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1. Daily practices in chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma: METESTOMAC French prospective cohort

Author

Sylvain Manfredi, Marie Dior, Olivier Bouche, Emilie Barbier, Vincent Hautefeuille, Marielle Guillet, Justine Turpin, Vincent Bourgeois, Dall Osto Helene, Romain Desgrippes, Franck Audemar, Yann Molin, Christophe Locher, Thierry Chatellier, Thierry Lecomte, Nathalie Baize, Cedric Lecaille, Dominique Spaeth, Gael Goujon, Come Lepage, David Tougeron, and For The Metestomac Investigators/Collaborators

Subjects
cohort, gastric cancer, real life, strategy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Around 50% of gastric cancers are diagnosed at an advanced stage. Several chemotherapy regimens are now internationally validated. Few data are available on the routine daily management of advanced gastric or gastroesophageal junction cancers. We aimed to describe chemotherapy practices, tolerance, and efficacy overall survival (OS) and Progression free survival (PFS) in a prospective French cohort. Methods Patients starting palliative chemotherapy were prospectively enrolled in 49 French centres. The primary objective was to report and describe patients' characteristics and treatment strategies. Secondary objectives were OS, PFS, objective response rate, adverse events rate, performance status deterioration during the chemotherapy. Results A total of 182 patients were included; 179 were analysed. Most patients received platinium‐based chemotherapy as the first treatment and FOLFIRI as second; 62.0% of patients received a second line, and 32.4% a third line. More than two thirds of Her2‐positive patients were first treated with trastuzumab. The FOLFIRI regimen was the most frequently used second‐line therapy. Median OS was 13.3 months, similar whatever the chemotherapy or combinations used in the first line. One‐ and 2‐year OS increased with the number of chemotherapy lines received, from respectively 24.7% and 5.7% (1 line), to 46.9% and 12.4% (2 lines) and 88.1% and 29.9% (3 or more lines) (p

Published
2023
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2. Prognosis and chemosensitivity of non-colorectal alimentary tract cancers with microsatellite instability

Author

Claire Boyer, David Sefrioui, Romain Cohen, Romain Chautard, Marine Perrier, Hugo Lebrun, Gael Goujon, Vincent Hautefeuille, Marie Dior, Thomas Walter, Florence Mary, Silvain Manfredi, Francois-Xavier Caroli-Bosc, Baptiste Cervantes, Romain Coriat, Elise Deluche, Aziz Zaanan, Raphael Olivier, Olivier Bouché, Guillaume Piessen, Thierry Lecomte, Christophe Louvet, Pierre Michel, Thomas Aparicio, Thierry André, Julien Taieb, Violaine Randrian, David Tougeron, Centre hospitalier universitaire de Poitiers (CHU Poitiers), 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Université Paris Cité (UPCité), Centre de Bioinformatique (CBIO), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Hôpital Avicenne [AP-HP], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital Cochin [AP-HP], CHU Limoges, 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), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Hepatology, [SDV]Life Sciences [q-bio], Gastroenterology, Humans, Microsatellite Instability, Middle Aged, Prognosis, Colorectal Neoplasms, Colorectal Neoplasms, Hereditary Nonpolyposis, DNA Mismatch Repair
Abstract

Data on outcomes of microsatellite instable and/or mismatch repair deficient (dMMR/MSI) digestive non-colorectal tumors are limited.To evaluate overall survival (OS) of patients with dMMR/MSI digestive non-colorectal tumor.All consecutive patients with a dMMR/MSI digestive non-colorectal tumor were included in this French retrospective multicenter study.One hundred and sixteen patients were included with a mean age of 63.6 years and 32.6% with a Lynch syndrome. Most tumors were oesophago-gastric (54.3%) or small bowel (32.8%) adenocarcinomas and at a localized stage at diagnosis (86.7%). In patients with localized tumors and R0 resection, median OS was 134.0 ± 64.2 months. Median disease-free survival (DFS) was 100.3 ± 65.7 months. Considering oesophago-gastric tumors, median DFS was improved when chemotherapy was added to surgery (not reached versus 22.8 ± 10.0 months, p = 0.03). In patients with advanced tumors treated by chemotherapy, median OS was 14.2 ± 1.9 months and median progression-free survival was 7.4 ± 1.6 months.dMMR/MSI digestive non-colorectal tumors are mostly diagnosed at a non-metastatic stage with a good prognosis. Advanced dMMR/MSI digestive non-colorectal tumors have a poor prognosis with standard chemotherapy.

