Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined ...irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer)
C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper
C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p +
B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses
B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy's ballistic precision with the higher RBE promised by BNCT and
C-ion therapy is thus demonstrated.
Background
Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro‐ and nanodosimetry, imaging, radiation protection, and nuclear ...medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing.
Aims
To respond to these needs, we developed G4‐Med, a benchmarking and regression testing system of Geant4 for medical physics.
Materials and Methods
G4‐Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4‐Med are executed on the CERN computing infrastructure via the use of the geant‐val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes.
Results
This paper describes the tests included in G4‐Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data.
Discussion
Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics.
Conclusion
The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.
Proton beams are widely used worldwide to treat localized tumours, the lower entrance dose and no exit dose, thus sparing surrounding normal tissues, being the main advantage of this treatment ...modality compared to conventional photon techniques. Clinical proton beam therapy treatment planning is based on the use of a general relative biological effectiveness (RBE) of 1.1 along the whole beam penetration depth, without taking into account the documented increase in RBE at the end of the depth dose profile, in the Bragg peak and beyond. However, an inaccurate estimation of the RBE can cause both underdose or overdose, in particular it can cause the unfavourable situation of underdosing the tumour and overdosing the normal tissue just beyond the tumour, which limits the treatment success and increases the risk of complications. In view of a more precise dose delivery that takes into account the variation of RBE, experimental microdosimetry offers valuable tools for the quality assurance of LET or RBE-based treatment planning systems. The purpose of this work is to compare the response of two different microdosimetry systems: the mini-TEPC and the MicroPlus-Bridge detector. Microdosimetric spectra were measured across the 62 MeV spread out Bragg peak of CATANA with the mini-TEPC and with the Bridge microdosimeter. The frequency and dose distributions of lineal energy were compared and the different contributions to the spectra were analysed, discussing the effects of different site sizes and chord length distributions. The shape of the lineal energy distributions measured with the two detectors are markedly different, due to the different water-equivalent sizes of the sensitive volumes: 0.85 μm for the TEPC and 17.3 μm for the silicon detector. When the Loncol's biological weighting function is applied to calculate the microdosimetric assessment of the RBE, both detectors lead to results that are consistent with biological survival data for glioma U87 cells. Both the mini-TEPC and the MicroPlus-Bridge detector can be used to assess the RBE variation of a 62 MeV modulated proton beam along its penetration depth. The microdosimetric assessment of the RBE based on the Loncol's weighting function is in good agreement with radiobiological results when the 10% biological uncertainty is taken into account.
We exploited the power of the Geant4 Monte Carlo toolkit to study and validate new approaches for the averaged linear energy transfer (LET) calculation in 62 MeV clinical proton beams. The ...definitions of the averaged LET dose and LET track were extended, so as to fully account for the contribution of secondary particles generated by target fragmentation, thereby leading to a more general formulation of the LET total. Moreover, in the proposed new strategies for the LET calculation, we minimised the dependencies in respect to the transport parameters adopted during the Monte Carlo simulations (such as the production cut of secondary particles, voxel size and the maximum steplength). The new proposed approach was compared against microdosimetric experimental spectra of clinical proton beams, acquired at the Italian eye proton therapy facility of the Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare (INFN-LNS, Catania, I) from two different detectors: a mini-tissue equivalent proportional chamber (TEPC), developed at the Legnaro National Laboratories of the National Institute for Nuclear Physics (LNL-INFN) and a silicon-on-insulator (SOI) microdosimeter with 3D sensitive volumes developed by the Centre for Medical Radiation Physics of Wollongong University (CMRP-UoW). A significant increase of the LET in the entrance region of the spread out Bragg peak (SOBP) was observed, when the contribution of the generated secondary particles was included in the calculation. This was consistent with the experimental results obtained.
