crystal assembly. In this work, we present a DOI mini PET/SPECT prototype for pre-clinical small animal studies using CsI(Tl) and ceramic GAGG(Ce) crystals in phoswich configuration, with a readout that primarily features a large area avalanche photodiode and an electronic chain inherited from CALIFA, a gamma-ray detector of the R3B experiment at FAIR, and designed for high-resolution gamma spectroscopy. We will present the state of the art of this innovative configuration, as well as the characteristics of the current setup, first results and future improvements for this proof of concept.

Measurement with pure LaCl3 crystal for range monitoring in proton therapy.

• Angie Carolina Fonseca Vargas (Instituto de física corpuuscular)

Proton therapy has become a promising technique for cancer treatment, specifically targeting tumors and minimizing the impact on surrounding healthy tissues. Despite its benefits, there is uncertainty in the verification of the proton range, which implies higher doses in adjacent healthy tissues, this leads to use of wide safety margins in the doses, limiting the total potential of the technique. To reduce this uncertainty and infer the real range of the protons, F. Hueso proposes in his work [Hueso 2020], the determination of the Bragg peak through the count rate in a detector located coaxially to the patient, using the gamma prompts emitted by the patient after interaction with the proton beam. The PRIDE project wants to apply this method but with the simultaneous detection and discrimination of neutrons and gamma. So far, we have used a non-commercial pure LaCl3 scintillator with excellent neutron-gamma discrimination and energy resolution [Vuong2021] provided by our collaborators Phan Quoc Vuong and Hongjoo Kim from the Department of Physics at Kyungpook National University (South Korea). In this contribution we will present a series of measurements made in local facilities with 4-6 MeV alpha particles in a Be9 target (CMAM Jun-2023), evaluating the sensitivity of the detector to neutrons and gammas using pulse shape discrimination and comparing the results obtained with Monte Carlo simulation made in Geant4. [Hueso2020] F. Hueso-Gonzalez and T. Bortfeld, IEEE Trans Radiat Plasma Med. Sci. 4, p. 170 (2020) [Vuong2021] P. Vuong, H. Kim et al., Nuclear Engineering and Technology 53, p. 3784 (2021)

Prevention of mechanical collisions during proton therapy treatment planning in RayStation: a shared platform for all Spanish proton centers

• Fernando Hueso Gonzalez (IFIC (CSIC - UV))

We present a RayStation script to aid medical dosimetrists in preventing collisions between proton gantry head and patient or couch during treatment planning. The script imports 3D models of the treatment machine elements in STL format. These are visualized in the Patient Modeling tab together with the contoured patient surface. A graphical dialog with sliders allows for the interactive adjustment of gantry angle, couch angle and snout retraction. Hence, treatment planners can assess in advance beam orientations with a potential risk of collision. The script is publicly available on GitHub and has been validated for RayStation 8B or higher. The goal of this tool is to minimize the risk of replanning and thus of treatment delays when a collision is found during a dry run. The clinical workflow can be streamlined at the treatment planning stage and at no cost. Furthermore, by providing real-time feedback and assurance of clearance, the script might foster the use of couch angles that are optimum from the dosimetric perspective, but that a planner might shy away from if the plan feasibility is uncertain. The arrival of 10 proton therapy centers to Spain, all of them with RayStation as the underlying planning software and exactly the same machine, offers a unique opportunity to establish a robust, collaborative and shared framework for collision detection and plan feasibility assessment. References: - https://github.com/mghro/rad-collision/ - F Hueso-González et al 2020 [Biomed. Phys. Eng. Express 6 055013][2] ![Example of a treatment plan collision visualized within RayStation][1] [1]: https://github.com/mghro/rad-collision/blob/main/RayStation/screenshot.png?raw=true [2]: https://doi.org/10.1088/2057-1976/aba442

Novel experimental hybrid PGI-PET imaging for ion-range monitoring in hadron therapy

• Jorge Lerendegui Marco (Instituto de Física Corpuscular)

Hadron Therapy has advantages over conventional radiotherapy due to the maximization of the dose at the Bragg peak. However, owing to different systematic uncertainty sources associated with the technique, quasi-real-time monitoring for ion-range verification is required to reduce safety margins and enhance its potential benefits. Two of the most promising methodologies for in-room real-time monitoring are positron-emission tomography (PET) and prompt-gamma imaging (PGI). The PGI technique is well-suited for real-time monitoring due to the prompt nature of the emitted radiation [Ler22], whereas PET imaging can provide tomographic and functional information relevant to studying physiological processes and tumor response. We have implemented hybrid imaging monitoring based on the combination of both PGI and PET within the same system [Bal22], thus exploiting the advantages of both techniques. This is accomplished by means of an array of Compton cameras in a twofold front-to-front configuration operating in synchronous mode. In this contribution, I will present a summary of a proof-of-concept experiment performed at CNA-Sevilla and the first results from the HIT-Heidelberg facility, where clinical conditions were used to validate the hybrid technique with protons, alpha, and C-ion beams. [Ler22] J. Lerendegui-Marco et al., “Towards machine learning aided real-time range imaging in proton therapy”, Sci Rep 12, 2735 (2022). https://doi.org/10.1038/s41598-022-06126-6 [Bal22] J. Balibrea-Correa et al., “Hybrid in-beam PET- and Compton prompt-gamma imaging aimed at enhanced proton-range verification”, The Eur. Phys. Jour. Plus, Volume 137, Issue 11, article id.1258 (2022) https://doi.org/10.1140/epjp/s13360-022-03414-y

From MACACO to FALCON: Compton camera prototypes for proton beam range verification

• Rita Viegas (IFIC (CSIC - U. Valencia))

Proton therapy's precision in targeting tumors while minimizing damage to healthy tissues has become increasingly important in clinical settings. However, accurate in-vivo verification of proton beam range is essential due to planning and delivery uncertainties. Compton cameras (CCs) are a promising solution for this challenge. The IRIS group at IFIC-Valencia has developed two CC prototypes: MACACO III, which uses VATA64HDR16 ASIC readout electronics, and its improved version, MACACOp, equipped with TOFPET2 ASIC. Both prototypes consist of detector modules featuring LaBr3 monolithic scintillation crystals coupled to SiPM arrays. These prototypes underwent extensive laboratory testing and high photon energy characterization [1], [2], as well as practical assessments at the Cyclotron Centre Bronowice (CCB) in Krakow, Poland. Notably, MACACOp demonstrates a significantly improved time resolution of 1.5 ns FWHM compared to MACACO III, a key advancement for effectively discriminating against neutron background [3] and random events [4] in in-vivo proton therapy monitoring. During measurement campaigns at the CCB, where the IBA Proteus C-235 isochronous cyclotron is employed, both prototypes demonstrated their efficacy by detecting range shifts as small as 2 mm with a 90 MeV proton beam at a 60 pA current [5]. In these conditions, MACACOp outperformed MACACO III, exhibiting reduced saturation and enhanced detection capabilities. To further enhance the system’s performance, particularly in terms of efficiency and high-rate handling, an upgraded version of MACACOp, named FALCON (Fast Medical Applications Compton Camera), was developed. FALCON is a dual-plane CC; the first detector plane mirrors that of MACACOp, while the second plane comprises four secondary detector modules. This new prototype was characterized in laboratory conditions and underwent in-beam testing at the Quirónsalud proton therapy centre in Madrid, Spain. At Quirónsalud, the IBA S2C2 imposes additional challenges, since it rapidly delivers a high concentration of protons due to its brief duty time [6]. Consequently, to avoid system saturation, the experiments were carried out using lower beam energy and current. Measurements involved irradiating an RW3 phantom with a 70 MeV monoenergetic proton beam, creating well-defined depth-dose curves (“pristine Bragg peaks”), at an instantaneous beam current of 5 nA. To assess the system's capability to detect range shifts under these conditions, the proton beam energy was varied to 79.4 MeV, corresponding to a 10 mm shift in the position of photon emission. Energy spectra were successfully obtained in Compton mode, and the photon emission distribution at 4.439 MeV generated in the graphite target was retrievable. FALCON effectively detected the range shift, despite the challenging conditions presented by the S2C2 accelerator. [1] R. Viegas et al., Radiat. Phys. Chem., vol. 202, 2023. [2] L. Barrientos et al., Radiat. Phys. Chem., vol. 208, 2023. [3] A. Biegun et al., Radiother Oncol, vol. 102, 2012. [4] M. Borja-Lloret et al., 2023, submitted. [5] R. Viegas et al., 2023, in preparation. [6] J. Van de Walle et al., Cyclotrons2016.

