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1. How to Balance Prognostic Factors in Controlled Phase II Trials: Stratified Permuted Block Randomization or Minimization? An Analysis of Clinical Trials in Digestive Oncology

Author

Elodie Martin, Karine Le Malicot, Catherine Guérin-Charbonnel, François Bocquet, Olivier Bouché, Anthony Turpin, Thomas Aparicio, Jean-Louis Legoux, Laetitia Dahan, Julien Taieb, Côme Lepage, Louis-Marie Dourthe, Caroline Pétorin, Vincent Bourgeois, Jean-Luc Raoul, and Valérie Seegers

Subjects
minimization, randomization, phase II trials, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

In controlled phase II trials, major prognostic factors need to be well balanced between arms. The main procedures used are SPBR (Stratified Permuted Block Randomization) and minimization. First, we provide a systematic review of the treatment allocation procedure used in gastrointestinal oncology controlled phase II trials published in 2019. Second, we performed simulations using data from six phase II studies to measure the impacts of imbalances and bias on the efficacy estimations. From the 40 articles analyzed, all mentioned randomization in both the title and abstract, the median number of patients included was 109, and 77.5% were multicenter. Of the 27 studies that reported at least one stratification variable, 10 included the center as a stratification variable, 10 used minimization, 9 used SBR, and 8 were unspecified. In real data studies, the imbalance increased with the number of centers. The total and marginal imbalances were higher with SBR than with minimization, and the difference increased with the number of centers. The efficiency estimates per arm were close to the original trial estimate in both procedures. Minimization is often used in cases of numerous centers and guarantees better similarity between arms for stratification variables for total and marginal imbalances in phase II trials.

Published
2024
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2. FFCD-1004 Clinical Trial: Impact of Cytidine Deaminase Activity on Clinical Outcome in Gemcitabine-Monotherapy Treated Patients.

Author

Cindy Serdjebi, Johan Gagnière, Jérôme Desramé, Francine Fein, Rosine Guimbaud, Eric François, Thierry André, Jean-François Seitz, Carole Montérymard, Dominique Arsene, Julien Volet, Abakar Abakar-Mahamat, Thierry Lecomte, Véronique Guerin-Meyer, Jean-Louis Legoux, Gaël Deplanque, Pierre Guillet, Joseph Ciccolini, Côme Lepage, and Laetitia Dahan

Subjects
Medicine, Science
Abstract

Because cytidine deaminase (CDA) is the key enzyme in gemcitabine metabolism, numerous studies have attempted to investigate impact of CDA status (i.e. genotype or phenotype) on clinical outcome. To date, data are still controversial because none of these studies has fully investigated genotype-phenotype CDA status, pharmacokinetics and clinical outcome relationships in gemcitabine-treated patients. Besides, most patients were treated with gemcitabine associated with other drugs, thus adding a confounding factor. We performed a multicenter prospective clinical trial in gemcitabine-treated patients which aimed at investigating the link between CDA deficiency on the occurrence of severe toxicities and on pharmacokinetics, and studying CDA genotype-phenotype relationships.One hundred twenty patients with resected pancreatic adenocarcinoma eligible for adjuvant gemcitabine monotherapy were enrolled in this study promoted and managed by the Fédération Francophone de Cancérologie Digestive. Toxicities were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4. They were considered severe for grade ≥ 3, and early when occurring during the first eight weeks of treatment. CDA status was evaluated using a double approach: genotyping for 79A>C and functional testing. Therapeutic drug monitoring of gemcitabine and its metabolite were performed on the first course of gemcitabine.Five patients out of 120 (i.e., 4.6%) were found to be CDA deficient (i.e., CDA activity

Published
2015
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3. 337 Pembrolizumab in combination with xelox bevacizumab in patients with microsatellite stable (MSS) metastatic colorectal cancer and a high immune infiltrate: a proof of concept study. FFCD 1703 POCHI

Author

Come Lepage, Harry Sokol, Julien Taieb, Thierry Lecomte, Vincent Hautefeuille, Romain Coriat, David Tougeron, Laétitia Dahan, Pierre Laurent-Puig, Jean Francois Emile, Stephano Kim, Carole Monterymard, Marine Gilabert, BEZ Jérémie, Astrid Lievre, Laurent Mineur, Jean Louis Legoux, Jean marc Phelip, Claude Capron, Claire Gallois, and Violaine Randrian

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
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4. Lanreotide as maintenance therapy after first-line treatment in patients with non-resectable duodeno-pancreatic neuroendocrine tumours: An international double-blind, placebo-controlled randomised phase II trial – Prodige 31 REMINET: An FFCD study

Author

Côme Lepage, Jean-Marc Phelip, Astrid Lievre, Karine Le-Malicot, Laetitia Dahan, David Tougeron, Christos Toumpanakis, Frédéric Di-Fiore, Catherine Lombard-Bohas, Ivan Borbath, Romain Coriat, Thierry Lecomte, Rosine Guimbaud, Caroline Petorin, Jean-Louis Legoux, Pierre Michel, Jean-Yves Scoazec, Denis Smith, Thomas Walter, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, 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), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Royal Free Hospital [London, UK], Communications Cellulaires et Différenciation (CCD), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Cliniques Universitaires Saint-Luc [Bruxelles], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Gustave Roussy (IGR), Département de biologie et pathologie médicales [Gustave Roussy], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Amgen, Bristol-Myers Squibb, BMS, Bayer, Merck, Novartis, Roche, Celgene, Sandoz, Advanced Accelerator Applications, AAA, Agence Nationale de la Recherche, ANR: ANR-11-LABX-0021, Ligue Contre le Cancer, Servier, Ipsen, and ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011)

Subjects
Pancreatic Neoplasms, Clinical trial, Neuroendocrine Tumors, Cancer Research, Neuroendocrine tumours, Oncology, Duodeno-pancreatic, Maintenance, Non-resectable, Humans, [SDV.CAN]Life Sciences [q-bio]/Cancer, Somatostatin, Peptides, Cyclic
Abstract

International audience; Background: Following European guidelines, patients with aggressive metastatic or locally advanced, non-resectable, duodeno-pancreatic (DP) neuroendocrine tumours (NETs) should receive systemic combination chemotherapy until progression. Aggressive disease is defined as progressive and/or symptomatic metastases with or without significant hepatic invasion (>30–50%), and/or bone metastases. Methods: This academic randomised, double-blind, placebo-controlled phase II study aims to evaluate lanreotide autogel 120 mg (LAN) as maintenance treatment after at least 2 months of first-line treatment (L1) in aggressive G1-G2 DP-NET. Patients were randomly assigned in a 1:1 ratio to receive LAN or placebo (PBO), every 28 days, until progression or toxicity. The primary end-point was progression-free survival (PFS) at 6 months. Results: Among the 118 planned patients, 53 were included. Of these, 81.1% had a G2 tumour, and 90.6% had metastatic disease. L1 therapy consisted of chemotherapy (96.8%). Median duration of L1 was 4.6 months (range: 2.0–7.7). At the time of randomisation, 81.1% of patients had stable disease. Median follow-up was 27.0 months (95% CI: 19.5; 31.2). PFS at 6 months was 73.1% (90% CI: 55.3; 86.6) in LAN versus 54.2% (90% CI: 35.8; 71.8) in PBO. Median PFS was 19.4 months (95% CI: 7.6; 32.6) and 7.6 months (95% CI: 3.0; 9.0), respectively. Median overall survival was 41.9 months in PBO and was not reached in LAN. The toxicity profile was mainly grade 1–2 expected toxicities. Conclusions: The encouraging results of lanreotide autogel 120 mg as a maintenance treatment after L1 in aggressive G1/2 DP-NET should be confirmed. Trial registration: NCT02288377 (clinicaltrials.gov). © 2022 The Authors

Published
2022
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5. Predictive factors of severe early treatment-related toxicity in patients receiving first-line treatment for metastatic colorectal cancer: Pooled analysis of 2190 patients enrolled in Fédération Francophone de Cancérologie Digestive (FFCD) trials

Author

Clémence Breton, Jean-Baptiste Bachet, Jaafar Bennouna, Sylvain Manfredi, Jean-Louis Legoux, Aimery de Gramont, Karine Le Malicot, Thomas Aparicio, Thierry Lecomte, Olivier Bouché, Michel Ducreux, Olayidé Boussari, Julien Taieb, and Jean-Marc Gornet

Subjects
Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, Neoplasm Metastasis, Aged, Aflibercept, Chemotherapy, Performance status, business.industry, Middle Aged, Prognosis, medicine.disease, Oxaliplatin, Irinotecan, Treatment Outcome, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Toxicity, Female, Colorectal Neoplasms, business, medicine.drug
Abstract

Few studies have explored the association between baseline characteristics and the occurrence of early toxicities in patients treated with first-line chemotherapy for metastatic colorectal cancer (mCRC).Individual patient data of 2190 patients enrolled in 10 prospective FFCD (Fédération Francophone de Cancérologie Digestive) trials were analysed. Severe early toxicity was defined as the occurrence of grade ≥III toxicity within 3 months after initiation of chemotherapy (ET3).Patients received monotherapy based on 5-FU (n = 1068), a cytotoxic doublet (n = 395) or tritherapy with a cytotoxic doublet plus anti-VEGF agent or a cytotoxic triplet (n = 727). The patients received 5-FU (100%), Irinotecan (39.6%), Oxaliplatin (13.4%), Bevacizumab (29.6%) or Aflibercept (1.8%). ET3 occurred in 244 patients (22.8%) with monotherapy, 248 patients (62.8%) with doublet and 392 patients (53.9%) with tritherapy. The most frequent ET3s were related to biological abnormalities and/or gastrointestinal, general and vascular disorders. The prognostic factors for the occurrence of an ET3 in multivariate analysis were a performance status of 2 rather than 0-1 (OR 2.57; 95% CI [1.16, 5.73]; p = 0.02), tritherapy versus monotherapy (OR 2.31; 95% CI [0.84, 6.33]; p = 0.02), alkaline phosphatase 300 UI/l (OR 3.07; 95% CI [1.79, 5.27]; p 0.001) and non-resected primary tumour versus resection (OR 1.59; 95% CI [1.06, 2.39]; p = 0.02). Median overall survival in patients without ET3 was significantly longer than that in patients with ET3 (HR 0.87; 95% CI [0.80-0.96]; p = 0.004).ET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation.

Published
2021
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6. Does neoadjuvant FOLFOX chemotherapy improve the prognosis of high‐risk Stage II and III colon cancers? Three years' follow‐up results of the PRODIGE 22 phase II randomized multicentre trial

Author

Olivier Bouché, Guillaume Piessen, Benoit Romain, Claire Gallois, Emilie Barbier, Olivier Glehen, Jean-Marc Regimbeau, Mehdi Karoui, Gael Goujon, Johannes Hartwig, Julien Taieb, Guillaume Portier, Jean-Louis Legoux, Cécile de Chaisemartin, Astrid Lièvre, Francesco Brunetti, Hanifa Ammarguellat, Cedric Lecaille, Michel Prudhomme, Côme Lepage, for Prodige investigators, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Lille, Centre Hospitalier Régional d'Orléans (CHRO), Laboratoire de Neurosciences Cognitives & Computationnelles (LNC2), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Polyclinique Bordeaux Nord Aquitaine (PBNA), Centre Hospitalier Universitaire de Reims (CHU Reims), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Chirurgie digestive [CHU Amiens], CHU Amiens-Picardie, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Cancer Research and Personalized Medicine - CARPEM [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), AOM10242, Ministère de la Santé, Polyclinique Bordeaux Nord Aquitaine, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], and École pratique des hautes études (EPHE)

Subjects
Oncology, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, Leucovorin, survival, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, education, Neoplasm Staging, Colectomy, education.field_of_study, business.industry, Hazard ratio, Gastroenterology, Perioperative, colectomy, Prognosis, Interim analysis, medicine.disease, Neoadjuvant Therapy, digestive system diseases, colon cancer, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Colonic Neoplasms, 030211 gastroenterology & hepatology, Fluorouracil, Neoplasm Recurrence, Local, business, neoadjuvant chemotherapy, Follow-Up Studies, medicine.drug
Abstract

International audience; Aim Neoadjuvant chemotherapy has proven valuable in locally advanced resectable colon cancer (CC) but its effect on oncological outcomes is uncertain. The aim of the present paper was to report 3-year oncological outcomes, representing the secondary endpoints of the PRODIGE 22 trial. Method PRODIGE 22 was a randomized multicentre phase II trial in high-risk T3, T4 and/or N2 CC patients on CT scan. Patients were randomized between 6 months of adjuvant FOLFOX (upfront surgery) or perioperative FOLFOX (four cycles before surgery and eight cycles after; FOLFOX perioperative). In wild-type RAS patients, a third arm testing perioperative FOLFOX-cetuximab was added. The primary endpoint was the tumour regression grade. Secondary endpoints were 3-year overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and time to recurrence (TTR). Results Overall, 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped for futility. The remaining 104 patients represented our intention-to-treat population. In the perioperative group, 96% received the scheduled four neoadjuvant cycles and all but one had adjuvant FOLFOX for eight cycles. In the control arm, 38 (73%) patients received adjuvant FOLFOX. The median follow-up was 54.3 months. Three-year OS was 90.4% in both arms [hazard ratio (HR) = 0.85], 3-year DFS, RFS and TTR were, respectively, 76.8% and 69.2% (HR=0.94), 73% and 69.2% (HR = 0.86) and 82% and 72% (HR = 0.67) in the perioperative and control arms, respectively. Forest plots did not show any subgroup with significant difference for survival outcomes. No benefit from adding cetuximab was observed. Conclusion Perioperative FOLFOX has no detrimental effect on long-term oncological outcomes and may be an option for some patients with locally advanced CC.