Published
2023
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3. <scp>FOLFIRI</scp> plus <scp>BEvacizumab</scp> or <scp>aFLIbercept</scp> after <scp>FOLFOX</scp> ‐bevacizumab failure for <scp>COlorectal</scp> cancer ( <scp>BEFLICO</scp> ): An <scp>AGEO</scp> multicenter study

Author

Cécile Torregrosa, Simon Pernot, Pauline Vaflard, Audrey Perret, Christophe Tournigand, Violaine Randrian, Solene Doat, Cindy Neuzillet, Valérie Moulin, Morgane Stouvenot, Gael Roth, Tiffany Darbas, Benjamin Auberger, Tiphaine Godet, Marion Jaffrelot, Aurélien Lambert, Olivier Dubreuil, Cassandre Gluszak, Alice Bernard‐Tessier, Anthony Turpin, Lola‐Jade Palmieri, Olivier Bouche, Gael Goujon, Thierry Lecomte, David Sefrioui, Christophe Locher, Lucien Grados, Pauline Gignoux, Stéphanie Trager, Elise Nassif, Angélique Saint, Pascal Hammel, Cédric Lecaille, Mathilde Bureau, Marine Perrier, Damien Botsen, Vincent Bourgeois, Julien Taieb, and Edouard Auclin

Subjects
Cancer Research, Oncology
Published
2022
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4. Daily practices in chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma: METESTOMAC French prospective cohort

Author

Sylvain, Manfredi, Marie, Dior, Olivier, Bouche, Emilie, Barbier, Vincent, Hautefeuille, Marielle, Guillet, Justine, Turpin, Vincent, Bourgeois, Dall Osto, Helene, Romain, Desgrippes, Franck, Audemar, Yann, Molin, Christophe, Locher, Thierry, Chatellier, Thierry, Lecomte, Nathalie, Baize, Cedric, Lecaille, Dominique, Spaeth, Gael, Goujon, Come, Lepage, and David, Tougeron

Abstract

Around 50% of gastric cancers are diagnosed at an advanced stage. Several chemotherapy regimens are now internationally validated. Few data are available on the routine daily management of advanced gastric or gastroesophageal junction cancers. We aimed to describe chemotherapy practices, tolerance, and efficacy overall survival (OS) and Progression free survival (PFS) in a prospective French cohort.Patients starting palliative chemotherapy were prospectively enrolled in 49 French centres. The primary objective was to report and describe patients' characteristics and treatment strategies. Secondary objectives were OS, PFS, objective response rate, adverse events rate, performance status deterioration during the chemotherapy.A total of 182 patients were included; 179 were analysed. Most patients received platinium-based chemotherapy as the first treatment and FOLFIRI as second; 62.0% of patients received a second line, and 32.4% a third line. More than two thirds of Her2-positive patients were first treated with trastuzumab. The FOLFIRI regimen was the most frequently used second-line therapy. Median OS was 13.3 months, similar whatever the chemotherapy or combinations used in the first line. One- and 2-year OS increased with the number of chemotherapy lines received, from respectively 24.7% and 5.7% (1 line), to 46.9% and 12.4% (2 lines) and 88.1% and 29.9% (3 or more lines) (p 0.0001).Our study showed that treatment strategies in France are based on a succession of doublets, making it possible to offer a second and third line of treatment more often. This treatment strategy must be taken into account for future trials with immunotherapy combinations.

