Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX.

Jean-François Emile 1, * Catherine Julié 2 Karine Le Malicot 3 Come Lepage 4, 5, 6 Josep Tabernero 7 Enrico Mini 8 Gunnar Folprecht 9 Jean-Luc Van Laethem 10 Stéphanie Dimet Camille Boulagnon-Rombi Marc-Antoine Allard 11 Frédérique Penault-Llorca 12 Jaafar Bennouna 13, 14, 15 Pierre Laurent-Puig 16 Julien Taieb Jos Thaler 17 Richard Greil 18 Johannes Gaenzer Wolfgang Eisterer Joerg Tschmelitsch Felix Keil 19 Hellmut Sa August Zabernigg Franz Schmid 20 Günther Steger 21 Rob Steinacher Johannes Andel 22 Björn Jagdt Alois Lang Michael Fridrik 23 Reinhold Függer Friedrich Hofbauer Ewald Woell Dietmar Geissler 24 Alfred Lenauer Manfred Prager 25 Geert D'Haens Gauthier Demolin Josep Kerger Guido Deboever Gilbert Gil 26 Marc Polus Eric Van Cutsem 27, 28 Hassan Rezaie Kalantari 29 Thierry Delaunoit Jean Charles Goeminne Marc Peeters 30 Philippe Vergauwe Ghislain Houbiers Yves Humblet Jan Janssens Dirk Schrijvers 31 Erik Vanderstraeten 32 Jan Vermorken 33 Daniel Van Daele Michel Michel 34 F. Forget 35 Alain Hendlisz Mette Yilmaz 36 Svend Erik Nielsen 37 Lene Vestermark 38, 39 Jim Larsen 40 Mohamed Zawadi Olivier Bouche 41 Laurent Mineur Jaafar Bennouna-Louridi Louis Marie Dourthe Marc Ychou 42 Eveline Boucher 43 Denis Denis 44 Francoise Desseigne Patrick Texereau 45 Laurent Miglianico Philippe Rougier 46 Serge Fratte 47 Charles-Briac Levache 48 Yacine Merrouche 49 Stephen Ellis Christophe Locher 50 Jean-Francois Ramee 51 Claire Garnier 52 Frederic Viret 53 Bruno Chauffert 54 Isabelle Cojean-Zelek 55 Pierre Michel 56 Cedric Lecaille Christian Borel 57 Jean-Francois Seitz 58 Catherine Lombard-Bohas 59 Thierry Andre 60, 61 Jean-Marc Gornet 62 Francine Fein 63 Marie-Aude Coulon-Sfairi Marie-Christine Kaminsky 64 Jean-Paul Lagasse Dominique Luet 45 Pierre Etienne 65 Mohamed Gasmi 66 Andre Vanoli Suzanne Nguyen 67 Thomas Aparicio 68 Hervé Perrier Noel Stremsdoerfer Philippe Laplaige 69 Dominique Arsene 70 Dominique Auby 71 Laurent Bedenne 72 Romain Coriat 73 Patrick Geoffroy 74, 75 Gilles Gil 26 Yves Becouarn 76 Gael Deplanque 77 Olivier Dupuis 78 Frederic Fruge Rosine Guimbaud 79 Thierry Lecomte 80 Gérard Lledo 81, 42 Iradej Sobhani 82 Amani Asnacios 83 Ahmed Azzedine Christophe Desauw Pierre Galais Dany Gargot You-Heng Lam Abakar Abakar-Mahamat Jean-Francois Berdah 84 Sylviane Catteau Marie-Christine Clavero-Fabri Jean-Francois Codoul Jean-Louis Legoux 85 Denis Goldfain Pierre Guichard 86 Denis Verge 87 Jocelyne Provencal Bruno Vedrenne Catherine Brezault-Bonnet Denis Cleau 63 Jean-Paul Desir 88 David Fallik Bruno Garcia Marie-Hélène Gaspa Dominique Genet 89 Johannes Hartwig Yves Krummel 90 Tamara Matysiak Budnik Vanessa Palascak-Juif 91 Harizo Randrianarivelo Yves Rinaldi 92 Albert Aleba Ariane Darut-Jouve Aimery De Gramont 60 Herve Hamon Frederic Wendehenne Axel Matzdorff 93 Michael Stahl Wolfgang Schepp Martin Burk Lothar Mueller 94 Michael Geissler Luis Mantovani Thomas Hoehler 95 Walter Asperger Hendrik Kroening Ludwig Fischer Von Weikersthal Stefan Fuxius Matthias Groschek Johannes Meiler 96 Tanja Trarbach Jacqueline Rauh Nicola Ziegenhagen Albrecht Kretzschmar 97 Ullrich Graeven Arnd Nusch Goetz Von Wichert Ralf-Dieter Hofheinz Gerhard Kleber Karl-Heinz Schmidt 98 Ursula Vehling-Kaiser Claudia Baum 99 Jochen Schuette Georg Haag 100 Wilhelm Holtkamp Jochen Potenberg Tobias Reiber Georg Schliesser Hans-Joachim Schmoll Wolfgang Schneider-Kappus Wolfgang Abenhardt Claudio Denzlinger Henning Henning Bartscht Marxsen Hans Guenter Derigs Helmut Lambertz Ingulf Becker-Boost Karel Caca Christian Constantin Thomas Decker 101 Henning Eschenburg Sigrun Gabius Holger Hebart 102 Albrecht Hoffmeister 103 Heinz-August Horst 104 Stephan Kremers Malte