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Thierry A.R.,French Institute of Health and Medical Research | Thierry A.R.,French National Center for Scientific Research | Mouliere F.,French Institute of Health and Medical Research | Mouliere F.,French National Center for Scientific Research | And 19 more authors.
Nature Medicine | Year: 2014

Assessment of KRAS status is mandatory in patients with metastatic colorectal cancer (mCRC) before applying targeted therapy. We describe here a blinded prospective study to compare KRAS and BRAF mutation status data obtained from the analysis of tumor tissue by routine gold-standard methods and of plasma DNA using a quantitative PCR-based method specifically designed to analyze circulating cell-free DNA (cfDNA). The mutation status was determined by both methods from 106 patient samples. cfDNA analysis showed 100% specificity and sensitivity for the BRAF V600E mutation. For the seven tested KRAS point mutations, the method exhibited 98% specificity and 92% sensitivity with a concordance value of 96%. Mutation load, expressed as the proportion of mutant alleles in cfDNA, was highly variable (0.5-64.1%, median 10.5%) among mutated samples. CfDNA was detected in 100% of patients with mCRC. This study shows that liquid biopsy through cfDNA analysis could advantageously replace tumor-section analysis and expand the scope of personalized medicine for patients with cancer. © 2014 Nature America, Inc. All rights reserved.


PubMed | Center Francois Baclesse, Institute Of Cancerologie Of Louest Nantes, Bordeaux University Hospital Center, Center Paul Strauss and 11 more.
Type: Journal Article | Journal: Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique | Year: 2016

Radiotherapy is a rare indication in paediatric oncology, with 800to 900children in treatment per year in France. Child cancers represent approximately 1% of cancers in France and half occur before the age of 5years. Paediatric radiation requires appropriate tools, local, time and specific training. In France, in 2015, 18centres are accredited by the French National Cancer Institute (INCa) for this activity.Survey conducted in February 2015on the care of children (0to 18years) in radiotherapy departments in France. The survey was sent to the radiation oncologists involved in the 18centres. The questions concerned the qualitative and quantitative aspect, medical and organizational aspects, and the involvement of assistant practitioners in the management of this activity.Seventeen centres responded. In 2014, 889children under 18were treated in radiotherapy departments. These departments are working together with one to four paediatric oncology departments. Regarding access to general anaesthesia: three centres perform one to seven treatment(s) under anaesthesia per year, three centres eight to ten treatments under anaesthesia per year, three centres ten to 24treatments under anaesthesia per year and nine centres out of 17use hypnosis techniques. In terms of human resources, in 2015, 29radiation therapists have a paediatric radiotherapy activity. Involvement of assistant practitioners is growing and specific training are desired. Regarding treatment preparation and delivery, 13centres have specific paediatric contentions, 14of 16centres employ radiation intensity modulated if dosimetry is more satisfying with 11regularly to the craniospinal irradiation. Radiotherapy on moving areas with respiratory gating or hypofractionation is under developed.Paediatric radiation therapy is a specific activity requiring a dedicated management, both in human, organizational, medical and scientific aspects.


PubMed | Service de gynecologie, Service de gastro enterologie, Service de pediatrie generale, Nancy University Hospital Center and 37 more.
Type: Journal Article | Journal: Geriatrie et psychologie neuropsychiatrie du vieillissement | Year: 2016

The number of serum 25-hydroxyvitamin D (25OHD) assays has increased tenfold in France in less than 10 years, sometimes for invalidated reasons. In 2013, the French National Authority for Health (Haute autorit de sant, or HAS) limited the indications for serum 25OHD measurements to rickets/osteomalacia, older adults with recurrent falls, monitoring of kidney transplant in adults, and surgical treatment of obesity in adults. Our aim here was to note that other indications for serum 25OHD measurements are supported by previous literature and by a number of national and international recommendations, in particular the following: any situation of bone fragility, any chronic renal failure <45 mL/min/1.73m


PubMed | University of Padua, Laboratoire National Of Sante, Molecular Pathology Unit, Queen Elizabeth Hospital and 10 more.
Type: Journal Article | Journal: PloS one | Year: 2016

Since the advent of monoclonal antibodies against epidermal growth factor receptor (EGFR) in colorectal cancer therapy, the determination of RAS mutational status is needed for therapeutic decision-making. Most prevalent in colorectal cancer are KRAS exon 2 mutations (40% prevalence); lower prevalence is observed for KRAS exon 3 and 4 mutations (6%) and NRAS exon 2, 3, and 4 mutations (5%). The Idylla KRAS Mutation Test on the molecular diagnostics Idylla platform is a simple (<2 minutes hands-on time), highly reliable, and rapid (approximately 2 hours turnaround time) in vitro diagnostic sample-to-result solution. This test enables qualitative detection of 21 mutations in codons 12, 13, 59, 61, 117, and 146 of the KRAS oncogene being clinically relevant according to the latest clinical guidelines. Here, the performance of the Idylla KRAS Mutation Assay, for Research Use Only, was assessed on archived formalin-fixed paraffin-embedded (FFPE) tissue sections by comparing its results with the results previously obtained by routine reference approaches for KRAS genotyping. In case of discordance, samples were assessed further by additional methods. Among the 374 colorectal cancer FFPE samples tested, the overall concordance between the Idylla KRAS Mutation Assay and the confirmed reference routine test results was found to be 98.9%. The Idylla KRAS Mutation Assay enabled detection of 5 additional KRAS-mutated samples not detected previously with reference methods. As conclusion the Idylla KRAS Mutation Test can be applied as routine tool in any clinical setting, without needing molecular infrastructure or expertise, to guide the personalized treatment of colorectal cancer patients.


