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Bouche O.,Center Hospitalier University Of Reims | Beretta G.D.,U.O. Oncologia Medica | Alfonso P.G.,Servicio de Oncologia Medica | Geissler M.,Municipal Hospital Esslingen
Cancer Treatment Reviews | Year: 2010

Despite the introduction of newer chemotherapeutic agents such as irinotecan, capecitabine and oxaliplatin, patients with metastatic colorectal cancer (mCRC) still have a poor prognosis. More effective and better-tolerated treatment strategies are needed to improve patient outcomes, particularly in subsequent lines of treatment following chemotherapy failure. The favourable efficacy and acceptable safety profiles of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) have led to the approval of panitumumab and cetuximab monotherapy for the treatment of patients with EGFR-expressing mCRC whose tumours express non-mutated (wildtype) KRAS, after failure of standard chemotherapy. Cetuximab is also approved in combination with chemotherapy for the treatment of mCRC in this patient population. In phase III monotherapy studies, panitumumab and cetuximab demonstrated significant improvements in progression-free survival when administered with best supportive care (BSC) vs. BSC alone in chemotherapy-refractory mCRC patients. A planned retrospective analysis of the panitumumab monotherapy trial was the first large-scale clinical demonstration that efficacy was confined to patients with tumours expressing wild-type KRAS. It is now recognised that anti-EGFR mAb therapy should only be used in patients whose tumours express wild-type KRAS. While generally well tolerated, anti-EGFR mAb monotherapy is associated with skin toxicity, and severity of the skin rash has been proposed as an early marker of response to treatment. BRAF, PTEN, and PI3K are also emerging as future potential predictive markers of response; however, further clinical studies are warranted to define the role of these biomarkers. © 2010 Elsevier Ltd. All rights reserved.

Potheegadoo J.,French Institute of Health and Medical Research | Potheegadoo J.,University of Strasbourg | Berna F.,French Institute of Health and Medical Research | Berna F.,University of Strasbourg | And 4 more authors.
Schizophrenia Research | Year: 2013

There is growing interest in clinical research regarding the visual perspective adopted during memory retrieval, because it reflects individuals' self-attitude towards their memories of past personal events. Several autobiographical memory deficits, including low specificity of personal memories, have been identified in schizophrenia, but visual perspective during autobiographical memory retrieval has not yet been investigated in patients. The aim of this study was therefore to investigate the visual perspective with which patients visualize themselves when recalling autobiographical memories and to assess the specificity of their memories which is a major determinant of visual perspective. Thirty patients with schizophrenia and 30 matched controls recalled personal events from 4 life periods. After each recall, they were asked to report their visual perspective (Field or Observer) associated with the event. The specificity of their memories was assessed by independent raters. Our results showed that patients reported significantly fewer Field perspectives than comparison participants. Patients' memories, whether recalled with Field or Observer perspectives, were less specific and less detailed. Our results indicate that patients with schizophrenia adopt Field perspectives less frequently than comparison participants, and that this may contribute to a weakened sense of the individual of being an actor of his past events, and hence to a reduced sense of self. They suggest that this may be related to low specificity of memories and that all the important aspects involved in re-experiencing autobiographical events are impaired in patients with schizophrenia. © 2013 Elsevier B.V.

Bredahl K.,Copenhagen University | Long A.,Center Hospitalier University Of Reims | Taudorf M.,Copenhagen University | Lonn L.,Copenhagen University | And 4 more authors.
European Journal of Vascular and Endovascular Surgery | Year: 2013

