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

Emile, Jean-François; Julié, Catherine; Le Malicot, Karine; Lepage, Come; Tabernero, Josep; Mini, Enrico; Folprecht, Gunnar; Van Laethem, Jean-Luc; Dimet, Stéphanie; Boulagnon-Rombi, Camille; Allard, Marc-Antoine; Penault-Llorca, Frédérique; Bennouna, Jaafar; Laurent-Puig, Pierre; Taieb, Julien; Thaler, Jos; Greil, Richard; Gaenzer, Johannes; Eisterer, Wolfgang; Tschmelitsch, Joerg; Keil, Felix; Sa, Hellmut; Zabernigg, August; Schmid, Franz; Steger, Günther; Steinacher, Rob; Andel, Johannes; Jagdt, Björn; Lang, Alois; Fridrik, Michael; Függer, Reinhold; Hofbauer, Friedrich; Woell, Ewald; Geissler, Dietmar; Lenauer, Alfred; Prager, Manfred; D'Haens, Geert; Demolin, Gauthier; Kerger, Josep; Deboever, Guido; Gil, Gilbert; Polus, Marc; Van Cutsem, Eric; Kalantari, Hassan Rezaie; Delaunoit, Thierry; Goeminne, Jean Charles; Peeters, Marc; Vergauwe, Philippe; Houbiers, Ghislain; Humblet, Yves; Janssens, Jan; Schrijvers, Dirk; Vanderstraeten, Erik; Vermorken, Jan; Van Daele, Daniel; Michel, Michel; Forget, F.; Hendlisz, Alain; Yilmaz, Mette; Nielsen, Svend Erik; Vestermark, Lene; Larsen, Jim; Zawadi, Mohamed; Bouche, Olivier; Mineur, Laurent; Bennouna-Louridi, Jaafar; Dourthe, Louis Marie; Ychou, Marc; Boucher, Eveline; Denis, Denis; Desseigne, Francoise; Texereau, Patrick; Miglianico, Laurent; Rougier, Philippe; Fratte, Serge; Levache, Charles-Briac; Merrouche, Yacine; Ellis, Stephen; Locher, Christophe; Ramee, Jean-Francois; Garnier, Claire; Viret, Frederic; Chauffert, Bruno; Cojean-Zelek, Isabelle; Michel, Pierre; Lecaille, Cedric; Borel, Christian; Seitz, Jean-Francois; Lombard-Bohas, Catherine; Andre, Thierry; Gornet, Jean-Marc; Fein, Francine; Coulon-Sfairi, Marie-Aude; Kaminsky, Marie-Christine; Lagasse, Jean-Paul; Luet, Dominique; Etienne, Pierre; Gasmi, Mohamed; Vanoli, Andre; Nguyen, Suzanne; Aparicio, Thomas; Perrier, Hervé; Stremsdoerfer, Noel; Laplaige, Philippe; Arsene, Dominique; Auby, Dominique; Bedenne, Laurent; Coriat, Romain; Geoffroy, Patrick; Gil, Gilles; Becouarn, Yves; Deplanque, Gael; Dupuis, Olivier; Fruge, Frederic; Guimbaud, Rosine; Lecomte, Thierry; Lledo, Gérard; Sobhani, Iradej; Asnacios, Amani; Azzedine, Ahmed; Desauw, Christophe; Galais, Pierre; Gargot, Dany; Lam, You-Heng; Abakar-Mahamat, Abakar; Berdah, Jean-Francois; Catteau, Sylviane; Clavero-Fabri, Marie-Christine; Codoul, Jean-Francois; Legoux, Jean-Louis; Goldfain, Denis; Guichard, Pierre; Verge, Denis; Provencal, Jocelyne; Vedrenne, Bruno; Brezault-Bonnet, Catherine; Cleau, Denis; Desir, Jean-Paul; Fallik, David; Garcia, Bruno; Gaspa, Marie-Hélène; Genet, Dominique; Hartwig, Johannes; Krummel, Yves; Budnik, Tamara Matysiak; Palascak-Juif, Vanessa; Randrianarivelo, Harizo; Rinaldi, Yves; Aleba, Albert; Darut-Jouve, Ariane; De Gramont, Aimery; Hamon, Herve; Wendehenne, Frederic; Matzdorff, Axel; Stahl, Michael; Schepp, Wolfgang; Burk, Martin; Mueller, Lothar; Geissler, Michael; Mantovani, Luis; Hoehler, Thomas; Asperger, Walter; Kroening, Hendrik; von Weikersthal, Ludwig Fischer; Fuxius, Stefan; Groschek, Matthias; Meiler, Johannes; Trarbach, Tanja; Rauh, Jacqueline; Ziegenhagen, Nicola; Kretzschmar, Albrecht; Graeven, Ullrich; Nusch, Arnd; von