Leithaeuser Sebastian Mueller 105 Siegfried Wagner 106 Severin Daum 107 Frank Schlegel Martina Stauch 108 Volker Heinemann Evaristo Maiello Luciano Latini Alberto Zaniboni Dino Amadori 109 Giuseppe Aprile Sandro Sa 110 Rodolfo Mattioli Andrea Martoni Rodolfo Passalacqua Mario Nicolini 111 Enzo Pasquini Carla Rabbi Enrico Aitini Alberto Ravaioli 112 Carlo Barone 113 Guido Biasco Stefano Tamberi Angelo Gambi 114 Claudio Verusio Marina Marzola 115 Giorgio Lelli Corrado Boni 116 Stefano Cascinu 117 Paolo Bidoli Massimo Vaghi Giorgio Cruciani Francesco Costa 118 Alberto Sobrero Rob Petrioli Massimo Aglietta Oscar Alabiso Federico Capuzzo Alfredo Falcone Domenico Cristi Corsi 119 Rob Labianca 120 Stefania Sa 110 Silvana Chiara Libero Ciuffreda Francesco Ferraù 121 Francesco Giuliani Sara Sa 110 Nicola Gebbia Giovanni Mantovani Evaristo Sa Juan Carlos Mellidez Pedro Sa Joao Freire Cristina Sa 122, 123 Luis Costa 124 Antonio Moreira Pinto 125, 126 Sergio Barroso Jorge Espirito Sa Fátima Guedes 127 Amélia Monteiro 128 Anabela Sa 129 Irene Furtado 130 Ramon Salazar Enrique Aranda Aguilar 131, 132 Fernando Rivera Herrero Javier Valera Manuel Valladares Ayerbes Jaime Feliu Batlle Silvia Gil 133 Albert Abad Esteve 134 Carlos Garcia Guillermo Lopez Lopez 135 Antonia Salud Salvia Vicente Alonso Orduña Ruth Vera Garcia 136 Javier Gallego Bartomeu Massuti Sureda Jordi Remon 137 Maria Jose Safont Aguilera Luis Cirera Nogueras Bernado Queralt Merino 138 Cristina Gravalos Castro 139 Purificacion Martinez Martinez 140 Carlos Pijaume Pericay Manuel Constenla Figueiras Inmaculada Guasch Jordan 141 Maria Jose Gome Reina Amelia Lopez-Ladron Garcia 142 Antonio Arrivi Garcia 142 Andres Cervantes 143 Carlos Fernandez Martos Eugenio Marcuello Gaspa Ines Cabezas Montero 144 Pilar Escudero Emperador Ana Leon Carbonero Manuel Gallen Castillo 145 Teresa Garcia Garcia 146 Jose Garcia Garcia Encarnacion Gonzalez Flores Monica Guillot Morales 147 Marta Llanos Muñoz 124 Ana López Martín 148 Joan Maurel Juan Carlos Camara 149 Rosario Dueñas Garcia 136 Mercedes Salgado 150 Isabel Hernandez Busquier Teresa Checa Ruiz 151 Adelaida Lacasta Muñoa Miquel Nogue Aliguer Amalia Velasco Ortiz De Taranco Miguel Mendez Ureña Ferran Losa Gaspa Jose Juan Ponce 152 Carlos Bosch Roig Jim Jimenez 153 Antonio Galan Brotons 154 Santiago Albiol Rodriguez 155 Jose Ales Martinez Liliana Canosa Ruiz 156 Margarita Centelles Ruiz 157, 158 John Bridgewater Rob Glynne-Jones Saad Tahir Tamas Hickish Jim Cassidy 159 Leslie Samuel
* Auteur correspondant
11 Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse
Modèles de Cellules Souches Malignes et Thérapeutiques
111 FEEM
122 NIPE
133 CARE - IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau
IRCELYON - Institut de recherches sur la catalyse et l'environnement de Lyon
Abstract : Background The 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 methods According 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. Results Among 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. Conclusion Although 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.
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Contributeur : Lnc - Université de Bourgogne <>
Soumis le : mercredi 30 août 2017 - 11:28:21
Dernière modification le : mardi 19 juin 2018 - 01:20:23

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Jean-François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, et al.. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX.. European journal of cancer (Oxford, England : 1990), 2017, 82, pp.16-24. 〈http://www.sciencedirect.com/science/article/pii/S0959804917309528?via%3Dihub#!〉. 〈10.1016/j.ejca.2017.04.025〉. 〈hal-01579009〉

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