21 results on '"Le Cesne, A."'
Search Results
2. Imatinib in combination with phosphoinositol kinase inhibitor buparlisib in patients with gastrointestinal stromal tumour who failed prior therapy with imatinib and sunitinib: a Phase 1b, multicentre study
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Gelderblom, Hans, Jones, Robin L., George, Suzanne, Valverde Morales, Claudia, Benson, Charlotte, Jean-Yves Blay, Renouf, Daniel J., Doi, Toshihiko, Le Cesne, Axel, Leahy, Michael, Hertle, Sabine, Aimone, Paola, Brandt, Ulrike, and Schӧffski, Patrick
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- 2020
- Full Text
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3. Expression and role of TYRO3 and AXL as potential therapeutical targets in leiomyosarcoma
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Carmela Dantas-Barbosa, Isabelle Ray-Coquard, Tom Lesluyes, Pierre Meeus, Jean-Yves Blay, Antoine Italiano, Pierre Saintigny, Marie-Pierre Sunyach, Hiba El Sayadi, M. Jean-Denis, Mehdi Brahmi, Sylvie Bonvalot, Laurent Alberti, Maud Toulmonde, Axel Le Cesne, Jean-Michel Coindre, Frédéric Chibon, Françoise Ducimetière, Isabelle Treilleux, François Le Loarer, Olivier Mir, Olivia Bally, and Dominique Ranchère
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Leiomyosarcoma ,Male ,0301 basic medicine ,Cancer Research ,Pathology ,sarcoma ,Pyridines ,Gene Expression ,Apoptosis ,Protein S ,chemistry.chemical_compound ,tyrosine kinase inhibitor ,0302 clinical medicine ,GAS6 ,Medicine ,Anilides ,Phosphorylation ,Tumor Stem Cell Assay ,Aged, 80 and over ,Gene knockdown ,Blood Proteins ,Middle Aged ,3. Good health ,G2 Phase Cell Cycle Checkpoints ,Oncology ,030220 oncology & carcinogenesis ,Quinolines ,Intercellular Signaling Peptides and Proteins ,Female ,Sarcoma ,TYRO3 ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Primary Cell Culture ,TAM receptors ,Disease-Free Survival ,Young Adult ,03 medical and health sciences ,Crizotinib ,Cell Line, Tumor ,Proto-Oncogene Proteins ,Humans ,Gene Silencing ,Aged ,Cell Proliferation ,Cell Nucleus ,Oncogene ,business.industry ,Receptor Protein-Tyrosine Kinases ,AXL ,Foretinib ,medicine.disease ,Axl Receptor Tyrosine Kinase ,030104 developmental biology ,chemistry ,Cancer research ,Pyrazoles ,Translational Therapeutics ,business - Abstract
Background: Leiomyosarcoma (LMS) are 15% of adult sarcomas and remain seldom curable in metastatic phase. The TAM receptors and their ligands are overexpressed or activated in multiple malignancies, including LMS. Methods: The TAM receptor and ligand expression was evaluated in LMS cell lines and 358 sarcoma samples by either gene expression or immunohistochemistry. TYRO3 and AXL were knocked down. Crizotinib and foretinib were investigated in vitro. Results: High expression of TYRO3 and AXL was detected in LMS cell lines. TYRO3 or AXL gene knockdown reduced cell proliferation/colony formation. Crizotinib and foretinib decreased TYRO3 and AXL phosphorylation, apoptosis, G2/arrest and reduced colony formation. Immunohistochemistry performed in 107 sarcomas showed higher expression of TYRO3 and GAS6 in LMS vs other sarcomas and nuclear TYRO3 only in LMS. Microarray gene expression performed in 251 sarcomas revealed significantly higher expression of TYRO3 and GAS6 in LMS than other sarcomas. Leiomyosarcoma patients with high expression of GAS6 or PROS1 present a significantly worse PFS. Conclusions: Leiomyosarcoma patients, especially those whom develop metastasis, express higher levels of TYRO3 and GAS6. Crizotinib and foretinib showed effective antitumour activity in LMS through TYRO3 and AXL deactivation indicating that clinical trials using TYRO3 and AXL inhibitors are warranted in advanced LMS.
