A. Attili

Extension of TOPAS for the simulation of proton radiation effects considering molecular and cellular endpoints

The aim of this work is to extend a widely used proton Monte Carlo tool, TOPAS, towards the modeling of relative biological effect (RBE) distributions in experimental arrangements as well as patients. TOPAS provides a software core which users configure by writing parameter files to, for instance, define application specific geometries and scoring conditions. Expert users may further extend TOPAS scoring capabilities by plugging in their own additional C++ code. This structure was utilized for the implementation of eight biophysical models suited to calculate proton RBE. As far as physics parameters are concerned, four of these models are based on the proton linear energy transfer, while the others are based on DNA double strand break induction and the frequency-mean specific energy, lineal energy, or delta electron generated track structure. The biological input parameters for all models are typically inferred from fits of the models to radiobiological experiments. The model structures have been implemented in a coherent way within the TOPAS architecture. Their performance was validated against measured experimental data on proton RBE in a spread-out Bragg peak using V79 Chinese Hamster cells. This work is an important step in bringing biologically optimized treatment planning for proton therapy closer to the clinical practice as it will allow researchers to refine and compare pre-defined as well as user-defined models.

Heuristic optimization of the scanning path of particle therapy beams

Quasidiscrete scanning is a delivery strategy for proton and ion beam therapy in which the beam is turned off when a slice is finished and a new energy must be set but not during the scanning between consecutive spots. Different scanning paths lead to different dose distributions due to the contribution of the unintended transit dose between spots. In this work an algorithm to optimize the scanning path for quasidiscrete scanned beams is presented. The classical simulated annealing algorithm is used. It is a heuristic algorithm frequently used in combinatorial optimization problems, which allows us to obtain nearly optimal solutions in acceptable running times. A study focused on the best choice of operational parameters on which the algorithm performance depends is presented. The convergence properties of the algorithm have been further improved by using the next-neighbor algorithm to generate the starting paths. Scanning paths for two clinical treatments have been optimized. The optimized paths are found to be shorter than the back-and-forth, top-to-bottom (zigzag) paths generally provided by the treatment planning systems. The gamma method has been applied to quantify the improvement achieved on the dose distribution. Results show a reduction of the transit dose when the optimized paths are used. The benefit is clear especially when the fluence per spot is low, as in the case of repainting. The minimization of the transit dose can potentially allow the use of higher beam intensities, thus decreasing the treatment time. The algorithm implemented for this work can optimize efficiently the scanning path of quasidiscrete scanned particle beams. Optimized scanning paths decrease the transit dose and lead to better dose distributions.

A novel algorithm for the calculation of physical and biological irradiation quantities in scanned ion beam therapy: the beamlet superposition approach.

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.

Monte Carlo simulation of ripple filters designed for proton and carbon ion beams in hadrontherapy with active scanning technique

Proton and carbon ion beams have a very sharp Bragg peak. For proton beams of energies smaller than 100 MeV, fitting with a gaussian the region of the maximum of the Bragg peak, the sigma along the beam direction is smaller than 1 mm, while for carbon ion beams, the sigma derived with the same technique is smaller than 1 mm for energies up to 360 MeV. In order to use low energy proton and carbon ion beams in hadrontherapy and to achieve an acceptable homogeneity of the spread out Bragg peak (SOBP) either the peak positions along the beam have to be quite close to each other or the longitudinal peak shape needs to be broaden at least few millimeters by means of a properly designed ripple filter. With a synchrotron accelerator in conjunction with active scanning techniques the use of a ripple filter is necessary to reduce the numbers of energy switches necessary to obtain a smooth SOBP, leading also to shorter overall irradiation times. We studied the impact of the design of the ripple filter on the dose uniformity in the SOBP region by means of Monte Carlo simulations, implemented using the package Geant4. We simulated the beam delivery line supporting both proton and carbon ion beams using different energies of the beams. We compared the effect of different kind of ripple filters and their advantages.

