Center Hospitalier Regional University

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Kanoun S.,Center Georges Francois Leclerc | Kanoun S.,University of Burgundy | Kanoun S.,Center Hospitalier Regional University | Walker P.,University of Burgundy | And 17 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2017

Purpose To compare the diagnostic performance of 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT), multiparametric prostate magnetic resonance imaging (mpMRI), and a combination of both techniques for the detection of local recurrence of prostate cancer initially treated by radiation therapy. Methods and Materials This was a retrospective, single-institution study of 32 patients with suspected prostate cancer recurrence who underwent both FCH-PET/CT and 3T mpMRI within 3 months of one another for the detection of recurrence. All included patients had to be cleared for metastatic recurrence. The reference procedure was systematic 3-dimensional (3D)-transperineal prostate biopsy for the final assessment of local recurrence. Both imaging modalities were analyzed by 2 experienced readers blinded to clinical data. The analysis was made per-patient and per-segment using a 4-segment model. Results The median prostate-specific antigen value at the time of imaging was 2.92 ng/mL. The mean prostate-specific antigen doubling time was 14 months. Of the 32 patients, 31 had a positive 3D-transperineal mapping biopsy for a local relapse. On a patient-based analysis, the detection rate was 71% (22 of 31) for mpMRI and 74% (23 of 31) for FCH-PET/CT. On a segment-based analysis, the sensitivity and specificity were, respectively, 32% and 87% for mpMRI, 34% and 87% for FCH-PET/CT, and 43% and 83% for the combined analysis of both techniques. Accuracy was 64%, 65%, and 66%, respectively. The interobserver agreement was κ = 0.92 for FCH-PET/CT and κ = 0.74 for mpMRI. Conclusions Both mpMRI and FCH-PET/CT show limited sensitivity but good specificity for the detection of local cancer recurrence after radiation therapy, when compared with 3D-transperineal mapping biopsy. Prostate biopsy still seems to be mandatory to diagnose local relapse and select patients who could benefit from local salvage therapy. © 2016 Elsevier Inc.


Damaj G.,Center Hospitalier University Sud | Duhamel A.,Center Hospitalier Regional University | Robin M.,University Paris Diderot | Beguin Y.,University of Liège | And 26 more authors.
Journal of Clinical Oncology | Year: 2012

Purpose: To investigate the impact of prior-to-transplantation azacitidine (AZA) on patient outcome after allogeneic stem-cell transplantation (alloSCT) for myelodysplastic syndrome (MDS). Patients and Methods: Of the 265 consecutive patients who underwent alloSCT for MDS between October 2005 and December 2009, 163 had received cytoreductive treatment prior to transplantation, including induction chemotherapy (ICT) alone (ICT group; n = 98), AZA alone (AZA group; n = 48), or AZA preceded or followed by ICT (AZA-ICT group; n = 17). At diagnosis, 126 patients (77%) had an excess of marrow blasts, and 95 patients (58%) had intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). Progression to more advanced disease before alloSCT was recorded in 67 patients. Donors were sibling (n = 75) or HLA-matched unrelated (10/10; n = 88). They received blood (n = 142) or marrow (n = 21) grafts following either myeloablative (n = 33) or reduced intensity (n = 130) conditioning. Results: With a median follow-up of 38.7 months, 3-year outcomes in the AZA, ICT, and AZA-ICT groups were 55%, 48%, and 32% (P = .07) for overall survival (OS); 42%, 44%, and 29% (P = .14) for event-free survival (EFS); 40%, 37%, and 36% (P = .86) for relapse; and 19%, 20%, and 35% (P = .24) for nonrelapse mortality (NRM), respectively. Multivariate analysis confirmed the absence of statistical differences between the AZA and the ICT groups in terms of OS, EFS, relapse, and NRM. Conclusion: With the goal of downstaging underlying disease before alloSCT, AZA alone led to outcomes similar to those for standard ICT. © 2012 by American Society of Clinical Oncology.


