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PURPOSE A high level of personalization in Molecular Radiotherapy (MRT) could bring advantages in terms of treatment effectiveness and toxicity reduction. Individual organ-level dosimetry is crucial to describe the radiopharmaceutical biodistribution expressed by the patient, to estimate absorbed doses to normal organs and target tissue(s). This paper presents a proof-of-concept Monte Carlo simulation study of "WIDMApp" (Wearable Individual Dose Monitoring Apparatus), a multi-channel radiation detector and data processing system for in vivo patient measurement and collection of radiopharmaceutical biokinetic data (i.e., time-activity data). Potentially, such a system can increase the amount of such data that can be collected while reducing the need to derive it via nuclear medicine imaging. METHODS a male anthropomorphic MIRD phantom was used to simulate photons (i.e., gamma-rays) propagation in a patient undergoing a 131 I thyroid treatment. The administered activity was set to the amount usually administered for the treatment of differentiated carcinoma while its initial distribution in different organs was assigned following the ICRP indications for the 131 I biokinetics. Using this information, the simulation computes the Time-dependent Counts Curves (TCCs) that would have been measured by seven WIDMApp-like sensors placed and oriented to face each one of five emitting organs plus two thyroid lobes. A deconvolution algorithm was then applied on this simulated data set to reconstruct the Time-Activity Curve (TAC) of each organ. Deviations of the reconstructed TACs parameters from values used to generate them were studied as a function of the deconvolution algorithm initialization parameters and assuming non-Poisson fluctuation of the TCCs data points. RESULTS This study demonstrates that it is possible, at least in the simple simulated scenario, to reconstruct the organ cumulated activity by measuring the time dependence of counts recorded by several detectors placed at selected positions on the patient's body. The ability to perform in vivo sampling more frequently than conventional biokinetic studies increases the number of time points and therefore the accuracy in TAC estimates. In this study, an accuracy on cumulated activity of 5% is obtained even with a 20% error on the TCC data points and a 50% error on the initial guess on the parameters of the deconvolution algorithm. CONCLUSIONS the WIDMApp approach could provide an effective tool to characterize more accurately the radiopharmaceutical biokinetics in MRT patients, reducing the need of resources of nuclear medicine departments, such as technologist and scanner time, to perform individualized biokinetics studies. The relatively simple hardware for the approach proposed would allow its application to large numbers of patients. The results obtained justify development of an actual prototype system to characterize this technique under realistic conditions.

Background: In neuroendocrine tumor (NET), complete surgery could better the prognosis. Radioguided surgery (RGS) with β−-radioisotopes is a novel approach focused on developing a new probe that, d...

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.

BACKGROUND: Spread through air spaces (STAS) has been reported as a negative prognostic factor in patients with lung cancer undergoing sublobar resection. Radiomics has been recently proposed to predict STAS using preoperative computed tomography (CT). However, limitations of previous studies included the strict selection of imaging acquisition protocols, leading to results hardly applicable to daily clinical practice. The aim of this study is to test a radiomics-based prediction model of STAS in a practice-based dataset. METHODS: A training cohort of 99 consecutive patients (65 STAS+ and 34 STAS−) with resected lung adenocarcinoma (ADC) was retrospectively collected. Preoperative CT images were collected from different centers regardless model and scanner manufacture, acquisition and reconstruction protocol, contrast phase and pixel size. Radiomics features were selected according to separation power and P value stability within different preprocessing setups and bootstrapping resampling. A prospective cohort of 50 patients (33 STAS+ and 17 STAS−) was enrolled for the external validation. RESULTS: Only the five features with the highest stability were considered for the prediction model building. Radiomics, radiological and mixed radiomics-radiological prediction models were created, showing an accuracy of 0.66±0.02 after internal validation and reaching an accuracy of 0.78 in the external validation. CONCLUSIONS: Radiomics-based prediction models of STAS may be useful to properly plan surgical treatment and avoid oncological ineffective sublobar resections. This study supports a possible application of radiomics-based models on data with high variance in acquisition, reconstruction and preprocessing, opening a new chance for the use of radiomics in the prediction of STAS. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04893200.