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- 2017
4. Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib
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Stefania Crippa, Javier Martin-Broto, Axel Le Cesne, Claudia Weiss, Sebastian Bauer, Elena Fumagalli, Olivier Bouché, Alessandro Comandone, Jean-Yves Blay, Antoine Adenis, M. Camozzi, Carlo Barone, Xavier Garcia del Muro, Antoine Italiano, Giovanni Grignani, Ramon Castellana, Claudia Valverde, Heikki Joensuu, Antonio López Pousa, University of Helsinki, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Gradenigo Hospital, Hospital Universitario Virgen del Rocío [Sevilla], Medical Genetics Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Candiolo Cancer Institute (IRCCS), Institut Català d'Oncologia-IDIBELL, 08907 L’Hospitalet (Barcelona) and Universitat de, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Vall d'Hebron University Hospital [Barcelona], Hospital de la Santa Creu i Sant Pau, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Bergonié [Bordeaux], UNICANCER, Universität Duisburg-Essen [Essen], Observatoire sociologique du changement (OSC), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Novartis Pharma AG, Novartis Vaccines and Diagnostics [Siena], Novartis Farmacéutica SA, Sarcome, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université de Lille-UNICANCER, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Università cattolica del Sacro Cuore [Milano] (Unicatt), Clinicum, Heikki Joensuu / Principal Investigator, and Department of Oncology
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,MULTICENTER ,Medizin ,Salvage therapy ,RESISTANT ,Quinolones ,gastrointestinal stromal tumour ,0302 clinical medicine ,Clinical endpoint ,FAILURE ,Gastrointestinal Neoplasms ,KIT MUTATIONS ,GiST ,Sunitinib ,Middle Aged ,Prognosis ,3. Good health ,Tolerability ,SAFETY ,030220 oncology & carcinogenesis ,PHASE-II ,Imatinib Mesylate ,Female ,TYROSINE KINASE INHIBITOR ,medicine.drug ,GIST ,Adult ,medicine.medical_specialty ,Gastrointestinal Stromal Tumors ,3122 Cancers ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,SUNITINIB ,03 medical and health sciences ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,MESH: Benzimidazoles/pharmacology ,Biomarkers, Tumor/metabolism ,Drug resistance, Neoplasm/drug therapy ,Adverse effect ,neoplasms ,Protein Kinase Inhibitors ,Aged ,Neoplasm Staging ,Salvage Therapy ,business.industry ,Imatinib ,EFFICACY ,refractory ,030104 developmental biology ,Imatinib mesylate ,imatinib ,Drug Resistance, Neoplasm ,Clinical Study ,Benzimidazoles ,dovitinib ,business ,Follow-Up Studies - Abstract
Background: This multicentre phase II trial (DOVIGIST) evaluated the antitumour activity of dovitinib as second-line treatment of patients with gastrointestinal stromal tumour (GIST) refractory to imatinib or who do not tolerate imatinib. Methods: Patients received oral dovitinib 500 mg day(-1), 5 days on/2 days off, until GIST progression or unacceptable toxicity, with an objective to evaluate efficacy, assessed as the disease control rate (DCR) at 12 weeks. Tumour assessment and response to dovitinib therapy were evaluated by Response Evaluation Criteria In Solid Tumours (RECIST v1.1) and the Choi criteria. Secondary objectives included assessment of progression-free survival (PFS), safety and tolerability, and DCR at the end of treatment. Results: Thirty-eight of the 39 patients enrolled had histologically confirmed GIST. The DCR at 12 weeks was 52.6% (90% confidence interval (CI), 38.2-66.7%) meeting the preset efficacy criterion for the primary end point. The objective response rate (complete response+partial response) was 2.6% (1 of 38; 90% CI, 0.1-11.9%), and 5.3% (n = 2; 90% CI, 0.9-15.7%) at the end of the study. The median PFS was 4.6 months (90% CI, 2.8-7.4 months). Dose interruption was required in 26 patients (66.7%), of which 18 (69.2%) were due to adverse events. The most frequently observed grade 3 adverse events included hypertension (n = 7), fatigue (n = 5), vomiting (n = 4), hypertriglyceridaemia (n = 4), and gamma-glutamyltransferase increase (n = 4). Conclusions: Dovitinib is an active treatment for patients with GIST who are intolerant to imatinib or whose GIST progresses on imatinib.
