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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.

In this paper, we investigate the use of a positron emission tomography (PET) system to monitor the proton therapy. The monitoring procedure is based on the comparison between the ${ \beta }+$ activity generated in the irradiated volume during the treatment, with the ${ \beta }+$ activity distribution obtained with Monte Carlo (MC) simulation. The dedicated PET system is a dual head detection system; each head is composed of nine scintillating LYSO crystal matrices read out independently with a custom modularized acquisition system. Our experimental data were acquired at the Cyclotron Centre Bronowice, Institute Nuclear Physics in Krakow, Poland, and were simulated with the FLUKA MC code. Homogeneous and heterogeneous plastic phantoms were irradiated with monoenergetic 130 MeV protons. The capabilities of our PET system to distinguish different irradiated materials were investigated, and the proton pencil-beams were used as probes. Our focus was to analyze the activity width and the total activity event number in several cases. Irradiations were performed using either single pencil-beams one at a time, or two pencil-beams during the same data taking. The comparison of 1-D activity profile for experimental data and MC simulation were always in good agreement showing that, the treatment quality assessment in proton therapy can be based on ${ \beta }+$ activity measurements.

Radiation therapy is currently the most utilized technique for the treatment of tumors by means of ionizing radiation, such as electrons, protons and x/gamma rays, depending on the type, size and depth of the cancer mass. Radiation therapy has in general fulfilled the main requirement of targeting thus damaging the malignant cells and sparing the healthy tissues as best as possible. In this scenario, electron linear accelerators have been operated as viable tools for the delivery of both high-energetic electrons and x-ray beams, which are obtained via the bremsstrahlung process of the electrons hitting on a high-Z material. Recently, it has been experimentally demonstrated that ultrahigh dose-rate bursts of electrons and x-ray beams increase the differential response between healthy and tumor tissues. This beneficial response is referred to as the FLASH effect. For this purpose, we have developed the first dedicated compact $S$-band linear accelerator for FLASH radiotherapy. This linac is optimized for a nominal energy of 7 MeV and a pulsed electron beam current of 100 mA and above. The accelerator is mounted on a remote-controlled system for preclinical research studies in the FLASH regime. We will show the rf and beam dynamics design of the $S$-band linac as well as the commissioning and high-power rf tests. Furthermore, the results of the dosimetric measurements will be illustrated.

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

The use and interest in Monte Carlo (MC) techniques in the field of medical physics have been rapidly increasing in the past years. This is the case especially in particle therapy, where accurate simulations of different physics processes in complex patient geometries are crucial for a successful patient treatment and for many related research and development activities. Thanks to the detailed implementation of physics processes in any type of material, to the capability of tracking particles in 3D, and to the possibility of including the most important radiobiological effects, MC simulations have become an essential calculation tool not only for dose calculations but also for many other purposes, like the design and commissioning of novel clinical facilities, shielding and radiation protection, the commissioning of treatment planning systems, and prediction and interpretation of data for range monitoring strategies. MC simulations are starting to be more frequently used in clinical practice, especially in the form of specialized codes oriented to dose calculations that can be performed in short time. The use of general purpose MC codes is instead more devoted to research. Despite the increased use of MC simulations for patient treatments, the existing literature suggests that there are still a number of challenges to be faced in order to increase the accuracy of MC calculations for patient treatments. The goal of this review is to discuss some of these remaining challenges. Undoubtedly, it is a work for which a multidisciplinary approach is required. Here, we try to identify some of the aspects where the community involved in applied nuclear physics, radiation biophysics, and computing development can contribute to find solutions. We have selected four specific challenges: i) the development of models in MC to describe nuclear physics interactions, ii) modeling of radiobiological processes in MC simulations, iii) developments of MC-based treatment planning tools, and iv) developments of fast MC codes. For each of them, we describe the underlying problems, present selected examples of proposed solutions, and try to give recommendations for future research.

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 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.

In proton therapy, secondary fragments are created in nuclear interactions of the beam with the target nuclei. The secondary fragments have low kinetic energies and high atomic numbers as compared to primary protons. Fragments have a high LET and deposit all their energy close to the generation point. For their characteristics, secondary fragments can alter the dose distribution and lead to an increase of RBE for the same delivered physical dose. Moreover, the radiobiological impact of target fragmentation is significant mostly in the region before the Bragg peak, where generally healthy tissues are present, and immediately after Bragg peak. Considering the high biological impact of those particles, especially in the case of healthy tissues or organs at risk, the inclusion of target fragmentation processes in the dose calculation of a treatment planning system can be relevant to improve the treatment accuracy and for this reason it is one of the major tasks of the MoVe IT project. In this study, Monte Carlo simulations were employed to fully characterize the mixed radiation field generated by target fragmentation in proton therapy. The dose averaged LET has been evaluated in case of a Spread Out Bragg Peak (SOBP). Starting from LET distribution, RBE has been evaluated with two different phenomenological models. In order to characterize the mixed radiation field, the production cross section has been evaluated by means of the FLUKA code. The future development of present work is to generate a MC database of fragments fluence to be included in TPS.