Fast low-dose pencil beam proton and helium radiographs for motion management

• Alexander Pryanichnikov (DKFZ)

The HELium Imaging Oncology Scanner (HELIOS) is a novel project to develop helium radiography based on existing proton imaging technologies for mixed carbon and helium beams. Its primary purpose is to enable range-guided particle therapy (RGPT) for non-small-cell lung cancer (NSCLC). One of the challenges in treating NSCLC is dealing with motion-induced changes in patient anatomy that occur on time scales ranging from seconds (intrafractional) to days or weeks (interfractional). Motion management in ion therapy is critical due to the finite range of charged particle beams and their sensitivity to density variations caused by these anatomical changes. The potential of the RGPT system lies in its ability to mitigate toxicity by providing real-time monitoring of the dose delivered to a moving tumor. The current study aimed to assess the viability of using fast low-dose proton (pRad) and helium (HeRad) radiography to detect anatomical displacements during treatment delivery. The evaluation included proton, helium, or mixed carbon-helium beams using state-of-the-art imaging detectors, reconstruction techniques, and particle beam delivery systems. Materials and methods involved obtaining 4D computed tomography (4DCT), 4D cone-beam CT as well as experimental pRad scans of a moving phantom. Monte Carlo simulations were performed using open and anonymized patient 4DCT data, modeling pRad and HeRad for helium and mixed beams. Treatment plans for mixed carbon-helium beams were calculated using matRad. The results showed that experimental pRad achieved a high spatial resolution of 1 mm and a frame rate of 8 fps, while simulated pRad and HeRad showed the same resolution and the ability to detect patient displacements up to 1 mm using 2000 particles per spot for 20 cm × 20 cm full scans. In the case of mixed carbon-helium beams, both integral and single iso-energy, HeRad successfully detected water-equivalent path length differences with sub-millimeter accuracy for different phases of 4DCT data and manual shifts for the same data sets. In addition, HeRad offered potential for respiratory phase determination and beam extraction control in mixed particle therapy. In conclusion, low-dose proton and helium radiography using pencil beam scanning provides accurate millimeter-level information on inter- and intrafractional (in the case of mixed carbon-helium beams) anatomical displacements in patients. The technique demonstrated sub-second temporal resolution, making it a promising approach for motion management during radiation treatment.

On-the-fly dose reconstruction from in-beam PET activation

• Andrea Espinosa (Universidad Complutense de Madrid)

Background and aims: In-beam PET offers rapid treatment feedback, yet faces challenges with high event rates. Clinical implementation requires on-the-fly integration of a fast dose reconstruction algorithm. In this work, we present on-the-fly dose reconstruction from clinical in-beam PET data, using a novel In-beam Dose Estimation tool (IDE-PET), capable of obtaining on-line dose and of detecting range deviations. Methods: The specific PET setup consisted of 6 phoswich detector blocks with 338 pixels each, with 1.55 x 1.55 x LYSO (7mm)+GSO (8mm) detectors. The system was coupled to a fast data acquisition system able to sustain rates up to 10 Msingles/sec. Several cylindrical (50-mm diameter and 50-mm height) homogeneous PMMA phantoms were irradiated with a monoenergetic proton beam of 70 MeV oriented along the longitudinal axis of the scanner. Additionally, 5 PMMA range shifter foils of varying thickness (from 1 to 5 mm) were also placed at the proximal surface to investigate range shift prediction accuracy. For real-time dose estimation, we have developed the IDE-PET tool, which combines a GPU-based 3D reconstruction algorithm [2] with a dictionary-based software capable of estimating deposited doses from the 3D PET activity images [3]. Results: The dose estimation algorithm requires from 0.25 to 1.0 seconds to calculate and display the deposited dose. For a 2 Gy dose fraction, the method was able to spot range variations as small as 1 mm. The average range estimation has a statistical error of 0.1 mm (1σ). Assessment of system sensitivity to proton number changes showed satisfactory results for doses as low as 0.2 Gy. Conclusions: We can reconstruct dose maps from PET activation on-line, at clinically relevant dose levels and during the beam-on period, with an accuracy better than one millimeter, in the BP fall-off region. This validates the feasibility of the proposed experimental setup to be used for in-beam on-the-fly reconstruction of the 3D dose in a clinical scenario. [1]Parodi, K., et al (2007). Patient study of in vivo verification of beam delivery and range, using positron emission tomography and computed tomography imaging after proton therapy. International Journal of Radiation Oncology* Biology* Physics, 68(3), 920-934. [2] Galve, P. et al (2020). GPU based fast and flexible iterative reconstructions of arbitrary and complex PET scanners: application to next generation dedicated brain scanners. In 2020 IEEE (NSS/MIC). [3] Onecha, V. V., et al, (2022). Dictionary-based software for proton dose reconstruction and submilimetric range verification. Phys. Med. Biol., 67(4), 045002.

Study of epitaxial graphene contacts for Silicon Carbide radiation dosimetry and detection

• Ivan Lopez Paz (IMB-CNM-CSIC)

Silicon Carbide (SiC) is a radiation hard wide bandgap semiconductor, which makes it an interesting alternative for radiation detection applications such as radiotherapy instrumentation. Reducing the amount of metal over the active can positively affect the accuracy of the measurement. The first SiC diodes with epitaxial graphene contacts were produced at IMB-CNM for radiation detection. These detector prototypes have been characterised by means of a pulsed laser transient current measurement and a radioactive alpha source, showcasing the charge collection properties. These measurements have been followed by a characterisation by means of a Linac at the University of Santiago de Compostela. These show a percent-level dose rate linearity of the prototypes, which is promising for future iterations for the medical application.

Quality assurance programs for PBS proton beams

• Severine Rossomme (IBA)

A New Strategy for Range Verification in Proton Therapy: the Coaxial Approach

• Fernando Hueso Gonzalez (IFIC (CSIC - UV))

Nine years ago, the milestone of first-in-human range verification of a proton therapy treatment using prompt gamma-rays was achieved using a collimated gamma-ray camera. Despite being developed by a major proton accelerator vendor, the widespread clinical application and commercial availability of this device is not yet in sight. It remains unsure whether its size and weight will allow their integration on every treatment room worldwide. To address this shortcoming, a new method without collimation was recently proposed: the monitoring of prompt gamma-rays with a single detector, coaxial to the proton beam, behind the treated area. This orientation exploits the solid angle effect, as the number of gamma-rays reaching the detector will increase in case of an overshoot, or decrease in case of an undershoot. By solely counting the number of detections per proton, one would be able to identify range deviations with respect to the treatment plan. With this compact and affordable method, the integration in the treatment room would be facilitated compared to the state-of-the-art collimated gamma-ray cameras. Nonetheless, this novel orientation entails unexplored challenges, namely high count rates and large neutron background in forward direction. We report on initial developments of a demonstrator system specifically tailored to cope with up to 10 million counts per second. It comprises a cerium bromide scintillator coupled to a photomultiplier tube and a fast digitizer. First experimental tests show the ability of acquiring continuous waveforms at 2.5 GSPS without any dead time during a time span typical of a clinical treatment field, which in turn allows for a sophisticated decomposition of pile-up events. Dedicated photomultiplier supply electronics able to sustain high count rate variations have been designed with the help of behavioral circuit simulations and are being tested with controlled light sources. In parallel, detailed Monte Carlo simulations of the detector and photomultiplier tube are under development. During this year, we plan to analyze first tests at a bremsstrahlung beam and conduct experiments at a clinical proton beam to obtain the first experiment proof-of-principle of coaxial detection for proton therapy range verification.

Neutron dosimetry and radiation protection in particle therapy facilities with LINrem dosimeters

• Ariel Tarifeño-Saldivia (Instituto de Fisica Corpuscular (CSIC-UV))

Neutrons, as a form of radiation, possess high penetrating capabilities, contributing significantly to the total absorbed dose within the human body. Consequently, the monitoring of neutron dose rates is paramount for assessing the potential risks to workers, patients, and the public. Typically, commercial portable neutron detectors, known as ambient neutron dosimeters, fulfill this purpose. However, concerns have arisen regarding the reliability of these detectors, especially in modern facilities generating radiation fields with high-energy components (E>20MeV) or intricate time structures (such as pulsed or quasi-pulsed neutron fields). This concern becomes particularly pronounced in medical facilities like proton therapy centers, where secondary stray radiation includes high-energy neutrons reaching up to 250 MeV. Additionally, the International Commission on Radiation Units and Measurements (ICRU) has recently proposed alternative definitions for operational quantities employed in radiation protection. This has consequences for the performance of neutron dosimeters, especially in energy ranges surpassing 50 MeV. This range is particularly pertinent to proton therapy centers. This work reviews the technical challenges associated with active and time-resolved neutron dosimetry in particle therapy. It also presents the current status of the LINrem dosimeters, encompassing the validation of prototypes and our latest experimental findings in proton therapy. Finally, we discuss the future of the LINrem project and the impact of the new ICRU recommendation for radioprotection in proton therapy centers.

