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1. Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil–cisplatin regimen in oesophageal cancer

Author: M.P. Galais, Antoine Adenis, J.-Y. Douillard, P.L. Etienne, O. Bouche, Sophie Gourgou, Thierry Conroy, C. Bascoul-Mollevi, Beata Juzyna, Laurent Bedenne, Jean-Luc Raoul, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'hépato-gastro-entérologie et cancérologie digestive [CHU de Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), CRLCC René Gauducheau, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, UNICANCER [Paris], Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département d’Oncologie Médicale [Vandoeuvre Les Nancy], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Université de Lille-UNICANCER
Subjects: Male, Oncology, Cancer Research, Time Factors, Esophageal Neoplasms, Organoplatinum Compounds, Leucovorin, 0302 clinical medicine, Quality of life, FOLFOX, Risk Factors, Surveys and Questionnaires, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Oesophageal cancer, Chemoradiotherapy, Middle Aged, Dysphagia, 3. Good health, Oxaliplatin, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Esophageal Squamous Cell Carcinoma, France, medicine.symptom, medicine.drug, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Prognostic factors, Disease-Free Survival, Carcinoma, Adenosquamous, 03 medical and health sciences, Internal medicine, medicine, Humans, Neoplasm Staging, business.industry, Regimen, Multivariate Analysis, Linear Models, Quality of Life, Dose Fractionation, Radiation, Cisplatin, business
Abstract: IF 6.029; International audience; BackgroundA recent prospective randomised trial did not reveal significant differences in median progression-free survival between two chemoradiotherapy (CRT) regimens for inoperable non-metastatic oesophageal cancer patients. This secondary analysis aimed to describe the impact of CRT on health-related quality of life (HRQOL), physical functioning, dysphagia, fatigue and pain and to evaluate whether baseline HRQOL domains can predict overall survival.Patients and methodsA total of 267 patients were randomly assigned to receive with 50 Gy of radiotherapy in 25 fractions six cycles of FOLFOX or four cycles of fluorouracil and cisplatin on day 1. HRQOL was prospectively assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 with the oesophageal cancer module (QLQ-OES18).ResultsBoth groups showed high baseline compliance. Subsequently, compliance reduced to 41% at the 6-month follow-up. Baseline HRQOL scores showed no statistical differences between treatment arms. During treatment, both groups exhibited lower physical and social functioning and increased fatigue and dyspnoea, although dysphagia moderately improved in the fluorouracil–cisplatin arm only (p = 0.047).During follow-up, HRQOL scores revealed no significant differences between chemotherapy regimens. Linear mixed model exhibited a treatment-by-time interaction effect for dysphagia (p = 0.017) with a greater decrease in dysphagia in the fluorouracil–cisplatin group. Time until definitive deterioration analysis showed no significant differences in global HRQOL, functional or main symptom domains. However, time until definitive deterioration was significantly longer for the fluorouracil and cisplatin arm compared with FOLFOX for appetite loss (p = 0.002), QLQ-OES-18 pain (p = 0.008), trouble swallowing saliva (p = 0.011) and trouble talking (p = 0.020).ConclusionAnalyses of HRQOL scores revealed no statistically significant differences between patients with inoperable non-metastatic oesophageal cancer treated by FOLFOX versus those treated with a fluorouracil–cisplatin regimen as part of definitive CRT.
Published: 2017
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2. Is it still time for meta-analyses in operable esophageal cancers, or rather for a change of paradigm?

Author: Karine Le Malicot, Antoine Drouillard, and Laurent Bedenne
Subjects: Pulmonary and Respiratory Medicine, Radiation therapy, Oncology, Chemotherapy, medicine.medical_specialty, Text mining, business.industry, medicine.medical_treatment, Internal medicine, medicine, Esophageal cancer, business, medicine.disease
Abstract: Since the eighties, several generally small and powerless trials compared surgery alone with surgery preceded or followed by radiotherapy (RT), chemotherapy (CT) or radiochemotherapy (CRT) in esophageal cancer.
Published: 2017
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3. First-Line Chemotherapy for Metastatic Esophageal Squamous Cell Carcinoma: Clinico-Biological Predictors of Disease Control

Author: Stéphanie Clisant, Laetitia Dahan, Christophe Mariette, Emmanuelle Samalin, Meher Ben Abdelghani, Pierre-Luc Etienne, Eric Francois, Farid El Hajbi, Emmanuelle Tresch, Charlotte Peugniez, Guillaume Piessen, Antoine Adenis, Laurent Bedenne, Pierre Michel, Andrew Kramar, Marie Pierre Galais, Nuria Kotecki, François Ghiringelli, Nicolas Penel, Jafaar Bennouna, and Sandrine Hiret
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, Esophageal Neoplasms, Organoplatinum Compounds, medicine.medical_treatment, Leucovorin, Body Mass Index, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Prospective cohort study, Vinorelbine, General Medicine, Middle Aged, Vinblastine, Survival Rate, Treatment Outcome, Fluorouracil, Response Evaluation Criteria in Solid Tumors, Area Under Curve, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, medicine.drug, medicine.medical_specialty, Bone Neoplasms, Models, Biological, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Carcinoma, Humans, Survival rate, Serum Albumin, Retrospective Studies, Chemotherapy, business.industry, medicine.disease, 030104 developmental biology, ROC Curve, Cisplatin, business
Abstract: Objective: This study aimed to identify predictors of tumor control (TC) in metastatic esophageal squamous cell carcinoma patients receiving first-line chemotherapy. Methods: A development cohort of 68 patients from a prospective multicenter trial (NCT01248299) was used to identify predictors of TC at first radiological tumor assessment and to generate a predictive score for TC. That score was applied in an independent retrospective single-center validation cohort of 60 consecutive patients. Results: Multivariate analysis identified three predictors of TC: body mass index ≥18.5 (OR 4.5, 95% CI 0.91-22.5), absence of bone metastasis (OR 4.6, 95% CI 0.91-23.2) and albumin ≥35 g/l (OR 3.5, 95% CI 1.0-12.1). Based on the presence or absence of these three independent prognosticators, we built a predictive model using a score from 0 to 3. In the development cohort, the TC rates were 14.3 and 78.0% and in the validation cohort 12.5 and 44.2%, for scores of 0-1 and 2-3, respectively. With negative predictive values of 85 and 88% in the development and validation cohorts, respectively, we were able to identify patients with a very low probability of TC. Conclusion: We have developed and validated a score that can be easily determined at the bedside to predict TC in metastatic esophageal squamous cell carcinoma patients.
Published: 2016
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4. Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials

Author: Mireille Mousseau, Eric Francois, A. Fatisse, A. Bedjaoui, Abakar Mahamat, C. Lombard-Bohas, J. Ezenfis, Marc Porneuf, F. Subtil, M. Tissot, Emilie Maillard, M. Fayolle, J.F. Dor, A. Votte, P. Chiappa, P. Prost, Denis Cléau, P. Bergerault, J.C. Souquet, K. Beerblock, P. Chatrenet, J.M. Sabate, M. Carreiro, S. Beorchia, Vincent Hautefeuille, Jessika Moreau, N. Delas, C. Vilain, Christian Borel, Franck Audemar, M. Duluc, Touraj Mansourbakht, Bernard Denis, Gael Deplanque, Jean-Marc Phelip, C. Brezault, Anne Thirot-Bidault, L. Gasnault, Jean-Louis Jouve, Y. Rinaldi, B. Leduc, Y. Courouble, A. Alessio, Matthieu Schnee, P. Cassan, Antoine Adenis, Jocelyne Provencal, A. Botton, Laurent Cany, Françoise Desseigne, Marie-Christine Kaminsky, Mohamed Ramdani, B. Lafforgue, L. Rob, J.C. Barbare, S. Jacquot, A. Zaanan, J.-Y. Douillard, C. Cornila, B. Rhein, Benjamin Linot, Z. Ladhib, D. Zylberait, Cedric Lecaille, N. Hess-Laurens, H. Brixi-Benmansour, C. Rebischung, C. Giraud, L. Stefani, D. Pillon, J.P. Lafargue, J. Forestier, P. Laplaige, C. Paoletti, S. Lavau Denes, Etienne Suc, A. Patenotte, E. Echinard, François-Xavier Caroli-Bosc, D. Goldfain, V. Quentin, Hervé Perrier, J.D. Grangé, A. Marre, M. Baconnier, Bruno Coudert, Thomas Walter, R. Benoit, A. Blanchi, A.C. Dupont-Gossart, Emilie Barbier, X. Coulaud, D. Besson, Isabelle Trouilloud, D. Sevin-Robiche, M Giovannini, O. Boulat, C. Lobry, H. Castanie, Y. Molin, Thomas Aparicio, Valérie Boige, P. Lehair, J.P. Robin, J.P. Latrive, J. Goineau, Clément Belletier, G. Medinger, C. Lepere, Philippe Rougier, N. Bouaria, E. Carola, V. Derias, Bernard Paillot, Yves Becouarn, F. Kikolski, Martin Combe, Julie Vincent, C. Briac-Levaché, C. Becht, François Ghiringhelli, J. Charneau, Dany Gargot, Julien Vergniol, Denis Péré-Vergé, P. Pienkowski, Patrick Texereau, I. Baumgaertner, J.P. Ramain, Pierre-Luc Etienne, P. Claudé, Jean Francois Paitel, J.P. Plachot, M.-C. Clavero-Fabri, P. Geoffroy, A. Cadier-Lagnes, Y. Le Bricquir, S. Fratte, O. Favre, Aimery de Gramont, J. Butel, David Tougeron, B. Winkfield, E. Janssen, J. Meunier, Julien Volet, N. Gérardin, D. Soubrane, Vincent Bourgeois, Xavier Adhoute, Y.H. Lam, P.A. Haineaux, A. Rotenberg, J-B. Bachet, C. Berger, F. Almaric, J. Tuaillon, G. Gatineau-Saillant, F. Zerouala-Boussaha, E. Cuillerier, R. Lamy, D. Luet, D. Baudet-Klepping, E.A. Pariente, M. Gignoux, J. Martin, M. Blasquez, Romain Coriat, C. Bineau, J. Boutin, A. Aouakli, F. Dewaele, A.M. Queuniet, V. Sebbagh, P. Couzigou, N. Barrière, Faiza Khemissa, P. Follana, Laurence Chone, F. Petit-Laurent, N. Abdelli, Olivier Capitain, D. Bechade, Corinne Sarda, J.P. Herr, P. Pouderoux, Julien Taieb, M. Pauwels, E. Zrihen, L. Wander, Gael Goujon, G. Boilleau-Jolimoy, Anne Thirot Bidault, B. Landi, V. Jestin Le Tallec, Jaafar Bennouna, O. Berthelet, M. Glikmanas, H. Salloum, Côme Lepage, Thierry Lecomte, P. Amoyal, C. Platini, Veronique Guerin-Meyer, B. Garcia, Laetitia Dahan, Pascal Burtin, J. Villand, S. Nguyen, A. Roussel, F. Di Fiore, S. Oddou-Lagraniere, J.P. Aucouturier, Veronique Lorgis, Gerard Cavaglione, J.P. Lagasse, Dominique Auby, Pierre Michel, F. Bonnetain, Gilles Breysacher, R. Mackiewicz, Philippe Ruszniewski, T. Morin, J. Thaury, Clara Locher, J.M. Vantelon, S. Nasca, J.P. Barbieux, H. Maechel, Y. Coscas, May Mabro, S. Montembault, P. Novello, M. Charbit, J. Deguiral, A. Gagnaire, D. Festin, A. Gueye, Hélène Senellart, Achim Weber, Nadia Bouarioua, Jérôme Dauba, Michel Ducreux, Jean-Luc Raoul, G. Coulanjon, J.N. Vaillant, S. Chaussade, A. Gilbert, Anne-Laure Villing, Dominique Genet, P. Martin, M. Ben Abdelghani, M.P. Galais, A. Azzedine, A. Lemaire, C. Barberis, C. Buffet, J. Egreteau, G. Roquin, M. Mornet, Isabelle Cumin, M. Pelletier, P. Feydy, J. Lacourt, T. Chatellier, Jean-Louis Legoux, M. Benchalal, I. Graber, S. Nahon, P. Pantioni, A. Hollebecque, M. Zawadi, Pascal Hammel, M. Mignot, Roger Faroux, J. Lafon, Mohamed Gasmi, Jean-Philippe Spano, S. Pesque-Penaud, C. de la Fouchardiere, J. Cretin, Olivier Bouché, D. Smith, E. Norguet-Monnereau, G. Bordes, Sylvain Manfredi, Thévenet P, Herve Lacroix, E. Dorval Danquechin, Eric Terrebonne, Laurent Bedenne, P. Godeau, David Malka, V. Veuillez, Emmanuel Mitry, F. Riot, Sandrine Hiret, François Morvan, M.C. Gouttebel, Jean-François Seitz, Karine Bouhier-Leporrier, N. Stremsdoerfer, P. Souillac, M. Mozer, C. Couffon, F. Husseini, J.M. Cheula, J.-M. Gornet, K. Slimane Fawzi, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Université Paris-Saclay, Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), CHD Vendee (La Roche Sur Yon), Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Privé des Côtes d'Armor (HPCA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut de Cancérologie de la Loire [Saint-Priest en Jarez], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Service d'hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Service De Gastroenterologie, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Hôpital Louis Pasteur [Colmar] (CH Colmar), Département d'hépato-gastro-entérologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut des Maladies de l’Appareil Digestif [CHU Nantes], Service d'oncologie [Institut Hospitalier Franco-Britannique : Levallois-Perret], Institut hospitalier Franco-Britannique [Levallois-Perret], Département d'oncologie médicale (CHU Robert Debré, Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN)
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, Angiogenesis Inhibitors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Overweight, Gastroenterology, Pooled analysis, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Outcome Assessment, Health Care, Individual data, medicine, Overall survival, Humans, Neoplasm Metastasis, Objective response, Aged, 2. Zero hunger, Clinical Trials as Topic, Prognostic factor, business.industry, nutritional and metabolic diseases, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Prognosis, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, Normal weight, 030220 oncology & carcinogenesis, Female, medicine.symptom, Colorectal Neoplasms, business, medicine.drug
Abstract: IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI
Published: 2018
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5. Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08)

Author: Wilfried Budach, Ludwig Plasswilm, Hanne Hawle, Michael Stahl, Jorge Riera Knorrenschild, Wolfgang Eisterer, Peter Brauchli, Laurent Bedenne, M. Girschikofsky, Sabina Schacher, S. C. Schmidt, Viviane Hess, Stefanie Hayoz, Michael Bitzer, Christophe Mariette, Annelies Schnider, Thomas Ruhstaller, Michael Montemurro, W. Mingrone, Peter C. Thuss-Patience, Brustzentrum Kantonsspital St. Gallen, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], SAKK Coordinating Center (Berne), Kantonsspital Winterthur (KSW), University Hospital of Giessen and Marburg (UKGM), Stadtspital Triemli Zürich, University Hospital of Düsseldorf, The Medical University of Innsbruck, Hôpital Claude Huriez [Lille], CHU Lille, University Hospital Basel [Basel], Cantonal Hospital of Olten, University Hospital of Lausanne, Ordensklinikum Linz Elisabethinen, Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and Kliniken Essen-Mitte
Subjects: 0301 basic medicine, Male, Esophageal Neoplasms, medicine.medical_treatment, Docetaxel, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, cetuximab, Clinical endpoint, Medicine, Prospective Studies, esophageal cancer, neoadjuvant chemoradiation, Neoadjuvant therapy, Cetuximab, Hazard ratio, Hematology, Chemoradiotherapy, Esophageal cancer, Middle Aged, Prognosis, Combined Modality Therapy, Neoadjuvant Therapy, 3. Good health, Survival Rate, Oncology, 030220 oncology & carcinogenesis, resectable, Carcinoma, Squamous Cell, Female, medicine.drug, neoadjuvant chemotherapy, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, 03 medical and health sciences, locally advanced, Humans, Survival rate, neoplasms, Aged, Chemotherapy, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Surgery, Esophagectomy, 030104 developmental biology, Cisplatin, business, Follow-Up Studies
Abstract: IF 13.926 (2017); International audience; BackgroundThis open-label, phase III trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma.Patients and methodsPatients were randomly assigned (1 : 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary end point was progression-free survival (PFS).ResultsIn total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5–2.8) with control [hazard ratio (HR), 0.79; 95% CI, 0.58–1.07; P = 0.13]. Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2–4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52–1.01; P = 0.055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31–0.90; P = 0.017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64–1.59, P = 0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings.ConclusionAdding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma.Clinical trial informationNCT01107639
Published: 2018
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6. Patterns of care and outcomes in oesophageal cancer

Author: Marie Napoleon, Laurent Bedenne, Anne-Marie Bouvier, Valérie Jooste, Sylvain Manfredi, Antoine Drouillard, Jean Faivre, and Imène Marref
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Time Factors, Esophageal Neoplasms, Population, Adenocarcinoma, Gastroenterology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Esophagus, Randomized controlled trial, law, Internal medicine, medicine, Humans, Registries, education, Net Survival, Aged, Patterns of care, education.field_of_study, Hepatology, business.industry, Cancer, Histology, Chemoradiotherapy, Middle Aged, medicine.disease, Survival Rate, Treatment Outcome, 030220 oncology & carcinogenesis, Surgical Procedures, Operative, Multivariate Analysis, Carcinoma, Squamous Cell, 030211 gastroenterology & hepatology, Female, France, Neoplasm Recurrence, Local, business
Abstract: Background The optimal treatment for oesophageal cancer is a matter of debate. The aim of this study was to describe patterns of care and survival in a well-defined population for squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the oesophagus. Design Data were provided by the Digestive Cancer Registry of Burgundy (France). Recurrence, excess mortality and net survival were calculated. Results Among non-metastatic patients, the proportion of patients resected for cure decreased between 2004 and 2013 from 16% to 9% for SCC and 48% to 22% for AC. The administration of chemoradiation increased from 45 to 53% for SCC and 21 to 30% for AC. A complete clinical response to chemoradiation was reported in 40% of the patients. Five-year net survival did not vary according to histology. It was 55% in the selected group of patients resected for cure, 44% in patients treated with chemoradiation with a complete clinical response. In multivariate analysis, treatment modality only was associated with survival. In metastatic patients, 3-year net survival was 14% for those treated with chemoradiation. Conclusion Chemoradiation has become the most frequently administered treatment. Cancelling or postponing surgery after chemoradiation with complete response should be assessed by a randomized clinical trial.
Published: 2018

7. Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20 study results

Author: Julien Taieb, Roger Faroux, M. Baconnier, Laurent Bedenne, Alice Oden-Gangloff, Elena Paillaud, F. Khemissa Akouz, F. Retornaz, Sandrine Lavau-Denes, F. El Hajbi, P.L. Etienne, Christophe Locher, O. Bouche, S. Kirscher, E. Maillard, Yves Rinaldi, Thomas Aparicio, Dominique Genet, E. Francois, Thierry Lecomte, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Sorbonne Paris Cité ( USPC ), Service d'hépato-gastro-entérologie et cancérologie digestive [CHU de Reims], Centre Hospitalier Universitaire de Reims ( CHU de Reims ), Service de chirurgie digestive, générale et cancérologique [Hôpital européen Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Fédération Francophone de la Cancérologie Digestive, FFCD, Institut Sainte Catherine [Avignon], Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, CRLCC Oscar Lambret, Service des maladies de l'appareil digestif (CH Meaux), CH Meaux, Service de gastro-entérologie (Hôpital Européen de Marseille), Hôpital Européen [Fondation Ambroise Paré - Marseille], Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), CHU Dupuytren, Service d'hépato-gastro-entérologie et endoscopies (CH Annecy), CH Annecy Genevois, CHU Rouen, Polyclinique de Limoges - site François Chénieux [Limoges], Unité de médecine gériatrique ( Gériatrie - Henri Mondor ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Laboratoire de Physique Atmosphérique et Planétaire ( LPAP ), Université de Liège, CRLCC Antoine Lacassagne, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de chirurgie digestive, générale et cancérologique [CHU HEGP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Normandie Université (NU), Unité de médecine gériatrique (Gériatrie - Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Laboratoire de Physique Atmosphérique et Planétaire (LPAP), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Université de Lille-UNICANCER, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, Organoplatinum Compounds, Colorectal cancer, Leucovorin, law.invention, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Randomized controlled trial, FOLFOX, law, Antineoplastic Combined Chemotherapy Protocols, randomized trial, Neoplasm Metastasis, Aged, 80 and over, education.field_of_study, Standard treatment, Age Factors, Hematology, Corrigenda, 3. Good health, Bevacizumab, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Fluorouracil, Colorectal Neoplasms, medicine.drug, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, colorectal cancer, elderly, 03 medical and health sciences, Internal medicine, Gastrointestinal Tumors, medicine, FOLFIRI Regimen, Humans, education, Survival rate, Aged, business.industry, antiangiogenic, Original Articles, medicine.disease, composite criteria, Camptothecin, business
Abstract: IF 11.855; International audience; Background :Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population.Patients and methods :Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator’s choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria.Results :About 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75–91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT).Conclusion :Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.
Published: 2018
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8. Small bowel adenocarcinoma: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO)

Author: Thomas Aparicio, Emmanuelle Samalin, Pierre Michel, Olivier Bouché, Blaise Batumona, Laurent Bedenne, Christophe Cellier, Benoit Chibaudel, Yves Becouarn, Marc Pocard, Yann Parc, Pauline Afchain, Nicolas Carrere, Christophe Locher, Centre Hospitalier de Meaux, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Purpan (CHU Purpan), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Rouen, Normandie Université (NU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-APHP, Institut hospitalier Franco-Britannique [Levallois-Perret], and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: medicine.medical_specialty, Colorectal cancer, Small bowel adenocarcinoma, Colonoscopy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Adenocarcinoma, Guidelines, 03 medical and health sciences, 0302 clinical medicine, Intestinal Neoplasms, Intestine, Small, National recommendations, medicine, Humans, Stage (cooking), Intersectoral Collaboration, Neoplasm Staging, Hepatology, medicine.diagnostic_test, business.industry, General surgery, Gastroenterology, Cancer, Platinum salts, medicine.disease, 3. Good health, Surgery, Clinical Practice, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Surgical Procedures, Operative, 030211 gastroenterology & hepatology, France, business
Abstract: IF 3.061; International audience; BackgroundThis document is a summary of the French intergroup guidelines regarding the management of small bowel adenocarcinoma published in October 2016.MethodThis collaborative work, co-directed by most French Medical Societies, summarizes clinical practice recommendations (guidelines) on the management of small bowel adenocarcinoma. Given the lack of specific data in the literature, all references are given by analogy with colon cancer. The classification used is the AJCC (American Joint Committee on Cancer) pTNM classification (7th edition 2009).ResultsSmall bowel adenocarcinoma has a poor prognosis; less than 30% of patients survive for 5 years after the (first) diagnosis (5-year survival of less than 30%). Due to the rarity of the disease and the retrospective data, most recommendations are based on expert agreement. The initial evaluation is based on chest-abdomen-pelvis CT scan, CEA assay, GI endoscopy and colonoscopy in order detect lesions associated with a predisposing disease. Surgical treatment is currently the only curative option for stage I and II. Adjuvant chemotherapy can be discussed for Stage III and Stage II with T4 (expert agreement). With regard to metastatic tumors, treatment with fluoropyrimidine combined with platinum salts should be considered (expert agreement).ConclusionFew specific data exist in the literature on this type of tumor; most of the recommendations come from expert agreements or by analogy with colon cancer. Thus, each case must be discussed within a multidisciplinary team.
Published: 2018
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9. Factors influencing inclusion in digestive cancer clinical trials: A population-based study

Author: Anne-Marie Bouvier, Valérie Jooste, Christine Binquet, Mathilde Frerot, Laurent Bedenne, and Isabelle Fournel
Subjects: Clinical Trials as Topic, Pediatrics, medicine.medical_specialty, Multivariate analysis, Hepatology, business.industry, Patient Selection, Age Factors, Gastroenterology, Odds ratio, Logistic regression, Clinical trial, Population based study, Logistic Models, Socioeconomic Factors, Multivariate Analysis, medicine, Humans, Registries, business, Inclusion (education), Digestive cancer, Gastrointestinal Neoplasms, Therapeutic strategy
Abstract: Inclusion in a randomized therapeutic trial represents an optimal therapeutic strategy.To determine the influence of demographic characteristics and deprivation on the enrolment of patients in digestive cancer clinical trials.Between 2004 and 2010, 4632 patients were recorded by the Burgundy Digestive Cancer Registry. According to a balancing score, the 136 patients included in a clinical trial were matched with 272 patients who met the eligibility criteria for trials. Deprivation was measured by the ecological European deprivation index. A conditional multivariate logistic regression was performed.Patients aged over 75 years were significantly less likely to be included in clinical trials than younger patients (odds ratio 0.33; [0.13-0.87]). Patients treated in private institutions were also less likely to be enrolled than those treated in public institutions (odds ratio 0.04; [0.01-0.16]; p0.001). A relationship between type of institution and the European deprivation index was observed (p=0.017). Deprived patients were less likely to be included in clinical trials when they were managed in private institutions (odds ratio 0.706; [0.524-0.952]; p=0.022). The European deprivation index had no impact when patients were managed in other institutions.The relationship between type of institution and deprivation underlines the necessity for improving patients' chance of being recruited in digestive cancer clinical trials.
Published: 2015
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10. Impact of Neoadjuvant Chemoradiation on Lymph Node Status in Esophageal Cancer

Author: Emilie Maillard, Pascal-Alexandre Thomas, Jean-Yves Mabrut, Valérie Le Brun-Ly, Jean-François Bosset, Laetitia Dahan, Christophe Mariette, William B. Robb, Jean-Pierre Triboulet, Denis Pezet, Laurent Bedenne, Jean-François Seitz, Françoise Mornex, Bernard Meunier, Valérie Boige, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, and Surgery
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Esophageal Neoplasms, Disease, law.invention, Text mining, SDG 3 - Good Health and Well-being, Randomized controlled trial, law, Internal medicine, Post-hoc analysis, Humans, Medicine, Lymph node, Pathological, Aged, Neoplasm Staging, integumentary system, business.industry, hemic and immune systems, Chemoradiotherapy, Middle Aged, respiratory system, Esophageal cancer, medicine.disease, Survival Analysis, Neoadjuvant Therapy, medicine.anatomical_structure, Lymphatic Metastasis, Lymph Node Excision, Female, Surgery, Lymph Nodes, Lymph, business, tissues
Abstract: Objective: The study objectives were to analyze the impact of the number of lymph nodes (LNs) reported as resected (NLNr) and the number of LNs invaded (NLNi) on the prognosis of esophageal cancer (EC) after neoadjuvant chemoradiotherapy. Background: Pathological LN status is a major disease prognostic factor and marker of surgical quality. The impact of neoadjuvant chemoradiation (nCRT) on LN status remains poorly studied in EC. Methods: Post hoc analysis from a phase III randomized controlled trial comparing nCRT and surgery (group nCRT) to surgery alone (group S) in stage I and II EC (NCT00047112). Only patients who underwent surgical resection were considered (n = 170). Results: nCRT resulted in tumoral downstaging (pT0, 40.7% vs 1.1%, P 3 vs 0) 3.5, 95% CI: 2.0-6.2, P = 15) 0.95, 95% CI: 0.6-1.4, P = 0.807 and HR ( = 23) 1.4, 95% CI: 0.9-2.0, P = 0.131] did not. In Poisson regression analysis, nCRT was an independent predictive variable for reduced NLNr [exp(coefficient) 0.80, 95% CI: 0.66-0.96, P = 0.018]. Conclusions: nCRT is not only responsible for disease downstaging but also predicts fewer LNs being identified after surgical resection for EC. This has implications for the current quality criteria for surgical resection
Published: 2015
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11. Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset

Author: Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Alois Lang, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Jean-Luc Van Laethem, Eric Van Cutsem, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Hassan RezaieKalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Marc Ychou, Ayman Zawadi, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Eveline Boucher, Julien Taieb, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara MatysiakBudnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Gunnar Folprecht, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans GuenterDerigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Roberto Labianca, Giuseppe Colucci, Dino Amadori, Enrico Mini, Alfredo Falcone, Corrado Boni, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Domenico Cristi Corsi, Stefania Salvagni, Silvana Chiara, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Josep Tabernero, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel ValladaresAyerbes, Jaime FeliuBatlle, Silvia Gil, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis CireraNogueras, BernadoQueralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos PijaumePericay, Manuel ConstenlaFigueiras, InmaculadaGuasch Jordan, Maria Jose GomeReina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio MarcuelloGaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica GuillotMorales, Marta LlanosMuñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel HernandezBusquier, Teresa Checa Ruiz, Adelaida LacastaMuñoa, MiquelNogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio GalanBrotons, Santiago AlbiolRodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita CentellesRuiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, and Leslie Samuel
Subjects: Oncology, Hematology
Published: 2015
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12. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX

Author: Jean-François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Stéphanie Dimet, Camille Boulagnon-Rombi, Marc-Antoine Allard, Frédérique Penault-Llorca, Jaafar Bennouna, Pierre Laurent-Puig, Julien Taieb, Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Felix Keil, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Björn Jagdt, Alois Lang, Michael Fridrik, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Eric Van Cutsem, Hassan Rezaie Kalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Marc Ychou, Eveline Boucher, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara Matysiak Budnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans Guenter Derigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Dino Amadori, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Corrado Boni, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Alfredo Falcone, Domenico Cristi Corsi, Roberto Labianca, Stefania Salvagni, Silvana Chiara, Libero Ciuffreda, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel Valladares Ayerbes, Jaime Feliu Batlle, Silvia Gil, Albert Abad Esteve, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis Cirera Nogueras, Bernado Queralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos Pijaume Pericay, Manuel Constenla Figueiras, Inmaculada Guasch Jordan, Maria Jose Gome Reina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio Marcuello Gaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica Guillot Morales, Marta Llanos Muñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel Hernandez Busquier, Teresa Checa Ruiz, Adelaida Lacasta Muñoa, Miquel Nogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio Galan Brotons, Santiago Albiol Rodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita Centelles Ruiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, Leslie Samuel, UE 1373 Fourrages Environnement Ruminants Lusignan, Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Environnement et Agronomie ( E.A. ) -Biologie et Amélioration des Plantes ( BAP ) -Fourrages Environnement Ruminants Lusignan ( FERLUS ), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Service de Biostatistique, Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Vall d'Hebron University Hospital [Barcelona], Dpt of Internal Medicine, Section of Immunoallergology and Respiratory [Florence] Diseases, University of Florence, Carl Gustav Carus University Hospital, Erasme Hospital, Brussels, Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse, Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Nantes ( UN ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Klinikum Wels Grieskirchen, Oncology department [Salzburg], Salzburger Landesklinikum - Uniklinikum Salzburg ( SALK ), Institute of Chemical Reaction Engineering, Hamburg University of Technology, Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung ( AWI ), Department of Medical Oncology, Medical University Vienna, Department of Internal Medicine, Hospital of Steyr, Department Internal Medicine 3, Centre for Hematology and Medical Oncology, General Hospital Linz, Department Medicine LKH, Institut für Festköperfirschung, Institut des Sciences Moléculaires de Marseille ( ISM2 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Centrale de Marseille ( ECM ) -Aix Marseille Université ( AMU ), University Hospitals Leuven [Leuven], Katholieke Universiteit Leuven ( KU Leuven ), Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Institut de Biologie Computationnelle ( IBC ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Moléculaires ( ISM ), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique ( CNRS ), Faculty of Veterinary Medicine, Ghent University [Belgium] ( UGENT ), Medical Oncology, Antwerp University Hospital [Edegem], Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier de L'Ardenne (Libramont), Department of Cardiology [Sivas, Turkey], Cumhuriyet University [Sivas, Turkey], Department of Earth Sciences, Durham University, Department of Oncology, Rigshospitalet [Copenhagen], Odense Hospital, CP Kelco ApS, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Institut de Recherche en Cancérologie de Montpellier ( IRCM - U1194 Inserm - UM ), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Université du Québec à Montréal ( UQAM ), Université Panthéon-Sorbonne ( UP1 ), École nationale supérieure d'architecture de Nantes ( ENSA Nantes ), Department of Hepatogastroenterology and Oncology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France., Hôpital Ambroise Paré, CH Belfort-Montbéliard, Polyclinique Francheville, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Centre Hospitalier de Meaux, Service d'hématologie, Clinique Catherine de Sienne, Unité de recherche sur les Biopolymères, Interactions Assemblages ( BIA ), Institut National de la Recherche Agronomique ( INRA ), Université de la Méditerranée - Aix-Marseille 2, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), CHU Amiens-Picardie, Pôle oncologie médicale, Hôpital des Diaconesses, Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bretagne Occidentale - École de sages-femmes ( UBO UFR MSS ESF ), Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Service Gastro-Entérologie, CHU Besançon, Université de Franche-Comté ( UFC ) -Université de Franche-Comté ( UFC ), Centre Alexis Vautrin ( CAV ), Ecophysiologie Végétale, Agronomie et Nutritions ( EVA ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Recherche Agronomique ( INRA ), Image et ville ( IV ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Département informatique ( INFO ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Agence de l'Environnement et de la Maîtrise de l'Energie - ADEME, Service d'hépato-gastroentérologie, CHU Caen-Hôpital côte de nacre, Département de Médecine, Centre hospitalier de Libourne, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Fondation FondaMental, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Variabilité de réponse aux psychotropes ( VariaPsy - U1144 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ), Département d'oncologie digestive, Institut Bergonié - CRLCC Bordeaux, Hôpital St Joseph, Service de Gynécologie et d'Obstétrique ( CHU Lyon ), Hospices Civils de Lyon ( HCL ), Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 1 ( UM1 ), Service de gastro-entérologie - Hôpital Henri Mondor, Laboratoire Matière et Systèmes Complexes ( Laboratoire MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -UFR de Physique, France, Amériques, Espagne – Sociétés, pouvoirs, acteurs ( FRAMESPA ), Université Toulouse - Jean Jaurès ( UT2J ) -Centre National de la Recherche Scientifique ( CNRS ), Regional Hospital of Orleans, Histoire, Archéologie et littératures des Mondes chrétiens et musulmans médiévaux ( CIHAM ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -École des hautes études en sciences sociales ( EHESS ) -Université Jean Moulin - Lyon III ( UJML ) -Université d'Avignon et des Pays de Vaucluse ( UAPV ) -Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie des signaux intercellulaires ( NSI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Dept Med Genet, Hôpital Erasme (Bruxelles), Polyclinique de Limoges - site François Chénieux [Limoges], Clinique Médicale B, CHU Strasbourg, Service de gastro-entérologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Hôpital Européen [Fondation Ambroise Paré - Marseille], Asklepios Klinikum Uckermark GmbH, DESY, Notkestr 85, D-22607 Hamburg, Germany, NASA Ames Research Center ( ARC ), Department of Chemistry, Center for Structural Biology, Vanderbilt University [Nashville], Biostatistique et Processus Spatiaux ( BIOSP ), Institute of Ecology [Jena], Friedrich-Schiller-Universität Jena, University of Rostock [Germany], Universität Stuttgart [Stuttgart], Oneonta, Zentrum für Innere Medizin, Klinikum Schwäbisch Gmünd/Stauferklinik, Physiopathologie du stress pancréatique, Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, Institut de Mathématiques de Marseille ( I2M ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Science [Freiburg], University of Freiburg [Freiburg], Institut für Mathematik [Berlin], Technische Universität Berlin ( TUB ), Department of Information Engineering, Computer Science and Mathematics, Università degli Studi dell'Aquila [L'Aquila] ( UNIVAQ.IT ), Department of Animal Sciences, North Carolina Agricultural and Technical State University, FEEM, Romagna Cancer Registry, IRST, Luigi Pierantoni Hospital, Observatoire sociologique du changement ( OSC ), Sciences Po-Centre National de la Recherche Scientifique ( CNRS ), Dipartimento di Chimica, Fisica e Ambiente, Università degli Studi di Udine - University of Udine [Italie], Department of Nuclear Medicine, PET/CT Centre, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Clinica di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche [Ancona] ( UNIVPM ), Universidade Nova de Lisboa ( UNINOVA ), Ottawa Hospital Research Institute [Ottawa] ( OHRI ), Oncologia Medica, Ospedali Riuniti, Ospedale 'San Vincenzo', NIPE, CIPES, European Synchrotron Radiation Facility ( ESRF ), Departamento de Engenharia Informática, Faculdade de Engenharia [Porto] ( FEUP ), Universidade do Porto [Porto]-Universidade do Porto [Porto], 3Decide, Unité de recherche Amélioration, Génétique et Physiologie Forestières ( UAGPF ), Universidade Federal de Campina Grande [Campina Grande] ( UFCG ), Instituto de Engenharia de Sistemas e Computadores ( INESC ), Departamento de Ciências Biológicas, Universidade Regional do Cariri ( URCA Brasil ), Department of Biochemistry and Molecular Biology [Barcelona, Spain], Universitat de Barcelona ( UB ), Associated Unit to Consejo Superior de Investigaciones Científicas - CSIC [Barcelona, Spain], University of Barcelona-Institute of Biomedicine - IBUB [Barcelona, Spain], IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau ( CARE ), Institut de recherches sur la catalyse et l'environnement de Lyon ( IRCELYON ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'analyse et d'architecture des systèmes [Toulouse] ( LAAS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Institut National Polytechnique [Toulouse] ( INP ), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Instituto de Ciencia de Materiales de Madrid [Madrid] ( ICMM ), Interactions, Corpus, Apprentissages, Représentations ( ICAR ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique ( CNRS ), Institut d'Investigacions Biomèdiques August Pi i Sunyer ( IDIBAPS ), North Region Cancer Registry of Portugal, UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux ( EPOC ), Observatoire aquitain des sciences de l'univers ( OASU ), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Paediatrics and Intensive Care, Hospital Universitari Sant Joan de Deu, Laboratoire de Psychologie Sociale ( LPS ), Aix Marseille Université ( AMU ), Universitat de València ( UV ), Instituto de Cienca de Materiales de Madrid [Madrid] ( ICMM ), Biology, New Mexico State University, New Mexico State University, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department - Carnegie Mellon University, University of Pittsburgh, Laboratoire de Sciences Actuarielle et Financière ( SAF ), Université de Lyon-Université de Lyon, Instituto de Oncologia Corachan ( IDOC ), Laboratoire d'informatique de l'école normale supérieure ( LIENS ), École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Experimental Quantum Optics and Photonics Group, University of Strathclyde, Institut de recherches Asiatiques ( IrAsia ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Européen de Réalité Virtuelle ( CERV ), École Nationale d'Ingénieurs de Brest ( ENIB ), Sol Agro et hydrosystème Spatialisation ( SAS ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), Centre de recherche cerveau et cognition ( CERCO ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Géomatériaux et Environnement ( LGE ), Université Paris-Est Marne-la-Vallée ( UPEM ), Hôpital Ambroise Paré [AP-HP], Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université de Nantes (UN), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Salzburger Landesklinikum - Uniklinikum Salzburg (SALK), Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Biologie Computationnelle (IBC), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University [Belgium] (UGENT), Antwerp University Hospital [Edegem] (UZA), Hillerød Hospital, Copenhagen University Hospital-Copenhagen University Hospital, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Université Paris 1 Panthéon-Sorbonne (UP1), École nationale supérieure d'architecture de Nantes (ENSA Nantes), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bretagne Occidentale - École de sages-femmes (UBO UFR MSS ESF), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Alexis Vautrin (CAV), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Département informatique (INFO), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Libourne, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation FondaMental [Créteil], Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service de Gynécologie et d'Obstétrique (CHU Lyon), Hospices Civils de Lyon (HCL), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Hôpital privé Toulon Hyères : Sainte Marguerite, Clinique des Quatre Pavillons, Lormont, France, Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), NASA Ames Research Center (ARC), Biostatistique et Processus Spatiaux (BioSP), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], University of Rostock, State University of New York at Oneonta (SUNY Oneonta), State University of New York (SUNY), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Klinikum Deggendorf, Technische Universität Berlin (TU), Università degli Studi dell'Aquila (UNIVAQ), North Carolina A&T State University, University of North Carolina System (UNC)-University of North Carolina System (UNC), Observatoire sociologique du changement (OSC), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Università Politecnica delle Marche [Ancona] (UNIVPM), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ottawa Hospital Research Institute [Ottawa] (OHRI), European Synchrotron Radiation Facility (ESRF), Departamento de Engenharia Informática [Porto], Faculdade de Engenharia da Universidade do Porto (FEUP), Universidade do Porto-Universidade do Porto, Universidade Federal de Campina Grande [Campina Grande] (UFCG), Instituto de Engenharia de Sistemas e Computadores (INESC), Universidade Regional do Cariri (URCA Brasil), Universitat de Barcelona (UB), IRCELYON-Catalytic and Atmospheric Reactivity for the Environment (CARE), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitario de Valme, Anenida de Bellavista s/n, Sevilla 41014, Spain, Hospital Son Llatzer, Universitat de València (UV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hospital Universitari Son Espases, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Instituto de Oncologia Corachan (IDOC), Laboratoire d'informatique de l'école normale supérieure (LIENS), École normale supérieure - Paris (ENS Paris), Institut de recherches Asiatiques (IrAsia), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Sol Agro et hydrosystème Spatialisation (SAS), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Géomatériaux et Environnement (LGE), Université Paris-Est Marne-la-Vallée (UPEM), Fédération Francophone de Cancérologie Digestive (FFCD), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Department of Information Engineering, Computer Science and Mathematics = Dipartimento di Ingegneria e Scienze dell'Informazione e Matematica [L'Aquila] (DISIM), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département d'informatique - ENS Paris (DI-ENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institute of Biomedicine - IBUB [Barcelona, Spain]-University of Barcelona, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Environnement et Agronomie (E.A.)-Biologie et Amélioration des Plantes (BAP)-Fourrages Environnement Ruminants Lusignan (FERLUS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, University of Florence (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Ghent University [Belgium] (UGENT), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université du Québec à Montréal (UQAM), Université Panthéon-Sorbonne (UP1), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Franche-Comté (UFC)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Biostatistique et Processus Spatiaux (BIOSP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Technische Universität Berlin (TUB), Università degli Studi dell'Aquila [L'Aquila] (UNIVAQ.IT), Universidade Nova de Lisboa (NOVA), Faculdade de Engenharia [Porto] (FEUP), Unité de recherche Amélioration, Génétique et Physiologie Forestières (UAGPF), IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau (CARE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Emile, J, Julie, C, Le Malicot, K, Lepage, C, Tabernero, J, Mini, E, Folprecht, G, Van Laethem, J, Dimet, S, Boulagnon-Rombi, C, Allard, M, Penault-Llorca, F, Bennouna, J, Laurent-Puig, P, Taieb, J, Bidoli, P, Emile, J. -F., Julie, C., Le Malicot, K., Lepage, C., Tabernero, J., Mini, E., Folprecht, G., Van Laethem, J. -L., Dimet, S., Boulagnon-Rombi, C., Allard, M. -A., Penault-Llorca, F., Bennouna, J., Laurent-Puig, P., Taieb, J., Thaler, J., Greil, R., Gaenzer, J., Eisterer, W., Tschmelitsch, J., Keil, F., Samonigg, H., Zabernigg, A., Schmid, F., Steger, G., Steinacher, R., Andel, J., Jagdt, B., Lang, A., Fridrik, M., Fugger, R., Hofbauer, F., Woell, E., Geissler, D., Lenauer, A., Prager, M., D'Haens, G., Demolin, G., Kerger, J., Deboever, G., Ghillebert, G., Polus, M., Van Cutsem, E., Kalantari, H. R., Delaunoit, T., Goeminne, J. C., Peeters, M., Vergauwe, P., Houbiers, G., Humblet, Y., Janssens, J., Schrijvers, D., Vanderstraeten, E., Vermorken, J., Van Daele, D., Ferrante, M., Forget, F., Hendlisz, A., Yilmaz, M., Nielsen, S. E., Vestermark, L., Larsen, J., Zawadi, M. -A., Bouche, O., Mineur, L., Bennouna-Louridi, J., Dourthe, L. M., Ychou, M., Boucher, E., Pezet, D., Desseigne, F., Ducreux, M., Texereau, P., Miglianico, L., Rougier, P., Fratte, S., Levache, C. -B., Merrouche, Y., Ellis, S., Locher, C., Ramee, J. -F., Garnier, C., Viret, F., Chauffert, B., Cojean-Zelek, I., Michel, P., Lecaille, C., Borel, C., Seitz, J. -F., Smith, D., Lombard-Bohas, C., Andre, T., Gornet, J. -M., Fein, F., Coulon-Sfairi, M. -A., Kaminsky, M. -C., Lagasse, J. -P., Luet, D., Etienne, P. -L., Gasmi, M., Vanoli, A., Nguyen, S., Aparicio, T., Perrier, H., Stremsdoerfer, N., Laplaige, P., Arsene, D., Auby, D., Bedenne, L., Coriat, R., Denis, B., Geoffroy, P., Piot, G., Becouarn, Y., Bordes, G., Deplanque, G., Dupuis, O., Fruge, F., Guimbaud, R., Lecomte, T., Lledo, G., Sobhani, I., Asnacios, A., Azzedine, A., Desauw, C., Galais, M. -P., Gargot, D., Lam, Y. -H., Abakar-Mahamat, A., Berdah, J. -F., Catteau, S., Clavero-Fabri, M. -C., Codoul, J. -F., Legoux, J. -L., Goldfain, D., Guichard, P., Verge, D. P., Provencal, J., Vedrenne, B., Brezault-Bonnet, C., Cleau, D., Desir, J. -P., Fallik, D., Garcia, B., Gaspard, M. -H., Genet, D., Hartwig, J., Krummel, Y., Budnik, T. M., Palascak-Juif, V., Randrianarivelo, H., Rinaldi, Y., Aleba, A., Darut-Jouve, A., de Gramont, A., Hamon, H., Wendehenne, F., Matzdorff, A., Stahl, M. K., Schepp, W., Burk, M., Mueller, L., Geissler, M., Mantovani-Loeffler, L., Hoehler, T., Asperger, W., Kroening, H., von Weikersthal, L. F., Fuxius, S., Groschek, M., Meiler, J., Trarbach, T., Rauh, J., Ziegenhagen, N., Kretzschmar, A., Graeven, U., Nusch, A., von Wichert, G., Hofheinz, R. -D., Kleber, G., Schmidt, K. -H., Vehling-Kaiser, U., Baum, C., Schuette, J., Haag, G. M., Holtkamp, W., Potenberg, J., Reiber, T., Schliesser, G., Schmoll, H. -J., Schneider-Kappus, W., Abenhardt, W., Denzlinger, C., Henning, J., Marxsen, B., Derigs, H. G., Lambertz, H., Becker-Boost, I., Caca, K., Constantin, C., Decker, T., Eschenburg, H., Gabius, S., Hebart, H., Hoffmeister, A., Horst, H. -A., Kremers, S., Leithaeuser, M., Mueller, S., Wagner, S., Daum, S., Schlegel, F., Stauch, M., Heinemann, V., Maiello, E., Latini, L., Zaniboni, A., Amadori, D., Aprile, G., Barni, S., Mattioli, R., Martoni, A., Passalacqua, R., Nicolini, M., Pasquini, E., Rabbi, C., Aitini, E., Ravaioli, A., Barone, C., Biasco, G., Tamberi, S., Gambi, A., Verusio, C., Marzola, M., Lelli, G., Boni, C., Cascinu, S., Bidoli, P., Vaghi, M., Cruciani, G., Di Costanzo, F., Sobrero, A., Petrioli, R., Aglietta, M., Alabiso, O., Capuzzo, F., Falcone, A., Corsi, D. C., Labianca, R., Salvagni, S., Chiara, S., Ciuffreda, L., Ferrau, F., Giuliani, F., Lonardi, S., Gebbia, N., Mantovani, G., Sanches, E., Mellidez, J. C., Santos, P., Freire, J., Sarmento, C., Costa, L., Pinto, A. M., Barroso, S., Santo, J. E., Guedes, F., Monteiro, A., Sa, A., Furtado, I., Salazar, R., Aguilar, E. A., Herrero, F. R., Valera, J. S., Ayerbes, M. V., Batlle, J. F., Gil, S., Esteve, A. A., Garcia-Giron, C., Vivanco, G. L., Salvia, A. S., Orduna, V. A., Garcia, R. V., Gallego, J., Sureda, B. M., Remon, J., Safont Aguilera, M. J., Nogueras, L. C., Merino, B. Q., Castro, C. G., de Prado, P. M., Pericay, C. P., Figueiras, M. C., Jordan, I. G., Gome Reina, M. J., Garcia, A. L. -L., Garcia-Ramos, A. A., Cervantes, A., Martos, C. F., Gaspar, E. M., Montero, I. C., Emperador, P. E., Carbonero, A. L., Castillo, M. G., Garcia, T. G., Lopez, J. G., Flores, E. G., Morales, M. G., Munoz, M. L., Martin, A. L., Maurel, J., Camara, J. C., Garcia, R. D., Salgado, M., Busquier, I. H., Ruiz, T. C., Munoa, A. L., Aliguer, M. N., de Taranco, A. V. O., Urena, M. M., Gaspa, F. L., Ponce, J. J., Roig, C. B., Jimenez, P. V., Brotons, A. G., Rodriguez, S. A., Martinez, J. A., Ruiz, L. C., Ruiz, M. C., Bridgewater, J., Glynne-Jones, R., Tahir, S., Hickish, T., Cassidy, J., and Samuel, L.
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Medizin, Leucovorin, Prospective cohort study, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, FOLFOX, Organoplatinum Compounds/therapeutic use, Antineoplastic Combined Chemotherapy Protocols, tudy, Lymphocytes, Prospective Studies, Leucovorin/therapeutic use, Middle Aged, Prognosis, 3. Good health, Colorectal carcinoma, Fluorouracil, 030220 oncology & carcinogenesis, Predictive value of tests, Colonic Neoplasms, Biomarker (medicine), Lymphocytes/pathology, Female, Adjuvant, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fluorouracil/therapeutic use, Biomarkers, Tumor/analysis, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Predictive Value of Tests, Biomarker, Immune response, Internal medicine, medicine, Biomarkers, Tumor, Humans, Survival analysis, Aged, business.industry, medicine.disease, Survival Analysis, Surgery, 030104 developmental biology, Prospective cohort&nbsp, Multivariate Analysis, Colonic Neoplasms/diagnosis, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, business
Abstract: IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations of LI with patient recurrence and survival were analysed, and multivariable models were adjusted for treatment and relevant factors. Automated testing of LI was performed on virtual slides without access to clinical data.ResultsAmong the 1220 CC patients enrolled, LI was high, low and not evaluable in 241 (19.8%), 790 (64.8%) and 189 (15.5%), respectively. Primary objective was met with a 2-year recurrence rate of 14.4% versus 21.1% in patients with high and low LI, respectively (p = 0.02). Patients with high LI also had better disease free survival (DFS) and overall survival (OS). Tumour stage, grade, RAS status and BRAF status were with LI the only prognostic markers in multivariable analysis for OS. Subgroup analyses revealed that high LI had better DFS and OS in mismatch repair (MMR) proficient patients, and in patients without RAS mutation, but not in MMR deficient and RAS mutated patients.ConclusionAlthough this is the first validation with high level of evidence (IIB) of the prognostic value of a LI test in colon cancers, it still needs to be confirmed in independent series of colon cancer patients.
Published: 2017
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13. Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort

Author: Sylvain Manfredi, Eric Terrebonne, Gael Deplanque, Jean-Yves Scoazec, Anne-Laure Ran-Royo, Marc Ferec, Guillaume Cadiot, Eric Maringe, C. Desauw, Philippe Rougier, Thomas Aparicio, Castex, Guillaume Geslin, Jean-François Seitz, François Dewaele, Karine Bouhier-Leporrier, Vincent Hautefeuille, Anne Thirot-Bidault, Olivia Hentic, G. Roquin, David Tougeron, Olivier Dubreuil, C. Rebischung, Laetitia Dahan, Ivan Borbath, Jean-Louis Legoux, Laurent Bedenne, Sandrine Lavau denes, Catherine Ligeza, Mathieu Baconnier, K. Le Malicot, Laurent Cany, Côme Lepage, Thierry Lecomte, Céline Lepère, I. Bonnet, Valérie Rossi, Isabelle Wanicki Caron, Laetitia Stephanie, Cedric Lecaille, Eric Baudin, Thomas Walter, David Malka, Patricia Niccoli, Vincent Bourgeois, Etienne Suc, Joël Guigay, Romain Coriat, Rosine Guimbaud, Catherine Lombard-Bohas, Caroline Petorin, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Gustave Roussy (IGR), Fédération Francophone de la Cancérologie Digestive, FFCD, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], CHU Valenciennes, CHU Toulouse [Toulouse], Hôpital Cochin [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU de Lille, Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Hôpital de la source, CHU Lyon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France, affiliation inconnue, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Clinique Saint-Jean Languedoc [Toulouse] (CSJL), CHU Amiens-Picardie, Hôpital Duchenne, CH Boulogne sur Mer, Polyclinique Francheville, Centre Catherine-de-Sienne [Nantes] (CCS), Polyclinique Bordeaux Nord Aquitaine, Hôpital Michallon, CH du Haut Anjou (Château-Gontier), CH Annecy Genevois, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier du pays de Morlaix, Hôpital Saint-Joseph, Assistance Publique-Hôpitaux de Paris, Cabinet privé des Dr Geslin Provost (Vannes), CHU Rouen, Normandie Université (NU), CHU Dupuytren, CHU Dijon, Clinique Mutualiste de l'Estuaire (Saint Nazaire), Hospices Civils de Beaune [Centre hospitalier de Beaune], Centre de radiothérapie et d'oncologie médicale privée (Béziers), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Côte d'Azur (UCA)-UNICANCER
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Carboplatin, Cohort Studies, 03 medical and health sciences, Gastrointestinal cancer, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, FOLFIRI Regimen, Humans, Neoplasm Metastasis, Prospective cohort study, Aged, Etoposide, Gastrointestinal Neoplasms, Univariate analysis, Performance status, business.industry, Large cell, Hazard ratio, Ki67 index, medicine.disease, Prognosis, 3. Good health, Carcinoma, Neuroendocrine, Pancreatic Neoplasms, Treatment, Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, Neuroendocrine carcinoma, Female, Cisplatin, business, Cohort study
Abstract: IF 6.029; International audience; BackgroundDiagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC.Patients and methodsAll patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded.Results253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0–1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20–100). Median overall survival was 15.6 (13.6–17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE > 2 upper limit of normal [ULN]; HR = 3.2), CgA > 2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72).ConclusionsWe report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.
Published: 2017
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14. Rectal cancer: French Intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO)

Author: Thierry Conroy, Guillaume Cadiot, Thierry André, Société Française de Chirurgie Digestive, Jean-François Bosset, Frédéric Bibeau, Jean-Pierre Gerard, Jean-Louis Legoux, Olivier Bouché, Laurent Bedenne, Guillaume Portier, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Hospitalier Régional d'Orléans (CHRO), CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Reims (CHU Reims), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: medicine.medical_specialty, Colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Guidelines, 03 medical and health sciences, 0302 clinical medicine, Risk groups, Neoadjuvant treatment, National recommendations, medicine, Rectal Adenocarcinoma, Humans, Rectal cancer, Pathological, Neoplasm Staging, Gynecology, Hepatology, medicine.diagnostic_test, business.industry, Rectal Neoplasms, General surgery, Proctocolectomy, Restorative, Gastroenterology, Rectum, Evidence-based medicine, medicine.disease, Neoadjuvant Therapy, 3. Good health, Endoscopy, Clinical Practice, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, Follow-Up Studies
Abstract: IF 3.061; International audience; IntroductionThis document is a summary of the French Intergroup guidelines regarding the management of rectal adenocarcinoma published in February 2016.MethodThis collaborative work, under the auspices of most of the French medical societies involved in the management of rectal cancer, is based on the previous guidelines published in 2013. Recommendations are graded into 3 categories according to the level of evidence of data found in the literature.ResultsIn agreement with the ESMO guidelines (2013), non-metastatic rectal cancers have been stratified in 4 risk groups according to endoscopy, MRI or endorectal-ultrasonography. Locally-advanced tumors are limited to groups 3 and 4 (T3 ≥4 cm or T3c–d or N1-2 or T4). These tumors are usually treated using neoadjuvant treatment and total proctectomy (TME). Adjuvant treatment depends on the pathological findings. Very early (group 1) or early (group 2) tumors are managed mainly by surgery, and organ preservation may be an option in selected cases. For metastatic tumors, the recommendations are based on less robust evidence and chemotherapy plays a major role.ConclusionSuch recommendations are constantly being optimized and each individual case must be discussed within a Multi-Disciplinary Team.
Published: 2017
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15. Prospective, Randomized, Multicenter, Phase III Study of Fluorouracil, Leucovorin, and Irinotecan Versus Epirubicin, Cisplatin, and Capecitabine in Advanced Gastric Adenocarcinoma: A French Intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) Study

Author: Pauline Ries, Olivier Bouché, Eveline Boucher, Laurent Bedenne, Emilie Maillard, Philippe Rougier, S. Nguyen, Rosine Guimbaud, Pierre-Luc Etienne, Pascal Hammel, Christine Rebischung, Thierry André, Ahmed Azzedine, Jean-Marc Gornet, Thomas Aparicio, Marc Ychou, and Christophe Louvet
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Leucovorin, Adenocarcinoma, Irinotecan, Deoxycytidine, Capecitabine, Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Prospective Studies, Epirubicin, business.industry, Cancer, Middle Aged, medicine.disease, Survival Analysis, Clinical trial, Treatment Outcome, Fluorouracil, Quality of Life, FOLFIRI, Camptothecin, Female, Esophagogastric Junction, France, Cisplatin, business, Follow-Up Studies, medicine.drug
Abstract: Purpose To compare epirubicin, cisplatin, and capecitabine (ECX) with fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatments in patients with advanced gastric or esophagogastric junction (EGJ) adenocarcinoma. Patients and Methods This open, randomized, phase III study was carried out in 71 centers. Patients with locally advanced or metastatic gastric or EGJ cancer were randomly assigned to receive either ECX as first-line treatment (ECX arm) or FOLFIRI (FOLFIRI arm). Second-line treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). The primary criterion was time-to-treatment failure (TTF) of the first-line therapy. Secondary criteria were progression-free survival (PFS), overall survival (OS), toxicity, and quality of life. Results In all, 416 patients were included (median age, 61.4 years; 74% male). After a median follow-up of 31 months, median TTF was significantly longer with FOLFIRI than with ECX (5.1 v 4.2 months; P = .008). There was no significant difference between the two groups in median PFS (5.3 v 5.8 months; P = .96), median OS (9.5 v 9.7 months; P = .95), or response rate (39.2% v 37.8%). First-line FOLFIRI was better tolerated (overall rate of grade 3 to 4 toxicity, 69% v 84%; P < .001; hematologic adverse events [AEs], 38% v 64.5%; P < .001; nonhematologic AEs: 53% v 53.5%; P = .81). Conclusion FOLFIRI as first-line treatment for advanced gastric and EGJ cancer demonstrated significantly better TTF than did ECX. Other outcome results indicate that FOLFIRI is an acceptable first-line regimen in this setting and should be explored as a backbone regimen for targeted agents.
Published: 2014
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16. Incidence and Patterns of Late Recurrences in Rectal Cancer Patients