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- 2017
5. Trabectedin is a feasible treatment for soft tissue sarcoma patients regardless of patient age: a retrospective pooled analysis of five phase II trials
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A. Tanovic, Shanta Chawla, Axel Le Cesne, Federica Grosso, Scott M. Schuetze, Antonio Nieto, George D. Demetri, Ian Judson, Robert G. Maki, Margaret von Mehren, and J.-Y. Blay
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,sarcoma ,Dioxoles ,Neutropenia ,STS ,elderly ,Disease-Free Survival ,Young Adult ,Tetrahydroisoquinolines ,Internal medicine ,older ,medicine ,Humans ,Young adult ,Antineoplastic Agents, Alkylating ,Trabectedin ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Incidence (epidemiology) ,Soft tissue sarcoma ,Age Factors ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Surgery ,Clinical trial ,Treatment Outcome ,age ,Oncology ,trabectedin ,Cohort ,Clinical Study ,Female ,business ,medicine.drug - Abstract
Background: This retrospective pooled analysis assessed the effect of age on the efficacy and safety of trabectedin in young and elderly patients with recurrent advanced soft tissue sarcoma (STS). Methods: Data from 350 adults with STS treated in five phase II trials with trabectedin were divided in the younger (
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- 2013
6. Cytokine and angiogenic factors associated with efficacy and toxicity of pazopanib in advanced soft-tissue sarcoma: an EORTC-STBSG study
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Peter Hohenberger, J.-Y. Blay, Stefan Sleijfer, Sandrine Marreaud, A. Le Cesne, Lini Pandite, T Gorlia, Herman Burger, Cor H. J. Lamers, Michelle Scurr, F. Collin, and Medical Oncology
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Oncology ,Male ,Cancer Research ,medicine.medical_treatment ,Polycomb-Group Proteins ,Angiogenesis Inhibitors ,Pregnancy Proteins ,chemistry.chemical_compound ,pazopanib ,Sulfonamides ,Interleukin-12 Subunit p40 ,Soft tissue sarcoma ,Interleukin ,Sarcoma ,Middle Aged ,Vascular endothelial growth factor ,Cytokine ,Toxicity ,Hepatocyte growth factor ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Indazoles ,Adolescent ,soft-tissue sarcomas ,Antineoplastic Agents ,Disease-Free Survival ,Pazopanib ,Young Adult ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Humans ,Aged ,Placenta Growth Factor ,business.industry ,Growth factor ,Membrane Proteins ,medicine.disease ,Vascular Endothelial Growth Factor Receptor-2 ,cytokines ,Repressor Proteins ,Pyrimidines ,chemistry ,Immunology ,Clinical Study ,prognosis ,business - Abstract
BACKGROUND: Pazopanib has activity in relapsed non-adipocytic soft-tissue sarcomas (STS). A series of serum cytokines and angiogenic factors (CAFs) at baseline and changes in soluble vascular endothelial growth factor receptor-2 (sVEGFR2) or placental-derived growth factor (PlGF) levels during treatment were explored for their association with outcome. METHODS: Twenty-three baseline CAFs, and sVEGFR2 and PlGF changes were measured in 85 and 32 patients, respectively. Associations between baseline CAF levels and efficacy parameters, plus between-week 12 sVEGFR2 and PlGF levels and pazopanib-specific toxicities were investigated. RESULTS: At baseline, low interleukin (IL)-12 p40 subunit and MPC3 levels were associated with better progression-free survival (PFS) at 12 weeks (PFS12wks), low basic nerve growth factor and hepatocyte growth factor with a better PFS, and low inter-cellular adhesion molecule-1 and IL-2 receptor alpha with prolonged overall survival (OS; all P
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- 2012
7. Identification of biological factors predictive of response to imatinib mesylate in aggressive fibromatosis
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Armelle Dufresne, François Bertucci, Christine Chevreau, Binh Bui, Didier Cupissol, Marta Jimenez, J-Y. Blay, Nicolas Penel, A. Goncalves, D Perol, Isabelle Ray-Coquard, Pierre-Paul Bringuier, M. Tubiana-Hulin, and A. Le Cesne
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Adult ,Male ,Oncology ,Cancer Research ,Pathology ,medicine.medical_specialty ,predictive factors ,medicine.drug_class ,Piperazines ,Tyrosine-kinase inhibitor ,aggressive fibromatosis ,Young Adult ,imatinib mesylate ,hemic and lymphatic diseases ,Internal medicine ,Biomarkers, Tumor ,Humans ,Medicine ,neoplasms ,Aged ,business.industry ,Fibromatosis ,Imatinib ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Predictive factor ,Fibromatosis, Aggressive ,Proto-Oncogene Proteins c-kit ,Pyrimidines ,Treatment Outcome ,Imatinib mesylate ,Multicenter study ,Benzamides ,Aggressive fibromatosis ,Female ,Translational Therapeutics ,business ,medicine.drug - Abstract
