16 research outputs found

    Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas

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    Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively (P < .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy. (C) 2017 by American Society of Clinical Oncolog

    Cervical screening : ESGO-EFC position paper of the European Society of Gynaecologic Oncology (ESGO) and the European Federation of Colposcopy (EFC)

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    This paper summarises the position of ESGO and EFC on cervical screening based on existing guidelines and opinions of a team of lead experts. HPV test is replacing cytology as this offers greater protection against cervical cancer and allows longer screening intervals. Only a dozen of HPV tests are considered as clinically validated for screening. The lower specificity of HPV test dictates the use of triage tests that can select women for colposcopy. Reflex cytology is currently the only well validated triage test; HPV genotyping and p16 immunostaining may be used in the future, although methylation assays and viral load also look promising. A summary of quality assurance benchmarks is provided, and the importance to audit the screening histories of women who developed cancer is noted as a key objective. HPV-based screening is more cost-effective than cytology or cotesting. HPV-based screening should continue in the post-vaccination era. Only a fraction of the female population is vaccinated, and this varies across countries. A major challenge will be to personalise screening frequency according to vaccination status. Still the most important factor for successful prevention by screening is high population coverage and organised screening. Screening with self-sampling to reach under-screened women is promising.Peer reviewe

    End-performance evaluation of thiourea-modified bituminous binders through viscous flow and linear viscoelasticy testing

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    Straight-run bitumens are no longer suitable in new asphalt mixtures. Consequently, the use of modified bitumens has become more important. In order to both improve binders mechanical properties and prevent it from phase separation whilst stored at high temperature, the paving industry is currently developing new modification routes based on reactive agents. This work studies the use of thiourea, which has proven to efficiently broaden the temperature interval over which the binder demonstrates an adequate performance. On the one hand, viscous flow and dynamic shear tests indicate an enhancement in the high in-service temperature strength, along with a reduced thermal susceptibility. On the other hand, results of dynamic flexural tests reveal a significant decrease in the binder glass transition temperature. Finally, the use of master curves and a further frequency/temperature conversion are proposed, in order to attain a suitable viscoelastic characterisation of bituminous binders at low temperatures.This work is part of a research project sponsored by Junta de Andalucia-CEIC (TEP6689) and also by "Ministerio de Educacion" through its Research Mobility Programme (Partal's grant Ref. PR2010-0593) and through the Cuadri's F.P.U. research grant (AP2008-01419). Authors gratefully acknowledge their finncial support.This work is part of a research project sponsored by Junta de Andalucia-CEIC (TEP6689) and also by “Ministerio de Educacion” through its Research Mobility Programme (Partal’s grant Ref. PR2010-0593) and through the Cuadri’s F.P.U. research grant (AP2008-01419). Authors gratefully acknowledge their financial support
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