Casasnovas R.-O.,Hematologie Clinique |
Meignan M.,Hopital Henri Mondor |
Berriolo-Riedinger A.,Center Georges Francois Leclerc |
Bardet S.,Center Francois Baclesse |
And 9 more authors.
Blood | Year: 2011
The prognostic value of interim positron emission tomography (PET) interpreted according to visual criteria is a matter of debate in diffuse large B-cell lymphoma (DLBCL). Maximal standardized uptake value reduction (ΔSUVmax) may better predict outcome. To compare the prognostic value of both methods, we analyzed PET done at baseline (PET0) and after 2 (PET2) and 4 (PET4) cycles in 85 patients with high-risk DLBCL enrolled on a prospective multicenter trial. All images were centrally reviewed and interpreted visually according to the International Harmonization Project criteria and by computing ΔSUVmax between PET0 and PET2 (ΔSUVmaxPET0-2) or PET4 (ΔSUVmaxPET0-4). Optimal cutoff to predict progression or death was 66% for ΔSUVmaxPET0-2 and 70% for ΔSUVmaxPET0-4. Outcomes did not differ significantly whether PET2 and PET4 were visually positive or negative. Inversely, ΔSUVmaxPET0-2 analysis (> 66% vs ≤ 66%) identified patients with significantly different 2-year progression-free survival (77% vs 57%; P = .0282) and overall survival (93% vs 60%; P < .0001). ΔSUVmaxPET0-4 analysis (> 70% vs ≤ 70%) seemed even more predictive for 2-year progression-free survival (83 vs 40%; P < .0001) and overall survival (94% vs 50%; P < .0001). ΔSUVmax analysis of sequential interim PET is feasible for highrisk DLBCL and better predicts outcome than visual analysis. The trial was registered at http://clinicaltrials.gov as NCT00498043. © 2011 by The American Society of Hematology.
French Institute of Health, Medical Research, Institute Gustave Roussy, Assistance Publique Hopitaux De Paris, Center Henri Becquerel, University of Paris Descartes, University Pierre, Marie Curie and University Paris - Sud | Date: 2016-06-08
The present invention concerns an in vitro method for diagnosing a myeloid tumour or a lymphoid tumour in a subject, which comprises the step of analyzing a biological sample from said subject by (i) detecting the presence of a mutation in the Ten Eleven Translocation protein family member 2 gene (TET2) coding for the polypeptide having the sequence SEQ ID NO: 2, and/or (ii) analyzing the expression of the TET2 gene; wherein the detection of such a TET2 mutation, of the absence of expression of TET2 or of the expression of a truncated TET2 is indicative of a subject developing or predisposed to develop a myeloid tumour or a lymphoid tumour.
Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): An open-label, randomised phase 3 trial
von Minckwitz G.,Neu Isenburg and University Womens Hospital |
Puglisi F.,University of Udine |
Cortes J.,University of Barcelona |
Vrdoljak E.,University of Split |
And 13 more authors.
The Lancet Oncology | Year: 2014
Background: Combining bevacizumab with first-line or second-line chemotherapy improves progression-free survival in HER2-negative locally recurrent or metastatic breast cancer. We assessed the efficacy and safety of further bevacizumab therapy in patients with locally recurrent or metastatic breast cancer whose disease had progressed after treatment with bevacizumab plus chemotherapy. Methods: In this open-label, randomised, phase 3 trial, we recruited patients who had HER2-negative locally recurrent or metastatic breast cancer that had progressed after receiving 12 weeks or more of first-line bevacizumab plus chemotherapy from 118 centres in 12 countries. Patients were randomly assigned (1:1) by use of a central interactive voice response system using a block randomisation schedule (block size four) stratified by hormone receptor status, first-line progression-free survival, selected chemotherapy, and lactate dehydrogenase concentration, to receive second-line single-agent chemotherapy either alone or with bevacizumab (15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks). Second-line therapy was continued until disease progression, unacceptable toxicity, or consent withdrawal. At progression, patients randomly assigned to chemotherapy alone received third-line chemotherapy without bevacizumab; those randomly assigned to bevacizumab continued bevacizumab with third-line chemotherapy. The primary endpoint was progression-free survival from randomisation to second-line progression or death in the intention-to-treat population. This trial is ongoing, and registered with ClinicalTrials.gov, number NCT01250379. Findings: Between Feb 17, 2011, and April 3, 2013, 494 patients were randomly assigned to treatment (247 in each group). The median duration of follow-up at the time of this prespecified primary progression-free survival analysis was 15·9 months (IQR 9·1-21·7) in the chemotherapy-alone group and 16·1 months (10·6-22·7) in the combination group. Progression-free survival was significantly longer for those patients treated with bevacizumab plus chemotherapy than for those with chemotherapy alone (median: 6·3 months [95% CI 5·4-7·2] vs 4·2 months [3·9-4·7], respectively, stratified hazard ratio [HR] 0·75 [95% CI 0·61-0·93], two-sided stratified log-rank p=0·0068). The most common grade 3 or more adverse events were hypertension (33 [13%] of 245 patients receiving bevacizumab plus chemotherapy vs 17 [7%] of 238 patients receiving chemotherapy alone), neutropenia (29 [12%] vs 20 [8%]), and hand-foot syndrome (27 [11%] vs 25 [11%]). Grade 3 proteinuria occurred in 17 (7%) of 245 patients receiving combination therapy and one (<1%) of 238 patients receiving chemotherapy alone. Serious adverse events were reported in 61 (25%) of 245 patients receiving bevacizumab plus chemotherapy versus 44 (18%) of 238 patients receiving chemotherapy alone. Interpretation: These results suggest that continued VEGF inhibition with further bevacizumab is a valid treatment option for patients with locally recurrent or metastatic HER2-negative breast cancer whose disease was stabilised or responded to first-line bevacizumab with chemotherapy. Funding: F Hoffmann-La Roche. © 2014 Elsevier Ltd.