Background: Imatinib induces responses and disease stabilisations in non-resectable patients with aggressive fibromatosis (AF). The precise target of imatinib in AF and predictive factors for response to treatment are unknown. Methods: We investigated factors potentially predictive of response to imatinib in a series of 40 patients with progressive AF included in a phase II trial of imatinib: we tested the presence of KIT exon 10 variant (M541L), the expression of imatinib-sensitive kinases and cell cycle proteins by immunohistochemistry (IHC), and other clinical and biological factors. Results: Of 10 patients for whom DNA could be extracted, 3 had a KIT exon 10 variant (30%), with no correlation with response or progression-free survival (PFS). The expression of other imatinib targets (PDGFRA/B, macrophage colony-stimulating factor receptor (M-CSFR)) and of downstream components of the cell cycle, cell proliferation and proliferation pathway (cyclin D1, ERK, MEK 1–2) did not correlate with PFS. Pre-treatment lymphopenia (120 mm correlated with shorter PFS in univariate and multivariate analyses. Conclusion: Our findings show that a baseline biological characteristic of the patient is the major parameter influencing response to imatinib in aggressive fibromatosis. Tumour characteristics, including the presence of a KIT exon 10 M541L variant, may influence tumour control but this needs to be confirmed and better explained.
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- 2010
8. Prognosis and predictive value of KIT exon 11 deletion in GISTs
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P. Terrier, A. Le Cesne, Isabelle Hostein, Séverine Tabone-Eglinger, J.F. Emile, Florence Duffaud, Alain Beauchet, B. Bui, J-Y. Blay, S. Brahimi, J-B Bachet, J.-M. Coindre, and F Subra
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Adult ,Male ,Cancer Research ,Gastrointestinal Stromal Tumors ,Antineoplastic Agents ,PDGFRA ,gastrointestinal stromal tumour ,survival ,Receptor tyrosine kinase ,Disease-Free Survival ,Piperazines ,Exon ,Young Adult ,Clinical Studies ,medicine ,metastasis ,Humans ,neoplasms ,Aged ,Retrospective Studies ,Genetics ,Aged, 80 and over ,biology ,GiST ,Kinase ,Cancer ,Imatinib ,Exons ,Middle Aged ,medicine.disease ,Survival Rate ,Proto-Oncogene Proteins c-kit ,Pyrimidines ,Oncology ,Benzamides ,biology.protein ,Cancer research ,Imatinib Mesylate ,Female ,prognostic ,Gene Deletion ,medicine.drug ,GIST - Abstract
Gastrointestinal stromal tumours (GISTs) are the most frequent mesenchymal tumours of the digestive tract and occur typically in the stomach for two-third or in the small intestine for 25% in most series (Emile et al, 2004). Gain of function mutations of either KIT or platelet-derived growth factor receptor alpha polypeptide (PDGFRA) receptor tyrosine kinases play a critical role in GIST pathogenesis, and are found in 85% of GISTs (Rubin et al, 2007). Many types of gain of function mutations of KIT and PDGFRA have been described in GISTs, but 60% occurred within the exon 11 of KIT (Corless et al, 2004; Emile et al, 2004), which comprises 33 codons (codons 550–582). The two tyrosines Tyr568 and Tyr570, first residues to be phosphorylated during activation, are consensus sites for binding of Src family kinases and could be implicated in activation of different signalling pathways (Roskoski, 2005). More than 90 mutations of exon 11 have been published, and consist in insertions, substitutions and deletions; however, delWK557–558, in the proximal part of exon 11, is the most frequent, accounting for 8–25% of KIT exon 11 mutations. Others deletions, in the distal part of the exon, include in particular deletions of Tyr568 and/or Tyr570, and may thus have more specific effects on KIT signalling pathways and degradation. Such deletions account for 3–8% of exon 11 mutations in published series (Ernst et al, 1998; Taniguchi et al, 1999; Debiec-Rychter et al, 2004, 2006; Wardelmann et al, 2004; Martin et al, 2005; Penzel et al, 2005; Andersson et al, 2006; Emile et al, 2006; DeMatteo et al, 2008). After surgical resection, the type of KIT mutations may be a prognostic factor of relapse. KIT exon 11 deletions and deletions affecting codons 557–558 of KIT exon 11 were described to be independent adverse prognostic factors in patients with GIST (Wardelmann et al, 2003; Martin et al, 2005; DeMatteo et al, 2008). Conversely, in another study, GISTs in which the last part of exon 11 (codons 562–579) was deleted were most frequently associated with malignancy than GISTs with deletion of the first part of exon 