Author: Véronique Bouvier, Anne-Marie Bouvier, Fabien Rollot, Guy Launoy, Valérie Jooste, Jean Faivre, Laurent Bedenne, and Vanessa Cottet
Subjects: Male, medicine.medical_specialty, Time Factors, Colorectal cancer, Population, Metastasis, Surgical oncology, medicine, Humans, Registries, Stage (cooking), education, Aged, Retrospective Studies, education.field_of_study, Rectal Neoplasms, business.industry, Incidence, Incidence (epidemiology), Hazard ratio, Middle Aged, Prognosis, medicine.disease, Confidence interval, Surgery, Oncology, Population Surveillance, Female, France, Neoplasm Recurrence, Local, business
Abstract: Long-term recurrences of rectal cancer raised questions about the possible benefit of prolonging the recommended active 5-year clinical and endoscopic surveillance. The aim of this study was to determine for the first time, incidence and patterns of late 10-year recurrence after curative resection of rectal cancer. The study included 1,222 patients with rectal cancer resected for cure between 1985 and 2000 from those registered in two French population-based digestive cancer registries. Information about local recurrences and distant metastases at 10 years was retrospectively and actively collected up to January 1, 2011. Although the overall 5-year cumulated rate was 39.5 %, the 10-year cumulated rate was 44.1 % (25.6 % for local recurrence and 29.9 % for distant metastases). In multivariate analyses, TNM stage was associated with a higher risk of local recurrence (hazard ratio [HR] stage III vs. stage I = 3.98 [95 % confidence interval, 2.66–5.94]) and of distant metastasis (HR = 3.60 [2.65–4.91]). Preoperative radiotherapy decreased the risk of local recurrence (HR = 0.43 [0.28–0.66]), but not the risk of metastasis. Patients diagnosed between 1995 and 2000 were less prone to develop long-term metastasis than those diagnosed between 1985 and 1989 (HR = 0.66 [0.49–0.88]). Among patients without recurrence 5 years after diagnosis, one patient in 13 developed a recurrence between 5 and 10 years. Late recurrences do exist. A personalised surveillance could be extended until 10 years according to the characteristics of primary tumour and the patient.
Published: 2014
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17. Surgery Alone Versus Chemoradiotherapy Followed by Surgery for Stage I and II Esophageal Cancer: Final Analysis of Randomized Controlled Phase III Trial FFCD 9901

Author: Emilie Maillard, F. Mornex, William B. Robb, Pascal-Alexandre Thomas, Laetitia Dahan, Valérie Le Brun-Ly, Valérie Boige, Jean-Yves Mabrut, Jean-François Bosset, Bernard Meunier, Jean-François Seitz, Denis Pezet, Christophe Mariette, Jean-Pierre Triboulet, and Laurent Bedenne
Subjects: Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, Esophageal cancer, medicine.disease, law.invention, Surgery, Clinical trial, Radiation therapy, Oncology, Randomized controlled trial, law, Fluorouracil, Concomitant, Clinical endpoint, Medicine, business, Chemoradiotherapy, medicine.drug
Abstract: Purpose Although often investigated in locally advanced esophageal cancer (EC), the impact of neoadjuvant chemoradiotherapy (NCRT) in early stages is unknown. The aim of this multicenter randomized phase III trial was to assess whether NCRT improves outcomes for patients with stage I or II EC. Methods The primary end point was overall survival. Secondary end points were disease-free survival, postoperative morbidity, in-hospital mortality, R0 resection rate, and prognostic factor identification. From June 2000 to June 2009, 195 patients in 30 centers were randomly assigned to surgery alone (group S; n = 97) or NCRT followed by surgery (group CRT; n = 98). CRT protocol was 45 Gy in 25 fractions over 5 weeks with two courses of concomitant chemotherapy composed of fluorouracil 800 mg/m2 and cisplatin 75 mg/m2. We report the long-term results of the final analysis, after a median follow-up of 93.6 months. Results Pretreatment disease was stage I in 19.0%, IIA in 53.3%, and IIB in 27.7% of patients. For group CRT compared with group S, R0 resection rate was 93.8% versus 92.1% (P = .749), with 3-year overall survival rate of 47.5% versus 53.0% (hazard ratio [HR], 0.99; 95% CI, 0.69 to 1.40; P = .94) and postoperative mortality rate of 11.1% versus 3.4% (P = .049), respectively. Because interim analysis of the primary end point revealed an improbability of demonstrating the superiority of either treatment arm (HR, 1.09; 95% CI, 0.75 to 1.59; P = .66), the trial was stopped for anticipated futility. Conclusion Compared with surgery alone, NCRT with cisplatin plus fluorouracil does not improve R0 resection rate or survival but enhances postoperative mortality in patients with stage I or II EC.
Published: 2014
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18. Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial

Author: John Bridgewater, Eric Van Cutsem, Josef Thaler, Côme Lepage, Lone Petersen, Jean-Luc Van Laethem, Fabien Subtil, Josep Tabernero, Julien Taieb, Laurence Collette, Philippe Rougier, Pierre Laurent-Puig, Enrico Mini, Jean-François Emile, Hélène Blons, Laurent Bedenne, Ramon Salazar, Gunnar Folprecht, Taieb, J, Tabernero, J, Mini, E, Subtil, F, Folprecht, G, Van Laethem, J, Thaler, J, Bridgewater, J, Petersen, L, Blons, H, Collette, L, Van Cutsem, E, Rougier, P, Salazar, R, Bedenne, L, Emile, J, Laurent-Puig, P, Lepage, C, Bidoli, P, Meiler, Johannes (Beitragende*r), Trarbach, Tanya (Beitragende*r), Taieb J, Tabernero J, Mini E, Subtil F, Folprecht G, Van Laethem JL, Thaler J, Bridgewater J, Petersen LN, Blons H, Collette L, Van Cutsem E, Rougier P, Salazar R, Bedenne L, Emile JF, Laurent-Puig P, Lepage C, PETACC-8 Study Investigator, and Biasco G
Subjects: Male, Oncology, Organoplatinum Compounds, Colorectal cancer, stage III, Medizin, medicine.disease_cause, Antineoplastic Combined Chemotherapy Protocols, cetuximab, Infusions, Intravenous, oxaliplatinum, education.field_of_study, Cetuximab, Exons, Middle Aged, Intention to Treat Analysis, 3. Good health, Oxaliplatin, colon cancer, Chemotherapy, Adjuvant, Colonic Neoplasms, 5-FLUOROURACIL, Female, Drug Eruptions, Fluorouracil, KRAS, medicine.drug, Adult, Diarrhea, Mucositis, medicine.medical_specialty, phase 3 trial, Bevacizumab, Perforation (oil well), Population, Adenocarcinoma, open-label, Antibodies, Monoclonal, Humanized, Disease-Free Survival, Proto-Oncogene Proteins p21(ras), Proto-Oncogene Proteins, Internal medicine, medicine, Humans, education, neoplasms, Aged, Neoplasm Staging, fluouracil, leucovorin, (PETACC-8), business.industry, medicine.disease, digestive system diseases, ras Proteins, FOLFOX4, business
Abstract: Summary Background Since the 1990s, fluorouracil-based adjuvant chemotherapy has significantly reduced the risk of tumour recurrence in patients with stage III colon cancer. We aimed to assess whether the addition of cetuximab to standard adjuvant oxaliplatin, fluorouracil, and leucovorin chemotherapy (FOLFOX4) in patients with stage III colon cancer improved disease-free survival (DFS). Methods For this open-label, randomised phase 3 study done in nine European countries, we enrolled patients through an interactive voice response system to the central randomisation centre, with a central stratified permuted block randomisation procedure. We randomly assigned patients with resected (R0) stage III disease (1:1) to receive 12 cycles of FOLFOX4 twice a week with or without cetuximab. Patients were stratified by N-status (N1 vs N2), T-status (T1-3 vs T4), and obstruction or perforation status (no obstruction and no perforation vs obstruction or perforation or both). A protocol amendment (applied in June, 2008, after 2096 patients had been randomly assigned to treatment-restricted enrolment to patients with tumours wild-type at codons 12 and 13 in exon 2 of the KRAS gene ( KRAS exon 2 wild-type). The primary endpoint was DFS. Analysis was intention to treat in all patients with KRAS exon 2 wild-type tumours. The study is registered at EudraCT, number 2005-003463-23. Findings Between Dec 22, 2005, and Nov 5, 2009, 2559 patients from 340 sites in Europe were randomly assigned. Of these patients, 1602 had KRAS exon 2 wild-type tumours (intention-to-treat population), 791 in the FOLFOX4 plus cetuximab group and 811 in the FOLFOX4 group. Median follow-up was 3·3 years (IQR 3·2–3·4). In the experimental and control groups, DFS was similar in the intention-to-treat population (hazard ratio [HR] 1·05; 95% CI 0·85–1·29; p=0·66), and in patients with KRAS exon 2/ BRAF wild-type (n=984, HR 0·99; 95% CI 0·76–1·28) or KRAS exon 2-mutated tumours (n=742, HR 1·06; 95% CI 0·82–1·37). We noted heterogeneous responses to the addition of cetuximab in preplanned subgroup analyses. Grade 3 or 4 acne-like rash (in 209 of 785 patients [27%] vs four of 805 [ vs 70 [9%]), mucositis (63 [8%] vs 10 [1%]), and infusion-related reactions (55 [7%] vs 30 [4%]) were more frequent in patients treated with FOLFOX4 plus cetuximab than in those patients who received FOLFOX4 alone. Interpretation The addition of cetuximab to FOLFOX4 did not improve DFS compared with FOLFOX4 alone in patients with KRAS exon 2 wild-type resected stage III colon cancer. This trial cannot conclude on the benefit of cetuximab in the studied population, but the heterogeneity of response suggests that further investigation of the role of FOLFOX4 plus cetuximab in specific patient subgroups is warranted. Funding Federation Francophone de Cancerologie Digestive (FFCD), Merck KGaA, and Sanofi-Aventis.
Published: 2014
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19. Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial

Author: Alban Denys, Jean-Louis Jouve, Marc Bardou, Patrick Hillon, Sandrine Dabakuyo, Maeva Wendremaire, Franck Bonnetain, Boris Guiu, Côme Lepage, Jean-Pierre Cercueil, Mathieu Boulin, Bruno Chauffert, P. Guerard, A. Grandvuillemin, Anne Minello, and Laurent Bedenne
Subjects: medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, medicine.disease, Pharmacokinetic analysis, Surgery, Pharmacokinetics, Internal medicine, Hepatocellular carcinoma, Toxicity, medicine, Idarubicin, Pharmacology (medical), Myocardial infarction, business, Adverse effect, Objective response, medicine.drug
Abstract: SummaryBackground A phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC). Aim To estimate the maximum-tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life. Methods Patients received a single TACE session with injection of 2 mL drug-eluting beads (DEBs; DC Bead 300–500 μm) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of patients. Results Twenty-one patients were enrolled, including nine patients at 5 mg, six patients at 10 mg, and six patients at 15 mg. One patient at each dose level experienced DLT (acute myocardial infarction, hyperbilirubinaemia and elevated aspartate aminotransferase (AST) at 5-, 10- and 15-mg, respectively). The calculated MTD of idarubicin was 10 mg. The most frequent grade ≥3 adverse events were pain, elevated AST, elevated γ-glutamyltranspeptidase and thrombocytopenia. At 2 months, the objective response rate was 52% (complete response, 28%, and partial response, 24%) by modified Response Evaluation Criteria in Solid Tumours. The median time to progression was 12.1 months (95% CI 7.4 months – not reached); the median overall survival was 24.5 months (95% CI 14.7 months – not reached). Pharmacokinetic analysis demonstrated the ability of DEBs to release idarubicin slowly. Conclusions Using drug-eluting beads, the maximum-tolerated dose of idarubicin was 10 mg per TACE session. Encouraging responses and median time to progression were observed. Further clinical investigations are warranted (NCT01040559).
Published: 2014
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20. Predictive factors of transarterial chemoembolisation toxicity in unresectable hepatocellular carcinoma

Author: Patrick Hillon, Jean Louis Jouve, Ludwig Serge Aho, Héloïse Adam, Cyrille Di Martino, Anne Minello, Laurent Bedenne, Boris Guiu, P. Fagnoni, Jean-Pierre Cercueil, Mathieu Boulin, and Côme Lepage
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Multivariate analysis, Logistic regression, Gastroenterology, Cohort Studies, Hepatitis B, Chronic, Liver Cirrhosis, Alcoholic, Risk Factors, Internal medicine, medicine, Humans, In patient, Aspartate Aminotransferases, Chemoembolization, Therapeutic, Adverse effect, Aged, Retrospective Studies, Aged, 80 and over, Hepatology, business.industry, Liver Neoplasms, Retrospective cohort study, Acute Kidney Injury, Hepatitis C, Chronic, Liver Failure, Acute, Middle Aged, medicine.disease, University hospital, Tumor Burden, Surgery, Logistic Models, Treatment Outcome, Doxorubicin, Hepatic Encephalopathy, Hepatocellular carcinoma, Multivariate Analysis, Toxicity, Female, Chemical and Drug Induced Liver Injury, Idarubicin, business
Abstract: Background Transarterial chemoembolisation (TACE) is an effective treatment for unresectable hepatocellular carcinoma (HCC), but can cause severe toxicity. Aim To identify predictive factors of severe TACE-related toxicity in patients with unresectable HCC. Methods All HCC patients who underwent TACE at the Dijon University Hospital between 2008 and 2011 were included in this retrospective study. Severe TACE-related toxicity was defined as the occurrence of any adverse event grade ≥4, or any adverse event that caused a prolongation of hospitalisation of >8 days, or any additional hospitalisation within 1 month after TACE. Factors predicting toxicity were identified using a logistic regression model. The robustness of the final model was confirmed using bootstrapping (500 replications). Results 124 patients were included, median age was 67 years and 90% were male; 22 patients (18%) experienced severe TACE-related toxicity. Factors that independently predicted severe TACE-related toxicity in multivariate analysis were total tumour size (OR, 1.15 cm −1 ; 95%CI, 1.04–1.26; p = 0.01), and high serum AST levels (OR, 1.10 per 10 IU/l; 95%CI, 1.01–1.21; p = 0.04). The results were confirmed by bootstrapping. Conclusions Total tumour size and high serum AST levels were predictive factors of severe TACE-related toxicity in this hospital-based series of patients with unresectable HCC.
Published: 2014
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21. Adjuvant treatments for gastric cancer: From practice guidelines to clinical practice

Author: Laurent Bedenne, Anne Marie Bouvier, Caroline Azelie, Nicolas Cheynel, Jean Louis Jouve, Jean Faivre, Gilles Créhange, Philippe Maingon, and Côme Lepage
Subjects: Male, Oncology, medicine.medical_specialty, medicine.medical_treatment, Population, Stomach Neoplasms, Internal medicine, Carcinoma, Humans, Medicine, Registries, education, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, Hepatology, business.industry, Gastroenterology, Cancer, Retrospective cohort study, Chemoradiotherapy, Adjuvant, Middle Aged, medicine.disease, Cancer registry, Radiation therapy, Regimen, Logistic Models, Treatment Outcome, Chemotherapy, Adjuvant, Multivariate Analysis, Practice Guidelines as Topic, Female, France, Guideline Adherence, business, Adjuvant
Abstract: Background For gastric cancers, the benefits of adjuvant radiochemotherapy and of perioperative chemotherapy have been demonstrated since 2001 and 2006 respectively. The aim of this study was to evaluate the diffusion of adjuvant treatments in a French population. Methods 334 incident gastric cancers UICC Stage IB, II, III or IVM0 resected for cure and recorded in the Burgundy digestive cancer registry were retrospectively included. Patients were classified as having received an effective adjuvant treatment if they had been treated by adjuvant radiochemotherapy since 2001 or perioperative chemotherapy since 2006. Results The proportion of patients treated with an effective adjuvant treatment increased from 21.8% (2001–2005) to 40.1% (2006–2009). Patients treated in 2006–2009 were twice as likely to receive effective adjuvant treatment as those treated during the period 2001–2005. During the 2004–2009 period, 62.4% of cases were presented in a multidisciplinary team meeting. These patients were almost three times more likely to receive effective adjuvant treatment than patients excluded from multidisciplinary team consultation. Age was a significant factor, independent of comorbidities. Conclusion Administration of adjuvant treatment is still far from being considered a reference regimen in routine practice for R0 resected gastric cancer. The increase in multidisciplinary team meetings should improve the situation.
Published: 2014
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22. Effect of 5 years of imaging and CEA follow-up to detect recurrence of colorectal cancer: The FFCD PRODIGE 13 randomised phase III trial

Author: Philippe Deguiral, Roger Faroux, Sylvain Manfredi, Laurent Cany, Côme Lepage, Olivier Bouché, Antoine Adenis, Laurent Bedenne, M. Baconnier, Jean-Marc Phelip, Jean-Francois Ain, Denis Pezet, Eric Terrebone, and Karine Le Malicot
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Adenoma, Colorectal cancer, Colonoscopy, Clinical Protocols, Internal medicine, medicine, Carcinoma, Humans, Prospective Studies, Stage (cooking), Prospective cohort study, Early Detection of Cancer, Survival analysis, Aged, Ultrasonography, Aged, 80 and over, Hepatology, medicine.diagnostic_test, business.industry, General surgery, Gastroenterology, Middle Aged, medicine.disease, Survival Analysis, Carcinoembryonic Antigen, Intention to Treat Analysis, Dysplasia, Female, Neoplasm Recurrence, Local, Colorectal Neoplasms, Tomography, X-Ray Computed, business, Follow-Up Studies
Abstract: Colorectal cancer (CRC), the most common digestive cancer in rance, is a major public health problem. There are an estimated 0,000 new cases every year and 200,000 prevalent cases [1]. Its ncidence has increased by more than 50% over the past 20 years 24,000 new cases/year in 1980, 36,600 in 2000). On the other and, over the same period, the number of deaths has remained table (16,000 deaths in 2000), which reflects a major therapeutic rogress [2,3]. Around 75% of patients may benefit from surgical resection ith curative intent [4]. Among them, nearly 30% stage II and over 5% stage III patients present a loco-regional or distant recurrence r a metachronous cancer within 5 years of initial treatment [5]. his high risk of recurrence raises the question of postoperative onitoring in order to detect early recurrences and metachronous ancers at a curable stage. The annual incidence of adenomas is between 3 and 5%, and the umulative risk of metachronous cancer is 2% at 5 years and 7% t 20 years. Endoluminal recurrences and metachronous cancers re rare, therefore intensive endoscopic monitoring is not useful 5,6]. After resection of CRC, the French national thesaurus of good ractices in digestive cancer (TNCD) [7] recommends a colonoscopy ithin 6 months after surgery (if incomplete or of poor quality efore surgery), followed by another at 3 years and then every 5 ears in case of normal results. After excision of more than 3 adeomas or of one at-risk adenoma (size > 1 cm, villous contingent, igh grade dysplasia or in situ carcinoma), the first colonoscopy is erformed after 1 year.
Published: 2015
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23. Chemoradiation as medical treatment for esophageal cancer. Is surgery always necessary?

