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The correct quantification of the dose released in charged particle therapy treatments requires the knowledge of the double differential fragmentation cross section of particles composing both the beam and the target. The FragmentatiOn Of Target (FOOT) experiment aims at measuring these cross sections for ions of interest for charged particle therapy applications. This article describes the performance of the time-of-flight (TOF)-wall detector of the experiment. The detector is composed of two layers of 44 cm $\times 2$ cm $\times 3$ mm plastic scintillator bars (20 for each layer), arranged orthogonally and read-out by silicon photomultipliers. The detector is designed to identify the charge of fragments ranging from protons to oxygen ions, with a maximum energy of 700 MeV/u, by measuring the energy released in the scintillators and the TOF with respect to a start counter. In this study, the detector was scanned with carbon ions of energy between 115 and 400 MeV/u and with a 60-MeV proton beam. The measurements show an energy resolution ( $\sigma _{E}/\mu _{E}$ ) between 6% and 4% and a contribution of the detector to the TOF system time resolution between 25 and 20 ps (standard deviation) for carbon ions and between 100 and 80 ps for protons.

This paper provides a first insight of the potential of the β - Radio Guided Surgery ( β - -RGS) in a complex surgical environment like the abdomen, where multiple sources of background concur to the signal at the tumor site. This case is well reproduced by ex-vivo samples of 90 Y -marked Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP NET) in the bowel. These specimens indeed include at least three wide independent sources of background associated to three anatomical districts (mesentery, intestine, mucose). The study is based on the analysis of 37 lesions found on 5 samples belonging to 5 different patients. We show that the use of electrons, a short range particle, instead of γ particles, allows to limit counts read on a lesion to the sum of the tumor signal plus the background generated by the sole hosting district. The background on adjacent districts in the same specimen/patient is found to differ up to a factor 4, showing how the specificity and sensitivity of the β - -RGS technique can be fully exploited only upon a correct measurement of the contributing background. This locality has been used to set a site-specific cut-off algorithm to discriminate tumor and healthy tissue with a specificity of 100% and a sensitivity, on this test data sample, close to 100%. Factors influencing the sensitivity are also discussed. One of the specimens set allowed us evaluate the volume of the lesions, thus concluding that the probe was able to detect lesions as small as 0.04 mL in that particular case.

The possibility to use β− decaying isotopes for radioguided surgery (RGS) has been recently proposed, and first promising tests on ex-vivo samples of Meningioma and intestinal Neuroendocrine Tumor (NET) have been published. This paper reports a study of the uptake of 68Ga-DOTATOC in pancreatic NETs (pNETs) in order to assess the feasibility of a new RGS approach using 90Y-DOTATOC. Tumor and healthy pancreas uptakes were estimated from 68Ga-DOTATOC PET/CT scans of 30 patients with pNETs. From the obtained SUVs (Standardised Uptake Value) and TNRs (Tumor Non tumor Ratio), an analysis algorithm relying on a Monte Carlo simulation of the detector has been applied to evaluate the performances of the proposed technique. Almost all considered patients resulted to be compatible with the application of β−-RGS assuming to administer 1.5 MBq/kg of activity of 90Y-DOTATOC 24 h before surgery, and a sampling time of few seconds. In just 2 cases the technique would have required a mildly increased amount of activity or of sampling time. Despite a high physiological uptake of 68Ga-DOTATOC in the healthy pancreas, the proposed RGS technique promises to be effective. This approach allows RGS to find application also in pancreatic diseases, where traditional techniques are not viable.

Purpose Radio-guided surgery with β - decays is a novel technique under investigation. One of the main advantages is its capability to detect small ( ⩽ 0.1 ml) samples after injecting the patient with low activity of radiopharmaceutical. This paper presents an experimental method to quantify this feature based on ex-vivo tests on specimens from meningioma patients. Methods Patients were enrolled on the basis of the standard uptake value (SUV) and the tumour-to-non-tumour activity ratio (TNR) resulted from 68Ga-DOTATOC PET exams. After injecting the patients with 93–167 MBq of 90Y-DOTATOC, 26 samples excised during surgery were analyzed with a β - probe. The radioactivity expected on the neoplastic specimens was estimated according to the SUV found in the PET scan and the correlation with the measured counts was studied. The doses to surgeon and medical personnel were also evaluated. Results Even injecting as low as 1.4 MBq/kg of radiotracer, tumour residuals of 0.1 ml can be detected. A negligible dose to the medical personnel was confirmed. Conclusions Radio-guided surgery with β - decays is a feasible technique with a low radiation dose for both personnel and patient, in particular if the patient is injected with the minimum required activity. A correlation greater than 80% was observed between the measured counts and the expected activity for the lesion samples based on the individual SUV and the TNR. This makes identifiable the minimum injectable radiotracer activity for cases where 90Y is the utilized radionuclide.