Published
2022

5. 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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6. Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study)

Author

Isabelle Trouilloud, Nabil Baba-Hamed, Marie-Pierre Galais, David Tougeron, Romain Coriat, Jean-Philippe Metges, Olivier Bouché, Jean-Marc Phelip, Lola-Jade Palmieri, Laurent Mineur, Benoit Rousseau, Victoire Granger, Lea Saban-Roche, Pierre Michel, Julie Henriques, Jean-Marc Gornet, Emilie Soularue, Astrid Lièvre, Denis Smith, Dewi Vernery, Stéphane Obled, Gael Goujon, Christophe Locher, Anne-Laure Bignon-Bretagne, Gaetan Des Guetz, Sylvain Manfredi, Solene Doat, Bruno Buecher, Marie Dior, Carole Vitellius, Simon Pernot, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Sainte Catherine [Avignon], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Centre Hospitalier Universitaire [Grenoble] (CHU), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Bordeaux [Bordeaux], CHU Pontchaillou [Rennes], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-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), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut Curie [Paris], Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier de Meaux, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Louis Mourier - AP-HP [Colombes], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Michallon, 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), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Growth factor receptor, Interquartile range, Internal medicine, Gastrointestinal Cancer, Antineoplastic Combined Chemotherapy Protocols, Anti‐epidermal growth factor receptor, Humans, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Chemotherapy, Metastatic colorectal cancer, business.industry, Hazard ratio, Antibodies, Monoclonal, medicine.disease, RAS status, 3. Good health, 030220 oncology & carcinogenesis, Propensity score matching, Fluorouracil, Colorectal Neoplasms, business, medicine.drug
Abstract

Background Patients with RAS wild‐type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti‐epidermal growth factor receptor (EGFR) combined with first‐line, 5‐fluorouracil‐based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti‐EGFR. Our objective was to compare both strategies in a routine practice setting. Materials and Methods This multicenter, retrospective, propensity score–weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5‐FU‐based chemotherapy, with either delayed anti‐EGFR or immediate anti‐vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression‐free survival (PFS) and objective response rate (ORR). Results A total of 262 patients (129 in the anti‐VEGF group and 133 in the anti‐EGFR group) were included. Patients receiving an anti‐VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13–26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69–1.08, p = .2024). The delayed introduction of anti‐EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61–0.90, p = .0024). ORR was significantly higher in the anti‐EGFR group (66.7% vs. 45.6%, p = .0007). Conclusion Delayed introduction of anti‐EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti‐VEGF. Implications for Practice For RAS/RAF wild‐type metastatic colorectal cancer, patients may receive 5‐fluorouracil‐based chemotherapy plus either bevacizumab or an anti‐epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti‐EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti‐EGFR on survival, compared with the introduction of an anti‐vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti‐EGFR while waiting for RAS status., More than half of the cases of metastatic colorectal cancer harbor a RAS mutation; however, the time to obtain RAS status might be long enough to consider delayed anti‐EGFR treatment. This article reports on the two main treatment strategies for these cases.

Published
2019
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7. Prevalence and prognosis of microsatellite instability in oesogastric adenocarcinoma, NORDICAP 16-01

Author

Gael Goujon, Nathalie Théou-Anton, Nicolas Poté, My-Linh Tran-Minh, Philippe Bertheau, Marie Dior, Nahla Cucherousset, Charlotte Gardair, for Nordicap, Rachid Kaci, Olivier Schischmanoff, Anne Couvelard, Florence Mary, Thomas Aparicio, Jérôme Lambert, and Jacqueline Lehmann-Che

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Adenocarcinoma, MLH1, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Internal medicine, medicine, Prevalence, Humans, In patient, Cumulative incidence, neoplasms, Genotyping, Retrospective Studies, Hepatology, business.industry, nutritional and metabolic diseases, Microsatellite instability, medicine.disease, Prognosis, digestive system diseases, Multicenter study, 030220 oncology & carcinogenesis, DNA methylation, 030211 gastroenterology & hepatology, Microsatellite Instability, business, MutL Protein Homolog 1
Abstract

