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1. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER PRODIGE 23): Health-related quality of life longitudinal analysis

Author: Caroline Bascoul-Mollevi, Sophie Gourgou, Christophe Borg, Pierre-Luc Etienne, Emmanuel Rio, Eric Rullier, Beata Juzyna, Florence Castan, and Thierry Conroy
Subjects: Cancer Research, Oncology
Published: 2023
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2. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial

Author: Thierry Conroy, Jean-François Bosset, Pierre-Luc Etienne, Emmanuel Rio, Éric François, Nathalie Mesgouez-Nebout, Véronique Vendrely, Xavier Artignan, Olivier Bouché, Dany Gargot, Valérie Boige, Nathalie Bonichon-Lamichhane, Christophe Louvet, Clotilde Morand, Christelle de la Fouchardière, Najib Lamfichekh, Béata Juzyna, Claire Jouffroy-Zeller, Eric Rullier, Frédéric Marchal, Sophie Gourgou, Florence Castan, Christophe Borg, Philippe Ronchin, Jean-François Seitz, Stéphane Corbinais, Emmanuel Maillard, Monique Noirclerc, Farid El Hajbi, Anne-Laure Villing, Yves Bécouarn, Lam Foong Fat Lam Kam Sang, Pascal Artru, Jean-Baptiste Bachet, Fayçal Hocine, Catherine Ligeza-Poisson, Claire Vautravers, Meher Ben Abdelghani, Thomas Aparicio, Elise Desot, and Isabelle Marquis
Subjects: Adult, Male, medicine.medical_specialty, FOLFIRINOX, medicine.medical_treatment, Population, Leucovorin, Irinotecan, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Adjuvant therapy, Humans, 030212 general & internal medicine, education, Neoadjuvant therapy, Aged, education.field_of_study, Performance status, Rectal Neoplasms, business.industry, Chemoradiotherapy, Middle Aged, Total mesorectal excision, Neoadjuvant Therapy, Oxaliplatin, Oncology, 030220 oncology & carcinogenesis, Quality of Life, Female, Fluorouracil, business, medicine.drug
Abstract: Summary Background Treatment of locally advanced rectal cancer with chemoradiotherapy, surgery, and adjuvant chemotherapy controls local disease, but distant metastases remain common. We aimed to assess whether administering neoadjuvant chemotherapy before preoperative chemoradiotherapy could reduce the risk of distant recurrences. Methods We did a phase 3, open-label, multicentre, randomised trial at 35 hospitals in France. Eligible patients were adults aged 18–75 years and had newly diagnosed, biopsy-proven, rectal adenocarcinoma staged cT3 or cT4 M0, with a WHO performance status of 0–1. Patients were randomly assigned (1:1) to either the neoadjuvant chemotherapy group or standard-of-care group, using an independent web-based system by minimisation method stratified by centre, extramural extension of the tumour into perirectal fat according to MRI, tumour location, and stage. Investigators and participants were not masked to treatment allocation. The neoadjuvant chemotherapy group received neoadjuvant chemotherapy with FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 intravenously every 14 days for 6 cycles), chemoradiotherapy (50 Gy during 5 weeks and 800 mg/m2 concurrent oral capecitabine twice daily for 5 days per week), total mesorectal excision, and adjuvant chemotherapy (3 months of modified FOLFOX6 [intravenous oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2, followed by intravenous 400 mg/m2 fluorouracil bolus and then continuous infusion at a dose of 2400 mg/m2 over 46 h every 14 days for six cycles] or capecitabine [1250 mg/m2 orally twice daily on days 1–14 every 21 days]). The standard-of-care group received chemoradiotherapy, total mesorectal excision, and adjuvant chemotherapy (for 6 months). The primary endpoint was disease-free survival assessed in the intention-to-treat population at 3 years. Safety analyses were done on treated patients. This trial was registered with EudraCT (2011-004406-25) and ClinicalTrials.gov ( NCT01804790 ) and is now complete. Findings Between June 5, 2012, and June 26, 2017, 461 patients were randomly assigned to either the neoadjuvant chemotherapy group (n=231) or the standard-of-care group (n=230). At a median follow-up of 46·5 months (IQR 35·4–61·6), 3-year disease-free survival rates were 76% (95% CI 69–81) in the neoadjuvant chemotherapy group and 69% (62–74) in the standard-of-care group (stratified hazard ratio 0·69, 95% CI 0·49–0·97; p=0·034). During neoadjuvant chemotherapy, the most common grade 3–4 adverse events were neutropenia (38 [17%] of 225 patients) and diarrhoea (25 [11%] of 226). During chemoradiotherapy, the most common grade 3–4 adverse event was lymphopenia (59 [28%] of 212 in the neoadjuvant chemotherapy group vs 67 [30%] of 226 patients in the standard-of-care group). During adjuvant chemotherapy, the most common grade 3–4 adverse events were lymphopenia (18 [11%] of 161 in the neoadjuvant chemotherapy group vs 42 [27%] of 155 in the standard-of-care group), neutropenia (nine [6%] of 161 vs 28 [18%] of 155), and peripheral sensory neuropathy (19 [12%] of 162 vs 32 [21%] of 155). Serious adverse events occurred in 63 (27%) of 231 participants in the neoadjuvant chemotherapy group and 50 (22%) of 230 patients in the standard-of-care group (p=0·167), during the whole treatment period. During adjuvant therapy, serious adverse events occurred in 18 (11%) of 163 participants in the neoadjuvant chemotherapy group and 36 (23%) of 158 patients in the standard-of-care group (p=0·0049). Treatment-related deaths occurred in one ( Interpretation Intensification of chemotherapy using FOLFIRINOX before preoperative chemoradiotherapy significantly improved outcomes compared with preoperative chemoradiotherapy in patients with cT3 or cT4 M0 rectal cancer. The significantly improved disease-free survival in the neoadjuvant chemotherapy group and the decreased neurotoxicity indicates that the perioperative approach is more efficient and better tolerated than adjuvant chemotherapy. Therefore, the PRODIGE 23 results might change clinical practice. Funding Institut National du Cancer, Ligue Nationale Contre le Cancer, and R&D Unicancer.
Published: 2021
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3. Gemcitabine plus nab-paclitaxel until progression or alternating with FOLFIRI.3, as first-line treatment for patients with metastatic pancreatic adenocarcinoma: The Federation Francophone de Cancérologie Digestive-PRODIGE 37 randomised phase II study (FIRGEMAX)

Author: David Malka, Benoît Dupont, Alain Gratet, Pamela Biondiani, Marion Chauvenet, Dany Gargot, Pierre-Emmanuel Henneresse, Hortense Laharie, Johann Dreanic, Valérie Lebrun Lyat, Catherine Brezault-Bonnet, Morgan Andre, Géraldine Perkins, Philippe Houyau, Yves Rinaldi, Etienne Suc, Dominique Besson, Valérie Boige, Cécile Julien, Julien Taieb, Simon Pernot, Benoît Avisse, Pauline Regnault, Ahmed Bedjaoui, Marie-Pierre Galais, Côme Lepage, Céline Lepère, Mme E. Barbier, Antoine Holllebecque, Anne Escande, Julie Vincent, Sandrine Lavau denes, Marie-Claude Gouttebel, Leila Bengrine Lefevre, Anne Thirot Bidault, Anne-Laure Pointet, Julie Gigout, Faiza Khemissa Akouz, Louis-Marie Dourthe, Frederick Moryoussef, Maxime Lesouef, Vincent Bourgeois, François Ghiringhelli, Patrick Texereau, Samy Louafi, Gildas Phelip, Yann Berge, Jean-François Codoul, Jérôme Chamois, Eric Terrebonne, Karine Bouhier Leporrier, Bidaut Wahiba, X. Artignan, Pr Pierre Michel, Iulia Pripon, David Sefrioui, Pierre-Luc Etienne, Romain Coriat, Aurélie Parzy, Mustapha Atlassi, Aziz Zaanan, Jean-Baptiste Bachet, Philippe Dominici, Jean Martin, Mathilde Martinez, Dominique Genet, Raymond Despax, Karine Le Malicot, Laurent Miglianico, Salvatore Caruso, Bruno Valenza, Nicolas Barriere, and Oana Zveltlana Cojocarasu
Subjects: Adult, Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Paclitaxel, Population, Leucovorin, Phases of clinical research, Adenocarcinoma, Neutropenia, Irinotecan, Deoxycytidine, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Albumins, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, education, Aged, education.field_of_study, Drug Substitution, business.industry, Middle Aged, medicine.disease, Gemcitabine, Neoadjuvant Therapy, Progression-Free Survival, Pancreatic Neoplasms, Treatment Outcome, 030104 developmental biology, Oncology, Tolerability, 030220 oncology & carcinogenesis, Disease Progression, FOLFIRI, Camptothecin, Female, Fluorouracil, France, business, Febrile neutropenia, medicine.drug
Abstract: Background Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination. Patients and methods We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0–2 to alternately receive gemcitabine + nab-paclitaxel for 2 months then FOLFIRI.3 for 2 months in arm A, or gemcitabine + nab-paclitaxel alone until progression in arm B. The primary objective was to increase the 6-month progression-free survival (PFS) rate from 40% (H0) to 60% (H1); using the binomial exact method, 124 patients were required. Analyses were carried out in preplanned modified intention-to-treat (mITT) and per-protocol (PP) populations. Results Between November 2015 and November 2016, 127 patients were enrolled. Main grade III–IV toxicities (% in arm A/B) were: diarrhoea (12.5/1.7), neutropenia (46.9/31, including febrile neutropenia: 1.6/0), skin toxicity (6.3/13.8), and peripheral neuropathy (6.3/8.6). No toxic deaths occurred. The objective response rate was 40.3% (95% confidence interval [CI]: 28.1–53.6) in arm A and 26.7% (95% CI: 16.1–39.7) in arm B. The primary end-point (6-month PFS rate) was 45.2% [one-sided 95% CI: 34.3–56.4] in arm A and 23.3% in arm B [one-sided 95% CI: 14.3–32.3] in the mITT population. In the PP population, median PFS and OS were 7.6 months and 6 months and 14.5 months and 12.2 months in arm A and B, respectively. Conclusions The FIRGEMAX strategy with gemcitabine + nab-paclitaxel alternating with FOLFIRI.3 every 2 months, appears feasible and effective, with manageable toxicities, in patients able to reach >2mo of treatment. Trial registration information EudraCT: 2014-004449-28: NCT: 0282701.
Published: 2020
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4. Evaluation of Nurses’ and Patients’ Overall Satisfaction with New and Previous Formulations of Octreotide Long-acting Release (Sandostatin LAR®): A French Observational Study

Author: Guillaume Cadiot, Denis Smith, Thierry Nguyen-Tan-Hon, Brigitte Delemer, F Schillo, Bénédicte Decoudier, Pierre-Luc Etienne, Romain Coriat, Alexandre Santos, Isabelle Raingeard, Ségolène Bisot-Locard, Iradj Sobhani, and Gérald Raverot
Subjects: 030213 general clinical medicine, medicine.medical_specialty, Visual analogue scale, business.industry, Octreotide, General Medicine, Long acting release, 03 medical and health sciences, Safety profile, 0302 clinical medicine, Patient satisfaction, Quality of life, Multicenter study, 030220 oncology & carcinogenesis, medicine, Physical therapy, Pharmacology (medical), Observational study, business, medicine.drug
Abstract: The first long-acting release (LAR) formulation of octreotide was marketed in France in the late 1990s. An injectable formulation of Sandostatin LAR® (Novartis SAS) with a new diluent has been developed to facilitate its preparation and administration and to improve its use in practice. We conducted an observational, cross-sectional and multicenter study in France whose main outcome was to compare nurses’ satisfaction with the preparation and administration of both previous and new formulations of octreotide LAR. Secondary outcomes included assessment of patient satisfaction (quality of life and pain felt during the injection) and product tolerance. Data were collected at two time points (one for the first formulation group and one for the second formulation group) through paper questionnaires administered to physicians, patients and nurses including a visual analog scale (VAS) from 0 (unsatisfied) to 10 (very satisfied). Results showed that overall nurse satisfaction improved from 5.3 (95% CI 4.9–5.8) with the previous formulation to 7.5 (95% CI 7–7.9) with the new formulation (p
Published: 2020
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5. Renal function in patients receiving streptozocin for locally advanced or metastatic digestive neuroendocrine tumours: results of the Streptotox-FFCD 0906 study