Prostate cancer is among the most common cancers in men and one of the leading causes of death worldwide. Different therapies are adopted for its treatment and generally radiotherapy with photons (RT) is the preferred solution in almost all cases. Up to now, in addition to photons, only protons have been implemented as alternative radiotherapy. The use of Very High Energy Electron (VHEE) beams (100-200 MeV) has been suggested in literature but the needed accelerators are more demanding, as far as space and cost are concerned, with respect to standard photon devices, with only limited advantages when compared to protons or other heavy ions. In this contribution we investigate how recent developments in electron beam therapy could reshape the landscape of prostate treatments. The VHEE Treatment Planning System obtained combining an accurate Monte Carlo (MC) simulation with a simple modelling of the FLASH effect (healthy tissues sparing at very high dose rates) is compared with conventional RT. The results demonstrate that FLASH therapy with VHEE beams of 70-130 MeV could represent a valid alternative to standard RT allowing a better sparing of the healthy tissues surrounding the tumour, in the framework of an affordable technological development.

PURPOSE In-beam Positron Emission Tomography (PET) is one of the modalities that can be used for in-vivo non-invasive treatment monitoring in proton therapy. Although PET monitoring has been frequently applied for this purpose, there is still no straightforward method to translate the information obtained from the PET images into easy to interpret information for clinical personnel. The purpose of this work is to propose a statistical method for analyzing in-beam PET monitoring images that can be used to locate, quantify and visualize regions with possible morphological changes occurring over the course of treatment. MATERIALS AND METHODS We selected a patient treated for Squamous Cell Carcinoma (SCC) with proton therapy, to perform multiple Monte Carlo (MC) simulations of the expected PET signal at the start of treatment, and to study how the PET signal may change along the treatment course due to morphological changes. We performed voxel-wise two-tailed statistical tests of the simulated PET images, resembling the Voxel-Based Morphometry (VBM) method commonly used in neuroimaging data analysis, to locate regions with significant morphological changes and to quantify the change. RESULTS The VBM resembling method has been successfully applied to the simulated in-beam PET images, despite the fact that such images suffer from image artifacts and limited statistics. Three dimensional probability maps were obtained, that allowed to identify inter-fractional morphological changes and to visualize them superimposed on the Computed Tomography (CT) scan. In particular, the characteristic color patterns resulting from the two-tailed statistical tests lend themselves to trigger alarms in case of morphological changes along the course of treatment. CONCLUSIONS The statistical method presented in this work is a promising method to apply to PET monitoring data to reveal inter-fractional morphological changes in patients, occurring over the course of treatment. Based on simulated in-beam PET treatment monitoring images, we showed that with our method it was possible to correctly identify the regions that changed. Moreover we could quantify the changes, and visualize them superimposed on the CT scan. The proposed method can possibly help clinical personnel in the replanning procedure in adaptive proton therapy treatments. This article is protected by copyright. All rights reserved.

Open physics 19(1), 383 - 394 (2021). doi:10.1515/phys-2021-0032, Published by de Gruyter, Berlin

Charged Particle Therapy is a non-invasive technique for radio-resistant tumor treatment performed with protons or light ions, aiming to deliver a high precision treatment. Compared to conventional radiotherapy, ions allow for a higher dose deposition in the tumor region while sparing the surrounding healthy tissue. To really exploit the potential benefits of this technique, the highest possible accuracy in the calculation of dose and its spatial distribution is required in treatment planning. Commonly used Treatment Planning Software solutions adopt a simplified beam-body interaction model. An alternative is the use of Monte Carlo simulations which explicitly take into account the interaction of charged particles with actual human tissues hence providing highly accurate results. However, Monte Carlo simulations are used in a restricted number of cases due to substantial computational resources required. The code FRED has been developed to allow a fast optimization of the treatment plans in Charged Particle Therapy while profiting from the dose release accuracy of a Monte Carlo tool. Currently, the most refined module is the transport of proton beams in water. A comparison with measurements shows that the lateral dose tails are reproduced within 2% in the field size factor test up to 20 cm. Models for the interaction of ion with the matter are currently under development in the FRED code. The status of new developments and the performance of FRED will be presented.

The high dose conformity and healthy tissue sparing achievable in Particle Therapy when using C ions calls for safety factors in treatment planning, to prevent the tumor under-dosage related to the possible occurrence of inter-fractional morphological changes during a treatment. This limitation could be overcome by a range monitor, still missing in clinical routine, capable of providing on-line feedback. The Dose Profiler (DP) is a detector developed within the INnovative Solution for In-beam Dosimetry in hadronthErapy (INSIDE) collaboration for the monitoring of carbon ion treatments at the CNAO facility (Centro Nazionale di Adroterapia Oncologica) exploiting the detection of charged secondary fragments that escape from the patient. The DP capability to detect inter-fractional changes is demonstrated by comparing the obtained fragment emission maps in different fractions of the treatments enrolled in the first ever clinical trial of such a monitoring system, performed at CNAO. The case of a CNAO patient that underwent a significant morphological change is presented in detail, focusing on the implications that can be drawn for the achievable inter-fractional monitoring DP sensitivity in real clinical conditions. The results have been cross-checked against a simulation study.