Background The prevalence and prognosis association of microsatellite instability (MSI) in oesogastric junction and gastric adenocarcinoma (OGC) have been reported with conflicting results. Methods Patients with OGC from 2010 to 2015 were enrolled in this retrospective multicenter study. MSI was determined by genotyping. MLH1 promoter methylation and BRAF V600E mutation were screened in the MSI tumors. Results Among 315 tumors analyzed, 39 (12.4%) were of the MSI phenotype. Compared to MSS tumors, MSI tumors were more frequent in patients > 70 years (17% vs 9%, p = 0.048) and in gastric antral primary (20% versus 5% in junction tumor and 12% in fundus tumor. Among 29 MSI tumors analyzed, 28 had a loss of MLH1 protein expression and 27 had MLH1 promotor hypermethylation. None had a BRAF V600E mutation. The 4-year cumulative incidence of recurrence for patients with resected tumor was significantly lower in dMMR tumors versus pMMR tumors (17% versus 47%, p = 0.01). For the patients with unresectable tumor the median overall survival was 11 months in MSS group and 14 months in MSI group (p = 0.24). Conclusion MSI prevalence in OGC was 12.4%, associated with antral localization and advanced age. Patients with MSI tumors had a lower cumulative incidence of recurrence after surgery. MSI phenotype was mainly associated with loss of MLH1 protein expression, MLH1 promotor hypermethylation and had no BRAF V600E mutation.

Published
2020

8. 1454P PARAFIRIGAST: Paclitaxel/ramucirumab versus FOLFIRI as second line chemotherapy of metastatic gastric cancer: An AGEO multicenter comparative study with a propensity score analysis

Author

A. Pellat, C. Toullec, M. Kroemer, David Tougeron, J. Vivier-Chicoteau, J. Lavole, B. De Rauglaudre, Astrid Pozet, Gael Goujon, David Sefrioui, Yann Touchefeu, Vincent Hautefeuille, A.L. Bignon Bretagne, Carole Vitellius, J. Wasselin, Anthony Turpin, O. Bouche, A. Zaanan, S. Racine Doat, and Cristina Smolenschi

Subjects
Oncology, medicine.medical_specialty, business.industry, Hematology, Second line chemotherapy, Metastatic gastric cancer, Ramucirumab, chemistry.chemical_compound, Paclitaxel, chemistry, Internal medicine, Propensity score matching, medicine, FOLFIRI, business
Published
2020
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9. Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: An AGEO retrospective multicenter study

Author

Cedric Lecaille, Yann Touchefeu, Julien Taieb, Aurélie Ferru, Gael Goujon, Gaetan Des Guetz, Vincent Hautefeuille, Romain Coriat, Thomas Aparicio, David Tougeron, Camille Evrard, David Sefrioui, Julie Henriques, Thierry Lecomte, Lucie Gentilhomme, Romain Chautard, Dewi Vernerey, Thierry André, Christophe Locher, Christelle De La Fouchardiere, Aziz Zaanan, Pascal Artru, Romain Cohen, Benjamin Sueur, and Valérie Moulin

Subjects
Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, Colorectal cancer, medicine.medical_treatment, Population, Irinotecan, DNA Mismatch Repair, Targeted therapy, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, education, neoplasms, Aged, Retrospective Studies, Aged, 80 and over, Chemotherapy, education.field_of_study, business.industry, Microsatellite instability, Middle Aged, medicine.disease, Prognosis, Chemotherapy regimen, Survival Analysis, digestive system diseases, Progression-Free Survival, Oxaliplatin, DNA Repair Enzymes, 030220 oncology & carcinogenesis, Female, Microsatellite Instability, Fluorouracil, business, Colorectal Neoplasms, medicine.drug
Abstract

Mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI) colorectal cancers (CRC) represent about 5% of metastatic CRC (mCRC). Prognosis and chemosensitivity of dMMR/MSI mCRC remain unclear. This multicenter study included consecutive patients with dMMR/MSI mCRC from 2007 to 2017. The primary endpoint was the progression-free survival (PFS) in a population receiving first-line chemotherapy. Associations between chemotherapy regimen and survival were evaluated using a Cox regression model and inverse of probability of treatment weighting (IPTW) methodology in order to limit potential biases. Overall, 342 patients with dMMR/MSI mCRC were included. Median PFS and overall survival (OS) on first-line chemotherapy were 6.0 and 26.3 months, respectively. For second-line chemotherapy, median PFS and OS were 4.4 and 21.6 months. Longer PFS (8.1 vs. 5.4 months, p = 0.0405) and OS (35.1 vs. 24.4 months, p = 0.0747) were observed for irinotecan-based chemotherapy compared to oxaliplatin-based chemotherapy. The association was no longer statistically significant using IPTW methodology. In multivariable analysis, anti-VEGF as compared to anti-EGFR was associated with a trend to longer OS (HR = 1.78, 95% CI 1.00-3.19, p = 0.0518), whatever the backbone chemotherapy used. Our study shows that dMMR/MSI mCRC patients experienced short PFS with first-line chemotherapy with or without targeted therapy. OS was not different according to the chemotherapy regimen used, but a trend to better OS was observed with anti-VEGF. Our study provides some historical results concerning chemotherapy in dMMR/MSI mCRC in light of the recent nonrandomized trials with immune checkpoint inhibitors.

Published
2019

10. 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

11. Efficacy of modern chemotherapy and prognostic factors in patients with ovarian metastases from gastric cancer: A retrospective AGEO multicentre study

Author

Gael Goujon, Bertrand Brieau, Astrid Pozet, Olivier Bouché, Caroline Prieux, Julien Taieb, Pauline Soibinet, David Tougeron, Michel Ducreux, Thierry Lecomte, Franck Bonnetain, Claire Auzolle, Aziz Zaanan, Philippe Rougier, Romain Coriat, and Lysiane Marthey

Subjects
0301 basic medicine, Oncology, endocrine system diseases, medicine.medical_treatment, Kaplan-Meier Estimate, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Prospective cohort study, Aged, 80 and over, Ovarian Neoplasms, Gastroenterology, Middle Aged, Prognosis, Magnetic Resonance Imaging, female genital diseases and pregnancy complications, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Taxoids, Fluorouracil, France, medicine.drug, Epirubicin, Adult, Bridged-Ring Compounds, medicine.medical_specialty, Adolescent, Ovariectomy, Antineoplastic Agents, Irinotecan, Young Adult, 03 medical and health sciences, Stomach Neoplasms, Internal medicine, Humans, Aged, Proportional Hazards Models, Retrospective Studies, Chemotherapy, Taxane, Hepatology, business.industry, Oophorectomy, Cancer, Retrospective cohort study, medicine.disease, 030104 developmental biology, Multivariate Analysis, Camptothecin, Cisplatin, Tomography, X-Ray Computed, business
Abstract

Background Ovarian metastases from gastrointestinal tumours frequently lead to locoregional complications and undermine quality of life. The chemosensitivity of ovarian metastases from gastric cancer is unknown. Aim To evaluate the efficacy of modern chemotherapy regimens in first-line treatment for patients with ovarian metastases from gastric cancer. Methods All consecutive patients with ovarian metastases from gastric cancer who received at least one cycle of chemotherapy were included in this retrospective study. Results Thirty-five patients were included (median age, 50.5 years; synchronous ovarian metastases, 60%). Seventeen patients (48.6%) underwent oophorectomy. Patients were treated with first-line chemotherapy based on platinum (n = 14), irinotecan (n = 8), taxane plus platinum (n = 4) or epirubicin plus platinum (n = 9). The median PFS and OS were 6.8 and 18.8 months, respectively. The objective response rate (ORR) for extra-ovarian (13.6%) and ovarian (20.9%) metastatic sites was not significantly different (p = 0.55). There was no significant difference in terms of ORR on ovarian metastatic site according to the first-line chemotherapy (p = 0.21). In multivariate analysis, oophorectomy was an independent prognostic factor for OS (p Conclusions This study suggests that ovarian metastases from gastric cancer are not more resistant than extra-ovarian metastases, and that oophorectomy is an independent prognostic factor significantly linked to OS. Prospective studies are needed to confirm these results.