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

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.

The use of charged particles and nuclei in cancer therapy is one of the most successful cases of application of nuclear physics to medicine. The physical advantages in terms of precision and select...

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.

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.

Nuclear physics processes are an important source of uncertainty in dose calculations in particle therapy and radioprotection in space. Accurate cross section measurements are a crucial ingredient in improving the understanding of these processes. The FOOT (FragmentatiOn Of Target) experiment aims at measuring the production cross sections of fragments for energies, beams and targets that are relevant in particle therapy and radioprotection in space. An experimental apparatus composed of several sub-detectors will provide the mass, charge, velocity and energy of fragments produced in nuclear interactions in a thin target. A crucial component of the FOOT apparatus will be the Δ E-TOF detector, designed to identify the charge of the fragments using plastic scintillators to measure the energy deposited and the time of flight with respect to a start counter. In this work, we present a charge reconstruction procedure of produced fragments at particle therapy energies. We validate it by measuring the charges of various fragments at an angle of 3.2°and 8.3°with respect the beam-axis, using a small-scale detector and clinical beams of carbon ions at the CNAO oncology center. Experimental results agree well with FLUKA Monte Carlo simulations.

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.

The FOOT experiment aims at identifying the fragments produced in the human body during hadrontherapy and at measuring their cross sections. The apparatus is composed of several detectors which allow a complete reconstruction of the tracks of the fragments. In particular, the Δ E-TOF detector measures the energy released in a thin plastic scintillator and the time of flight of the fragments. In this work, we report the energy and time resolution of a Δ E-TOF detector prototype with proton and carbon irradiations, and we compare the results with a Monte Carlo simulation of the optical transport in the detector. With carbon ions, we measured time resolutions of ∼ 50 ps and energy resolutions of ∼ 6%. The Monte Carlo simulation was able to model the dependence of the number of detected photons on the proton interaction position.

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 pharmacological costs of regimens used as front-line therapy in advanced colorectal cancer patients and their impact on the liver resection rates have not been considered. In this paper, we made a review of published randomized Phase II and III trials that reported the liver resection rates following upfront chemotherapy and linked this outcome to the pharmacological costs of drugs used. The costs are calculated based on the price at Pharmacy of our Hospital in Legnago (Italy), and as a measure of activity, we used the number of patients needed to treat to get one complete liver resection. Number needed to treat is highly variable among the different trials according to patient's characteristics, tumor biology and the efficacy of chemotherapy administered. The range of activity is greatly amplified when the costs are compared.

The INSIDE collaboration aims to build an on-line hadrontherapy monitoring system, based on a dual-head in-beam PET scanner and a secondary charged particles profiler. In this work preliminary experimental results are presented. The validation of the FLUKA-based Monte Carlo simulation tool is shown together with the expected scanner performances.

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 Advanced ion beam therapeutic techniques, such as hypofractionation, respiratory gating, or laser-based pulsed beams, have dose rate time structures which are substantially different from those found in conventional approaches. The biological impact of the time structure is mediated through the β parameter in the linear quadratic (LQ) model. The aim of this study was to assess the impact of changes in the value of the β parameter on the treatment outcomes, also accounting for noninstantaneous intrafraction dose delivery or fractionation and comparing the effects of using different primary ions. Methods An original formulation of the microdosimetric kinetic model (MKM) is used (named MCt-MKM), in which a Monte Carlo (MC) approach was introduced to account for the stochastic spatio-temporal correlations characteristic of the irradiations and the cellular repair kinetics. A modified version of the kinetic equations, validated on experimental cell survival in vitro data, was also introduced. The model, trained on the HSG cells, was used to evaluate the relative biological effectiveness (RBE) for treatments with acute and protracted fractions. Exemplary cases of prostate cancer irradiated with different ion beams were evaluated to assess the impact of the temporal effects. Results The LQ parameters for a range of cell lines (V79, HSG, and T1) and ion species (H, He, C, and Ne) were evaluated and compared with the experimental data available in the literature, with good results. Notably, in contrast to the original MKM formulation, the MCt-MKM explicitly predicts an ion and LET-dependent β compatible with observations. The data from a split-dose experiment were used to experimentally determine the value of the parameter related to the cellular repair kinetics. Concerning the clinical case considered, an RBE decrease was observed, depending on the dose, ion, and LET, exceeding up to 3% of the acute value in the case of a protraction in the delivery of 10 min. The intercomparison between different ions shows that the clinical optimality is strongly dependent on a complex interplay between the different physical and biological quantities considered. Conclusions The present study provides a framework for exploiting the temporal effects of dose delivery. The results show the possibility of optimizing the treatment outcomes accounting for the correlation between the specific dose rate time structure and the spatial characteristic of the LET distribution, depending on the ion type used.

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

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.

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.