The MONDO (MOnitor for Neutron Dose in hadrOntherapy) project addresses the technical challenges posed by a neutron tracker detector: high detection efficiency and good backtracking precision. The project main goal is to develop a tracking device capable of fully reconstructing the four-momentum of the ultra-fast secondary neutrons produced in Particle Therapy treatments via double elastic scattering interactions. The tracker – a 16 × 16 × 20 cm 3 matrix – is made by a matrix of thin squared scintillating fibres (250 μ m ) arranged in layers orthogonally oriented. A custom readout system called SBAM (SPAD-Based Acquisition readout for MONDO experiment), matched to the MONDO needs of single photon detection capability, high spatial resolution and compactness, has been developed in collaboration with Fondazione Bruno Kessler (FBK). A small detector prototype ( 4 × 4 × 4 . 8 cm 3 ) has been built and tested with a sensor prototype, SPADnet-I, in order to experimentally evaluate the light output expected and consequently optimise the final readout. The simulation characterisation of the detector response with monochromatic neutrons in the [20-300] MeV will be presented together with the expected performances of MONDO as neutron beam monitor. The preliminary measurements at electron and proton beams of the prototype with the SPAD array readout will be reported.

In a carbon ion treatment the nuclear fragmentationof both target and beam projectiles impacts on the dose releasedon the tumor and on the surrounding healthy tissues. Carbon ionfragmentation occurring inside the patient body has to be stud-ied in order to take into account this contribution. These dataare also important for the development of the range monitoringtechniques with charged particles. The production of chargedfragments generated by carbon ion beams of 115-353 MeV/ukinetic energy impinging on carbon, oxygen, and hydrogen tar-gets has been measured at the CNAO particle therapy center(Pavia, Italy). The use of thin targets of graphite (C), PMMA(C2O5H8) and polyvinyl-toluene [plastic scintillator (PS), CbHa]allowed to measure fragments production cross sections, exploit-ing a time-of-flight (ToF) technique. PS detectors have been usedto perform the ToF measurements, while LYSO crystals havebeen used for the deposited energy measurement and to performparticle identification. Cross sections have been measured at 90◦and 60◦with respect to the beam direction. The measured pro-ton, deuteron, and triton differential production cross sectionson C, O, and H, obtained exploiting the target subtraction strat-egy, are presented here as a function of the fragment kineticenergy.

Particle therapy is increasingly used for the treatment of solid tumours, especially when the tolerance of organs at risk for conventional radiotherapy becomes dose limiting. To take full advantage of the particle therapy potential, the beam range in tissues has to be precisely known and the secondary particles production during the treatment has to be accurately characterised, as it can lead to unwanted dose deposition far from the target volume. Secondary neutrons can release a remarkable dose, also far from the tumour, increasing the probability of secondary cancer late insurgence in the patient. Currently, the treatment planning system software used in clinical routine suffer from the lack of high precision data related to the secondary neutron production in particle therapy treatments. The aim of the MONDO (MOnitor for Neutron Dose in hadrOntherapy) project is to develop a tracking detector for secondary neutrons in the energy range of 20 − 400 MeV. Neutrons flux, energy spectra and angular distribution will become experimentally available by tracking the recoil protons produced after two consecutive neutron elastic scattering interactions in a 10 × 10 × 20 cm 3 matrix of scintillating fibres. A Monte Carlo simulation based on the FLUKA code was developed to optimise the MONDO detector layout, define the tracker trigger logic, evaluate the background contamination and possible strategies for its reduction: preliminary results are reported in this manuscript. A 4 × 4 × 4.8 cm 3 detector prototype was tested with protons at the APSS Proton Therapy Centre in Trento (Italy), where calibration and efficiency measurements were performed. Experimental and simulated results were compared.

Particle therapy (PT) is a radiation therapy technique in which solid tumors are treated with charged ions and exploits the achievable highly localized dose delivery, allowing to spare healthy tissues and organs at risk. The development of a range monitoring technique to be used online, during the treatment, capable to reach millimetric precision is considered one of the important steps toward an optimization of the PT efficacy and of the treatment quality. To this aim, charged secondary particles produced in the nuclear interactions between the beam particles and the patient tissues can be exploited. Besides charged secondaries, neutrons are also produced in nuclear interactions. The secondary neutron component might cause an undesired and not negligible dose deposition far away from the tumor region, enhancing the risk of secondary malignant neoplasms that can develop even years after the treatment. An accurate neutron characterization (flux, energy and emission profile) is, hence, needed for a better evaluation of long-term complications. In this contribution, two tracker detectors, both based on scintillating fibers, are presented. The first one, named dose profiler (DP), is planned to be used as a beam range monitor in PT treatments with heavy ion beams, exploiting the charged secondary fragments production. The DP is currently under development within the Innovative Solutions for In-Beam DosimEtry in Hadrontherapy project. The second one is dedicated to the measurement of the fast and ultrafast neutron component produced in PT treatments, in the framework of the monitor for neutron dose in hadrontherapy project. Results of the first calibration tests performed at the Trento Protontherapy Center and at Centro Nazionale di Adroterapia Oncologica (Italy) are reported, as well as simulation studies.

