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

Jean-François Emile * Catherine Julié 1 Karine Le Malicot 2 Come Lepage 3, 4, 5 Josep Tabernero 6 Enrico Mini 7 Gunnar Folprecht 8 Jean-Luc Van Laethem 9 Stéphanie Dimet Camille Boulagnon-Rombi Marc-Antoine Allard 10 Frédérique Penault-Llorca 11 Jaafar Bennouna 12, 13 Pierre Laurent-Puig 14 Julien Taieb Jos Thaler 15 Richard Greil 16 Johannes Gaenzer Wolfgang Eisterer Joerg Tschmelitsch Felix Keil 17 Hellmut Sa August Zabernigg Franz Schmid 18 Günther Steger 19 Rob Steinacher Johannes Andel 20 Björn Jagdt Alois Lang Michael Fridrik 21 Reinhold Függer Friedrich Hofbauer Ewald Woell Dietmar Geissler 22 Alfred Lenauer Manfred Prager 23 Geert D'Haens Gauthier Demolin Josep Kerger Guido Deboever Gilbert Gil 24 Marc Polus Eric Van Cutsem 25, 26 Hassan Rezaie Kalantari 27 Thierry Delaunoit Jean Charles Goeminne Marc Peeters 28, 29 Philippe Vergauwe Ghislain Houbiers Yves Humblet Jan Janssens Dirk Schrijvers 30 Erik Vanderstraeten 31 Jan Vermorken 32 Daniel Van Daele Michel Michel F. Forget 33 Alain Hendlisz Mette Yilmaz 34 Svend Erik Nielsen 35 Lene Vestermark 36, 37 Jim Larsen 38 Mohamed Zawadi Olivier Bouche 39 Laurent Mineur Jaafar Bennouna-Louridi Louis Marie Dourthe Marc Ychou 40 Eveline Boucher 41 Denis Denis 42 Francoise Desseigne Patrick Texereau 43 Laurent Miglianico Philippe Rougier 44 Serge Fratte 45 Charles-Briac Levache 46 Yacine Merrouche 47 Stephen Ellis Christophe Locher 48 Jean-Francois Ramee 49 Claire Garnier 50 Frederic Viret 51 Bruno Chauffert 52 Isabelle Cojean-Zelek 53 Pierre Michel 54 Cedric Lecaille Christian Borel 55 Jean-Francois Seitz 56 Catherine Lombard-Bohas 57 Thierry Andre 58, 59 Jean-Marc Gornet 60 Francine Fein Marie-Aude Coulon-Sfairi Marie-Christine Kaminsky 61 Jean-Paul Lagasse Dominique Luet 43 Pierre Etienne 62 Mohamed Gasmi 63 Andre Vanoli Suzanne Nguyen 64 Thomas Aparicio 65 Hervé Perrier 66, 67 Noel Stremsdoerfer Philippe Laplaige 68 Dominique Arsene 69 Dominique Auby 70 Laurent Bedenne 71 Romain Coriat 72 Patrick Geoffroy 73, 74 Gilles Gil 24 Yves Becouarn 75 Gael Deplanque 76 Olivier Dupuis 77 Frederic Fruge Rosine Guimbaud 78 Thierry Lecomte 79 Gérard Lledo 80, 40 Iradej Sobhani 81 Amani Asnacios 82 Ahmed Azzedine Christophe Desauw Pierre Galais Dany Gargot You-Heng Lam Abakar Abakar-Mahamat Jean-Francois Berdah 83 Sylviane Catteau Marie-Christine Clavero-Fabri Jean-Francois Codoul Jean-Louis Legoux 84 Denis Goldfain Pierre Guichard 85 Denis Verge 86 Jocelyne Provencal Bruno Vedrenne Catherine Brezault-Bonnet Denis Cleau Jean-Paul Desir 87 David Fallik Bruno Garcia Marie-Hélène Gaspa Dominique Genet 88 Johannes Hartwig Yves Krummel 89 Tamara Matysiak Budnik Vanessa Palascak-Juif 90 Harizo Randrianarivelo Yves Rinaldi 91 Albert Aleba Ariane Darut-Jouve Aimery De Gramont 58 Herve Hamon Frederic Wendehenne Axel Matzdorff 92 Michael Stahl Wolfgang Schepp Martin Burk Lothar Mueller 93 Michael Geissler Luis Mantovani Thomas Hoehler 94 Walter Asperger Hendrik Kroening Ludwig Fischer Von Weikersthal Stefan Fuxius Matthias Groschek Johannes Meiler 95 Tanja Trarbach Jacqueline Rauh Nicola Ziegenhagen Albrecht Kretzschmar 96 Ullrich Graeven Arnd Nusch Goetz Von Wichert Ralf-Dieter Hofheinz Gerhard Kleber Karl-Heinz Schmidt 97 Ursula Vehling-Kaiser Claudia Baum 98 Jochen Schuette Georg Haag 99 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 