G.A.P. Cirrone

Geant4 developments and applications

Geant4 is a software toolkit for the simulation of the passage of particles through matter. It is used by a large number of experiments and projects in a variety of application domains, including high energy physics, astrophysics and space science, medical physics and radiation protection. Its functionality and modeling capabilities continue to be extended, while its performance is enhanced. An overview of recent developments in diverse areas of the toolkit is presented. These include performance optimization for complex setups; improvements for the propagation in fields; new options for event biasing; and additions and improvements in geometry, physics processes and interactive capabilities

A 62 MeV proton beam for the treatment of ocular melanoma at Laboratori Nazionali del Sud-INFN (CATANIA)

At the INFN Laboratori Nazionali del Sud in Catania (Italy) the first Italian protontherapy facility, named CATANA (Centre di AdroTerapia e Applicazioni Nucleari Avanzate) has been realized in collaboration with the University of Catania. It is based on the use of the 62 MeV proton beam delivered by the K = 800 superconducting cyclotron installed and working at LNS since 1995. The facility is mainly devoted to the treatment of ocular diseases like uveal melanoma. A beam treatment line in air has been realized together with a dedicated positioning patient system. The facility is in operation since the beginning of 2002 and 52 patients have been successfully treated up to now. The main features of CATANA together with the clinical and dosimetric features will be extensively reported; particularly, will be described the proton beam line, that has been entirely realized at LNS, with all its elements, the experimental transversal and depth dose distributions of the 62 MeV proton beam obtained for a final collimator of 25 mm diameter and the experimental depth dose distributions of a modulated proton beam obtained for the same final collimator. Finally, the clinical results over one year of treatments, describing the features of the treated diseases will be reported.

Diamond detector versus silicon diode and ion chamber in photon beams of different energy and field size

The aim of this work was to test the suitability of a PTW diamond detector for nonreference condition dosimetry in photon beams of different energy (6 and 25 MV) and field size (from 2.6 cm x 2.6 cm to 10 cm x 10 cm). Diamond behavior was compared to that of a Scanditronix p-type silicon diode and a Scanditronix RK ionization chamber. Measurements included output factors (OF). percentage depth doses (PDD) and dose profiles. OFs measured with diamond detector agreed within 1% with those measured with diode and RK chamber. Only at 25 MV, for the smallest field size, RK chamber underestimated OFs due to averaging effects in a pointed shaped beam profile. Agreement was found between PDDs measured with diamond detector and RK chamber for both 6 MV and 25 MV photons and down to 5 cm x 5 cm field size. For the 2.6 cm x 2.6 cm field size, at 25 MV, RK chamber underestimated doses at shallow depth and the difference progressively went to zero in the distal region. PDD curves measured with silicon diode and diamond detector agreed well for the 25 MV beam at all the field sizes. Conversely, the nontissue equivalence of silicon led, for the 6 MV beam, to a slight overestimation of the diode doses in the distal region, at all the field sizes. Penumbra and field width measurements gave values in agreement for all the detectors but with a systematic overestimate by RK measurements. The results obtained confirm that ion chamber is not a suitable detector when high spatial resolution is required. On the other hand, the small differences in the studied parameters, between diamond and silicon systems, do not lead to a significant advantage in the use of diamond detector for routine clinical dosimetry.

A goodness-of-fit statistical toolkit

Statistical methods play a significant role throughout the life-cycle of physics experiments, being an essential component of physics analysis. The present project in progress aims to develop an object-oriented software Toolkit for statistical data analysis. The Toolkit contains a variety of Goodness-of-Fit (GoF) tests, from Chi-squared to Kolmogorov-Smirnov, to less known, but generally much more powerful tests such as Anderson-Darling, Goodman, Fisz-Cramer-von Mises, Kuiper. Thanks to the component-based design and the usage of the standard abstract interfaces for data analysis, this tool can be used by other data analysis systems or integrated in experimental software frameworks. In this paper we describe the statistical details of the algorithms and the computational features of the Toolkit. With the aim of showing the consistency between the code and the mathematical features of the algorithms, we describe the results we obtained reproducing by means of the Toolkit a couple of Goodness-of-Fit testing examples of relevance in statistics literature.

Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment

PURPOSE The biological optimization of proton therapy can be achieved only through a detailed evaluation of relative biological effectiveness (RBE) variations along the full range of the Bragg curve. The clinically used RBE value of 1.1 represents a broad average, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak (SOBP). With particular attention to the key endpoint of cell survival, our work presents a comparative investigation of cell killing RBE variations along monoenergetic (pristine) and modulated (SOBP) beams using human normal and radioresistant cells with the aim to investigate the RBE dependence on LET and intrinsic radiosensitvity. METHODS AND MATERIALS Human fibroblasts (AG01522) and glioma (U87) cells were irradiated at 6 depth positions along pristine and modulated 62-MeV proton beams at the INFN-LNS (Catania, Italy). Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and the local effect model (LEM). RESULTS We observed significant cell killing RBE variations along the proton beam path, particularly in the distal region showing strong dose dependence. Experimental RBE values were in excellent agreement with the LEM predicted values, indicating dose-averaged LET as a suitable predictor of proton biological effectiveness. Data were also used to validate a parameterized RBE model. CONCLUSIONS The predicted biological dose delivered to a tumor region, based on the variable RBE inferred from the data, varies significantly with respect to the clinically used constant RBE of 1.1. The significant RBE increase at the distal end suggests also a potential to enhance optimization of treatment modalities such as LET painting of hypoxic tumors. The study highlights the limitation of adoption of a constant RBE for proton therapy and suggests approaches for fast implementation of RBE models in treatment planning.

Cellular and molecular effects of protons: Apoptosis induction and potential implications for cancer therapy

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.

Characterisation of CVD diamond dosimeters in on-line configuration

Abstract The high sensitivity and the nearly tissue equivalence of diamond make it a material suitable as detector for on-line dosimetry. The tremendous development of the CVD diamond technology allows to employ polycrystalline diamond films with controlled dimensions and a potential low cost as on-line radiation dosimeters. In this paper a characterisation and a comparison of the response of two “detector-grade” CVD diamond films under photon and electron beams are presented. The results show that both samples can be used as on-line dosimeters for applications in radiotherapy.

Characterization of a Silicon Strip Detector and a YAG:Ce Calorimeter for a Proton Computed Radiography Apparatus

Today, there is a steadily growing interest in the use of proton beams for tumor therapy, as they permit to tightly shape the dose delivered to the target reducing the exposure of the surrounding healthy tissues. Nonetheless, accuracy in the determination of the dose distribution in proton-therapy is up to now limited by the uncertainty in stopping powers, which are presently calculated from the photon attenuation coefficients measured by X-ray tomography. Proton computed tomography apparatus (pCT) has been proposed to directly measure the stopping power and reduce this uncertainty. Main problem with proton imaging is the blurring effect introduced by multiple Coulomb scattering: single proton tracking is a promising technique to face this difficulty. As a first step towards a pCT system, we designed a proton radiography (pCR) prototype based on a silicon microstrip tracker (to characterize particle trajectories) and a segmented YAG:Ce calorimeter (to measure their residual energy). Aim of the system is to detect protons with a ~1 MHz particle rate of and with kinetic energy in the range 250-270 MeV, high enough to pass through human body. Design and development of the pCR prototype, as well as the characterization of its single components, are described in this paper.

Charged particle’s flux measurement from PMMA irradiated by 80 MeV/u carbon ion beam

Hadrontherapy is an emerging technique in cancer therapy that uses beams of charged particles. To meet the improved capability of hadrontherapy in matching the dose release with the cancer position, new dose-monitoring techniques need to be developed and introduced into clinical use. The measurement of the fluxes of the secondary particles produced by the hadron beam is of fundamental importance in the design of any dose-monitoring device and is eagerly needed to tune Monte Carlo simulations. We report the measurements carried out with charged secondary particles produced from the interaction of a 80 MeV/u fully stripped carbon ion beam at the INFN Laboratori Nazionali del Sud, Catania, with a poly-methyl methacrylate target. Charged secondary particles, produced at 90° with respect to the beam axis, have been tracked with a drift chamber, while their energy and time of flight have been measured by means of a LYSO scintillator. Secondary protons have been identified exploiting the energy and time-of-flight information, and their emission region has been reconstructed backtracking from the drift chamber to the target. Moreover, a position scan of the target indicates that the reconstructed emission region follows the movement of the expected Bragg peak position. Exploiting the reconstruction of the emission region, an accuracy on the Bragg peak determination in the submillimeter range has been obtained. The measured differential production rate for protons produced with E(Prod)(kin) > 83 MeV and emitted at 90° with respect to the beam line is dN(P)/(dN(C)dΩ) (E(Prod)(kin) > 83 MeV, θ = 90°) = (2.69 ± 0.08(stat) ± 0.12(sys)) × 10⁻⁴ sr⁻¹.

Precise measurement of prompt photon emission from 80 MeV/u carbon ion beam irradiation

Proton and carbon ion therapy is an emerging technique used for the treatment of solid cancers. The monitoring of the dose delivered during such treatments is still a matter of research. A possible technique exploits the information provided by single photon emission from nuclear decays induced by the irradiation. This paper reports the measurements of the spectrum and rate of such photons produced from the interaction of a 80 MeV/u fully stripped carbon ion beam at the Laboratori Nazionali del Sud of INFN, Catania, with a Poly-methyl methacrylate target. The differential production rate for photons with energy E > 2 MeV and emitted at 90° is found to be dNγ/(dNCdΩ) = (2.92±0.19) × 10−2sr−1.