The MOnitor for Neutron Dose in hadrOntherapy (MONDO) project addresses the technical challenges posed by a neutron tracker detector aiming for a high detection efficiency and a good backtracking precision. The project aims to develop a tracking device capable of fully reconstructing the four momentum of fast and ultrafast secondary neutrons produced, e.g., in particle therapy (PT) treatments or in other physical processes. The MONDO tracker uses, as active material, squared scintillating fibers readout by dedicated CMOS-based digital single-photon avalanche diode (SPAD) array sensors. The expected light output, when operating in neutron monitoring applications, was experimentally evaluated in order to optimize the design of the MONDO detector readout. A small detector prototype ( $4 \times 4 \times 4.8$ cm) has been built and tested at a test beam facility. The detection capabilities have been measured using a traditional photomultiplier (PMT) and a particle beam of 450-MeV electrons crossing a single layer of fibers. The observed number of photoelectrons in this case is (7.2 ± 1.4). A detector prototype was also tested with an SPAD-based SBAM (SPAD-Based Acquisition readout for MONDO experiment) sensor ( SPADnet-I ) to study the tracking performances. SBAM is a novel sensor developed to match the need of high single-photon detection efficiency and high spatial resolution and compactness. The sensor expected performance is discussed in view of an operation tailored for PT applications. In this contribution, we also report the results of a simulation performed to optimize the full MONDO detector layout.

Tumour control is performed in particle therapy using particles and ions, whose high irradiation precision enhances the effectiveness of the treatment, while sparing the healthy tissue surrounding the target volume. Dose range monitoring devices using photons and charged particles produced by the beam interacting with the patient's body have already been proposed, but no attempt has been made yet to exploit the detection of the abundant neutron component. Since neutrons can release a significant dose far away from the tumour region, precise measurements of their flux, production energy and angle distributions are eagerly sought in order to improve the treatment planning system (TPS) software. It will thus be possible to predict not only the normal tissue toxicity in the target region, but also the risk of late complications in the whole body. The aforementioned issues underline the importance of an experimental effort devoted to the precise characterisation of neutron production, aimed at the measurement of their abundance, emission point and production energy. The technical challenges posed by a neutron detector aimed at high detection efficiency and good backtracking precision are addressed within the MONDO (monitor for neutron dose in hadrontherapy) project, whose main goal is to develop a tracking detector that can target fast and ultrafast neutrons. A full reconstruction of two consecutive elastic scattering interactions undergone by the neutrons inside the detector material will be used to measure their energy and direction. The preliminary results of an MC simulation performed using the FLUKA software are presented here, together with the DSiPM (digital SiPM) readout implementation. New detector readout implementations specifically tailored to the MONDO tracker are also discussed, and the neutron detection efficiency attainable with the proposed neutron tracking strategy are reported.

Hadrontherapy is a technique for cancer treatment that exploits ion beams (mostly protons and carbons). A critical issue is the accuracy that is achievable when monitoring the dose released by the beam to the tumor and to the surrounding tissues. We present the design of a tracking device, developed in the framework of the INSIDE project [1] , capable of monitoring in real time the longitudinal profile of the dose delivered in the patient. This is possible by detecting the secondary particles produced by the interaction of the beam in the tissues. The position of the Bragg peak can be correlated to the charged particles emission point distribution measurement. The tracking device will be able to provide a fast response on the dose pattern by tracking the secondary charged fragments. The tracks are detected using 6 planes of scintillating fibers, providing the 3D coordinates of the track intersection with each plane. The fibers planes are followed by a plastic scintillator and by a small calorimeter built with a pixelated Lutetium Fine Silicate (LFS) crystal. A complete detector simulation, followed by the event reconstruction, has been performed to determine the achievable monitoring spatial resolution.

Charged particle therapy is a technique for cancer treatment that exploits hadron beams, mostly protons and carbon ions. A critical issue is the monitoring of the beam range so to check the correct dose deposition to the tumor and surrounding tissues. The design of a new tracking device for beam range real-time monitoring in pencil beam carbon ion therapy is presented. The proposed device tracks secondary charged particles produced by beam interactions in the patient tissue and exploits the correlation of the charged particle emission profile with the spatial dose deposition and the Bragg peak position. The detector, currently under construction, uses the information provided by 12 layers of scintillating fibers followed by a plastic scintillator and a pixelated Lutetium Fine Silicate (LFS) crystal calorimeter. An algorithm to account and correct for emission profile distortion due to charged secondaries absorption inside the patient tissue is also proposed. Finally detector reconstruction efficiency for charged particle emission profile is evaluated using a Monte Carlo simulation considering a quasi-realistic case of a non-homogenous phantom.

Summary: Charged particle therapy exploits proton or 12C beams to treat deep-seated solid tumors. Due to the advantageous characteristics of charged particles energy deposition in matter, the maximum of the dose is released to the tumor at the end of the beam range, in the Bragg peak region. However, the beam nuclear interactions with the patient tissues induces fragmentation both of projectile and target nuclei and needs to be carefully taken into account. In proton treatments, target fragmentation produces low energy, short range fragments along all the beam range, which deposit a non negligible dose in the entry channel. In 12C treatments the main concern is represented by long range fragments due to beam fragmentation that release their dose in the healthy tissues beyond the tumor. The FOOT experiment (FragmentatiOn Of Target) of INFN is designed to study these processes, in order to improve the nuclear fragmentation description in next generation Treatment Planning Systems and the treatment plans quality. Target (16O and 12C nuclei) fragmentation induced by –proton beams at therapeutic energies will be studied via an inverse kinematic approach, where 16O and 12C therapeutic beams impinge on graphite and hydrocarbon targets to provide the nuclear fragmentation cross section on hydrogen. Projectile fragmentation of 16O and 12C beams will be explored as well. The FOOT detector includes a magnetic spectrometer for the fragments momentum measurement, a plastic scintillator for ΔE and time of flight measurements and a crystal calorimeter to measure the fragments kinetic energy. These measurements will be combined in order to make an accurate fragment charge and isotopic identification. Keywords: Hadrontherapy, Nuclear fragmentation cross sections, Tracking detectors, Scintillating detectors