Published
2016
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12. 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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13. 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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14. FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide–platinum combination in patients with neuroendocrine carcinomas grade 3

Author

Vinciane Rebours, Olivia Hentic, Magaly Zappa, Frédérique Maire, Anne Couvelard, Gael Goujon, Pascal Hammel, Adeline Gillet, Maxime Palazzo, Philippe Lévy, and Philippe Ruszniewski

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Leucovorin, Neutropenia, Disease-Free Survival, Endocrinology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, FOLFIRI Regimen, Humans, Prospective cohort study, Etoposide, Aged, Pelvic Neoplasms, Platinum, Chemotherapy, Performance status, business.industry, Liver Neoplasms, Middle Aged, Anus Neoplasms, medicine.disease, Carcinoma, Neuroendocrine, Pancreatic Neoplasms, Irinotecan, Treatment Outcome, FOLFIRI, Camptothecin, Female, Fluorouracil, Neoplasm Grading, business, medicine.drug
Abstract

Patients with neuroendocrine carcinomas (NECs) grade 3 have a poor prognosis. Etoposide–platinum combination is the standard chemotherapy but the role of a second-line therapy remains unknown. Irinotecan alone or in combination has shown some efficacy in patients treated for small cell lung cancer which had pathological similarities with neuroendocine tumors. The aim of this study is to determine safety and efficacy of the FOLFIRI regimen in patients with NECs grade 3 after failure of etoposide–platinum combination. This study was retrospective, including patients with NECs grade 3 and treated with the FOLFIRI regimen after progression or toxicity of etoposide–platinum combination in first-line. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≥3 and/or serum alkaline phosphatase ≥5×upper limit of normal value (ULN) and/or bilirubin ≥1.5×ULN were excluded. Among 39 patients who failed etoposide–platinum combination, 19 (49%; 12 women, median age 53 (29–78) years) received the FOLFIRI regimen with a median number of 6 (1–16) courses. Six patients (31%) had at least one episode of grades 3–4 toxicity (neutropenia, n=3; diarrhea, n=3) without toxic death. Six patients (31%) had objective response, 6 (31%) stable disease, and 7 (38%) tumor progression. Median progression-free survival under FOLFIRI was 4 months. Overall survival was 18 vs 6.8 months in noneligible patients. FOLFIRI regimen is a safe and potentially efficient chemotherapy given as second-line in patients with NECs grade 3 who remain in good condition and with correct liver tests after failure of etoposide–platinum combination. These results should be confirmed in a future prospective study.

Published
2012
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15. A large multicenter study evaluating prognosis and chemosensitivity of metastatic colorectal cancers with microsatellite instability.

Author

Tougeron, David, primary, Sueur, Benjamin, additional, Sefrioui, David, additional, Gentilhomme, Lucie, additional, Lecomte, Thierry, additional, Aparicio, Thomas, additional, DES Guetz, Gaetan, additional, Artru, Pascal, additional, De La Fouchardiere, Christelle, additional, Moulin, Valérie, additional, Hautefeuille, Vincent, additional, Coriat, Romain, additional, Touchefeu, Yann, additional, Lecaille, Cedric, additional, Gael, Goujon, additional, Ferru, Aurélie, additional, Tourani, Jean-Marc, additional, Emambux, Sheik, additional, Taieb, Julien, additional, and Zaanan, Aziz, additional

Published
2017
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16. A large retrospective multicenter study evaluating prognosis and chemosensitivity of metastatic colorectal cancer with microsatellite instability

Author

Pascal Artru, Régis Cohen, Vincent Hautefeuille, Yann Touchefeu, Julien Taieb, Benjamin Sueur, Gael Goujon, Romain Coriat, Cedric Lecaille, Thomas Aparicio, Aurélie Ferru, G. Des Guetz, David Tougeron, C. de la Fouchardiere, T. Andre, A. Zaanan, Valérie Moulin, Lucie Gentilhomme, Thierry Lecomte, and David Sefrioui