PubMed | Center Georges Francois Leclerc, CERMEP Imagerie du Vivant, University of Strasbourg, Center Leon Berard and 5 more.
Type: Journal Article | Journal: European radiology | Year: 2016

To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation.Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n=13) and control group (n=12). The time of last MR acquisition was tThe fraction of hypoperfused tumor volume (F_hPIterative analysis of F_hP Related rCBV biomarkers from DSC were assessed to anticipate GBM progression. Biomarkers were assessed through their patterns of variation during the follow-up. The fraction of hypoperfused tumour volume (F_hP


Conroy T.,Institut Universitaire de France | Galais M.-P.,Center Francois Baclesse | Raoul J.-L.,Center Eugene Marquis | Bouche O.,Center Hospitalier University Robert Debre | And 13 more authors.
The Lancet Oncology | Year: 2014

Background: Definitive chemoradiotherapy is a curative treatment option for oesophageal carcinoma, especially in patients unsuitable for surgery. The PRODIGE5/ACCORD17 trial aimed to assess the efficacy and safety of the FOLFOX treatment regimen (fluorouracil plus leucovorin and oxaliplatin) versus fluorouracil and cisplatin as part of chemoradiotherapy in patients with localised oesophageal cancer. Methods: We did a multicentre, randomised, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 24 centres in France between Oct 15, 2004, and Aug 25, 2011. Eligible participants had confirmed stage I-IVA oesophageal carcinoma (adenocarcinoma, squamous-cell, or adenosquamous), Eastern Cooperative Oncology Group (ECOG) status 0-2, sufficient caloric intake, adequate haematological, renal, and hepatic function, and had been selected to receive definitive chemoradiotherapy. Patients were randomly assigned (1:1) to receive either six cycles (three concomitant to radiotherapy) of oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, bolus fluorouracil 400 mg/m2, and infusional fluorouracil 1600 mg/m2 (FOLFOX) over 46 h, or four cycles (two concomitant to radiotherapy) of fluorouracil 1000 mg/m2 per day for 4 days and cisplatin 75 mg/m2 on day 1. Both groups also received 50 Gy radiotherapy in 25 fractions (five fractions per week). Random allocation to treatment groups was done by a central computerised randomisation procedure by minimisation, stratified by centre, histology, weight loss, and ECOG status, and was achieved independently from the study investigators. The primary endpoint was progression-free survival. Data analysis was primarily done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00861094. Findings: 134 participants were randomly allocated to the FOLFOX group and 133 to the fluorouracil and cisplatin group (intention-to-treat population), and 131 patients in the FOLFOX group and 128 in the fluorouracil and cisplatin group actually received the study drugs (safety population). Median follow-up was 25·3 months (IQR 15·9-36·4). Median progression-free survival was 9·7 months (95% CI 8·1-14·5) in the FOLFOX group and 9·4 months (8·1-10·6) in the fluorouracil and cisplatin group (HR 0·93, 95% CI 0·70-1·24; p=0·64). One toxic death occurred in the FOLFOX group and six in the fluorouracil-cisplatin group (p=0·066). No significant differences were recorded in the rates of most frequent grade 3 or 4 adverse events between the treatment groups. Of all-grade adverse events that occurred in 5% or more of patients, paraesthesia (61 [47%] events in 131 patients in the FOLFOX group vs three [2%] in 128 patients in the cisplatin-fluorouracil group, p<0·0001), sensory neuropathy (24 [18%] vs one [1%], p<0·0001), increases in aspartate aminotransferase concentrations (14 [11%] vs two [2%], p=0·002), and increases in alanine aminotransferase concentrations (11 [8%] vs two [2%], p=0·012) were more common in the FOLFOX group, whereas serum creatinine increases (four [3%] vs 15 [12%], p=0·007), mucositis (35 [27%] vs 41 [32%], p=0·011), and alopecia (two [2%] vs 12 [9%], p=0·005) were more common in the fluorouracil and cisplatin group. Interpretation: Although chemoradiotherapy with FOLFOX did not increase progression-free survival compared with chemoradiotherapy with fluorouracil and cisplatin, FOLFOX might be a more convenient option for patients with localised oesophageal cancer unsuitable for surgery. Funding: UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer. © 2014 Elsevier Ltd.


PubMed | Center Georges Francois Leclerc, University of Strasbourg, Center Leon Berard, The Christie NHS Foundation Trust and 3 more.
Type: Journal Article | Journal: Journal of neuro-oncology | Year: 2016

To assess the value of T2* dynamic-susceptibility contrast MRI (DSC-MRI) and diffusion-weighted imaging (DWI) to predict the glioblastoma relapse sites after chemoradiation. From a cohort of 44 patients, primarily treated with radiotherapy (60Gy) and concomitant temozolomide for glioblastoma, who were included in the reference arm of a prospective clinical trial (NCT01507506), 15 patients relapsed and their imaging data were analyzed. All patients underwent anatomical MRI, DSC-MRI and DWI before radiotherapy and every 2 months thereafter until relapse. Voxels within the sites of relapse were correlated with their perfusion and/or diffusion abnormality (PDA) pretreatment status after rigid co-registration. The relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were used as biomarkers. Several PDA areas were thresholded: hyperperfused voxels using a 1.75 fixed rCBV threshold (HP

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