PEPITES : A Transparent Beam Profiler based on Secondary Electrons Emission for Hadrontherapy

• Christophe Thiebaux (Laboratoire Leprince-Ringuet CNRS-Ecole polytechnique)

The PEPITES detector is an ultra-thin, radiation-resistant profiler capable of continuous operation on mid-energy (O(100 MeV)) charged particle accelerators. With a water equivalent thickness of 10 microns, it induces minimal beam disturbance and is highly resistant to radiation. Secondary electron emission (SEE) is used for the signal because it only requires a small amount of material (10 nm); very linear, it also offers large dynamics. The lateral beam profile is sampled using segmented electrodes, constructed by thin film methods. Gold strips, as thin as the electrical conductivity allows (~ 50 nm), are deposited on an insulating substrate as thin as possible. While crossing the gold, the beam ejects the electrons by SEE, the current thus formed in each strip allows the sampling. The detector works in the vacuum of the beam line. SEE signal was characterized at ARRONAX* cyclotron with 68 MeV proton beams and at medical energies at CPO**. Electrodes were subjected to doses of up to 10^9 Gy without showing significant degradation. A demonstrator with dedicated electronics (CEA) is installed at ARRONAX where it is used routinely with proton beams of 17-68 MeV for intensities from 100fA to 100nA. Measurements of a Flash 68 MeV proton beam were also done here (10 ms pulses with mA intensity). Carbon ion beam profiles with an energy between 115 MeV and 395 MeV were measured at CNAO using a portable version of the detector. An overview of the design and first measurements will be presented, and system performances will be assessed. *ARRONAX cyclotron, Saint Herblain (France) **Orsay Protontherapy Center (Institut Curie, Orsay, France)

Development of microdosimetric detectors for radiobiology in hadron therapy facilities

• Cristiana Rodrigues (LIP/FCUL/C2TN)

The ability to measure the effects of radiation on healthy and tumorous tissues at the microscale can highly contribute to describing the dose distribution and establish correlations with the effects observed at the cellular level. Developing instruments with this characteristic is essential for planning particle radiotherapy for cancer treatment. The RADART (Radiation Dosimetry to Advance Radio Therapy) group at LIP is developing new detectors and materials with applications in micro- and nanodosimetry. A prototype, based on an array of 64 1 mm-diameter scintillating plastic optical fibres (SPOF), was introduced in the workshop in Santiago de Compostela. In 2023, the first beam tests with clinical protons at HollandPTC, Delft, on the prototype under development by our group were made. More recently, the development of materials that can achieve micro-scale sensitivity to use in radiobiology experiments has started within our group. Micrometric SPOF (mSPOF) and aluminium oxide (Al2O3) doped crystals are the options for building active and passive microdosimetric detectors. Multiple methods to produce mSPOF, namely electrospinning, melt-electrospinning, and fibre drawing, were investigated. Polystyrene-based mSPOF was produced via fibre drawing successfully. The mSPOF had a diameter between 50-70 micrometres and had proven good optical properties (e.g. light transmission). The production of Al2O3 crystals, the base matrix of a fluorescent nuclear tracking detector (FNTD), was achieved using the flux method for crystal growth. Flux and process optimizations resulted in the production of good-quality clear crystals (i.e., no defects). Intending to improve the sensitivity for low-mass particles and neutrons, doping the crystals with several element combinations is foreseen.

Determination of neutron dose equivalent in organs from in-phantom measurements in proton therapy facilities.

• Carles Domingo (GRRI. Dep. de Física. Univ. Autònoma de Barcelona.)

Poly-Allyl-Diglicol-Carbonate (PADC) track detectors, most commonly known by the name of one of its commercial brands (CR39), are the basis of the neutron dosimeter developed by the Radiation Physics Group at Universitat Autònoma de Barcelona (UAB). These dosimeters allow measuring the neutron component in general mixed radiation fields, including those encountered in proton radiotherapy. Essentially, the whole dosimeter is constituted by a layer of PADC and several layers of diverse materials acting as neutron converters, in which incident neutrons produce protons. These protons originate submiscroscopic damage (latent tracks) in the PADC, which can be afterwards enhanced through an electrochemical process that allows visualising and counting the tracks and, therefore, quantifying the neutron field. The physics and working principles of this dosimeter are explained elsewhere [1]. One great advantage of this dosimeter is that it is not sensitive to the photon component, so its use is of specific interest in photon-neutron mixed fields. Our group participates in the task of characterizing the radiation field present in proton therapy installations in the frame of WG9 (Radiation dosimetry in Radiotherapy) of EURADOS (The European Radiation Dosimetry Group). One of the aims, is to determine the out-of-field dose equivalent due to neutrons at patient’s radiological organs of interest. For this purpose, water slab and anthropomorphic phantoms are filled with several types of dosimeters, which need accurate and specific characterization. On one hand, dose equivalent in tissue is a quantity which is not measurable as such, and it must be evaluated from modelling the interaction of radiation with the tissue, via a calibration coefficient applied to a measured physical quantity, such as particle fluence. This calibration coefficient depends on the energy distribution of the neutron field to be measured. On the other hand, the track detector response is also highly energy-dependent, so that calibrations in a field having a given energy distribution cannot be used to determine dose equivalents in a radiation field with a different energy distribution. In this work we will present the methodology that we use to evaluate neutron dose-equivalents in organs from measurements with our PADC-based dosimeters. Results of dose equivalent from irradiations performed in proton therapy facilities will also be presented. References: [1] Domingo C., et al. Estimation of the response function of a PADC based neutron dosimeter in terms of fluence and Hp(10). Radiation Measurements 50 (2013) 82-86.

Tests of the IEM proton-scanner prototype

• Amanda Nathali Nerio Aguirre (IEM-CSIC)

Proton therapy requires precise knowledge of the patient's anatomy to guarantee an accurate dose delivery [1]. X-ray computed tomography (CT) images are used nowadays to calculate the relative stopping power (RSP) needed for proton therapy treatment planning [2]. Recent studies indicate that tomographic imaging using protons has the potential to provide a more accurate and direct measurement of RSP with a significantly lower radiation dose than X-rays [3]. The proton CT (pCT) scanner prototype developed at IEM-CSIC is composed of a tracking system of two double-sided silicon strip detectors, and the CEPA4 detector as the residual energy detector. Our pCT scanner prototype was tested at the Cyclotron Centre Bronowice (CCB) facility in Krakow, Poland during three experimental campaigns conducted in 2021 and 2022. Radiographs were generated from pixelated detectors. Volumetric phantoms composed of matrices made of PMMA with inserts of air, ethanol, water, Delrin, Teflon, and aluminum were imaged. The radiographs displayed great fidelity with respect to the shapes of the studied samples. The spatial resolution of this proton imaging scanner prototype is better than 2 mm and the MTF-10%=0.3 line pairs per mm [4]. We are currently engaged in the data analysis of new samples for the study of radiographs and tomography scans using proton beams with energies up to 200 MeV. At this conference, we will present preliminary findings, including the imaging capabilities of our prototype, showcasing its potential applications for the future of medical imaging detectors. **References** [1] C. Sarosiek et al., Med. Phys. 48, 2271 (2021). [2] P. Wohlfahrt and C. Richter, Br. J. Radiol. 93, 20190590 (2020). [3] R. P. Johnson Rep. Prog. Phys. 81, 016701 (2018). [4] J. A. Briz et al., IEEE Trans. Nucl. Sci. 69, 696 (2022).

First radiation hardness tests of new silicon carbide dosimeters for proton beam therapy.

• Marcio Alfonso Jiménez Venegas (IMB-CN)

Proton therapy is an important radiotherapy that achieves very high dose conformity around the target, allowing a better protection of the organs at risk (decreasing radiation side effect). However, the dose delivered to a tumor is still conditioned by the dose that can be tolerated by the surrounding normal tissues. An emerging approach called FLASH therapy [2,3] delivers a therapeutic dose several orders of magnitude faster (≈ 100 Gy/s) than in current clinical cases (0.05Gy/s). The physical properties of silicon carbide (SiC) make it an interesting material for radiation dosimetry. The wide SiC band-gap decreases the rate of thermally generated charge carriers, reducing the leakage current and the noise compared to silicon. It also makes SiC essentially insensitive to visible light and temperature variations. SiC has a higher displacement energy threshold and thus a higher radiation hardness than silicon, and has a higher thermal conductivity which makes it more resistant to thermal shocks. At IMB-CNM we have designed and fabricated novel silicon carbide PiN diodes with the aim to respond to the technological challenges of new radiotherapy approaches such as proton therapy and FLASH therapy and have performed their validation in relevant beams. For example, in a first characterization with FLASH electron beams, these diodes have shown their suitability for relative dosimetry up to a dose per pulse of 11 Gy [4]. In this contribution we will present the tests carried out with these detectors at the CNA in Sevilla, with the aim of studying their signal response, sensitivity and radiation hardness with 14MeV proton beams up to a cumulative dose of 1.5 kGy. The diodes were operated without external bias voltage and an ionization chamber was used for reference dosimetry. The diodes show a pre-irradiation sensitivity of 3.2 ± 0.4 nC/Gy. The diode response is stable up to 1.5 kGy with a ±4% deviation that can be attributed to beam drift during the irradiation. The diode dark current was not affected by the accumulated dose. These results make SiC diodes a very promising option for dosimetry in proton beams. [1] Schardt, D. et al.,Reviews of Modern Physics, 82(1), 383–425 [2] Favaudon V. et al., Science Translational Medicine, Vol. 6, Issue 245, pp. 245Ra93, 2014 [3] Zhang Q. et al., Radiation Research, 194(6), 656-664, (27 August 2020). [4] Fleta C. et al., Physics in Medicine and Biology, submitted