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Colorectal cancer, business.industry, Microsatellite instability, Hematology, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Multicenter study, 030220 oncology & carcinogenesis, Internal medicine, medicine, business
Published
2017
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17. Colorectal cancer (CRC) patients surveyed by 18FDGPET-CT (PET-CT): An open-label multicenter randomized trial (NCT 00624260)

Author

Isabelle Durand-Zaleski, Thierry André, Michel Ducreux, Julien Taieb, Richard Layese, Iradj Sobhani, Thomas Aparicio, Gael Goujon, Christophe Tournigand, Jean Marc Gornet, Pierre Andre Natella, Isabelle Baumgaertner, Emmanuel Itti, Jean-Baptiste Bachet, Alain Luciani, François Hemery, and Sylvie Bastuji Garin

Subjects
Cancer Research, medicine.medical_specialty, PET-CT, business.industry, Colorectal cancer, medicine.disease, law.invention, 03 medical and health sciences, 0302 clinical medicine, Oncology, Randomized controlled trial, law, Curative surgery, Medicine, 030211 gastroenterology & hepatology, 030212 general & internal medicine, Radiology, Open label, business
Abstract

3520 Background: Curative surgery is the best therapy of CRC and recurrences. We assessed whether adding semi-annual PET-CT to the usual surveillance would be cost-effective in high risk recurrent CRC patients. Methods: CRC patients (stage II tumor perforated, stages III and IV) in remission after curative surgery were randomly assigned (1:1) to trimester usual surveillance (control) or usual surveillance + semi-annual course PET-CT (intervention) for a 3-yr follow up period. Every 3 months, multidisciplinary committee decided about recurrence by yes/no/doubtful. If yes, curative surgery alone (when relevant), or chemotherapy alone (unresecable recurrence) were conducted; additional exams could be performed if doubtful. Primary composite endpoint (failure) comprised unresectable recurrence & death. The economic assessments according to standards (CHEERS) were performed and costs were compared between groups. Statistical tests for calculation of the relative risk (RR) were used and survival was analyzed using Kaplan-Meier method, Log-Rang test and Cox models. Results: Baseline characteristics of 239 patients (120/119) enrolled in 12 centers were balanced. The failure rate was 29.2% (31 unresectable recurrences & 4 deaths) and 23.5% (27 & 1) in Interventional vs Control, respectively with no significant difference (RR = 1.24, 95% CI: 0.81-1.90; P = .32). Similar results were observed in multivariate analysis (Cox models) adjusted for stage and tumor differentiation (HR = 1.33, 95% CI: 0.8-2.19, P = .27). Period until the unresectable recurrence was significantly shorter in Interventional (median = 7; IQR: 3-20 months) than in Control group (14.3; 7.3-27; P= 0.016). This was consistent with lower elevation (median; IQR) of tumour marker in interventional (3.8; 2.8-19) than in control group (10; 5.2-28.6) at the first recurrence time as compared to the baseline (p = 0.007). Overall (mean; SD) cost (euros)/patient was higher in the PET-Scan (9385; 11658) than in the control group (7027; 7656). Conclusions: Although recurrences were detected earlier in PET-CT group, the strategy was less effective, more expensive. This exam should not be advised routinely. Clinical trial information: NCT 00624260.

Published
2017
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18. Solid and pseudopapillary tumours of the pancreas: Are the epidemiology and imaging features changing?

Author

Marie-Pierre Vullierme, Philippe Ruszniewski, Jérôme Cros, Alain Sauvanet, Sébastien Gaujoux, Vinciane Rebours, Frédérique Maire, Gael Goujon, Anne Couvelard, Philippe Lévy, Pascal Hammel, and Olivia Hentic

Subjects
medicine.medical_specialty, Pathology, medicine.anatomical_structure, Hepatology, business.industry, Endocrinology, Diabetes and Metabolism, Epidemiology, Gastroenterology, medicine, Pancreas, business
Published
2012
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