Author: J. L. Jouve, Laurent Bedenne, and S. Hamza
Subjects: Oncology
Abstract: Il estmaintenant prouve que la chimiotherapie (CT) et la radiochimiotherapie (RTCT) preoperatoire augmentent le taux de resection R0 et la survie globale. En plus, la RTCT entraine environ 30 % de reponses completes pathologiques. Par ailleurs, deux essais randomises ont montre que la survie etait similaire apres RTCT a visee curative ou apres RTCT preoperatoire suivie de chirurgie; ces resultats ont ete obtenus dans les cancers epidermoides localement avances, malgre des recidives locales plus frequentes. Dans l’un des essais (FFCD 9102), seuls les repondeurs cliniques a la RTCT etaient randomises entre chirurgie ou non; ainsi, les non-repondeurs pouvaient etre operes sans delai. De fait, les patients randomises et les nonrepondeurs operes avaient une survie non differente. Le benefice de la chirurgie est moins evident pour les recidives plus tardives. Quelques petites etudes non randomisees ont aborde cette question. Les taux de resection R0 y variaient entre 50 et 87 %, avec une survie a cinq ans de 0 a 33%et une mortalite operatoire de 12,5 a 25 %. Un changement radical de strategie se profile dans le cancer de l’oesophage, a savoir commencer par une RTCT a visee curative et n’operer que les nonrepondeurs ou les rechuteurs resecables. Avant de recommander cela, le benefice de la resection « de sauvetage » pour recidive retardee devra etre evalue dans un essai randomise strategique, actuellement en preparation par la FFCD et la FRENCH.
Published: 2013
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24. Impact of primary tumour resection on survival of patients with colorectal cancer and synchronous metastases treated by chemotherapy: Results from the multicenter, randomised trial Fédération Francophone de Cancérologie Digestive 9601

Author: S. Louafi, J.P. Pignon, C. Allonier, Michel Ducreux, Valérie Boige, Laurent Bedenne, O. Bouche, P. Deguiral, David Malka, B. Leduc, Jean-Luc Raoul, F.R. Ferrand, Abderrahmane Bourredjem, Matthieu Faron, and Mireille Mousseau
Subjects: Male, Oncology, Cancer Research, Prognostic variable, medicine.medical_specialty, Colorectal cancer, Antineoplastic Agents, Kaplan-Meier Estimate, Disease-Free Survival, Internal medicine, medicine, Humans, Progression-free survival, Digestive System Surgical Procedures, Aged, Proportional Hazards Models, Performance status, business.industry, Proportional hazards model, Hazard ratio, Middle Aged, medicine.disease, Log-rank test, Treatment Outcome, Female, Prior Primary, France, Colorectal Neoplasms, business
Abstract: To assess the impact of primary tumour resection on overall survival (OS) of patients diagnosed with stage IV colorectal cancer (CRC).Among the 294 patients with non-resectable colorectal metastases enrolled in the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 phase III trial, which compared different first-line single-agent chemotherapy regimens, 216 patients (73%) presented with synchronous metastases at study entry and constituted the present study population. Potential baseline prognostic variables including prior primary tumour resection were assessed by univariate and multivariate Cox analyses. Progression-free survival (PFS) and OS curves were compared with the logrank test.Among the 216 patients with stage IV CRC (median follow-up, 33 months), 156 patients (72%) had undergone resection of their primary tumour prior to study entry. The resection and non-resection groups did not differ for baseline characteristics except for primary tumour location (rectum, 14% versus 35%; p=0.0006). In multivariate analysis, resection of the primary was the strongest independent prognostic factor for PFS (hazard ratio (HR), 0.5; 95% confidence interval [CI], 0.4-0.8; p=0.0002) and OS (HR, 0.4; CI, 0.3-0.6; p0.0001). Both median PFS (5.1 [4.6-5.6] versus 2.9 [2.2-4.1] months; p=0.001) and OS (16.3 [13.7-19.2] versus 9.6 [7.4-12.5]; p0.0001) were significantly higher in the resection group. These differences in patient survival were maintained after exclusion of patients with rectal primary (n=43).Resection of the primary tumour may be associated with longer PFS and OS in patients with stage IV CRC starting first-line, single-agent chemotherapy.
Published: 2013
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25. Prognostic factor analysis for elderly patients treated for metastatic colorectal cancer in the randomized phase II trial PRODIGE 20

Author: F. Retornaz, Julien Taieb, E. Francois, S. Kirscher, Thomas Aparicio, Thierry Lecomte, O. Bouche, F. Khemissa Akouz, Dominique Genet, Alice Oden-Gangloff, Laurent Bedenne, F. El Hajbi, Sandrine Lavau-Denes, Elena Paillaud, M. Baconnier, Christophe Locher, E. Maillard, P.L. Etienne, Roger Faroux, Y. Rinaldi, Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Fédération Francophone de la Cancérologie Digestive, FFCD, Institut Sainte Catherine [Avignon], Service de gastroenterologie [CHU Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Hôpital Privé des Côtes d'Armor ( HPCA ), Centre Hospitalier Départemental Les Oudairies, Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, CRLCC Oscar Lambret, Centre Hospitalier de Meaux, Hôpital Européen [Fondation Ambroise Paré - Marseille], CHU Trousseau [Tours], CHRU Tours, CHU Limoges, CH Annecy, Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, CHU Rouen, Polyclinique de Limoges - site François Chénieux [Limoges], Unité de médecine gériatrique ( Gériatrie - Henri Mondor ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Programme Hospitalier de Recherche Clinique, Laboratoires Roche, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Privé des Côtes d'Armor (HPCA), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Normandie Université (NU), Unité de médecine gériatrique (Gériatrie - Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Université de Lille-UNICANCER
Subjects: 0301 basic medicine, Oncology, Prognostic factor, medicine.medical_specialty, Colorectal cancer, business.industry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, medicine.disease, 3. Good health, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016
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26. Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil: Results from the randomised phase III Pan-European Trial in Adjuvant Colon Cancer 01 (PETACC-1)

Author: Alberto Sobrero, J. Welch, Alfredo Carrato, Evaristo Sanches, Mark Vincent, Ivan Popov, Roberto Labianca, Jacques Wils, David J. Kerr, Angelo Raffaele Bianco, Enrico Mini, Mostafa El-Serafi, Laurence Collette, Bernard Paillot, Laurent Bedenne, and M. Praet
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Antimetabolites, Antineoplastic, medicine.drug_class, Colorectal cancer, medicine.medical_treatment, Leucovorin, Thiophenes, Antimetabolite, Gastroenterology, Young Adult, Bolus (medicine), Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Survival analysis, Aged, Aged, 80 and over, Chemotherapy, business.industry, Middle Aged, medicine.disease, Survival Analysis, Surgery, Clinical trial, Treatment Outcome, Oncology, Fluorouracil, Chemotherapy, Adjuvant, Colonic Neoplasms, Quinazolines, Female, business, Raltitrexed, medicine.drug
Abstract: Objectives PETACC-1 assessed if raltitrexed is non-inferior to 5-fluorouracil and leucovorin for relapse-free survival (RFS) and overall survival (OS) in adjuvant stage III colon cancer. Methods Non-inferiority required both HR for RFS and OS α = 0.05. Patients (1921) were randomised to six cycles of 5-FU/LV ( n = 969) or eight cycles of raltitrexed ( n = 952). We report the final results in 993 eligible patients who started and completed the allocated treatment (489 5-FU/LV and n = 504 Raltitrexed) of whom respectively 146 and 148 died, respectively. Results The trial closed prematurely when 17 (1.9%) raltitrexed-related deaths were reported. Haematological and gastrointestinal toxicities were more frequent with 5-FU/LV, liver toxicities with raltitrexed. Raltitrexed was stopped for toxicity in 13.2% and 5-FU/LV in 8.5%. Sixty-day mortality was 9% versus 7%. With 4.1 years median follow-up, the HR for RFS was 1.16 (90% CI 0.99–1.37) and that for OS was 1.01 (90% CI 0.84–1.23). Conclusion The trial failed to demonstrate non-inferiority of raltitrexed. Funding Free drugs and financial support from AstraZeneca.
Published: 2016

27. Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001–02)

Author: Gilles Breysacher, F. Masskouri, C. Choine, François Morvan, Pascal Hammel, Jean-François Seitz, P. Amoyal, J. Cretin, G. Gatineau-Sailliant, Christophe Locher, Thomas Aparicio, G. Bordes, O. Boulat, David Tougeron, I. Cumin, O. Berthelet, Anne Thirot Bidault, M. Pauwels, X. Moncoucy, Faiza Khemissa, F. Petit-Laurent, X. Adhoute, P. Prost, J.P. Lagasse, Jean-Louis Legoux, J. Ezenfis, N. Le Provost, Pierre Michel, A. Gueye, P. Pouderoux, G. Le Pessec, Julien Taieb, B. Landi, H. Fattouh, A. Azzedine, Mohamed Ramdani, Matthieu Schnee, Laurent Bedenne, Jean-Louis Jouve, C. Rebischung, J. Thaury, Ph. Rougier, C. Lobry, F. Guiliani, Jean-Baptiste Bachet, F. Ricard, L. Stefani, R. Mackiewicz, Dominique Genet, E. Cuillerier, C. Bineau, A.M. Queuniet, P. Couzigou, Jean-Marc Phelip, Eveline Boucher, B. Garcia, D. Cleau, M. Schneider, Iradj Sobhani, M. Mozer, Roger Faroux, Mohamed Gasmi, J. Charneau, Côme Lepage, Thierry Lecomte, Céline Lepère, D. Auby, Eric Terrebonne, R. Benoit, Emmanuel Mitry, D. Gargot, J. Martin, M. Baconnier, V. Derias, Achim Weber, Nadia Bouarioua, L. Chone, Catherine Lombard-Bohas, Patrick Texereau, B. Denis, May Mabro, Emilie Maillard, Sandrine Lavau-Denes, F. Di Fiore, C. Girault, J. Provençal, O. Bouche, F. Bonnetain, A. Gagnaire, Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier de Blois (CHB), Hôpital Nord [CHU - APHM], Centre Hospitalier de Meaux, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Métropole Savoie [Chambéry], Hôpital pasteur [Colmar], Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Duchenne, CH Boulogne sur Mer, Clinique Bonnefon, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]
Subjects: Oncology, Male, medicine.medical_specialty, Leucovorin, colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Irinotecan, chemotherapy, Gastroenterology, elderly, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Progression-free survival, geriatric oncology, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Hazard ratio, Hematology, Chemotherapy regimen, 3. Good health, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, Multivariate Analysis, FOLFIRI, 030211 gastroenterology & hepatology, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract: International audience; BACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771.
Published: 2016
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28. Clinical Outcome of the ACCORD 12/0405 PRODIGE 2 Randomized Trial in Rectal Cancer

Author: Jean-Pierre Gérard, David Azria, Sophie Gourgou-Bourgade, Isabelle Martel-Lafay, Christophe Hennequin, Pierre-Luc Etienne, Véronique Vendrely, Eric François, Guy de La Roche, Olivier Bouché, Xavier Mirabel, Bernard Denis, Laurent Mineur, Jean-François Berdah, Marc-André Mahé, Yves Bécouarn, Olivier Dupuis, Gérard Lledo, Jean-François Seitz, Laurent Bedenne, Béata Juzyna, and Thierry Conroy
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Leucovorin, Deoxycytidine, Disease-Free Survival, law.invention, Capecitabine, chemistry.chemical_compound, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Neoadjuvant therapy, Aged, Neoplasm Staging, Rectal Neoplasms, business.industry, Radiotherapy Dosage, Chemoradiotherapy, Adjuvant, Middle Aged, medicine.disease, Neoadjuvant Therapy, Surgery, Oxaliplatin, Treatment Outcome, chemistry, Fluorouracil, Female, business, Chemoradiotherapy, medicine.drug
Abstract: Purpose The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years. Patients and Methods Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin). Total mesorectal excision was planned 6 weeks after CT-RT. The primary end point was sterilization of the operative specimen, which was achieved in 13.9% versus 19.2% of patients, respectively (P = .09). Clinical results were analyzed for all randomly assigned patients according to the intention-to-treat principle. Results At 3 years, there was no significant difference between CAP45 and CAPOX50 (cumulative incidence of local recurrence, 6.1% v 4.4%; overall survival, 87.6% v 88.3%; disease-free survival, 67.9% v 72.7%). Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group. Bowel continence, erectile dysfunction, and social life disturbance were not different between groups. In multivariate analysis, the sterilization rate (Dworak score) of the operative specimen was the main significant prognostic factor (hazard ratio, 0.32; 95% CI, 0.21 to 0.50). Conclusion At 3 years, no significant difference in clinical outcome was achieved with the intensified CAPOX regimen. When compared with other recent randomized trials, these results indicate that concurrent administration of oxaliplatin and RT is not recommended.
Published: 2012
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29. Screening of anticancer drugs for chemoembolization of hepatocellular carcinoma

Author: Séverine Guiu, Boris Guiu, Bruno Chauffert, Serge Aho, Jean-Pierre Cercueil, Mathieu Boulin, Laurent Bedenne, Patrick Hillon, Denis Krausé, P. Fagnoni, and François Ghiringhelli
Subjects: Cancer Research, Carcinoma, Hepatocellular, Antineoplastic Agents, chemistry.chemical_compound, Cell Line, Tumor, medicine, Humans, Idarubicin, Pharmacology (medical), Chemoembolization, Therapeutic, Pharmacology, Cisplatin, Mitoxantrone, Dose-Response Relationship, Drug, business.industry, Liver Neoplasms, Hep G2 Cells, Carboplatin, Gemcitabine, Oxaliplatin, Nonlinear Dynamics, Oncology, chemistry, Paclitaxel, Cancer research, Regression Analysis, Colorimetry, business, medicine.drug, Epirubicin
Abstract: The aim of this study was to select the best candidate drug for transarterial chemoembolization by in-vitro cytotoxic evaluations of 11 anticancer drugs on three human hepatocellular carcinoma (HCC) cell lines. The SNU-398, HepG2, and SNU-449 human HCC cell lines were exposed for 30 min to 11 concentrations of doxorubicin, epirubicin, idarubicin, mitoxantrone, carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, gemcitabine, mitomycin C, or paclitaxel. Cytotoxicity was measured using a quantitative colorimetric assay. For each drug and cell line, we calculated the drug concentration that caused 90% cell death (IC90). To enable comparisons of drugs with different concentration ranges, we computed the cytotoxic index (CyI) as the ratio of maximal drug concentration of more than IC90. Parameters were estimated using nonlinear regression models. Idarubicin was the most active drug on all three cell lines. With SNU-398 cells, the idarubicin CyI was 2.4-fold, 2.5-fold, 57-fold, 148-fold, and more than 58 748-fold higher than the CyIs of mitoxantrone, epirubicin, doxorubicin, gemcitabine, and other drugs, respectively. With HepG2 cells, the idarubicin CyI was 27-fold, 28-fold, 51-fold, and more than 1343-fold higher than the CyIs of doxorubicin, epirubicin, mitoxantrone, and other drugs, respectively. On the resistant SNU-449 cell line, the idarubicin CyI was 2.9-fold and 14-fold higher than the CyIs of paclitaxel and gemcitabine, respectively, the only other drugs effective on this cell line. Among 11 chemotherapeutic agents including doxorubicin, cisplatin, and epirubicin, the most effective on three HCC cell lines was idarubicin. Further clinical investigations are needed to evaluate the safety and efficacy of idarubicin for transarterial chemoembolization in HCC.
Published: 2011
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30. Cancer du pancréas localement évolué non resécable : chimioradiothérapie d’induction suivie de chimiothérapie par gemcitabine contre chimiothérapie exclusive par gemcitabine : résultats définitifs de l’étude de phase III 2000–2001de la FFCD et de la SFRO

Author: Ph. Rougier, P. Maingon, Thomas Aparicio, A. Azzedine, Bruno Chauffert, J.-F. Bosset, O. Bouche, M. Barhoumi, J. Butel, F. Mornex, L. Mineur, Laurent Bedenne, F. Bonnetain, N. Stremsdoerfer, P. Hammel, and C. Mariette
Subjects: Gynecology, 0303 health sciences, medicine.medical_specialty, business.industry, Gemcitabine, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Combined treatment, Oncology, 030220 oncology & carcinogenesis, Overall survival, medicine, Radiology, Nuclear Medicine and imaging, business, INDUCTION TREATMENT, 030304 developmental biology, medicine.drug
Abstract: Resume Objectif de l’etude Etudier l’apport de la chimioradiotherapie concomitante suivie de chimiotherapie dans le cancer pancreatique localement evolue, par rapport a la chimiotherapie seule. Patients et methodes Cent dix-neuf patients atteints d’un cancer pancreatique localement evolue, avec indice de performance de 0 a 2 selon l’Organisation mondiale de la sante, ont ete randomises entre une chimioradiotherapie concomitante d’induction (60 Gy, 2 Gy/fraction ; perfusion concomitante de 5-fluoro-uracile de 300 mg/m2 par jour, de j1 a j5 pendant six semaines ; cisplatine, 20 mg/m2 par jour, de j1 a j5 pendant la premiere et la cinquieme semaines) et une chimiotherapie d’induction par gemcitabine (1000 mg/m2 par semaine pendant sept semaines). La gemcitabine a ete maintenue dans les deux groupes (1000 mg/m2 par semaine) jusqu’a progression de la maladie ou toxicite. Resultats La survie globale etait plus courte dans le bras chimioradiotherapie concomitante que dans le bras gemcitabine (medianes de survie de 8,6 [intervalle de confiance a 99 % : 7,1-11,4] contre 13 mois [1,7,8,8–18], p = 0,03). Les probabilites de survie a un an etaient respectivement de 32 et 53 %. Ces resultats ont ete confirmes par une analyse per protocol pour les patients ayant recu 75 % ou plus de la dose prevue de radiotherapie. Un nombre plus important d’effets secondaires de grade 3–4 a ete recense dans le bras chimioradiotherapie concomitante, aussi bien durant l’induction (36 contre 22 %) que lors du maintien par gemcitabine (32 contre 18 %). Conclusion Ce schema d’induction intensive par chimioradiotherapie concomitante est plus toxique et moins efficace que la gemcitabine seule.
Published: 2011
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31. Impact économique de la chimioembolisation avec microsphères chargées dans le traitement du carcinome hépatocellulaire

Author: M.-H. Guignard, Angela Musat, Boris Guiu, P. Fagnoni, Laurent Bedenne, Charlotte Malbranche, Jean-Pierre Cercueil, Mathieu Boulin, Ludwig Serge Aho, Patrick Hillon, and Corinne Pernot
Subjects: Cancer Research, Oncology, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine
Abstract: Resume La chimioembolisation est le traitement de premiere ligne pour les patients atteints d’un carcinome hepatocellulaire (CHC) non resecable, non metastatique. Les microspheres chargees d’anticancereux recemment commercialisees ont pour objectif d’augmenter l’efficacite de la chimioembolisation en permettant un relargage controle et prolonge de l’anticancereux au plus proche de la tumeur. Notre etude monocentrique compare selon deux methodes de valorisation, les couts medicaux hospitaliers directs d’une premiere cure de chimioembolisation conventionnelle et d’une premiere cure de chimioembolisation avec microspheres chez 30 patients atteints de CHC. Le cout moyen valorise par la comptabilite analytique de notre etablissement s’eleve a 4 332 € pour une premiere chimioembolisation conventionnelle et a 3 577 € pour une premiere chimioembolisation avec microspheres. Le cout moyen valorise par les tarifs nationaux s’eleve a 4 507 € (+ 175 €) pour une premiere chimioembolisation conventionnelle et a 2 852 € (− 725 €) pour une premiere chimioembolisation avec microspheres. En conclusion, une premiere cure de chimioembolisation avec microspheres, valorisee d’apres les tarifs d’hospitalisation des GHS, est significativement ( p = 0,006) moins couteuse qu’une chimioembolisation conventionnelle.
Published: 2011
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32. Is surgery always necessary in esophageal cancer?