One of the obstacles to the application of Boron Neutron Capture Therapy (BNCT) and Proton Boron Fusion Therapy (PBFT) concerns the measurement of borated carriers' biodistribution. The objective of the present study was to evaluate the in vitro internalization of theTheOur studies suggested thatThe ability of

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

We present a detailed description of the electromagnetic filter for the PTOLEMY project to directly detect the Cosmic Neutrino Background (CNB). Starting with an initial estimate for the orbital magnetic moment, the higher-order drift process of E×B is configured to balance the gradient-B drift motion of the electron in such a way as to guide the trajectory into the standing voltage potential along the mid-plane of the filter. As a function of drift distance along the length of the filter, the filter zooms in with exponentially increasing precision on the transverse velocity component of the electron kinetic energy. This yields a linear dimension for the total filter length that is exceptionally compact compared to previous techniques for electromagnetic filtering. The parallel velocity component of the electron kinetic energy oscillates in an electrostatic harmonic trap as the electron drifts along the length of the filter. An analysis of the phase-space volume conservation validates the expected behavior of the filter from the adiabatic invariance of the orbital magnetic moment and energy conservation following Liouville's theorem for Hamiltonian systems., CGT is supported by the Simons Foundation (#377485) and John Templeton Foundation (#58851)

The study of ions in the gas phase has a long history and has involved both chemists and physicists. The interplay of their competences with the use of very sophisticated commercial and/or homemade instrumentations and theoretical models has improved the knowledge of thermodynamics and kinetics of many chemical reactions, even if still many stages of these processes need to be fully understood. The new technologies and the novel free-electron laser facilities based on plasma acceleration open new opportunities to investigate the chemical reactions in some unrevealed fundamental aspects. The synchrotron light source can be put beside the FELs, and by mass spectrometric techniques and spectroscopies coupled with versatile ion sources it is possible to really change the state of the art of the ion chemistry in different areas such as atmospheric and astro chemistry, plasma chemistry, biophysics, and interstellar medium (ISM). In this manuscript we review the works performed by a joint combination of the experimental studies of ion–molecule reactions with synchrotron radiation and theoretical models adapted and developed to the experimental evidence. The review concludes with the perspectives of ion–molecule reactions by using FEL instrumentations as well as pump probe measurements and the initial attempt in the development of more realistic theoretical models for the prospective improvement of our predictive capability.

Radiography and CT are diagnostic tools that make use of ionizing radiation and therefore, while providing clear benefits, can potentially cause harm. The use of radiation is indeed not risk free and any possible improvement that can minimize its use is welcome. Therefore, in the assessment of the benefit–risk ratio a knowledge both of medical and of radiation risks is needed. This chapter will give an overview of the characteristics of the radiation that is used in radiology and its properties and it will quantify the risks introduced by X-ray exams and compare them with the exposure to natural radiation and with other medical exams.

In particle therapy, the uncertainty of the delivered particle range during the patient irradiation limits the optimization of the treatment planning. Therefore, an in vivo treatment verification device is required, not only to improve the plan robustness, but also to detect significant interfractional morphological changes during the treatment itself. In this article, an effective and robust analysis to detect regions with a significant range discrepancy is proposed. This study relies on an in vivo treatment verification by means of in-beam Positron Emission Tomography (PET) and was carried out with the INSIDE system installed at the National Center of Oncological Hadrontherapy (CNAO) in Pavia, which is under clinical testing since July 2019. Patients affected by head-and-neck tumors treated with protons have been considered. First, in order to tune the analysis parameters, a Monte Carlo (MC) simulation was carried out to reproduce a patient who required a replanning because of significant morphological changes found during the treatment. Then, the developed approach was validated on the experimental measurements of three patients recruited for the INSIDE clinical trial (ClinicalTrials.govID: NCT03662373), showing the capability to estimate the treatment compliance with the prescription both when no morphological changes occurred and when a morphological change did occur, thus proving to be a promising tool for clinicians to detect variations in the patients treatments.