The Geant4 toolkit provides a wide set of alternative models to describe the electromagnetic interaction of photons with matter. The photon cross-sections that are used by the Geant4 electromagnetic ...models have been compared to external reference libraries (NIST, EPDL97, SANDIA) for several elements and compounds. The agreement of the Geant4 cross-section with the reference data has been quantified by means of statistical analysis. In particular, the cross-sections of all the Geant4 photon models are in statistical agreement with the NIST database, with the exception of Rayleigh scattering. A critical discussion is presented for those cases where a disagreement is found.
Nuclear fragmentation measurements are necessary when using heavy-ion beams in hadrontherapy to predict the effects of the ion nuclear interactions within the human body. Moreover, they are also ...fundamental to validate and improve the Monte Carlo codes for their use in planning tumor treatments. Nowadays, a very limited set of carbon fragmentation cross sections are being measured, and in particular, to our knowledge, no double-differential fragmentation cross sections at intermediate energies are available in the literature. In this work, we have measured the double-differential cross sections and the angular distributions of the secondary fragments produced in the 12C fragmentation at 62 A MeV on a thin carbon target. The experimental data have been used to benchmark the prediction capability of the Geant4 Monte Carlo code at intermediate energies, where it was never tested before. In particular, we have compared the experimental data with the predictions of two Geant4 nuclear reaction models: the Binary Light Ions Cascade and the Quantum Molecular Dynamic. From the comparison, it has been observed that the Binary Light Ions Cascade approximates the angular distributions of the fragment production cross sections better than the Quantum Molecular Dynamic model. However, the discrepancies observed between the experimental data and the Monte Carlo simulations lead to the conclusion that the prediction capability of both models needs to be improved at intermediate energies.
The ELIMED transport and dosimetry beamline for laser-driven ion beams Romano, F.; Schillaci, F.; Cirrone, G.A.P. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
09/2016, Letnik:
829
Journal Article
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A growing interest of the scientific community towards multidisciplinary applications of laser-driven beams has led to the development of several projects aiming to demonstrate the possible use of ...these beams for therapeutic purposes. Nevertheless, laser-accelerated particles differ from the conventional beams typically used for multiscipilinary and medical applications, due to the wide energy spread, the angular divergence and the extremely intense pulses. The peculiarities of optically accelerated beams led to develop new strategies and advanced techniques for transport, diagnostics and dosimetry of the accelerated particles. In this framework, the realization of the ELIMED (ELI-Beamlines MEDical and multidisciplinary applications) beamline, developed by INFN-LNS (Catania, Italy) and that will be installed in 2017 as a part of the ELIMAIA beamline at the ELI-Beamlines (Extreme Light Infrastructure Beamlines) facility in Prague, has the aim to investigate the feasibility of using laser-driven ion beams for multidisciplinary applications. In this contribution, an overview of the beamline along with a detailed description of the main transport elements as well as the detectors composing the final section of the beamline will be presented.
Fluence, depth absorbed dose and linear energy transfer (LET) distributions of proton and carbon ion beams have been investigated using the Monte Carlo code Geant4 (GEometry ANd Tracking). An open ...source application was developed with the aim to simulate two typical transport beam lines, one used for ocular therapy and cell irradiations with protons and the other for cell irradiations with carbon ions. This tool allows evaluation of the primary and total dose averaged LET and predict their spatial distribution in voxelized or sliced geometries. In order to reproduce the LET distributions in a realistic way, and also the secondary particles' contributions due to nuclear interactions were considered in the computations. Pristine and spread-out Bragg peaks were taken into account both for proton and carbon ion beams, with the maximum energy of 62 MeV/n. Depth dose distributions were compared with experimental data, showing good agreement. Primary and total LET distributions were analysed in order to study the influence of contributions of secondary particles in regions at different depths. A non-negligible influence of high-LET components was found in the entrance channel for proton beams, determining the total dose averaged LET by the factor 3 higher than the primary one. A completely different situation was obtained for carbon ions. In this case, secondary particles mainly contributed in the tail that is after the peak. The results showed how the weight of light and heavy secondary ions can considerably influence the computation of LET depth distributions. This has an important role in the interpretation of results coming from radiobiological experiments and, therefore, in hadron treatment planning procedures.
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