Delarue R.,Service dHematologie |
Haioun C.,Service dHematologie |
Ribrag V.,Institute Gustave Roussy |
Brice P.,Service dHematologie |
And 8 more authors.
Blood | Year: 2013
Treatment of mantle cell lymphoma (MCL) in younger patients remains a challenge. We report results of a phase 2 trial using cytarabine and rituximab as induction regimen before autologous stem cell transplantation. Patients younger than 66 years with stage 3 or 4 MCL were included. Treatment consisted of 3 courses of CHOP21 with rituximab at the third one and 3 of R-DHAP. Responding patients were eligible for autologous stem cell transplantation with TAM6 or BEAM. Sixty patients were included. Median age was 57 years. Characteristics of patients were: BM involvement 85%, leukemic disease 48%, gastrointestinal involvement 52%, Performance Status > 16%, lactate dehydrogenase > 1N 38%, Mantle Cell Lymphoma International Prognostic Index (low 55%, intermediate 38%, high 13%). The overall response rate was 93% after (R)-CHOP and 95% after R-DHAP. Although uncommon after (R)-CHOP (12%), 57% of patients were in complete response after R-DHAP. With median follow-up of 67 months, median event-free survival is 83 months, and median overall survival is not reached. Five-year overall survival is 75%. Comparison with a previous study without rituximab shows improvement of outcome (median event-free survival, 51 vs 83 months). No toxic death or unexpected toxicities were observed. This study confirms that induction with rituximab and cytarabine-based regimens is safe and effective in MCL patients. This regimen is currently compared with R-CHOP21 induction in a multicentric European protocol. © 2013 by The American Society of Hematology.
Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: A study by the Groupe d'Etudes des Lymphomes de l'Adulte
Coiffier B.,University of Lyon |
Thieblemont C.,Hopital Saint Louis |
Van Den Neste E.,Catholic University of Louvain |
Lepeu G.,Center Hospitalier General Henri Duffaut |
And 10 more authors.
Blood | Year: 2010
We report the outcome of patients included in the LNH-98.5 study, which compared cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to rituximab plus CHOP (R-CHOP) therapy in 399 patients with diffuse large B-cell lymphoma (DLBCL) aged 60 to 80 years, with a median follow-up time of 10 years. Clinical event information was updated in all living patients (with the exception of 3 patients) in 2009. Survival end points were improved in patients treated with R-CHOP: the 10-year progression-free survival was 36.5%, compared with 20% with CHOP alone, and the 10-year overall survival was 43.5% compared with 27.6%. The same risk of death due to other diseases, secondary cancers, and late relapses was observed in both study arms. Relapses occurring after 5 years represented 7% of all disease progressions. The results from the 10-year analysis confirm the benefits and tolerability of the addition of rituximab to CHOP. Our findings underscore the need to treat elderly patients as young patients, with the use of curative chemotherapy. © 2010 by The American Society of Hematology.
University of Rouen and Center Henri Becquerel | Date: 2014-09-11
A method for diagnosing a cancer in a subject, notably with the aim of finding fusion transcripts, includes an RT-MLPA step carried out on a biological sample obtained from the subject using the probes SEQ ID NO: 1 to 25, 30, 31 and 113 to 120, and/or with at least the probes SEQ ID NO: 374 to 405, and/or with at least the probes SEQ ID NO: 524 to 559, each of the probes being fused, at one end at least, with a priming sequence.
