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, 31 Philippe Vergauwe Ghislain Houbiers Yves Humblet Jan Janssens Dirk Schrijvers 32 Erik Vanderstraeten 33 Jan Vermorken 34 Daniel Van Daele Michel Michel 35 F. Forget 36 Alain Hendlisz Mette Yilmaz 37 Svend Erik Nielsen 38 Lene Vestermark 39, 40 Jim Larsen 41 Mohamed Zawadi Olivier Bouche 42 Laurent Mineur Jaafar Bennouna-Louridi Louis Marie Dourthe Marc Ychou 43 Eveline Boucher 44 Denis Denis 45 Francoise Desseigne Patrick Texereau 46 Laurent Miglianico Philippe Rougier 47 Serge Fratte 48 Charles-Briac Levache 49 Yacine Merrouche 50 Stephen Ellis Christophe Locher 51 Jean-Francois Ramee 52 Claire Garnier 53 Frederic Viret 54 Bruno Chauffert 55 Isabelle Cojean-Zelek 56 Pierre Michel 57 Cedric Lecaille Christian Borel 58 Jean-Francois Seitz 59 Catherine Lombard-Bohas 60 Thierry Andre 61, 62 Jean-Marc Gornet 63 Francine Fein 64 Marie-Aude Coulon-Sfairi Marie-Christine Kaminsky 65 Jean-Paul Lagasse Dominique Luet 46 Pierre Etienne 66 Mohamed Gasmi 67 Andre Vanoli Suzanne Nguyen 68 Thomas Aparicio 69 Hervé Perrier Noel Stremsdoerfer Philippe Laplaige 70 Dominique Arsene 71 Dominique Auby 72 Laurent Bedenne 73 Romain Coriat 74 Patrick Geoffroy 75, 76 Gilles Gil 26 Yves Becouarn 77 Gael Deplanque 78 Olivier Dupuis 79 Frederic Fruge Rosine Guimbaud 80 Thierry Lecomte 81 Gérard Lledo 82, 43 Iradej Sobhani 83 Amani Asnacios 84 Ahmed Azzedine Christophe Desauw Pierre Galais Dany Gargot You-Heng Lam Abakar Abakar-Mahamat Jean-Francois Berdah 85 Sylviane Catteau Marie-Christine Clavero-Fabri Jean-Francois Codoul Jean-Louis Legoux 86 Denis Goldfain Pierre Guichard 87 Denis Verge 88 Jocelyne Provencal Bruno Vedrenne Catherine Brezault-Bonnet Denis Cleau 64 Jean-Paul Desir 89 David Fallik Bruno Garcia Marie-Hélène Gaspa Dominique Genet 90 Johannes Hartwig Yves Krummel 91 Tamara Matysiak Budnik Vanessa Palascak-Juif 92 Harizo Randrianarivelo Yves Rinaldi 93 Albert Aleba Ariane Darut-Jouve Aimery De Gramont 61 Herve Hamon Frederic Wendehenne Axel Matzdorff 94 Michael Stahl Wolfgang Schepp Martin Burk Lothar Mueller 95 Michael Geissler Luis Mantovani Thomas Hoehler 96 Walter Asperger Hendrik Kroening Ludwig Fischer Von Weikersthal Stefan Fuxius Matthias Groschek Johannes Meiler 97 Tanja Trarbach Jacqueline Rauh Nicola Ziegenhagen Albrecht Kretzschmar 98 Ullrich Graeven Arnd Nusch Goetz Von Wichert Ralf-Dieter Hofheinz Gerhard Kleber Karl-Heinz Schmidt 99 Ursula Vehling-Kaiser Claudia Baum 100 Jochen Schuette Georg Haag 101 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 102 Henning Eschenburg Sigrun Gabius Holger Hebart 103 Albrecht Hoffmeister 104 Heinz-August Horst 105 Stephan Kremers Malte Leithaeuser Sebastian Mueller 106 Siegfried Wagner 107 Severin Daum 108 Frank Schlegel Martina Stauch 109 Volker Heinemann Evaristo Maiello Luciano Latini Alberto Zaniboni Dino Amadori 110 Giuseppe Aprile Sandro Sa 111 Rodolfo Mattioli Andrea Martoni Rodolfo Passalacqua Mario Nicolini 112 Enzo Pasquini Carla Rabbi Enrico Aitini Alberto Ravaioli 113 Carlo Barone 114 Guido Biasco Stefano Tamberi Angelo Gambi 115 Claudio Verusio Marina Marzola 116 Giorgio Lelli Corrado Boni 117 Stefano Cascinu 118 Paolo Bidoli Massimo Vaghi Giorgio Cruciani Francesco Costa 119 Alberto Sobrero Rob Petrioli Massimo Aglietta Oscar Alabiso Federico Capuzzo Alfredo Falcone Domenico Cristi Corsi 120 Rob Labianca 121 Stefania Sa 111 Silvana Chiara Libero Ciuffreda Francesco Ferraù 122 Francesco Giuliani Sara Sa 111 Nicola Gebbia Giovanni Mantovani Evaristo Sa 123 Juan Carlos Mellidez Pedro Sa Joao Freire Cristina Sa 124, 125 Luis Costa 126 Antonio Moreira Pinto 127, 128 Sergio Barroso Jorge Espirito Sa Fátima Guedes 129 Amélia Monteiro 130 Anabela Sa 131 Irene Furtado 132 Ramon Salazar Enrique Aranda Aguilar 133, 134 Fernando Rivera Herrero Javier Valera Manuel Valladares Ayerbes Jaime Feliu Batlle Silvia Gil 135 Albert Abad Esteve 136 Carlos Garcia Guillermo Lopez Lopez 137 Antonia Salud Salvia Vicente Alonso Orduña Ruth Vera Garcia 138 Javier Gallego Bartomeu Massuti Sureda Jordi Remon 139 Maria Jose Safont Aguilera Luis Cirera Nogueras Bernado Queralt Merino 140 Cristina Gravalos Castro 141 Purificacion Martinez Martinez 142 Carlos Pijaume Pericay Manuel Constenla Figueiras Inmaculada Guasch Jordan 143 Maria Jose Gome Reina Amelia Lopez-Ladron Garcia 144 Antonio Arrivi Garcia 144 Andres Cervantes 145 Carlos Fernandez Martos Eugenio Marcuello Gaspa Ines Cabezas Montero 146 Pilar Escudero Emperador Ana Leon Carbonero Manuel Gallen Castillo 147 Teresa Garcia Garcia 148 Jose Garcia Garcia Encarnacion Gonzalez Flores Monica Guillot Morales 149 Marta Llanos Muñoz 126 Ana López Martín 150 Joan Maurel Juan Carlos Camara 151 Rosario Dueñas Garcia 138 Mercedes Salgado 152 Isabel Hernandez Busquier Teresa Checa Ruiz 153 Adelaida Lacasta Muñoa Miquel Nogue Aliguer Amalia Velasco Ortiz De Taranco Miguel Mendez Ureña Ferran Losa Gaspa Jose Juan Ponce 154 Carlos Bosch Roig Jim Jimenez 155 Antonio Galan Brotons 156 Santiago Albiol Rodriguez 157 Jose Ales Martinez 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
11 Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse
Modèles de Cellules Souches Malignes et Thérapeutiques
31 MAB - Méthodes et Algorithmes pour la Bioinformatique
LIRMM - Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier
112 FEEM
124 NIPE
135 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
152 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
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.
Type de document :
Article dans une revue
Liste complète des métadonnées

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 : mardi 14 novembre 2017 - 15:22:02

Identifiants

Citation

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〉

Partager

Métriques

Consultations de la notice

996