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Saint-Sauveur-en-Rue, France

Coiffier B.,University of Lyon | Van Den Neste E.,Catholic University of Louvain | Lepeu G.,Center Hospitalier General Henri Duffaut | Plantier I.,Hopital V Provo | And 7 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.

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.

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.

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.

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