Search

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.

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.

The helium (4He) component of the primary particles in the galactic cosmic ray spectrum makes significant contributions to the total astronaut radiation exposure. 4He ions are also desirable for direct applications in ion therapy. They contribute smaller projectile fragmentation than carbon (12C) ions and smaller lateral beam spreading than protons. Space radiation protection and ion therapy applications need reliable nuclear reaction models and transport codes for energetic particles in matter. Neutrons and light ions (1H, 2H, 3H, 3He, and 4He) are the most important secondary particles produced in space radiation and ion therapy nuclear reactions; these particles penetrate deeply and make large contributions to dose equivalent. Since neutrons and light ions may scatter at large angles, double differential cross sections are required by transport codes that propagate radiation fields through radiation shielding and human tissue. This work will review the importance of 4He projectiles to space radiation and ion therapy, and outline the present status of neutron and light ion production cross section measurements and modeling, with recommendations for future needs.

International audience; Biomedical applications at high-energy particle accelerators have always been an important section of the applied nuclear physics research. Several new facilities are now under constructions or undergoing major upgrades. While the main goal of these facilities is often basic research in nuclear physics, they acknowledge the importance of including biomedical research programs and of interacting with other medical accelerator facilities providing patient treatments. To harmonize the programs, avoid duplications, and foster collaboration and synergism, the International Biophysics Collaboration is providing a platform to several accelerator centers with interest in biomedical research. In this paper, we summarize the programs of various facilities in the running, upgrade, or construction phase.

Secondary neutrons produced in Particle Therapy (PT) treatments are responsible for the delivery of a large fraction of the out-of-target dose as they feebly interact with the patient body. To properly account for their contribution to the total dose delivered to the patient, a high precision experimental characterisation of their production energy and angular distributions is eagerly needed. The experimental challenge posed by the detection and tracking of such neutrons will be addressed by the MONDO tracker: a compact scintillating fibres detector exploiting single and double elastic scattering interactions allowing for a complete neutron four momentum reconstruction. To achieve a high detection efficiency while matching the fibres (squared, 250 $\mu$m side) high granularity, a single photon sensitive readout has been developed using the CMOS based SPAD technology. The readout sensor, with pixels of $125\times250\ \micro\meter^2$ size, will be organised in tiles covering the full detector surface and will implement an auto-trigger strategy to identify the events of interest. The expected detector performance in the context of neutron component characterisation in PT treatments delivered using carbon ions has been evaluated using a Monte Carlo simulation accounting for the detector response and the neutrons production spectra.

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.

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.

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

Hadrontherapy is a method for treating cancer with very targeted dose distributions and enhanced radiobiological effects. To fully exploit these advantages, in vivo range monitoring systems are required. These devices measure, preferably during the treatment, the secondary radiation generated by the beam-tissue interactions. However, since correlation of the secondary radiation distribution with the dose is not straightforward, Monte Carlo (MC) simulations are very important for treatment quality assessment. The INSIDE project constructed an in-beam PET scanner to detect signals generated by the positron-emitting isotopes resulting from projectile-target fragmentation. In addition, a FLUKA-based simulation tool was developed to predict the corresponding reference PET images using a detailed scanner model. The INSIDE in-beam PET was used to monitor two consecutive proton treatment sessions on a patient at the Italian Center for Oncological Hadrontherapy (CNAO). The reconstructed PET images were updated every 10 s providing a near real-time quality assessment. By half-way through the treatment, the statistics of the measured PET images were already significant enough to be compared with the simulations with average differences in the activity range less than 2.5 mm along the beam direction. Without taking into account any preferential direction, differences within 1 mm were found. In this paper, the INSIDE MC simulation tool is described and the results of the first in vivo agreement evaluation are reported. These results have justified a clinical trial, in which the MC simulation tool will be used on a daily basis to study the compliance tolerances between the measured and simulated PET images.