Author: Eric Terrebonne, Hedia Brixi, Bernard Paule, Karine Le Malicot, Côme Lepage, Jean-Louis Legoux, Abakar Mahamat-Abakar, Thierry Lecomte, Pierre-Luc Etienne, Catherine Lombard-Bohas, Gabriel Choukroun, Sophie Dominguez, Philippe Ruszniewski, Pierre Michel, François-Xavier Caroli-Bosc, for Streptotox-FFCD investigators, Laetitia Dahan, Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID), 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, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Privé des Côtes d'Armor (HPCA), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hôpital Paul Brousse, Hôpital Cardiologique du Haut Lévêque [Pessac], CHU Rouen, Normandie Université (NU), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, BOURGEAIS, Véronique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Lille Nord de France (COMUE)-UNICANCER, and 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)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Locally advanced, Renal function, Digestive System Neoplasms, Kidney, Gastroenterology, Streptozocin, Nephrotoxicity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Hepatology, business.industry, Incidence (epidemiology), Retrospective cohort study, 3. Good health, [SDV] Life Sciences [q-bio], Neuroendocrine Tumors, Treatment Outcome, 030220 oncology & carcinogenesis, Toxicity, business
Abstract: Introduction Streptozocin can impair renal function. The purpose of this study was to evaluate the evolution of renal function in patients receiving this anti-mitotic for the treatment of locally advanced/metastatic digestive well differentiated neuroendocrine tumours. Methods A prospective and a retrospective cohort of patients with normal baseline renal function were analysed. The primary endpoint was the incidence of a decrease in the estimated glomerular filtration rate ≥ 25% during treatment. Secondary endpoints were the evaluation of glomerular filtration rate changes, the impact of combined nephrotoxic treatments, other toxicities, compliance, and the objective response rate. Results After screening 142 patients, 27 were included in the prospective and 84 in the retrospective cohort. A decrease in estimated glomerular filtration rate ≥ 25% was observed in 32 patients (30%): respectively four (15.4%) and 28 patients (34.1%) among respectively 26 and 82 patients with numerous measures (P = 0.0097). Altogether, 39 patients (35%) experienced grade 1–2 renal toxicity, while no grade 3−4 occurred in the prospective and 1 occurred in the retrospective cohort. Renal toxicity was more frequent in the retrospective cohort with a less careful follow up. As best responses, objective response was achieved in 27% of patients with pancreatic primary tumours, disease control in 78.9% of patients with pancreatic primary tumours, in 87% of those with small bowel tumours and in 72.7% of patients with other primary locations. Conclusions Strongly recommended for pancreatic NET, streptozocin is associated with frequent mild renal toxicity but low occurrence of renal impairment in patients with baseline normal renal function and under adequate hydration.
Published: 2021
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6. MRI-Based Radiomics Input for Prediction of 2-Year Disease Recurrence in Anal Squamous Cell Carcinoma

Author: Christelle De La Fouchardiere, Arnaud Hocquelet, Véronique Vendrely, Emilie Barbier, Louis-Arnaud Bazire, Thomas Charleux, Meher Ben Abdelghani, Xavier Mirabel, Ariane Darut-Jouve, Wulfran Cacheux, Thomas Aparicio, Delphine Argo-Leignel, Nicolas Giraud, Pierre-Luc Etienne, Nicolas Magné, Hervé Trillaud, Olivier Saut, Gilles Breysacher, Philippe Ronchin, Alexandre Tessier, Claire Lemanski, Côme Lepage, Astrid Lièvre, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Modélisation Mathématique pour l'Oncologie (MONC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Azuréen de Cancérologie [Mougins, France], Institut Curie [Paris], Fédération Francophone de Cancérologie Digestive (FFCD), Institut du Cancer de Montpellier (ICM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Hôpital privé Pays de Savoie, Institut de Cancérologie de Bourgogne, Centre Léon Bérard [Lyon], Hôpitaux Civils de Colmar, Groupe Hospitalier Bretagne Sud (GHBS), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut de Cancérologie de Strasbourg Europe (ICANS), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], Université de Lille-UNICANCER, and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Cancer Research, medicine.medical_specialty, Multivariate analysis, anal cancer, precision medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Logistic regression, lcsh:RC254-282, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Anal cancer, magnetic resonance imaging, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Univariate analysis, Proportional hazards model, business.industry, Standard treatment, Univariate, Anal Squamous Cell Carcinoma, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, 3. Good health, machine learning, Oncology, radiomics, prediction medicine, 030220 oncology & carcinogenesis, Radiology, business
Abstract: Simple Summary Exclusive chemo-radiotherapy (CRT) is the standard treatment for non-metastatic anal squamous cell carcinomas. Identifying novel prognostic factors could help to improve CRT outcomes, notably for locally advanced diseases where relapses still occur in around 35% of patients. In this study, we aim to assess the potential value of a pre-therapeutic MRI radiomic analysis added to standard clinical variables in order to build a logistic regression model predicting 2-year recurrence after CRT. In a population of 82 patients randomly divided in training (n = 54) and testing (n = 28) sets, after selection of optimal variables, a model using two radiomic (FirstOrder_Entropy and GLCM_JointEnergy) and two clinical (tumor size and CRT length) features was able to predict the 2-year recurrence with good performances in the testing set. Radiomic biomarkers provided valuable additional and independent information added to clinical data, and could help contribute to identify high risk patients amenable to treatment intensification with view of personalized medicine. Abstract Purpose: Chemo-radiotherapy (CRT) is the standard treatment for non-metastatic anal squamous cell carcinomas (ASCC). Despite excellent results for T1-2 stages, relapses still occur in around 35% of locally advanced tumors. Recent strategies focus on treatment intensification, but could benefit from a better patient selection. Our goal was to assess the prognostic value of pre-therapeutic MRI radiomics on 2-year disease control (DC). Methods: We retrospectively selected patients with non-metastatic ASCC treated at the CHU Bordeaux and in the French FFCD0904 multicentric trial. Radiomic features were extracted from T2-weighted pre-therapeutic MRI delineated sequences. After random division between training and testing sets on a 2:1 ratio, univariate and multivariate analysis were performed on the training cohort to select optimal features. The correlation with 2-year DC was assessed using logistic regression models, with AUC and accuracy as performance gauges, and the prediction of disease-free survival using Cox regression and Kaplan-Meier analysis. Results: A total of 82 patients were randomized in the training (n = 54) and testing sets (n = 28). At 2 years, 24 patients (29%) presented relapse. In the training set, two clinical (tumor size and CRT length) and two radiomic features (FirstOrder_Entropy and GLCM_JointEnergy) were associated with disease control in univariate analysis and included in the model. The clinical model was outperformed by the mixed (clinical and radiomic) model in both the training (AUC 0.758 versus 0.825, accuracy of 75.9% versus 87%) and testing (AUC 0.714 versus 0.898, accuracy of 78.6% versus 85.7%) sets, which led to distinctive high and low risk of disease relapse groups (HR 8.60, p = 0.005). Conclusion: A mixed model with two clinical and two radiomic features was predictive of 2-year disease control after CRT and could contribute to identify high risk patients amenable to treatment intensification with view of personalized medicine.
Published: 2021
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7. Baseline Splenic Volume as a Prognostic Biomarker of FOLFIRI Efficacy and a Surrogate Marker of MDSC Accumulation in Metastatic Colorectal Carcinoma

Author: Julie Blanc, Marc Porneuf, Corinne Sarda, François-Xavier Caroli-Bosc, Julie Niogret, Karine Le Malicot, Emeric Limagne, M. Baconnier, Pierre-Luc Etienne, Franck Audemar, S. Nguyen, C. Lombard-Bohas, Jean-Louis Legoux, Thomas Aparicio, Miguel Carreiro, Marion Thibaudin, François Ghiringhelli, Y. Rinaldi, Aurélie Bertaut, Christophe Locher, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), École Nationale Supérieure de Formation de l'Enseignement Agricole de Toulouse-Auzeville (ENSFEA), 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), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Le CHCB, Centre Hospitalier de la Côte Basque, CHU Pau, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Grand Hôpital de l'Est Francilien (GHEF), Centre hospitalier de Montauban, Centre Hospitalier Régional d'Orléans (CHRO), Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Yves LE FOLL [Saint-Brieuc], Hopital Saint-Louis [AP-HP] (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, [SDV]Life Sciences [q-bio], MDSC, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Prognostic biomarker, prognostic biomarker, Chemotherapy, splenomegaly, business.industry, Surrogate endpoint, metastatic colorectal cancer, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, digestive system diseases, 3. Good health, Irinotecan, 030104 developmental biology, 030220 oncology & carcinogenesis, Myeloid-derived Suppressor Cell, FOLFIRI, circulating monocytic myeloid derived suppressor cells, business, medicine.drug
Abstract: Background: Predictive biomarkers of response to chemotherapy plus antiangiogenic for metastatic colorectal cancer (mCRC) are lacking. The objective of this study was to test the prognostic role of splenomegaly on baseline CT scan. Methods: This study is a sub-study of PRODIGE-9 study, which included 488 mCRC patients treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab in first line. The association between splenic volume, and PFS and OS was evaluated by univariate and multivariable Cox analyses. The relation between circulating monocytic Myeloid derived suppressor cells (mMDSC) and splenomegaly was also determined. Results: Baseline splenic volume &gt, 180 mL was associated with poor PFS (median PFS = 9.2 versus 11.1 months, log-rank p = 0.0125), but was not statistically associated with OS (median OS = 22.6 versus 28.5 months, log-rank p = 0.1643). The increase in splenic volume at 3 months had no impact on PFS (HR 0.928, log-rank p = 0.56) or on OS (HR 0.843, log-rank p = 0.21). Baseline splenic volume was positively correlated with the level of baseline circulating mMDSC (r = 0.48, p-value = 0.031). Conclusion: Baseline splenomegaly is a prognostic biomarker in patients with mCRC treated with FOLFIRI and bevacizumab, and a surrogate marker of MDSC accumulation.
Published: 2020
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8. Evaluation of Nurses' and Patients' Overall Satisfaction with New and Previous Formulations of Octreotide Long-acting Release (Sandostatin LAR

Author: Brigitte, Delemer, Thierry, Nguyen-Tan-Hon, Romain, Coriat, Denis, Smith, Frank, Schillo, Isabelle, Raingeard, Iradj, Sobhani, Pierre-Luc, Etienne, Benedicte, Decoudier, Ségolène, Bisot-Locard, Alexandre, Santos, Gerald, Raverot, and Guillaume, Cadiot
Subjects: Adult, Male, Antineoplastic Agents, Hormonal, Administration, Oral, Middle Aged, Octreotide, Injections, Cross-Sectional Studies, Patient Satisfaction, Delayed-Action Preparations, Acromegaly, Quality of Life, Humans, Female, Nursing Staff, France, Aged
Abstract: The first long-acting release (LAR) formulation of octreotide was marketed in France in the late 1990s. An injectable formulation of Sandostatin LARWe conducted an observational, cross-sectional and multicenter study in France whose main outcome was to compare nurses' satisfaction with the preparation and administration of both previous and new formulations of octreotide LAR. Secondary outcomes included assessment of patient satisfaction (quality of life and pain felt during the injection) and product tolerance. Data were collected at two time points (one for the first formulation group and one for the second formulation group) through paper questionnaires administered to physicians, patients and nurses including a visual analog scale (VAS) from 0 (unsatisfied) to 10 (very satisfied).Results showed that overall nurse satisfaction improved from 5.3 (95% CI 4.9-5.8) with the previous formulation to 7.5 (95% CI 7-7.9) with the new formulation (p 0.0001). Regarding secondary outcomes, the simplicity of the injection increased (84% for the previous formulation and 94% for the new formulation) and the purge problem disappeared (36% for the previous formulation and 4% for the new formulation).The improvement due to the new formulation of Sandostatin LAR
Published: 2020

9. Regorafenib (REGO) plus FOLFIRINOX as frontline treatment in patients (pts) with RAS-mutated metastatic colorectal cancer (mCRC): A phase I/II, dose-escalation and dose-expansion study

Author: Antoine Adenis, François Ghiringhelli, Ludovic Gauthier, Thibault Mazard, Ludovic Evesque, Pierre-Luc Etienne, Alexandre Evrard, Patrick Chalbos, Jean-Pierre Bleuse, Diego Tosi, Sophie Gourgou, and Marc Ychou
Subjects: Cancer Research, Oncology
Abstract: 3561 Background: Standard treatment options for RAS-mutated mCRC pts include the combination of bevacizumab with FOLFIRINOX, a three-drug chemotherapy regimen. Unlike bevacizumab, REGO – an oral multi-tyrosine kinase agent - exhibits not only antiangiogenic properties with cytostatic effects but also true cytotoxic effects. We report the preliminary results of the FOLFIRINOX-R trial (NCT03828799), in which we evaluated the safety and the efficacy of REGO in combination with FOLFIRINOX in pts with RAS-mutated mCRC. Methods: FOLFIRINOX-R trial is a prospective, dose-finding, phase I/II study whose dose-escalation part has been completed. Dose escalation was implemented following a 3 + 3 design and included three dose levels (DL). FOLFIRINOX regimen includes oxaliplatin (85 mg/m²), folinic acid (400 mg/m²), irinotecan (150–180 mg/m²), 5-fluorouracil (400 mg/m² in bolus then 2400 mg/m² over 46h), and was administered every 14 days. REGO (80 to 160 mg per day, as per DL) was administered on days 4 to 10 of each cycle. Treatment was continued up to 12 cycles or until progression or unacceptable toxicity. The primary objectives of the dose-finding part of the study were to determine the maximum tolerated dose (MTD) using as endpoint the incidence of DLTs during the three first cycles of treatment, and to select the recommended phase 2 dose (RP2D). Key eligibility criteria include ECOG PS ≤1 and RAS-mutated mCRC not amenable to surgery with curative intent and not previously treated for metastatic disease. Patients with the 7/7 variant of the UGT1A1*28 polymorphism were not eligible. Prophylactic G-CSF was administered from Day-7 to Day-12. Results: Thirteen pts were enrolled across the 3 DL (DL 1: 3 pts, DL 2: 6 pts, DL 3: 4 pts); 46% of pts were female, the median age was 65 yo [range: 40 ; 76]. One pt (at DL 3) was not evaluable for DLT because of poor observance during the first 2 cycles. At data cut-off, median treatment duration and median follow-up were 4.6 mo. (range: 2.3; 10) and 13.4 mo. (range: 3.8; 18.0), respectively. One DLT (a grade 3 hypokalaemia related to grade 2 diarrhoea) occurred at DL 2. MTD was not reached at DL 3 (REGO 160 mg/day). The most common grade ≥3 TRAE per patient were grade 3 neutropenia (n = 1), grade 4 neutropenia (n = 1), grade 3 neuropathy (n = 2) and grade 3 diarrhoea (n = 7). Dose reductions/discontinuations due to grade ≥3 TRAE were necessary in 12/13 (92%) pts. The ORR was 62% (95% CI 32%-86%) and median PFS was 9.1 mo (range: 3.1; 15.4). Conclusions: Full-dose FOLFIRINOX plus full-dose REGO (160mg/day, days 4 to 10) can be administered safely. Due to the manageable toxicity profile and the promising efficacy observed in the dose-escalation stage, this regimen deserves to be evaluated in the dose-expansion stage. Clinical trial information: NCT03828799.
Published: 2022
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10. STRATEGIC-1: Multi-line therapy trial in unresectable wild-type KRAS/NRAS/BRAF metastatic colorectal cancer—A GERCOR-PRODIGE randomized open-label phase III study

