Dosimétrie in vivo des traitements de radiothérapie conformationnelle avec modulation d'intensité par imageur portal haute énergie au silicium amorphe

La réalisation de la dosimétrie in vivo (DIV) en radiothérapie externe reste difficilement applicable dans le cadre d'irradiations conformationnelles avec modulation d'intensité (RCMI) où la mesure obtenue à l'aide de détecteurs ponctuels placés en entrée de patient est trop peu représentative de la dose réellement délivrée au volume cible. L'utilisation des imageurs haute énergie au silicium amorphe ("Electronic Portal Imaging Device", EPID) dans ce contexte est une alternative intéressante à condition de disposer en parallèle d'algorithmes permettant de convertir le plus précisément possible le signal de l'EPID en dose absorbée dans le patient. Ce travail de thèse s'inscrit donc dans cette démarche et consiste à développer des méthodes de calculs applicables en clinique permettant d'utiliser l'EPID pour la pratique de la DIV des traitements par RCMI. En premier lieu nous présentons le dispositif d'imagerie utilisé tout au long de ces travaux ainsi que la caractérisation de sa réponse en fonction de plusieurs paramètres d'irradiation. Une méthode permettant de déterminer la dose reçue par le patient en un point situé sur l'axe du faisceau à partir du signal de l'EPID a par la suite fait l'objet d'une étude sur 92 patients traités par RCMI dynamique pour des pathologies pelviennes. Dans un second temps, un algorithme de rétroprojection permettant de reconstruire la dose reçue par le patient en deux dimensions a été développé. Pour cela, le signal de l'EPID obtenu en sortie de patient est d'abord converti en dose absorbée dans l'eau par convolution de l'image avec plusieurs kernels de redistribution. La dose ainsi calculée est ensuite rétroprojetée par l'intermédiaire de facteurs correctifs dépendants de la morphologie du patient et de sa transmission. L'évaluation de la méthode a été réalisée sur 26 faisceaux issus de 6 plans de traitements différents d'abord en condition de prétraitement (i.e. sans patient placé entre la source et le détecteur), puis sur fantôme homogène et enfin in vivo. L'introduction de fonctions d'atténuation dépendantes de la profondeur de calcul dans notre modèle a finalement permis d'obtenir un algorithme capable de reconstruire la dose dans le patient en trois dimensions.In vivo dosimetry (IVD) is still a complex procedure for intensity-modulated radiation therapy (IMRT). The use of conventional point detectors does not give a good representation of the actual dose delivered to the target volume. On the other hand, EPID-based in vivo dosimetry methods appears to be an interesting and efficient option for carrying out such measurements provided that accurate algorithms allowing to convert EPID signal into patient absorbed dose are available. The present work consists in developing clinically applicable calculation methods to perform EPID-based IVD on intensity-modulated fields. As a starting point, the imaging device used throughout this work is described before considering its response with respect to several irradiation parameters. An IVD method enabling the calculation of the on-axis patient point dose from EPID signal was studied and evaluated for 92 pelvic cancer patients treated with IMRT. Then, a 2D back-projection in vivo dose reconstruction algorithm was developed. In this model, the EPID signal was first converted into absorbed dose in water by convolving the EPID image with dose redistribution kernels. The 2D dose distribution was then back-projected applying correction factors calculated from the patient morphology and transmission factor. The validity of the method was checked for 6 treatment plans (26 fields) in pretreatment situation (i.e. without patient) with homogeneous phantom and finally in vivo. The last part of this work deals with the introduction of mathematical attenuation functions in order to devise a complete in vivo 3D dose reconstruction algorithm

Principles and Experiments of a Multi-Agent Approach for Large Co-Simulation Networks Initialization

ICAART 2017 will be held in conjunction with ICORES 2017 and ICPRAM 2017.International audienceSimulating large systems, such as smart grids, often requires to build a network of specific simulators. Makingheterogeneous simulators work together is a challenge in itself, but recent advances in the field of co-simulationare providing answers. However, one key problem arises, and has not been sufficiently addressed: the initial-ization of such networks. Many simulators need to have proper input values to start. But in the network, eachinput is another simulator’s output. One have to find the initial input values of all simulators so their computedoutput is equal to the initial input value of the other linked simulators. Given that simulators often containdifferential equations, this is hard to solve even with a small number of simulators, and nearly impossible witha large number of them. In this paper, we present a mutli-agent system designed to solve the co-simulationinitialization problem, and show preliminary results on large networks

The Modelica Language and the FMI Standard for Modeling and Simulation of Smart Grids

