TP53 outperforms other androgen receptor biomarkers to predict abiraterone or enzalutamide outcome in metastatic castration-resistant prostate cancer.

PURPOSE: To infer the prognostic value of simultaneous androgen receptor (AR) and TP53 profiling in liquid biopsies from metastatic castration-resistant prostate cancer (mCRPC) patients starting a new line of AR signalling inhibitors (ARSi). EXPERIMENTAL DESIGN: Between March 2014 and April 2017, we recruited mCRPC patients (n=168) prior to ARSi in a cohort study encompassing 10 European centres. Blood samples were collected for comprehensive profiling of CellSearch-enriched circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA). Targeted CTC RNA-seq allowed the detection of eight AR splice variants (ARVs). Low-pass whole-genome and targeted gene-body sequencing of AR and TP53 was applied to identify amplifications, loss-of-heterozygosity, mutations and structural rearrangements in ctDNA. Clinical or radiological progression-free survival (PFS) was estimated by Kaplan-Meier analysis, and independent associations were determined using multivariable Cox-regression models. RESULTS: Overall, no single AR perturbation remained associated with adverse prognosis after multivariable analysis. Instead, tumour burden estimates (CTC counts, ctDNA fraction, and visceral metastases) were significantly associated with PFS. TP53 inactivation harbored independent prognostic value (HR 1.88, 95%CI 1.18-3.00, p = 0.008), and outperformed ARV expression and detection of genomic AR alterations. Using Cox coefficient analysis of clinical parameters and TP53 status, we identified three prognostic groups with differing PFS estimates (median, 14.7 vs 7.51 vs 2.62 months, p < 0.0001), which was validated in an independent mCRPC cohort (n=202) starting first-line ARSi (median, 14.3 vs 6.39 vs 2.23 months, p < 0.0001). CONCLUSIONS: In an all-comer cohort, tumour burden estimates and TP53 outperform any AR perturbation to infer prognosis

New lithostratigraphical, sedimentological, mineralogical and palaeontological data on the Mesozoic of Belgian Lorraine: a progress report

A multidisciplinary study of some extensively cored boreholes together with the new 1/25.000 geological mapping of wallonia lead us to propose a new lithostratigraphic canvas for belgian lorraine. This area is located on the n-e border of the paris basin, south of the ardennes; the studied stratigraphic interval covers the keuper to the toarcian. Each of the newly defined units is sedimentologicaly interpreted on the basis of macroscopic and microscopic observations. Detailed palynological and claystratigraphical analyses have been performed, providingadditional stratigraphical, palaeoecological and sedimentological data. Moreover, a first sequence stratigraphic interpretation is proposed for this highly transgressive sedimentary body. The habay formation (conglomerates and red mudstones) is a fluvial unit, with immature channel conglomerates and paleosoils; the attert formation (dolomitic marls with gypsum and pseudomorphs) exhibites an evaporitic trend. The Mortinsart formation (sands and marls) corresponds to a restricted marine unit, evolving towards an alluvial plain (levallois member). The second cycle begins with the Jamoigne Formation (bioturbated marls and limestones), a marine subtidal restricted unit, evolving towards a more sandy sedimentary body (Metzert Member). The base of the third cycle corresponds to the rest of the Luxemburg Formation, comprising a succession of sandy waves. The Ethe Formation (laminar mudstones and marls) marks a deepening of the basin and the outset of open marine dysaerobic conditions. The Aubange Formation (bioturbated marls with sandstones and limestones) is characterized by the reappearance of a normal benthic fauna. The Grandcourt Formation (laminar mudstones and marls) marks a return to open marine dysaerobic conditions. The Mont-Saint-Martin Formation (marls, sandy marls and oolitic ironstone) is a highly regressive unit, while the Longwy Formation (limestones) marks the initiation of a carbonate platform

Imputabilité en toxicologie postmortem : exemple d'un travail sur la pholcodine

Date du colloque&nbsp;: 10/2008</p

Imputabilité en toxicologie postmortem : exemple d'un travail sur la pholcodine

Date du colloque&nbsp;: 10/2008</p