First microdosimetry maps in low energy proton beams

• Carla Riera-Llobet (CNM-IMB (CSIC))

**ABSTRACT** Around 40$\%$ of people surviving cancer do so because of radiotherapy. However, to improve this statistic, treatments based on hadron radiotherapy (HT) are rapidly expanding worldwide [1]. HT achieves very high dose conformity around the tumor target, allowing better protection of the organs at risk. This is particularly critical for radioresistant tumors, for tumors localized near organs at risk, and for pediatric cancers. Nevertheless, some toxicities have recently been reported [2‒5]. It might be because ions deliver higher linear energy transfer (LET), which may generate collateral damages, e.g., acute and late effects, and even secondary cancer induction. However, there are no tools capable of measuring LET during treatments. In this context, the National Center of Microelectronics (IMB-CNM) has designed and manufactured new silicon 3D detectors [6‒8] based on a novel architecture of cylindrical electrodes with microscopic sizes as those from a cellular level (15-25 $\mu$m) [7]. This allows quantifying the LET at micrometer scale, namely lineal energy.\\ Moving towards their clinical implementation requires designing large layouts covering several centimeters based on these successful prototypes and performing significant pre-clinical trials. The advanced detectors that we proposed could also be used for beam monitoring and dose evaluation during radiobiology trials in real-time. Quantifying LET with micrometer spatial resolution would allow us to optimize RBE-weighted treatments. RBE optimization can be carried out by removing high‒LET spots from critical structures, focalizing high‒LET regions into the target, and assessing the potential biological impact of the treatment plans on the target and surrounding normal tissue. It would allow guiding beam arrangements to enhance therapeutic ratios and minimize dose excesses due to physical uncertainties. This can be performed by using LET-painting [9], which has already demonstrated an increase of the tumor control probability in hypoxic tumors. The present work shows the performance of the first multi-pad-type array of those 3D microdetectors containing 3 × 3 unit-cells with 200 $\mu$m of pitch between them. The 9 microdetectors in each array are connected to the same readout channel in the readout chip (ROC) [10]. The system has 8 pad-type arrays stacked laterally, each array contains 25 3 × 3 units, covering a total radiation-sensitive area of 0.4 mm × 12 cm. The system has been tested at Centro Nacional de Aceleradores (Sevilla, Spain) under low-energy proton beam irradiations at different energies between 6.2 and 13.6 MeV with therapeutic-equivalent fluence rates ($10^7 p \cdot cm^{-2} \cdot s^{-1}$) to obtain the corresponding microdosimetry quantities along the Bragg peak and distal edge.The microdosimetry quantities were successfully obtained with spatial resolutions of 200 $\mu$m. Experimental results were compared to Monte Carlo simulations based on TOPAS [11] and an overall good agreement was found. Microdosimetry spectra of lineal energy were recorded as well as the first microdosimetry 2D maps that show the number of particles detected in each case and the experimental $\bar{y}_f$ values, which cover from (7$\pm$1) to (17.4$\pm$0.5) keV$\mu m^{-1}$ in good agreement with the literature [10]. In addition, a double-check was performed to ensure the accuracy of the beam profile reaching the sensors using a radiochromic film. For this, we convoluted both the spectra from the detector map and the ones collected with the films to their cross-section profiles. A general good agreement between the plots of the detector and film data has been achieved. This compelling consistency underscores the robustness of our microdosimeter arrays and the reliability of the data obtained. It demonstrates that the system can be clinically used as microdosimeters for measuring the lineal energy distributions in the context of proton therapy treatments. Additionally, they could be also used for beam monitoring. **REFERENCES** [1] Schardt, D. et al.,Reviews of Modern Physics, 82(1), 383–425 [2] Yock TI et al., Radiother Oncol. 2014 Oct; 113(1):89-94. [3] McGovern et al., Int. J. Radiat. Oncol. Biol. Phys., Volume 90, Issue 5, 1143-1152 [4] Indelicato DJ, et al., Acta Oncol. 2014 Oct;53(10):1298-304. [5] Durante M., Br J Radiol. 2014 Mar;87(1035):20130626. [6] Guardiola C. et al., Phys Med Biol. 2021;66(11):10.1088/1361-6560/abf811 [7] Guardiola C. et al., Appl. Phys. Lett. 107, 023505 (2015). [8] Prieto-Pena J. et al., IEEE Transactions on Nuclear Science, Vol. 66, No. 7, July 2019 [9] Bassler, N., Jäkel, O., Søndergaard, C. S., Petersen, J. B. (2010). Dose-and LET-painting with particle therapy. Acta oncologica, 49(7), 1170-1176. [10] Bachiller-Perea, D., Zhang, M., Fleta, C., Quirion, D., Bassignana, D.,Gómez, F., & Guardiola, C. (2022). Microdosimetry performance of the first multi-arrays of 3D-cylindrical microdetectors. Scientific Reports,12(1),12240. [11] https://www.topasmc.org/

First test of an ionoacoustic imaging system for dose monitoring in FLASH proton therapy

• Teresa Rodríguez González (Massachusetts General Hospital. Harvard Medical School)

Recently, the use of ultra-high dose rates (FLASH) in radiation treatments has emerged as a new promising modality, where a pulsated ultra-high dose rate (>40 Gy/s) is delivered in comparison to conventional radiation therapy (~0.05 Gy/s). FLASH radiotherapy has demonstrated an unprecedented ability to reduce healthy tissue toxicity while maintaining tumor control, as shown in several in vivo preclinical [1-6] and early clinical [7] studies performed mostly with electron beams. However, these studies have also revealed the associated risks FLASH-RT may have for clinical implementation without proper real-time “image-pulse” guidance to mitigate discrepancies between planned and delivered dose. The clinical translation of this technique is limited by the lack of proper dosimetric methods that can accurately measure, in real-time, the dose distribution in deep tissues as expected from modern proton to ensure its safe delivery in such high-risk mode [8,9]. On the other hand, FLASH radiotherapy using protons is expected to be the de facto therapy for deep-seated tumors and pediatric tumors, because it can combine FLASH tissue sparing with the spatial advantages of protons to shape the dose (Bragg peak) [10-12]. However, its associated higher risks with respect to conventional proton therapy without proper real-time “image-pulse” guidance results in barely a few preclinical studies [6,7] of the FLASH effect, and just one clinical study that has recently announced the completion of accrual for symptomatic bone metastases [13]. Therefore, there is an urgent need that demand investigating the unknown physical requirements (e.g., dose/pulse, dose/s, pulse width, beam size, etc.) of the proton beam to produce tumor control while sparing healthy tissues [14]. This work aims to overcome these two challenges by leveraging the concept of ionizing radiation acoustic dosimetry, where acoustic waves are generated following the absorption of pulsated high energy radiation. In this work, an ionizing radiation-induced acoustic imaging (iRAI) system has been developed to achieve real-time pulse-by-pulse 3D dose monitoring using FLASH dose rates with proton beams. Furthermore, the combination of iRAI with an ultrasound imaging system will facilitate the mapping of dose on anatomical structures [15,16]. This dual system has been tested at the Massachusetts General Hospital (USA) in tissue-mimicking phantoms. A description of the system and preliminary results will be presented. In addition, future work combining proton FLASH dosimetry and its correlation to tissue damage/toxicity response will be discussed to achieve a better understanding of the physical requirements to produce the FLASH effect during proton delivery. References [1] Montay-Gruel et al. Radiother Oncol 124(3) (2017) [2] Bourhis et al. Radiother Oncol 139:11-7 (2019) [3] Schuler et al. Int J Radiat Oncol Biol Phys 97(1) (2017) [4] Diffenderfer et al. Int J Radiat Oncol 106(2) (2020) [5] Beyreuther et al. Radiother Oncol 139 (2019) [6] Vozenin al. Clin Cancer Res 25(1) (2019) [7] Bourhis et al. Radiother Oncol 139:18-22 (2019) [8] Favaudon et al. Sci Transl Med 6(245) (2014) [9] Favaudon et al. Cancer Radiother 19(6-7) (2015) [10] Lin et al. Frontiers in Oncology 11 (2021) [11] Hughes et al. Int J Mol Sci 21(18) (2020) [12] Wu et al. Appl Rad Oncol 10(2) (2021) [13] Varian press reléase https://www.varian.com/about-varian/newsroom/press-releases/varian-and-cincinnati-childrensuc-health-proton-therapy-0 [14] Vozenin et al. Radiat Res 194(6) (2020) [15] Oraiqat et al. Med Phys 47(10) (2020) [16] Zhang et al. Nature Biotechnol (2023)

Advances in compact accelerators for medical applications

• Daniel Esperante Pereira (IFIC)
• Daniel Esperante Pereira (IFIC - U. de Valencia / CSIC)

High-gradient radiofrequency accelerators for radiotherapy.