Background: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. Aims: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. Materials and Methods: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. Results: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. Discussion: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. Conclusion: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application. Ministerio de Economía y Competitividad FPA2016-77689-C2-1-R National Institutes of Health U24CA215123 France-Greece PICS 8235 European Space Agency 4000126645/19/NL/BW Australian Research Council ARC DP170100967, DP170102423 Susan G Komen Foundation for the Cure IIR13262248

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.

Background Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET tracers during robot-assisted tumor-receptor-targeted. In this study, we have engineered and validated the performance of a novel DROP-IN beta particle (DROP-INβ) detector. Methods Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of ~ 70 MBq 68Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-INβ probe prototype, which merged a scintillating detector with a housing optimized for a 12-mm trocar and prograsp instruments. Results After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-INβ probe prototype was tested in a robotic setting. In the ex vivo setting, the probe—positioned by the robot—was able to identify 68Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located 68Ga-PSMA-11 containing (and PET positive) lymph nodes, as found in two patients, were also confirmed with the DROP-INβ probe (S/B > 3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta-tracing. Conclusions This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-INβ detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes.

Background: Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. This study explores the use of a novel DROP-IN beta-particle (DROP-IN b ) detection probe to support the implementation of the large number of PET-tracers available during robot-assisted tumor-receptor-targeted resections. Methods: Following engineering of the DROP-IN b probe, robotic implementation was investigated using surgical specimens. Seven prostate cancer patients with PSMA-PET positive tumors received an intraoperative injection of ~100 MBq 68 Ga-PSMA-11, followed by prostatectomy and extended pelvic lymph node dissection. Results: The probe was able to identify the position of the tumor in the prostate specimens: S/B was > 5 when pathology confirmed that the tumor was located 3). Conclusions: This ex vivo study underlines the potential to use a DROP-IN b probe for intraoperative tumor identification on the prostate surface and confirmation of PSMA-PET positive lymph nodes.

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.

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

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.

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.

Nowadays there is a growing interest in Particle Therapy treatments exploiting light ion beams against tumors due to their enhanced Relative Biological Effectiveness and high space selectivity. In particular promising results are obtained by the use of $^4$He projectiles. Unlike the treatments performed using protons, the beam ions can undergo a fragmentation process when interacting with the atomic nuclei in the patient body. In this paper the results of measurements performed at the Heidelberg Ion-Beam Therapy center are reported. For the first time the absolute fluxes and the energy spectra of the fragments - protons, deuterons, and tritons - produced by $^4$He ion beams of 102, 125 and 145 MeV/u energies on a poly-methyl methacrylate target were evaluated at different angles. The obtained results are particularly relevant in view of the necessary optimization and review of the Treatment Planning Software being developed for clinical use of $^4$He beams in clinical routine and the relative benchmarking of Monte Carlo algorithm predictions.

Purpose Radio Guided Surgery (RGS) is a technique that helps the surgeon to achieve an as complete as possible tumor resection, thanks to the intraoperative detection of particles emitted by a radio tracer that bounds to tumoral cells. In the last years, a novel approach to this technique has been proposed that, exploiting β - emitting radio tracers, overtakes some limitations of established γ -RGS. In this context, a first prototype of an intraoperative β particle detector, based on a high light yield and low density organic scintillator, has been developed and characterised on pure β - emitters, like 90 Y . The demonstrated very high efficiency to β - particles, together with the remarkable transparency to photons, suggested the possibility to use this detector also with β + emitting sources, that have plenty of applications in nuclear medicine. In this paper, we present upgrades and optimisations performed to the detector to reveal such particles. Methods Laboratory measurement have been performed on liquid Ga 68 source, and were used to validate and tune a Monte Carlo simulation. Results The upgraded detector has an ~ 80 % efficiency to electrons above ~ 110 keV , reaching a plateau value of ~ 95 % . At the same time, the probe is substantially transparent to photons below ~ 200 keV , reaching a plateau value of ~ 3 % . Conclusions The new prototype seems to have promising characteristics to perform RGS also with β + emitting isotopes.