Published
2021
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7. Maintenance treatment with fluoropyrimidine plus bevacizumab versus fluoropyrimidine alone after induction chemotherapy for metastatic colorectal cancer: The BEVAMAINT - PRODIGE 71 - (FFCD 1710) phase III study

Author

Aziz Zaanan, Anthony Turpin, Astrid Lièvre, Pierre Laurent-Puig, David Tougeron, Vincent Hautefeuille, Emilie Barbier, Laeticia Dahan, Thomas Aparicio, Jean-Louis Legoux, David Malka, Pierre Michel, Côme Lepage, Jean-Marc Phelip, and Sylvain Manfredi

Subjects
Adult, Male, Oncology, Antimetabolites, Antineoplastic, medicine.medical_specialty, Bevacizumab, medicine.medical_treatment, Leucovorin, Capecitabine, 03 medical and health sciences, Folinic acid, Antineoplastic Agents, Immunological, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Chemotherapy, Hepatology, business.industry, Gastroenterology, Induction chemotherapy, Induction Chemotherapy, Middle Aged, Chemotherapy regimen, Regimen, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Fluorouracil, Colorectal Neoplasms, business, medicine.drug
Abstract

Background Maintenance treatments with fluoropyrimidine alone or combined with bevacizumab after induction chemotherapy are two standard options in first-line metastatic colorectal cancer (mCRC). However, no trial has compared these two maintenance regimens. Methods BEVAMAINT is a multicenter, open-label, randomized phase III trial comparing fluoropyrimidine alone or plus bevacizumab as maintenance treatment after induction polychemotherapy in mCRC. The primary endpoint is the time-to-treatment failure (TTF), calculated from date of randomization to first radiological progression, death, start of a new chemotherapy regimen (different from induction or maintenance chemotherapy) or end of maintenance treatment without introduction of further chemotherapy. We expect a 2-month TTF improvement from 6 months in the monotherapy arm to 8 months in the combination arm (hazard ratio [HR], 0.75). Based on a two-sided α risk of 5% and a power of 80%, using Schoenfeld method, 379 events are required (planned enrolment, 400 patients). Patients with mCRC, whose disease is measurable according to RECIST 1.1 criteria and controlled (objective response or stable disease) – but remains unresectable – after 4 to 6 months of induction polychemotherapy (doublet or triplet chemotherapy with or without anti-EGFR or bevacizumab), and who have recovered from limiting adverse events of induction polychemotherapy are eligible for randomization. Randomization is stratified according to center, response to induction chemotherapy (objective response vs stable disease), ECOG performance status (0-1 vs 2), maintenance fluoropyrimidine (5-fluorouracil vs capecitabine) and primary tumor status (resected vs not). Capecitabine or bolus and infusional 5-fluorouracil plus folinic acid (simplified LV5FU2 regimen) are both accepted for maintenance chemotherapy, at investigator's discretion. Clinical evaluation, tumor imaging, carcinoembryonic antigen and circulating tumor DNA dosages are planned at enrolment and every 9 weeks. The maintenance treatment will be discontinued in the event of unbearable toxicity, progression or patient refusal. After maintenance discontinuation, reintroduction of induction polychemotherapy is recommended; otherwise a second-line treatment is started. The enrolment has begun in January 2020.

Published
2020
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8. Narrow-band imaging versus Lugol chromoendoscopy for esophageal squamous cell cancer screening in normal endoscopic practice: randomized controlled trial

Author

Béatrice Guerrier, Pascal Renkes, Sandrine Touzet, Melissa Gruner, B. Prost, Christophe Cellier, Mathieu Pioche, Angélique Denis, Verena Landel, Medhi Kaasis, Dominique Luet, Anne-Laure Tarreirias, Michel Antonietti, E Metivier-Cesbron, Gabriel Rahmi, Morgane Amil, Thierry Ponchon, Serge Fratte, Philippe Balian, Laurent Lefrou, P. Rey, Marc Le Rhun, Elia Samaha, Claude Masliah, Stéphane Lecleire, Jean-Louis Legoux, and Emmanuel Coron

Subjects
medicine.medical_specialty, Esophageal Neoplasms, Sensitivity and Specificity, law.invention, Chromoendoscopy, Narrow Band Imaging, Randomized controlled trial, law, Multicenter trial, Carcinoma, Humans, Medicine, Prospective Studies, Coloring Agents, Prospective cohort study, Early Detection of Cancer, Squamous cell cancer, Narrow-band imaging, medicine.diagnostic_test, business.industry, Gastroenterology, Iodides, medicine.disease, Endoscopy, Carcinoma, Squamous Cell, Esophageal Squamous Cell Carcinoma, Esophagoscopy, Radiology, business
Abstract

Background Narrow-band imaging (NBI) is as sensitive as Lugol chromoendoscopy to detect esophageal squamous cell carcinoma (SCC) but its specificity, which appears higher than that of Lugol chromoendoscopy in expert centers, remains to be established in general practice. This study aimed to prove the superiority of NBI specificity over Lugol chromoendoscopy in the detection of esophageal SCC and high grade dysplasia (HGD) in current general practice (including tertiary care centers, local hospitals, and private clinics). Methods This prospective randomized multicenter trial included consecutive patients with previous or current SCC of the upper aerodigestive tract who were scheduled for gastroscopy. Patients were randomly allocated to either the Lugol or NBI group. In the Lugol group, examination with white light and Lugol chromoendoscopy were successively performed. In the NBI group, NBI examination was performed after white-light endoscopy. We compared the diagnostic characteristics of NBI and Lugol chromoendoscopy in a per-patient analysis. Results 334 patients with history of SCC were included and analyzed (intention-to-treat) from 15 French institutions between March 2011 and December 2015. In per-patient analysis, sensitivity, specificity, positive and negative likelihood values were 100 %, 66.0 %, 21.2 %, and 100 %, respectively, for Lugol chromoendoscopy vs. 100 %, 79.9 %, 37.5 %, and 100 %, respectively, for NBI. Specificity was greater with NBI than with Lugol (P = 0.002). Conclusions As previously demonstrated in expert centers, NBI was more specific than Lugol in current gastroenterology practice for the detection of early SCC, but combined approaches with both NBI and Lugol could improve the detection of squamous neoplasia.

Published
2020
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9. 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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10. Intérêts et limites de la recherche du déficit en dihydropyrimidine déshydrogénase dans le suivi des patients traités par fluoropyrimidines : résultats de deux enquêtes nationales de pratiques réalisées auprès des médecins et des biologistes

Author

Olivier Bouché, Marie-Christine Etienne-Grimaldi, Karine Le Malicot, Jean-Christophe Boyer, Jean-François Seitz, Joseph Ciccolini, Jean-Louis Legoux, Thierry André, Marie-Anne Loriot, Chantal Barin-Le-Guellec, Joël Guigay, Pierre Michel, Fabienne Thomas, David Malka, Paolo Carni, Juliette Thariat, Fadil Masskouri, Roger Faroux, and Suzette Delaloge

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, business.industry, French, Hematology, General Medicine, language.human_language, 3. Good health, 03 medical and health sciences, Health insurance system, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Family medicine, language, Medicine, Radiology, Nuclear Medicine and imaging, National level, business, Reimbursement
Abstract

Dihydropyrimidine dehydrogenase (DPD) deficiency is the main cause of early severe toxicities induced by fluoropyrimidines (FP). The French Group of Clinical Oncopharmacology (GPCO)-Unicancer and the French Pharmacogenetics Network (RNPGx) initiated two surveys, one addressed to oncologists, the other to biologists, in order to evaluate routine practices regarding DPD deficiency screening at national level, as well as compliance, motivations and obstacles for implementation of these tests. These anonymized online surveys were performed with the logistic assistance of the Francophone Federation of Digestive Oncology (FFCD) and the support of numerous medical and biological societies. The surveys were conducted in 2016-2017 before the creation of the French INCa/HAS expert panel, which contributed to the drafting of rules and recommendations for DPD deficiency screening published in December 2018. In all, 554 questionnaires from clinicians were analyzed (23% participation) and 35 from biologists. The main arguments raised by clinicians for justifying the limited practice of DPD deficiency screening were: the lack of recommendations from medical societies or Health Authorities, delays in obtaining results, and the lack of adequate reimbursement by the health insurance system. The goal of these surveys was to provide the French Health Authorities with an overview on nationwide DPD-deficiency screening practices and thus help to design recommendations for the standardization and improvement of the management and safety of cancer patients receiving FP-based chemotherapy.

Published
2019
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11. Comparison of Temozolomide-Capecitabine to 5-Fluorouracile-Dacarbazine in 247 Patients with Advanced Digestive Neuroendocrine Tumors Using Propensity Score Analyses

Author

Hedia Brixi, Thomas Walter, Philippe Ruszniewski, Jérôme Cros, Pascal Hammel, Catherine Lombard-Bohas, Jean-Louis Legoux, David Tougeron, Vinciane Rebours, Guillaume Cadiot, Olivia Hentic, Paul de Boissieu, Camille Evrard, and Louis de Mestier

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Multivariate analysis, Endocrinology, Diabetes and Metabolism, Dacarbazine, 030209 endocrinology & metabolism, Neuroendocrine tumors, Digestive System Neoplasms, Disease-Free Survival, 030218 nuclear medicine & medical imaging, Capecitabine, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Temozolomide, medicine, Humans, Propensity Score, Antineoplastic Agents, Alkylating, Aged, Gastrointestinal Neoplasms, Endocrine and Autonomic Systems, business.industry, Hazard ratio, Confounding, Middle Aged, medicine.disease, Pancreatic Neoplasms, Neuroendocrine Tumors, Propensity score matching, Female, business, medicine.drug
Abstract

Introduction: Although chemotherapy combining 5-fluorouracil (5FU)-dacarbazine (DTIC) or temozolomide (TEM)-capecitabine (CAP) is extensively used in patients with neuroendocrine tumors (NET), they were never compared. We compared their tolerance and efficacy in advanced NET. Methods: We evaluated the records of consecutive patients with pancreatic or small-intestine advanced NET who received 5FU-DTIC or TEM-CAP between July 2004 and December 2017 in 5 French centers. Tolerance, tumor response and progression-free survival (PFS) were compared. Factors associated with PFS were analyzed using Cox multivariate regression model. To reduce the confounding bias of the nonrandomized design, PFS was compared using propensity score analyses. Results: Ninety-four (5FU-DTIC) patients and 153 (TEM-CAP) patients were included. Pancreatic NET represented 82.3% of cases and 17.1, 61.8 and 10.9% of patients had G1, G2 or G3 NET respectively. Progression at baseline was reported in 92.7% of patients with available data. Grades 3–4 adverse events occurred in 24.7 and 8.5% of TEM-CAP and 5FU-DTIC patients respectively (p = 0.002). The overall response rate was 38.3 and 39.2% respectively (p = 0.596). Median PFS on raw analysis was similar to 5FU-DTIC and TEM-CAP (13.9 vs. 18.3 months, respectively p = 0.86). TEM-CAP was associated with an increased risk of progression on the raw multivariate analysis (hazard ratio [HR] 1.90, 95% CI [1.32–2.73], p = 0.001) and when adjusted on propensity score (HR 1.65, 95% CI [1.18–2.31], p = 0.004). Conclusion: PFS may be longer with 5FU-DTIC than TEM-CAP in patients with advanced NET. Although patients often prefer oral chemotherapy, 5FU-DTIC is a relevant alternative. A randomized comparison is needed to confirm these results.