Targeted dose enhancement in radiotherapy for breast cancer using gold nanoparticles, part 1: A radiobiological model study

Purpose Gold nanoparticles (GNPs) are being proposed in combination with radiotherapy to improve tumor control. However, the exact mechanisms underlying GNP radiosensitization are yet to be understood, thus, we present a new approach to estimate the nanoparticle‐driven increase in radiosensitivity. Methods A stochastic radiobiological model, derived from the Local Effect Model (LEM), was coupled with Monte Carlo simulations to estimate the increase in radiosensitivity produced by the interactions between photons and GNPs at nanometric scale. The model was validated using in vitro survival data of MDA‐MB‐231 breast cancer cells containing different concentrations of 2 nm diameter GNPs receiving different doses using 160 kVp, 6 MV, and 15 MV photons. A closed analytical formulation of the model was also derived and a study of RBE and TCP behavior was conducted. Results Results support the increased radiosensitivity due to GNP‐driven dose inhomogeneities on a nanometric scale. The model is in good agreement with experimental clonogenic survival assays for 160 kVp, 6 MV, and 15 MV photons. The model suggests a RBE and TCP enhancement when lower energies and lower doses per fraction are used in the presence of GNPs. Conclusions The evolution of the local effect model was implemented to assess cellular radiosensitization in the presence of GNPs and then validated with in vitro data. The model provides a useful framework to estimate the nanoparticle‐driven radiosensitivity in treatment irradiations and could be applied to real clinical treatment predictions (described in a second part of this paper)

Hadrontherapy: An open source, Geant4-based application for proton-ion therapy studies

Hadrontherapy is an open source application based on the Geant4 Monte Carlo libraries. It can be downloaded with the Geant4 official code and can be found in the category of the advanced examples (

The CNAO system to monitor and control hadron beams for therapy

G4Install/examples/advanced folder of the Geant4 distribution). Since its original version, released in 2004, Hadrontherapy permitted the simulation of a typical proton therapy beam line, together with all it elements (collimators, scattering systems, etc.) and the calculation of the corresponding dose distribution curves in water and other materials. In this paper we will report on the newest development and improvement of Hadrontherapy as it will be released in the Geant4 9.3 version. The new version of application will furnish a set of tools useful for Users interested in studies related to proton/ion therapy. The new version of Hadrontherapy will permit, in fact, the transport of carbon beams, using the state-of-art of the Geant4 electromagnetic and hadronic models, the calculation of some basic parameters like stopping powers, or the possibility to easily change the geometrical configuration for the simulation of typical nuclear physics experiment of interest in the hadrontherapy field. Other capabilities are inserted in the new Hadrontherapy version even if not all are reported in this paper. For more information the reader can refer to the on-line manual of Hadrontherapy that can be found inside the Geant4 official website (www.cern.ch/geant4).

Quality assurance of carbon ion and proton beams: A feasibility study for using the 2D MatriXX detector

Hadrotherapy might be the last chance option for patients with cancers growing deep in the body or surrounded by very sensitive organs. The Italian National Center of Oncological Hadrotherapy (CNAO) in Pavia is a synchrotron based center for the treatment of tumors with protons and carbon ion beams. The result of this sophisticated technique is strongly affected by the beam delivery performances. A powerful on-line system to monitor and deliver particles inside the target will be available at CNAO.

A large dynamic range charge measurement ASIC family for beam monitoring in radiotherapy applications

PURPOSE The quality assurance (QA) procedures in particle therapy centers with active beam scanning make extensive use of films, which do not provide immediate results. The purpose of this work is to verify whether the 2D MatriXX detector by IBA Dosimetry has enough sensitivity to replace films in some of the measurements. METHODS MatriXX is a commercial detector composed of 32×32 parallel plate ionization chambers designed for pre-treatment dose verification in conventional radiation therapy. The detector and GAFCHROMIC® films were exposed simultaneously to a 131.44MeV proton and a 221.45MeV/u carbon-ion therapeutic beam at the CNAO therapy center of Pavia - Italy, and the results were analyzed and compared. RESULTS The sensitivity MatriXX on the beam position, beam width and field flatness was investigated. For the first two quantities, a method for correcting systematic uncertainties, dependent on the beam size, was developed allowing to achieve a position resolution equal to 230μm for carbon ions and less than 100μm for protons. The beam size and the field flatness measured using MatriXX were compared with the same quantities measured with the irradiated film, showing a good agreement. CONCLUSIONS The results indicate that a 2D detector such as MatriXX can be used to measure several parameters of a scanned ion beam quickly and precisely and suggest that the QA would benefit from a new protocol where the MatriXX detector is added to the existing systems.

Direct evaluation of radiobiological parameters from clinical data in the case of ion beam therapy: an alternative approach to the relative biological effectiveness.

A family of Application Specific Integrated Circuits ( ASICs ) called TERA have been developed for the readout of pixel and strip gas detectors used in radiotherapy applications. The TERA ASICs are based on the charge balancing integration technique in order to obtain a good linearity over a dynamic range of five order of magnitude.