100 Henning Eschenburg Sigrun Gabius Holger Hebart 101 Albrecht Hoffmeister 102 Heinz-August Horst 103 Stephan Kremers Malte Leithaeuser Sebastian Mueller 104 Siegfried Wagner 105 Severin Daum 106 Frank Schlegel Martina Stauch 107 Volker Heinemann Evaristo Maiello Luciano Latini Alberto Zaniboni Dino Amadori 108 Giuseppe Aprile Sandro Sa 109 Rodolfo Mattioli Andrea Martoni Rodolfo Passalacqua Mario Nicolini 110 Enzo Pasquini Carla Rabbi Enrico Aitini Alberto Ravaioli 111 Carlo Barone 112 Guido Biasco Stefano Tamberi Angelo Gambi 113 Claudio Verusio Marina Marzola 114 Giorgio Lelli Corrado Boni 115 Stefano Cascinu 116 Paolo Bidoli Massimo Vaghi Giorgio Cruciani Francesco Costa 117 Alberto Sobrero Rob Petrioli Massimo Aglietta Oscar Alabiso Federico Capuzzo Alfredo Falcone Domenico Cristi Corsi 118 Rob Labianca 119 Stefania Sa 109 Silvana Chiara Libero Ciuffreda Francesco Ferraù 120 Francesco Giuliani Sara Sa 109 Nicola Gebbia Giovanni Mantovani Evaristo Sa 121 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 135 Guillermo Lopez Lopez 136 Antonia Salud Salvia Vicente Alonso Orduña Ruth Vera Garcia 137 Javier Gallego Bartomeu Massuti Sureda Jordi Remon 138 Maria Jose Safont Aguilera Luis Cirera Nogueras Bernado Queralt Merino 139 Cristina Gravalos Castro 140 Purificacion Martinez Martinez 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 137 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, 153 Carlos Bosch Roig Jim Jimenez 154 Antonio Galan Brotons 155 Santiago Albiol Rodriguez 156 Jose Ales Martinez 157 Liliana Canosa Ruiz 158 Margarita Centelles Ruiz 159, 160 John Bridgewater Rob Glynne-Jones Saad Tahir Tamas Hickish Jim Cassidy 161 Leslie Samuel
* Auteur correspondant
10 Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse
Modèles de Cellules Souches Malignes et Thérapeutiques
29 MAB - Méthodes et Algorithmes pour la Bioinformatique
LIRMM - Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier
66 R3AM - Rendu Réaliste pour la Réalité Augmentée Mobile
LIRIS - Laboratoire d'InfoRmatique en Image et Systèmes d'information
67 M2DisCo - Geometry Processing and Constrained Optimization
LIRIS - Laboratoire d'InfoRmatique en Image et Systèmes d'information
110 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
135 imagine - Extraction de Caractéristiques et Identification
LIRIS - Laboratoire d'InfoRmatique en Image et Systèmes d'information
150 SAF- Laboratoire de Sciences Actuarielle et Financière ISFA
SAF - Laboratoire de Sciences Actuarielle et Financière, ISEOR - Institut de Socio-économie des Entreprises et des ORganisations, Centre de Recherche Magellan
152 WILLOW - Models of visual object recognition and scene understanding
DI-ENS - Département d'informatique de l'École normale supérieure, Inria de Paris
157 ALICE - Geometry and Lighting
Inria Nancy - Grand Est, LORIA - ALGO - Department of Algorithms, Computation, Image and Geometry
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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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01579009
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : mercredi 30 août 2017 - 11:28:21
Dernière modification le : samedi 23 septembre 2017 - 01:07:49

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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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