Published
2019
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12. Pembrolizumab with Capox Bevacizumab in patients with microsatellite stable metastatic colorectal cancer and a high immune infiltrate: The FFCD 1703-POCHI trial

Author

Romain Coriat, Nicolas Loménie, Côme Lepage, Thierry Lecomte, Violaine Randrian, Camille Kurtz, Jean-Louis Legoux, Jean-Marc Phelip, Astrid Lièvre, Pierre Laurent-Puig, Julien Taieb, Jean-François Emile, Carole Monterymard, David Tougeron, Harry Sokol, Jérémie Bez, Laurent Mineur, Claire Gallois, Laetitia Dahan, Stefano Kim, Vincent Hautefeuille, Claude Capron, Marine Gilabert, 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), Hôpital Ambroise Paré [AP-HP], Hôpital JeanMinjoz, 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), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Sainte Catherine [Avignon], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional d'Orléans (CHRO), CHU Amiens-Picardie, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Informatique Paris Descartes (LIPADE (URP_2517)), Université de Paris (UP), HalioDX and the 'Ligue nationale contre le cancer', 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 Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Jonchère, Laurent, École Pratique des Hautes Études (EPHE), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
Oncology, medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pembrolizumab, Antibodies, Monoclonal, Humanized, DNA Mismatch Repair, 03 medical and health sciences, Antineoplastic Agents, Immunological, Clinical Trials, Phase II as Topic, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Checkpoint blockade, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Humans, Medicine, Immune Checkpoint Inhibitors, Chemotherapy, Hepatology, business.industry, Tumour-infiltrating lymphocytes, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, Oxaliplatin, Clinical trial, 030220 oncology & carcinogenesis, Microsatellite Instability, 030211 gastroenterology & hepatology, Colorectal Neoplasms, business, medicine.drug
Abstract

International audience; Pembrolizumab, a PD1 immune checkpoint inhibitor (ICI), was recently reported to be very effective in patients with microsatellite instable/deficient mismatch repair metastatic colorectal cancer (MSI/dMMR mCRC), unlike patients with microsatellite stable/proficient MMR (MSS/pMMR) mCRC, in whom ICIs are generally ineffective. However, about 15% of MSS/pMMR CRCs are highly infiltrated by tumour infiltrating lymphocytes. In addition, both oxaliplatin and bevacizumab have been shown to have immunomodulatory properties that may increase the efficacy of an ICI. We formulated the hypothesis that patients with MSS/pMMR mCRC with a high immune infiltrate can be sensitive to ICI plus oxalipatin and bevacizumab-based chemotherapy. POCHI is a multicenter, open-label, single-arm phase II trial to evaluate efficacy of Pembrolizumab with Capox Bevacizumab as first-line treatment of MSS/pMMR mCRC with a high immune infiltrate for which we plan to enrol 55 patients. Primary endpoint is progression-free survival (PFS) at 10 months, which is expected greater than 50%, but a 70% rate is hoped for. Main secondary objectives are overall survival, secondary resection rate and depth of response. Patients must have been resected of their primary tumour so as to evaluate two different immune scores (Immunoscore® and TuLIS) and are eligible if one score is "high";. The first patient was included on April 20, 2021.

Published
2021
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13. Aflibercept-LV5FU2 as first-line treatment of non-resectable metastatic colorectal cancers: Results of the FOLFA randomized phase II trial

Author

Jean-Louis Legoux, Roger Faroux, Nicolas Barrière, Karine Le Malicot, David Tougeron, Veronique Lorgis, Veronique Guerin-Meyer, Vincent Bourgeois, David Malka, Thomas Aparicio, Mathieu Baconnier, Valérie Lebrun Ly, Joëlle Egreteau, Faïza Khemissa Akouz, Come Lepage, and Valérie Boige

Subjects
Cancer Research, Oncology
Abstract

3555 Background: Previous trials have demonstrated that bevacizumab and fluoropyrimidine combination is effective and well-tolerated in older patients (pts) with non-aggressive unresectable metastatic colorectal cancer. We evaluated in this trial safety and efficacy of aflibercept and infusional 5-fluorouracil/folinic acid (LV5FU2 regimen) combination versus LV5FU2 alone in older pts, asymptomatic and/or frail, deemed unsuitable for doublet cytotoxic chemotherapy. Methods: The main eligibility criteria for this randomized phase II trial were age ≥ 65 and WHO performance status < 2. Randomization was stratified according to thymidylate synthase (TS)- 5’UTR germline polymorphism. Common (also called simplified) LV5FU2 regimen was preceded or not by aflibercept (4mg/kg). The primary endpoint was the 6-month progression-free survival (PFS) rate, achieved if > 40% in the experimental arm. Secondary objectives were safety, quality of life, overall survival (OS), and the prognostic impact of TS -5’UTR polymorphism. Results: 117 patients (pts) were included, 59 in arm A (5FU-aflibercept), 58 in arm B (5FU alone), of median age 81 years (range 67-91; > 75 years: 81%). RAS/ BRAF status (available in 112 pts [96%]) was mutated in 49% and 7%, respectively. The 6-month PFS was 54% in both arms (same 90% CI 42-65). The disease control rate was 83% in arm A and 87% in arm B. The median OS was 21.8 months in arm A and 25.1 months in arm B. The toxicities were more common in arm A: at least 1 grade 3-4 toxicity > 2 in 82% versus (vs) 58.2% pts, hypertension grade > 3 in 42% vs 18% pts, proteinuria (any grade) in 51% vs 11% pts, dysphonia (grade < 3) in 19% vs 2%, 1 colic perforation in arm A. Treatment delays for toxicities were required for 4% of the 753 courses in arm A vs 2% of the 780 courses in arm B , 5FU bolus suppression was decided for 29.8% pts vs 20% (arm A vs arm B), median 29 days vs 73 days after the first course (arm A vs B), without difference in the doses of infusional 5FU. A second and third line of treatment were received in 41% and 14% of pts in arm A vs 67% and 29% of pts in arm B, respectively. The TS 5’UTR polymorphism (3R3R vs 2R2R or 2R3R) had no impact on PFS or OS. Regarding the quality of life (QLQ C30 score), the difference of overall health score was on average -6.39 (SD = 26.68) in arm A vs -4.91 (SD = 27.15) in arm B, and was very similar in all components. The median time to definitive deterioration in quality of life was 15 months (95% CI: 9-22.8) in arm A vs 9.6 (95% CI: 5.1-19.4) in arm B. Conclusions: FOLFA trial meets is primary endpoint with 53.6% of 6-month PFS with LV5FU2-aflibercept. Nevertheless, as compared with LV5FU2 alone we observed no increase in PFS or OS and more toxicities. These results do not argue for an evaluation of LV5FU2-aflibercept combination in a randomized phase III trial. Clinical trial information: EudraCT 2014-001837-10.

Published
2022
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14. 337 Pembrolizumab in combination with xelox bevacizumab in patients with microsatellite stable (MSS) metastatic colorectal cancer and a high immune infiltrate: a proof of concept study. FFCD 1703 POCHI

Author

Julien Taieb, Jean-François Emile, Claude Capron, David Tougeron, Romain Coriat, Stephano Kim, Jean-Marc Phelip, Laetitia Dahan, Violaine Randrian, Jean Louis Legoux, Marine Gilabert, Vincent Hautefeuille, Claire Gallois, Pierre Laurent-Puig, Laurent Mineur, Harry Sokol, Bez Jérémie, Carole Monterymard, Côme Lepage, Thierry Lecomte, and Astrid Lièvre

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Bevacizumab, business.industry, Colorectal cancer, Tumor-infiltrating lymphocytes, Pembrolizumab, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Primary tumor, lcsh:RC254-282, Oxaliplatin, Capecitabine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, FOLFOX, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, medicine.drug
Abstract

Background Immune checkpoint inhibitors (ICI) are very effective in deficient DNA mismatch-repair system (dMMR)/microsatellite instable (MSI) metastatic colorectal cancer (mCRC). About 15% of MSS/pMMR CRCs are highly infiltrated by tumor infiltrating lymphocyte (TIL) with a good prognosis. Some immune scores based on CD3+ and/or CD8+ T-cells infiltration are validated and reproducible, especially TuLIS1 and Immunoscore®.2 No data are available concerning efficacy of ICI in this subpopulation of mCRC. Pembrolizumab, an anti-PD1 (programmed death-1) monoclonal antibody has been recently reported very effective in patients with MSI/dMMR mCRC. Immunogenic cell death induced by chemotherapy, such as oxaliplatin, could increase the efficacy of ICI. We formulated the hypothesis that patients with a pMMR mCRC with a high immune infiltrate can be sensitive to ICI plus oxalipatin-based chemotherapy. Methods POCHI is a multicenter, open-label, single-arm phase II trial to evaluate efficacy of pembrolizumab in combination with chemotherapy as first-line treatment of pMMR mCRC with a high immune infiltrate. Primary objective is PFS at 10 months, i.e. number of patients alive and without radiological and/or clinical progression at 10 months evaluated by the investigator. Main secondary objectives are overall survival, secondary resection rate, depth of response and early tumour shrinkage. Main inclusion criteria are pMMR mCRC untreated for metastatic disease and with at least one measurable metastatic target according to RECIST v1.1 criteria. Patients must have resected primary tumor to evaluate two different immune scores (Immunoscore® and TuLIS) and patients are eligible if one score is ‘high’. Patients will receive combination of pembrolizumab (200 mg), bevacizumab (7.5 mg/kg), oxaliplatin (130 mg/m²) and capecitabine (2000 mg/m²/day, on day 1 to 14). Treatment will be repeated every 3 weeks until disease progression or unacceptable toxicity. The clinical hypotheses are to increase PFS at 10 months from 50% to 70%. With a one-sided type error of 5%, power of 85%, 10% rate of patients lost to follow-up or not evaluable, 55 patients have to be included. If 32 patients or more are alive and without progression at 10 months, the treatment will be considered as effective. Thus, with 15% ‘high’ immune score, about 400 patients must be tested in order to include 55 patients in POCHI trial. The ancillary study will consist to identify predictive biomarkers of response and included expression of PD-L1, circulating lymphocytes circulating tumour DNA, mutational load and gut microbiota. Inclusions will start in September 2020 and theoretical end of recruitment is 2023. Results N/A Conclusions N/A Acknowledgements We thank all the cooperative groups (FFCD – UNICANCER GI– GERCOR) for their contribution and participation to the present trial. We thank MSD and HalioDX for their support. Trial Registration NCT04262687 Ethics Approval This study was approved by ‘Agence Nationale de Securite du Medicament et des produits de sante (ANSM)’ on 24/03/2020; approval number MEDAECNAT-2020-01-00038_2019-002407-18.’ Consent N/A References Emile JF, et al., Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX. Eur J Cancer 2017 Sep;82:16–24 Pages, et al. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet 2018 May 26;391(10135):2128–2139.