This paper describes the development and characterization of a Δ E-TOF detector composed of a plastic scintillator bar coupled at both ends to silicon photomultipliers. This detector is a prototype of a larger version which will be used in the FOOT (FragmentatiOn Of Target) experiment to identify the fragments produced by ion beams accelerated onto a hydrogen-enriched target. The final Δ E-TOF detector will be composed of two layers of plastic scintillator bars with orthogonal orientation and will measure, for each crossing fragment, the energy deposited in the plastic scintillator ( Δ E), the time of flight (TOF), and the coordinates of the interaction position in the scintillator. To meet the FOOT experimental requirements, the detector should have energy resolution of a few percents and time resolution of 70 ps, and it should allow to discriminate multiple fragments belonging to the same event. To evaluate the achievable performances, the detector prototype was irradiated with protons of kinetic energy in the 70–230 MeV range and interacting at several positions along the bar. The measured energy resolution σ Δ E ∕ Δ E was 6–14%, after subtracting the fluctuations of the deposited energy. A time resolution σ between 120 and 180 ps was obtained with respect to a trigger detector. A spatial resolution σ of 1.9 cm was obtained for protons interacting at the center of the bar.

Particle therapy (PT) can exploit heavy ions (such as He, C or O) to enhance the treatment efficacy, profiting from the increased Relative Biological Effectiveness and Oxygen Enhancement Ratio of these projectiles with respect to proton beams. To maximise the gain in tumor control probability a precise online monitoring of the dose release is needed, avoiding unnecessary large safety margins surroundings the tumor volume accounting for possible patient mispositioning or morphological changes with respect to the initial CT scan. The Dose Profiler (DP) detector, presented in this manuscript, is a scintillating fibres tracker of charged secondary particles (mainly protons) that will be operating during the treatment, allowing for an online range monitoring. Such monitoring technique is particularly promising in the context of heavy ions PT, in which the precision achievable by other techniques based on secondary photons detection is limited by the environmental background during the beam delivery. Developed and built at the SBAI department of "La Sapienza", within the INSIDE collaboration and as part of a Centro Fermi flagship project, the DP is a tracker detector specifically designed and planned for clinical applications inside a PT treatment room. The DP operation in clinical like conditions has been tested with the proton and carbon ions beams of Trento proton-therapy center and of the CNAO facility. In this contribution the detector performances are presented, in the context of the carbon ions monitoring clinical trial that is about to start at the CNAO centre.

Charged Particle Therapy (CPT) is a powerful radiotherapy technique for the treatment of deep-seated tumours characterized by a large dose released in the Bragg peak area (corresponding to the tumour region) and a small dose delivered to the surrounding healthy tissues. The precise measurement of the fragments produced in the nuclear interactions of charged particle beams with patient tissues is a crucial task to improve the clinical treatment plans. The FOOT (FragmentatiOn Of Target) experiment is an international project, funded by the Istituto Nazionale di Fisica Nucleare (INFN), aimed to study the dose released by the tissues and particle beams fragmentation. The target (16O, 12C) fragmentation induced by 150-400 MeV/n proton beams will be studied via the inverse kinematic approach, where 16O and 12C therapeutic beams collide on graphite and hydrocarbon target to provide the cross section on Hydrogen. A table-top detector is being developed and it includes a drift chamber as a beam monitor upstream of the target to measure the beam direction, a magnetic spectrometer based on silicon pixel and strip detectors, a scintillating crystal calorimeter able to stop the heavier produced fragments, and a ΔE detector, with TOF capability, for the particle identification. A setup based on the concept of the “Emulsion Cloud Chamber”, coupled with the interaction region of the electronic FOOT setup, will complement the physics program by measuring lighter charged fragments to extend the angular acceptance up to about 70 degrees. In this work, the experimental design and the requirements of the FOOT experiment will be discussed and preliminary results on the emulsion spectrometer tests will be presented.

In hadron therapy, the accelerated ions, interacting with the body of the patient, cause the fragmentation of both projectile and target nuclei. The fragments interact with the human tissues depositing energy both in the entrance channel and in the volume surrounding the tumor. The knowledge of the fragments features is crucial to determine the energy amount deposited in the human body, and - hence - the damage to the organs and to the tissues around the tumor target. The FOOT (FragmentatiOn Of Target) experiment aims at studying the fragmentation induced by the interaction of a proton beam (150-250 MeV/n) inside the human body. The FOOT detector includes an electronic setup for the identification of Z ≥ 3 fragments integrated with an emulsion spectrometer to measure Z ≤ 3 fragments. Charge identification by nuclear emulsions is based on the development of techniques of controlled fading of the particle tracks inside the nuclear emulsion, that extend the dynamical range of the films developed for the tracking of minimum ionising particles. The controlled fading strongly depends on temperature, relative humidity and treatment duration. In this study the performances in terms of charge separation of proton, helium and carbon particles, obtained on a batch of new emulsion films produced in Japan are reported.