International audienceThe smart power grids will extensively rely on network control to increase efficiency, reliability, and safety; to enable plug-and-play asset integration, such as in the case of distributed generation and alternative energy sources; to support market dynamics as well as reduce peak prices and stabilize costs when supply is limited. In turn, network control requires an advanced communication infrastructure with support for safety and real-time communication. Simulating such complex systems is a key objective for the development of Smart Grids. Several simulation tools are available on the market but these tools have two major drawbacks: • They are generally not designed to import models developed for other tools. • They are not adapted to large scale complex system of systems or cyber-physical systems as smart grids which require time-consuming calculation. One solution to bypass these drawbacks is to use a co-simulation platform which can connect together several simulators and FMUs (Functional Mock-up unit). ER and D is funding the development of its own co-simulation platform dedicated to the Smart Grids in partnership with LORIA-INRIA. A first release of this tool named MECSYCO is available under the Affero GPL license v3 (http://mecsyco.loria.fr/). The next published version (at the end of 2015) will upgrade MECSYCO with the coupling of different types of discrete-time or continuous-time simulators (including the FMUs) divided in three domains: • The physics domain (process) : FMUs exported according to the FMI 2.0 standard from Dymola with models built from the EDF Modelica library GridSysPro or historical tools widely used at EDF (e.g. EMTP-RV) now compatible with the FMI standard; • The telecommunication domain: NS-3, OMNeT++ or OPNeT ; • The Information System domain with models designed with UML/SysML oriented tools. MECSYCO is based on the Multi-Agent concept (one agent per simulator to describe a heterogeneous multi-model) and on the DEVS formalism (to conceive a decentralized execution algorithm respecting the causality constraints). This paper provides first an overview of the ER and D Modelica library GridSysPro (GSP) composed of electrical components mapped on the zone related to the process of a Smart Grid. Besides that, to comply with the modeling of large scale electrical networks, a solution to co-initialize several interconnected FMUs exported from Dymola is described

Early Development of Atherosclerotic Plaques in the Coronary Arteries after Radiotherapy for Breast Cancer (BACCARAT Study)

International audienceBackground—Radiotherapy (RT) for breast cancer (BC) can lead to an increased risk of coronary artery disease several years after RT. The aim of this study was to evaluate the development of overall, non-calcified and calcified atherosclerotic plaques over 2 years after BC for RT and associations with cardiac exposure. Methods—The study included 101 left- or right-sided BC patients treated with RT without chemotherapy. A coronary CT angiography was performed before and 2 years after RT. Plaque development thorough the entire coronary network was defined as an increased number of plaques. Cardiac exposure was quantified with mean doses to the heart, left ventricle, and coronary arteries. Logistic regression models were used to assess association with doses. Results—At inclusion, 37% of patients had plaques, increasing to 42% two years after RT. Overall plaque development was observed in seven patients: five with calcified plaque development and four with non-calcified plaque development. The risk of overall plaque development was significantly associated with doses to the Left Main and Circumflex coronary arteries (OR at 1 Gy = 2.32, p = 0.03 and OR at 1 Gy = 2.27, p = 0.03, respectively). Specific analyses for calcified and non-calcified plaque development showed similar results. Conclusion—Our study suggests an association between coronary arteries exposure and the risk of developing both calcified and non-calcified atherosclerotic plaques over 2 years after BC RT. Trial registration number: NCT02605512

Early Coronary Artery Calcification Progression over Two Years in Breast Cancer Patients Treated with Radiation Therapy: Association with Cardiac Exposure (BACCARAT Study)

Background: Radiotherapy (RT) for breast cancer (BC) can induce coronary artery disease many years after RT. At an earlier stage, during the first two years after RT, we aimed to evaluate the occurrence of increased coronary artery calcium (CAC) and its association with cardiac exposure. Methods: This prospective study included 101 BC patients treated with RT without chemotherapy. Based on CAC CT scans performed before and two years after RT, the event ‘CAC progression’ was defined by an increase in overall CAC score (CAC RT+ two years—CAC before RT > 0). Dosimetry was evaluated for whole heart, left ventricle (LV), and coronary arteries. Multivariable logistic regression models were used to assess association with doses. Results: Two years after RT, 28 patients presented the event ‘CAC progression’, explained in 93% of cases by a higher CAC score in the left anterior descending coronary (LAD). A dose–response relationship was observed with LV exposure (for Dmean LV: OR = 1.15, p = 0.04). LAD exposure marginally explained increased CAC in the LAD (for D2 LV: OR =1.03, p = 0.07). Conclusion: The risk of early CAC progression may be associated with LV exposure. This progression might primarily be a consequence of CAC increase in the LAD and its exposure

Low predictive value of mean heart dose for coronary artery dosimetry in breast cancer radiotherapy