Author: Julie Vincent, Jean-Louis Jouve, and Laurent Bedenne
Subjects: medicine.medical_specialty, Randomization, business.industry, medicine.medical_treatment, Gastroenterology, Induction chemotherapy, Esophageal cancer, medicine.disease, Surgery, law.invention, Radiation therapy, Randomized controlled trial, Cardiothoracic surgery, Surgical oncology, law, Carcinoma, Medicine, business
Abstract: Two randomized trials showed that survival was similar after definitive chemoradiation (CRT) or after CRT and surgery in locally advanced esophageal squamous cell cancer, despite more frequent local recurrences. In one trial randomization was done at inclusion, whereas in the other trial a workup was performed after initial CRT; only clinical responders were randomized between surgery and additional CRT. Therefore, clinical non-responders could be operated on without delay. Indeed, randomized patients and nonrandomized operated patients had a similar survival, even if no response was seen on the specimen. However, evidence of benefit is poor in cases of delayed recurrence. Only small nonrandomized studies have considered this issue. R0 resection rates ranged from 50 to 87%, 5-year survival rates from 0 to 33%, and operative mortality from 12.5 to 25%; only R0 resection was associated with long survival. Therefore, the benefit of delayed salvage resection should be assessed in a prospective strategic randomized trial, after a CRT intensive enough to eradicate a sensitive tumor without increasing the risk of eventual surgery. The FFCD (Federation Francophone de Cancerologie Digestive) is working on such a trial in locally advanced operable esophageal carcinoma: CRT and systematic surgery compared with CRT followed by surgery in case of proven persistent tumor or resectable local recurrence. CRT will be improved with induction chemotherapy, new drugs, and up-to-date protracted radiotherapy.
Published: 2011
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33. Combination 5-fluorouracil, folinic acid and cisplatin (LV5FU2-CDDP) followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: final results of a randomised strategic phase III trial (FFCD 0301)

Author: Laurent Bedenne, Emmanuel Mitry, Jean-Marc Phelip, Jean-Luc Raoul, Philippe Rougier, Jean-François Seitz, Pascal Hammel, Bruno Chauffert, Marc Ychou, Pierre Michel, F. Bonnetain, Jean-Louis Legoux, Laetitia Dahan, Mohamed Gasmi, and Stéphane Cattan
Subjects: Adult, Male, Oncology, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Leucovorin, Adenocarcinoma, Deoxycytidine, Antimetabolite, Drug Administration Schedule, Folinic acid, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Aged, 80 and over, Chemotherapy, Performance status, business.industry, Gastroenterology, Middle Aged, Metastatic Pancreatic Adenocarcinoma, medicine.disease, Survival Analysis, Gemcitabine, Surgery, Pancreatic Neoplasms, Treatment Outcome, Fluorouracil, Disease Progression, Female, France, Cisplatin, business, medicine.drug
Abstract: Purpose Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma. Although the 5-fluorouracil (5FU), folinic acid and cisplatin combination (LV5FU2-CDDP) is an option, the optimal order of the regimens must be determined. The first strategic phase III trial comparing LV5FU2-CDDP followed by gemcitabine versus gemcitabine followed by LV5FU2-CDDP was conducted. Methods Patients with metastatic pancreatic adenocarcinoma, performance status (PS) 0–2, without prior chemotherapy were randomly assigned (1:1) to receive either LV5FU2-CDDP followed by gemcitabine at disease progression or toxicity (Arm A), or the opposite sequence (Arm B). 202 patients had to be included and 170 deaths had to be observed to detect an expected improvement in median overall survival (OS) from 6.5 to 10 months in Arm A (two-sided α = 5% and β = 20%). Results 202 patients were included (Arm A, 102; Arm B, 100). Median age, male/female ratio, PS 0–1 and previous surgery were similar in the two arms. After a median follow-up of 44 months, median OS in Arm A was 6.6 months versus 8.0 months in Arm B (p = 0.85). Median progression-free survival was similar between Arms A and B. More grade 3/4 toxicities were observed when LV5FU2-CDDP was administered as a first-line treatment compared with gemcitabine: 79% versus 64% (p = 0.018). Conclusion This trial did not show any strategic advantage to using LV5FU2-CDDP as a first-line treatment and suggests that gemcitabine remains the standard first-line treatment. Sixty-one per cent of patients were able to receive a second line of chemotherapy.
Published: 2010
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34. Time until definitive quality of life score deterioration as a means of longitudinal analysis for treatment trials in patients with metastatic pancreatic adenocarcinoma

Author: Pascal Hammel, Laurent Bedenne, Jean-Louis Legoux, Laetitia Dahan, Jean-François Seitz, Franck Bonnetain, Emilie Maillard, Emmanuel Mitry, Marc Ychou, and Philippe Rougier
Subjects: Male, Cancer Research, medicine.medical_specialty, Time Factors, Emotions, Pain, Kaplan-Meier Estimate, Adenocarcinoma, law.invention, Randomized controlled trial, Quality of life, law, Surveys and Questionnaires, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Longitudinal Studies, Neoplasm Metastasis, Fatigue, Proportional hazards model, business.industry, Surrogate endpoint, Minimal clinically important difference, Metastatic Pancreatic Adenocarcinoma, medicine.disease, humanities, Surgery, Pancreatic Neoplasms, Clinical trial, Oncology, Quality of Life, Female, business
Abstract: Background The Federation Francophone de Cancerologie Digestive phase III trial in patients with metastatic pancreatic adenocarcinoma comparing 5FU, folinic acid and cisplatin combination followed by gemcitabine (Arm A) versus the opposite sequence (Arm B) failed to demonstrate a benefit in overall survival. To longitudinally compare the quality of life (QoL) we explored different definitions of time until definitive deterioration (TUDD) of QoL scores according to minimal clinically important difference (MCID) cut-offs. Methods QoL was evaluated using the EORTC QLQ-C30 every 8 weeks until death. The following scores were analysed: global health, emotional functioning, physical functioning, fatigue and pain. TUDD was defined as the time interval between randomisation and the first occurrence of a decrease in QLQ-C30 score ⩾5 points without any further improvement in QoL score ⩾5 points or any further available QoL data. Analyses were repeated using a 10 point MCID and/or including death as event. Results From 08/2003 to 05/2006, 102 patients in Arm A and 100 in Arm B were included. Using a 5 and a 10 point MCID, TUDD curves of the 5 scores did not differ according to treatment arm., The median TUDD of global health was 5.2 months (4.3–6.2) in Arm A and 6.1 months (5.1–8.5) in Arm B (log-rank p = 0.50) including death as an event for a 5 point MCID. Multivariate Cox model showed that tumour localisation and progression were independently associated with TUDD (p Conclusions The strategy of chemotherapy did not influence the deterioration of QoL. The TUDD approach seems to provide meaningful clinical results that are adapted to metastatic pancreatic adenocarcinoma trials.
Published: 2010
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35. High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn’s Disease

Author: Laurent Beaugerie, Fabrice Carrat, Stéphane Nahon, Jean-David Zeitoun, Jean-Marc Sabaté, Laurent Peyrin-Biroulet, Jean-Frédéric Colombel, Matthieu Allez, Jean-François Fléjou, Julien Kirchgesner, Magali Svrcek, Jacques Cosnes, Jean-Pierre Gendre, Marc Lémann, Xavier Hébuterne, Antoine Cortot, Yoram Bouhnik, David Laharie, Jean Louis Dupas, Bernard Flourié, Eric Lerebours, Bernard Messing, Guillaume Cadiot, Philippe Marteau, Jean-Claude Soulé, Jean-Marc Gornet, Michel Veyrac, Bernard Duclos, Philippe Beau, Arnaud Bourreille, Philippe Baumer, Franck Carbonnel, Denis Heresbach, Etienne-Henry Metman, Christian Florent, Antoine Blain, Jean-Luc Faucheron, Bruno Bonaz, Xavier Roblin, Pascal Potier, Christian Boehm, Thierry Kurtz, Hervé Lamouliatte, Isabelle Nion-Larmurier, Jean-Charles Delchier, Stanislas Chaussade, Anne Marie Weiss, Jean Pierre Cézard, Laurent Siproudhis, Daniel Sondag, Raymond Jian, Jean-Christophe Souquet, Pierre Bord, Benoit Coffin, Hélène D’almagne, Patrick Delasalle, Régis Fournier, Maryan Cavicchi, Marc-Henry Souffran, Luc Vandromme, Claire Guedon, Philippe Seksik, Christophe Michiels, Pascal Renard, Patrice Rogier, Sylvie Gouilloud, André Rotenberg, Guillaume Savoye, Alain Thevenin, Laurent Mallet, Franck Brazier, Francois Jean, Anne-Marie Justum, Jean-Paul Latrive, Jean-Luc Gerbal, Robert Pierrugues, Gérard Chardonnal, Laurence Picon, Nicole Reix, Nicolas Drouët D’aubigny, Hervé Uettwiller, Anne Courillon Mallet, Alain Palacci, Raoul-Jacques Bensaude, Pierre Bonniaud, Olivier Empinet, Andrée Nisard, Alain Rudelli, Bernard Tubiana, Philippe Capelle, Alain Dabadie, Daniel Evard, Pierre-Emile Julien, Magali Picon-Coste, Stéphane Schneider, Denis Goldfain, Jérôme Bellanger, Jean-Pierre Blondelot, Philippe Lamy, Sébastien Lemière, Jean Francois Mockly, Benoit Pellat, Gilles Gatineau-Sailliant, Bernard Nalet, Stéphane Nancey, Daniel Kusielewicz, Patrick Loison, Jean-Michel Popot, François Merite, Jean-Pol Roux, Pauline Afchain, Alain Blanquart, Laurent Heyries, Marc Reville, Dominique Viron, Frank Zerbib, Christophe Claviere, Didier Léostic, Philippe Pouderoux, Alain Moitry, Hervé Hagège, Jean-Pierre Hugot, Benoit Humeau, Jean-Marc Sabate, Emmanuel Lederman, Dominique Lescut, Fabrice Luneau, Bruno Mesnard, Lionel Smadja, Michel Steinberg, Marc Brun, Gilles Macaigne, Jean Luc Marchal, Stéphane Ollivier, Dominique Ouvry, Jean Paul Perche, Serge Rambaud, Robert Benamouzig, Jean Louis Cazenave, Jean-Charles Coffin, Martine Blazquez, Marion Lagneau, Bruno Person, Christian Wittersheim, Bertrand Napoleon, Israël Cemachovic, Franck Iglicki, Mehran Howaizi, Eric Leprince, Bruno Leurent, Thierry Morin, Riad Darsouni, Alain Attar, Philippe Baron, Anne Breton, Jean Marie Gillion, Jean-Marc Guemene, Claude Jouffre, Xavier Moreau, Pierre Claude, André Quinton, Vered Abitbol, Jean Michel Brichard, Benoit Desaint, Martin Bouygues, Philippe Chatrenet, Marcelo Salmeron, Jean Silvie, Bruno Waldner, Yves Emery, Armand Moraillon, Daniel Kunkel, Philippe Dubois, Patrick Faure, Christian L'Hirondel, Jean-Eric Labérenne, Pierre Moreau, Adelino Pereira, Genevieve Plihon, Thierry Wolff, Yann Ngo, Arnaud Boruchowicz, Béatrice Jost, Jean Pierre Gotlib, Odile Danne, Philippe Raoux, Marie-José Ramond-Bouhali, Andre Baetz, Bruno Veyres, Christian Chapoutot, Gérard Le Dréau, Jérôme Filippi, Jean Mudry, Philippe Kalt, Sophie Minault, Pierre-André Bounin, Tony Andréani, Jacky Charneau, Didier Reijasse, Jean-Louis Bolze, Jean Luc Thaunat, Christian Le Couteulx, Chantal Maurage, Robert Bader, Philippe Codjovi, Jean-Luc Migairou, Alain Morali, Philippe Rey, Bruno Richard Molard, Richard Petit, Stéphane Koch, Philippe Cassan, Jean-Paul Deschamps, Christine Meicler Caby, Jean-Jacques Meurisse, Philippe Prades, James Boulant, Michel Diacono, Jean-Marie Monsch, J-François Dupuy, Guy Bellaiche, Martine Guegan, Jean-Marc Comte, Jean-Michel Cayla, Francois Le Tallec, Franck Meurisse, Philippe Desurmont, Laurent Roget, Philippe Bouyssou, Bruno Le Gall, Francis Bloch, Loic Larvol, Monique Jullien, Jacques Moreau, Laurent Rebouissoux, Bruno Decroix, Nina Dib, Paul Dieterling, Frédéric Lenormand, Emmanuel Lagier, Philippe Fallourd, Serge Charpin, Hugues Bertrand, Gilles Bommelaer, Daniel Battistelli, Bernard Delon, Lionel Dentant, Etienne Dorval, Jérôme Dumortier, Eric Gaye-Bareyt, Yves Gerosa, Chantal Guez, Martine Mornet, Paul Benfredj, René Piperaud, Noel Stremsdoerfer, Eric Verdier, Alain Grinholtz, Georges Barjonet, Antoine See, Ramuntxo Arotçarena, Anne Baudet, Joel Broyer, Antoine Charachon, Hugues Blondon, Pascal Mouton, Hubert Claudez, Jacques Labat-Labourdette, Jacques Haëm, Patrick Estable, Patrick Levy, Alain Rosenbaum, Yvon Balavoine, Alain Blanchi, Pierre Coutarel, Nadege Delaperriere, Michel Dervichian, Francis Marois, Jacques Seroka, Laurent Michaud, Olivier Leroy, Emmanuel Meyran, Bernard Poilroux, Abdallah Tensaouti, Thierry Paupard, Dominique Agard, Sandrine Beaulieu, Kader Benfiguig, Patrice Capony, Jean Cottereau, Pierre Desreumaux, Jean-Michel Dramard, Mathieu Duché, Patrick Mamou, Isabelle Etienney, Gilles D'Abrigeon, Béatrice Godeberge, Gilbert Tucat, Jean Puech, Jean Roger, Marie-George Lapalus, Paul Bauret, Philippe Houcke, Béatrice Pornin, Bruno Champigneulle, Laurent Cuissard, Xavier-Richard David, Frédéric Lombard, Antoine Granveau, Jean-François Hamon, Olivier Ink, Fabienne Blondel, Alain Namias, Didier Pillon, Antoine Reignier, Gilles Tordjman, Christos Christidis, Simon Zirabe, Michel Audebert, Eric Bion, Claude Bourgeaux, Cécile Poupardin, Philippe Deplaix, Gérard Fratini, Thierry Garnier, Gerard Desseaux, Hervé Magois, Sylvain Lochum, Jean-Francois Vergier, Patrick Texereau, Christel Rat, Francoise Uzzan, Alain Vidal, Nadia Vinante, Bernard Watrin, Cécile Wurtz-Huckert, Bruno Barre, Dominique Chaslin Ferbus, Jean-François Contou, Dominique Coupier, Benoit David, Dany Gargot, Denis Huc, Remy Barraya, Roger Faroux, Jean-Luc Fourgeaud, Hubert Grimprel, Jean Auroux, Jean-François Rey, Jean Pierre Arnoux, Franck Lentini, Ludovic Tardy, Olivier Mouterde, Claire Spyckerelle, Bruno Vacherot, Alain Weissman, Michel Alpérine, Anne Le Sidaner, Pierre-Olivier Bonnet-Eymard, Jean Louis Colson, Daniel Pellet, Bernard Deltombe, André Edouard, Henri Maechel, Jean-Claude Jaillet, Julien Genes, Anne-Marie Leveque, Damien Lucidarme, Philippe Maignan, Nathalie Mallier Gehrke, Jérôme Sanchez, Frank Tusseau, Alban Casteur, Jacques Bottlaender, Denis Constantini, Thierry Coton, Philippe Even, Francois Druart, François Riot, Jean-Michel Gauchet, Geneviève Hecquet, Gerard Henry, Patrick Hochain, Jean Pierre Arpurt, Abdelkrim Medini, Michele Dartois-Hoguin, Henri Moindrot, Philippe Emery, Pierre Periac, Annie Prunier, Pascal Renkes, Christine Tawil-Longreen, Edmond Vincent, René-Louis Vitte, Christian Loeb, Alain Carwana, Didier Barbereau, Philippe Bohon, Céline Corrieri-Baizeau, Daniel Sahy, Philippe Derreveaux, Dominique David, François Desbazeille, Patrick Fontenelle, Jean Luc Slama, Yvon Le Mercier, Michel Certin, Jean Jacques Reig, Isabelle Rosa, Thierry Helbert, Patrick Tounian, Luc Turner, Valéry Perot, Luc Aillet, Arnaud Pauwels, Philippe Barré, Bernard Nury, Claude Cazalbou, Franck Devulder, Alain Durget, Jeanne Dubroca, Daniele Gaudy, Michel Greff, Christian Jacques, Jocelyne Lafarge, Gilles Kezachian, Ronan Le Gall, Alex Pariente, Tiphaine Pinault, Michaël Bismuth, Nathalie Boyer-Darrigrand, Philippe Bretagnolle, Stephane Carpentier, Franck Cholet, Christian Theodore, Rémi Combes, Francois Combet, Christophe Delanoe, Stéphanie De Montigny, Denis Soudan, Olivier Fourdan, Gilles Minier, Jeanne Languepin, Jean Roche, Jean-Louis Ginies, Olivier Nouel, Philippe Petitgars, Edith Robin, Romain Hamm, Jean François Roques, Sylvie Roussin-Bretagne, Agnès Sénéjoux, Sophie Muron, Nicolas Bardoux, Philippe Berthelemy, Patrick Madonia, Bertrand Carles, Catherine Reynier, Emmanuel Cuillerier, Innocenti Dadamessi, Jacques Danis, Bernard Debenes, Nathalie Dubuc-Rey, Gilles Lesur, Pauline Jouet, Catherine Lenaerts, Marc Garret, Alexandra Mineur, Bernard Chabry, Francois Pigot, Valérie Rossi, Ruth Tennenbaum, Julien Salloum, Maurice Hakim Slaoui, Stéphane Mathieu, Valérie Papapietro, Sheila Viola, Alexis Bezet, Claude Altman, Alain Audan, Jean Calabet, Claude Masliah, Laurent Fayemendy, Marc Duruy, Benoit Gauffeny, Ludovic Helie, Kamran Imani, Raoul Janin-Manificat, Jean-Paul Galmiche, Anne Kerlirzin, Laurent Bedenne, Christophe Locher, Gilles Michaudel, Gilles Missonnier, Michel Rinaldi-Dovio, Jean-Michel Rouillon, Stéphane Ecuer, Arnaud Patenotte, Jean Ariel Bronstein, Vincent Baty, Michel Bougnol, Pierre Bourbon, Philippe Cerbelaud, Annick Chavaillon, Franck Boiffin, Béatrice Dubern, Isabelle Duval De Laguierce, Fernand Greco, Florence Bouhot, Philippe Godeberge, Brigitte Grandmaison, Pascal Gros, Guy Targues, Jacques Corallo, Jean Boutin, Jacques Guillan, Jean Pierre Barbieux, Isabelle Loury Lariviere, Henri Le Genissel, Henri Leroi, Marc Bellaiche, Marie-Claire Elie-Legrand, Michel Dapoigny, Philippe Denoyel, Patrice Pienkowski, Philippe Pouche, Marc Michel Saurfelt, Jean Marie Thorel, Thierry Piche, Bruno Travers, Patrick Tuvignon, Marc Zalcberg, Guy Boulay, Christophe Zamora, Joelle Samama, Etienne Ricotie, Patrice De Fleury, Francois Maille, Jean Louis Mougenel, Olivier Gonot, Jean Philippe Menat, Mehdi Kaassis, Francoise Lang, Laurent Abramowitz, Nathalie Ganne, Olivier Pecriaux, Jacques-Arnaud Seyrig, Iradj Sobhani, Thierry Parmentier, Antoine Van Nieuwenhuyse, Francois-Xavier Weber, André Glibert, Catherine Bineau, Bernard Canet, Catherine Collin, Frederic Cordet, David David Parlier, Dominique Carre, Annie Peytier, Francine Fein, Jerome Barouk, Jacques Dewannieux, Johannes Hartwig, Jean-Louis Jouve, Bertrand Laplane, Gilles Lascar, Christophe Legrand, Pierre Le Marchand, Marie Pierre Liebaert, Michele Terdiman-Pire, Naceur Abdelli, Dominique Neveu, Philippe De La Lande, Patrick De Saint Louvent, Cécile Pelatan, Agnès Petit, Martial Richecoeur, Frederic Texier, Jean Brice Cazals, Bertrand Tissot, Christian Mourrut, Marie Doubremelle, Marc Foltz, Florence Gautier-Jubé, Jacques Martin, Elie Khouri, Thierry Lons, Martine Carlier-Bandu, Jean-Luc Monnin, Hervé Roche, Bernard Willemin, Xavier Houard, Abdelaziz Fatisse, Michèle Algard, Kamel Arab, Isabelle Borel, Cécile Lagarrigue, Ariane Chryssostalis, Dominique Boutroux, Jean-Pierre Dupuychaffray, Saïd Khaddari, François Mion, Thierry Puy-Montbrun, Jean-Philippe Girardet, Bruno Gury, Alain Landau, Monique Le Bihan, Sandrine Nieuviarts, Jean Ollivry, Philippe Le Bourgeois, Marie-Astrid Piquet, Michel -Pierre Escartin, Remi Systchenko, Franck Venezia, Michel Wantiez, Xavier Lesage, Elie Zrihen, Philippe Aygalenq, Barbara Dieumegard, Bernard Savarieau, Philippe Bulois, Stéphane Cattan, Jean-Lucien Diez, Olivier Fauchot, Eric Durous, Valérie Gazut, Christian Guilleminet, Jean-Marc Bories, Isabelle Joly Le Floch, Jean-Paul Vove, Stéphane Lelouch, Philippe Lévy, François Lhopital, Norma Marcato, Marianne Mozer-Bernardeau, Jean-Baptiste Nousbaum, Philippe Cattan, Alain Plane, Jean-Michel Raymond, Gilles Roseau, Gerald Rozental, Christian Boustière, Corinne Bonny, Mariepierre Cordier-Collet, Laurent Courat, Bernard Croguennec, Karine Delaunay- Tardy, Damien Labarriere, Edmond Geagea, Frédéric Gottrand, Eve Gelsi, Gerard Thiefin, Eric Wohlschies, Mathieu Miguet, Philippe Ponsot, Jean Suzanne, Yves Teste, Anne-Claire Dupont Gossart, Jean-Luc Baroni, Benabdallah Benchaa, Georges Blanc, Bernard Maroy, Philippe Bonjean, Catherine Brézault, Laure Bridoux-Henno, Claude Chayette, Dominique Auby, Robert Fiorucci, Georges Galindo, Gilles Hubert, Gilles Bonneau, Evelyne Marinier, Michele Pouteau, Afchine Alamdari, Bruno Delbende, Patrick Chamouard, Pascale D'Abravanel, Hélène Dall'Osto, Sophie Hervé, Jean Lefebvre, Damien Levoir, Philippe Lillo, Michel Rouch, Muriel Mathonnet, Mercédes De Lustrac, François-Jean Ramond, Bernard Roupret, and Alain Soupison
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Colorectal cancer, Population, Risk Assessment, Gastroenterology, Inflammatory bowel disease, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Risk Factors, Internal medicine, medicine, Humans, Anal cancer, education, Aged, education.field_of_study, Crohn's disease, Hepatology, Rectal Neoplasms, business.industry, Incidence, Cancer, Odds ratio, Middle Aged, Anus Neoplasms, medicine.disease, Ulcerative colitis, Case-Control Studies, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, France, business, Follow-Up Studies
Abstract: Background & Aims Little is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn's disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn's perianal disease followed up in the Cancers Et Surrisque Associe aux Maladies Inflammatoires Intestinales En France (CESAME) cohort. Methods We collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn's disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex. Results Among the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn's lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn's disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03). Conclusions In an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn's disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer.
Published: 2018
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36. Phase III trial of chemotherapy using 5-fluorouracil and streptozotocin compared with interferon α for advanced carcinoid tumors: FNCLCC–FFCD 9710