Yakoubi R.,Lille 2 University of Health and Law | Yakoubi R.,Cleveland Clinic | Monga M.,Cleveland Clinic | Villers A.,Center Hospitalier Regional University | Koenig P.,Center Hospitalier Regional University
Journal of Urology | Year: 2011

Purpose: We evaluated the efficacy of α-blockers to improve ureteral stent related morbidity and quality of life. Materials and Methods: We performed a search of MEDLINE®, Embase™ and The Cochrane Library plus a hand search of conference proceedings from January 2000 to October 2010 to identify randomized, controlled trials comparing treatment for ureteral stent symptoms with α-blockers. Two reviewers independently screened studies and extracted data. Trial methodological quality was assessed by The Cochrane Collaboration quality assessment tool. Placebo randomized, controlled trials with the ureteral stent symptom questionnaire as the outcome were eligible for meta-analysis. Meta-analysis was done using the mean difference to determine the aggregate effect size. Results: A total of 12 randomized, controlled trials including 2 α-blockers in a total of 946 patients were eligible, including 4 (33%) presented only as an abstract at a urological meeting and 4 (33%) eligible for meta-analysis. Meta-analysis using a random effects model showed that α-blockers were associated with a significant decrease in urinary symptoms (MD -6.76, 95% CI -11.52 to -2.00, p = 0.005), a significant decrease in pain (MD -3.55, 95% CI -5.51 to -1.60, p = 0.0004) and significant improvement in general health (MD -1.90, 95% CI -3.05 to -0.75, p = 0.001). However, they were not associated with a benefit in work (MD 2.41, 95% CI -1.62 to 6.44, p = 0.24) or sexual matters (MD 0.20, 95% CI -1.06 to 1.45, p = 0.33). Eight studies were not included in the meta-analysis, of which 7 showed a significant clinical decrease in urinary symptoms and pain. Conclusions: Existing evidence from randomized, controlled trials shows that α-blockers are associated with improvement in ureteral stent symptoms and supports their use in routine clinical practice. © 2011 American Urological Association Education and Research, Inc.


Kanoun S.,Center Georges Francois Leclerc | Kanoun S.,French National Center for Scientific Research | Kanoun S.,Center Hospitalier Regional University | Tal I.,Beth Israel Deaconess Medical Center | And 14 more authors.
PLoS ONE | Year: 2015

Aim To investigate the respective influence of software tool and total metabolic tumor volume (TMTV0) calculation method on prognostic stratification of baseline 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET) in newly diagnosed Hodgkin lymphoma (HL). Methods 59 patients with newly diagnosed HL were retrospectively included. [18F]FDG-PET was performed before any treatment. Four sets of TMTV0 were calculated with Beth Israel (BI) software: based on an absolute threshold selecting voxel with standardized uptake value (SUV) >2.5 (TMTV02.5), applying a per-lesion threshold of 41% of the SUVmax (TMTV041) and using a per-patient adapted threshold based on SUVmax of the liver (>125% and >140% of SUVmax of the liver background; TMTV0125 and TMTV0140). TMTV041 was also determined with commercial software for comparison of software tools. ROC curves were used to determine the optimal threshold for each TMTV0 to predict treatment failure. Results Median follow-up was 39 months. There was an excellent correlation between TMTV041 determined with BI and with the commercial software (r = 0.96, p<0.0001). The median TMTV0 value for TMTV041, TMTV02.5, TMTV0125 and TMTV0140 were respectively 160 (used as reference), 210 ([28;154] p = 0.005), 183 ([-4;114] p = 0.06) and 143ml ([-58;64] p = 0.9). The respective optimal TMTV0 threshold and area under curve (AUC) for prediction of progression free survival (PFS) were respectively: 313ml and 0.70, 432ml and 0.68, 450ml and 0.68, 330ml and 0.68. There was no significant difference between ROC curves. High TMTV0 value was predictive of poor PFS in all methodologies: 4-years PFS was 83% vs 42% (p = 0.006) for TMTV02.5, 83% vs 41% (p = 0.003) for TMTV041, 85% vs 40% (p<0.001) for TMTV0125 and 83% vs 42% (p = 0.004) for TMTV0140. Conclusion In newly diagnosed HL, baseline metabolic tumor volume values were significantly influenced by the choice of the method used for determination of volume. However, no significant differences were found in term of prognosis. © Copyright: 2015 Kanoun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