Author: Benoist Chibaudel, Louis-Marie Dourthe, Thierry Andre, Julie Henriques, Vincent Bourgeois, Pierre-Luc Etienne, Jérôme Desrame, Elisabeth Carola, Olivier Dupuis, Nabil Baba-Hamed, Dominique Auby, Christophe Louvet, Emmanuel Maillard, Olivier Romano, Christophe Tournigand, Marie-Line Garcia-Larnicol, Einat Shacham Shmueli, Brian Healey Bird, François Ghiringhelli, and Aimery De Gramont
Subjects: Cancer Research, Oncology
Abstract: 3504 Background: The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents have become available. Ultimately, strategy trials are needed to define the optimal use and the best sequencing of these agents. Methods: Patients with previously untreated RAS/BRAF wild-type unresectable mCRC were randomly assigned (1:1 ratio) to receive either FOLFIRI-cetuximab followed by mFOLFOX6-bevacizumab (arm A) or OPTIMOX-bevacizumab followed by FOLFIRI-bevacizumab followed by EGFR mab +/- irinotecan (arm B). This trial was designed as a superiority study (hypothesis arm B > arm A) with Duration of Disease Control (DDC) as primary endpoint, defined as the sum of PFS of each active sequence of treatment (Chibaudel B, J Clin Oncol, 2011). Secondary endpoints were overall survival (OS), Time to Failure of Strategy (TFS), Progression-free survival (PFS) and response rate (RECIST version 1.1) per sequence, salvage surgery rate, safety, and Quality of life (QoL). Results: Between October 2013 and May 2019, 263 eligible patients were randomized (arm A, n = 131; arm B, N = 132). After a median follow-up of 51.2 months (95% CI 43.3-57.4), 188 events for DDC were observed. Efficacy outcomes are presented in table. Median DDC was similar in both arms (HR 0.97, 95% CI 0.72-1.29; P = 0.805). Salvage surgery for metastasis (+/- radiofrequency ablation) was done in 36 (27.5%) patients in arm A and 28 (21.2%) in arm B. Median time until definitive deterioration of QoL (global health status) were 18.3 and 18.0 months (P = 0.628). The safety profiles were consistent with the established safety profiles of each treatment regimen. Conclusions: STRATEGIC-1 is the first randomized phase III study comparing multi-line standard treatment strategies in patients with KRAS/NRAS/BRAF wild-type mCRC. This study did not meet its primary endpoint of DDC. The treatment strategy starting with FOLFIRI-cetuximab followed by mFOLFOX6-bevacizumab led to higher response rates and to a trend for better median OS exceeding 3 years. These findings may add to our understanding of treatment sequencing in mCRC. Clinical trial information: NCT01910610. [Table: see text]
Published: 2022
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11. Artificial intelligence-guided tissue analysis combined with immune infiltrate assessment predicts stage III colon cancer outcomes in PETACC08 study

Author: S. Nguyen, Quentin Klopfenstein, Oana Cojocarasu, Francis Fein, Mohamed Gasmi, Cynthia Reichling, Pierre-Laurent Puig, Karine Le Malicot, Jean Paul Lagasse, Côme Lepage, Pierre-Luc Etienne, Jean-Marc Gornet, Julien Taieb, Jean-François Emile, Hakim Becheur, Dominique Luet, François Ghiringhelli, André Vanoli, Hervé Perrier, Marie Christine Kaminsky, Valentin Derangère, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER
Subjects: 0301 basic medicine, Colorectal cancer, Lymphocyte, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, immunohistopathology, MESH: Lymphocytes, Tumor-Infiltrating, biology, Gastroenterology, MESH: Neoplasm Staging, Prognosis, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Colonic Neoplasms, Stromal cell, CD3, adjuvant treatment, colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Disease-Free Survival, MESH: Prognosis, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Immune system, computerised image analysis, Stroma, Artificial Intelligence, Image Interpretation, Computer-Assisted, Humans, MESH: Artificial Intelligence, Neoplasm Invasiveness, Pathological, Neoplasm Staging, MESH: Colonic Neoplasms, MESH: Humans, business.industry, MESH: Adenocarcinoma, MESH: Neoplasm Invasiveness, medicine.disease, 030104 developmental biology, MESH: Disease-Free Survival, biology.protein, Artificial intelligence, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, MESH: Image Interpretation, Computer-Assisted, CD8
Abstract: ObjectiveDiagnostic tests, such as Immunoscore, predict prognosis in patients with colon cancer. However, additional prognostic markers could be detected on pathological slides using artificial intelligence tools.DesignWe have developed a software to detect colon tumour, healthy mucosa, stroma and immune cells on CD3 and CD8 stained slides. The lymphocyte density and surface area were quantified automatically in the tumour core (TC) and invasive margin (IM). Using a LASSO algorithm, DGMate (DiGital tuMor pArameTErs), we detected digital parameters within the tumour cells related to patient outcomes.ResultsWithin the dataset of 1018 patients, we observed that a poorer relapse-free survival (RFS) was associated with high IM stromal area (HR 5.65; 95% CI 2.34 to 13.67; pConclusionThese findings suggest that artificial intelligence can potentially improve patient care by assisting pathologists in better defining stage III colon cancer patients’ prognosis.
Published: 2020
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12. Quality of life and cost of strategies of two chemotherapy lines in metastatic colorectal cancer: results of the FFCD 2000-05 trial

Author: Côme Lepage, Jean-Pierre Pignon, Pierre Michel, Pierre-Luc Etienne, Mohamed Gasmi, Dany Gargot, Patrick Texereau, Michel Ducreux, Ahmed Azzedine, Isabelle Borget, Benjamin Lacas, Dominique Auby, Bernard Denis, Olivier Bouché, Catherine Lombard-Bohas, and Patrick Geoffroy
Subjects: Adult, Male, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Health Status, Leucovorin, Drug Costs, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, Surveys and Questionnaires, Antineoplastic Combined Chemotherapy Protocols, Global health, Health insurance, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Prospective Studies, Neoplasm Metastasis, Aged, Aged, 80 and over, Chemotherapy, business.industry, 030503 health policy & services, Health Policy, General Medicine, Middle Aged, medicine.disease, Oxaliplatin, Irinotecan, FOLFIRI, Quality of Life, Camptothecin, Female, Fluorouracil, France, 0305 other medical science, business, Colorectal Neoplasms, medicine.drug
Abstract: Objectives: This study compared the cost and quality of life (QoL) of 407 advanced colorectal cancer patients, randomly assigned to receive LV5FU2 followed by FOLFOX6 (sequential strategy) or FOLFOX6 followed by FOLFIRI (combination strategy). Methods: Costs were compared from the French health insurance perspective, until the end of the second line of treatment. Consumed resources, collected during the trial, included medicines, hospitalizations, examinations, and transportation. Valuations were made using 2009 and 2016 tariffs. QoL was assessed using the QLQ-C30 questionnaire and clinically significant variations were searched. Results: In 2009, the mean cost per patient was significantly lower for the sequential strategy compared to the combination strategy (18,061€ and 23,119€, p = 0.001). In 2016, the difference was no longer significant (16,876€ and 18,090€, p = 0.41) because oxaliplatin and irinotecan became generics. The QoL analysis (292 patients) showed that there was significantly less improvement of global health status in the sequential strategy than in the combination strategy (29% and 42%; p = 0.02) during first-line therapy. No significant differences were observed for emotional functioning (p = 0.45) and physical functioning (p = 0.07) or during second-line therapy. Conclusion: The choice to treat patients with advanced colorectal cancer using one or the other strategy cannot be based on costs or QoL.
Published: 2019

13. Prognostic factors in patients treated with second-line chemotherapy for advanced gastric cancer: results from the randomized prospective phase III FFCD-0307 trial

Author: Pierre-Luc Etienne, A. Azzedine, Laurent Mineur, Thomas Aparicio, Yann Touchefeu, J.-M. Gornet, K. Le Malicot, Pascal Hammel, S. Nguyen, Laetitia Dahan, Emmanuelle Samalin, Emilie Barbier, C. Louvet, Rosine Guimbaud, N. Chapelle, J.M. Phelip, David Sefrioui, Romain Cohen, Côme Lepage, Olivier Bouché, Service d'Oncologie Médicale Thoracique et Digestive [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Oncologie Digestive [CHU Toulouse], CHU Toulouse [Toulouse], Cooperator Multidisciplinary Oncology Group (GERCOR), 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), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Equipe EPICAD (LNC - U1231), 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 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, Service d'Oncologie Médicale [CHU Saint -Antoine], 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), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [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), Service d'Hémato-oncologie [CHU 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), Centre Hospitalier Montélimar, CH Montélimar, Électronique et Commande des Systèmes Laboratoire (ECS-Lab), Ecole Nationale Supérieure de l'Electronique et de ses Applications, Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Service de Pathologie [Clichy], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité d'Oncologie Digestive, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut Sainte Catherine [Avignon], 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, Département d'oncologie médicale (CHU Robert Debré, Reims), and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: Male, Cancer Research, Survival, Leucovorin, Gastroenterology, Second-line chemotherapy, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Aged, 80 and over, General Medicine, Middle Aged, Prognosis, 3. Good health, Survival Rate, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Gastric neoplasm, FOLFIRI, Adenocarcinoma, 030211 gastroenterology & hepatology, Female, Esophagogastric Junction, Epirubicin, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Irinotecan, Capecitabine, 03 medical and health sciences, Stomach Neoplasms, Internal medicine, medicine, Humans, Aged, business.industry, Proportional hazards model, medicine.disease, Cisplatin, business, Abdominal surgery, Follow-Up Studies
Abstract: IF 5.045 (2017); International audience; AIM: The aim of this study was to determine prognostic factors in patients treated with second-line therapy (L2) for locally advanced or metastatic gastric and gastro-esophageal junction (GEJ) adenocarcinoma in a randomized phase III study with predefined L2.METHODS: In the FFCD-0307 study, patients were randomly assigned to receive in L1 either epirubicin, cisplatin, and capecitabine (ECX arm) or fluorouracil, leucovorin, and irinotecan (FOLFIRI arm). L2 treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). Chi square tests were used to compare the characteristics of patients treated in L2 with those of patients who did not receive L2. Prognostic factors in L2 for progression-free survival (PFS) and overall survival (OS) were analyzed using a Cox model.RESULTS: Among 416 patients included, 101/209 (48.3%) patients in the ECX arm received FOLFIRI in L2, and 81/207 (39.1%) patients in the FOLFIRI arm received ECX in L2. Patients treated in L2, compared with those who only received L1 had : a better ECOG score (0-1: 90.4% versus 79.7%; p=0.0002), more frequent GEJ localization (40.8% versus 27.6%; p=0.005), and lower platelet count (median: 298000 versus 335000/mm3; p=0.02). In multivariate analyses, age
Published: 2018
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14. 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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15. 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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16. EGFR Expression Is Unreliable to Decide for Cetuximab Treatment in Patients with Metastatic Colorectal Cancer: Results from 'ERBITUX-OUEST'

Author: Corinne Alleaume, F. Grude, Arnaud Uguen, Nacr Eddine Achour, Daniel Ten Martin, Gilles Lemasson, A. Volant, Joseph Politis, Olivier Capitain, Claire Stampfli, Laurent Miglianico, Jérome Chettrit, Jean-François Ramée, Philippe Deguiral, Véronique Verriele, Claire Magois, Norbert Padilla, Annie Wdowik, Sophie Michalak, Murielle Broyer-Petit, Erick Gamelin, Pierre-Luc Etienne, Pierre Marie Girardot, Jean-Philippe Metges, Jean-Jacques Auger, Christian Laboisse, Roger Faroux, Serge Eloit, V. Klein, Fanny Marhuenda, A. Gourlaouen, Marie-Aude Coulon, Delphine Deniel Lagadec, Isabelle Cumin, Louis-Rémi De Ybarlucea, Christian Riche, Bruno Turlin, Olivier Dupuis, Alain Bargain, Eric Lavoine, Ludovic Rosenfeld, Alain Penchet, Jean-Luc Raoul, Jean-Yves Douillard, Viorel Vasiliu, Nathalie Heresbach, Yann Touchefeu, Karine Bideau, and Frédéric Staroz
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, biology, Cetuximab, business.industry, Colorectal cancer, medicine.disease, digestive system diseases, Egfr expression, Oxaliplatin, Irinotecan, 03 medical and health sciences, Regimen, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, biology.protein, Immunohistochemistry, Epidermal growth factor receptor, business, medicine.drug
Abstract: Purpose: Although controversial, assessment of epidermal growth factor receptor (EGFR) expression is required for the approved indications of Cetuximab in metastatic colorectal cancer (mCRC). With the objective of improving patient selection, “ERBITUX-OUEST” study aimed at analyzing EGFR status in a large cohort of mCRC patients who received cetuximab without preliminary EGFR screening, and assessing the correlation between EGFR status and response to treatment retrospectively. Patients and methods: 332 patients treated with Irinotecan Cetuximab based regimen after progression on irinotecan or oxaliplatin therapy were included. EGFR status was assessed using three available immunohistochemistry (IHC) tests and in situ hybridization in case of negativity. Clinical outcomes of EGFR-positive and EGFR-non-detected (or considered as negative with at least one test) patients were compared. Results: Of the 332 samples centrally screened, 194 were classified as full-positive (i.e., EGFR-positive for all three tests), 86 as full-negative, and 52 as discordant. One third of the 131 negative samples with FDA approved test should be reclassified as positive with at least one of the two others tests. Regarding results from FDA approved test only, neither objective response rate (ORR), progression-free survival (PFS) nor overall survival (OS) differed significantly between EGFR-negative and EGFR-positive patients (P = 0.788, 0.326 and 0.888, respectively). Similarly, comparison of full-negative to other groups did not show any significant difference in terms of ORR (P = 0.507), PFS (P = 0.222) or OS (P = 0.686). Conclusion: These data strongly argue against mCRC patients selection for Cetuximab treatment based on EGFR expression as measured by currently available IHC technics.
Published: 2016
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17. 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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18. 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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19. 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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20. Anti-epidermal growth factor receptor therapy in combination with chemoradiotherapy for the treatment of locally advanced anal canal carcinoma: Results of a phase II study with panitumumab (FFCD 0904)

