CATANA Facility Research Articles

Sensitivity of a mini-TEPC to radiation quality variations in clinical proton beams

PurposeThis work aims at studying the sensitivity of a miniaturized Tissue-Equivalent Proportional Counter to variations of beam quality in clinical radiation fields, to further investigate its performances as radiation quality monitor. MethodsMeasurements were taken at the CATANA facility (INFN-LNS, Catania, Italy), in a monoenergetic and an energy-modulated proton beam with the same initial energy of 62 MeV. PMMA layers were placed in front of the detector to measure at different depths along the depth-dose profile. The frequency- and dose-mean lineal energy were compared to the track- and dose-averaged LET calculated by Monte Carlo simulations. A microdosimetric evaluation of the Relative Biological Effectiveness (RBE) was performed and compared with cell survival experiments. ResultsMicrodosimetric distributions measured at identical depths in the two beams show spectral differences reflecting their different radiation quality. Discrepancies are most evident at depths corresponding to the Spread-Out Bragg Peak, while spectra at the entrance and in the dose fall-off regions are similar. This can be explained by the different energy components that compose the pristine and spread-out peaks at each depth. The trend of microdosimetric mean values matches that of calculated LET averages along the entire penetration depth, and the microdosimetric estimation of RBE is consistent with radiobiological data not only at 2 Gy but also at lower dose levels, such as those absorbed by healthy tissues. ConclusionsThe mini-TEPC is sensitive to differences in radiation quality resulting from different modulations of the proton beam, confirming its potential for beam quality monitoring in proton therapy.

Experimental investigation at CATANA facility of n-10B and p-11B reactions for the enhancement of proton therapy.

The aim of the NEPTUNE (Nuclear process-driven Enhancement of Proton Therapy UNravEled) project is to investigate in detail both the physical and radiobiological phenomena that could justify an increase of the proton-induced cytogenetic effects in cells irradiated in presence of an agent containing natural boron. In this work, a double-stage silicon telescope coupled to different boron converters was irradiated at the CATANA proton therapy facility (INFN-LNS) for studying the proton boron fusion and the neutron boron capture reactions by discriminating secondary particles from primary protons. Different boron targets were developed by depositing boric acid, enriched with a higher than 99% content of 10B or 11B, on a 50 µm thick PolyMethilMetacrylate (PMMA) substrate. The 10B target allows to evaluate the contribution of lithium and alpha particles produced by the boron neutron capture reaction triggered by secondary thermal neutrons, while the 11B target is exploited for studying the effect of the p + 11B → 3α nuclear reaction directly triggered by primary protons. Experimental results clearly show the presence of alpha particles from both the reactions. The silicon telescope is capable of discriminating, by means of the so-called "scatter plots", the contribution of alpha particles originated by thermal neutrons on 10B with respect to the ones produced by protons impinging on 11B. Although a reliable quantitative study of the alpha production rate has not been achieved yet, this work demonstrates that low energy and, therefore, high-LET particles from both the reactions can be measured.

Monte Carlo GEANT4-based application for in vivo RBE study using small animals at LNS-INFN preclinical hadrontherapy facility

Preclinical studies represent an important step towards a deep understanding of the biological response to ionizing radiations. The effectiveness of proton therapy is higher than photons and, for clinical purposes, a fixed value of 1.1 is used for the relative biological effectiveness (RBE) of protons considered 1.1. Recent in vitro studies have reported that the RBE along the spread-out Bragg peak (SOBP) is not constant and, in particular, the RBE value increases on the distal part of SOBP. The present work has been carried-out in the perspective of a preclinical hadrontherapy facility at LNS-INFN and was focused on the experimental preparation of an in vivo study concerning the RBE variation along the SOBP. The main purpose of this work was to determine, using GEANT4-based Monte Carlo simulations, the best configuration for small animal treatments. The developed GEANT4 application simulates the proton-therapy beam line of LNS-INFN (CATANA facility) and allows to import the DICOM-CT images as targets. The RBE will be evaluated using a deterministic radiation damage like myelopathy as end-point. In fact, the dose at which the 50% of animals will show the myelopathy is supposed to be LET-dependent. In this work, we studied different treatment configurations in order to choose the best two that maximize the LET difference reducing as much as possible the dose released to healthy tissue. The results will be useful to plan hadrontherapy treatments for preclinical in vivo studies and, in particular, for the future in vivo RBE studies.