The purpose of this work is to investigate the capability of the FLUKA Monte Carlo (MC) code to simulate the Elekta Leksell Gamma Knife Perfexion (LGK-PFX) and reproduce the Treatment Planning System (TPS) Leksell GammaPlan version 8.2 (LGP) dose calculations for the case of a water equivalent phantom target. Thanks to the collaboration with Elekta Instruments AB, the collimation system geometry, the source positions and all the involved material have been simulated in detail. The relative linear dose distribution along the three coordinate axes, for each collimator size, and the Relative Output Factors (ROF) have been investigated. The simulation has been validated comparing simulated linear dose profiles with measurements performed with EBT radiochromic films. The acceptance criterion between experimental data and FLUKA results is based on the gamma index (GI) method. The FLUKA MC calculation for the ROF provided the values of 0.920 for the 8 mm collimators and 0.800 for the 4 mm collimators. These values are in good agreement with the Elekta reference data of 0.924 and 0.805 respectively. The percentage difference between calculated and reference values for the ROF is under 1% and within the FLUKA uncertainty. Also the simulated relative dose profiles show a good agreement with the LGP calculation expressed by means of the gamma index method. This established accuracy proves that FLUKA is a suitable and powerful tool in order to reproduce successfully the LGP calculations for the homogeneous media.

Hadrontherapy permits treating cancer with very conformable dose distributions and increased radiobiological effects. Monitoring systems to verify particle range while treating are needed to fully exploit these advantages. The INSIDE project aims at building a bimodal system to acquire photons, coming from positron annihilations, and prompt charge particles related to the beam position inside patients [1] . In January 2016, the in-beam PET detector was installed at the Italian Center of Oncological Hadrontherapy (CNAO) and characterized with phantoms [2] , [3] . In December 2016, the INSIDE in-beam PET monitored two consecutive treatment sessions with protons on its first patient. In-beam PET images must be compared with an expected prior image, therefore a FLUKA-based [4] , [5] simulation tool has been developed. The framework includes the simulations of the patient/phantom, the detector, the beam line and temporal structure. The beam delivery follows either the treatment plan or the measurements from the Dose Delivery System and the detector geometry and resolution are taken into account. During the characterization phase, a good agreement between measurements and simulations was found [2] , [3] . Preliminary results on the first patient treatments indicate that after about two minutes of a four-minutes long irradiation the PET image has significant statistics to be compared with the prior image. During the 2017, the INSIDE in-beam PET system and simulation tool will be further tested in-vivo and optimized for clinical routine.

Boron Neutron Capture Therapy (BNCT) is an experimental radiotherapy that uses the combination of neutron irradiation and 10B to treat neoplasms. By means of this technique, many clinical trials were performed worldwide with promising results [1] using research nuclear reactors as neutron sources. Anyhow, these machines have several problems that hinder the development of dedicated BNCT hospitals. This issue can now be overcome by using intense-current proton accelerators, which coupled with beryllium or lithium targets yield more than 1014 neutron per second. This can be a boost to BNCT because accelerators are more compact and can be installed within hospitals.The Italian National Institute of Nuclear Physics (INFN) designed and manufactured a Radiofrequency Quadrupole proton accelerator (RFQ) [2], which delivers 5 MeV protons with 30 mA current in a Continuous Wave (CW) mode and it is coupled to a beryllium target. This accelerator could be installed at Centro Nazionale di Adroterapia Oncologica (CNAO) in Pavia.In this work we present the MC calculations for the tailoring of a BNCT neutron beam obtained by the described RFQ. Firstly, we show that MC transport codes such as MCNP and PHITS are not able to simulate the correct neutron spectra from 5 MeV protons interacting on beryllium. Therefore, the neutron double differential source implemented in MCNP was extracted from the measurements performed by Agosteo et al. [3]. As the energy range goes up to 3.5 MeV, neutrons need to be moderated and collimated by a Beam Shaping Assembly (BSA), because BNCT requires a spectrum peaked between 1 and 10 keV. Differently from the past, where the optimal configuration was chosen according to physical characteristics of the beam, in this case the results were evaluated on the basis of the dosimetry obtained in a real clinical case by treatment planning simulation. What emerges, is that the classical figures of merit employed for the tailoring of a clinical BNCT [4] should be taken as a first guideline, while the dosimetric assessment on realistic clinical scenarios is the most appropriate criterion for beam evaluations. Fil: Postuma, I.. Unit of Pavia; Italia Fil: Bortolussi, S.. University of Pavia; Italia Fil: Protti, N.. Unit of Pavia; Italia Fil: Fatemi, S.. Unit of Pavia; Italia. University of Pavia; Italia Fil: González, Sara Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina Fil: Provenzano, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina Fil: Battistoni, G.. Unit of Milan; Italia Fil: Altieri, S.. Unit of Pavia; Italia. University of Pavia; Italia

