Transport and dosimetric solutions for the ELIMED laser-driven beam line

Within 2017, the ELIMED (ELI-Beamlines MEDical applications) transport beam-line and dosimetric systems for laser-generated beams will be installed at the ELI-Beamlines facility in Prague (CZ), inside the ELIMAIA (ELI Multidisciplinary Applications of laser-Ion Acceleration) interaction room. The beam-line will be composed of two sections: one in vacuum, devoted to the collecting, focusing and energy selection of the primary beam and the second in air, where the ELIMED beam-line dosimetric devices will be located. This paper briefly describes the transport solutions that will be adopted together with the main dosimetric approaches. In particular, the description of an innovative Faraday Cup detector with its preliminary experimental tests will be reported

Applications of Monte Carlo methods to special radiotherapeutic techniques

Monte Carlo (MC) methods are considered one of the most powerful and precise approaches to study and solve medical physics issues. They, indeed, can be applied in all the situations where to use deterministic algorithms is infeasible or impossible. Surprising improvements in computer technology have promoted a wide diffusion of this technique, giving rise to the born of several Monte Carlo codes, such as the GEANT4 toolkit. In this paper we show some of the applications we developed using GEANT4. In particular, the simulation of two different radiotherapy techniques, such as proton/ion therapy and stereotactic radiosurgery will be discussed. In the first case we show the main features of our last public version of the GEANT4 Hadrontherapy program, also discussing the issues related to the nuclear fragmentation. In the second case, we show the procedures followed for the simulation of a Gamma Knife device, in order to validate the Treatment Planning System (TPS) used for the dose computation

Alteration of p53 and Bax/ Bcl-2 ratio by fotemustine and proton irradiation

Deregulation of apoptosis commonly occurs in melanoma cells and could be a reason for resistance. The effectiveness of different treatments depends on their ability to activate this process. In this study the effects of combined treatments with fotemustine (FM) and proton irradiation on the regulators of apoptosis were analyzed. Sub-confluent HTB140 human melanoma cells were treated with FM (100, 250 µM) 24 h prior to irradiation (12, 16 Gy). Cells were irradiated in the middle of the therapeutic 62 MeV proton spread out Bragg peak. Flow cytometric analysis of apoptosis and the Western blot analysis of apoptotic regulators were performed 6 or 48 h after treatments. Percent of apoptotic nuclei increased after applied treatments, reaching the level of 4 to 41 %. Induction of apoptosis was associated with p53 and Bax up regulation and Bcl-2 down regulation. The obtained results imply that analyzed treatments induce apoptosis through the activation of the mitochondrial apoptotic pathway, with better pro-apoptotic effects achieved by combined treatments

Array of time-of-flight diamond detectors for particle discrimination in laser driven p-11B fusion experiments

The detection of radiation emission in laser induced plasma experiments is an helpful method for gaining information on the physics of laser-matter interaction. Time-of-Flight (TOF) approach is a powerful and effective method to obtain timely spectra of particles accelerated from laser-generated plasma. To this respect, diamond-based detectors are very attractive due to their interesting features such as fast signal collection time, signal proportional to the energy deposited by the incident radiation, blindness to visible radiation, high radiation hardness and low leakage current at room temperature operation. Unfortunately, they cannot supply discrimination on the species of the incoming ions, but only their energies. This may be overcome using specific filtering foils to exploit the different stopping powers of ions of different species and energies. In this work we describe the method to distinguish particles using an array of TOF diamond detectors. A first prototype array, consisting of 2×2 diamond detectors, nominally identical and featuring by aluminum filters of different thicknesses, was developed and preliminary tested at PALS facility in Prague

Study of the 12C + 12C reaction at 62 A MeV for hadrontherapy applications

The largest uncertainty on the physical dose deposition in hadrontherapy is due to ion’s nuclear interaction through the traversed material. Today the simulation codes are not able to reproduce the fragmentation process with the required precision. To improve the knowledge of 12C fragmentation at intermediate energies we have measured at the Laboratori Nazionali del Sud in Catania production cross sections, energy spectra and angular distributions of fragments produced in 12C fragmentation on thin 12C target, at 62A MeV

Proton therapy and src family kinase inhibitor combined treatments on U87 human glioblastoma multiforme cell line

Glioblastoma Multiforme (GBM) is the most common of malignant gliomas in adults with an exiguous life expectancy. Standard treatments are not curative and the resistance to both chemotherapy and conventional radiotherapy (RT) plans is the main cause of GBM care failures. Proton therapy (PT) shows a ballistic precision and a higher dose conformity than conventional RT. In this study we investigated the radiosensitive effects of a new targeted compound, SRC inhibitor, named Si306, in combination with PT on the U87 glioblastoma cell line. Clonogenic survival assay, dose modifying factor calculation and linear-quadratic model were performed to evaluate radiosensitizing effects mediated by combination of the Si306 with PT. Gene expression profiling by microarray was also conducted after PT treatments alone or combined, to identify gene signatures as biomarkers of response to treatments. Our results indicate that the Si306 compound exhibits a radiosensitizing action on the U87 cells causing a synergic cytotoxic effect with PT. In addition, microarray data confirm the SRC role as the main Si306 target and highlights new genes modulated by the combined action of Si306 and PT. We suggest, the Si306 as a new candidate to treat GBM in combination with PT, overcoming resistance to conventional treatments

Radiobiological outcomes, microdosimetric evaluations and monte carlo predictions in eye proton therapy

CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) was the first Italian protontherapy facility dedicated to the treatment of ocular neoplastic pathologies. It is in operation at the LNS Laboratories of the Italian Institute for Nuclear Physics (INFN-LNS) and to date, 500 patients have been successfully treated. Even though proton therapy has demonstrated success in clinical settings, there is still a need for more accurate models because they are crucial for the estimation of clinically relevant RBE values. Since RBE can vary depending on several physical and biological parameters, there is a clear need for more experimental data to generate predictions. Establishing a database of cell survival experiments is therefore useful to accurately predict the effects of irradiations on both cancerous and normal tissue. The main aim of this work was to compare RBE values obtained from in-vitro experimental data with predictions made by the LEM II (Local Effect Model), Monte Carlo approaches, and semi-empirical models based on LET experimental measurements. For this purpose, the 92.1 uveal melanoma and ARPE-19 cells derived from normal retinal pigmented epithelium were selected and irradiated in the middle of clinical SOBP of the CATANA proton therapy facility. The remarkable results show the potentiality of using microdosimetric spectrum, Monte Carlo simulations and LEM model to predict not only the RBE but also the survival curves

Proton range monitoring with in-beam PET: Monte Carlo activity predictions and comparison with cyclotron data

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