Particle therapy is a therapy technique that exploits protons or light ions to irradiate tumor targets with high accuracy. Protons and 12C ions are already used for irradiation in clinical routine, while new ions like 4He and 16O are currently being considered. Despite the indisputable physical and biological advantages of such ion beams, the planning of charged particle therapy treatments is challenged by range uncertainties, i.e. the uncertainty on the position of the maximal dose release (Bragg Peak - BP), during the treatment. To ensure correct 'in-treatment' dose deposition, range monitoring techniques, currently missing in light ion treatment techniques, are eagerly needed. The results presented in this manuscript indicate that charged secondary particles, mainly protons, produced by an 16O beam during target irradiation can be considered as candidates for 16O beam range monitoring. Hereafter, we report on the first yield measurements of protons, deuterons and tritons produced in the interaction of an 16O beam impinging on a PMMA target, as a function of detected energy and particle production position. Charged particles were detected at 90° and 60° with respect to incoming beam direction, and homogeneous and heterogeneous PMMA targets were used to probe the sensitivity of the technique to target inhomogeneities. The reported secondary particle yields provide essential information needed to assess the accuracy and resolution achievable in clinical conditions by range monitoring techniques based on secondary charged radiation.

The use of C, He and O as beam particles in Particle Therapy (PT) treatments is getting more and more widespread as a consequence of the enhanced relative biological effectiveness and oxygen enhancement ratio of such projectiles with respect to protons. The advantages in the tumor control probability, related to the improved efficacy of ions, are calling for an online monitor of the dose release spatial distribution. Such technology is currently missing in PT treatments clinical routine. In this contribution the status of Z > 1 ions PT treatments monitoring, exploiting the detection of either charged secondary particles or neutrons, is reviewed. While charged fragments can be used to provide an online feedback to the beam control system, by correlating their emission profile with the position of the Bragg peak, neutrons have to be monitored to improve the experimental description of the secondary radiation component that significantly contributes to an undesired and not negligible dose deposition far away from the tumor region, enhancing the risk of secondary malignancies development after the treatment. Two tracker detectors, employing scintillating fibers , are presented: the Dose Profiler designed for charged secondary fragments measurements and the MONDO tracker dedicated to the characterisation of the secondary fast and ultrafast neutron component, within the MONDO (MOnitor for Neutron Dose in hadrOntherapy) project.

The advantages of using C, He and O ions as therapeutical beam particles in Particle Therapy is related to their enhanced Relative Biological Effectiveness and Oxygen Enhancement Ratio, resulting in an improved efficacy in damaging the cancerous cells. However, an accurate on-line control of the dose release spatial distribution is required to spare the healthy tissues surrounding the tumor area, preventing undesired damages caused by, for example, morphological changes occurred in the patient during the treatment with respect to the initial CT scan. This monitor technology is currently missing in clinical practice, and several studies are being performed to develop beam range verification systems exploiting the detection of the emitted secondary radiation. Charged secondary particles, produced by the projectile fragmentation in the collisions with the patient tissues, represent an interesting chance for C, He and O treatments since they are also emitted at large angles with respect to the beam direction and can be detected with high efficiency in a nearly background free environment. The Dose Profiler detector is a scintillating fibre tracker that allows an online charged fragments reconstruction and backtracking. The construction and preliminary tests performed on the DP, carried out using the Carbon ions beam of the CNAO treatment centre using an anthropomorphic phantom as a target, will be reviewed in this contribution.

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.

Radio Guided Surgery is a technique helping the surgeon in the resection of tumors: a radiolabeled tracer is administered to the patient before surgery and then the surgeon evaluates the completeness of the resection with a handheld detector sensitive to emitted radiation. Established methods rely on γ emitting tracers coupled with γ detecting probes. The efficacy of this technique is however hindered by the high penetration of γ radiation, limiting its applicability to low background conditions. To overtake such limitations, a novel approach to RGS has been proposed, relying on β− emitting isotopes together with a dedicated β probe. This technique has been proved to be effective in first ex-vivo trials. We discuss in this paper the possibility to extend its application cases to 68Ga, a β+ emitting isotope widely used today in nuclear medicine. To this aim, a retrospective study on 45 prostatic cancer patients was performed, analysing their 68Ga-PSMA PET images to asses if the molecule uptake is enough to apply this technique. Despite the expected variability both in terms of SUV (median 4.1, IQR 3.0–6.1) and TNR (median 9.4, IQR 5.2–14.6), the majority of cases have been found to be compatible with β-RGS with reasonable injected activity and probing time (5 s).