PubMed | Beth Israel Deaconess Medical Center, Center Georges Francois Leclerc, French National Center for Scientific Research, University of Burgundy and Center Hospitalier Regional University
Type: Clinical Trial | Journal: PloS one | Year: 2015

To investigate the respective influence of software tool and total metabolic tumor volume (TMTV0) calculation method on prognostic stratification of baseline 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET) in newly diagnosed Hodgkin lymphoma (HL).59 patients with newly diagnosed HL were retrospectively included. [18F]FDG-PET was performed before any treatment. Four sets of TMTV0 were calculated with Beth Israel (BI) software: based on an absolute threshold selecting voxel with standardized uptake value (SUV) >2.5 (TMTV02.5), applying a per-lesion threshold of 41% of the SUV max (TMTV041) and using a per-patient adapted threshold based on SUV max of the liver (>125% and >140% of SUV max of the liver background; TMTV0125 and TMTV0140). TMTV041 was also determined with commercial software for comparison of software tools. ROC curves were used to determine the optimal threshold for each TMTV0 to predict treatment failure.Median follow-up was 39 months. There was an excellent correlation between TMTV041 determined with BI and with the commercial software (r = 0.96, p<0.0001). The median TMTV0 value for TMTV041, TMTV02.5, TMTV0125 and TMTV0140 were respectively 160 (used as reference), 210 ([28;154] p = 0.005), 183 ([-4;114] p = 0.06) and 143 ml ([-58;64] p = 0.9). The respective optimal TMTV0 threshold and area under curve (AUC) for prediction of progression free survival (PFS) were respectively: 313 ml and 0.70, 432 ml and 0.68, 450 ml and 0.68, 330 ml and 0.68. There was no significant difference between ROC curves. High TMTV0 value was predictive of poor PFS in all methodologies: 4-years PFS was 83% vs 42% (p = 0.006) for TMTV02.5, 83% vs 41% (p = 0.003) for TMTV041, 85% vs 40% (p<0.001) for TMTV0125 and 83% vs 42% (p = 0.004) for TMTV0140.In newly diagnosed HL, baseline metabolic tumor volume values were significantly influenced by the choice of the method used for determination of volume. However, no significant differences were found in term of prognosis.


Berthet L.,Center Georges Francois Leclerc | Cochet A.,Center Georges Francois Leclerc | Cochet A.,French National Center for Scientific Research | Kanoun S.,Center Georges Francois Leclerc | And 9 more authors.
Journal of Nuclear Medicine | Year: 2013

In newly diagnosed diffuse large B-cell lymphoma (DLBCL), the sensitivity of bone marrow biopsy (BMB) for the detection of bone marrow involvement (BMI) can be low because of sampling error if the BMI is focal and not diffuse. Although 18F-FDG PET/CT is now recommended for initial staging of DLBCL, its role regarding BMI is not well defined. This study evaluated whether 18F-FDG PET/CT, in comparison with BMB, is useful for the detection of BMI and predictive of outcome. Methods: From the 142 patients who were referred to our institution for newly diagnosed DLBCL from June 2006 to October 2011, 133 were retrospectively enrolled in our study. All patients underwent whole-body 18F-FDG PET/CT and a BMB from the iliac crest before any treatment. 18F-FDG PET/CT was considered positive for BMI in cases of uni- or multifocal bone marrow 18FFDG uptake that could not be explained by benign findings on the underlying CT image or history. A final diagnosis of BMI was considered if the BMB was positive or if the positive 18F-FDG PET/CT was confirmed by guided biopsy or targeted MR imaging or in cases of disappearance of focal bone marrow uptake concomitant with the disappearance of uptake in other lymphoma lesions on 18F-FDG PET/CT monitoring. Progression-free survival and overall survival were analyzed using the Cox proportional hazards regression model. Results: Thirty-three patients were considered to have BMI. Of these, 8 were positive according to the BMB and 32 were positive according to 18F-FDG PET/CT. 18F-FDG PET/CT was more sensitive (94% vs. 24%; P < 0.001), showed a higher negative predictive value (98% vs. 80%), and was more accurate (98% vs. 81%) than BMB. Median follow-up was 24 mo (range, 1-67 mo). Twentynine patients (22%) experienced recurrence or disease progression during follow-up, and 20 patients died (15%). In multivariate analysis, only the International Prognostic Index and the 18F-FDG PET/CT bone marrow status were independent predictors of progressionfree survival (P = 0.005 and 0.02, respectively), whereas only the International Prognostic Index remained an independent predictor of overall survival (P = 0.004). Conclusion: Assessment of BMI with 18F-FDG PET/CT provides better diagnostic performance and prognostic stratification in newly diagnosed DLBCL than does BMB. COPYRIGHT © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.