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.

Radio-Guided Surgery (RGS) is a surgical technique aimed at assisting the surgeon to reach as complete a resection of the tumoural lesion as possible. Established methods to date make use of \( \gamma \)-emitting tracers to radio-mark the neoplastic tissue. However, in case of uptake from healthy organs around the lesion the large penetration of photons yields a non-negligible background that can limit the RGS application. The adoption of \( \beta^{ - } \) radiation has been proposed to overcome this limit. To validate the entire RGS procedure, from the evaluation of the tracer uptake of the tumor, to the assumptions on the bio-distribution and the signal detection, tests on ex vivo specimens of meningioma brain tumour were performed. Meningioma was selected due to the well known high receptivity to a \( \beta^{ - } \) emitting radio-tracer already in use in the clinical practice: 90Y-labelled DOTATOC. Patients were enrolled according to the tumour Standard Uptake Value (SUV \( > \) 2) and the expected Tumour to Non-tumour Ratio (TNR \( > \) 10) estimated from 68Ga-DOTATOC PET images. After injecting the patients with 93–167 MBq of \( ^{90} Y - DOTATOC \), 26 samples excised during surgery were examined with a dedicated \( \beta^{ - } \) detecting probe to assess the sensitivity of millimetre-sized tumour remnants in case of administration of low activity value compatible with those injected for diagnostic exams. Even injecting as low as 1.4 MBq/kg of radio-tracer, tumour remnants greater than 0.06 ml would be discriminated by the healthy tissue in few seconds.

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.

Purpose To develop and validate an Artificial Intelligence (AI) model based on texture analysis of high-resolution T2 weighted MR images able 1) to predict pathologic Complete Response (CR) and 2) to identify non-responders (NR) among patients with locally-advanced rectal cancer (LARC) after receiving neoadjuvant chemoradiotherapy (CRT). Method Fifty-five consecutive patients with LARC were retrospectively enrolled in this study. Patients underwent 3 T Magnetic Resonance Imaging (MRI) acquiring T2-weighted images before, during and after CRT. All patients underwent complete surgical resection and histopathology was the gold standard. Textural features were automatically extracted using an open-source software. A sub-set of statistically significant textural features was selected and two AI models were built by training a Random Forest (RF) classifier on 28 patients (training cohort). Model performances were estimated on 27 patients (validation cohort) using a ROC curve and a decision curve analysis. Results Sixteen of 55 patients achieved CR. The AI model for CR classification showed good discrimination power with mean area under the receiver operating curve (AUC) of 0.86 (95% CI: 0.70, 0.94) in the validation cohort. The discriminatory power for the NR classification showed a mean AUC of 0.83 (95% CI: 0.71,0.92). Decision curve analysis confirmed higher net patient benefit when using AI models compared to standard-of-care. Conclusions AI models based on textural features of MR images of patients with LARC may help to identify patients who will show CR at the end of treatment and those who will not respond to therapy (NR) at an early stage of the treatment.

The development of the $\beta^-$ based radio-guided surgery aims to extend the technique to those tumours where surgery is the only possible treatment and the assessment of the resection would most profit from the low background around the lesion, as for brain tumours. Feasibility studies on meningioma, glioma, and neuroendocrine tumors already estimated the potentiality of this new treatment. To validate the technique, prototypes of the intraoperative probe required by the technique to detect $\beta^-$ radiation have been developed. This paper discusses the design details of the device and the tests performed in laboratory. In such tests particular care has to be taken to reproduce the surgical field conditions. The innovative technique to produce specific phantoms and the dedicated testing protocols is described in detail., Comment: 7 pages, 15 figures

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).