Radio Guided Surgery is a technique helping the surgeon in the resection of tumors: a radiolabeled tracer is administered to the patient before surgery and then the surgeon evaluates the completeness of the resection with a handheld detector sensitive to emitted radiation. Established methods rely on γ emitting tracers coupled with γ detecting probes. The efficacy of this technique is however hindered by the high penetration of γ radiation, limiting its applicability to low background conditions. To overtake such limitations, a novel approach to RGS has been proposed, relying on β− emitting isotopes together with a dedicated β probe. This technique has been proved to be effective in first ex-vivo trials. We discuss in this paper the possibility to extend its application cases to 68Ga, a β+ emitting isotope widely used today in nuclear medicine. To this aim, a retrospective study on 45 prostatic cancer patients was performed, analysing their 68Ga-PSMA PET images to asses if the molecule uptake is enough to apply this technique. Despite the expected variability both in terms of SUV (median 4.1, IQR 3.0–6.1) and TNR (median 9.4, IQR 5.2–14.6), the majority of cases have been found to be compatible with β-RGS with reasonable injected activity and probing time (5 s).

Purpose Beta-particle radioguided tumor resection may potentially overcome the limitations of conventional gamma-ray guided surgery by eliminating, or at least minimizing, the confounding effect of counts contributed by activity in adjacent normal tissues. The current study evaluates the clinical feasibility of this approach for a variety of radionuclides. Nowadays, the only β - radioisotope suited to radioguided surgery is 90Y. Here, we study the β - probe prototype capability to different radionuclides chosen among those used in nuclear medicine. Methods The counting efficiency of our probe prototype was evaluated for sources of electrons and photons of different energies. Such measurements were used to benchmark the Monte Carlo (MC) simulation of the probe behavior, especially the parameters related to the simulation of the optical photon propagation in the scintillation crystal. Then, the MC simulation was used to derive the signal and the background we would measure from a small tumor embedded in the patient body if one of the selected radionuclides is used. Results Based on the criterion of detectability of a 0.1 ml tumor for a counting interval of 1 s and an administered activity of 3 MBq/kg, the current probe yields a detectable signal over a wide range of Standard Uptake Values (SUVs) and tumor-to-non-tumor activity-concentration ratios (TNRs) for 31Si, 32P, 97Zr, and 188Re. Although efficient counting of 83Br, 133I, and 153Sm proved somewhat more problematic, the foregoing criterion can be satisfied for these isotopes as well for sufficiently high SUVs and TNRs.

Particle therapy uses protons or $^{12}$C beams for the treatment of deep-seated solid tumors. Due to the features of the energy deposition of charged particles in matter, a limited amount of dose is released to the healthy tissue in the beam entrance region, while the maximum of the dose is released to the tumor at the end of the beam range, in the Bragg peak region. However nuclear interactions between beam and patient tissues induce fragmentation both of projectile and target. This has to be carefully taken into account since different ions have different effectiveness in producing a biological damage. par In $^{12}$C treatments the main concern are long range forward emitted secondary ions produced in projectile fragmentation that release dose in the healthy tissue after the tumor. Instead, in a proton treatment, the target fragmentation produces low energy, short range fragments along all the beam range. The FOOT experiment (FragmentatiOn Of Target) is designed to study these processes. Target nuclei ($^{16}$O, $^{12}$C) fragmentation induced by 150-250 MeV proton beam will be studied by means of the inverse kinematic approach: $^{16}$O,$^{12}$C therapeutic beams, at the quoted kinetic energy per nucleon, collide on graphite and hydrocarbons target. The cross section on Hydrogen can be then extracted by subtraction. This configuration explores also the projectile fragmentation of these O and C beams, or other ions of therapeutic interest, such as $^4$He for instance. The detector includes a magnetic spectrometer based on silicon pixel and strip detectors, a scintillating crystal calorimeter able to stop the heavier produced fragments, and a $\Delta E$ detector, with TOF capability, to achieve the needed energy resolution and particle identification. In addition to the electronic apparatus, an alternative setup based on the concept of the "Emulsion Cloud Chamber", coupled with the interaction region of the electronic FOOT setup, will provide the measurement of lighter charged fragments: protons, deuterons, tritons and Helium nuclei. The FOOT data taking is foreseen in the available experimental rooms existing in the presently operational charged particle therapy facilities in Europe, and possibly at GSI. An initial phase with the emulsion setup will start in early 2018, while the complete electronic detector will take data starting in 2019. In this work a general description of the FOOT experiment and of its expected performances is presented.