11 (codons 550–561; Emile et al, 2004, 2006). So, the prognostic value of some types of KIT exon 11 mutations for risk of relapse is still debated. The mutational status of KIT or PDGFRA is predictive of clinical response to imatinib (Glivec, Gleevec, Novartis, Basel, Switzerland) and best results are obtained in patients with GISTs harbouring KIT exon 11 mutations (Heinrich et al, 2003; Debiec-Rychter et al, 2006). Nevertheless, the role of the type of KIT exon 11 mutations for the response and survival under imatinib remains to be determined. Thus, to better understand the prognostic significance of the type of KIT exon 11 deletions, we have compared the clinical characteristics and outcome of patients with GIST and deletion of both Tyr568 and Tyr570 with the most frequent deletion of KIT exon 11, delWK557–558.
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- 2009
9. Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib
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Joensuu, Heikki, primary, Blay, Jean-Yves, additional, Comandone, Alessandro, additional, Martin-Broto, Javier, additional, Fumagalli, Elena, additional, Grignani, Giovanni, additional, Del Muro, Xavier Garcia, additional, Adenis, Antoine, additional, Valverde, Claudia, additional, Pousa, Antonio Lopez, additional, Bouché, Olivier, additional, Italiano, Antoine, additional, Bauer, Sebastian, additional, Barone, Carlo, additional, Weiss, Claudia, additional, Crippa, Stefania, additional, Camozzi, Maura, additional, Castellana, Ramon, additional, and Le Cesne, Axel, additional
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- 2017
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10. Baseline and early lymphopenia predict for the risk of febrile neutropenia after chemotherapy
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I Philip, P. Biron, J.-Y. Blay, A. Le Cesne, F Chauvin, G Clapisson, Christophe Borg, I.L. Ray-Coquard, Th Bachelot, and Catherine Sebban
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Neutropenia ,Adolescent ,Population ,Antineoplastic Agents ,chemotherapy ,Models, Biological ,Cohort Studies ,Clinical ,risk model ,Risk Factors ,Lymphopenia ,Neoplasms ,Internal medicine ,Humans ,Medicine ,Lymphocyte Count ,Prospective Studies ,Risk factor ,Prospective cohort study ,education ,Aged ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,Leukopenia ,business.industry ,toxicity ,Retrospective cohort study ,Middle Aged ,Prognosis ,medicine.disease ,Blood Cell Count ,Surgery ,febrile neutropenia ,Oncology ,Female ,Lymphocytopenia ,medicine.symptom ,business ,Febrile neutropenia - Abstract
A risk model for febrile neutropenia (FN) after conventional cytotoxic chemotherapy, based on early (day 5) lymphopenia and the dose of chemotherapy, has been described. A risk index based on parameters available at day 1 would be easier in daily practice. The objectives of this work were (1) to investigate a risk model for FN using only day 1 blood cell count and (2) to compare the day 1 and day 5 risk models. Three series of patients were used for the delineation and/or validation of these two risk models: (1) the exhaustive cohort of 950 patients treated in the Department of Medicine of the CLB in 1996 (CLB-1996 series), (2) the Elypse 1 series, a prospective series of 321 patients treated in community hospitals and regional cancer centres, and (3) a previously reported Elypse 0 series of 329 patients. Day 1 blood cell count was available in all three series, while day 5 blood cell count was available only in the Elypse 0 and 1 series. In the CLB-1996 series, 92 (9.7%) patients experienced FN; only chemotherapy dose and day 1 lymphopenia < or =700 microl(-1) had an independent prognostic value for FN in multivariate analysis. In patients with both risk factors ('high-risk group'), the incidence of FN was 44, 50 and 61% in the CLB-1996. Elypse 1 and 0 series, respectively, indicating that the 'day 1' risk model enables one to identify patients at high-risk for FN. Besides, the observed incidence of FN in the high-risk group of the 'day 5' model (i.e. patients with day 5 lymphopenia < or =700 microl(-1) and receiving high-risk CT) was 45 and 69% in the Elypse 0 and 1 series, respectively. In the Elypse 1 and 0 series, 15 and 12% of all patients who experienced FN were in the high-risk group of the 'day 1' risk model as compared to 25 and 62% for the high-risk group of the 'day 5' risk model. Both day 1 and day 5 lymphopenia are associated with an increased risk of FN in patients treated with chemotherapy. The 'day 1' model identifies a small population of patients at high risk for FN, but has a lower sensitivity than the day 5 model.