Perturbing fluids of neutrons and protons (nuclear matter) may lead, as the most catastrophic effect, to the rearrangement of the fluid into clusters of nucleons. A similar process may occur in a single atomic nucleus undergoing a violent perturbation, like in heavy-ion collisions tracked in particle accelerators at around 30 to 50 MeV per nucleon: in this conditions, after the initial collision shock, the nucleus expands and then clusterises into several smaller nuclear fragments. Microscopically, when violent perturbation are applied to nuclear matter, a process of clusterisation arises from the combination of several fluctuation modes of large-amplitude where neutrons and protons may oscillate in phase or out of phase. The imposed perturbation leads to conditions of instability, the wavelengths which are the most amplified have sizes comparable to small atomic nuclei. We found that these conditions, explored in heavy-ion collisions, correspond to the splitting of a nucleus into fragments ranging from Oxygen to Neon in a time interval shorter than one zeptosecond (10$^{-21}$s). From the out-of-phase oscillations of neutrons and protons another property arises, the smaller fragments belonging to a more volatile phase get more neutron enriched: in the heavy-ion collision case this process, called distillation, reflects in the isotopic distributions of the fragments. The resulting dynamical description of heavy-ion collisions is an improvement with respect to more usual statistical approaches, based on the equilibrium assumption. It allows in fact to characterise also the very fast early stages of the collision process which are out of equilibrium. Such dynamical description is the core of the Boltzmann-Langevin One Body (BLOB) model, which unifies in a common description fluctuations in nuclear matter and the disintegration of nuclei into nuclear fragments., Comment: Contribution to the symposium "Nuclear Reactions on Nucleons and Nuclei", Messina (Italy), October 25-26, 2017

The aim of the present work has been the mass spectrometry characterization of the Nimotuzumab (NIM) antibody chemically modified with the bifunctional chelating agent para-S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraaza cyclododecanetetraacetic acid (p-SCN-Bn-DOTA). The conjugate, upon labeling with the pure β--emitter 90Y3+, could represent a promising candidate as radiotracer for an innovative radio-guided surgery (RGS) technique, developed and patented by researchers of our group, which uses a probe system for intraoperative detection of tumor residues exploiting the selective uptake of β--emitting tracers. The results reported in this study show that multiple DOTA molecules bind to lysine residues of both light and heavy chains of the antibody and, probably, some of them are linked to the variable region of antibody. Moreover, the new mass spectrometric analysis highlights the presence of unreacted NIM in the final product. The information obtained by this work is of fundamental importance in the perspective to utilize this conjugate as a radiocompound after its labeling with 90Y3+ radioisotope. Indeed, the conjugation efficiency and the presence of unreacted NIM affect the specific activity of the final radiotracer which binds specific receptor.

The aim of the present work has been the mass spectrometry characterization of the Nimotuzumab (NIM) antibody chemically modified with the bifunctional chelating agent para-S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraaza cyclododecanetetraacetic acid (p-SCN-Bn-DOTA). The conjugate, upon labeling with the pure β

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.

The recent interest in beta- radionuclides for radio-guided surgery derives from the feature of the beta radiation to release energy in few millimeters of tissue. Such feature can be used to locate residual tumors with a probe located in its immediate vicinity, determining the resection margins with an accuracy of millimeters. The drawback of this technique is that it does not allow to identify tumors hidden in more than few mm of tissue. Conversely, the bremsstrahlung X-rays emitted by the interaction of the beta- radiation with the nuclei of the tissue are relatively penetrating. To complement the beta- probes, we have therefore developed a detector based on cadmium telluride, an X-ray detector with a high quantum efficiency working at room temperature. We measured the secondary emission of bremsstrahlung photons in a target of Polymethylmethacrylate (PMMA) with a density similar to living tissue. The results show that this device allows to detect a 1 ml residual or lymph-node with an activity of 1 kBq hidden under a layer of 10 mm of PMMA with a 3:1 signal to noise, i.e. with a five sigma discrimination in less than 5 s.