Published
2020

15. 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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16. 444P PRODIGE 25 (FFCD 11-01)-FOLFA: A randomized phase II trial evaluating aflibercept associated with LV5FU2 regimen as first-line treatment of non-resectable metastatic colorectal cancers

Author

F. Khemissa Akouz, Joëlle Egreteau, K. Le Malicot, Vincent Bourgeois, Nicolas Barriere, M. Baconnier, Jean-Louis Legoux, David Malka, Thomas Aparicio, V. Lorgis, Veronique Guerin-Meyer, David Tougeron, Valérie Boige, V. Lebrun-Ly, Roger Faroux, and Côme Lepage

Subjects
First line treatment, Oncology, medicine.medical_specialty, Regimen, business.industry, Internal medicine, medicine, Hematology, business, Aflibercept, medicine.drug
Published
2020
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17. Perioperative FOLFOX 4 Versus FOLFOX 4 Plus Cetuximab Versus Immediate Surgery for High-Risk Stage II and III Colon Cancers: A Phase II Multicenter Randomized Controlled Trial (PRODIGE 22)

Author

Mehdi Karoui, Cedric Lecaille, C. de Chaisemartin, Johannes Hartwig, Julien Taieb, O. Bouche, Guillaume Piessen, Emilie Barbier, G. Portier, Jean-Marc Regimbeau, Olivier Glehen, Hanifa Ammarguellat, Côme Lepage, Michel Prudhomme, for Prodige investigators, Astrid Lièvre, Gael Goujon, Francesco Brunetti, Jean-Louis Legoux, Anne Rullier, and Benoit Romain

Subjects
Adult, Male, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Population, Leucovorin, Cetuximab, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, education, Colectomy, Aged, Neoplasm Staging, Tumor Regression Grade, education.field_of_study, business.industry, Perioperative, Middle Aged, medicine.disease, Interim analysis, digestive system diseases, Neoadjuvant Therapy, 3. Good health, Surgery, Tolerability, 030220 oncology & carcinogenesis, Colonic Neoplasms, 030211 gastroenterology & hepatology, Female, Fluorouracil, France, business, Tomography, X-Ray Computed, medicine.drug
Abstract

BACKGROUND Perioperative chemotherapy has proven valuable in several tumors, but not in colon cancer (CC). OBJECTIVE The aim of this study was to evaluate the efficacy and safety of perioperative chemotherapy in patients with locally advanced nonmetastatic CC. METHODS This is a French multicenter randomized phase II trial in patients with resectable high-risk T3, T4, and/or N2 CC on baseline computed tomography (CT) scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type patients, a third arm testing perioperative FOLFOX-cetuximab was added. Tumor Regression Grade (TRG1) of Ryan et al was the primary endpoint. Secondary endpoints were toxicity, perioperative morbidity, and quality of surgery. RESULTS A total of 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped (lack of efficacy). The remaining 104 patients (control, n = 52; FOLFOX preop n = 52) represented our intention-to-treat population. In the FOLFOX perioperative group, 96% received the scheduled 4 cycles before surgery. R0 resection and complete mesocolic excision rate were 94% and 93%, respectively. Overall mortality and morbidity rates were similar in both groups. Perioperative FOLFOX chemotherapy did not improve major pathological response rate (TRG1 = 8%) but was associated with a significant pathological regression (TRG1-2 = 44% vs 8%, P < 0.001) and a trend to tumor downstaging as compared to the control group. CT scan criteria were associated with a 33% rate of overstaging in control group. CONCLUSIONS Perioperative FOLFOX for locally advanced resectable CC is feasible with an acceptable tolerability but is not associated with an increased major pathological response rate as expected. However, perioperative FOLFOX induces pathological regression and downstaging. Better preoperative staging tools are needed to decrease the risk of overtreating patients.

Published
2019

18. Resection of small bowel adenocarcinoma metastases: Results of the ARCAD-NADEGE cohort study

Author

Cedric Lecaille, Mohamad Chehimi, Romain Coriat, Marc Pocard, Thomas Aparicio, Sylvain Manfredi, David Tougeron, Eric Terrebonne, Isabelle Baumgaertner, Aziz Zaanan, Jean-Louis Legoux, Jean-Baptiste Bachet, Olivier Bouché, Anne-Laure Villing, Pauline Afchain, Jean-Marc Gornet, Robert Benamouzig, Johan Gagnière, Corinne Sarda, Jean-Luc Faucheron, Pierre Rompteaux, J. Forestier, Nathalie Bonichon-Lamichhane, Thierry Lecomte, Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'Hépato-Gastro-Entérologie [Hôpital Saint-Louis, AP-HP], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastro-entérologie et hépatologie [Hôpital Cochin], [AP-HP], Hôpital Cochin [AP-HP], Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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), 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), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Clinique Tivoli Ducos [Bordeaux], CHU Robert Debré [Reims], Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Polyclinique Bordeaux Nord Aquitaine, 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 Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Saint-Quentin, Hôpital d'Auxerre, Partenaires INRAE, Hopital de castres, Service Hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHRO), A.R.C.A.D. (Aide et Recherche en CAncerologie Digestive) fundation [NA2009], Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service Chirurgie Disgestive, Centre Hospitalier Universitaire Estaing, Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut Cochin (IC 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), AP HP, Departement Oncologie, Centre Hospitalier Universitaire Henri Mondor, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Cooperator Multidisciplinary Oncology Group (GERCOR), Service de Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Reims Champagne-Ardenne (URCA), Unité de Chirurgie Colorectale, CHU Grenoble-Hôpital Michallon, Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Pontchaillou, Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département d'hépatologie et de gastroentérologie [CHU Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Université de Picardie Jules Verne (UPJV), Regional Hospital of Orleans, Centre de Recherche en Nutrition Humaine, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), CHU Trousseau [APHP], Service d'Oncologie Médicale [CHU Saint-Antoine], and CHU Saint-Antoine [AP-HP]

Subjects
Male, Lymphovascular invasion, [SDV]Life Sciences [q-bio], Gastroenterology, Metastasis, 0302 clinical medicine, Duodenal Neoplasms, Positron Emission Tomography Computed Tomography, Clinical endpoint, Prospective Studies, Neoplasm Metastasis, Digestive System Surgical Procedures, Aged, 80 and over, Univariate analysis, Small bowel adenocarcinoma, General Medicine, Middle Aged, Prognosis, Magnetic Resonance Imaging, Primary tumor, 3. Good health, Survival Rate, medicine.anatomical_structure, Oncology, Metastases resection, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, France, Cohort study, medicine.drug, Adult, Ampulla of Vater, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Adenocarcinoma, Disease-Free Survival, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, Neoplasm Staging, Lung, business.industry, medicine.disease, Oxaliplatin, Adjuvant chemotherapy, Hepatic metastases, Surgery, business, Follow-Up Studies
Abstract

Introduction Data are lacking with regard to curative resection of metastasis from small bowel adenocarcinoma (SBA). This study evaluated outcomes and prognostic factors in patients with curatively resected metastatic SBA. Methods A series of 34 patients undergoing resection of metastatic SBA from January 2009 to November 2014 at French centers were included into this cohort study. The primary endpoint was overall survival (OS). Secondary endpoints were recurrence-free survival (RFS) and prognostic factors. Univariate analyses were performed to determine prognostic risk factors. Results The sites of SBA metastases were peritoneal (29.4%), liver (26.5%), lymph nodes (11.8%), lung (2.9%), multiple (14.7%), and other (14.7%). Thirty (88.2%) patients received adjuvant or perioperative chemotherapy, mainly was oxaliplatin-based (76.5%). The median OS was 28.6 months and RFS was 18.7 months. Fourteen (41.2%) patients survived for more than 36 months. In univariate analysis, poor differentiation (P = 0.006), invaded margins (P = 0.003), and lymphatic invasion in the primary tumor (P = 0.039) were associated with decreased OS. Conclusion Overall survival of patients after resection of metastatic SBA remains poor, but long-term survivors are observed. Resection of metastatic SBA should be consider if patients are expected to be operated on with curative intent and have moderately or well-differentiated tumors.

Published
2019
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19. 522TiP PRODIGE 71 - BEVAMAINT: A randomized phase III study comparing maintenance treatment with fluoropyrimidine + bevacizumab versus fluoropyrimidine after induction chemotherapy for a metastatic colorectal cancer

Author

Pierre Laurent-Puig, Emilie Barbier, D. Gonzalez, Anthony Turpin, Jean-Louis Legoux, David Malka, C. Lepage, Thomas Aparicio, David Tougeron, Vincent Hautefeuille, A. Zaanan, C. Choine, and Sylvain Manfredi

Subjects
Oncology, medicine.medical_specialty, Bevacizumab, Colorectal cancer, business.industry, Internal medicine, medicine, Induction chemotherapy, Hematology, medicine.disease, business, medicine.drug
Published
2020
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20. 1163P Lanreotide as maintenance therapy after first-line treatment in patients with non-resectable duodeno-pancreatic neuroendocrine tumours (NETs): An international double-blind, placebo-controlled randomized phase II trial

Author

J.-Y. Scoazec, Astrid Lièvre, David Tougeron, C. Lepage, F. Di Fiore, Pierre Michel, D. Smith, Jean-Louis Legoux, Thomas Walter, Caroline Petorin, M. Caulet, Laetitia Dahan, K. Le Malicot, Romain Coriat, Ivan Borbath, Christos Toumpanakis, Rosine Guimbaud, J.M. Phelip, Guillaume Cadiot, and C. Lombard Bohas

Subjects
medicine.medical_specialty, business.industry, Hematology, Lanreotide, Placebo, Gastroenterology, Double blind, First line treatment, chemistry.chemical_compound, Oncology, chemistry, Maintenance therapy, Internal medicine, Medicine, In patient, business
Published
2020
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21. Does neoadjuvant FOLFOX chemotherapy improve the oncological prognosis of high-risk stage II and III colon cancers ? Three years’ follow-up results of the Prodige 22 phase II randomized multicenter trial

Author

Astrid Lièvre, Johannes Hartwig, Julien Taieb, Emilie Barbier, Jean-Marc Regimbeau, Medhi Karoui, Olivier Glehen, Claire Gallois, Côme Lepage, Guillaume Portier, Michel Prudhomme, Jean-Louis Legoux, Olivier Bouché, Gael Goujon, Guillaume Piessen, Cedric Lecaille, Hanifa Ammarguellat, Benoit Romain, Cécile de Chaisemartin, and Francesco Brunetti

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, business.industry, Colorectal cancer, medicine.medical_treatment, Locally advanced, Follow up results, Perioperative, Stage ii, medicine.disease, digestive system diseases, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, 030220 oncology & carcinogenesis, Multicenter trial, Internal medicine, Medicine, business, 030215 immunology, medicine.drug
Abstract

4110 Background: Neoadjuvant chemotherapy in a perioperative setting has proven valuable in locally advanced resectable colon cancer (CC) in terms of toxicity, postoperative morbidity and downstaging, but its effect on oncological outcomes remains uncertain. Methods: Prodige 22 was a randomized multicenter phase II trial in patients with resectable high-risk T3, T4 and/or N2 CC on baseline CT-scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type (wt) patients a third arm testing perioperative FOLFOX-cetuximab was added. Primary endpoint was the Tumor Regression Grade. Secondary endpoints were 3-years overall (OS), disease-free survival (DFS) and time to recurrence (TTR). Results: 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped for futility. The remaining 104 patients (control, n = 52; FOLFOX peri-op n = 52) represented our intention-to-treat population. In the FOLFOX peri-op group, 96% received the schedule 4 cycles prior to surgery and all but one underwent adjuvant FOLFOX for a total of 12 cycles. In the control arm, 38 patients received adjuvant FOLFOX (1 postoperative death and 13 low-risk stage II patients). Median follow-up was 54.3 months [48.5-57.2]. Nineteen deaths and 26 disease recurrences were observed leading to a 3 years-OS of 90.3% in both arms (p = 0.7) and to a 3-years DFS of 76.8% and 69.2% in the peri-op and control arm respectively (p = 0.6). A trend to a better TTR in the peri-op arm was observed with a 3-years TTR of 82% as compared to 72% in the control arm (p = 0.3). No benefit from adding Cetuximab was observed in the 16 RAS-wt treated patients. Conclusions: In this pilot randomized study, perioperative FOLFOX chemotherapy has no detrimental effect on long term oncological outcomes and may be an option for some patients with locally advanced CC. A pooled analysis of randomized trials testing peri-operative strategies in this setting is warranted. Clinical trial information: NCT01675999 .