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- 2003
11. Adjuvant chemotherapy for primary cardiac sarcomas: the IGR experience
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M. Spielmann, Xavier Pivot, J. P. Delord, Geneviève Contesso, A. Le Cesne, Thomas Tursz, A. Rhor-Alvarado, and Antonio Llombart-Cussac
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Leiomyosarcoma ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Dacarbazine ,Disease-Free Survival ,Heart Neoplasms ,medicine ,Humans ,Angiosarcoma ,Rhabdomyosarcoma ,Survival rate ,Aged ,Retrospective Studies ,Chemotherapy ,Ifosfamide ,business.industry ,Sarcoma ,Middle Aged ,medicine.disease ,Surgery ,Survival Rate ,Oncology ,Chemotherapy, Adjuvant ,Female ,France ,Neoplasm Recurrence, Local ,business ,medicine.drug ,Research Article - Abstract
The effect of additional treatments after surgery in patients with primary cardiac sarcoma (PCS) remains unknown. The present study aims to evaluate the benefit of chemotherapy in patients with non-metastatic cardiac sarcomas after optimal resection. Between October 1979 and December 1995, 15 patients with a median age of 45 (range 16-66) and a resected primary cardiac sarcoma [angiosarcoma (six), malignant fibrous histiocytoma (three), leiomyosarcoma (two), rhabdomyosarcoma (two), liposarcoma (one) and synoviosarcoma (one)] received a doxorubicin-containing regimen within 6 weeks of surgery. Adjuvant chemotherapy combinations included cyclophosphamide, vincristine and dacarbazine in four patients; ifosfamide in nine; methotrexate and vincristine in one; and doxorubicin alone in one patient. At present, 13 patients have relapsed (five during therapy), with a median time to progression of 10 months. Twelve patients developed local relapse, in four cases without metastatic disease. Two patients remain in complete remission 27 and 25 months after surgery. The median time to progression was shorter in patients presenting a cardiac angiosarcoma than other histological types (3 vs 14 months, P < 0.01). Twelve patients have died, with a median overall survival of 12 months. The 2-year survival rate is 26%. Survival was significantly longer for patients with completely resected tumours (22 vs 7 months; P = 0.02) and those who did not have angiosarcoma (18 vs 7 months; P = 0.04). In conclusion, post-operative conventional doxorubicin-based chemotherapy failed to modify the natural history of patients with resected cardiac sarcomas. Locoregional failure remains the main problem even after histologically complete resection. New approaches must be tested in patients with primary cardiac sarcoma.
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- 1998
12. High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management
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P. Terrier, A. Le Cesne, Julien Domont, Ludovic Lacroix, Armelle Dufresne, Véronique Brouste, S. Bonvalot, Patrick Saulnier, Coindre Jm, Agnès Neuville, J.-Y. Blay, Jean Bénard, Raf Sciot, Sébastien Salas, Louis Guillou, Dominique Ranchère, F. Collin, and Agnès Leroux
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Male ,Cancer Research ,Mutation rate ,medicine.medical_specialty ,Pathology ,Heterozygote ,DNA Mutational Analysis ,Mutation, Missense ,Fibroma ,Biology ,medicine.disease_cause ,Gastroenterology ,Loss of heterozygosity ,Gene Frequency ,Internal medicine ,Genotype ,Outcome Assessment, Health Care ,medicine ,Biomarkers, Tumor ,Humans ,prognostic factor ,Allele frequency ,Molecular Diagnostics ,beta Catenin ,Retrospective Studies ,Mutation ,Base Sequence ,Fibromatosis ,Cancer ,β-catenin mutation ,medicine.disease ,Prognosis ,Oncology ,Molecular Diagnostic Techniques ,Aggressive fibromatosis ,Female ,fibromatosis - Abstract
Background: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for β-catenin mutations in a European multicentre series of fibromatosis tumours to relate β-catenin mutational status to disease outcome. Methods: Direct sequencing of exon 3 β-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients). Results: Mutations of β-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with β-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in β-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02). Conclusion: A high frequency (87%) of β-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type β-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.