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

Purpose A very promising technique for radio-guided surgery (RGS) based on β -radiation is being developed. The lower background, with respect to the established approach with high penetrant γ radiation, can allow for a large diffusion of such a technique and extending the RGS to cases with a large uptake of surrounding healthy organs, such as abdominal and brain neoplastic disease or tumor of infancy. Methods To validate the β -RGS feasibility study, tests on ex-vivo specimens of brain meningioma and gastro-entero-pancreatic neuroendocrine tumors have been performed. These clinical cases were selected between the tumors known to express receptors to a β -emitting radio-tracer already in use in the clinical routine: 90Y-labelled DOTATOC. Voluntary patients were enrolled according to the standard uptake value (SUV) and the expected tumor-to-non-tumor ratios (TNR) estimated from PET/CT images after administration of 68 Ga-DOTATOC. All of them gave written informed consent to participate in the clinical trial, already approved by the Ethics Committee. After administration of a low activity (about 2.5 mCi) of 90Y-DOTATOC, the extracted ex-vivo specimens and the healthy tissue around the lesions were examined to assess the correlation between the counting rates measured by the developed β -detecting probe and the expected 90Y activity. Results All the neoplastic samples were correctly identified. A dependence of the counting rate both on the volume V and on the total activity of the sample were observed. Even injecting as low as 1.4 MBq/kg of radio-tracer, tumor remnants of 0.1 ml would be detectable in few seconds. Conclusions The results of the clinical tests showed the validity of the underlying assumptions and strengthening the feasibility studies already published. Small radiopharmaceutical activity is required to detect a tumor remnant as expected due to the low background rates. The negligible medical staff exposure was also confirmed.

Proton and carbon ion beams are used in the clinical practice for external radiotherapy treatments achieving, for selected indications, promising and superior clinical results with respect to x-ray based radiotherapy. Other ions, like [Formula: see text] have recently been considered as projectiles in particle therapy centres and might represent a good compromise between the linear energy transfer and the radiobiological effectiveness of [Formula: see text] ion and proton beams, allowing improved tumour control probability and minimising normal tissue complication probability. All the currently used p, [Formula: see text] and [Formula: see text] ion beams allow achieving sharp dose gradients on the boundary of the target volume, however the accurate dose delivery is sensitive to the patient positioning and to anatomical variations with respect to photon therapy. This requires beam range and/or dose release measurement during patient irradiation and therefore the development of dedicated monitoring techniques. All the proposed methods make use of the secondary radiation created by the beam interaction with the patient and, in particular, in the case of [Formula: see text] ion beams are also able to exploit the significant charged radiation component. Measurements performed to characterise the charged secondary radiation created by [Formula: see text] and [Formula: see text] particle therapy beams are reported. Charged secondary yields, energy spectra and emission profiles produced in a poly-methyl methacrylate (PMMA) target by [Formula: see text] and [Formula: see text] beams of different therapeutic energies were measured at 60° and 90° with respect to the primary beam direction. The secondary yield of protons produced along the primary beam path in a PMMA target was obtained. The energy spectra of charged secondaries were obtained from time-of-flight information, whereas the emission profiles were reconstructed exploiting tracking detector information. The obtained measurements are in agreement with results reported in the literature and suggests the feasibility of range monitoring based on charged secondary particle detection: the implications for particle therapy monitoring applications are also discussed.