Fichou Y.,French Institute of Health and Medical Research | Gehannin P.,French Institute of Health and Medical Research | Corre M.,French Institute of Health and Medical Research | Le Guern A.,French Institute of Health and Medical Research | And 9 more authors.
Transfusion | Year: 2015

BACKGROUND Among more than 300 mutated alleles identified so far within the RHD gene, almost 40 are assumed to alter cellular splicing and therefore may have a direct effect on Rh phenotype both at the quantitative and at the qualitative levels. Functional data are, however, mostly unavailable to assess the direct involvement of splicing defect in the underlying physiology. STUDY DESIGN AND METHODS We generated plasmid constructs to carry out an exhaustive investigation of 38 RHD variants located within or in the vicinity of exon-intron junctions by a minigene splicing assay, further characterized the transcript structures by sequencing, and identified cryptic sites activated by the genetic defect. Bioinformatics predictions were carried out in parallel and compared with the functional data. RESULTS For the first time we demonstrate that a product including the full-length Exon 9 is transcribed in the presence of the c.1227G>A substitution frequently carried by Asians with DEL phenotype and confirmed that splicing is altered in the RHD∗weak D Type 2 allele, a rare variant most commonly found in Caucasians. CONCLUSION Overall we 1) show significant correlation between functional analyses, bioinformatics predictions, and phenotypes, when available, especially for variants in close proximity of the consensus splice sites; 2) classify the variations as splicing or nonsplicing variants; and 3) provide functional data to further improve bioinformatics splicing tools. Conversely assessment of seven silent exonic variants was mainly inconclusive. © 2015 AABB.


Selton-Suty C.,University of Lorraine | Celard M.,Center National Of Reference Des Staphylocoques | Le Moing V.,Center Hospitalier Regional University | Le Moing V.,CIRAD - Agricultural Research for Development | And 15 more authors.
Clinical Infectious Diseases | Year: 2012

Background. Observational studies showed that the profile of infective endocarditis (IE) significantly changed over the past decades. However, most studies involved referral centers. We conducted a population-based study to control for this referral bias. The objective was to update the description of characteristics of IE in France and to compare the profile of community-acquired versus healthcare-associated IE. Methods. A prospective population-based observational study conducted in all medical facilities from 7 French regions (32% of French individuals aged ≥18 years) identified 497 adults with Duke-Li-definite IE who were first admitted to the hospital in 2008. Main measures included age-standardized and sex-standardized incidence of IE and multivariate Cox regression analysis for risk factors of in-hospital death. Results. The age-standardized and sex-standardized annual incidence of IE was 33.8 (95% confidence interval [CI], 30.8-36.9) cases per million inhabitants. The incidence was highest in men aged 75-79 years. A majority of patients had no previously known heart disease. Staphylococci were the most common causal agents, accounting for 36.2% of cases (Staphylococcus aureus, 26.6%; coagulase-negative staphylococci, 9.7%). Healthcare-associated IE represented 26.7% of all cases and exhibited a clinical pattern significantly different from that of community-acquired IE. S. aureus as the causal agent of IE was the most important factor associated with in-hospital death in community-acquired IE (hazard ratio [HR], 2.82 [95% CI, 1.72-4.61]) and the single factor in healthcare-associated IE (HR, 2.54 [95% CI, 1.33-4.85]). Conclusions. S. aureus became both the leading cause and the most important prognostic factor of IE, and healthcare-associated IE appeared as a major subgroup of the disease. © 2012 The Author.

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