Corrigendum: Clinical and Research Activities at the CATANA Facility of INFN-LNS: From the Conventional Hadrontherapy to the Laser-Driven Approach.

[This corrects the article on p. 223 in vol. 7, PMID: 28971066.].

Abstract ID: 35 Monte Carlo dosimetric study for preclinical small animal hadrontherapy using Geant4 toolkit

Preclinical studies represent an important step to study molecular mechanism induced inside cells in response to ionizing radiations. The scope was the study of the preliminary steps to perform particle treatment of cancer cells inoculated in small animals and to realize a preclinical hadrontherapy facility. At this scope, a well-defined dosimetric protocol was developed to perform the steps needed in order to perform a precise proton irradiation in small animals and achieve highly conformal dose. Homemade positioning system for small animals was developed at INFN-LNS(Italy) and an accurate Monte Carlo simulation was developed. The application, developed using Geant4.10.03 version, includes in the current version of the advanced example “Hadrontherapy” [1] the main functionalities of the “DICOM” extended example [2] . In this way, this application simulates the CATANA beam line geometry and includes the capability to implement DICOM-TC images as target. The application will be used to carry out dosimetric and LET studies [3] using the real target composition. This application was validated comparing its results with experimental measurements. A validation test, using solid water slabs phantom, and a treatment simulation, irradiating a PMMA phantom that simulate subcutaneous tumours, were executed at CATANA facility using in both cases EBT3-Gafchromic films as dose detector. The dosimetric results were compared with the simulation ones using Kolmogorov and gamma index test. Experimental data are in good agreement with the simulation ones. The phantom targets were included in the simulation environment using DICOM-TC images. Dosimetric measurements were useful to determine the efficiency of the developed Geant4 application and to demonstrate that it is a valid instrument to study the dose distribution in different types of phantoms with different kinds of geometry. This work has been carried-out in the perspective of realization of a preclinical hadrontherapy facility at INFN-LNS in order to implement interesting future in vivo studies using small animals.

Abstract ID: 37 The BIANCA biophysical model/MC code: calculations of radiation-induced cell damage in view of hadrontherapy treatments

A biophysical model and Monte Carlo code simulating cell death and chromosome damage by different ionizing radiations, including those used in hadrontherapy, will be presented. The model, called BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations [1] , [2] ), assumes that DNA “Cluster Lesions” (CLs) can produce chromosome aberrations (i.e., distance-dependent incorrect rearrangements of chromosome fragments), some of which can lead to cell death. The mean number of CLs per Gy and per cell is the first adjustable parameter; the second parameter is either the probability that a chromosome fragment remains unrejoined, or the characteristic distance governing chromosome-fragment rejoining, depending on which model version is used. Comparisons with experimental dose-response curves for cell survival and/or chromosome aberrations allowed tuning the model parameters for a radioresistant cell line (representative of tumour cell response) and a normal one (representative of the response of healthy tissues), thus producing a database of CL yields for different particle types and LET values. Since the CL yield for a given particle type showed a linear-quadratic increase with LET, a fit of such database allows performing full predictions of cell death and chromosome aberrations in principle for any LET value within the range covered by the experiments. Recently, the model was applied to calculate the dependence of cell death and chromosome damage on depth in tissue for SOBP profiles used in different centres, including the CATANA facility for eye melanoma treatment at INFN-LNS and the CNAO hadrontherapy centre in Pavia. In particular for protons, the biological effectiveness was found to increase in the distal region, and significant levels of damage beyond the distal dose fall-off were observed. In line with other studies, these results suggest that assuming a constant biological effectiveness along a proton SOBP may be sub-optimal.

Clinical and Research Activities at the CATANA Facility of INFN-LNS: From the Conventional Hadrontherapy to the Laser-Driven Approach.

The CATANA proton therapy center was the first Italian clinical facility making use of energetic (62 MeV) proton beams for the radioactive treatment of solid tumors. Since the date of the first patient treatment in 2002, 294 patients have been successful treated whose majority was affected by choroidal and iris melanomas. In this paper, we report on the current clinical and physical status of the CATANA facility describing the last dosimetric studies and reporting on the last patient follow-up results. The last part of the paper is dedicated to the description of the INFN-LNS ongoing activities on the realization of a beamline for the transport of laser-accelerated ion beams for future applications. The ELIMED (ELI-Beamlines MEDical and multidisciplinary applications) project is introduced and the main scientific aspects will be described.