French Institute of Health, Medical Research, University of Rouen and Center Henri Becquerel | Date: 2015-03-10
The present invention relates to a method for classifying a diffuse large B-cell lymphoma (DLBCL) of a subject into a GCB-DLBCL or into a ABC-DLBCL comprising the step of determining the expression level of 10 genes in a tumor tissue sample obtained from the subject by performing a Reverse Transcriptase Multiplex Ligation dependent Probe Amplification (RT-MLPA) assay wherein the 10 genes are NEK6, IRF4, IGHM, LMO2, FOXP1, TNFRSF9, BCL6, TNFRSF13B, CCND2 and MYBL1.
Joyard Y.,INSA Rouen |
Papamicael C.,INSA Rouen |
Bohn P.,Center Henri Becquerel |
Bischoff L.,INSA Rouen
Organic Letters | Year: 2013
Starting from alkyl halides or Michael acceptors, thioacetates were prepared in situ and further treated with t-BuOCl, affording the corresponding sulfonyl chlorides which were trapped with nucleophiles such as water, alcohol, or amines. The three steps can be achieved in a one-pot procedure. Oxidative deprotection also proved to be efficient with S-trityl and S-tert-butyl groups, making it a convenient route toward cysteic acid derivatives. © 2013 American Chemical Society.
Joly F.,Center Francois Baclesse |
Joly F.,Caen University Hospital Center |
Rigal O.,Center Henri Becquerel |
Noal S.,Center Francois Baclesse |
Giffard B.,University of Caen Lower Normandy
Psycho-Oncology | Year: 2011
Objectives: The aim of this review is to stress the importance of cognitive dysfunction in cancer survivors, and to discuss the way of assessing and managing these troubles in clinical practice. Method: Original studies and reviews reporting the effect of cancer and chemotherapy on cognition and published since January 2000 were selected from the Medline® database using 'cognition' or 'cognitive function' and 'cancer' as subject headings. Results: Main reports concerned women with advanced breast cancer or children with hematological or brain cancers. Overall, chemotherapy was found to be associated with subtle and transient cognitive dysfunctions, which were detectable only with neuropsychological testing and affected most particularly memory, concentration and speed of information processing. Some factors associated with the patient, like depression, may favor cognitive impairment, while the role of others, like age or educational level, remains to be defined. Screening of patients at risk remains limited due to the lack of standardized neuropsychological tests in clinical oncology practice. Few studies have addressed the benefits of interventional strategies but methylphenidate, modafinil and erythropoietin, as well as rehabilitation in children, have shown encouraging results. Formal studies assessing the value of a multidisciplinary approach to detect and manage cognitive impairment must be recommended. Conclusion: Cognitive dysfunction induced by cancer or the treatment represents a real challenge in clinical practice. Based on limited published data, few clinical recommendations can be made regarding prevention, evaluation and management of this trouble. Longitudinal studies must be conducted to evaluate its real impact on quality of life. Copyright © 2011 John Wiley & Sons, Ltd.
Dekker T.J.A.,Leiden University |
Van De Velde C.J.H.,Leiden University |
Van Pelt G.W.,Leiden University |
Kroep J.R.,Leiden University |
And 4 more authors.
Breast Cancer Research and Treatment | Year: 2013
The tumor-stroma ratio has previously been shown to be prognostic for patients with invasive breast cancer. We present a validation study to assess the prognostic significance in lymph node-negative, premenopausal patients from the perioperative chemotherapy trial (POP trial, 10854) conducted by the European Organization for Research and Treatment of Cancer. The POP trial assessed the efficacy of one course of perioperative chemotherapy (consisting of fluorouracil, doxorubicin, and cyclophosphamide). Hematoxylin and eosin (H&E) stained sections were retrieved from a subset of premenopausal, node-negative patients from this trial and were scored for the percentage of intra-tumoral stroma. The tumor-stroma ratio was associated with disease-free survival in univariate and multivariate analysis. Tumors with a high tumor-stroma ratio had an increased hazard of 1.853 for disease relapse (95 %CI 1.327-2.585, P < 0.001) independent of other parameters. Combining other parameters with the tumor-stroma ratio improved risk stratification. For triple-negative tumors, the tumor-stroma ratio was associated with an increased hazard for disease relapse, independent of other parameters (HR 2.711, 95 %CI 1.111-6.614, P = 0.028). The tumor-stroma ratio was also independently associated with locoregional recurrence even in breast cancer patients ≤40 years of age (HR 2.201, 95 %CI 1.038-4.669, P = 0.040). This study validates the prognostic value of the tumor-stroma ratio. This parameter can be easily assessed on HE slides and can be implemented next to pathological staging reports to determine patient prognosis. © 2013 Springer Science+Business Media New York.