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 Pierre Laurent-Puig 15 Julien Taieb Jos Thaler 16 Richard Greil 17 Johannes Gaenzer Wolfgang Eisterer Joerg Tschmelitsch Felix Keil 18 Hellmut Sa August Zabernigg Franz Schmid 19 Günther Steger 20 Rob Steinacher Johannes Andel 21 Björn Jagdt Alois Lang Michael Fridrik 22 Reinhold Függer Friedrich Hofbauer Ewald Woell Dietmar Geissler 23 Alfred Lenauer Manfred Prager 24 Geert d'Haens Gauthier Demolin Josep Kerger Guido Deboever Gilbert Gil 25 Marc Polus Eric Van Cutsem 26, 27 Hassan Rezaie Kalantari 28 Thierry Delaunoit Jean Charles Goeminne Marc Peeters 29 Philippe Vergauwe Ghislain Houbiers Yves Humblet Jan Janssens Dirk Schrijvers 30 Erik Vanderstraeten 31 Jan Vermorken 32 Daniel Van Daele Michel Michel 33 F. Forget 34 Alain Hendlisz Mette Yilmaz 35 Svend Erik Nielsen 36 Lene Vestermark 37, 38 Jim Larsen 39 Mohamed Zawadi Olivier Bouche 40 Laurent Mineur Jaafar Bennouna-Louridi Louis Marie Dourthe Marc Ychou 41 Eveline Boucher 42 Denis Denis 43 Francoise Desseigne Patrick Texereau 44 Laurent Miglianico Philippe Rougier 45 Serge Fratte 46 Charles-Briac Levache 47 Yacine Merrouche 48 Stephen Ellis Christophe Locher 49 Jean-Francois Ramee 50 Claire Garnier 51 Frederic Viret 52 Bruno Chauffert 53 Isabelle Cojean-Zelek 54 Pierre Michel 55 Cedric Lecaille Christian Borel 56 Jean-Francois Seitz 57 Catherine Lombard-Bohas 58 Thierry Andre 59, 60 Jean-Marc Gornet 61 Francine Fein 62 Marie-Aude Coulon-Sfairi Marie-Christine Kaminsky 63 Jean-Paul Lagasse Dominique Luet 44 Pierre Etienne 64 Mohamed Gasmi 65 Andre Vanoli Suzanne Nguyen 66 Thomas Aparicio 67 Hervé Perrier Noel Stremsdoerfer Philippe Laplaige 68 Dominique Arsene 69 Dominique Auby 70 Laurent Bedenne 71 Romain Coriat 72 Patrick Geoffroy 73, 74 Gilles Gil 25 Yves Becouarn 75 Gael Deplanque 76 Olivier Dupuis 77 Frederic Fruge Rosine Guimbaud 78 Thierry Lecomte 79 Gérard Lledo 80, 41 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 62 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 59 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 Juan Carlos Mellidez Pedro Sa Joao Freire Cristina Sa 121, 122 Luis Costa 123 Antonio Moreira Pinto 124, 125 Sergio Barroso Jorge Espirito Sa Fátima Guedes 126 Amélia Monteiro 127 Anabela Sa 128 Irene Furtado 129 Ramon Salazar Enrique Aranda Aguilar 130, 131 Fernando Rivera Herrero Javier Valera Manuel Valladares Ayerbes Jaime Feliu Batlle Silvia Gil 132 Albert Abad Esteve 133 Carlos Garcia Guillermo Lopez Lopez 134 Antonia Salud Salvia Vicente Alonso Orduña Ruth Vera Garcia 135 Javier Gallego Bartomeu Massuti Sureda Jordi Remon 136 Maria Jose Safont Aguilera Luis Cirera Nogueras Bernado Queralt Merino 137 Cristina Gravalos Castro 138 Purificacion Martinez Martinez 139 Carlos Pijaume Pericay Manuel Constenla Figueiras Inmaculada Guasch Jordan 140 Maria Jose Gome Reina Amelia Lopez-Ladron Garcia 141 Antonio Arrivi Garcia 142 Andres Cervantes 143 Carlos Fernandez Martos Eugenio Marcuello Gaspa Ines Cabezas Montero 135 Pilar Escudero Emperador Ana Leon Carbonero Manuel Gallen Castillo 144 Teresa Garcia Garcia 145 Jose Garcia Garcia Encarnacion Gonzalez Flores Monica Guillot Morales 146 Marta Llanos Muñoz 123 Ana López Martín 147 Joan Maurel Juan Carlos Camara 148 Rosario Dueñas Garcia 135 Mercedes Salgado Isabel Hernandez Busquier Teresa Checa Ruiz 149 Adelaida Lacasta Muñoa Miquel Nogue Aliguer Amalia Velasco Ortiz de Taranco Miguel Mendez Ureña Ferran Losa Gaspa Jose Juan Ponce 150 Carlos Bosch Roig Jim Jimenez 151 Antonio Galan Brotons 152 Santiago Albiol Rodriguez 153 Jose Ales Martinez Liliana Canosa Ruiz 154 Margarita Centelles Ruiz 155, 156 John Bridgewater Rob Glynne-Jones Saad Tahir Tamas Hickish Jim Cassidy 157 Leslie Samuel
* Auteur correspondant
110 FEEM
121 NIPE
132 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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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 : lundi 17 juin 2019 - 18:26:05

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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, Elsevier, 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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