Author: Laetitia Dahan, Frank Bonnetain, Philippe Rougier, Jean-Luc Raoul, Eric Gamelin, Pierre-Luc Etienne, Guillaume Cadiot, Emmanuel Mitry, Denis Smith, Frédérique Cvitkovic, Bruno Coudert, Floriane Ricard, Laurent Bedenne, and Jean-François Seitz
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, Carcinoid tumors, medicine.medical_treatment, Carcinoid Tumor, Interferon alpha-2, Gastroenterology, Streptozocin, Endocrinology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Endocrine Gland Neoplasms, Clinical endpoint, Humans, Medicine, Survival rate, Aged, Chemotherapy, business.industry, Therapeutic effect, Hazard ratio, Interferon-alpha, Middle Aged, Prognosis, medicine.disease, Recombinant Proteins, Surgery, Survival Rate, Radiation therapy, Treatment Outcome, Oncology, Fluorouracil, Lymphatic Metastasis, Disease Progression, Female, business, medicine.drug
Abstract: The aim of this randomized multicenter phase III trial was to compare chemotherapy and interferon (IFN) in patients with metastatic carcinoid tumors. Patients with documented progressive, unresectable, metastatic carcinoid tumors were randomized between 5-fluorouracil plus streptozotocin (day 1–5) and recombinant IFN-α-2a (3 MU×3 per week). Primary endpoint was progression-free survival (PFS). From February 1998 to June 2004, 64 patients were included. The two arms were well matched for median age, sex ratio, PS 0–1, previous chemotherapy, surgery, or radiotherapy. The median PFS for chemotherapy was 5.5 months versus 14.1 for IFN (hazard ratio=0.75 (0.41–1.36)). Overall survival (OS), tolerance, and effects on carcinoid symptoms were not significantly different. Despite a trend in favor of IFN, there was no difference in PFS and OS in advanced metastatic carcinoid tumors and therapeutic effect of both treatments was mild.
Published: 2009
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37. Comment surveiller les patients opérés à visée curative d’un cancer colorectal ?

Author: Jean-François Seitz, Laurent Bedenne, Laetitia Dahan, and Côme Lepage
Subjects: Gynecology, medicine.medical_specialty, biology, business.industry, Colorectal cancer, Gastroenterology, Rectum, Cancer, medicine.disease, Colorectal surgery, Carcinoembryonic antigen, medicine.anatomical_structure, Internal Medicine, medicine, biology.protein, business, Rectal disease, Colonic disease
Abstract: Malgre leur frequence, les modalites de surveillance des cancers colorectaux operes a visee curative restent mal codifiees. La place respective du scanner thoracoabdominopelvien, de l’echographie hepatique et de la radio de thorax est encore a preciser. L’utilite de la surveillance de l’ACE reste discutee.
Published: 2009
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38. Pilot Study of Transarterial Chemoembolization With Pirarubicin and Amiodarone for Unresectable Hepatocellular Carcinoma

Author: Emmanuelle Ferrant, Romaric Loffroy, Bruno Chauffert, François Ghiringhelli, Boris Guiu, Patrick Hillon, Jean-Louis Jouve, Anne Minello, Cédric Colin, Séverine Guiu, Jean-Pierre Cercueil, Mathieu Boulin, Laurent Bedenne, Denis Krausé, and Franck Bonnetain
Subjects: Male, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Pirarubicin, Amiodarone, Antineoplastic Agents, Pilot Projects, Gastroenterology, Internal medicine, Carcinoma, Humans, Medicine, Chemoembolization, Therapeutic, Survival rate, Aged, Aged, 80 and over, business.industry, Liver Neoplasms, Hazard ratio, Cancer, Iodized Oil, Middle Aged, Prognosis, medicine.disease, Confidence interval, Survival Rate, Treatment Outcome, Oncology, Doxorubicin, Hepatocellular carcinoma, Lipiodol, Female, Radiology, Tomography, X-Ray Computed, business, Immunosuppressive Agents, medicine.drug
Abstract: Objective: Further to a previous study whereby we reported that an in vitro emulsion of pirarubicin, amiodarone, and lipiodol was more stable and cytotoxic than a classic doxorubicin-lipiodol mixture, we designed a pilot study to evaluate efficacy and toxicity of a transarterial chemoembolization (TACE) procedure using a combination of pirarubicin, amiodarone, lipiodol, and gelatin sponge. Methods: The 43 patients included in this study underwent TACE for unresectable hepatocellular carcinoma. Computed tomography scans were performed to assess tumor response (RECIST) and lipiodol uptake after the first session. Median follow-up lasted 30 months. Endpoints were overall and progression-free survival. Survival was estimated using Kaplan Meier estimations and compared using log-rank tests. Univariate and multivariate Cox analyses were used to calculate hazard ratios with their 95% confidence interval (CI). Results: Twenty-seven (67.5%) patients had alcoholic cirrhosis. Mean tumor size was 9.5 cm (1―20 cm) and 37/43 were multifocal or diffuse. Cancer of the liver Italian program score was 0 in 7/40 and 1 in 16/40. Mean number of TACE sessions was 3.5 (1―11). There were 3 treatment-related deaths (2 severe sepsis, 1 bowel perforation). A partial response and a stable disease were observed in 12 (28%) and 29 (67%) patients, respectively. Median overall and progression-free survivals were 29 months (95% CI: 13.8―45) and 15 months (95% CI: 11.5―20.8), respectively. Cancer of the liver Italian program score ≤1 (P = 0.042) and lipiodol uptake >25% (P = 0.003) were independent prognostic factors for better overall survival. Conclusion: This new TACE procedure is safe with a high overall survival rate and certainly deserves phase III investigation to compare it with classic treatments such as doxorubicin-lipiodol TACE.
Published: 2009
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39. Surveillance des cancers coliques opérés à visée curative : faut-il revoir les recommandations de la conférence de consensus ?

Author: Mehdi Ouaissi, Laurent Bedenne, J.F. Seitz, Côme Lepage, Bernard Sastre, and Laetitia Dahan
Subjects: Gynecology, medicine.medical_specialty, business.industry, Gastroenterology, Medicine, General Medicine, business
Abstract: Resume Le cancer colorectal se situe au premier rang des cancers. Le traitement initial reste la resection chirurgicale a visee curative mais pres de la moitie des patients operes presenteront une recidive locoregionale ou a distance. Ce risque eleve de rechute et les possibilites therapeutiques avaient fait recommander une strategie de surveillance lors de la conference de consensus (Paris, 1998) avec un niveau de preuve faible. La question de la strategie de surveillance afin de detecter les recidives plus precocement et a un stade curable n’est toujours pas resolue et les modalites de suivi font toujours l’objet d’un important debat. Les etudes controlees et les meta-analyses publies depuis, comparant une strategie intensive de surveillance a une strategie moins intensive, seront analysees. Si elles apportent des arguments en faveur de la surveillance, elles ne permettent pas de conclure et d’etablir des recommandations precises. Une etude randomisee multicentrique sur un effectif important pourrait etre conduite pour repondre a ces interrogations.
Published: 2008
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40. Prise en charge des adénocarcinomes de la jonction œsogastrique résécables : quel traitement périopératoire ?

Author: Philippe Maingon, P. Rat, Gilles Créhange, F. Bonnetain, Laurent Bedenne, and Bruno Chauffert
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, General surgery, Standard treatment, Context (language use), Perioperative, Gastroesophageal Junction Adenocarcinoma, medicine.disease, Preoperative care, digestive system diseases, Surgery, Radiation therapy, Oncology, medicine, Adenocarcinoma, Radiology, Nuclear Medicine and imaging, business, Survival rate
Abstract: Adenocarcinoma of the oesophagogastric junction has an ominous prognosis. Until now, oesophageal adenocarcima care was close to the squamous cell cancer one whereas adenocarcinoma of the cardia was mixed with gastric cancers. Results from randomised studies mixed them without making distinctions. Nevertheless, context, natural history and clinical outcome differ. Five-year survival rate is around 40 %, all stages included. Results from several phase-III studies or meta-analysis allowed to define three therapeutic strategies applicable to adenocarcinoma of the oesophagus and the oesophagogastric junction. In Europe, in the case of a resectable tumour, preoperative chemotherapy became a standard treatment since results from the Magic trial. In the United States, post-operative radiochemotherapy according to the "Macdonald" scheme is used in case of a resected tumour with a R0 surgery. Actually, modern techniques of irradiation could reduce the rate of gastro-intestinal toxicities. The survival benefit from preoperative radiochemotherapy is still very controversial with high rates of postoperative morbidity and mortality. We have performed a review of the literature with a methodological analysis of data with a high level of evidence in order to advise perioperative treatment guidelines for patients with a resectable adenocarcinoma of the lower oesophagus or gastro-oesophageal junction. Results from pre- or postoperative strategies and the role of radiotherapy will need to be analysed in the future through a randomised study.
Published: 2008
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41. Prognosis of advanced hepatocellular carcinoma: comparison of three staging systems in two French clinical trials

Author: F. Masskouri, F. Bonnetain, Jean-Luc Raoul, S. Collette, J.C. Barbare, M. Doffoel, Philippe Rougier, Xavier Paoletti, O. Bouche, Laurent Bedenne, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Carcinoma, Hepatocellular, Palliative care, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Liver Cirrhosis, Alcoholic, Internal medicine, medicine, Carcinoma, Humans, ComputingMilieux_MISCELLANEOUS, Survival analysis, Aged, Neoplasm Staging, Aged, 80 and over, Performance status, Proportional hazards model, business.industry, Liver Neoplasms, Palliative Care, Hematology, Middle Aged, Prognosis, medicine.disease, Survival Analysis, Confidence interval, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, France, business
Abstract: Objective: The objective of this study was to assess the performance of three staging systems (Okuda, Cancer of the Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer group (BCLC)), for predicting survival in patients with hepatocellular carcinoma (HCC) and to explore how to improve prognostic classification among French patients with HCC whose main etiology is alcoholic cirrhosis. Methods: We have pooled two randomized clinical trials in palliative condition from the Federation Francophone de Cancerologie Digestive. They had included 416 and 122 patients. Performances of Okuda, CLIP and BCLC scores have been compared using Akaike information criterion, discriminatory ability (Harrell's C and the Royston's D statistics), monotonicity of gradients and predictive accuracy (Schemper statistics Vs). To explore how to improve classifications, univariate and multivariate Cox model analyses were carried out. Results: The pooled database included 538 patients. The median survival was 5.3 months (95% confidence interval 4.6-6.2). For all statistics CLIP staging system had a better prognostic ability. Performances of all staging systems were rather disappointing. World Health Organization performance status (WHO PS) for CLIP or a-fetoprotein for BCLC allowed a significant improvement of prognostic information. Conclusion: Our results indicate that CLIP staging seems to be most adapted to palliative setting and that it could be better by associating WHO PS.
Published: 2008
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42. Multicentre randomised phase III trial comparing Tamoxifen alone or with Transarterial Lipiodol Chemoembolisation for unresectable hepatocellular carcinoma in cirrhotic patients (Fédération Francophone de Cancérologie Digestive 9402)

Author: F. Bonnetain, Philippe Rougier, S. Fratte, X. Causse, M. Doffoel, Jean-Didier Grangé, O. Bouche, N. Stremsdoerfer, A. Blanchi, A. Abergel, D. Vetter, Laurent Bedenne, Jean-Pierre Bronowicki, F.X. Caroli-Bosc, F. Masskouri, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service d’Hépato-Gastro-Entérologie [Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'hépato-gastroentérologie, CHU Strasbourg-Hopital Civil, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Université de Reims Champagne-Ardenne (URCA), Département de Radiologie, Hôpitaux Universitaires de Strasbourg, Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS)-Clermont Université, CH Belfort-Montbéliard, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Liver Cirrhosis, Male, Quality of life, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Antineoplastic Agents, Hormonal, Hepatocellular carcinoma, [SDV]Life Sciences [q-bio], Alcoholic hepatitis, Gastroenterology, Randomised clinical trial, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Infusions, Intra-Arterial, Overall survival, Chemoembolization, Therapeutic, Chemoembolisation, business.industry, Liver Neoplasms, Iodized Oil, Length of Stay, Middle Aged, medicine.disease, Antiestrogen, Combined Modality Therapy, Survival Analysis, 3. Good health, Surgery, Portal vein thrombosis, Tamoxifen, Treatment Outcome, Alcoholic cirrhosis, Oncology, 030220 oncology & carcinogenesis, Lipiodol, Female, 030211 gastroenterology & hepatology, Liver cancer, business, medicine.drug
Abstract: International audience; The FFCD 9402 multicentre phase III trial was designed to compare the effects of the combination of Transarterial Lipiodol Chemoembolisation (TACE) and tamoxifen with tamoxifen alone on overall survival and quality of life in the palliative treatment of hepatocellular carcinoma with cirrhosis. From 1995 to 2002, 138 patients were randomised between the two groups. One hundred and twenty three patients were eligible including 61 in the Tamoxifen group and 62 in the TACE group. Baseline characteristics were similar: Child-Pugh class A: 70%, alcoholic cirrhosis: 76%, Okuda stage I: 71%, multinodular tumour: 70% and segmental portal vein thrombosis: 10%. At 2 years, the overall survival was 22% and 25% in the Tamoxifen and TACE groups (P = .68), respectively. Multivariate analysis identified four independent prognostic factors for survival: α-fetoprotein (AFP) > 400 ng/mL (P = .008), abdominal pain (P = .011), hepatomegaly (P = .023) and Child-Pugh score (P = .032). The Spitzer Index level assessing the quality of life during follow-up did not differ between the two groups (P = .70). Amongst patients with stage Okuda I, the 2-year overall survival was 28% in the Tamoxifen group and 32% in the TACE group (P = .58). In this subgroup, two prognostic factors were statistically significant for survival: AFP > 400 ng/mL (P = .004) and Spitzer Index (P = .013) as shown by multivariable analysis.In conclusion, this study suggests that TACE improves neither the survival nor the quality of life in patients with HCC and cirrhosis.
Published: 2008
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43. Cetuximab plus FOLFOX-4 for fully resected stage III colon carcinoma: scientific background and the ongoing PETACC-8 trial

Author: Laurent Bedenne, Julien Taieb, and Pierre Laurent Puig
Subjects: Male, Oncology, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, Leucovorin, Cetuximab, Antibodies, Monoclonal, Humanized, Disease-Free Survival, law.invention, FOLFOX, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Humans, Medicine, Neoplasm Invasiveness, Pharmacology (medical), Colectomy, Neoplasm Staging, business.industry, Antibodies, Monoclonal, Prognosis, medicine.disease, Survival Analysis, digestive system diseases, Oxaliplatin, Europe, Clinical trial, Regimen, Treatment Outcome, Chemotherapy, Adjuvant, Colonic Neoplasms, Female, Fluorouracil, business, medicine.drug
Abstract: The standard adjuvant treatment for stage III colon cancer in Europe is the 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX-4) regimen, given for 6 months. Cetuximab, a monoclonal antibody directed against the EGF receptor, appears to be effective and safe when combined with oxaliplatin-based regimens, including FOLFOX-4, in patients with metastatic colorectal cancer. PETACC-8, a randomized, multicenter, European Phase III trial, is comparing the efficacy of cetuximab plus FOLFOX-4 with that of FOLFOX-4 alone in patients with stage III colon cancer. The study began in December 2005 and approximately 2000 patients are to be enrolled in nine European countries. The primary end point is disease-free survival time, analyzed after a minimum follow-up of 3 years per patient. Secondary end points include overall survival, treatment compliance, safety and pharmacogenomic parameters.
Published: 2008
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44. Which patients with colorectal cancer are followed up by general practitioners? A population-based study