Wichert, Goetz; Hofheinz, Ralf-Dieter; Kleber, Gerhard; Schmidt, Karl-Heinz; Vehling-Kaiser, Ursula; Baum, Claudia; Schuette, Jochen; Haag, Georg; Holtkamp, Wilhelm; Potenberg, Jochen; Reiber, Tobias; Schliesser, Georg; Schmoll, Hans-Joachim; Schneider-Kappus, Wolfgang; Abenhardt, Wolfgang; Denzlinger, Claudio; Henning, Henning; Marxsen, Bartscht; Derigs, Hans Guenter; Lambertz, Helmut; Becker-Boost, Ingulf; Caca, Karel; Constantin, Christian; Decker, Thomas; Eschenburg, Henning; Gabius, Sigrun; Hebart, Holger; Hoffmeister, Albrecht; Horst, Heinz-August; Kremers, Stephan; Leithaeuser, Malte; Mueller, Sebastian; Wagner, Siegfried; Daum, Severin; Schlegel, Frank; Stauch, Martina; Heinemann, Volker; Maiello, Evaristo; Latini, Luciano; Zaniboni, Alberto; Amadori, Dino; Aprile, Giuseppe; Sa, Sandro; Mattioli, Rodolfo; Martoni, Andrea; Passalacqua, Rodolfo; Nicolini, Mario; Pasquini, Enzo; Rabbi, Carla; Aitini, Enrico; Ravaioli, Alberto; Barone, Carlo; Biasco, Guido; Tamberi, Stefano; Gambi, Angelo; Verusio, Claudio; Marzola, Marina; Lelli, Giorgio; Boni, Corrado; Cascinu, Stefano; Bidoli, Paolo; Vaghi, Massimo; Cruciani, Giorgio; Costa, Francesco; Sobrero, Alberto; Petrioli, Rob; Aglietta, Massimo; Alabiso, Oscar; Capuzzo, Federico; Falcone, Alfredo; Corsi, Domenico Cristi; Labianca, Rob; Sa, Stefania; Chiara, Silvana; Ciuffreda, Libero; Ferraù, Francesco; Giuliani, Francesco; Sa, Sara; Gebbia, Nicola; Mantovani, Giovanni; Sa, Evaristo; Mellidez, Juan Carlos; Sa, Pedro; Freire, Joao; Sa, Cristina; Costa, Luis; Pinto, Antonio Moreira; Barroso, Sergio; Sa, Jorge Espirito; Guedes, Fátima; Monteiro, Amélia; Sa, Anabela; Furtado, Irene; Salazar, Ramon; Aguilar, Enrique Aranda; Herrero, Fernando Rivera; Valera, Javier; Ayerbes, Manuel Valladares; Batlle, Jaime Feliu; Gil, Silvia; Esteve, Albert Abad; Garcia, Carlos; Lopez, Guillermo Lopez; Salvia, Antonia Salud; Orduña, Vicente Alonso; Garcia, Ruth Vera; Gallego, Javier; Sureda, Bartomeu Massuti; Remon, Jordi; Safont Aguilera, Maria Jose; Nogueras, Luis Cirera; Merino, Bernado Queralt; Castro, Cristina Gravalos; Martinez, Purificacion Martinez; Pericay, Carlos Pijaume; Figueiras, Manuel Constenla; Jordan, Inmaculada Guasch; Gome Reina, Maria Jose; Garcia, Amelia Lopez-Ladron; Garcia, Antonio Arrivi; Cervantes, Andres; Martos, Carlos Fernandez; Gaspa, Eugenio Marcuello; Montero, Ines Cabezas; Emperador, Pilar Escudero; Carbonero, Ana Leon; Castillo, Manuel Gallen; Garcia, Teresa Garcia; Garcia, Jose Garcia; Flores, Encarnacion Gonzalez; Morales, Monica Guillot; Muñoz, Marta Llanos; Martín, Ana López; Maurel, Joan; Camara, Juan Carlos; Garcia, Rosario Dueñas; Salgado, Mercedes; Busquier, Isabel Hernandez; Ruiz, Teresa Checa; Muñoa, Adelaida Lacasta; Aliguer, Miquel Nogue; de Taranco, Amalia Velasco Ortiz; Ureña, Miguel Mendez; Gaspa, Ferran Losa; Ponce, Jose Juan; Roig, Carlos Bosch; Jimenez, Jim; Brotons, Antonio Galan; Rodriguez, Santiago Albiol; Martinez, Jose Ales; Ruiz, Liliana Canosa; Ruiz, Margarita Centelles; Bridgewater, John; Glynne-Jones, Rob; Tahir, Saad; Hickish, Tamas; Cassidy, Jim; Samuel, Leslie

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

2017

BackgroundThe 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 methodsAccording 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.ResultsAmong 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.ConclusionAlthough 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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