• Marçà Boronat Arevalo (IFIC)

High-frequency hadron therapy linear accelerators (linacs) have undergone extensive research and development, becoming integral components of proton therapy centers. Linacs operating at frequencies of 200-400 Hz provide the advantage of dynamically adjusting the output energy pulse by pulse. This capability enables the precise deposition of the dose with continuous depth variation, rapidly covering the volume of a tumor and even facilitating the targeting of moving tumors. However, treating solid tumors at a maximum depth of 27 cm requires the use of beams with 200 MeV protons and 400 MeV/u fully stripped carbon ions. Therefore, the machines must be large to generate these beams. Recent research has focused on minimizing the footprint of compact 'single-room' proton machines while enhancing power efficiency for both proton and carbon ion treatments. This presentation will provide a summary of the studies and results conducted on high-gradient radio-frequency accelerator structures.

Recent progress on laser-driven ion acceleration and its application to proton therapy

• Aarón Alejo (IGFAE, Universidade de Santiago de Compostela)

Laser-plasma accelerators have attracted significant interest, particularly thanks to the extreme accelerating fields in the plasma, offering a cost-effective and compact alternative to traditional accelerators. Significant progress has been made in recent years in laser-driven ion acceleration, including acceleration of protons with unprecedented properties, such as ultra-short duration, low emittance and high brightness, reaching energies in excess of 100 MeV. Furthermore, the ongoing progress has opened up the possibility of using these beams in proof-of-principle applications in a wide range of fields, particularly in those related to medical uses, such as production of nuclear activation of materials for medical imaging and therapy, or proton-based ultra-high-dose-rate radiation therapy. Here, an overview of recent progress on laser-driven ion acceleration will be presented, particularly on the efforts to increase the energy, flux, and repetition rate at which these sources can be operated. Results on the use of these ion beams in medicine will be presented. The generation of pre-clinical and clinical levels of carbon-11 useful for positron-emission-tomography (PET) imaging will be discussed, including our latest measurements using a petawatt-class facility. Furthermore, recent studies reported of the use of laser-accelerated proton beams for radiation therapy with dose rates in excess of giga-Gray per second will be introduced, including in-vitro and in-vivo experiments. Ongoing efforts to perform these experiments at national facilities such as L2A2 (Santiago de Compostela) or CLPU (Salamanca) will be examined [see M. Seimetz contribution for latest results].

Technological challenges and efficient solutions for the development of a compact low energy proton accelerator with FLASH capabilities in the Basque Country

• Amaia Villa Abaunza (Tekniker)
• Iñaki Hernandez (Egile S.L.)
• Unai Etxebeste (Egile S.L.)
• Joaquín Portilla (IZPILab-Beam Laboratory. UPV/EHU)
• Jorge FEUCHTWANGER MORALES (IZPILab-Beam Laboratory. UPV/EHU)
• Victor Etxebarria (IZPILab-Beam Laboratory. UPV/EHU)

Within the framework of the Science Industry strategy of the Basque Country, LINAC7 is a project that pursues the generation of knowledge and qualification in the field of accelerator science and technology. With the design and construction of a compact low energy (7 MeV) proton accelerator, the project presents the ideal framework to develop efficient technological solutions and meet the needs of the scientific and industrial communities. TEKNIKER participates in the project with the main role of transforming the requirements and characteristics of the system, defined with the University of the Basque Country, to reality. The project includes many different tasks, such as state of the art requirement definition, dimensional and geometrical tolerance definition, thermal and mechanical calculations, magnetic calculations, analysis of the beam, 3D design, prototyping of the intermediate validators, integration and assembly of the whole solution in an aligned functional compact Linac (example in Figure 1). Currently, the ion source, LEBT and beam dump are already finished, tested, and characterized, and shortly also the RFQ will be integrated in the line (Figure 2). Recently, TEKNIKER conducted an assessment to determine the necessary shielding for maintaining a dose rate below 2.5 μSv/h near the shielding walls. This assessment was part of the request for an appropriate facility on the UPV/EHU campus to install an accelerator. The accelerator is anticipated to generate a 5 MeV proton beam later this year, as outlined in Figure 2 of the system scheme. Taking these safety measures into account is crucial to ensure a secure environment for the accelerator installation. TEKNIKER has repurposed its accelerator, originally designed for generating radioisotopes for Positron Emission Tomography (PET) [1], to explore its potential for ultra-high dose rates (UHDR) and the production of the FLASH effect [2]. Promising results were obtained for irradiating cell cultures at dose rates exceeding 103 Gy/s with pulses of 250 μs and total irradiation times of the order of milliseconds. To enhance the system’s FLASH capability, TEKNIKER plans to incorporate a chopper to allow for the delivery of radiation in shorter pulses. This modification will permit to perform experiments with variations in pulse duration and frequency, crucial parameters in FLASH studies [3]. TEKNIKER's decision to specialize in FLASH technology for accelerators and biomedical research demonstrates its commitment to contributing to advancements in cancer treatment and radiobiological research. The focus on FLASH technology is driven by the potential benefits it may offer in terms of more effective and targeted cancer treatments, utilizing accelerated irradiation methods. In summary, TEKNIKER aims to leverage its expertise and resources to advance in the field of FLASH technology, with the ultimate goal of making significant contributions to cancer treatment and radiobiological research.

Proton acceleration and detection for clinical and preclinical research

• Michael Seimetz (CSIC - Instituto de Instrumentación para Imagen Molecular (i3M))

Research at the Institute for Instrumentation in Molecular Imaging (i3M, Valencia) is related to the development of diagnostic systems and clinical or preclinical applications of nuclear physics techniques. We present two recent advances related to particle therapy. The necessity for online range measurement for the real-time determination of the position of the Bragg peak has been much discussed throughout the last decade. We have developed a beam trigger detector based on scintillating fibers which can be used for precise coincidence timing at clinical beam intensities and thereby allows for background suppression in prompt-gamma detection and spectroscopy. Tests with an upgrade version are ongoing. The second research topic relies on proton and ion acceleration with ultra-short laser pulses. This type of radiation sources generate ultra-intense particle bunches and have attracted much attention as a tool for investigating radiobiological effects in the ultra-high dose rate (UHDR) regime. In close collaboration with IGFAE (Universidade de Santiago de Compostela) we have performed the first experiments on cell culture irradiation with laser-produced x-rays and protons in Spain. First measurements were realized at the Laser Laboratory for Acceleration and medical Applications (L2A2, Santiago de Compostela) using a stabilized x-ray source at the 1 mJ/1 kHz laser line. A dedicated campaign with laser-accelerated protons was recently completed at the Spanish Pulsed Laser Centre (CLPU, Salamanca). Cell samples were prepared and analyzed by the Fundación Pública Galega de Medicina Xenómica (FPGMX, Santiago de Compostela) and by Instituto de Biología Funcional y Genómica (IBFG, Salamanca). Our aim is to perform systematic studies of the cellular response to damage caused by different types of ionizing radiation (protons, x-rays) and their comparison to clinical radiation fields.