FLUKA is a Monte-Carlo code able to simulate interaction and transport of hadrons, heavy ions and electromagnetic particles from few keV (or thermal neutron) to cosmic ray energies in whichever material. The highest priority in the design and development of the code has always been the implementation and improvement of sound and modern physical models. A summary of the FLUKA physical models is given, while recent developments are described in detail: among the others, extensions of the intermediate energy hadronic interaction generator, refinements in photon cross sections and interaction models, analytical on-line evolution of radio-activation and remnant dose. In particular, new developments in the nucleus–nucleus interaction models are discussed. Comparisons with experimental data and examples of applications of relevance for space radiation are also provided.

The calculation algorithm of a modern treatment planning system for ion-beam radiotherapy should ideally be able to deal with different ion species (e.g. protons and carbon ions), to provide relative biological effectiveness (RBE) evaluations and to describe different beam lines. In this work we propose a new approach for ion irradiation outcomes computations, the beamlet superposition (BS) model, which satisfies these requirements. This model applies and extends the concepts of previous fluence-weighted pencil-beam algorithms to quantities of radiobiological interest other than dose, i.e. RBE- and LET-related quantities. It describes an ion beam through a beam-line specific, weighted superposition of universal beamlets. The universal physical and radiobiological irradiation effect of the beamlets on a representative set of water-like tissues is evaluated once, coupling the per-track information derived from FLUKA Monte Carlo simulations with the radiobiological effectiveness provided by the microdosimetric kinetic model and the local effect model. Thanks to an extension of the superposition concept, the beamlet irradiation action superposition is applicable for the evaluation of dose, RBE and LET distributions. The weight function for the beamlets superposition is derived from the beam phase space density at the patient entrance. A general beam model commissioning procedure is proposed, which has successfully been tested on the CNAO beam line. The BS model provides the evaluation of different irradiation quantities for different ions, the adaptability permitted by weight functions and the evaluation speed of analitical approaches. Benchmarking plans in simple geometries and clinical plans are shown to demonstrate the model capabilities.

Examples are given which prove the ICARUS detector quality through relevant physics measurements. We study the μ decay energy spectrum from a sample of stopping μ events acquired during the test run of the ICARUS T600 detector. This detector allows the spatial reconstruction of the events with fine granularity, hence, the precise measurement of the range and dE/dx of the μ with high sampling rate. This information is used to compute the calibration factors needed for the full calorimetric reconstruction of the events. The Michel ρ parameter is then measured by comparison of the experimental and Monte Carlo simulated μ decay spectra, obtaining ρ=0.72±0.06(stat.)±0.08(syst.). The energy resolution for electrons below ∼50 MeV is finally extracted from the simulated sample, obtaining (Eemeas−EeMC)/EeMC=11%/E[MeV]−−−−−−−√⊕2%., The European Physical Journal C, 33 (2), ISSN:1434-6044, ISSN:1434-6052

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.

We report on the performance of a liquid Argon Time Projection Chamber, operating in a 10 m 3 cryostat. This device built in the framework of the ICARUS T600 programme to serve as a full test facility for the adopted cryogenics and mechanical solutions, was successfully tested in 2000 as the last step before the tests of the first 600 t ICARUS module 1 year later. In a final run at the Gran Sasso Laboratory, whose outcome provides the main subject of this paper, also the readout and imaging capabilities of the installed wire chamber and the overall performance of the detector have been successfully tested.

Dosimetry in Hadrontherapy M. Marafini, A. Attili, G. Battistoni, N. Belcari, M.G. Bisogni, N. Camarlinghi, F. Cappucci, M. Cecchetti, P. Cerello, F. Ciciriello , G.A.P. Cirrone, S. Coli, F. Corsi , G. Cuttone, E. De Lucia, S. Ferretti, R. Faccini, E. Fiorina, P.M. Frallicciardi, G. Giraudo, E. Kostara, A. Kraan, F. Licciulli , B. Liu, N. Marino, C. Marzocca , G. Matarrese , C. Morone, M. Morrocchi, S. Muraro, V. Patera, F. Pennazio, C. Peroni, L. Piersanti, M.A. Piliero, G. Pirrone, A. Rivetti, F. Romano, V. Rosso, P. Sala, A. Sarti, A. Sciubba, G. Sportelli, C. Voena, R. Wheadon and A. Del Guerra Museo Storico della Fisica e Centro Studi e Ricerche E. Fermi , Roma, Italy b−f INFN Sezione di: Roma, Roma; Torino, Torino; Milano, Milano; Pisa, Pisa; Bari, Bari; Italy Laboratori Nazionali del Sud dell'INFN, Catania, Italy Laboratori Nazionali di Frascati dell'INFN, Frascati, Italy Dipartimento di Scienze di Base e Applicate per Ingegneria, Sapienza Universita di Roma, Roma, Italy

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.

The FLUKA code has been used to reproduce experimental data concerning muon fluxes in atmosphere in a wide energy range with the aim of testing the performance of this Monte Carlo model in predicting secondary cosmic ray spectra in atmosphere. Here new results are presented, concerning in particular the cases of BESS and L3+C experiments.