Purpose: In Charged Particle Therapy (CPT), besides protons, there has been recently a growing interest in 4He, 12C and 16O beams. The secondary radiation produced in the interaction of those beams with a patient could be potentially used for on-line monitoring of range uncertainties in order to fully exploit the advantages of those light ions resulting from increased Radio Biological Effectiveness, reduced multiple scattering and Oxygen Enhancement Ratio. The study and precise characterization of secondary radiation (beta+, prompt gamma, charged fragments) is the cornerstone of any R&D activity aiming for online monitoring development and purpose of the analysis presented here. Methods: We present the measurements of the secondary radiation generated by He, C and O beams impinging on a beam stopping PMMA target. The data has been collected at the Heidelberg Ionbeam Therapy center (HIT), where several millions of collisions were recorded at different energies, relevant for therapeutical applications. Results: The experimental setup, as well as the analysis strategies will be reviewed. The detected particle fluxes as a function of the primary beam energy and the emission angle with respect to the beam direction will be presented and compared to the results of other available measurements. In addition, the energy spectra and emission shapes of charged secondary particles will be shown and discussed in the context of the primary beam range monitoring technique that is being developed by the ARPG collaboration, within the INSIDE project funded by the Italian research ministry. The implications for dose monitoring applications will be discussed, in the context of the current (or planned) state-of- the-art detector solutions. Conclusion: The characterization of the radiation produced by 12C, 4He and 16O beams fully supports the feasibility of on-line range monitoring in the clinical practice of CPT by means of secondary particles detection.

Reliable nuclear fragmentation models are of utmost importance in hadrontherapy, 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 β + 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 [1] , [2] , [3] . We will present a benchmark of the Geant4 models with double-differential cross section and angular distributions of the secondary fragments produced in the 12C fragmentation at 62 MeV/A on thin carbon target, such a benchmark includes the recently implemented model INCL++ [4] , [5] . Moreover, we will present the preliminary results, obtained in simulating the same interaction, with SMF [6] and BLOB [7] . Both, SMF and BLOB are semiclassical one-body approaches to solve the Boltzmann-Langevin equation. They include an identical treatment of the mean-field propagation, on the basis of the same effective interaction, but they differ in the way fluctuations are included. In particular, while SMF employs a Uehling-Uhlenbeck collision term and introduces fluctuations as projected on the density space, BLOB introduces fluctuations in full phase space through a modified collision term where nucleon-nucleon correlations are explicitly involved. Both of them, SMF and BLOB, have been developed to simulate the heavy ion interactions in the Fermi-energy regime. We will show their capabilities in describing 12C fragmentation foreseen their implementation in Geant4.

Particle therapy planning gets fundamental information from MC codes. Its millimetric precision needs the assurance of the successfulness of the treatment session. Different range monitoring techniques are under development exploiting secondary particles which are generated in the patient during the treatment: prompt gammas, annihilation gammas from beta+ induced activity, charged fragments. The yield of produced particles and their propagation in the human tissue must be studied with MC codes. In this contribution, in the framework of the INSIDE collaboration (Innovative Solutions for In-beam Dosimetry in hadrontherapy), the case of secondary charged fragments emission during the treatment is considered [1] . A detector named Dose Profiler (DP), able to track secondary charged fragments (mainly protons) emitted at large angles with respect to the beam direction, is under construction and test. The tracker is made by six layers (20 × 20 cm2) of BCF-12 square scintillating fibres (500 μm) coupled to Silicon Photo-Multipliers, followed by two plastic scintillator layers of 6 mm thickness. The detector characterization with cosmic rays has been performed and a calibration data taking campaign with protons is currently undergoing. The attenuation of the secondary charged particles emission profile due to the crossed material is studied and parametrized with the FLUKA MC code. A full simulation of a treatment in a realistic patient-detector system and the secondary charged fragments reconstruction is presented. Track reconstruction is performed by means of a Kalman filter algorithm using the GenFit code. The on-line operation of DP requires the real-time reconstruction of the amount of material crossed in the patient by each detected proton. This task will be accomplished using FRED, a fast GPU-MC code.