Published
2020
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22. Pravastatin combination with sorafenib does not improve survival in advanced hepatocellular carcinoma

Author

Jean-Pierre Bronowicki, Jean-Louis Legoux, Thierry Lecomte, Jean-François Seitz, Olivier Bouché, Sylvain Manfredi, Prodige Investigators, Emilie Barbier, Jean-Marc Phelip, Eric Nguyen Khac, Ghassan Riachi, Isabelle Ollivier-Hourmand, Jacques Denis, Jean-Louis Jouve, Julien Vergniol, Anne-Laure Villing, Maryline Debette-Gratien, Jean-François Ramée, Roger Faroux, and Faiza Khemissa Akouz

Subjects
0301 basic medicine, Oncology, Sorafenib, Adult, Diarrhea, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Antineoplastic Agents, Kaplan-Meier Estimate, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, neoplasms, Aged, Pravastatin, Aged, 80 and over, Univariate analysis, Hepatology, Performance status, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Prognosis, digestive system diseases, Progression-Free Survival, Clinical trial, 030104 developmental biology, Hepatocellular carcinoma, Quality of Life, 030211 gastroenterology & hepatology, Female, business, Liver cancer, medicine.drug, Follow-Up Studies
Abstract

Background & Aims Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC). Combining sorafenib with another treatment, to improve overall survival (OS) within an acceptable safety profile, might be the next step forward in the management of patients with advanced HCC. We aimed to assess whether a combination of sorafenib and a statin improved survival in patients with HCC. Methods The objective of the PRODIGE-11 trial was to compare the respective clinical outcomes of the sorafenib-pravastatin combination (arm A) versus sorafenib alone (arm B) in patients with advanced HCC. Child-Pugh A patients with advanced HCC who were naive to systemic treatment (n = 323) were randomly assigned to sorafenib-pravastatin combination (n = 162) or sorafenib alone (n = 161). The primary endpoint was OS; secondary endpoints were progression-free survival, time to tumor progression, time to treatment failure, safety, and quality of life. Results After randomization, 312 patients received at least 1 dose of study treatment. After a median follow-up of 35 months, 269 patients died (arm A: 135; arm B: 134) with no difference in median OS between treatments arms (10.7 months vs. 10.5 months; hazard ratio = 1.00; p = 0.975); no difference was observed in secondary survival endpoints either. In the univariate analysis, the significant prognostic factors for OS were CLIP score, performance status, and quality of life scores. The multivariate analysis showed that the only prognostic factor for OS was the CLIP score. The main toxicity was diarrhea (which was severe in 11% of patients in arm A, and 8.9% in arm B), while severe nausea-vomiting was rare, and no toxicity-related deaths were reported. Conclusion Adding pravastatin to sorafenib did not improve survival in patients with advanced HCC. Lay summary Sorafenib has proven efficacy for the treatment of patients with advanced hepatocellular carcinoma. However, overall survival remains poor in these patients, so we were interested to see if the addition of a statin, pravastatin, improved outcomes in patients with advanced HCC. This randomized-controlled trial demonstrated that the sorafenib-pravastatin combination did not improve overall survival in this study population compared to sorafenib alone. Clinical trial number: NCT01075555.

Published
2018

23. 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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24. NARROW-BAND IMAGING (NBI) VERSUS LUGOL CHROMOENDOSCOPY IN THE DETECTION OF OESOPHAGUS SQUAMOUS NEOPLASMS IN A HIGH-RISK POPULATION: A REAL-LIFE RANDOMISED CONTROLLED MULTICENTRE TRIAL

Author

Michel Antonietti, M Kaasis, B. Prost, Morgane Amil, Angélique Denis, Christophe Cellier, S Fratte, Emmanuel Coron, Claude Masliah, P Balian, Melissa Gruner, G Rahmi, Mathieu Pioche, B Guerrier, AL Tarreirrias, P. Rey, Pascal Renkes, L Lefrou, Thierry Ponchon, S Elia, M Le Rhun, E Metivier-Cesbron, Jean-Louis Legoux, Stéphane Lecleire, Sandrine Touzet, and Dominique Luet

Subjects
education.field_of_study, medicine.medical_specialty, Narrow-band imaging, business.industry, Population, Medicine, Radiology, education, business, Chromoendoscopy
Published
2018
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25. Narrow-Band Imaging (NBI) versus coloration Lugol dans la détection du carcinome de l'oesophage dans une population à haut risque: un essai contrôlé randomisé multicentrique en situation de vraie vie

Author

Dominique Luet, F Dewaele, Mathieu Pioche, M Kaassis, D. Pere-Verge, B. Prost, Michel Antonietti, Jean-Louis Legoux, S Fratte, Elia Samaha, Claude Masliah, B Guerrier, A. L. Tarrerias, Pascal Renkes, E Metiver, Christophe Cellier, T. Ponchon, M Le Rhun, Stéphane Lecleire, Emmanuel Coron, G Rahmi, P. Rey, and Melissa Gruner

Subjects
Gynecology, medicine.medical_specialty, business.industry, medicine, business
Published
2018
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26. 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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27. Chemotherapy for Well-Differentiated Pancreatic Neuroendocrine Tumours with a Ki-67 Index ≥10%: Is There a More Effective Antitumour Regimen? A Retrospective Multicentre Study of the French Group of Endocrine Tumours (GTE)

Author

Anne Couvelard, Eric Baudin, François-Xavier Caroli-Bosc, Guillaume Roquin, Aline Ramond-Roquin, Jean-Yves Scoazec, Jean-Louis Legoux, Olivia Hentic, Vincent Rohmer, C. Lombard-Bohas, Sophie Dominguez, Guillaume Cadiot, Michel Ducreux, Patricia Niccoli, Thomas Walter, Rosine Guimbaud, Philippe Ruszniewski, Emmanuel Mitry, Service d’Hépato-Gastroentérologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut Gustave Roussy (IGR), 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), Centre Hospitalier Universitaire de Reims (CHU Reims), Département d'oncologie médicale, Institut Claudius Regaud, Biochimie Endocrinienne et Métabolique [Marseille] (U38 Inserm - CHU Timone), Université de la Méditerranée - Aix-Marseille 2- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Institut Curie [Paris], Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), DOCOMO Euro-Labs, DOCOMO Communications Laboratories Europe GmbH, Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de pathologie [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de biologie et pathologie médicales [Gustave Roussy], Laboratoire d'Ergonomie et d'Épidémiologie en Santé au Travail (LEEST), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Institut de Veille Sanitaire (INVS), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service de Gastroentérologie [Hôpital Beaujon], and Hôpital Beaujon [AP-HP]

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Antineoplastic Agents, Neuroendocrinology, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Biomarkers, Tumor, Endocrine system, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Chemotherapy, biology, Endocrine and Autonomic Systems, business.industry, Middle Aged, Chemotherapy regimen, 3. Good health, Well differentiated, Pancreatic Neoplasms, [STAT]Statistics [stat], Regimen, Neuroendocrine Tumors, Ki-67 Antigen, 030220 oncology & carcinogenesis, Ki-67, biology.protein, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business
Abstract

Background: The best chemotherapy regimen for well- differentiated pancreatic neuroendocrine tumours (pNETs) with a Ki-67 index ≥10% is still debated. We evaluated the antitumour efficacy of various first-line chemotherapy regimens (streptozocin based, platinum based, or dacarbazine/temozolomide based) in this situation. Methods: In this retrospective multicentre study of the French Group of Endocrine Tumours (GTE), we recruited consecutive patients with advanced well-differentiated pNETs and a Ki-67 index ≥10% receiving chemotherapy between 2000 and 2012. The primary endpoint was progression-free survival (PFS) according to RECIST. Results: Seventy-four patients (42 men, median age 55.5 years) were enrolled from 10 centres. Fifty-one patients (69%) had grade 2 NET and 61 (82%) were stage IV. Median overall survival was 36.3 months. Forty-four patients (59%) received streptozocin-based, 18 (24%) platinum-based, and 12 (16%) dacarbazine/temozolomide-based chemotherapy regimens. These 3 groups were similar regarding age, functioning tumours, grade, the number of metastatic sites, and surgery for primary tumours, but not regarding surgery for metastases and time since diagnosis. Grade 3 NET (HR 2.15, 95% CI: 1.18-3.92, p = 0.012) and age above 55 years (HR 1.84, 95% CI: 1.06-3.18, p = 0.030) were associated with shorter median PFS in the multivariate analyses. Compared to streptozocin-based chemotherapy, no difference was found in terms of PFS for the platinum-based or for the dacarbazine/temozolomide-based chemotherapy regimen: median PFS was 7.2, 7.5, and 7.2 months, respectively (p = 0.51). Conclusions: Patients with intermediate or highly proliferative well-differentiated pNETs may benefit from 1 of the 3 chemotherapy regimens. Increased age and grade 3 were associated with shorter median PFS. Randomised studies searching for response predictors and the best efficacy-tolerance ratio are required to personalise the strategy.

Published
2017
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28. 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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29. Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort

Author

Sylvain Manfredi, Eric Terrebonne, Gael Deplanque, Jean-Yves Scoazec, Anne-Laure Ran-Royo, Marc Ferec, Guillaume Cadiot, Eric Maringe, C. Desauw, Philippe Rougier, Thomas Aparicio, Castex, Guillaume Geslin, Jean-François Seitz, François Dewaele, Karine Bouhier-Leporrier, Vincent Hautefeuille, Anne Thirot-Bidault, Olivia Hentic, G. Roquin, David Tougeron, Olivier Dubreuil, C. Rebischung, Laetitia Dahan, Ivan Borbath, Jean-Louis Legoux, Laurent Bedenne, Sandrine Lavau denes, Catherine Ligeza, Mathieu Baconnier, K. Le Malicot, Laurent Cany, Côme Lepage, Thierry Lecomte, Céline Lepère, I. Bonnet, Valérie Rossi, Isabelle Wanicki Caron, Laetitia Stephanie, Cedric Lecaille, Eric Baudin, Thomas Walter, David Malka, Patricia Niccoli, Vincent Bourgeois, Etienne Suc, Joël Guigay, Romain Coriat, Rosine Guimbaud, Catherine Lombard-Bohas, Caroline Petorin, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Gustave Roussy (IGR), Fédération Francophone de la Cancérologie Digestive, FFCD, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], CHU Valenciennes, CHU Toulouse [Toulouse], Hôpital Cochin [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU de Lille, Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Hôpital de la source, CHU Lyon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France, affiliation inconnue, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Clinique Saint-Jean Languedoc [Toulouse] (CSJL), CHU Amiens-Picardie, Hôpital Duchenne, CH Boulogne sur Mer, Polyclinique Francheville, Centre Catherine-de-Sienne [Nantes] (CCS), Polyclinique Bordeaux Nord Aquitaine, Hôpital Michallon, CH du Haut Anjou (Château-Gontier), CH Annecy Genevois, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier du pays de Morlaix, Hôpital Saint-Joseph, Assistance Publique-Hôpitaux de Paris, Cabinet privé des Dr Geslin Provost (Vannes), CHU Rouen, Normandie Université (NU), CHU Dupuytren, CHU Dijon, Clinique Mutualiste de l'Estuaire (Saint Nazaire), Hospices Civils de Beaune [Centre hospitalier de Beaune], Centre de radiothérapie et d'oncologie médicale privée (Béziers), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Côte d'Azur (UCA)-UNICANCER

Subjects
Oncology, Male, Cancer Research, medicine.medical_specialty, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Carboplatin, Cohort Studies, 03 medical and health sciences, Gastrointestinal cancer, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, FOLFIRI Regimen, Humans, Neoplasm Metastasis, Prospective cohort study, Aged, Etoposide, Gastrointestinal Neoplasms, Univariate analysis, Performance status, business.industry, Large cell, Hazard ratio, Ki67 index, medicine.disease, Prognosis, 3. Good health, Carcinoma, Neuroendocrine, Pancreatic Neoplasms, Treatment, Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, Neuroendocrine carcinoma, Female, Cisplatin, business, Cohort study
Abstract

IF 6.029; International audience; BackgroundDiagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC.Patients and methodsAll patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded.Results253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0–1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20–100). Median overall survival was 15.6 (13.6–17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE > 2 upper limit of normal [ULN]; HR = 3.2), CgA > 2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72).ConclusionsWe report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.