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- 2010
13. Ca125 and neuron-specific enolase (NSE) as tumour markers for intra-abdominal desmoplastic small round-cell tumours
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Karim Fizazi, Christine Theodore, Olivier Rixe, T. Le Chevalier, Fadi Farhat, A. Le Cesne, and E. Comoy
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Adult ,Male ,endocrine system ,Cancer Research ,Pathology ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Enolase ,Pharmacotherapy ,Carcinoembryonic antigen ,Drug Therapy ,Biomarkers, Tumor ,medicine ,Round cell ,Humans ,Chemotherapy ,medicine.diagnostic_test ,biology ,business.industry ,medicine.disease ,Treatment Outcome ,medicine.anatomical_structure ,nervous system ,Oncology ,Therapeutic drug monitoring ,CA-125 Antigen ,Phosphopyruvate Hydratase ,Sarcoma, Small Cell ,Disease Progression ,biology.protein ,Abdomen ,Female ,Sarcoma ,business ,Research Article - Abstract
Seven consecutive patients with intra-abdominal desmoplastic small round-cell tumours were screened at presentation for carcinoembryonic antigen (CEA), Ca19-9, Ca15-3, Ca125, alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG) and neuron-specific enolase (NSE). Initially elevated tumour markers were used to monitor therapy and follow-up. Tumour marker assays were all in the normal range, with the exception of Ca125 and NSE. The Ca125 level was initially high in six of the seven patients (86%) with a median value of 200 U ml-1 and a range of 22-735 U ml-1. The NSE value was elevated before therapy in three of the five patients (60%) for whom assay results were available, with a median of 19 ng ml-1 and a range of 6.8-37.5 ng ml-1 . Ca1 25 normalized in five out of six cases and NSE always normalized during chemotherapy, but neither of these two tumour markers correlated specifically with response, as only one patient experienced a partial response, five tumour stabilization and the remaining patient tumour progression. At progression, Ca125 was again elevated in two out of four cases several weeks before clinical relapse and NSE in only one out of three cases. Ca125 and NSE are frequently raised in the serum of patients with intra-abdominal desmoplastic small round-cell tumours before therapy, but are not reliable monitors of the course of the disease. However, normalization is frequently associated with an improvement of symptoms or a moderate clinical response.
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- 1997
14. Cytokine and angiogenic factors associated with efficacy and toxicity of pazopanib in advanced soft-tissue sarcoma: an EORTC-STBSG study
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Sleijfer, S, primary, Gorlia, T, additional, Lamers, C, additional, Burger, H, additional, Blay, J-Y, additional, Le Cesne, A, additional, Scurr, M, additional, Collin, F, additional, Pandite, L, additional, Marreaud, S, additional, and Hohenberger, P, additional
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- 2012
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15. Identification of biological factors predictive of response to imatinib mesylate in aggressive fibromatosis
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Dufresne, A, primary, Bertucci, F, additional, Penel, N, additional, Le Cesne, A, additional, Bui, B, additional, Tubiana-Hulin, M, additional, Ray-Coquard, I, additional, Cupissol, D, additional, Chevreau, C, additional, Perol, D, additional, Goncalves, A, additional, Jimenez, M, additional, Bringuier, P P, additional, and Blay, J Y, additional
- Published
- 2010
- Full Text
- View/download PDF
16. High frequency of β-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management
- Author
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Dômont, J, primary, Salas, S, additional, Lacroix, L, additional, Brouste, V, additional, Saulnier, P, additional, Terrier, P, additional, Ranchère, D, additional, Neuville, A, additional, Leroux, A, additional, Guillou, L, additional, Sciot, R, additional, Collin, F, additional, Dufresne, A, additional, Blay, J-Y, additional, Le Cesne, A, additional, Coindre, J-M, additional, Bonvalot, S, additional, and Bénard, J, additional
- Published
- 2010
- Full Text
- View/download PDF
17. Prognosis and predictive value of KIT exon 11 deletion in GISTs
- Author
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Bachet, J-B, primary, Hostein, I, additional, Le Cesne, A, additional, Brahimi, S, additional, Beauchet, A, additional, Tabone-Eglinger, S, additional, Subra, F, additional, Bui, B, additional, Duffaud, F, additional, Terrier, P, additional, Coindre, J-M, additional, Blay, J-Y, additional, and Emile, J-F, additional
- Published
- 2009
- Full Text
- View/download PDF
18. Adjuvant chemotherapy for primary cardiac sarcomas: the IGR experience
- Author
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Llombart-Cussac, A, primary, Pivot, X, additional, Contesso, G, additional, Rhor-Alvarado, A, additional, Delord, JP, additional, Spielmann, M, additional, Türsz, T, additional, and Le Cesne, A, additional
- Published
- 1998
- Full Text
- View/download PDF
19. Ca125 and neuron-specific enolase (NSE) as tumour markers for intra-abdominal desmoplastic small round-cell tumours
- Author
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Fizazi, K, primary, Farhat, F, additional, Theodore, C, additional, Rixe, O, additional, Le Cesne, A, additional, Comoy, E, additional, and Le Chevalier, T, additional