Author: Catherine Lejeune, Laurent Bedenne, Anne-Marie Bouvier, Claire Bonithon-Kopp, Christine Binquet, Romain Coriat, Sophie Béjean, and Amel Mahboubi
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Epidemiology, Colorectal cancer, medicine, Humans, Registries, Physician's Role, Physical Examination, Aged, Retrospective Studies, Aged, 80 and over, Physician-Patient Relations, Diagnostic Tests, Routine, business.industry, Public Health, Environmental and Occupational Health, Physicians, Family, Middle Aged, medicine.disease, Survival Analysis, Population based study, Oncology, Population Surveillance, Family medicine, Female, Guideline Adherence, Neoplasm Recurrence, Local, Colorectal Neoplasms, business, Follow-Up Studies
Abstract: The aim of the study was to assess the contribution of general practitioners in the surveillance of colorectal cancer, and to examine characteristics and survival of patients with routine general practitioner follow-up. This French registry-based study included 389 patients diagnosed with first colorectal cancer in 1998 and free of disease at least 6 months after curative surgery. For each physician involved, medical records were thoroughly reviewed to collect information about the clinical examinations and follow-up tests prescribed within 3 years after surgery or until death or detection of recurrence. Five-year vital status was obtained through registry records. The proportion of routine clinical examinations performed by general practitioners increased from 35% in the first year to 65% in the third year. Patients having undergone regular general practitioner routine examinations (or =one examination every 6-month period) had significantly less advanced disease (odds ratio: 0.45; 95% confidence interval: 0.21-0.96), preoperative complications (odds ratio: 0.28; 95% confidence interval: 0.08-0.91) and routine examinations by gastroenterologists/oncologists (odds ratio: 0.37; 95% confidence interval: 0.14-0.98) compared with those without general practitioner examinations. Routine general practitioner follow-up had no influence on 3 and 5-year survival. General practitioners detected significantly more recurrences than specialists in patients over 75 and in those presenting symptoms. French general practitioners are widely involved in the surveillance of patients with early-stage colorectal cancer, without any unfavourable impact on the patient's survival. Some suggestions exist that continuing education in oncology may increase the implication of general practitioners in colorectal cancer surveillance.
Published: 2007
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45. How do gastroenterologists follow patients with colorectal cancer after curative surgical resection? A three-year population-based study

Author: Romain Coriat, Catherine Lejeune, Amel Mahboubi, Claire Bonithon-Kopp, Anne-Marie Bouvier, and Laurent Bedenne
Subjects: Adult, Male, Radiography, Abdominal, medicine.medical_specialty, Colorectal cancer, Colonoscopy, Disease, Abdomen, Health care, medicine, Humans, Registries, Practice Patterns, Physicians', Aged, Retrospective Studies, Ultrasonography, Aged, 80 and over, medicine.diagnostic_test, business.industry, General surgery, Age Factors, Gastroenterology, Cancer, Retrospective cohort study, General Medicine, Continuity of Patient Care, Middle Aged, medicine.disease, Surgery, Endoscopy, medicine.anatomical_structure, Chemotherapy, Adjuvant, Population Surveillance, Female, Radiotherapy, Adjuvant, France, Guideline Adherence, Neoplasm Recurrence, Local, Colorectal Neoplasms, business
Abstract: Summary Objectives To assess the contribution of gastroenterologists (GEs) to the surveillance of colorectal cancer after curative surgery. Patients and methods This registry-based study included 407 patients residing in two French administrative areas diagnosed with newly diagnosed colorectal cancer in 1998 and free of disease six months after curative surgery. All surveillance examinations performed either in the three years after surgery or until death or recurrence were collected retrospectively. Results One hundred nine patients (27%) had a regular clinical check-up with a GE at least once a year. Factors independently associated with GE follow-up were young age (P=0.004), use of adjuvant chemotherapy (P=0.013), and surgeon follow-up (P=0.068). GEs ordered 84% of colonoscopies, 44% of abdominal ultrasound examinations and 52% of abdominal CT scans. They detected 35% of recurrences. A significant proportion of patients (20%) had no regular follow-up, irrespective of the physicians involved. Conclusions GEs play a modest role in the routine follow-up of patients with colorectal cancer, but are largely involved in ordering surveillance tests. They might play an important role in the surveillance of patients who presently have poor access to health care.
Published: 2007
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46. Chemoradiation Followed by Surgery Compared With Chemoradiation Alone in Squamous Cancer of the Esophagus: FFCD 9102

Author: Olivier Bouché, Laurent Bedenne, Denis Pezet, Chantal Milan, Jean-François Seitz, Christophe Mariette, Christine Binquet, Franck Bonnetain, Thierry Conroy, Jean-Philippe Herr, Pierre Michel, Patrick Arveux, Bernard Roullet, Bernard Paillot, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Cancer Research, medicine.medical_specialty, Esophageal Neoplasms, medicine.medical_treatment, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Esophagus, Contraindication, Survival rate, ComputingMilieux_MISCELLANEOUS, Aged, Radiotherapy, business.industry, Esophageal disease, Radiotherapy Dosage, Length of Stay, Middle Aged, Esophageal cancer, medicine.disease, Combined Modality Therapy, 3. Good health, Surgery, Radiation therapy, medicine.anatomical_structure, Oncology, Fluorouracil, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Concomitant, Carcinoma, Squamous Cell, Quality of Life, Female, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract: Purpose Uncontrolled studies suggest that chemoradiation has similar efficacy as surgery for esophageal cancer. Therefore, a randomized trial was carried out to compare, in responders only, chemoradiation alone with chemoradiation followed by surgery in patients with locally advanced tumors. Patients and Methods Eligible patients had operable T3N0-1M0 thoracic esophageal cancer. Patients received two cycles of fluorouracil (FU) and cisplatin (days 1 to 5 and 22 to 26) and either conventional (46 Gy in 4.5 weeks) or split-course (15 Gy, days 1 to 5 and 22 to 26) concomitant radiotherapy. Patients with response and no contraindication to either treatment were randomly assigned to surgery (arm A) or continuation of chemoradiation (arm B; three cycles of FU/cisplatin and either conventional [20 Gy] or split-course [15 Gy] radiotherapy). Chemoradiation was considered equivalent to surgery if the difference in 2-year survival rate was less than 10%. Results Of 444 eligible patients, 259 were randomly assigned; 230 patients (88.8%) had epidermoid cancer, and 29 (11.2%) had glandular carcinoma. Two-year survival rate was 34% in arm A versus 40% in arm B (hazard ratio for arm B v arm A = 0.90; adjusted P = .44). Median survival time was 17.7 months in arm A compared with 19.3 months in arm B. Two-year local control rate was 66.4% in arm A compared with 57.0% in arm B, and stents were less required in the surgery arm (5% in arm A v 32% in arm B; P < .001). The 3-month mortality rate was 9.3% in arm A compared with 0.8% in arm B (P = .002). Cumulative hospital stay was 68 days in arm A compared with 52 days in arm B (P = .02). Conclusion Our data suggest that, in patients with locally advanced thoracic esophageal cancers, especially epidermoid, who respond to chemoradiation, there is no benefit for the addition of surgery after chemoradiation compared with the continuation of additional chemoradiation.
Published: 2007
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47. Early surgery for failure after chemoradiation in operable thoracic oesophageal cancer. Analysis of the non-randomised patients in FFCD 9102 phase III trial: Chemoradiation followed by surgery versus chemoradiation alone

Author: Julie, Vincent, Christophe, Mariette, Denis, Pezet, Emmanuel, Huet, Franck, Bonnetain, Olivier, Bouché, Thierry, Conroy, Bernard, Roullet, Jean-François, Seitz, Jean-Philippe, Herr, Frédéric, Di Fiore, Jean-Louis, Jouve, Laurent, Bedenne, M, Ducreux, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Claude Huriez [Lille], CHU Lille, CHU Clermont-Ferrand, Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie digestive [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Fédération Francophone de la Cancérologie Digestive, FFCD, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital privé Sainte-Marie - Ramsay Générale de Santé, Hôpital Charles Nicolle [Rouen], Butel J, Desselle P, Brice JC, Tissot B, Votte-Lambert A, Joly J, Burtin P, Arnaud JP, Cellier P, Estermann F, Chauvet B, Maringe E, Ozanne F, Varlet F, Becouarn Y, Avril A, Rougier P, Nordlinger B, Vincendet M, Charneau J, Pillon D, Stremsdoerfer N, Pelletier M, Clavero-Fabri MC, Leduc B, Segol P, Argouach LP, Roussel A, Maurel J, Salame R, Lacourt J, Janoray P, Ruget O, Baudet-Klepping D, Dupont G, Bommelaer G, Ruszniewski P, Hammel P, Chaussade S, Dousset B, Denis B, Wagner JD, Tamby E, Petit T, Weiss AM, Barbare JC, Jouve JL, Phelip JM, Senesse P, Michiels C, Maingon P, Coudert B, Fraisse J, Queuniet A, Gasnault L, Gstach JH, Guichard B, Howaizi M, Geoffroy P, Picot C, Fournet J, Mousseau M, Stampfli C, Michel P, Doll J, Durand S, Buffet C, Triboulet JP, Denimal F, Hebbar M, Quandalle P, Mirabel X, Lledo G, Giovannini M, Souillac P, Untereiner M, Leroy-Terquem E, Lacroix H, Francois E, Lagasse JP, Breteau N, Legoux JL, Etienne JC, Delattre JF, Lubrano D, Levy-Chazal N, Palot JP, Nasca S, Demange L, Nguyen TD, Seng S, Michel P, Teniere P, Thevenet P, Le Brise H, Fleury J, Kammerer J, Cosme H, Novello P, Avignon JP, Berton C, Legueul, Parisot P, Aunis G, Vetter D, Platini C, Cals L, Rouhier D, Robin B, Champetier T, Cartalat A, Marchal C, Guillemin F, Flamenbaum M, Cassan D, Ducreux M., Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU - HÔTEL-DIEU Clermont-Ferrand, Service de chirurgie digestive [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), CHU de Poitiers, and Hôpital de la Timone [CHU - APHM] ( TIMONE )
Subjects: Male, Cancer Research, Time Factors, Esophageal Neoplasms, Kaplan-Meier Estimate, MESH: Esophagectomy, law.invention, MESH: Proportional Hazards Models, MESH : Adenocarcinoma, 0302 clinical medicine, Randomized controlled trial, law, Risk Factors, MESH : Esophagectomy, MESH: Risk Factors, MESH : Neoplasm Staging, MESH : Female, MESH : Carcinoma, Squamous Cell, MESH: Treatment Outcome, MESH: Chemoradiotherapy, Randomised controlled trial, education.field_of_study, Hazard ratio, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Carcinoma, Squamous Cell, Chemoradiotherapy, MESH : Chemoradiotherapy, MESH: Neoplasm Staging, MESH : Risk Factors, Neoadjuvant Therapy, 3. Good health, Oesophageal neoplasms, Treatment Outcome, Oncology, Chemoradiation, 030220 oncology & carcinogenesis, MESH: Esophageal Neoplasms, Carcinoma, Squamous Cell, 030211 gastroenterology & hepatology, Female, Esophageal Squamous Cell Carcinoma, France, MESH : Time Factors, medicine.medical_specialty, MESH: Radiotherapy, Adjuvant, MESH : Male, Population, MESH: Neoadjuvant Therapy, Locally advanced, MESH : Treatment Outcome, Adenocarcinoma, MESH : Radiotherapy, Adjuvant, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Early surgery, medicine, Humans, Basal cell, Salvage surgery, education, MESH : France, Contraindication, MESH: Kaplan-Meier Estimate, Neoplasm Staging, Proportional Hazards Models, MESH: Humans, business.industry, MESH : Humans, MESH: Adenocarcinoma, MESH: Time Factors, Cancer, medicine.disease, MESH : Proportional Hazards Models, MESH: Male, Surgery, Esophagectomy, MESH: France, Radiotherapy, Adjuvant, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Esophageal Neoplasms, business, MESH : Neoadjuvant Therapy, MESH: Female
Abstract: International audience; BACKGROUND:Two randomised trials concerning thoracic oesophageal cancer concluded that for squamous cell carcinoma, chemoradiation alone leads to the same overall survival (OS) as chemoradiation followed by surgery. One of these trials, FFCD 9102, randomised only fit, compliant and operable responders to induction chemoradiation between continuation of chemoradiation and surgery. In the present analysis, the outcome in the patients not eligible for randomisation was calculated to determine if attempt of surgery should be recommended.METHODS:Eligible patients had operable T3-N0/N1-M0 thoracic oesophageal cancer. After initial chemoradiation, patients with no clinical response, or with contraindication to follow any attributed treatment, were not randomised. OS was studied first in the whole population of not randomised patients, and then specifically in clinical non-responders. The impact of surgery on OS was studied in these two populations.FINDINGS:Of the 451 registered patients in the trial, 192 were not randomised. Among them, 111 were clinical non-responders. Median OS was significantly shorter for non-randomised patients (11.5 months) than for randomised patients (18.9 months; p=0.0024). However, for the 112 non-randomised patients who underwent surgery, median OS was not different from that in randomised patients: 17.3 versus 18.9 months (p=0.58). Concerning clinical non-responders, median OS was longer for those who underwent surgery compared to non-operated patients: 17.0 versus 5.5 months (hazard ratio (HR)=0.39 [0.25-0.61]; p
Published: 2015
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48. Oesophageal cancer: exploring controversies overview of experts’ opinions of Austria, Germany, France, Netherlands and Switzerland

Author: Michael Stahl, Wolfgang Eisterer, Thomas Ruhstaller, Paul Martin Putora, Wilfried Budach, Robert Jäger, Christophe Mariette, Annelies Schnider, J. Jan B. van Lanschot, Ate van der Gaast, Laurent Bedenne, Medical Oncology, and Surgery
Subjects: Diagnostic Imaging, medicine.medical_specialty, Consensus, Esophageal Neoplasms, Controversy, MEDLINE, European, Multimodal Imaging, SDG 3 - Good Health and Well-being, Antineoplastic Combined Chemotherapy Protocols, medicine, Chemotherapy, Humans, Radiotherapy dose, Radiology, Nuclear Medicine and imaging, Disease management (health), Societies, Medical, Neoplasm Staging, Squamous cell cancer, Radiotherapy, business.industry, Research, Oesophageal cancer, Remission Induction, Disease Management, Induction chemotherapy, Cancer, Chemoradiotherapy, Oesophageal carcinoma, medicine.disease, Dissent and Disputes, Neoadjuvant Therapy, Surgery, Treatment, Esophagectomy, Europe, Oesophagus, Oncology, Radiology Nuclear Medicine and imaging, Family medicine, Level evidence, business
Abstract: Background Oesophageal carcinoma is a rare disease with often dismal prognosis. Despite multiple trials addressing specific issues, currently, many questions in management remain unanswered. This work aimed to specifically address areas in the management of oesophageal cancer where high level evidence is not available, performing trials is very demanding and for many questions high-level evidence will not be available in the forseeable future. Methods Two experts of each national, oesophageal cancer research group from Austria, France, Germany, the Netherlands and Switzerland were asked to provide statements to controversial issues. After an initial survey, further questions were formulated and answered by all experts. The answers were then discussed and qualitatively analysed for consensus and controversy. Results Topics such as indications for PET-CT, reasons for induction chemotherapy, radiotherapy dose, the choice of definitive chemo-radiotherapy versus surgery in squamous cell cancer, the role of radiotherapy in adenocarcinoma and selected surgical issues were identified as topics of interest and discussed. Conclusion Areas of significant controversy exist in the management of oesophageal cancer, mostly due to high-level evidence. This is not expected to change in the upcoming years. Electronic supplementary material The online version of this article (doi:10.1186/s13014-015-0418-4) contains supplementary material, which is available to authorized users.
Published: 2015
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49. High-Dose FOLFIRI plus Bevacizumab in the Treatment of Metastatic Colorectal Cancer Patients with Two Different UGT1A1 Genotypes: FFCD 0504 Study

Author: Laetitia Dahan, Marie-Anne Loriot, Pierre Michel, Pierre Luc Etienne, Faiza Khemissa, Gilles Breysacher, Sylvain Manfredi, Emilie Maillard, Karine Le Malicot, Jean Pierre Lafargue, Thierry Lecomte, Emmanuel Mitry, Jean Louis Legoux, Philippe Rougier, Cedric Lecaille, Olivier Bouché, Laurent Bedenne, and Thomas Aparicio
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Bevacizumab, Adolescent, Genotype, Colorectal cancer, Population, Leucovorin, Phases of clinical research, Gastroenterology, Disease-Free Survival, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Glucuronosyltransferase, Neoplasm Metastasis, education, Aged, education.field_of_study, Polymorphism, Genetic, business.industry, Middle Aged, medicine.disease, Interim analysis, Irinotecan, Oncology, Fluorouracil, FOLFIRI, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract: High-dose FOLFIRI has an acceptable safety profile and promising efficacy. UDP-glucuronosyltransferase: (UGT1A1) polymorphism may be predictive of toxicity and efficacy of irinotecan. This phase II study aimed to evaluate the combination of high-dose FOLFIRI plus bevacizumab in patients with previously untreated metastatic colorectal cancer (MCRC) based on their UGT1A1 genotype. Patients with the UGT1A1 *1/*1 (group 1) or *1/*28 (group 2) genotype received bevacizumab plus high-dose FOLFIRI every 2 weeks. Using the Bryant and Day design with objective response rate and toxicity as the primary endpoints, 54 patients in each group were required with a planned interim analysis after inclusion of 17 patients per group. We planned to stop the trial at the interim analysis if ≤7 patients exhibited an objective response (OR) and/or ≥3 patients exhibited severe toxicity. At the interim analysis, ORs were higher than the number expected: 52.9% (group 1) and 58.8% (group 2). More than three toxic events occurred in both groups and, according to the interim analysis rule, the trial was closed due to unacceptable toxicity. Recruitment was stopped when 86 patients were included and an analysis on overall population was done for overall survival (OS) and progression-free survival (PFS). The median PFS was 10.7 months (group 1) and 10.4 months (group 2). The median OS was 25.5 months (group 1) and 23.9 months (group 2). This trial does not support the use of the intensive treatment with HD-FOLFIRI plus bevacizumab combination for MCRC in patients with the UGTA1*1/UGT1A1*1 or UGT1A1*1/UGT1A1*28 genotype. Mol Cancer Ther; 14(12); 2782–8. ©2015 AACR.
Published: 2015

50. Quels changements dans le Thésaurus National de Cancérologie Digestive en 2005 ?

Author: Michel Ducreux, Christophe Louvet, Thierry André, Agnès Ruskoné-Foumestraux, Jean-Claude Barbare, David Malka, Didier Peiffert, Guillaume Cadiot, Philippe Rougier, Bruno Landi, Denis Pezet, Olivier Bouché, Laurent Bedenne, Jean-Louis Legoux, Jean-François Seitz, and Etienne Dorval
Subjects: business.industry, Gastroenterology, Library science, Medicine, General Medicine, business
Published: 2006
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