Published
2017
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30. Evaluating lanreotide as maintenance therapy after first-line treatment in patients with non-resectable duodeno-pancreatic neuroendocrine tumours

Author

Marianne Pavel, Denis Smith, M. Ducreux, Astrid Lièvre, Karine Bouhier-Leporrier, Karine Le Malicot, Jean-Louis Legoux, Anja Rinke, Olivia Hentic, Juan W. Valle, Nadia Bouarioua, Christos Toumpanakis, Guillaume Cadiot, David Tougeron, Thomas Walter, Rosine Guimbaud, Laetitia Dahan, Frédéric Di Fiore, Côme Lepage, Ivan Borbath, Roger Faroux, Jean-Yves Scoazec, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Fédération Francophone de la Cancérologie Digestive, FFCD, 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, 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, Hôpital de la Timone [CHU - APHM] (TIMONE), Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital, Regional Hospital of Orleans, Service de Biostatistique, Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], 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), Bases moléculaires de la réponse aux xénobiotiques (U775 (IFR95)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France, affiliation inconnue, Service d'Oncologie Médicale, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Hospitalier Départemental Les Oudairies, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'Oncologie Médicale, 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'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), 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 ) -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 ), 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 ), Hôpital de la Timone [CHU - APHM] ( TIMONE ), Hôpital Charles Nicolle [Rouen]-CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Bases moléculaires de la réponse aux xénobiotiques ( U775 (IFR95) ), 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 de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Fédération Francophone de Cancérologie Digestive (FFCD), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Oncology, Male, Duodenopancreatic neuroendocrine tumours, medicine.medical_treatment, Lanreotide, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, chemistry.chemical_compound, 0302 clinical medicine, Quality of life, Maintenance therapy, Clinical Protocols, Duodenal Neoplasms, Prospective Studies, Prospective cohort study, Gastroenterology, Middle Aged, 3. Good health, Europe, Clinical trial, Neuroendocrine Tumors, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Somatostatin, Adult, medicine.medical_specialty, Randomization, Adolescent, Maintenance, 030209 endocrinology & metabolism, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, Peptides, Cyclic, Disease-Free Survival, 03 medical and health sciences, Young Adult, Double-Blind Method, Internal medicine, medicine, Humans, Aged, Chemotherapy, Hepatology, business.industry, Surgery, Pancreatic Neoplasms, First line, chemistry, Quality of Life, business
Abstract

Introduction Patients with metastatic or locally advanced, non-resectable, grade 1 or 2 well-differentiated duodeno-pancreatic (WDDP) NETs are treated following European guidelines. Patients (Pts) with aggressive disease, i.e. progressive and/or symptomatic metastases and/or with significant hepatic invasion (>30–50%), and/or bone metastases, anti-tumour therapy should receive systemic combination of chemotherapy once disease control is obtained. Aim(s) The aim is to stop chemotherapy until progression. REMINET is an academic randomized, double-blind, placebo-controlled, phase II/III study designed to evaluate lanreotide (LAN) as maintenance treatment after L1 chemotherapy in G1-G2 WDDP NET. Materials and methods Main eligibility criteria: adults pts with a metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 1 or 2 WDDP NETs and documented control disease after L1 therapy at least 4 weeks prior to randomization. Results 222 patients will be randomly assigned in a 1:1 ratio to receive 120 mg LAN or placebo, every 28 days, until disease progression or unacceptable toxicity. The aim of the phase II part is to demonstrate a 6-months PFS >45% in LAN arm. Secondary endpoints are PFS according to central review, overall survival, safety and quality of life. A bio-bank of frozen blood will be constituted. Conclusion The study is currently open in France, Germany, Belgium, United Kingdom and Ireland. A total of 25 patients are randomized (NCT02288377).

Published
2017
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31. Rectal cancer: French Intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO)

Author

Thierry Conroy, Guillaume Cadiot, Thierry André, Société Française de Chirurgie Digestive, Jean-François Bosset, Frédéric Bibeau, Jean-Pierre Gerard, Jean-Louis Legoux, Olivier Bouché, Laurent Bedenne, Guillaume Portier, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Hospitalier Régional d'Orléans (CHRO), CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Reims (CHU Reims), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)

Subjects
medicine.medical_specialty, Colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Guidelines, 03 medical and health sciences, 0302 clinical medicine, Risk groups, Neoadjuvant treatment, National recommendations, medicine, Rectal Adenocarcinoma, Humans, Rectal cancer, Pathological, Neoplasm Staging, Gynecology, Hepatology, medicine.diagnostic_test, business.industry, Rectal Neoplasms, General surgery, Proctocolectomy, Restorative, Gastroenterology, Rectum, Evidence-based medicine, medicine.disease, Neoadjuvant Therapy, 3. Good health, Endoscopy, Clinical Practice, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, Follow-Up Studies
Abstract

IF 3.061; International audience; IntroductionThis document is a summary of the French Intergroup guidelines regarding the management of rectal adenocarcinoma published in February 2016.MethodThis collaborative work, under the auspices of most of the French medical societies involved in the management of rectal cancer, is based on the previous guidelines published in 2013. Recommendations are graded into 3 categories according to the level of evidence of data found in the literature.ResultsIn agreement with the ESMO guidelines (2013), non-metastatic rectal cancers have been stratified in 4 risk groups according to endoscopy, MRI or endorectal-ultrasonography. Locally-advanced tumors are limited to groups 3 and 4 (T3 ≥4 cm or T3c–d or N1-2 or T4). These tumors are usually treated using neoadjuvant treatment and total proctectomy (TME). Adjuvant treatment depends on the pathological findings. Very early (group 1) or early (group 2) tumors are managed mainly by surgery, and organ preservation may be an option in selected cases. For metastatic tumors, the recommendations are based on less robust evidence and chemotherapy plays a major role.ConclusionSuch recommendations are constantly being optimized and each individual case must be discussed within a Multi-Disciplinary Team.

Published
2017
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32. BIONADEGE: Genomic profiling of small bowel adenocarcinoma from the NADEGE prospective cohort

Author

Thomas Aparicio, Aziz Zaanan, Julie Henriques, Eric Terrebonne, David Tougeron, Astrid Lièvre, Cedric Lecaille, Jean-Marc Gornet, Guillaume Piessen, Johan Gagnière, Pierre Laurent-Puig, Marc Pocard, Sabine Helfen, Sandrine Lavau-Denes, Pauline Afchain, Jean-Louis Legoux, Thierry Lecomte, Magali Svrcek, Dewi Vernerey, and Mourad Benallaoua

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Genomic profiling, business.industry, Internal medicine, Cohort, medicine, Small bowel adenocarcinoma, Ancillary Study, Prospective cohort study, business
Abstract

4140 Background: Small bowel adenocarcinoma (SBA) is a rare tumour. Large genomic analyses with prognostic assessments are lacking. Methods: BIONADEGE is an ancillary study of the NADEGE cohort that enrolled 347 patients (pts) with SBA from 2009 to 2012. Next generation sequencing investigates the presence of 740 hot spot somatic mutations in 46 genes involved in carcinogenesis. The MSI (MicroSatellite Instable) status was assessed using 5 microsatellites. The MMR (MisMatch Repair) status was assessed by immunochemistry (4 antibodies). Results: A total of 196 tumour samples were collected and 125 pts had conclusive results for mutation analysis. The clinical and tumours characteristics were comparable in the NADEGE and BIONADEGE cohort except for metastatic stage at diagnostic underrepresented in the BIONADEGE cohort (17.7%) due to missing tumour sample. A predisposing disease was reported in 25 (20.0%) cases (among them 14 Lynch syndromes and 7 Crohn diseases). The number of mutation observed was 0 in 9.6% pts, only 1 in 32.0%, 2 in 26.4% and ≥3 in 32.0%. The most frequent genomic alteration were KRAS (44.0%), TP53 (38.4%), PIK3CA (20.0%), APC (18.4%), SMAD4 (14.4%) and ERBB2 (7.2%). Altogether, a genomic alteration was observed in 90.3% of tumour. KRAS mutation were more frequent in synchronous metastatic tumour than in localized tumour (72.7% vs 38.2%, p = 0.003). There was no significant difference of mutation rate according to primary location for the most frequently altered gene. With caution to small sample, IDH1 mutation is more frequent and APC mutation never seen in Crohn disease. The rate of dMMR tumor was 38.6% in localized tumour and 0% in synchronous metastatic tumour. After a median follow-up of 55 months (95%CI [44-63]), M0 stage, pN0, pT1-2 were associate with better survival in univariate analysis. No significant prognostic value of genomic alteration was associated with OS. dMMR status was associate with a better prognosis for OS in pts with MMR status determined by immunohistochemistry (HR = 0.55 [0.29-1.01], p = 0.055). Conclusions: A high frequency of targetable alteration is observed in SBA. There is several specificities according to predisposing disease. No association between genomic alteration and prognostic was observed except a trend for a better prognosis associate with dMMR.

Published
2019
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33. Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001–02)

Author

Gilles Breysacher, F. Masskouri, C. Choine, François Morvan, Pascal Hammel, Jean-François Seitz, P. Amoyal, J. Cretin, G. Gatineau-Sailliant, Christophe Locher, Thomas Aparicio, G. Bordes, O. Boulat, David Tougeron, I. Cumin, O. Berthelet, Anne Thirot Bidault, M. Pauwels, X. Moncoucy, Faiza Khemissa, F. Petit-Laurent, X. Adhoute, P. Prost, J.P. Lagasse, Jean-Louis Legoux, J. Ezenfis, N. Le Provost, Pierre Michel, A. Gueye, P. Pouderoux, G. Le Pessec, Julien Taieb, B. Landi, H. Fattouh, A. Azzedine, Mohamed Ramdani, Matthieu Schnee, Laurent Bedenne, Jean-Louis Jouve, C. Rebischung, J. Thaury, Ph. Rougier, C. Lobry, F. Guiliani, Jean-Baptiste Bachet, F. Ricard, L. Stefani, R. Mackiewicz, Dominique Genet, E. Cuillerier, C. Bineau, A.M. Queuniet, P. Couzigou, Jean-Marc Phelip, Eveline Boucher, B. Garcia, D. Cleau, M. Schneider, Iradj Sobhani, M. Mozer, Roger Faroux, Mohamed Gasmi, J. Charneau, Côme Lepage, Thierry Lecomte, Céline Lepère, D. Auby, Eric Terrebonne, R. Benoit, Emmanuel Mitry, D. Gargot, J. Martin, M. Baconnier, V. Derias, Achim Weber, Nadia Bouarioua, L. Chone, Catherine Lombard-Bohas, Patrick Texereau, B. Denis, May Mabro, Emilie Maillard, Sandrine Lavau-Denes, F. Di Fiore, C. Girault, J. Provençal, O. Bouche, F. Bonnetain, A. Gagnaire, Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier de Blois (CHB), Hôpital Nord [CHU - APHM], Centre Hospitalier de Meaux, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Métropole Savoie [Chambéry], Hôpital pasteur [Colmar], Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Duchenne, CH Boulogne sur Mer, Clinique Bonnefon, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]

Subjects
Oncology, Male, medicine.medical_specialty, Leucovorin, colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Irinotecan, chemotherapy, Gastroenterology, elderly, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Progression-free survival, geriatric oncology, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Hazard ratio, Hematology, Chemotherapy regimen, 3. Good health, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, Multivariate Analysis, FOLFIRI, 030211 gastroenterology & hepatology, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract

International audience; BACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771.

Published
2016
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34. Evaluation of efficacy and safety of FOLFIRI for elderly patients with gastric cancer: A first-line phase II study

Author

Carine Bellera, C. Mertens, Simone Mathoulin-Pélissier, Pierre Soubeyran, Laurent Traissac, Jérôme Dauba, Jean-Louis Legoux, Yves Becouarn, René Brunet, Muriel Rainfray, Denis Smith, Dominique Auby, L. Cany, Eric Terrebonne, and Marianne Fonck

Subjects
Male, Oncology, medicine.medical_specialty, Colorectal cancer, Leucovorin, Folinic acid, Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, FOLFIRI Regimen, Humans, Medicine, Aged, Aged, 80 and over, Hepatology, business.industry, Gastroenterology, Cancer, medicine.disease, Irinotecan, Regimen, FOLFIRI, Camptothecin, Female, Fluorouracil, business, Febrile neutropenia, medicine.drug
Abstract

Summary Objective Current chemotherapy protocols for gastric cancer present high toxicity. The FOLFIRI regimen has shown promising results with elderly colorectal cancer patients and for gastric cancer patients but this is the first report on elderly gastric cancer patients. Design In this multicenter non-randomized phase II trial, we administered the FOLFIRI chemotherapy protocol (irinotecan [180 mg/m2], fluorouracil [5-FU] [400 mg/m2] and folinic acid 400 mg/m2 or 200 mg/m2 of l-folinic acid) to patients aged over 70 years with locally-advanced or metastatic gastric cancer combined with Comprehensive Geriatric Assessment (CGA). Responses were assessed at 2 months. Results Forty-two patients received eight cycles of the FOLFIRI regimen, with 82.5% of patients showing disease control: 10 patients (26%) showing objective (partial or complete) responses and 23 (57.5%) showing stable disease. One-year overall survival (OS) was 41.5% [95%CI 26.5–56.0] and one-year progression-free survival (PFS) was 31.8% [95%CI 18.4–46.1%]. We observed 10 Grade 3/4 hematologic toxicities with one febrile neutropenia. CGA data demonstrated that geriatric functions were not altered by treatment and that nutritional status improved over treatment. Conclusions Results show excellent disease control and relatively high survival rates with limited toxicity similar to younger patients indicating that this regimen should be considered as a possible treatment in advanced gastric cancer of the elderly.