Author: Xavier Mirabel, Wulfran Cacheux, Astrid Lièvre, L. Bazire, Nicolas Magné, Meher Ben Abdelghani, Christelle De La Fouchardiere, Philippe Ronchin, Delphine Argo Leignel, Thomas Aparicio, Véronique Vendrely, Ariane Darut-Jouve, Alexandre Tessier, Gilles Breysacher, Karine Le Malicot, Claire Lemanski, Côme Lepage, and Pierre-Luc Etienne
Subjects: Cancer Research, business.industry, Standard treatment, Mitomycin C, Locally advanced, Anal Squamous Cell Carcinoma, Phases of clinical research, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Anti-Epidermal Growth Factor Receptor, Cancer research, Medicine, Panitumumab, business, Chemoradiotherapy, 030215 immunology, medicine.drug
Abstract: 3570 Background: Standard treatment of anal squamous cell carcinoma is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase II study studied the tolerance and complete response (CR) rate at 8 weeks of panitumumab (Pmab) combined with MMC-5FU based CRT. Methods: Patients with locally advanced tumor without metastases (Stage T2, T3 or T4, whatever N stage; Stage N1-N3 whatever T stage) were treated with two RT periods (45Gy in 5 weeks and a boost of 20Gy in 2 weeks) with concomitant CT sessions of 5FU/MMC at RT weeks 1 and 5. Pmab was administered on RT weeks 1, 3, 5 and 7 according to the doses defined by a previous phase 1.study (MMC: 10 mg/m² at J1 and J29; 5FU: 400 mg/m² from J1 to J4 and from J29 to J32, Pmab: 3mg/kg). The expected rate of CR at 8 weeks to continue in phase III was 80%. Results: Forty-five patients (male: 9 (20%), female: 36 (80%); median age: 60.1 [41.5-81]) were enrolled in 15 French centers. All patients but one completed the CRT. Median duration of CRT was 52 days [30-76].Fourteen patients had a RT interruption because of toxicity. Most common related grade 3-4 toxicities observed were digestive (51.1%), hematologic (lymphopenia: 73.4%; neutropenia: 11.1%), radiation dermatitis (28.8%) and asthenia (11.1%). On patient died because of mesenteric ischemia during the CRT (total dose: 36 Gy). In ITT analysis, the CR rate at 8 weeks after CRT was 66.7% [90%CI: 53.4-78.2]. Median follow-up was 16.2 months [14.1-18.2]. Overall survival, recurrence-free and colostomy-free survival at one year were 94.6% [95%CI: 75.8-98.7], 72.2% [95%CI: 55.0-83.7] and 78.2% [95%CI: 60.6 – 88.6] respectively. Six (13%) patients had a colostomy with abdomino-perineal amputation due to a tumour recurrence. Conclusions: Despite an acceptable tolerance, panitumumab in combination with CRT for locally advanced anal cancer failed to meet the expected CR rate to justify further clinical trials. Clinical trial information: NCT01581840.
Published: 2019
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21. Combination of tissues analysis and immune infiltrate in localized colon cancer using artificial intelligence in PETACC8 study

Author: Francine Fein, Pierre-Luc Etienne, Julien Taieb, Jean-François Emile, Marie-Christine Kaminsky, Hakim Becheur, Oana Cojocarasu, Mohamed Gasmi, Cynthia Reichling, Hervé Perrier, Valentin Derangère, François Ghiringhelli, Andr Vanoli, Quentin Klopfenstein, Côme Lepage, Jean Marc Gornet, J.P. Lagasse, S. Nguyen, Dominique Luet, and Karine Le Malicot
Subjects: Cancer Research, Oncology, business.industry, Colorectal cancer, Cohort, Medicine, Artificial intelligence, Stage ii, business, Outcome prediction, medicine.disease, Subclass, Immune infiltrate
Abstract: 3574 Background: We used artificial intelligence to perform tissue classification and count CD3 and CD8 in each subclass and determined their role in outcome prediction in PETACC8 cohort of stage III colon cancer treated with FOLFOX or FOLFOX plus cetuximab. Methods: We developed artificial intelligence aimed to detect tumor, healthy mucosa, stroma and immune cells on whole slide of CD3 and CD8 staining. The invasive margin (IM) was also automatically determined. Using a lasso algorithm, the software was able to detect digital parameters within the tumor core (TC) which were related to patients’ outcome (variable called DGMate for DiGital tuMor pArameTErs). CD3 and CD8 lymphocytes density were also quantified automatically by the software in TC and at IM. Associations with disease-free survival (DFS) were evaluated by multivariable Cox regression adjusting for age, T/N stage, sidedness, KRAS/BRAF, DNA mismatch repair (MMR). Results: On 1220 samples collected, data could be generated for 1018 patients. We observed that a high IM stromal area and a high DGMate were associated with a poorer DFS [HR 5.65 (95% CI, 2.34, 13.67), p < 0.0001; HR 2.72 (95% IC, 1.92, 3.85), p+ TC, CD3+ IM and CD8+ TC were significantly associated with a longer DFS (HR 0.75 (95% IC, .66, .87), p+ TC gave a similar prognostic value compared to the classical CD3/CD8 immunoscore (p=0.44). The combination of IM stromal area, DGMate and CD3 outperformed the classical CD3/CD8 immunoscore to estimate patients’ prognosis (C-index= 0.601 vs 0.578, p-value=0.04). Adding this new variable to classical clinical prognostic parameters we generated a nomogram which predicted the risk of relapse of stage III colon cancer with a stronger predictive value compared to clinical parameters or the immunoscore. Conclusions: We propose a new fully automated method of whole slide analysis using a software based on artificial intelligence which classify tissue and determine tumor and immune parameters on one single slide stained with CD3 antibody. This valuable strategy outperforms immunoscore and clinical outcome prediction models.
Published: 2019
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22. Erratum to: Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program

Author: Antoine Adenis, Christelle de la Fouchardiere, Bernard Paule, Pascal Burtin, David Tougeron, Jennifer Wallet, Louis-Marie Dourthe, Pierre-Luc Etienne, Laurent Mineur, Stéphanie Clisant, Jean-Marc Phelip, Andrew Kramar, and Thierry Andre
Subjects: Adult, Aged, 80 and over, Compassionate Use Trials, Male, Cancer Research, Pyridines, Phenylurea Compounds, Antineoplastic Agents, Kaplan-Meier Estimate, Middle Aged, Prognosis, Survival Analysis, Cohort Studies, Proto-Oncogene Proteins p21(ras), Treatment Outcome, Oncology, Mutation, Genetics, Humans, Female, Erratum, Neoplasm Metastasis, Colorectal Neoplasms, Aged
Abstract: Randomized trials have shown a survival benefit for regorafenib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies. We evaluated survival and safety outcomes in patients treated with regorafenib in a real-life setting.REBECCA is a cohort study nested within a compassionate use program designed to evaluate survival, safety, and potential prognostic factors for outcome associated with regorafenib in patients with mCRC refractory to standard therapies. Treatment effects according to various patient and tumour characteristics were evaluated using univariate and multivariate Cox proportional hazards regression models.Of 1178 patients in the compassionate use program, 654 were in the full analysis set. Median follow-up was 16.5 months. Median survival was 5.6 months. The 12-month survival rate was 22 %. Survival was independently and unfavourably affected by the following variables: poor performance status, short time from initial diagnosis of metastases to the start of regorafenib, low initial regorafenib dose,3 metastatic sites, presence of liver metastases, and KRAS mutations. We identified prognostic groups of patients with low, intermediate, and high risk of death, with a median survival of 9.2, 5.2, and 2.5 months, respectively. Five-hundred-twenty-four patients (80 %) experienced at least one regorafenib-related adverse event, most commonly, fatigue, hand-foot skin reaction, diarrhea, anorexia, arterial hypertension, and mucositis.The safety and efficacy profile of regorafenib in REBECCA are similar to those in randomized trials. Our prognostic model identified subgroups of mCRC patients who derived a minimal and maximum benefit from regorafenib.Clinicaltrials.gov NCT02310477 .
Published: 2016
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23. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program

Author: Laurent Mineur, Stéphanie Clisant, Louis-Marie Dourthe, Antoine Adenis, Jean-Marc Phelip, Andrew Kramar, Pierre-Luc Etienne, Pascal Burtin, Christelle De La Fouchardiere, Jennifer Wallet, Bernard Paule, Thierry André, and David Tougeron
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, law.invention, Metastatic disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Regorafenib, Internal medicine, Genetics, Mucositis, Medicine, Compassionate Use Trials, Survival rate, Survival analysis, business.industry, medicine.disease, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Antiangiogenic, Cohort study, business, Research Article
Abstract: Randomized trials have shown a survival benefit for regorafenib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies. We evaluated survival and safety outcomes in patients treated with regorafenib in a real-life setting. REBECCA is a cohort study nested within a compassionate use program designed to evaluate survival, safety, and potential prognostic factors for outcome associated with regorafenib in patients with mCRC refractory to standard therapies. Treatment effects according to various patient and tumour characteristics were evaluated using univariate and multivariate Cox proportional hazards regression models. Of 1178 patients in the compassionate use program, 654 were in the full analysis set. Median follow-up was 16.5 months. Median survival was 5.6 months. The 12-month survival rate was 22 %. Survival was independently and unfavourably affected by the following variables: poor performance status, short time from initial diagnosis of metastases to the start of regorafenib, low initial regorafenib dose, >3 metastatic sites, presence of liver metastases, and KRAS mutations. We identified prognostic groups of patients with low, intermediate, and high risk of death, with a median survival of 9.2, 5.2, and 2.5 months, respectively. Five-hundred-twenty-four patients (80 %) experienced at least one regorafenib-related adverse event, most commonly, fatigue, hand-foot skin reaction, diarrhea, anorexia, arterial hypertension, and mucositis. The safety and efficacy profile of regorafenib in REBECCA are similar to those in randomized trials. Our prognostic model identified subgroups of mCRC patients who derived a minimal and maximum benefit from regorafenib. Clinicaltrials.gov NCT02310477 .
Published: 2016
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24. 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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25. Comparison of Two Neoadjuvant Chemoradiotherapy Regimens for Locally Advanced Rectal Cancer: Results of the Phase III Trial ACCORD 12/0405-Prodige 2

Author: Jean-Pierre Gérard, David Azria, Sophie Gourgou-Bourgade, Isabelle Martel-Laffay, 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, Christine Montoto-Grillot, and Thierry Conroy
Subjects: Cancer Research, Chemotherapy, medicine.medical_specialty, Colorectal cancer, business.industry, medicine.medical_treatment, medicine.disease, Oxaliplatin, Surgery, Radiation therapy, Capecitabine, Oncology, medicine, Combined Modality Therapy, business, Neoadjuvant therapy, Chemoradiotherapy, medicine.drug
Abstract: Purpose Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin. Patients and Methods We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m2 twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m2 twice daily 5 days per week and oxaliplatin 50 mg/m2 once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR). Results Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02). Conclusion The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.
Published: 2010
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26. 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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27. Thirteen-Month Registration of Patients with Gastroenteropancreatic Endocrine Tumours in France

Author: F. Borson-Chazot, T. Aparicio, D. Pillon, Philippe Rougier, Jean-Louis Legoux, Pierre-Luc Etienne, Emmanuel Mitry, W. Cacheux, T. Lecomte, Guillaume Cadiot, J.A. Chayvialle, Michel Ducreux, C. Louvet, D. O'Toole, Philippe Ruszniewski, Jean Francois Seitz, and C. Lombard-Bohas
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, Endocrinology, Diabetes and Metabolism, Cellular and Molecular Neuroscience, Endocrinology, Internal medicine, Epidemiology, medicine, Humans, Endocrine system, Registries, Child, Radionuclide Imaging, Aged, Gastrointestinal Neoplasms, Aged, 80 and over, Endocrine and Autonomic Systems, business.industry, Middle Aged, Pancreatic Neoplasms, Neuroendocrine Tumors, Female, France, business
Abstract: The prevalence, clinical profiles and management of gastroenteropancreatic endocrine tumours (GEP) in France are not known. From August 1, 2001 to September 1, 2002, standardized records on patients with GEP were prospectively completed in 87 participating centres. The total group amounted to 668 patients (median age: 56 years, range: 12–89). WHO performance status was 0/1 for 80.2% of patients. The primary sites were the small bowel and colon (288), pancreas (211), unknown (77), stomach (33), non-digestive primary sites (24), appendix (20), rectum-anus (12), and oesophagus or cardia (3). GEP were functional in 260 patients (39%). Most pancreatic tumours were non-functional (72%). Metastatic disease was observed in 73.4% of cases. Most tumours (85.8%) were well or moderately differentiated. Somatostatin receptor scintigraphy was performed in only 55% of patients. The following treatment modalities were employed: resection of primary tumour: 66%; systemic chemotherapy: 41%; somatostatin analogues: 44 and 26% for GEP of small intestine and pancreas, respectively; interferon: 12%, and intra-arterial hepatic (chemo)embolization in 23 and 15% of GEP arising from the midgut and pancreas, respectively. Despite their low prevalence, well-differentiated GEP represent a significant and heterogeneous clinical group, which warrants improved medical education, referral to expert centres at an early stage, and the design of prospective therapeutic trials.
Published: 2008
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28. Reintroduction of Oxaliplatin Is Associated With Improved Survival in Advanced Colorectal Cancer