Radiobiology: Status and Prospects

• Marta Ibañez (CIEMAT)

Investigating the Potential Benefits of Proton Therapy in the Context of Neurodegenerative Disorders

• Carina Marques Coelho (FCUL, LIP, BioISI)

Ionizing radiation is widely employed for medical purposes, encompassing both diagnostic and therapeutic applications. Radiation therapy, a well-established medical modality routinely employed in cancer treatment, has demonstrated efficacy in addressing extra-cranial amyloidosis. Current evidence suggests its potential as a promising treatment for amyloid-associated neurodegenerative disorders, and emerging modalities could enhance biological effects while mitigating potential toxicity. Proton therapy stands out as one of the most effective radiation therapy techniques, due to the considerable clinical advantages of protons over conventional radiation therapy particles such as photons or electrons. These advantages include a favorable depth dose distribution, reduced lateral spread, and minimal scatter, facilitating a decrease in collateral damage. While this modality is currently undergoing testing in cancer settings, its application in the context of amyloidosis and neurodegenerative disorders remains largely unexplored. In our multidisciplinary research, ionizing radiation is being investigated as a potential treatment for neurodegeneration, with the capability to disassemble amyloid structures through the disruption of chemical bonds or by triggering cellular degradation mechanisms. We aim to simulate different radiation modalities using Monte Carlo tools (TOPAS/Geant4) and experimentally validate their effects on those abnormal protein deposits. The preliminary gamma-irradiation experiments conducted on cell lines expressing neurodegenerative disease-associated proteins, demonstrated a decrease in the expression and aggregation of the pathological proteins, which was proportional to the applied dose. Subsequently, we progressed to irradiating biological samples with photons and electrons using a clinical linear accelerator at a medical facility. To conduct experiments on biological models, the establishment of a system facilitating the desired measurements is crucial, emphasizing the need for reproducibility, ease of assembly, and swift setup. A phantom designed for cell irradiation at radiotherapy clinical facilities underwent characterization, requiring the implementation of Monte Carlo simulations with TOPAS. In this presentation, we will showcase the results of the dosimetric characterization of the designed and constructed phantom. Additionally, we will provide an update on the ongoing irradiation experiments conducted at the clinical linear accelerator, encompassing both photons and electrons. Our ongoing research is dedicated to laying the groundwork for the expansion of proton therapy applications beyond cancer. This expansion aims to amplify the adaptability of emerging proton therapy facilities and potentially transform the course of development for presently incurable neurodegenerative disorders.

Preliminary work to study proton-induced optical toxicity

• Juliette Thariat ( Université de Caen Normandie, ENSICAEN, CNRS/IN2P3, LPC Caen UMR6534, F-14000 Caen, France & Department of radiation therapy, Centre François Baclesse, Caen, France)
• Jean Claude Quintyn ( Department of ophthalmology, University hospital, Caen, France)
• Nathan AZEMAR (LPC Caen)
• Jean Marc Fontbonne ( Université de Caen Normandie, ENSICAEN, CNRS/IN2P3, LPC Caen UMR6534, F-14000 Caen, France)
• Dorothee Lebertz (Université de Caen Normandie, ENSICAEN, CNRS/IN2P3, LPC Caen UMR6534, F-14000 Caen, France & Department of radiation therapy, Centre François Baclesse, Caen, France)
• Cathy Fontbonne ( Université de Caen Normandie, ENSICAEN, CNRS/IN2P3, LPC Caen UMR6534, F-14000 Caen, France)

Tumors located near the optic pathways pose a particular challenge due to the risk of optical toxicities. For this reason, they are often treated with proton therapy. Such patients with paraoptic tumors represented more than half the whole patient population, suggesting referral biases to proton therapy toward difficult to treat tumors. The PIOTox study aims to conduct a voxel-scale analysis of optical toxicities induced by proton therapy [1]. For this study, patients with paraoptic head-neck/skull-base/CNS tumors undergoing proton therapy were consecutively included. A prospective database of 240 patients from the Cancer Center Baclesse comprises information on patient radiotherapy, such as proton therapy planning, millimetric CT scans, and comprehensive optic structure delineation. This database is complemented by patients' results from ophthalmologic examinations (field of view, visual evoked potential, and thickness measure of RNFL) conducted at the University Hospital of Caen before radiotherapy and at subsequent time points (1 month, 1 year, 2 years, etc.). This multicentric database is organized and anonymized using the ArDCore software [2]. The objective is to predict the future visual state of the patient based on the initial patient condition and the planned radiotherapy. For this purpose, preliminary work on paraclinical data is conducted (age effect correction, calibration, noise analysis, quality assurance). Subsequently, a model of the optic nerve is built on CT scans to enable the use of the dose deposited in each voxel as a feature for the future use of machine learning algorithms. The development of the geometric model of the optic nerve was carried out using the ESPADON package [3] deployed in the R language. As eye rotations and gaze may affect the dose to functional optic subunits (ESTRO 2024), the visual outcome predictions, has also highlighted that eye rotations and gaze may affect the dose to functional optic subunits. [1] Thariat J, SEQ-RTH22 INCa 16863 [2] Combes, S. & Bacry, E. & Fontbonne, Cathy. (2020). Health Data Hub; plateforme des données de santé en France, application à l’oncologie radiothérapie. Cancer/Radiothérapie. doi: 10.1016/j.canrad.2020.07.003. [3] Espadon, an R package for automation, exploitation and processing of DICOM files in medical physics and clinical research », C. Fontbonne, J.-M. Fontbonne, N. Azemar, Phys. Med. 109 (2023). doi: 10.1016/j.ejmp.2023.102580

Sinergy between photothermia and proton-therapy using gold nanoparticles

• Célia Tavares de Sousa (UAM)

In the recent years, proton-therapy has become one of the most researched techniques for irradiating tumours. This technique implies a clinical advantage over conventional photon therapies due to the unique depth-dose characteristics of protons, which can be exploited to target the tumoral cells while reducing the dose delivered to the healthy tissues. On the other hand, photothermal therapy (PTT) is a minimally invasive local treatment modality whose goal is to convert eletromagnetic radiation into heat by stimulation of photoabsorbing agents that are administrated to the body either intravenously or intratumorally. Laser light in the near-infrared (NIR) region (700-1100 nm) is the energy source used in PTT due to the higher tissue penetration capability and lower absorption in biological tissues [1]. Among several molecules and nanomaterials used, gold nanostructures have been extensively explored as photothermal agents due to their biocompatibility and ability to generate heat due to the absorption of electromagnetic radiation [1]. The strong photoelectric absorption coefficient of gold, the high-Z of this element, combined with high Auger and Coster–Kronig (C-K) electron emission yields, make the gold nanoparticles excellent radiosensitizers, offering local radiation dose enhancement of up to 200% [2] [3]. Recent studies have also evaluated this effect when proton-therapy is used in combination with the nanoparticles. Experimental studies using proton beams in cell lines have showed enhanced responses in the cells with internalized gold nanoparticles. The radiosensitizing effect of gold nanoparticles was studied for proton, megavoltage (MV) photon and kilovoltage (kV) photon beams. For each particle source, various treatment depths were achieved. The cell viability was significantly reduced for both proton and MV photon irradiations when nanoparticles were internalized in the cell, reaching a sensitizer enhancement ratio between 1.33 and 3.98 depending on the nanoparticles concentration and internalization by the cells [4]. The results of using the nanoparticles as radiosensitizers in proton therapy are promising, however, the possibility of combining proton and photo therapies must be explored. In this work we will present our most recent experiments at CMAM to study the synergy between photothermia and proton-therapy. First, several concentrations of gold nanoparticles in liquid were irradiated with a proton beam to evaluate the temperature evolution depending on the laser power [5]: (i) during the proton beam irradiation and (ii) after the proton beam irradiation to evaluate the impact of the proton beam irradiation in the photothermal behaviour. We observed a significant increase in the temperature and seems to indicate a synergic effect between proton and laser irradiation. Then glioblastoma multiform cells (U87mg) with and without internalized gold nanoparticles were also irradiated with several doses and proton beam intensities. The cell viability was evaluated after irradiation using Alamar Blue and clonogenic essays. We will also determine the reactive oxygen species (ROS) produced after laser and proton irradiation and the cell cycle by flow cytometry to explore the causes of cell death. In addition to experiments, we study the charge transfer and ionization processes in proton-uracil collisions, in the energy range of 0.05 < E < 2500 keV [6], in order to build a simple model that allow us to obtain inelastic cross sections from molecular orbital energies. Some efforts to the description of the molecular fragmentation after proton impact are also carried out within the group [7].

Hypoxia and radiation: their role in characterizing Circulating Cancer Stem Cell-like cells

• Martina Quartieri (UCM & GSI)

Despite the improvements in cancer treatment over the past decades, tumor recurrence and metastases are still the main concern for the therapy's success [1]. Tumors are composed by a heterogenous population of cells, among which the Circulating Cancer Stem Cells (CCSCs) are the real responsible for metastasis formation. These cells are radioresistant and express markers critical for migration and stemness (CD133), resistance to anoikis (TrKB) and immune evasion (CD47) [2]. An essential role in forming these cells is due to hypoxia. Moreover, a further selection is possible after exposing them to radiation. Photon irradiation could increase the CCSCs subpopulation, nevertheless particle irradiation (such as proton irradiation) could result in an increased treatment efficiency of cancer cells with a CCSC phenotype [3]. Identifying this subpopulation of cells in the blood circulation is challenging, since they are present only in few numbers in the bloodstream. Therefore, the possibility of culturing and characterizing this subpopulation of cells in vitro would significantly increase our knowledge about the mechanisms responsible for metastasis formation. For this purpose, in this study, we select cells with a CCSC-like phenotype using hypoxia (acute and chronic) and radiation (4 Gy of X-rays), for further characterization. This study will shed light on the mechanisms responsible for the CCSCs formation. [1] Riggio, A.I., Varley, K.E. & Welm, A.L. The lingering mysteries of metastatic recurrence in breast cancer. Br J Cancer 124, 13–26 (2021). [2] Quartieri M., Puspitasari A., Vitacchio T., Durante M., Tinganelli W. The role of hypoxia and irradiation in developing a CTC-like phenotype in murine osteosarcoma cells. Front Cell Dev Biol. 2023. [3] Tinganelli W, Durante M. Tumor Hypoxia and Circulating Tumor Cells. Int J Mol Sci. 2020;21(24):9592.