Published
2011
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35. ARCAD-NADEGE cohort: Result of a small bowel adenocarcinomas prospective cohort

Author

E. Terrebone, Jean-Louis Legoux, Julie Henriques, Romain Coriat, Thomas Aparicio, O. Bouche, Denis Pezet, David Tougeron, Marc Pocard, A. Zaanan, Sylvain Manfredi, Pauline Afchain, J.-M. Gornet, Dewi Vernerey, and Guillaume Piessen

Subjects
0301 basic medicine, medicine.medical_specialty, business.industry, Hematology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Cohort, Medicine, business, Prospective cohort study
Published
2018
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36. Phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients (pts) over 70 with previously treated metastatic colorectal adenocarcinoma (mCRC) FFCD 1404 - REGOLD

Author

M. Ben Abdelghani, G. Des Guetz, Eric Assenat, C. Le Foll, Olivier Romano, Jean-Louis Legoux, Côme Lepage, L. Cany, M. Dhooge, Catherine Delbaldo, A. Darut Jouve, Thomas Aparicio, Denis Smith, M. Duluc, Claire Falandry, Faiza Khemissa, Yves Rinaldi, Pascal Artru, Carole Monterymard, and Bruno Valenza

Subjects
Brachial Plexus Neuritis, medicine.medical_specialty, business.industry, Phases of clinical research, Hematology, Gastroenterology, 03 medical and health sciences, Large Intestine Adenocarcinoma, chemistry.chemical_compound, 0302 clinical medicine, Oncology, chemistry, 030220 oncology & carcinogenesis, Internal medicine, Regorafenib, medicine, 030211 gastroenterology & hepatology, Colorectal adenocarcinoma, In patient, Previously treated, business
Published
2018
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37. Combination 5-fluorouracil, folinic acid and cisplatin (LV5FU2-CDDP) followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: final results of a randomised strategic phase III trial (FFCD 0301)

Author

Laurent Bedenne, Emmanuel Mitry, Jean-Marc Phelip, Jean-Luc Raoul, Philippe Rougier, Jean-François Seitz, Pascal Hammel, Bruno Chauffert, Marc Ychou, Pierre Michel, F. Bonnetain, Jean-Louis Legoux, Laetitia Dahan, Mohamed Gasmi, and Stéphane Cattan

Subjects
Adult, Male, Oncology, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Leucovorin, Adenocarcinoma, Deoxycytidine, Antimetabolite, Drug Administration Schedule, Folinic acid, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Aged, 80 and over, Chemotherapy, Performance status, business.industry, Gastroenterology, Middle Aged, Metastatic Pancreatic Adenocarcinoma, medicine.disease, Survival Analysis, Gemcitabine, Surgery, Pancreatic Neoplasms, Treatment Outcome, Fluorouracil, Disease Progression, Female, France, Cisplatin, business, medicine.drug
Abstract

Purpose Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma. Although the 5-fluorouracil (5FU), folinic acid and cisplatin combination (LV5FU2-CDDP) is an option, the optimal order of the regimens must be determined. The first strategic phase III trial comparing LV5FU2-CDDP followed by gemcitabine versus gemcitabine followed by LV5FU2-CDDP was conducted. Methods Patients with metastatic pancreatic adenocarcinoma, performance status (PS) 0–2, without prior chemotherapy were randomly assigned (1:1) to receive either LV5FU2-CDDP followed by gemcitabine at disease progression or toxicity (Arm A), or the opposite sequence (Arm B). 202 patients had to be included and 170 deaths had to be observed to detect an expected improvement in median overall survival (OS) from 6.5 to 10 months in Arm A (two-sided α = 5% and β = 20%). Results 202 patients were included (Arm A, 102; Arm B, 100). Median age, male/female ratio, PS 0–1 and previous surgery were similar in the two arms. After a median follow-up of 44 months, median OS in Arm A was 6.6 months versus 8.0 months in Arm B (p = 0.85). Median progression-free survival was similar between Arms A and B. More grade 3/4 toxicities were observed when LV5FU2-CDDP was administered as a first-line treatment compared with gemcitabine: 79% versus 64% (p = 0.018). Conclusion This trial did not show any strategic advantage to using LV5FU2-CDDP as a first-line treatment and suggests that gemcitabine remains the standard first-line treatment. Sixty-one per cent of patients were able to receive a second line of chemotherapy.

Published
2010
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38. Time until definitive quality of life score deterioration as a means of longitudinal analysis for treatment trials in patients with metastatic pancreatic adenocarcinoma

Author

Pascal Hammel, Laurent Bedenne, Jean-Louis Legoux, Laetitia Dahan, Jean-François Seitz, Franck Bonnetain, Emilie Maillard, Emmanuel Mitry, Marc Ychou, and Philippe Rougier

Subjects
Male, Cancer Research, medicine.medical_specialty, Time Factors, Emotions, Pain, Kaplan-Meier Estimate, Adenocarcinoma, law.invention, Randomized controlled trial, Quality of life, law, Surveys and Questionnaires, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Longitudinal Studies, Neoplasm Metastasis, Fatigue, Proportional hazards model, business.industry, Surrogate endpoint, Minimal clinically important difference, Metastatic Pancreatic Adenocarcinoma, medicine.disease, humanities, Surgery, Pancreatic Neoplasms, Clinical trial, Oncology, Quality of Life, Female, business
Abstract

Background The Federation Francophone de Cancerologie Digestive phase III trial in patients with metastatic pancreatic adenocarcinoma comparing 5FU, folinic acid and cisplatin combination followed by gemcitabine (Arm A) versus the opposite sequence (Arm B) failed to demonstrate a benefit in overall survival. To longitudinally compare the quality of life (QoL) we explored different definitions of time until definitive deterioration (TUDD) of QoL scores according to minimal clinically important difference (MCID) cut-offs. Methods QoL was evaluated using the EORTC QLQ-C30 every 8 weeks until death. The following scores were analysed: global health, emotional functioning, physical functioning, fatigue and pain. TUDD was defined as the time interval between randomisation and the first occurrence of a decrease in QLQ-C30 score ⩾5 points without any further improvement in QoL score ⩾5 points or any further available QoL data. Analyses were repeated using a 10 point MCID and/or including death as event. Results From 08/2003 to 05/2006, 102 patients in Arm A and 100 in Arm B were included. Using a 5 and a 10 point MCID, TUDD curves of the 5 scores did not differ according to treatment arm., The median TUDD of global health was 5.2 months (4.3–6.2) in Arm A and 6.1 months (5.1–8.5) in Arm B (log-rank p = 0.50) including death as an event for a 5 point MCID. Multivariate Cox model showed that tumour localisation and progression were independently associated with TUDD (p Conclusions The strategy of chemotherapy did not influence the deterioration of QoL. The TUDD approach seems to provide meaningful clinical results that are adapted to metastatic pancreatic adenocarcinoma trials.

Published
2010
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39. 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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40. The efficacy and safety of duodenal stenting: a prospective multicenter study

Author

Remy Dumas, T. Ponchon, B. Napoléon, I. Graber, B Filoche, D Coumaros, Jean-Louis Legoux, H Lamouliatte, and Jean Boyer

Subjects
Adult, Male, Ampulla of Vater, medicine.medical_specialty, medicine.medical_treatment, Common Bile Duct Neoplasms, Duodenal stenosis, Constriction, Pathologic, Adenocarcinoma, Biliary Stenting, Prosthesis, Prosthesis Implantation, Neoplasms, medicine, Humans, Prospective Studies, Duodenoscopy, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, Palliative Care, Gastroenterology, Stent, Middle Aged, medicine.disease, Surgery, Endoscopy, Pancreatic Neoplasms, Stenosis, Treatment Outcome, Biliary tract, Female, Stents, Duodenal Obstruction, business, Complication
Abstract

BACKGROUND AND STUDY AIMS: Duodenal stenting has become a popular treatment in cases of malignant stenosis. However, a prospective evaluation of the efficacy and morbidity of this procedure has not been performed. A prospective multicenter study of duodenal stenting was conducted by the Societe Francaise d’Endoscopie Digestive (SFED). PATIENTS AND METHODS: A total of 51 patients were selected (mean age 72), the majority (69 %) having pancreatic adenocarcinoma. Palliative treatment was chosen because of irresectability (61.2 %), inoperability (18.4 %), or both (20.4 %). Enteral Wallstent prostheses were used, and the patients were followed up on day 3, after 1 month, and then every month, with weight measurement, and symptomatic and laboratory evaluation. RESULTS: One prosthesis was sufficient in 46 patients. Stent positioning and deployment were correct in 50/51 patients (98 %). Twenty patients also underwent biliary stenting in addition to the duodenal stenting. On day 3, 43 patients (84 %) were able to tolerate soft solids or a full diet. Six complications were attributed to stenting: three intestinal hemorrhages, two cases of peritonitis due to bowel perforation, and one case of septicemia, and these led to five deaths (mortality 9.8 %). Stent dysfunction was observed in 12 cases (23.5 %) after a mean delay of 75 days, comprising 11-malignant obstructions and one migration: a new stent was inserted inside the first one and was effective in eight cases; and no treatment was given in the other four patients because of their clinical state. The median survival was 71.5 days. CONCLUSIONS: Palliative endoscopic treatment of malignant duodenal stenosis using metallic prostheses is highly feasible, even with associated biliary stenting. Symptomatic improvement is fast. However, the mortality and the obstruction rate are high, suggesting that a prospective trial comparing this treatment with surgery is still required.

Published
2007
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41. 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

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

Author

Michel Ducreux, Christophe Louvet, Thierry André, Agnès Ruskoné-Foumestraux, Jean-Claude Barbare, David Malka, Didier Peiffert, Guillaume Cadiot, Philippe Rougier, Bruno Landi, Denis Pezet, Olivier Bouché, Laurent Bedenne, Jean-Louis Legoux, Jean-François Seitz, and Etienne Dorval

Subjects
business.industry, Gastroenterology, Library science, Medicine, General Medicine, business
Published
2006
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43. Rectal cancer

Author

Jean-Louis, Legoux, Paul-Antoine, Lehur, Christophe, Penna, Gilles, Calais, Gilles, Roseau, and Loïc De, Calan

Subjects
Clinical Trials as Topic, Chemotherapy, Adjuvant, Rectal Neoplasms, Practice Guidelines as Topic, Gastroenterology, Humans, Radiotherapy, Adjuvant, France, General Medicine, Adenocarcinoma, Neoplasm Recurrence, Local, Neoadjuvant Therapy, Neoplasm Staging
Published
2006
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44. Endoscopic screening for esophageal squamous-cell carcinoma in high-risk patients: a prospective study conducted in 62 french endoscopy centers

Author

G Boulay, J A Seyrig, J Dubuc, D. Sautereau, Jean-Yves Scoazec, J Butel, M Winnock, T. Barrioz, Thierry Ponchon, J P Barbier, D Grasset, D Grigoresco, R. Laugier, Jean-Louis Legoux, and Société Française d'Endoscopie Digestive

Subjects
Adult, Male, medicine.medical_specialty, Esophageal Neoplasms, Sensitivity and Specificity, Gastroenterology, Risk Factors, Internal medicine, Biopsy, medicine, Carcinoma, Humans, Esophagus, Coloring Agents, Prospective cohort study, Aged, Aged, 80 and over, Staining and Labeling, medicine.diagnostic_test, business.industry, Biopsy, Needle, Cancer, Iodides, Middle Aged, medicine.disease, Endoscopy, medicine.anatomical_structure, Dysplasia, Carcinoma, Squamous Cell, Pancreatitis, Female, Esophagoscopy, business, Precancerous Conditions
Abstract

BACKGROUND AND STUDY AIMS The prevalence of esophageal squamous-cell carcinoma in high-risk patients and the advantages of systematic Lugol staining during esophagoscopy have not yet been evaluated in a large prospective study. In this study we aimed to assess the prevalence of this type of tumor in high-risk patients, to examine the role of Lugol staining in endoscopic screening for esophageal squamous-cell carcinoma, and to establish whether it is possible to identify a particularly high-risk group which would benefit from systematic screening. PATIENTS AND METHODS A prospective study was undertaken in 62 endoscopy centers. A total of 1095 patients were enrolled, none of whom had any esophageal symptoms. These patients had presented with either a past history of or a recent head and neck or tracheobronchial squamous-cell carcinoma (group 1), with alcoholic chronic pancreatitis (group 2), with alcoholic cirrhosis (group 3), or were alcohol and tobacco addicts (group 4). The patients underwent a meticulous endoscopic examination of the esophagus, followed by Lugol staining. RESULTS The prevalence of esophageal squamous-cell carcinoma was 3.2 %. The group 1 patients showed the highest prevalence of carcinoma (5.3 %) and the highest prevalence of dysplasia (4.5 %). Of the 35 carcinomas detected in the 1095 patients, seven (20 %) were early lesions, and 20 % were only detected after Lugol staining (P = 0.02). High-grade dysplasia was only observed in group 1 patients and two-thirds of these lesions were only diagnosed after Lugol staining. The overall prevalence of low-grade dysplasia was 2.4 %, and 77 % of these were detected only after Lugol staining (P < 0.001). CONCLUSIONS Lugol dye staining increases the sensitivity of esophageal endoscopy for the detection of high-grade dysplasia and cancer. The prevalence of dysplasia and cancer reached 9.9 % in group 1, and we therefore believe that an endoscopic screening program could be justified for patients with head and neck or tracheobronchial cancer.