Purpose The real-time monitoring of the spread-out Bragg peak would allow the planned dose delivered during treatment to be directly verified, but this poses a major challenge in modern ion beam therapy. A possible method to achieve this goal is to exploit the production of secondary particles by the nuclear reactions of the beam with the patient and correlate their emission profile to the planned target volume position. In this study, we present both the production rate and energy spectra of the prompt-γ produced by the interactions of the 12C ion beam with a polymethyl methacrylate (PMMA) target. We also assess three different Monte Carlo models for prompt-γsimulation based on our experimental data. Methods The experiment was carried out at the GSI Helmholtz Centre for Heavy Ion Research, Germany with a 220 Me V/u 12C ions beam impinging on a 5×5×20 cm3polymethyl methacrylate beam stopping target, with the prompt-γbeing detected by a hexagonallyshaped barium uoride scintillator with a circumscribed radius of 5.4 cm and a length of 14 cm, placed at 60°and 90°with respect to the beam direction. Monte Carlo simulations were carried out with three different hadronic models from the GEANT4 code: binary ion cascade (BIC), quantum molecular dynamics (QMD), and Liege intranuclear cascade (INCL++) Results An experimental prompt-γ yield of 1.06×10-2 sr−1 was measured at 90°.A good agreement was observed between the shapes of the experimental and simulated energy spectra,especially with the INCL++physics list. The prompt-γ yield obtained with this physics list was compatible with the measurement within 2σ, with a relative difference of 26% on average. BIC and QMD physics lists proved to be less accurate than INCL++,with the difference between the measured and simulated yields exceeding 100%.The differences between the three physics lists were ascribed to important discrepancies between the models of the physical processes producing prompt-γ emissions. Conclusion In conclusion, this study provides prompt- γ yield values in agreement with previously published results for different carbon ions energies. his work demonstrates that the INCL++ physics list from GEANT4 is more accurate than BIC and QMD to reproduce prompt-γ emission properties. This article is protected by copyright. All rights reserved.

Charged particle beams are used in Particle Therapy (PT) to treat oncological patients due to their selective dose deposition in tissues and to their high biological effect in killing cancer cells with respect to photons and electrons used in conventional radiotherapy. Nowadays, protons and carbon ions are used in PT clinical routine but, recently, the interest on the potential application of helium and oxygen beams is growing due to their reduced multiple scattering inside the body and increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands for online dose monitoring techniques, crucial to improve the quality assurance of treatments. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Prompt photons are produced by nuclear de-excitation processes and, at present, different dose monitoring and beam range verification techniques based on the prompt {\gamma} detection have been proposed. It is hence of importance to perform the {\gamma} yield measurement in therapeutical-like conditions. In this paper we report the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a PMMA target. The measurements were performed at the Heidelberg Ion-beam Therapy center (HIT) with beams of different energies. A LYSO scintillator has been used as photon detector. The obtained {\gamma} yields for $^{12}$C ion beams are compared with results from literature, while no other results from $^{4}$He and $^{16}$O beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-{\gamma} based monitoring technique for PT treatments using helium, carbon and oxygen ion beams., Comment: Submitted to PMB

Radio-guided surgery (RGS) is a technique to intraoperatively detect tumour remnants, favouring a radical resection. Exploiting β − emitting tracers provides a higher signal to background ratio compared to the established technique with γ radiation, allowing the extension of the RGS applicability range. We developed and tested a detector based on para-terphenyl scintillator with high sensitivity to low energy electrons and almost transparent to γ s to be used as intraoperative probe for RGS with β − emitting tracer. Portable read out electronics was customised to match the surgeon needs. This probe was used for preclinical test on specific phantoms and a test on “ex vivo” specimens from patients affected by meningioma showing very promising results for the application of this new technique on brain tumours. In this paper, the prototype of the intraoperative probe and the tests are discussed; then, the results on meningioma are used to make predictions on the performance of the probe detecting residuals of a more challenging and more interesting brain tumour: the glioma.

Particle therapy is a technique that uses accelerated charged ions for cancer treatment and combines a high irradiation precision with a high biological effectiveness in killing tumor cells [1]. Informations about the secondary particles emitted in the interaction of an ion beam with the patient during a treatment can be of great interest in order to monitor the dose deposition. For this purpose an experiment at the HIT (Heidelberg Ion-Beam Therapy Center) beam facility has been performed in order to measure fluxes and emission profiles of secondary particles produced in the interaction of therapeutic beams with a PMMA target. In this contribution some preliminary results about the emission profiles and the energy spectra of the detected secondaries will be presented.

Purpose: A radio-guided surgery technique with beta- -emitting radio-tracers was suggested to overcome the effect of the large penetration of gamma radiation. The feasibility studies in the case of brain tumors and abdominal neuro-endocrine tumors were based on simulations starting from PET images with several underlying assumptions. This paper reports, as proof-of-principle of this technique, an ex-vivo test on a meningioma patient. This test allowed to validate the whole chain, from the evaluation of the SUV of the tumor, to the assumptions on the bio-distribution and the signal detection. Methods: A patient affected by meningioma was administered 300 MBq of 90Y-DOTATOC. Several samples extracted from the meningioma and the nearby Dura Mater were analyzed with a beta- probe designed specifically for this radio-guided surgery technique. The observed signals were compared both with the evaluation from the histology and with the Monte Carlo simulation. Results: we obtained a large signal on the bulk tumor (105 cps) and a significant signal on residuals of $\sim$0.2 ml (28 cps). We also show that simulations predict correctly the observed yields and this allows us to estimate that the healthy tissues would return negligible signals (~1 cps). This test also demonstrated that the exposure of the medical staff is negligible and that among the biological wastes only urine has a significant activity. Conclusions: This proof-of-principle test on a patient assessed that the technique is feasible with negligible background to medical personnel and confirmed that the expectations obtained with Monte Carlo simulations starting from diagnostic PET images are correct., Comment: 17 pages, 4 Figs, Accepted by Physica Medica