Monte Carlo codes are increasingly spreading in medical physics community due to their capability of performing a detailed description of radiation transport and interaction with matter. This contribution will address the recent developments of the FLUKA code and its practical application in medical physics. FLUKA is being used in radiation therapy and nuclear medicine. At present, it is of particular interest in the context of particle therapy, thanks to the development of accurate and reliable physical models capable of handling all components of the expected radiation field. At the same time, the code can be interfaced to different radiobiological models. These features become extremely important for correctly performing not only physical but also biologically based dose calculations, especially in cases where ions heavier than protons are involved. At the same time, in order to support the application of FLUKA in hospital-based environments, the FLUKA graphical interface has been enhanced with the capability of translating CT DICOM images into voxel-based computational phantoms in a fast and well-structured way. The interface is capable of importing also radiotherapy treatment data described in DICOM RT standard. Therefore, the FLUKA code not only is a reliable instrument for the simulation of therapeutic beams, but it is also used in some of the leading European hadron therapy centers as an accurate tool for Treatment Planning verification and correction. In addition, it allows an accurate prediction of emerging secondary radiation and this is of the utmost importance in innovative areas of research aiming at in vivo treatment verification. Here we shall review the features of the FLUKA code, pointing out the recent refinements of the nuclear models, relevant for the therapeutic energy interval, which lead to an improved description of the mixed radiation field. Benchmarks against experimental data with both proton and ion beams will be shown. Examples of clinical application will be presented, together with a review of some results in medical physics research.

4He ions are considered an attractive modality supplementary to protons and 12C ions for use in cancer radiation therapy. The accelerator and beam application system at the Heidelberg ion-beam therapy center (HIT) are currently commissioned for clinical application of 4He ions, which involves the calculation of basic data for the treatment planning system (laterally integrated depth dose profiles, lateral dose profiles and fragment distributions in water). For the commissioning of protons and 12C ions at HIT the FLUKA code [1] , [2] has been used [3] . The models for light ion interactions in FLUKA are undergoing several improvements and enhancements [4] particularly for 4He and their performances have already been investigated for calculation of 4He dosimetric data [5] . While the shape of the Bragg peak curve is mostly dominated by the Landau fluctuations in the projectile energy losses, its height is mainly determined by the nuclear interactions undergone by the primary ions. Furthermore, the fragments generated in nuclear interactions can give rise to a fragmentation tail after the Bragg peak and contribute to the quality of the mixed radiation field. Therefore, experimental data about the total nuclear cross-section and fragment distributions for 4He beams are needed to develop and validate the models available for 4He-induced nuclear reactions with the same level of reliability achieved for other ion species (e.g. 12C). The aim of this work is to present novel fragmentation data [6] , in particular mass-changing cross-sections for 4He+12C collisions over the entire energy range relevant for therapy, and to compare them with the 4He-nucleus reaction models currently under development for FLUKA. The presented work will have the potential to improve significantly the dose calculation for helium ion therapy and ensure that future basic data will be as reliable as possible.