The quality assurance of particle therapy treatment is a fundamental issue that can be addressed by developing reliable monitoring techniques and indicators of the treatment plan correctness. Among the available imaging techniques, positron emission tomography (PET) has long been investigated and then clinically applied to proton and carbon beams. In 2013, the Innovative Solutions for Dosimetry in Hadrontherapy (INSIDE) collaboration proposed an innovative bimodal imaging concept that combines an in-beam PET scanner with a tracking system for charged particle imaging. This paper presents the general architecture of the INSIDE project but focuses on the in-beam PET scanner that has been designed to reconstruct the particles range with millimetric resolution within a fraction of the dose delivered in a treatment of head and neck tumors. The in-beam PET scanner has been recently installed at the Italian National Center of Oncologic Hadrontherapy (CNAO) in Pavia, Italy, and the commissioning phase has just started. The results of the first beam test with clinical proton beams on phantoms clearly show the capability of the in-beam PET to operate during the irradiation delivery and to reconstruct on-line the beam-induced activity map. The accuracy in the activity distal fall-off determination is millimetric for therapeutic doses.

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 (LET), while the others are based on DNA Double Strand Break (DSB) 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.

Electronic and structural properties of the CuPc/Al(100) organic−inorganic interface were investigated by means of a multitechnique experimental approach based on synchrotron radiation. The chemical selectivity of X-ray photoelectron spectroscopy (XPS) was used to investigate the electronic structure of copper-phthalocyanine (CuPc) as a function of the molecular thickness ranging from the submonolayer to 40 Å. Photoemission from core levels shows a dramatic alteration of the electronic structure of molecules localized at the interface. At the lowest CuPc coverages, the complete reduction of the oxidation state of copper was observed, while C 1s and N 1s shake-up satellites were no longer visible. Both findings are explained with a sizable charge transfer from the substrate to the molecule involving the b1g (Cu 3d-derived) and the LUMO hybridized with the substrate conduction band. The linear polarization of the synchrotron light was employed in X-ray absorption near-edge spectroscopy (XANES) to determine the orientation of CuPc molecules. Molecular planes oriented almost perpendicular with respect to the metal surface were observed from the second layer on.

Purpose: Advanced ion beam therapeutic techniques, such as hypofractionation, respiratory gating, or laser-based pulsed beams, have dose rate time structures which are substantially different 15 from those found in conventional approaches. The biological impact of the time structure is mediated through the β parameter in the linear quadratic (LQ) model. The aim of this study is to assess the impact of changes in the value of the β parameter on the treatment outcomes, also accounting for non instantaneous intra-fraction dose delivery or fractionation and comparing the effects of using different primary ions. with good results. Notably, in contrast to the original MKM formulation, the MCt-MKM explicitly predicts an ion and LET dependent β compatible with observations. The data from a split-dose experiment were used to experimentally determine the value of the parameter related to the cellular repair kinetics. Concerning the clinical case considered, an RBE decrease was observed, depending on the dose, ion and LET, exceeding up to 3% of the acute value in the case of a protraction in Conclusions:The present study provides a framework for exploiting the temporal effects of dose delivery. The results show the possibility of optimizing the treatment outcomes accounting for the 40 correlation between the specific dose rate time structure and the spatial characteristic of the LET distribution, depending on the ion type used.2 *

Hadrontherapy is a C++ , free and open source application developed using the Geant4 Monte Carlo libraries. The basic version of Hadrontherapy is contained in the official Geant4 distribution (www.cern.ch/Geant4/download), inside the category of the advanced examples. This version permits the simulation of a typical proton/ion transport beam line and the calculation of dose and fluence distributions inside a test phantom.A more complete version of the program is separately maintained and released by the authors and it offers a wider set of tools useful for Users interested in proton/ion-therapy studies. It gives the possibility to retrieve ion stopping powers in arbitrary geometrical configuration, to calculate 3D distributions of fluences, dose deposited and LET of primary and of the generated secondary beams, to simulate typical nuclear physics experiments, to interactively switch between different implemented geometries, etc.In this work the main characteristics of the actual full version of Hadrontherapy will be reported and results discussed and compared with the available experimental data.For more information the reader can refer to the Hadrontherapy website.