International audiencePurpose or ObjectiveIn many studies that investigated radiation-induced cardiac toxicity of breast cancer radiotherapy, doses are described as those received by the entire heart and the mean heart dose is used as the reference dose for analyzing dose-response relationship. However the specific relationships between doses to cardiac substructures, in particular coronary arteries, and subsequent toxicity have not been well defined. Detailed individual dosimetry information for the heart and its sub-structures is required to better understand cardiac damage from radiation exposure. The aim of this dosimetric study was to analyze the distribution of individually-determined radiation exposure, in a population of breast cancer patients treated with three dimensional conformal radiation therapy (3D-CRT), and clarify whether mean heart dose is a good surrogate parameter for the dose to coronary arteries, in particular the left anterior descending artery.Material and MethodsPatients with left or right unilateral breast cancer (BC) treated with 3D-CRT between 2015 and 2017 were included (BACCARAT clinical study). Before RT, a coronary computed tomography angiography (CCTA) was performed. Registration of the planning CT and CCTA images allowed precise delineation of the coronary arteries on the planning CT images. Using the 3D dose matrix generated during treatment planning and the added coronary contours, dose distributions were generated for the following cardiac structures: whole heart, left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA). A descriptive analysis of the physical doses in Gray (Gy) was performed.ResultsDose distributions were generated for 89 left-sided BC and 15 right-sided BC patients. The treatment schedule with tangential beams was either 50 Gy delivered in 25 fractions of 2 Gy or 47 Gy in 20 fractions of 2.35 Gy, with or without irradiation of regional lymph nodes. Additional beams to tumor bed (boost) were used, if clinically indicated. The mean heart dose (Dmean Heart) was 2.9 ± 1.5 Gy for left-sided BC and 0.5 ± 0.1 Gy for right-sided BC. For left-sided BC patients, the mean ratio Dmean LAD/Dmean Heart was around 5. All other ratios were below 1 except for RCA in right-sided BC patients (ratio=2.7). However, the coefficients of determination R² indicated that the proportion of the variance in Dmean LAD or Dmean RCA predictable from Dmean Heart was low (R²=0.45 and 0.36 respectively). For left-sided BC patients with lower exposure (Dmean Heart 40Gy to 20% of the LAD volume on average (V40Gy).ConclusionOur study illustrates that the predictive value of the mean heart dose was not good enough for coronary arteries, in particular for LAD, illustrating the importance of considering the distribution of doses within these cardiac substructures rather than just the mean heart dose to enhance knowledge on the risk of radiation-induced cardiotoxicity in breast radiotherapy

Cardiac radiation exposure associated with breast cancer radiotherapy: dose distribution to the heart substructures and coronary arteries (BACCARAT study)

International audienceBackground: Radiotherapy (RT) is a major component of breast cancer treatment and advanced RT techniques allowed reducing irradiation of healthy tissue. However, the heart often remains partially exposed. Detailed individual heart dosimetry information is required to better understand radiation-induced cardiac damage. Purpose: To analyze the distribution of individually-determined radiation dose to the heart and its substructures, in particular coronary arteries, after RT in breast cancer patients from the BACCARAT cohort. Methods: BACCARAT is a monocentric prospective cohort study that included unilateral breast cancer patients treated with RT between 2015 and 2017 and followed for 2 years with repeated cardiac imaging examinations, including coronary computed tomography angiography. Using the 3D dose matrix generated during RT treatment planning and the added coronary contours, dose distributions were generated for the following cardiac structures: whole heart, left ventricle (LV), left main coronary artery (LM), left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA). A descriptive analysis of the physical doses in Gray (Gy) was performed.Results: Dose distributions were generated for 59 patients (50 left-sided breast cancer, 9 right-sided) who all received a treatment of 50 Gy to the breast. The mean heart dose was 2.98 Gy for left sided patients and 0.42 Gy for right sided and mean LV doses were respectively 6.23 Gy and 0.09 Gy. For left-sided patients, mean dose to LM (D_LM)=1.29 Gy, D_LAD=16.32 Gy, D_LCX=1.59 Gy and D_RCA=0.67Gy, whereas corresponding doses for right-sided patients were D_LM=0.35 Gy, D_LAD=0.11 Gy, D_LCX=0.14 Gy and D_RCA=1.10 Gy. For left sided patients, the most exposed part of the LAD could receive doses > 45 Gy.Conclusion: Our study illustrates the wide range of doses experienced by the heart substructures and thus the poor significance of the mean heart dose as a radiation damage indicator. Keywords: Radiotherapy; Breast Cancer; Radiation Dosimetry; Cardiotoxicit