- Published
- 1997
- Full Text
- View/download PDF
20. High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management.
- Author
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Dômont, J., Salas, S., Lacroix, L., Brouste, V., Saulnier, P., Terrier, P., Ranchère, D., Neuville, A., Leroux, A., Guillou, L., Sciot, R., Collin, F., Dufresne, A., Blay, J.-Y., Le Cesne, A., Coindre, J.-M., Bonvalot, S., Bénard, J., Dômont, J, and Ranchère, D
- Subjects
TUMORS ,GENETIC mutation ,DISEASE management ,DISEASE relapse ,GENETIC polymorphisms - Abstract
Background: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for beta-catenin mutations in a European multicentre series of fibromatosis tumours to relate beta-catenin mutational status to disease outcome.Methods: Direct sequencing of exon 3 beta-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients).Results: Mutations of beta-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with beta-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in beta-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02).Conclusion: A high frequency (87%) of beta-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type beta-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
21. Baseline and early lymphopenia predict for the risk of febrile neutropenia after chemotherapy.
- Author
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Ray-Coquard, I, Borg, C, Bachelot, Th, Sebban, C, Philip, I, Clapisson, G, Le Cesne, A, Biron, P, Chauvin, F, Blay, J Y, and ELYPSE study group
- Subjects
FEBRILE neutropenia ,CHEMOTHERAPY complications - Abstract
A risk model for febrile neutropenia (FN) after conventional cytotoxic chemotherapy, based on early (day 5) lymphopenia and the dose of chemotherapy, has been described. A risk index based on parameters available at day 1 would be easier in daily practice. The objectives of this work were (1) to investigate a risk model for FN using only day 1 blood cell count and (2) to compare the day 1 and day 5 risk models. Three series of patients were used for the delineation and/or validation of these two risk models: (1) the exhaustive cohort of 950 patients treated in the Department of Medicine of the CLB in 1996 (CLB-1996 series), (2) the Elypse 1 series, a prospective series of 321 patients treated in community hospitals and regional cancer centres, and (3) a previously reported Elypse 0 series of 329 patients. Day 1 blood cell count was available in all three series, while day 5 blood cell count was available only in the Elypse 0 and 1 series. In the CLB-1996 series, 92 (9.7%) patients experienced FN; only chemotherapy dose and day 1 lymphopenia < or =700 microl(-1) had an independent prognostic value for FN in multivariate analysis. In patients with both risk factors ('high-risk group'), the incidence of FN was 44, 50 and 61% in the CLB-1996. Elypse 1 and 0 series, respectively, indicating that the 'day 1' risk model enables one to identify patients at high-risk for FN. Besides, the observed incidence of FN in the high-risk group of the 'day 5' model (i.e. patients with day 5 lymphopenia < or =700 microl(-1) and receiving high-risk CT) was 45 and 69% in the Elypse 0 and 1 series, respectively. In the Elypse 1 and 0 series, 15 and 12% of all patients who experienced FN were in the high-risk group of the 'day 1' risk model as compared to 25 and 62% for the high-risk group of the 'day 5' risk model. Both day 1 and day 5 lymphopenia are associated with an increased risk of FN in patients treated with chemotherapy. The 'day 1' model identifies a small population of patients at high risk for FN, but has a lower sensitivity than the day 5 model. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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