Author: Pierre-Luc Etienne, Elisabeth Carola, Thierry André, Aimery de Gramont, Andrés Cervantes, Arie Figer, N. Perez-Staub, Isabelle Tabah-Fisch, Laurent Mineur, Fernando Rivera, Marc Buyse, Tomasz Burzykowski, Christophe Louvet, E. Quinaux, Christophe Tournigand, Gérard Lledo, M. Flesch, Isabel Chirivella, and José Cortiñas Abrahantes
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Leucovorin, Irinotecan, Gastroenterology, Drug Administration Schedule, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, Survival rate, Aged, Proportional Hazards Models, Chemotherapy, business.industry, Proportional hazards model, Hazard ratio, Middle Aged, Prognosis, medicine.disease, Oxaliplatin, Survival Rate, Treatment Outcome, Oncology, Fluorouracil, Disease Progression, Camptothecin, Female, Colorectal Neoplasms, business, medicine.drug
Abstract: Purpose In the OPTIMOX1 trial, previously untreated patients with advanced colorectal cancer were randomly assigned to two different schedules of leucovorin, fluorouracil, and oxaliplatin that were administered until progression in the control arm or in a stop-and-go fashion in the experimental arm. The randomly assigned treatment groups did not differ significantly in terms of response rate, progression-free survival, and overall survival (OS). However, the impact of oxaliplatin reintroduction on OS was potentially masked by the fact that a large number of patients did not receive the planned oxaliplatin reintroduction or received oxaliplatin after second-line therapy in both treatment groups. Patients and Methods A Cox model was fitted with all significant baseline factors plus time-dependent variables reflecting tumor progression, reintroduction of oxaliplatin, and use of second-line irinotecan. A shared frailty model was fitted with all significant baseline factors plus the number of lines of chemotherapy received by the patient and the percentage of patients with oxaliplatin reintroduction in the center. An adjusted hazard ratio (HR) was calculated for three reintroduction classes (1% to 20%, 21% to 40%, and > 40%), using centers with no reintroduction (0%) as the reference group. Results Oxaliplatin reintroduction had an independent and significant impact on OS (HR = 0.56, P = .009). The percentage of patients with oxaliplatin reintroductions also had a significant impact on OS. Centers in which more than 40% of the patients were reintroduced had an adjusted HR for OS of 0.59 compared with centers in which no patient was reintroduced. Conclusion Oxaliplatin reintroduction is associated with improved survival in patients with advanced colorectal cancer.
Published: 2007
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29. 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

30. Oxaliplatin combined with 5-FU in second line treatment of advanced pancreatic adenocarcinoma

Author: Olivier Bouché, Jean-François Seitz, J. M. Tigaud, Valérie Boige, Roland Bugat, Jean-Luc Breau, Philippe Rougier, Pierre-Luc Etienne, Francois Morvan, Emmanuel Mitry, Mahmoud Ould-Kaci, Esteban Cvitkovic, and Michel Ducreux
Subjects: Pancreas adenocarcinoma, Second line treatment, business.industry, Adenocarcinoma pancreas, Gastroenterology, General Medicine, medicine.disease, Oxaliplatin, Oxaliplatino, Medicine, Adenocarcinoma, business, Nuclear medicine, medicine.drug
Abstract: Resume Objectifs — L’efficacite et le benefice d’une chimiotherapie de seconde ligne dans le traitement des adenocarcinomes pancreatiques n’ont jamais ete demontres bien que ce traitement soit regulierement prescrit. Malades et methodes — Une etude de phase II randomisee evaluant une chimiotherapie par oxaliplatine (OXA), 5-fluorouracile infusionnel (5-FU) ou la combinaison des deux (OXFU) en traitement de premiere ligne des adenocarcinomes pancreatiques avances a ete realisee. Dans cette etude, une chimiotherapie de seconde ligne par OXFU (OXA 130 mg/m 2 IV 2h plus 5-FU 1000 mg/m 2 /j en perfusion continue de J1 a J4 toutes les 3 semaines) etait proposee aux malades progressant sous traitement par OXA ou 5-FU seuls. Resultats — Dix-huit des 32 malades (12 hommes, âge median 57 ans) en progression tumorale apres monochimiotherapie en premiere ligne ont recu la combinaison OXFU en traitement de seconde ligne. Le statut de performance selon l’OMS etait superieur ou egal a deux dans 61 % des cas. Aucune reponse objective n’a ete observee et trois patients (17 %) ont eu une stabilisation de leur maladie. Le delai median jusqu’a progression depuis le debut de la chimiotherapie de seconde ligne etait de 0,9 mois. La survie mediane etait de 4,9 mois depuis le debut du traitement de premiere ligne et de 1,3 mois depuis le debut du traitement de seconde ligne. Conclusion — Les resultats de cette etude apportent des arguments en faveur d’un role modeste de la chimiotherapie de seconde ligne dans le traitement des adenocarcinomes pancreatiques avances.
Published: 2006
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31. Docetaxel Plus Gemcitabine or Docetaxel Plus Cisplatin in Advanced Pancreatic Carcinoma: Randomized Phase II Study 40984 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group

Author: Bruno Genicot, Jacques Wils, Muriel Debois, Eric Gamelin, Udo Vanhoefer, Mustafa El-Serafi, Eric Van Cutsem, Jean-Luc Van Laethem, Pierre-Luc Etienne, Bernard Nordlinger, Jean Pierre Arnaud, Michel Ducreux, Thomas Lingenfelser, T. Wagener, C. Koehne, Peter Reichardt, Emmanuel Mitry, Faress Husseini, Manfred P. Lutz, and M. Praet
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, medicine.drug_class, Phases of clinical research, Docetaxel, Deoxycytidine, Antimetabolite, Gastroenterology, chemistry.chemical_compound, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Carcinoma, Humans, Infusions, Intravenous, Aged, Aged, 80 and over, Performance status, business.industry, Middle Aged, medicine.disease, Survival Analysis, Gemcitabine, Surgery, Pancreatic Neoplasms, Oncology, chemistry, Disease Progression, Female, Taxoids, Cisplatin, business, Febrile neutropenia, medicine.drug
Abstract: Purpose To define the efficacy and toxicity of docetaxel plus gemcitabine or docetaxel plus cisplatin for advanced pancreatic carcinoma. Patients and Methods Chemotherapy-naive patients with measurable disease and WHO performance status less than 2 were randomly assigned to receive 21-day cycles of gemcitabine 800 mg/m2 on days 1 and 8 plus docetaxel 85 mg/m2 on day 8 (arm A) or docetaxel 75 mg/m2 on day 1 plus cisplatin 75 mg/m2 on day 1 (arm B). Primary end points were tumor response and rate of febrile neutropenia grade. Results Of 96 randomly assigned patients (49 patients in arm A and 47 patients in arm B), 70 patients were analyzed for response (36 in arm A and 34 in arm B) and 89 patients were analyzed for safety (45 in arm A and 44 in arm B). Confirmed responses were observed in 19.4% (95% CI, 8.2% to 36.0%) of patients in arm A and 23.5% (95% CI, 10.7% to 41.2%) in arm B. In arm A, the median progression-free survival (PFS) was 3.9 months (95% CI, 3.0 to 4.7 months), median survival was 7.4 months (95% CI, 5.6 to 11.0 months), and 1-year survival was 30%. In arm B, the median PFS was 2.8 months (95% CI, 2.6 to 4.6 months), median survival was 7.1 months (95% CI, 4.8 to 8.7 months), and 1-year survival was 16%. Febrile neutropenia occurred in 9% and 16% of patients in arms A and B, respectively. Conclusion Both regimens are well tolerated and show activity in advanced pancreatic carcinoma. The safety profile and survival analyses favor docetaxel plus gemcitabine for further evaluation.
Published: 2005
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32. Longitudinal quality of life study in patients with metastatic gastric cancer

Author: Marc Giovannini, Philippe Rougier, Emmanuel Mitry, Jean-François Seitz, Franck Bonnetain, Jean-Luc Raoul, Cécile Girault, Pierre Luc Etienne, Olivier Bouché, Thierry Conroy, Laurent Bedenne, and Patrick Arveux
Subjects: medicine.medical_specialty, business.industry, Gastroenterology, General Medicine, medicine.disease, humanities, Metastatic gastric cancer, Surgery, Gastric adenocarcinoma, Quality of life, Internal medicine, medicine, Global health, In patient, Imputation (statistics), business, Stomach cancer
Abstract: Summary Objectives The aim of this study was to compare the longitudinal quality of life (QoL) between LV5FU2-irinotecan and LV5FU2 alone or LV5FU2-cisplatin in a randomized Phase II trial in patients with metastatic gastric adenocarcinoma. Methods Among 134 eligible patients, QLQ-C30 scores were collected and described at each 2 monthly follow-up visit during 6 months. The frequencies of QLQ-C30 score improvement were calculated and mixed models for repeated measurements were applied with or without extreme poorest imputation for missing scores. The “survival” until definitive global health score (GHS) deterioration was estimated. Results At the 3rd follow-up, patients with a stable or improved global health ranged from 11% in the LV5FU2-cisplatin arm to 18% in the LV5FU2-irinotecan arm. The irinotecan-based-therapy presented 14 to 15 scores with a better QoL. The time until definitive GHS deterioration was globally similar between treatment arms. Conclusion This study highlights a better impact of LV5FU2-irinotecan and the interest of QoL assessment in phase II trials to complement the risk-benefit judgement.
Published: 2005
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33. Randomized Multicenter Phase II Trial of a Biweekly Regimen of Fluorouracil and Leucovorin (LV5FU2), LV5FU2 Plus Cisplatin, or LV5FU2 Plus Irinotecan in Patients With Previously Untreated Metastatic Gastric Cancer: A Fédération Francophone de Cancérologie Digestive Group Study—FFCD 9803

Author: Gérard Lledo, Marie Christine Kaminsky, Jean-Luc Raoul, Philippe Rougier, Dominique Arsene, Emmanuel Mitry, Bruno Buecher, Olivier Bouché, Franck Bonnetain, Veronique Guerin-Meyer, Laurent Bedenne, Pierre Luc Etienne, Marc Giovannini, Chantal Milan, Jean Francois Seitz, and Jean Francois Paitel
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, medicine.drug_class, Leucovorin, Adenocarcinoma, Irinotecan, Antimetabolite, Gastroenterology, Bolus (medicine), Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Infusions, Intravenous, Stomach cancer, Survival rate, Aged, Cisplatin, Analysis of Variance, business.industry, Middle Aged, medicine.disease, Survival Analysis, Surgery, Survival Rate, Regimen, Treatment Outcome, Oncology, Fluorouracil, Quality of Life, Camptothecin, Female, France, business, medicine.drug
Abstract: Purpose To determine the efficacy and safety of a biweekly regimen of leucovorin (LV) plus fluorouracil (FU) alone or in combination with cisplatin or irinotecan in patients with previously untreated metastatic gastric adenocarcinoma and to select the best arm for a phase III study. Patients and Methods One hundred thirty-six patients (two were ineligible) were enrolled onto the randomized multicenter phase II trial. Patients received LV 200 mg/m2 (2-hour infusion) followed by FU 400 mg/m2 (bolus) and FU 600 mg/m2 (22-hour continuous infusion) on days 1 and 2 every 14 days (LV5FU2; arm A), LV5FU2 plus cisplatin 50 mg/m2 (1-hour infusion) on day 1 or 2 (arm B), or LV5FU2 plus irinotecan 180 mg/m2 (2-hour infusion) on day 1 (arm C). Results The overall response rates, which were confirmed by an independent expert panel, were 13% (95% CI, 3.4% to 23.3%), 27% (95% CI, 14.1% to 40.4%), and 40% (95% CI, 25.7% to 54.3%) for arms A, B, and C, respectively. Median progression-free survival and overall survival times were 3.2 months (95% CI, 1.8 to 4.6 months) and 6.8 months (95% CI, 2.6 to 11.1 months) with LV5FU2, respectively; 4.9 months (95% CI, 3.5 to 6.3 months) and 9.5 months (95% CI, 6.9 to 12.2 months) with LV5FU2-cisplatin, respectively; and 6.9 months (95% CI, 5.5 to 8.3 months) and 11.3 months (95% CI, 9.3 to 13.3 months) with LV5FU2-irinotecan, respectively. Conclusion Of the three regimens tested, the combination of LV5FU2-irinotecan is the most promising and will be assessed in a phase III trial.
Published: 2004
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34. CheckMate 649: A randomized, multicenter, open-label, phase III study of nivolumab (NIVO) + ipilimumab (IPI) or nivo + chemotherapy (CTX) versus CTX alone in patients with previously untreated advanced (Adv) gastric (G) or gastroesophageal junction (GEJ) cancer