Published
2006
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45. Classic or simplified LV5FU2 regimen: Multivariate analysis from a phase III study in metastatic colorectal cancer in elderly patients

Author

Jean-Marc Phelip, Christophe Locher, Thierry Lecomte, Jean-Louis Jouve, Jean-Louis Legoux, Olivier Bouché, Thomas Aparicio, Laurent Bedenne, Emilie Maillard, and Pierre Michel

Subjects
Cancer Research, medicine.medical_specialty, Multivariate analysis, business.industry, Colorectal cancer, medicine.disease, Gastroenterology, Folinic acid, Regimen, Bolus (medicine), Oncology, Internal medicine, Medicine, business, medicine.drug
Abstract

3550 Background: In the early 2000s, classic LV5FU2 (C) (folinic acid, 5FU bolus, then 5FU infusion on D1 and D2) was replaced with simplified LV5FU2 (S) (folinic acid and 5FU bolus on D1 only), considered as effective and less toxic. No trial proved this assertion. The LV5FU2 companion in the FOLFIRI or FOLFOX regimen was C or S. The FFCD 2001-02 study compared in a 2 x 2 factorial design, in not-pretreated elderly patients (75+) with metastatic colorectal cancer, C or S, with or without irinotecan. No significant differences in PFS and OS were observed in the comparison with or without irinotecan. The median OS was 15.2 months in C versus 11.4 months in S, HR = 0.71 (0.55–0.92) and objective response rate was 37.1% in C vs S 25.6% in S, p = 0.004. The aim of this study was to present the factors associated with these differences. Methods: Prognostic factors associated with OS were studied using a Cox model. The multivariate analysis used the significantly different items from the univariate analysis and the differences observed at the inclusion. For each of these items, a subgroup analysis was performed. The second- and third-line treatments were analysed. Results: The 282 patients from the intent-to-treat study were included in the model. In OS, the prognostic factors were C versus S, number of metastatic sites, alkaline phosphatases (AP) and CEA. The interaction test in each subgroup for OS was not significant but C was significantly better in the following subgroup: age > 80 years, male, Karnofsky 100%, 1-2 Charlson index, AP ≤ 2N, leucocyte count > 11,000, CEA > 2N, CA 19-9 ≤2N. No differences were observed in the NCI toxicities but 130 serious adverse events in S versus 102 in C. A second-line was used for 55% patients in C, 46% in S, 81% of them with oxaliplatin or irinotecan in C, 76% after S. The third-line administration (20%) and targeted therapy (15%) were similar in C and S. Conclusions: C-LV5FU2 was superior both in subgroups with better and lower prognostics and this difference cannot be explained by an imbalance between the populations. The toxicity was not higher and a second-line was more often possible after C. The switch from C to S without scientific proof was perhaps a mistake in our practices. Clinical trial information: NCT00303771.

Published
2017
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46. [Untitled]

Author

C. Moesch, B. Desaint, V. de Ledinghen, Jean-Louis Legoux, G. Grollier, B. Person, Pierre Ingrand, A. Le Sidaner, D. Sautereau, M. Greff, and Michel Beauchant

Subjects
medicine.medical_specialty, Physiology, business.industry, medicine.medical_treatment, Gastroenterology, Stent, medicine.disease, Ursodeoxycholic acid, Surgery, law.invention, Cholestasis, Randomized controlled trial, Biliary tract, law, Multicenter trial, medicine, business, Norfloxacin, medicine.drug, Antibacterial agent
Abstract

We report a prospective randomized multicenter trial that tested the efficacy of combining ursodeoxycholic acid and norfloxacin in the prevention of polyethylene stent clogging in patients with obstructive jaundice due to an unresectable malignancy at the level of the common bile duct. After insertion of a 10-Fr straight polyethylene stent, patients were allocated to receive oral treatment with ursodeoxycholic acid and norfloxacin, or conservative treatment. The primary outcome measure was stent blockage within six months. Thirty-three patients (group I) received ursodeoxycholic acid and norfloxacin, and 29 received conservative treatment (group II). At six months, cumulative stent patency rate did not differ significantly between group I (47 ± 11%, mean ± se, median 149 days) and group II patients (24 ± 10%, mean ± se, median 100 days, P = 0.23, log-rank test). Four stents were clogged by ursodeoxycholic acid. Survival did not differ between the two groups. Combined therapy with ursodeoxycholic acid and norfloxacin failed to improve stent patency. Moreover, ursodeoxycholic acid can cause stent obstruction.

Published
2000
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47. FOLFIRI+bevacizumab induction chemotherapy followed by bevacizumab or observation in metastatic colorectal cancer, a phase III trial (PRODIGE 9 – FFCD 0802)

Author

Karine Le Malicot, Julien Taieb, Thomas Aparicio, Eric Francois, François Ghiringhelli, Olivier Bouché, Laurent Bedenne, Laetitia Dahan, Meher Ben Abdelghani, Jean-Louis Legoux, Roger Faroux, Jean-Marc Phelip, Benjamin Linot, and Valérie Boige

Subjects
Oncology, medicine.medical_specialty, Bevacizumab, Colorectal cancer, Leucovorin, Angiogenesis Inhibitors, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Hemotherapy, Humans, Medicine, Neoplasm Metastasis, Randomized Controlled Trials as Topic, Hepatology, Cetuximab, business.industry, Gastroenterology, Induction chemotherapy, Induction Chemotherapy, medicine.disease, Regimen, Clinical Trials, Phase III as Topic, FOLFIRI, Camptothecin, Fluorouracil, Colorectal Neoplasms, business, Progressive disease, medicine.drug
Abstract

During the last 15 years, treatment of patients with metastatic olorectal cancer (mCRC) has undergone major improvements. irst-line treatment combination regimen with 5-fluorouracil and rinotecan (FOLFIRI) was associated with a significant increase in verall survival [1]. The addition of biological agents to chemotherpy, such as the anti-vascular endothelial growth factor and nti-epidermal growth factor receptor monoclonal antibodies evacizumab and cetuximab [2,3] increased survival compared o chemotherapy alone. The duration of first-line combination hemotherapy has been questioned because of toxicities during ong treatments, with a negative impact on patient quality of life. hree phase III studies evaluating sequential chemotherapy (firstine fluoropyrimidine monotherapy followed by second-line dual hemotherapy in case of progressive disease) revealed no survival dvantage compared to first-line combination [4–6]. Therefore, a step-up” strategy became an option in mCRC but has never been valuated with regimens including biological agents. To avoid toxicities, the concept of chemotherapy-free intervals CFIs) as a “top-down” strategy was proposed in different studies 7,8]. In the study by Labianca et al., the experimental arm was the epetition of sequences consisting of 2 months with FOLFIRI folowed by 2 months without chemotherapy, even in the absence f tumour progression [8]: overall survival was the same comared to the arm with continuous chemotherapy. In the OPTIMOX I study, chemotherapy was re-introduced only in case of progresion based on baseline status, and this strategy was less efficient han continuous chemotherapy [7]. Further to these two trials, an lternative therapy is the re-introduction of chemotherapy as soon s progression is detected, i.e. based on last tumour assessment uring chemotherapy; this could increase survival and allow longer

Published
2015
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48. Sclerotherapy with or without Octreotide for Acute Variceal Bleeding

Author

Isabelle Besson, Pierre Ingrand, Bruno Person, Dominique Boutroux, Denis Heresbach, Pierre Bernard, Patrick Hochain, Jacques Larricq, Alain Gourlaouen, Didier Ribard, Nassim Mostefa Kara, Jean-Louis Legoux, Bernard Pillegand, Marie-Claude Becker, Jacques Di Costanzo, Jean-Michel Metreau, Christine Silvain, and Michel Beauchant

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, medicine.medical_treatment, Octreotide, Esophageal and Gastric Varices, Placebo, Gastroenterology, chemistry.chemical_compound, Esophageal varices, Double-Blind Method, Recurrence, Internal medicine, Sclerotherapy, medicine, Humans, Blood Transfusion, Prospective Studies, Treatment Failure, Survival rate, Aged, Vapreotide, Varix, business.industry, General Medicine, Middle Aged, medicine.disease, Surgery, Survival Rate, chemistry, Acute Disease, Regression Analysis, Female, Gastrointestinal Hemorrhage, business, Varices, medicine.drug
Abstract

Sclerotherapy is considered the most effective way to stop bleeding from esophageal varices, but acute variceal bleeding is still associated with a high risk of rebleeding and death. We compared sclerotherapy alone with sclerotherapy and octreotide to control acute variceal bleeding and prevent early rebleeding in patients with cirrhosis.In a double-blind, prospective trial, 199 patients with cirrhosis and acute variceal bleeding who underwent emergency sclerotherapy were randomly assigned to receive a continuous infusion of octreotide (25 micrograms per hour) or placebo for five days. The primary outcome measure was survival without rebleeding five days after sclerotherapy.After five days, the proportion of patients who had survived without rebleeding was higher in the octreotide group (85 of 98 patients, or 87 percent) than in the placebo group (72 of 101, or 71 percent; 95 percent confidence interval for the difference, 4 to 27 percent; P = 0.009). The mean number of units of blood transfused within the first 24 hours after sclerotherapy was lower in the octreotide group (1.2 units; range, 0 to 7) than in the placebo group (2.0 units; range, 0 to 10; P = 0.006). A logistic-regression analysis showed that the treatment assignment (P = 0.003) and the number of blood units transfused before any other treatment was undertaken (P = 0.002) were the only two variables independently associated with survival without rebleeding. After adjustment for base-line differences between the two groups, the odds ratio for treatment failure in the placebo group, as compared with the octreotide group, was 3.3 (95 percent confidence interval, 1.5 to 7.3). The mean (+/- SD) 15-day cumulative survival rate (estimated by the Kaplan-Meier method) was 88 +/- 12 percent in both groups. Side effects were minor, and their incidence was similar in the two groups.In patients with cirrhosis, the combination of sclerotherapy and octreotide is more effective than sclerotherapy alone in controlling acute variceal bleeding, but there is no difference between the overall mortality rates associated with the two approaches to treatment.

Published
1995
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49. End of life (EOL) chemotherapy (CT) in gastro-intestinal (GI) cancer patients (pts): A retrospective AGEO study

Author

Astrid Lièvre, Christophe Locher, Cedric Lecaille, Géraldine Perkins, Alexandra Lapeyre-Prost, A. Pozet, David Tougeron, H. Jaulmes-Bouillot, Julien Taieb, B. Landi, M. Vallee, M. Maillet, Florence Mary, F. Bonnetain, Johann Dreanic, Jean-Louis Legoux, and J.-M. Sabate

Subjects
Chemotherapy, medicine.medical_specialty, Oncology, business.industry, medicine.medical_treatment, Internal medicine, medicine, Hematology, business, Gi cancer, Gastroenterology, Gastro intestinal
Published
2016
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50. PRODIGE 25 (FFCD 11-01) - Phase II randomized trial evaluating aflibercept associated with LV5FU2 regimen as first line treatment of non-resectable metastatic colorectal cancers (FOLFA)

Author

Jean-Louis Legoux, E. Maillard, Valérie Boige, Yann Touchefeu, Nicolas Barriere, M. Baconnier, Y. Rinaldi, Roger Faroux, Joëlle Egreteau, Thomas Aparicio, K. Le Malicot, S. Herrmann-Gandara, Cedric Lecaille, J. Raimbourg, and A. Vimal

Subjects
Oncology, medicine.medical_specialty, business.industry, Hematology, law.invention, First line treatment, Regimen, Randomized controlled trial, law, Internal medicine, Medicine, business, Aflibercept, medicine.drug
Published
2016
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