Objectives: Volume estimation is more sensitive than diameter measurement for detection of aneurysm growth after endovascular aneurysm repair (EVAR), but this has only been confirmed on three-dimensional, reconstructed computer tomography (3-D CT). The potential of 3-D ultrasound (3-D US) for volume estimation in EVAR surveillance is unknown. Design: Prospective validation study comparing 3-D US with 3-D CT, using 3-D CT as the gold standard. Materials and methods: From August 2011 to March 2012, 93 consecutive EVAR patients were enrolled and examined with both 3-D US and CT angiography (CTA). Image data were analysed in a mutual blinded setup using a 3-D interactive segmentation technique. Results: The technical success rate of 3D-US was 98% (91/93). In 91 EVAR patients (F/M; 10/81) eligible for further analysis, the mean maximum volume (SD) was 126 (58) ml using 3-D US and 128 (58) ml using 3-D CT. The mean difference was 1 ml (0.4%) and the limits of agreement were -14 to 16 ml (-11; 12%). Conclusion: Volume estimation of the aortic sac after EVAR using 3-D US is a feasible and accurate method using 3-D CT as the gold standard. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Long A.,Center Hospitalier University Of Reims | Rouet L.,Philips | Lindholt J.S.,Vascular Research Unit | Allaire E.,Center Hospitalier University Henri Mondor | Allaire E.,University Paris Est Creteil
European Journal of Vascular and Endovascular Surgery | Year: 2012

Objectives: Maximum diameter is a determinant parameter for the clinical management of asymptomatic abdominal aortic aneurysm (AAA). However, its measurement is not standardised. We review the different methods used to measure AAA maximum diameter, with ultrasound (US) or computed tomography (CT). Methods: A review of maximum diameter measurement methods with US and CT was performed, focussing on screening, surveillance before repair and decision for intervention. Diameter measurement methodology was described according to four parameters: plane of acquisition, axis of measurement, position of callipers and selected diameter. A quality score to evaluate methodology descriptions was defined (plane, axis, callipers placement and selected diameter), ranging from 0 (worst) to 4 (best). Results: Review showed a wide range of definitions and practices. The mean value of the quality score was 2.52 in screening studies, 1.66 in guidelines for screening, 2.81 in follow-up studies and 1.63 in studies describing decision for intervention. Conclusion: To improve the efficiency of AAA management (in screening programmes, follow-up and decision for intervention), and enable comparison between future studies, a standardised methodology for AAA maximum diameter measurement is necessary. Until such a consensus is reached, publications should at least clearly report the method of measurement. © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Robert C.,French Institute of Health and Medical Research | Karaszewska B.,Przychodnia Lekarska KOMED | Schachter J.,Medical University of Gdansk | Rutkowski P.,Center of Oncology of Poland | And 24 more authors.
New England Journal of Medicine | Year: 2015

Background The BRAF inhibitors vemurafenib and dabrafenib have shown efficacy as monotherapies in patients with previously untreated metastatic melanoma with BRAF V600E or V600K mutations. Combining dabrafenib and the MEK inhibitor trametinib, as compared with dabrafenib alone, enhanced antitumor activity in this population of patients. Methods In this open-label, phase 3 trial, we randomly assigned 704 patients with metastatic melanoma with a BRAF V600 mutation to receive either a combination of dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) or vemurafenib (960 mg twice daily) orally as first-line therapy. The primary end point was overall survival. Results At the preplanned interim overall survival analysis, which was performed after 77% of the total number of expected events occurred, the overall survival rate at 12 months was 72% (95% confidence interval [CI], 67 to 77) in the combination-therapy group and 65% (95% CI, 59 to 70) in the vemurafenib group (hazard ratio for death in the combination-therapy group, 0.69; 95% CI, 0.53 to 0.89; P = 0.005). The prespecified interim stopping boundary was crossed, and the study was stopped for efficacy in July 2014. Median progression-free survival was 11.4 months in the combinationtherapy group and 7.3 months in the vemurafenib group (hazard ratio, 0.56; 95% CI, 0.46 to 0.69; P<0.001). The objective response rate was 64% in the combinationtherapy group and 51% in the vemurafenib group (P<0.001). Rates of severe adverse events and study-drug discontinuations were similar in the two groups. Cutaneous squamous-cell carcinoma and keratoacanthoma occurred in 1% of patients in the combination-therapy group and 18% of those in the vemurafenib group. Conclusions Dabrafenib plus trametinib, as compared with vemurafenib monotherapy, significantly improved overall survival in previously untreated patients with metastatic melanoma with BRAF V600E or V600K mutations, without increased overall toxicity. © 2015 Massachusetts Medical Society.

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