Designing a range modulator wheel to spread-out the Bragg peak for a passive proton therapy facility

In proton beam therapy, a Spread-Out Bragg peak (SOBP) is used to establish a uniform dose distribution in the target volume. In order to create a SOBP, several Bragg peaks of different ranges, corresponding to different entrance energies, with certain intensities (weights) should be combined each other. In a passive beam scattering system, the beam is usually extracted from a cyclotron at a constant energy throughout a treatment. Therefore, a SOBP is produced by a range modulator wheel, which is basically a rotating wheel with steps of variable thicknesses, or by using the ridge filters. In this study, we used the Geant4 toolkit to simulate a typical passive scattering beam line. In particular, the CATANA transport beam line of INFN Laboratori Nazionali del Sud (LNS) in Catania has been reproduced in this work. Some initial properties of the entrance beam have been checked by benchmarking simulations with experimental data. A class dedicated to the simulation of the wheel modulators has been implemented. It has been designed in order to be easily modified for simulating any desired modulator wheel and, hence, any suitable beam modulation. By using some auxiliary range-shifters, a set of pristine Bragg peaks was obtained from the simulations. A mathematical algorithm was developed, using the simulated pristine dose profiles as its input, to calculate the weight of each pristine peak, reproduce the SOBP, and finally generate a flat dose distribution. Therefore, once the designed modulator has been realized, it has been tested at CATANA facility, comparing the experimental data with the simulation results.

Characterization of an In-Beam PET Prototype for Proton Therapy With Different Target Compositions

At the University of Pisa, the DoPET (Dosimetry with a Positron Emission Tomograph) project has focused on the development and characterization of an ad hoc, scalable, dual-head PET prototype for in-beam treatment planning verification of the proton therapy. In this paper we report the first results obtained with our current prototype, consisting of two opposing lutetium yttrium orthosilicate (LYSO) detectors, each one covering an area of 4.5 × 4.5 cm2. We measured the β+-activation induced by 62 MeV proton beams at Catana facility (LNS, Catania, Italy) in several plastic phantoms. Experiments were performed to evaluate the possibility to extract accurate phantom geometrical information from the reconstructed PET images. The PET prototype proved its capability of locating small air cavities in homogeneous PMMA phantoms with a submillimetric accuracy and of distinguishing materials with different 16O and 12C content by back mapping phantom geometry through the separation of the isotope contributions. This could be very useful in the clinical practice as a tool to highlight anatomical or physiological organ variations among different treatment sessions and to discriminate different tissue types, thus providing feedbacks for the accuracy of dose deposition.

Proton therapy detector studies under the experience gained at the CATANA facility

Proton therapy represents the most promising radiotherapy technique for external tumor treatments. At Laboratori Nazionali del Sud of the Istituto Nazionale di Fisica Nucleare (INFN-LNS), Catania (I), a proton therapy facility is active since March 2002 and 140 patients, mainly affected by choroidal and iris melanoma, have been successfully treated. Proton beams are characterized by higher dose gradients and linear energy transfer with respect to the conventional photon and electron beams, commonly used in medical centers for radiotherapy.In this paper, we report the experience gained in the characterization of different dosimetric systems, studied and/or developed during the last ten years in our proton therapy facility.

Preliminary results with a strip ionization chamber used as beam monitor for hadrontherapy treatments

Preliminary results are presented from a test of a parallel plate ionization chamber with the anode segmented in strips (MOPI) to be used as a beam monitor for therapeutical treatments on the 62 MeV proton beam line of the INFN-LNS Superconducting Cyclotron. Ocular pathologies have been treated at the Catana facility since March 2002. The detector, placed downstream of the patient collimator, will allow the measurement of the relevant beam diagnostic parameters during treatment such as integrated beam fluence, for dose determination; the beam baricentre, width and asymmetry will be obtained from the fluence profile sampled with a resolution of about 100 Urn at a rate up to 1 kHz with no dead time. In this test, carried out at LNS, the detector has been exposed to different beam shapes and the integrated fluence derived by the measured beam profiles has been compared with that obtained with other dosimeters normally used for treatment. The skewness of the beam profile has been measured and shown to be suitable to on-line check variations of the beam shape.