Author: Narikazu Boku, Fabio Franke, Jaffer A. Ajani, Markus Moehler, Mingshun Li, Antoine Adenis, Yelena Y. Janjigian, Kynan Tadao Feeney, Félix Couture, Jean-Sebastien Aucoin, Guillermo Mendez, Michael Schenker, James M. Cleary, Ian Chau, Pierre-Luc Etienne, Erika Hitre, and Michalis V. Karamouzis
Subjects: 0301 basic medicine, Cancer Research, Chemotherapy, medicine.medical_specialty, business.industry, medicine.medical_treatment, Cancer, Ipilimumab, medicine.disease, Gastroesophageal Junction, Gastroenterology, Surgery, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, medicine, In patient, Nivolumab, Open label, business, medicine.drug
Abstract: TPS192 Background: Pts with adv G/GEJ cancer have an OS of ≈ 1 y, indicating an unmet medical need for new first-line treatments. Expression of PD-L1 is observed in up to 40% of pts with G/GEJ cancer and is associated with poor prognosis. In the randomized phase 3 ATTRACTION-2 study, NIVO demonstrated superior overall survival vs placebo with a 38% reduction of the risk of death (median OS, 5.3 vs 4.1 mo; HR, 0.62 P< 0.0001) and increased the OS rate at 12 mo (27% vs 12%; Boku N et al ESMO 2017) in pts with adv CTX-R (≥ 2 lines) G/GEJ cancer. In the phase 1/2 CheckMate-032 study in pts with CTX-R G/GEJ/esophageal cancer (79% ≥ 2 prior Tx lines), NIVO 1 mg/kg + IPI 3 mg/kg had a manageable safety profile and resulted in 24% ORR (40% ORR in pts with PD-L1+ tumors), a median OS of 6.9 mo, and a 35% OS rate at 12 mo (Janjigian Y et al ASCO 2017). In the phase 1 CheckMate-012 trial, NIVO + CTX had clinical activity and manageable safety in pts with NSCLC (Rizvi NA et al J Clin Oncol 2016). These positive results support investigation of NIVO, NIVO + IPI, and NIVO + CTX in earlier lines of treatment for G/GEJ cancer. The open-label, phase 3 CheckMate 649 trial will evaluate NIVO + IPI and NIVO + CTX vs CTX alone as first-line treatment for pts with adv G/GEJ cancer (NCT02872116). Methods: 1266 pts aged ≥ 18 y with untreated, inoperable adv/metastatic G/GEJ cancer (histologically confirmed adenocarcinoma) regardless of PD-L1 status will be randomized to receive either NIVO + IPI, NIVO + CTX (capecitabine/oxaliplatin [XELOX] or fluorouracil/leucovorin/oxaliplatin [FOLFOX]), or investigator choice of XELOX or FOLFOX. Tumor tissue for determination of PD-L1 status (Dako assay) must be provided from ≤ 6 mo before study treatment. No prior systemic treatment, including HER2 inhibitors, are allowed. Pts with known HER2+ status, suspected autoimmune disease, grade > 1 peripheral neuropathy, or active infection are excluded. Primary endpoint is OS in pts with PD-L1+ (≥ 1%) tumors. Other endpoints include OS in all pts; PFS and time to symptom deterioration in all pts and in pts with PD-L1+ tumors; and safety. Clinical trial information: NCT02872116.
Published: 2018
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35. PRODIGE 34 ADAGE: Adjuvant chemotherapy in elderly patients with resected stage III colon cancer—A randomized phase III trial

Author: Roger Faroux, Eric Francois, L. Cany, Frédérique Retornaz, Laurence Cristol-Dalstein, Romain Desgrippes, Elena Paillaud, Jean C. Martin, Emilie Maillard, Elisabeth Carola, Sandrine Hiret, Laurent Mineur, Jean Francois Seitz, Olivier Bouché, Pierre-Luc Etienne, Thomas Aparicio, and Gilles Breysacher
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, Adjuvant chemotherapy, business.industry, medicine.disease, Stage III Colon Cancer, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Overall survival, 030211 gastroenterology & hepatology, business
Abstract: TPS3628 Background: Colon cancer (CC) occurs in around 50% of the patients after 70 years. Adjuvant chemotherapy (CT) has demonstrated a benefit on disease-free survival (DFS) and overall survival after a stage III CC resection. Nevertheless, adjuvant CT is poorly used in elderly patients. There is still concern about the efficacy of doublet CT with oxaliplatin in fit elderly patients and the usefulness of fluoropyrimidine monotherapy in unfit elderly patients. The selection of patients that should be treated remains a challenge. Geriatric evaluation and tumor biology should be explored to help for patient selection. Methods: ADAGE is a multicenter, randomized phase III study comparing 3-years DFS of 2 therapeutic strategies in 2 groups of patients aged over 70 with completely resected stage III CC. Patients are included in one of the 2 groups after a multidisciplinary team evaluation; Group 1 (arm A and B) is defined as “able” to be treated with doublet CT; Group 2 (arm C and D) is defined as “unable” to be treated with doublet CT. In each group, patients are randomized according to a 1:1 ratio. Randomization is stratified according to center, gender, stage (IIIA vs IIIB vs IIIC), occlusion and/or perforation (yes vs no) and independent activity of daily living score (IADL: normal vs abnormal). Arm A and D receive LV5FU2 or capecitabine, arm B FOLFOX4 or XELOX and arm C is an observation arm. The treatment is planned for 6 months. Adjuvant CT should start within 12 weeks after surgery. Geriatric questionnaires and Lee score must be completed before randomization. Radiological assessment is performed every 6 months for 3 years after randomization and then annually for 2 years. Hypotheses (α two-sided = 5%, power = 80%) are to improve 3-years DFS from 65% (arm A) to 72% (arm B) in group 1 (756 patients required) and from 40% (arm C) to 55% (arm D) in group 2 (226 patients required). Safety is evaluated based on laboratory and clinical tests before each cycle. Exploratory analysis are planned to determine geriatric prognostic factors for DFS. A biological ancillary study is planned to allow prognostic evaluation of mismatch repair status and other molecular signatures. At the 1stof February 2017 the accrual was 246 patients. Clinical trial information: NCT02355379.
Published: 2017
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36. Exclusive chemoradiotherapy with or without dose escalation in locally advanced esophageal carcinoma: The CONCORDE study (PRODIGE 26)

Author: Gilles Créhange, Georges Noël, Emmanuel Rio, Pierre-Luc Etienne, Karen Benezery, Elisabeth Le Prisé, Jean Francois Seitz, Didier Peiffert, Aurélie Bertaut, Franck Bonnetain, and R. Pereira
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, business.industry, Locally advanced, Local failure, Esophageal cancer, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Concomitant, Carcinoma, Dose escalation, Medicine, business, Chemoradiotherapy
Abstract: 4037 Background: In esophageal cancer (EC), 20 to 45% of patients suffer from local failure after 50Gy concomitant chemoradiation (cCRT). Improvements in staging together with target definitions led us to test dose escalation in the modern era of new technologies. Methods: Patients were randomly assigned cCRT to 40Gy elective nodal irradiation with either a 10Gy boost (Arm A) or 26Gy boost (Arm B) combined with FOLFOX-4. The primary endpoint of this phase II was acute toxicity according to the NCIC-CTCAE (version 4.0). Quality of life according to the EORTC QLQ-C30 and OG25 was a secondary endpoint. All analyses were performed in intent-to-treat. Results: 160 patients were randomized between Jun 2011 and Feb 2016: 81 patients in arm A and 79 patients in arm B. The mean age at diagnosis was 61.9 (7.9) years and 62.1 (7.8) years, respectively. Seventy patients in each arm had squamous cell carcinoma (86.4% in arm A and 88.6% in arm B) and 59 patients (72.8%) and 58 patients (73.4%) had stage III disease in arms A and B, respectively. IMRT was performed in 57 (70.4%) and 55 (69.6%) patients in arms A and B. The rates of grade ≥3 (G3+) non-hematological toxicity were not significantly different between arms A and B (76.5% vs 86.0%, p = 0.12). The rates of G3+ hematological toxicity were not significantly different between arms A and B (82.7% vs 88.6%, p = 0.29). The rates of G3+ non-hematological toxicity were not significantly different between patients treated with 3DRT (83.3%) and IMRT (81.3%) (p = 0.77). The mean global health scores at baseline and 3 months were 63.9 (sd = 21.4) vs 69.6 (sd = 23.1) in arm A (p = 0.10) and 65.27 (sd = 19.54) vs 58.8 (sd = 19.9) in arm B (p = 0.16). The presence of dysphagia was neither significantly different between arm A (89.23%) and arm B (86.21%) (p = 0.61) at baseline nor at 3 months (77.78% vs 86.84%, p = 0.29). Odynophagia was present at baseline in 78.46% in arm A and 75.86% in arm B (p = 0.73) while the rates observed at 3 months were 68.18% and 73.68%, respectively (p = 0.59). Conclusions: Dose escalated cCRT in patients with EC is feasible with no increased acute toxicity and no deterioration of QOL. A phase III trial is on-going to conclusively address the issue of local control with cCRT. Clinical trial information: NCT01348217.
Published: 2017
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37. CheckMate 649: A randomized, multicenter, open-label, phase 3 study of nivolumab (nivo) + ipilimumab (ipi) or nivo + chemotherapy (CTX) vs CTX alone in pts with previously untreated advanced (adv) gastric (G) or gastroesophageal junction (GEJ) cancer

Author: Markus H. Moehler, Yelena Yuriy Janjigian, Antoine Adenis, Jean-Sebastien Aucoin, Narikazu Boku, Ian Chau, James M. Cleary, Kynan Tadao Feeney, Fabio A. Franke, Guillermo Ariel Mendez, Michael Schenker, Mingshun Li, Erika Hitre, Felix Couture, Michalis Karamouzis, Pierre-Luc Etienne, and Jaffer A. Ajani
Subjects: Cancer Research, Oncology
Abstract: TPS4132 Background: Pts with adv G/GEJ cancer have an OS of ≈ 1 y, indicating an unmet medical need for new first-line treatments (Tx). Expression of the PD-1 ligands PD-L1/PD-L2 is observed in up to 40% of pts with G/GEJ cancer and is associated with poor prognosis. In a phase 3 study of the PD-1 inhibitor nivo vs placebo in pts with adv CTX-refractory (CTX-R; ≥ 2 lines) G/GEJ cancer, nivo reduced the risk of death by 37% (HR, 0.63; P < 0.0001) and increased the OS rate at 12 mo (27% vs 11%; Kang YK, et al. J Clin Oncol. 2017;35 (suppl 4S) [abstract 2]). In a phase 1/2 study in pts with CTX-R G/GEJ/esophageal cancer (79% ≥ 2 prior Tx lines), nivo 1 mg/kg + ipi 3 mg/kg had a manageable safety profile and resulted in 26% ORR (44% ORR in pts with PD-L1+ tumors), a median OS of 6.9 mo, and a 34% OS rate at 12 mo (Janjigian Y, et al. ASCO, 2016 [abstract 4010]). In the phase 1 CheckMate 012 trial, nivo + CTX had clinical activity and manageable safety in pts with NSCLC (Rizvi NA, et al. J Clin Oncol. 2016;34:2969-2979). These positive results support investigation of nivo, nivo + ipi, and nivo + CTX in earlier lines of Tx for G/GEJ cancer. The open-label, phase 3 CheckMate 649 trial will evaluate nivo + ipi and nivo + CTX vs CTX alone as first-line Tx for pts with adv G/GEJ cancer (NCT02872116). Methods: 1266 pts aged ≥ 18 y with untreated, inoperable adv/metastatic G/GEJ cancer (histologically confirmed adenocarcinoma) regardless of PD-L1 status will be randomized to receive either nivo + ipi, nivo + CTX (capecitabine/oxaliplatin [XELOX] or fluorouracil/leucovorin/oxaliplatin [FOLFOX]), or investigator choice of XELOX or FOLFOX. Tumor tissue for determination of PD-L1 status (Dako assay) must be provided from ≤ 6 mo before study Tx. No prior systemic Tx, including HER2 inhibitors, are allowed. Pts with known HER2+ status, suspected autoimmune disease, grade > 1 peripheral neuropathy, or active infection are excluded. Primary endpoint is OS in pts with PD-L1+ (≥ 1%) tumors. Other endpoints include OS in all pts; PFS and time to symptom deterioration in all pts and in pts with PD-L1+ tumors; and safety. Clinical trial information: NCT02872116.
Published: 2017
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38. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial

Author: Marie-Pierre Galais, Carmen Llacer-Moscardo, Thierry Conroy, Valérie Boige, Jean-Yves Douillard, Beata Juzyna, Eric Francois, Isabelle Martel-Lafay, Olivier Bouché, Gilles Créhange, Jean-Luc Raoul, Antoine Adenis, Laurent Bedenne, Pierre-Luc Etienne, Pierre Michel, Meher Ben Abdelghani, Sophie Gourgou-Bourgade, 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 (ICL), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CRLCC Eugène Marquis (CRLCC), Centre Hospitalier Universitaire de Reims (CHU Reims), CRLCC Val d'Aurelle - Paul Lamarque, Institut de Cancérologie de l'Ouest, Clinique Armoricaine de Radiologie [St. Brieuc], Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Hôpital Charles Nicolle [Rouen], Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre Paul Strauss, CRLCC Paul Strauss, UNICANCER, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Oscar Lambret - Centre Régional de Lutte contre le Cancer, UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer., 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 ), Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), CRLCC Eugène Marquis ( CRLCC ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -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 - Centre Georges-François Leclerc ( CRLCC - CGFL ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Université de Lille-UNICANCER
Subjects: Adult, Male, medicine.medical_specialty, Esophageal Neoplasms, Organoplatinum Compounds, Population, Leucovorin, Gastroenterology, Disease-Free Survival, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Mucositis, Humans, education, Aged, Aged, 80 and over, education.field_of_study, Intention-to-treat analysis, business.industry, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Chemoradiotherapy, Middle Aged, medicine.disease, digestive system diseases, 3. Good health, Surgery, Oxaliplatin, Oncology, Fluorouracil, Concomitant, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cisplatin, business, medicine.drug
Abstract: Definitive chemoradiotherapy is a curative treatment option for oesophageal carcinoma, especially in patients unsuitable for surgery. The PRODIGE5/ACCORD17 trial aimed to assess the efficacy and safety of the FOLFOX treatment regimen (fluorouracil plus leucovorin and oxaliplatin) versus fluorouracil and cisplatin as part of chemoradiotherapy in patients with localised oesophageal cancer.We did a multicentre, randomised, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 24 centres in France between Oct 15, 2004, and Aug 25, 2011. Eligible participants had confirmed stage I-IVA oesophageal carcinoma (adenocarcinoma, squamous-cell, or adenosquamous), Eastern Cooperative Oncology Group (ECOG) status 0-2, sufficient caloric intake, adequate haematological, renal, and hepatic function, and had been selected to receive definitive chemoradiotherapy. Patients were randomly assigned (1:1) to receive either six cycles (three concomitant to radiotherapy) of oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), bolus fluorouracil 400 mg/m(2), and infusional fluorouracil 1600 mg/m(2) (FOLFOX) over 46 h, or four cycles (two concomitant to radiotherapy) of fluorouracil 1000 mg/m(2) per day for 4 days and cisplatin 75 mg/m(2) on day 1. Both groups also received 50 Gy radiotherapy in 25 fractions (five fractions per week). Random allocation to treatment groups was done by a central computerised randomisation procedure by minimisation, stratified by centre, histology, weight loss, and ECOG status, and was achieved independently from the study investigators. The primary endpoint was progression-free survival. Data analysis was primarily done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00861094.134 participants were randomly allocated to the FOLFOX group and 133 to the fluorouracil and cisplatin group (intention-to-treat population), and 131 patients in the FOLFOX group and 128 in the fluorouracil and cisplatin group actually received the study drugs (safety population). Median follow-up was 25·3 months (IQR 15·9-36·4). Median progression-free survival was 9·7 months (95% CI 8·1-14·5) in the FOLFOX group and 9·4 months (8·1-10·6) in the fluorouracil and cisplatin group (HR 0·93, 95% CI 0·70-1·24; p=0·64). One toxic death occurred in the FOLFOX group and six in the fluorouracil-cisplatin group (p=0·066). No significant differences were recorded in the rates of most frequent grade 3 or 4 adverse events between the treatment groups. Of all-grade adverse events that occurred in 5% or more of patients, paraesthesia (61 [47%] events in 131 patients in the FOLFOX group vs three [2%] in 128 patients in the cisplatin-fluorouracil group, p0·0001), sensory neuropathy (24 [18%] vs one [1%], p0·0001), increases in aspartate aminotransferase concentrations (14 [11%] vs two [2%], p=0·002), and increases in alanine aminotransferase concentrations (11 [8%] vs two [2%], p=0·012) were more common in the FOLFOX group, whereas serum creatinine increases (four [3%] vs 15 [12%], p=0·007), mucositis (35 [27%] vs 41 [32%], p=0·011), and alopecia (two [2%] vs 12 [9%], p=0·005) were more common in the fluorouracil and cisplatin group.Although chemoradiotherapy with FOLFOX did not increase progression-free survival compared with chemoradiotherapy with fluorouracil and cisplatin, FOLFOX might be a more convenient option for patients with localised oesophageal cancer unsuitable for surgery.UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer.
Published: 2014
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39. Results in the elderly with locally advanced rectal cancer from the ACCOR12/PRODIGE 2 phase III trial: Tolerance and efficacy

Author: Christophe Hennequin, Thierry Conroy, Véronique Vendrely, Pierre-Luc Etienne, Jean-François Seitz, Sophie Gourgou-Bourgade, Isabelle Martel-Laffay, Beata Juzyna, Marta Jarlier, Jean-Pierre Gerard, Eric Francois, David Azria, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CRLCC Val d'Aurelle - Paul Lamarque, Centre Léon Bérard [Lyon], Service de cancérologie et radiothérapie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Clinique Armoricaine de Radiologie [St. Brieuc], Hôpital Saint-André, 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), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), CRLCC Antoine Lacassagne, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Bordeaux [Bordeaux]-Hôpital Saint -André, Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL)
Subjects: Oncology, Male, Organoplatinum Compounds, MESH : Retrospective Studies, Colorectal cancer, MESH : Antineoplastic Combined Chemotherapy Protocols, medicine.medical_treatment, MESH : Aged, Deoxycytidine, 0302 clinical medicine, Elderly, MESH: Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Rectal Adenocarcinoma, Medicine, MESH : Neoplasm Staging, MESH : Female, Stage (cooking), Rectal cancer, MESH : Rectal Neoplasms, MESH: Treatment Outcome, MESH: Chemoradiotherapy, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, MESH: Organoplatinum Compounds, Age Factors, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Hematology, Chemoradiotherapy, MESH : Chemoradiotherapy, MESH: Neoplasm Staging, Middle Aged, MESH : Adult, Neoadjuvant Therapy, 3. Good health, Neoadjuvant chemoradiotherapy, Oxaliplatin, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, 030220 oncology & carcinogenesis, MESH : Fluorouracil, 030211 gastroenterology & hepatology, Female, Fluorouracil, medicine.drug, Adult, medicine.medical_specialty, MESH : Male, MESH: Neoadjuvant Therapy, MESH : Treatment Outcome, MESH : Organoplatinum Compounds, MESH : Capecitabine, Capecitabine, 03 medical and health sciences, MESH : Deoxycytidine, Internal medicine, Humans, Radiology, Nuclear Medicine and imaging, MESH : Middle Aged, MESH : Aged, 80 and over, Aged, Neoplasm Staging, Retrospective Studies, MESH: Age Factors, Chemotherapy, MESH: Humans, business.industry, Rectal Neoplasms, MESH : Humans, MESH: Deoxycytidine, MESH: Capecitabine, MESH: Rectal Neoplasms, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Comorbidity, MESH: Male, Clinical trial, Exploratory analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Age Factors, business, MESH : Neoadjuvant Therapy, MESH: Female, MESH: Fluorouracil
Abstract: International audience; BACKGROUND:Rectal cancer predominantly affects the elderly. Unfortunately, this age category is under-represented in clinical trials because clinicians are loath to include patients with a high risk of comorbidity.PATIENTS AND METHODS:An exploratory analysis of the ACCORD12/PRODIGE 2 phase III trial was carried out to retrospectively compare the benefit of neoadjuvant chemotherapy between the elderly (≥70 years; n=142) and younger patients (
Published: 2014
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40. FOLFIRINOX as induction treatment in rectal cancer patients with synchronous metastases (RCSM): Results of the FFCD 1102 phase II trial

Author: Albert Aleba, Jean-Baptiste Bachet, Simon Pernot, Jean-Luc Raoul, Emilie Maillard, Mohamed Hebbar, Olivier Dupuis, Philippe Rougier, Julien Taieb, Pierre-Luc Etienne, J.P. Lagasse, Frédéric Di Fiore, C.B. Levaché, Gilles Breysacher, Côme Lepage, Thierry Lecomte, Olivier Lucidarme, and Fabien Brocard
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, FOLFIRINOX, business.industry, digestive, oral, and skin physiology, food and beverages, Front line, Disease, medicine.disease, Primary tumor, Surgery, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, In patient, business, INDUCTION TREATMENT, Therapeutic strategy
Abstract: 3513Background: Optimal therapeutic strategy in patients (pts) with RCSM remains discussed and many front line options can be discussed to best treat primary tumor and metastatic disease: surgery (...
Published: 2016
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41. PRODIGE 2 phase III trial neoadjuvant in rectal cancer: Quality of life and results at 5 years

Author: Olivier Bouché, Jean-François Seitz, Laurent Mineur, Thierry Conroy, Jean-Pierre Gerard, Marta Jarlier, Eric Francois, Pierre-Luc Etienne, Philippe Rouanet, Sophie Gourgou, David Azria, Jérôme Doyen, Véronique Vendrely, and Trevor Stanbury
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, Colorectal cancer, medicine.medical_treatment, medicine.disease, 030218 nuclear medicine & medical imaging, Oxaliplatin, Capecitabine, Radiation therapy, 03 medical and health sciences, 0302 clinical medicine, Quality of life, 030220 oncology & carcinogenesis, Internal medicine, Medicine, business, medicine.drug
Abstract: 3619Background: The ACCORD 12 -PRODIGE 2 trial randomly assigned patients to receive radiotherapy (RTH) 45 Gy (CAP-45) with capecitabine or RTH 50 Gy with capecitabine and weekly oxaliplatin(CAPOX-...
Published: 2016
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42. Obesity in metastatic colorectal cancer: Pooled analysis of FFCD trials

Author: Pierre Michel, Jaafar Bennouna, Philippe Rougier, Pierre-Luc Etienne, Michel Ducreux, Aimery de Gramont, Emilie Maillard, Jean-Louis Legoux, Sylvain Manfredi, Thomas Aparicio, Côme Lepage, Thierry Lecomte, Jean-Marc Phelip, Eric Francois, Roger Faroux, Mohamed Gasmi, Jean Francois Seitz, Olivier Bouché, Laurent Bedenne, and Gilles Breysacher
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, 030109 nutrition & dietetics, Colorectal cancer, business.industry, nutritional and metabolic diseases, medicine.disease, Obesity, 03 medical and health sciences, Pooled analysis, Internal medicine, medicine, Low body mass index, business
Abstract: 3532Background: Previous studies showed that high and low body mass index (BMI) are associated with worst prognosis in early-stage colorectal cancer (CRC) and low BMI is associated with a worst pro...
Published: 2016
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43. Discontinuation of first-line chemotherapy (CT) after 6 weeks of CT in patients (pts) with metastatic squamous-cell esophageal cancer (MSEC): A randomized phase II trial

Author: Laetitia Dahan, Emmanuelle Samalin, Eric Francois, Meher Ben Abdelghani, Nuria Kotecki, Jean-Philippe Metges, Jaafar Bennouna, Guillaume Piessen, Antoine Adenis, Laurent Bedenne, Emilie Bogart, Marie-Pierre Galais, Thierry Conroy, Nicolas Penel, Christophe Mariette, François Ghiringhelli, Pierre-Luc Etienne, Farid El Hajbi, Stephanie Clisant Delaine, and Pierre Michel
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Squamous cell esophageal cancer, business.industry, ECOG Performance Status, Discontinuation, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, medicine, In patient, Radiology, First line chemotherapy, business, medicine.drug
Abstract: 4002Background: Even though there is no evidence to support the use of CT in MSEC, many physicians treat pts with good ECOG performance status (PS) with fluorouracil (5FU)/platinum-based CT. Theref...
Published: 2016
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44. Sequential versus combination chemotherapy for the treatment of advanced colorectal cancer (FFCD 2000-05): an open-label, randomised, phase 3 trial

Author: Olivier Bouché, Bernard Denis, Laurent Bedenne, Moncef Abbas, Dany Gargot, Jean Mendiboure, Ahmed Azzedine, Jean-Pierre Pignon, Patrick Geoffroy, David Malka, Philippe Rougier, Pierre Michel, M. Castaing, Dominique Auby, Michel Ducreux, Catherine Lombard-Bohas, Patrick Texereau, Mohamed Gasmi, Pierre-Luc Etienne, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), and Université d'Angers (UA)
Subjects: Oncology, Male, medicine.medical_specialty, Time Factors, Organoplatinum Compounds, Colorectal cancer, [SDV]Life Sciences [q-bio], Leucovorin, Kaplan-Meier Estimate, Irinotecan, Risk Assessment, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Medicine, Humans, 030304 developmental biology, Aged, Proportional Hazards Models, 0303 health sciences, Chi-Square Distribution, Performance status, business.industry, Combination chemotherapy, Middle Aged, medicine.disease, 3. Good health, Oxaliplatin, Regimen, Treatment Outcome, 030220 oncology & carcinogenesis, FOLFIRI, Camptothecin, Female, Fluorouracil, France, business, Colorectal Neoplasms, medicine.drug
Abstract: International audience; BACKGROUND: The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined. Our aim was to investigate whether combination treatment is better than the sequential administration of the same drugs in patients with advanced colorectal cancer.METHODS: In this open-label, randomised, phase 3 trial, we randomly assigned patients (1:1 ratio) with advanced, measurable, non-resectable colorectal cancer and WHO performance status 0-2 to receive either first-line treatment with bolus (400 mg/m(2)) and infusional (2400 mg/m(2)) fluorouracil plus leucovorin (400 mg/m(2)) (simplified LV5FU2 regimen), second-line LV5FU2 plus oxaliplatin (100 mg/m(2)) (FOLFOX6), and third-line LV5FU2 plus irinotecan (180 mg/m(2)) (FOLFIRI) or first-line FOLFOX6 and second-line FOLFIRI. Chemotherapy was administered every 2 weeks. Randomisation was done centrally using minimisation (minimisation factors were WHO performance status, previous adjuvant chemotherapy, number of disease sites, and centre). The primary endpoint was progression-free survival after two lines of treatment. Analyses were by intention-to-treat. This trial is registered at ClinicalTrials.gov, NCT00126256.FINDINGS: 205 patients were randomly assigned to the sequential group and 205 to the combination group. 161 (79%) patients in the sequential group and 161 (79%) in the combination group died during the study. Median progression-free survival after two lines was 10·5 months (95% CI 9·6-11·5) in the sequential group and 10·3 months (9·0-11·9) in the combination group (hazard ratio 0·95, 95% CI 0·77-1·16; p=0·61). All six deaths caused by toxic effects of treatment occurred in the combination group. During first-line chemotherapy, significantly fewer severe (grade 3-4) haematological adverse events (12 events in 203 patients in sequential group vs 83 events in 203 patients in combination group; pINTERPRETATION: Upfront combination chemotherapy is more toxic and is not more effective than the sequential use of the same cytotoxic drugs in patients with advanced, non-resectable colorectal cancer.FUNDING: Sanofi-Aventis France.
Published: 2011
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45. Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer

Author: Emmanuel Rio, Y. Yataghene, Pierre-Luc Etienne, Xavier Mirabel, M. Rives, Didier Peiffert, Pierre Michel, B. Lamezec, Jean-Luc Raoul, L. Mineur, E. Le Prisé, Antoine Adenis, Hélène Senellart, Thierry Conroy, Centre Alexis Vautrin (CAV), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Quality of Life in oncology platform, Canceropole Grand-Est, Sanofi-Aventis R&D, SANOFI Recherche, Centre René Gauducheau, CRLCC René Gauducheau, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Sainte Catherine [Avignon], Institut Claudius Regaud, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Service de radiothérapie, CRLCC Eugène Marquis (CRLCC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Sainte Catherine, CRLCC Institut Claudius Regaud, Center Oscar Lambret, CRLCC Oscar Lambret, Université Lille Nord de France (COMUE)-UNICANCER, Centre Alexis Vautrin ( CAV ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and CRLCC Eugène Marquis ( CRLCC )
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, oesophageal cancer, Esophageal Neoplasms, Organoplatinum Compounds, medicine.drug_class, Leucovorin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, Antimetabolite, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, law.invention, chemoradiotherapy, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Combined Modality Therapy, Humans, Aged, Cisplatin, Aged, 80 and over, business.industry, oxaliplatin, Middle Aged, 3. Good health, Oxaliplatin, Surgery, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, Concomitant, Clinical Study, 030211 gastroenterology & hepatology, Female, business, Chemoradiotherapy, medicine.drug
Abstract: International audience; Background: Concurrent chemoradiotherapy is a valuable treatment option for localised oesophageal cancer (EC), but improvement is still needed. A randomised phase II trial was initiated to assess the feasibility and efficacy in terms of the endoscopic complete response rate (ECRR) of radiotherapy with oxaliplatin, leucovorin and fluorouracil (FOLFOX4) or cisplatin/fluorouracil. Methods: Patients with unresectable EC (any T, any N, M0 or M1a), or medically unfit for surgery, were randomly assigned to receive either six cycles (three concomitant and three post-radiotherapy) of FOLFOX4 (arm A) or four cycles (two concomitant and two post-radiotherapy) of cisplatin/fluorouracil (arm B) along with radiotherapy 50 Gy in both arms. Responses were reviewed by independent experts. Results: A total of 97 patients were randomised (arm A/B, 53/44) and 95 were assessable. The majority had squamous cell carcinoma (82%; arm A/B, 42/38). Chemoradiotherapy was completed in 74 and 66%. The ECRR was 45 and 29% in arms A and B, respectively. Median times to progression were 15.2 and 9.2 months and the median overall survival was 22.7 and 15.1 months in arms A and B, respectively. Conclusion: Chemoradiotherapy with FOLFOX4, a well-tolerated and convenient combination with promising efficacy, is now being tested in a phase III trial.
Published: 2010
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46. ACCORD12/0405-Prodige 2 phase III trial neoadjuvant treatment in rectal cancer: Results after 5 years of follow-up

Author: Jean-François Seitz, Laurent Mineur, Pierre-Luc Etienne, Olivier Bouché, Eric Francois, Sophie Gourgou-Bourgade, David Azria, Jérôme Doyen, Jean-Pierre Gerard, and Thierry Conroy
Subjects: Cancer Research, medicine.medical_specialty, Randomization, Colorectal cancer, business.industry, Rectum, medicine.disease, law.invention, Surgery, Oxaliplatin, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Oncology, Randomized controlled trial, law, Neoadjuvant treatment, 030220 oncology & carcinogenesis, medicine, Adenocarcinoma, 030211 gastroenterology & hepatology, Nuclear medicine, business, medicine.drug
Abstract: 490 Background: The ACCORD 12 randomized trial was aiming at improving ypCR by increasing the radiation dose and adding oxaliplatin (OX) to a standard RT 45 Gy with concurrent capecitabine. On short term benefit of OX was not demonstrated (Gérard JP et al. J Clin Oncol. 2010;28:1638-44) at 3 years no significant difference in clinical outcome was achieved (Gérard JP et al. J Clin Oncol. 2012;30:4558-65. François E et al. Radiother Oncol. 2014;110:144-9). This is an update of results at 5 years. Methods: Between 11/2005 and 07/2008, 598 patients were randomized. Inclusion criteria: adenocarcinoma of rectum accessible to digital examination, T3 Nx M0 (or T2 distal anterior rectum). Randomization was between two neoadjuvant treatments chemo radiotherapy: Cap45 (45 Gy + capecitabine) and Capox50 (50 Gy + cape. and oxaliplatin). Main end point was sterilization of the operative specimen. Bowel function for patients treated with anterior resection was analyzed with a global score (1 very poor to 7 excellent). A total of 253 patients received adjuvant chemotherapy usually with FOLFOX: 133 in Cap45, 120 in Capox50. Results: In the ITT population, with a median follow-up of 60 months, updated carcinologic results were calculated using the Kaplan-Meier method. Out of 299 pts randomized in CAP45 and 299 pts in CAPOX50 results were respectively the following 1) 5y-cumulative incidence of Loc. Recurrence : 8.8% vs 7.8% (p = 0.78 HR = 0.92 [0.51-1.66]) 2) 5y-cumulative incidence of dist metastasis : 29.3% vs 27.1% (p = 0.48 HR = 0.89 [0.62-1.54]) 3) 5y-disease free survival rate : 60.4% vs 64.7% (p = 0.25 HR = 0.86 [0.66-1.11]) 4) 5y-overall survival rate : 76.4% vs 81.9% (p = 0.06 HR = 0.71 [0.50-1.01]) 5) bowel function median score : 5.2 [1-7] vs 4.9 [1-7]. Conclusions: At 5 years there was no significant difference in terms of local recurrence or distant metastases rates between both regimens. The new finding is a trend for improved overall survival in the Capox 50 groups may be related to subsequent salvage secondary treatments. At time of meeting the prognostic factors will be available in details and these results put in perspective with other phase III trial testing the role of oxaliplatin in Europe and the US. Clinical trial information: NCT00227747.
Published: 2016
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47. Phase II/III randomized trial of exclusive chemoradiotherapy with or without dose escalation in locally advanced esophageal carcinoma: The CONCORDE study (PRODIGE 26)

Author: Emmanuel Rio, Georges Noël, Franck Bonnetain, Jean Francois Seitz, Didier Peiffert, Karen Benezery, R. Pereira, Elisabeth Le Prisé, Pierre-Luc Etienne, and Gilles Créhange
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, Locally advanced, Esophageal cancer, medicine.disease, Primary tumor, law.invention, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Randomized controlled trial, law, 030220 oncology & carcinogenesis, Concomitant, medicine, Carcinoma, Radiology, business, Nuclear medicine, Adjuvant, Chemoradiotherapy
Abstract: TPS190 Background: INT 0123 failed to demonstrate an overall survival benefit with chemoradiotherapy dose escalation in locally advanced esophageal cancer. Nearly 45% of the patients had local persistent or recurrent disease. Several drawbacks surround the interpretation of the results of INT 0123. Improvements in target definitions with planning CT and 18F FDG PET/CT in keeping with improvements in radiation dose delivery that better protect healthy tissues with 3D conformal radiation therapy and/or IMRT should lead to the retesting of dose escalation in the modern era of new technologies. Methods: Patients are randomized into two groups: Experimental group: 40Gy ENI followed by a 26-Gy boost to the primary tumor and involved nodes (i.e. 33 daily fractions of 2Gy) with concomitant and adjuvant FOLFOX-4 weeks 1, 3, 5, 7, 9 and 11. Control group: 40Gy ENI followed by a 10-Gy boost to the primary tumor and involved nodes (in 25 daily fractions of 2Gy) with concomitant and adjuvant FOLFOX-4 weeks 1, 3, 5, 7, 9 and 11. Randomization using minimization to ensure balanced allocation across: Center / Adeno vs Squamous cell carcinoma / stage III vs I-II / weight loss / 3D-CRT vs IMRT. The principal hypothesis is that the rate of survival without locoregional relapse at 2 years will reach 50% in the reference arm and 65% in the experimental arm (Hazard ratio = 0.62). With a risk α = 0.05 (bilateral test) and β = 0.15 (power 85%). If we use a rate of 5% for lost to follow-up, it will be necessary to recruit 266 patients. The main inclusion criteria are: age < 75 years, WHO Status 0, 1 and 2, Enteral or parenteral feeding planned before the start of treatment if oral calorie intake < 1500 kcal, Histologically proven carcinoma of the esophagus, adenocarcinoma or squamous cell, T3, N0-N3, M0 (UICC 7thedition), T1-T2, N0-N3, M0 with a contra-indication for surgery, Absence of tracheo-esophageal fistula, Absence of thoracic or upper abdominal irradiation for another tumor, Written informed consent. 141 of the 160 patients required in phase II of the trial were included by September 22nd 2015. (ClinicalTrials.gov Identifier: NCT01348217). Clinical trial information: NCT01348217.
Published: 2016
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48. PRODIGE 20: Bevacizumab + chemotherapy (BEV-CT) versus chemotherapy alone (CT) in elderly patients (pts) with untreated metastatic colorectal cancer (mCRC)—A randomized phase II trial

Author: Farid El Hajbi, Faiza Khemissa, Sylvie Kirscher, Christophe Locher, Dominique Genet, Julien Taieb, Thomas Aparicio, Yves Rinaldi, Pierre-Luc Etienne, Thierry Lecomte, Roger Faroux, Olivier Bouché, Laurent Bedenne, Alice Oden-Gangloff, Elena Paillaud, M. Baconnier, Emilie Maillard, Sandrine Lavau-Denes, Eric Francois, and Frederic Retornaz
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, Bevacizumab, Colorectal cancer, business.industry, medicine.medical_treatment, medicine.disease, digestive system diseases, Capecitabine, Internal medicine, medicine, business, medicine.drug
Abstract: 3541 Background: AVEX study has demonstrated increased progression-free survival (PFS) with capecitabine + bevacizumab compared to capecitabine alone in pts aged over 70 with mCRC. The treatment wi...
Published: 2015
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49. Oxaliplatin combined with 5-FU in second line treatment of advanced pancreatic adenocarcinoma. Results of a phase II trial

Author: Emmanuel, Mitry, Michel, Ducreux, Mahmoud, Ould-Kaci, Valérie, Boige, Jean-François, Seitz, Roland, Bugat, Jean-Luc, Breau, Olivier, Bouché, Pierre-Luc, Etienne, Jean-Marie, Tigaud, François, Morvan, Esteban, Cvitkovic, and Philippe, Rougier
Subjects: Adult, Male, Oxaliplatin, Pancreatic Neoplasms, Organoplatinum Compounds, Antineoplastic Combined Chemotherapy Protocols, Disease Progression, Humans, Female, Fluorouracil, Adenocarcinoma, Middle Aged, Aged
Abstract: The efficacy and benefit of second-line chemotherapy in advanced pancreatic adenocarcinoma has never been demonstrated although it is regularly used.A randomized phase II study evaluating oxaliplatin alone (OXA), infusional 5-fluorouracil alone (5-FU) and an oxaliplatin/infusional 5-FU combination (OXFU) in untreated advanced pancreatic adenocarcinoma has been conducted. In this trial, a second-line treatment with the OXFU regimen (OXA 130 mg/m2 2-h intravenous (i.v.) infusion combined with 5-FU (1000 mg/m2/day, continuous i.v., days 1-4), every 3 weeks) was offered to patients progressing after single agent treatment.Eighteen out of 32 patients (12 males, median age 57 years) treated in the single agent arms received the OXFU combination in second-line treatment. WHO performance status was at least 2 in 61% of the patients. There was no objective response and 3 patients (17%) had a disease stabilisation. Median time to progression from the start of second-line treatment was 0.9 months. Median overall survival was 4.9 months from the start of front-line therapy and 1.3 months from the start of second-line therapy.The results of this trial bring arguments to support a modest value of second-line chemotherapy for advanced pancreatic adenocarcinoma.
Published: 2006

50. Longitudinal quality of life study in patients with metastatic gastric cancer. Analysis modalities and clinical applicability of QoL in randomized phase II trial in a digestive oncology

Author: Franck, Bonnetain, Olivier, Bouché, Thierry, Conroy, Patrick, Arveux, Jean-Luc, Raoul, Marc, Giovannini, Pierre Luc, Etienne, Emmanuel, Mitry, Jean-François, Seitz, Philippe, Rougier, Cécile, Girault, and Laurent, Bedenne
Subjects: Adult, Male, Health Status, Leucovorin, Adenocarcinoma, Middle Aged, Irinotecan, Survival Analysis, Stomach Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Quality of Life, Humans, Camptothecin, Female, Fluorouracil, Longitudinal Studies, Cisplatin, Aged
Abstract: The aim of this study was to compare the longitudinal quality of life (QoL) between LV5FU2-irinotecan and LV5FU2 alone or LV5FU2-cisplatin in a randomized Phase II trial in patients with metastatic gastric adenocarcinoma.Among 134 eligible patients, QLQ-C30 scores were collected and described at each 2 monthly follow-up visit during 6 months. The frequencies of QLQ-C30 score improvement were calculated and mixed models for repeated measurements were applied with or without extreme poorest imputation for missing scores. The "survival" until definitive global health score (GHS) deterioration was estimated.At the 3rd follow-up, patients with a stable or improved global health ranged from 11% in the LV5FU2-cisplatin arm to 18% in the LV5FU2-irinotecan arm. The irinotecan-based-therapy presented 14 to 15 scores with a better QoL. The time until definitive GHS deterioration was globally similar between treatment arms.This study highlights a better impact of LV5FU2-irinotecan and the interest of QoL assessment in phase II trials to complement the risk-benefit judgement.
Published: 2006

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