Multi-beam FLASH-PT Strategy for Previously Treated Meningioma Case

• Joana Leitão (LIP/IST/DKFZ)

**Background & Aims:** In this study, we propose a strategy for multi-beam FLASH-PT combined with IMPT, applied to a meningioma case. The objective is to leverage the benefits of FLASH Bragg Peak-in-target beams in conjunction with IMPT. For this work, we defined “the FLASH effect” to occur in healthy tissue if irradiated with a minimum dose of 5 Gy, with a dose modifying factor (DMF) of 1.25. **Material and Methods:** Using Raystation (Version 11B) we created a two-fraction FLASH plan (9 Gy per fraction, 18 Gy in total, keeping the clinical BED) with the same 4-beam arrangement as the clinical plan. We chose a different beam direction as the FLASH beam for each fraction. The remaining CTV was irradiated with three IMPT beams. We applied the DMF to the brainstem and an area of the brainstem unavoidable in the clinical treatment, the irradiated brainstem (IB), in the FLASH-DMF plan. We adjusted the clinical plan to match the same fractionation scheme as the FLASH plan ("CONV") and compared it to the FLASH-DMF plan. **Results:** Figure 1 illustrates the dose distribution for CONV (a) and FLASH-DMF (b), and the dose-volume histogram comparing both plans (c). 1c Both plans had a V_95%of9Gy above 99 %, a comparable conformity index (0.54 and 0.60 for CONV and FLASH_DMF) and a homogeneity index (both 0.06). After applying the DMF, the near maximum dose in the brainstem (D_2%) was reduced by 3 Gy. **Conclusions:** We have shown that multi-beam FLASH-PT is possible for the current meningioma case, where toxicity in the brainstem was reduced because of the FLASH effect. Future work will include the dose rate analysis. **Figure 1:**  \[1\]: http://jleitao153915012024.imgur.com/all/?third_party=1 \[2\]: https://imgur.com/rtrl6sA

Dosimetría con películas radiocrómicas leída a tiempos cortos (<30 min) post-irradiación

• Laura García-Arias (UCM)

En entornos de irradiación experimental para protonterapia, como aceleradores de baja energía o usando el modo técnico de un acelerador clínico, donde no es posible usar el control automático de dosis mediante el planificador, se hace necesario implementar un sistema de dosimetría independiente para los experimentos. En este contexto, las películas radiocrómicas juegan un papel esencial debido a su bajo coste, alta resolución espacial, baja dependencia con la tasa de la dosis y la energía y su equivalencia con agua o tejidos blandos. El protocolo de postprocesado de las películas radiocrómicas tras su irradiación habitualmente incluye un tiempo de espera de al menos 24/48h, debido al oscurecimiento progresivo de las mismas, además de un número limitado de escaneos. Sin embargo, cuando se usan como método de dosimetría primaria en experimentos, en ocasiones es necesario caracterizar su comportamiento inmediato post-irradiación para poder hacer dosimetría de protones on the spot. Además, existen elementos presentes en los protocolos habituales que corresponden con tecnologías obsoletas (familias anteriores de las películas radiocrómicas, o escáneres con lámpara de filamento) y deben, por tanto, ser adaptados a las tecnologías existentes en cada laboratorio. En este trabajo, se presentan tres estudios diferentes para una serie de películas EBT3 irradiadas en un irradiador de Cs137: (A) Análisis de la homogeneidad del campo de escaneo en un escáner EPSON Perfection V850 en modo transmisión; (B) Influencia dosimétrica del tiempo post-encendido del escáner y el número de escaneos; y (C) Dependencia de la dosis obtenida del tiempo post-irradiación. De los resultados obtenidos se ha determinado una región de aceptación del escáner con homogeneidad superior al 99% y caracterizado una variación de la lectura de dosis de hasta el 10% en los primeros 20 minutos post-irradiación, seguido por un aumento posterior inferior al 2% en las 24h subsiguientes, ambos independientes del número de escaneos. Estos resultados han contribuido a la creación de un modelo de corrección para películas radiocrómicas escaneadas a tiempos inferiores a 30min post-irradiación que ha sido utilizado para realizar dosimetría inmediata en experimentos en el Centro de Protones de Quirónsalud o en el Centro de Microanálisis de Materiales (CMAM).

MINAS TIRITH: a simulation tool for assessing DNA damage in a cell population around the Bragg peak

• Carmen Villagrasa (IRSN, LDRI, Fontenay-aux-Roses, France)

Introduction: In proton therapy, in addition to better targeting of the dose delivered to the tumor, we expect greater biological effectiveness (RBE) due to the microscopic characteristics of the dose deposit. Protons are considered to be charged particles with high linear energy transfer (LET), particularly in the Bragg peak region. In this case the energy deposits are very close to each other in the track, leading to complex DNA damage that can be more difficult to repair compared to those produced by low LET irradiation such as photons and/or electrons. This effect is normally taken into account clinically by using an RBE=1.1 throughout the proton trajectory in the tissue. However, we know that the value of this relative efficiency varies with the energy of the protons, i.e. along their path, and can be very significant in the Bragg peak zone as well as in the cells at the edge of the tumor. Materials and Methods Existing Monte Carlo track structure codes, such as Geant4-DNA (1-4), can simulate in great detail the physical, physico-chemical and chemical processes underlying DNA damage in highly complex geometries representative of the cell cycle phase. However, the direct application of these calculations to a large cell population in order to obtain the distribution of DNA damage and its topology is unthinkable due to prohibitive computational times. Indeed, it is important to note that the stochastic nature of the energy-depositing interactions induces variation in response between different cells in the same population irradiated at the same dose, something that is often difficul to quantify. A new tool, MINAS TIRITH (5-6) has therefore been developed to calculate the distribution of double strand breaks (DSBs) produced by proton irradiations with energies corresponding to the Bragg peak irradiating a cell population at a known macroscopic dose D. To this end, MINAS TIRITH uses two database pre-generated with Geant4-DNA. The first database corresponds to microdosimetric spectra at cell nucleus level for different charged particles. By sampling, it calculates the number, energy and nature of particles depositing their energy within the cell nucleus according to the specific energy distribution characterizing the irradiation. The second, is a database of DNA damage associated with the nature of the particles and their track length. Sampling within these two databases allows to get equivalent information as that obtained using a detailed simulation chain(7-8) with Geant4-DNA but allows to estimate, with reasonable computing time, the damage distribution (and not just its mean value) at the cell population level. Results: Experimental validation of this tool was carried out by comparison with the results of the γ-H2AX damage distributions obtained experimentally 30 min after irradiation with 2.5 MeV and 15.1 MeV neutrons. The results of the validation will be presented. The usefulness of this calculation method for assessing damage and biological effectiveness in the cells around the Bragg peak, particularly at the edge of the tumor, will also be discussed. 1S. Incerti et al., Int. J. Model. Simul. Sci. Comput., 1(2,) (2010) 157-178 ; 2S. Incerti et al., Med. Phys., 37(9), (2010) 4692-4708 ; 3M. Bernal et al., Phys. Med., 31(8), (2015) 861-874 ; 4S. Incerti et al, Med. Phys., 45(8), (2018) 722-739 ; 5Thibaut et al. Phys. Med. Biol. 68 (3), (2023) 034002 ; 6Thibaut et al. Phys. Med. Biol. 68 (3), (2023) 225008 ; 7S. Meylan et al., Comput. Phys. Commun., 204, (2016) 159-169 ; 8N. Tang et al., Int. J. Mol. Sci., 20, (2019) 6204 ;

Monte Carlo Simulations for in vitro experiments using TOPAS toolkit

• Daniel Suarez-Garcia (Universidad de Sevilla)

Background and aims Radiopharmaceutical therapy (RPT) is a novel modality of oncology treatments which uses radiolabeled agents affine to biomolecules overexpressed in tumor cell environments. Alpha particle emitters are key in RPT by precisely targeting cancer cells while minimizing impact on healthy tissue, thanks to their limited range and localized energy delivery. In addition, this kind of treatment can be combined with protons, and heavy ions external radiotherapy to treat metastasis patient. Consequently, comprehending the distribution of doses with in vitro experiments is essential for advancing in the design of these treatments. In general, in vitro experiments involve three distinct and relevant processes occurring simultaneously: the injection of the radionuclide into the culture medium, the binding of the radiopharmaceutical to receptors on cell membranes, and the internalization process within the cell cytoplasm. We have developed a TOPAS Monte Carlo to model the in vitro radiopharmaceutical experiments. Methods In our simulations, we have established a dynamic equilibrium involving the three processes mentioned earlier. The entire decay chain is simulated, and decays take place throughout the culture medium, cell membranes, and cytoplasm, considering the dynamic binding and internalization processes, which are influenced by the temporal evolution of the experiment. The computational tool presents two newly developed geometries: a two-dimensional monolayer of cells and a three-dimensional tumor sphere culture. To replicate irradiation conditions, the simulation specifies the radionuclide, initial activity, and experiment duration for both geometric configurations. Results Using the tool developed, a radiopharmaceutical in vitro experiment published by Kasten et al. [Nucl Med Biol. 58, 2018] with PDAC cell and the alpha emitter 212Pb has been recreated. Dose and dose rate evolution along the experiment have been scored for each cell individually. Conclusions The results obtained provide insights into how alpha particles induce damage. The findings suggest that the accumulated dose over an extended period is not the primary indicator, but it is the dose administered in short time intervals that truly determines the probability of cell death. These results carry significant implications for the design and advancement of therapies involving protons, alphas, and heavy ions.

