Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations

BACKGROUND: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. METHODS: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. RESULTS: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). CONCLUSION: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design

The size of the Sun

International audienceWhy does the Sun have a radius around 696 000 km? We will see in this article that dimensional arguments can be used to understand the size of the Sun and of a few other things along the way. These arguments are not new and can be found scattered in textbooks. They are presented here in a succinct way in order to better confront the kinematic and mechanical viewpoints on size. We derive and compare a number of expressions for the size of the Sun and relate large and small scales. We hope that such presentation will be useful to students, instructors, and researchers alike

TOUGHNESS AND HEAT TREATMENT. RELATIONSHIP IN A 2091 ALUMINIUM ALLOY

The 2091 alloy was tested to determine toughness levels with respect to heat treatment. A drastic decrease in fracture toughness was observed as a function of heat treatment. The occurence of such a toughness drop was clearly related to fracture modes : . Transgranular and intergranular precipitation and deformation modes were studied. The loss of grain boundary strength could be explained by the precipitation of the quasi crystalline phase T

A multi-scale approach to model localized failure with softening

International audienceWe present a computational strategy for strongly coupled multi-scale analysis of heterogeneous material undergoing localized failure with softening. The proposed method can nicely fit within the standard architecture of finite element codes, with the key idea to replace the standard computation of the element tangent stiffness matrices and the residual vectors by an assembly of micro-scale computations whose contributions are statically condensed at the coarser level. The micro-scale elements act as local kinematic enrichments which allow us to deal with localized failure mechanism in essentially the same manner as the classical embedded discontinuity element enhancement, with the benefit of accounting for true microstructure of heterogeneous material with softening behavior. The proposed multi-scale solution strategy also incorporates a cylindrical arc-length procedure at the micro level which allows the softening phenomena to be handled. Some numerical examples dealing with localized failure of heterogeneous materials are presented in order to illustrate very satisfying performance of the proposed methodology