Deep-Learning Acceleration of Proton Therapy Monte Carlo Simulations

• Pablo Cabrales (Grupo de Física Nuclear, Dpto EMFTEL & IPARCOS, Facultad de Ciencias Físicas, Universidad Complutense de Madrid)

Proton therapy is a radiation treatment that targets tumoural masses more precisely than conventional radiotherapy. Simulations of clinical proton radiotherapy treatment plans and dose verification methods using Monte Carlo (MC) codes have been proven to be a valuable tool for basic research and clinical studies. TOPAS, a CPU-based, open-source software tool, can be considered a golden standard of proton therapy MC simulators. Nevertheless, the main limitation of this tool is the time required to complete the simulation. Simulating a complete treatment plan, with the necessary statistics for adequate modeling, can take around five hours on a high-performance computer. If multiple treatment plan variations are to be generated for model training, the total simulation times become prohibitive. To solve this problem, we propose to accelerate MC simulations in proton therapy with a deep learning (DL) model able to estimate high-statistics dose and activity images from low-statistics simulations. In this work, we simulated with TOPAS two treatment plans with 300 beams each: a high-statistics plan with 100k protons per beam and a low-statistics plan with 1k protons per beam. The DL model, based on the SwinUNETR architecture, was trained to predict the high-statistics beams from the low-statistics beams. It was trained for 50 epochs in one hour and was able to generate high-statistics activity images from low-statistics activity images with a mean squared error of 0.0016 and a gamma index (1mm, 3%) of 99.77%. For reference, the mean squared error and the gamma index between two high-statistics activity images, where only the simulation’s random seed was modified, was 0.0008 and 99.91% respectively, which is close to the results obtained with our model. These results show how DL methods can be used to reduce the computational time required for obtaining accurate proton therapy MC simulations. Even if new software tools are used to accelerate MC simulations (for instance, by using GPUs) our proposed approach could be also used in those cases to further accelerate the whole simulation workflow.

Monte Carlo Bunker Shielding Simulation for the HUMV Protontherapy Facility

• Jordi Duarte-Campderros (IFCA (CSIC-UC))

The Spanish Nuclear Safety Council (CSN) demands a Radiation Protection (RP) report for the commissioning of the Varian BEAMPRO250 cyclotron at Valdecilla Hospital (HUMV) to ensure compliance with legal requirements. In response, the Physics Institute of Cantabria (IFCA) has developed a Geant4-based simulation tool called BUNSHI. Given the machine's geometry and anticipated annual workload, this tool determines specific shielding conditions and Radiation Protection occupational zones, aligning with international safety standards. This paper showcases the application of BUNSHI code to the future Proton Therapy facility at Valdecilla Hospital.

Pulse and Average Dose Rate impact on background yield (B-yield) of radicals during CONV and FLASH

• Miguel Molina-Hernández (German Research Cancer Center (DKFZ), Laboratory of Instrumentation and Experimental Particles Physics (LIP))

**Introduction** We present an advanced pulse irradiation model (PIM) utilizing gMicroMC’s step-by- step algorithm (SBS) with the newly incorporated periodic boundary condition (PBC), along the modeling of the homogeneous stage with numerical ordinary differential equations (NumODEs). Our goal is to study the pulse structure effects on radical production during CONV and FLASH in pure water. **Methods** The PIMs input include the pulse dose rate (Drp), the average dose rate (Drav), and the pulse beam structure (frequency and width). To simulate the bulk characteristics of water, we implemented a PBC. The SBS is run during the beam-on time and for 1 μs after radiation stops to ensure the completion of the heterogenous stage. Meanwhile, the NumODEs are executed during the remaining beam-off time until the arrival of the next pulse (homogeneous stage). We define a Drav threshold for every Drp. Below the threshold (CONV), the concentration of radicals per unit of dose (G-yield) is constant; above it (FLASH), the G-yield depends on Drav. **Results** We irradiated pure water to a total dose of 20 Gy using a 70 MeV proton beam characterized by pulses with a duration of 1 μs. Figure 1 shows the G-yield of H2O2 as a Drav function. For Drp of 1.8·105 and 106 Gy/s, the Drav thresholds were ~10 Gy/s and ~100 Gy/s, respectively. In Figure 2, at the inception of every pulse, it can be observed a background yield (B-yield) of radicals. For CONV, the B-yield is constituted by H2 and H2O2, whereas for FLASH, it is a mixture of all the radicals. **Conclusions** Th B-yield determines the Dr threshold and, consequently the dependence of the G- yield with Drp and Drav. The FLASH effect has been demonstrated with comparable Drav thresholds for identical Drp [1]. Our findings suggest a potential correlation between the FLASH effect and radiochemistry. Figure 1: https://www.dropbox.com/scl/fi/1fnjx1n0mvl1b3fldnzhw/Figure1_Miguel_Molina-Hernandez_Abstract.png?rlkey=qde35hga2u3oexl2knnr9vr3y&dl=0 Figure 2: https://www.dropbox.com/scl/fi/wjacutjakeh5e94hrjfrj/Figure2_Miguel_Molina-Hernandez_Abstract.png?rlkey=67a2ryx66c5h6bvj61qagc248&dl=0 [1] https://www.sciencedirect.com/science/article/pii/S0936655519301517

Feasibility of a photodiode-based dosimeter use in protontherapy: study of the angular dependence using Monte Carlo simulation.

• Juan Alejandro de la Torre González (Universidad de Granada)

Ionization chambers are the devices most commonly used as dosimeters in radiotherapy. They show, however, some limitations compared to other systems based in semiconductors: large sizes, high voltage requirement for biasing, etc. Some current-mode semiconductor devices have been studied for the same purpose, such as photodiodes and phototransistors. For these devices, the absorbed dose is proportional to the current integrated over the exposure time. Nevertheless, one of the most important features of this type of dosimeters is its angular dependence. This characteristic refers to the possible change in the sensitivity of the dosimeter according to the direction of the incident radiation. The angular dependence of dosimeters can be important, especially in situations where the radiation source is not isotropic or when they are not positioned in the direction of the radiation. In such cases, dosimeters may not accurately measure the radiation dose received by the patient. Using the Monte Carlo codes PENH [1,2] and FLUKA [3,4], we have analyzed the response of a BPW34S photodiode, because this kind of sensor presents good properties for radiation measurements [5]. In the simulations, a monoenergetic 10x10 cm2 square field proton beam impinges in a water phantom, where the dosimeter is situated. A wide range of energies have been used: 50, 100, 150, 200 and 250 MeV. An air layer is considered between the phantom and the radiation source. The incidence angle of the radiation is changed to study the angular dependence. The angles considered in our analysis were 0º, 15º, 30º, 45º, 60º, 75º and 90º. The implemented geometry aims to reproduce the experimental setup that would be used to characterize the angular dependence of the device. The considered photodiode was modeled as a plastic housing with an internal silicon die according to the dimensions provided by the manufacturer. The energy deposited in the silicon die was calculated as a function of the incidence angle and compared to the response for the normal incidence that is considered as the reference value. Our results show a reduce angular dependence for the device for low energy protons. Besides, for high energy protons, a significant angular dependence is only found for large angles (close to 90º). References [1] F. Salvat, J.M. Fernández-Varea and J. Sempau, Nuclear Energy Agency, Barcelona 2018 [2] F. Salvat and J. M. Quesada, Nucl. Ins. Meth. Phys. Res. B 475 (2020) 49. [3] G. Batistoni et al., Annals of Nuclear Energy 82 10-18 (2015). [4] C. Ahdida et al., Frontiers in Physics 9, 788253 (2022). [5] I. Ruiz-García et al. Med. Phys. 48 5440-5447 (2021).

Round Table Discussion & Concluding Remarks