Résumé
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.
| langue originale | Anglais |
|---|---|
| Pages (de - à) | 16-24 |
| Nombre de pages | 9 |
| journal | European Journal of Cancer |
| Volume | 82 |
| Les DOIs | |
| état | Publié - 1 sept. 2017 |
Accès au document
Autres fichiers et liens
Contient cette citation
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
Dans: European Journal of Cancer, Vol 82, 01.09.2017, p. 16-24.
Résultats de recherche: Contribution à un journal › Article › Revue par des pairs
TY - JOUR
T1 - Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX
AU - Emile, Jean François
AU - Julié, Catherine
AU - Le Malicot, Karine
AU - Lepage, Come
AU - Tabernero, Josep
AU - Mini, Enrico
AU - Folprecht, Gunnar
AU - Van Laethem, Jean Luc
AU - Dimet, Stéphanie
AU - Boulagnon-Rombi, Camille
AU - Allard, Marc Antoine
AU - Penault-Llorca, Frédérique
AU - Bennouna, Jaafar
AU - Laurent-Puig, Pierre
AU - Taieb, Julien
AU - Thaler, Josef
AU - Greil, Richard
AU - Gaenzer, Johannes
AU - Eisterer, Wolfgang
AU - Tschmelitsch, Joerg
AU - Keil, Felix
AU - Samonigg, Hellmut
AU - Zabernigg, August
AU - Schmid, Franz
AU - Steger, Günther
AU - Steinacher, Robert
AU - Andel, Johannes
AU - Jagdt, Björn
AU - Lang, Alois
AU - Fridrik, Michael
AU - Függer, Reinhold
AU - Hofbauer, Friedrich
AU - Woell, Ewald
AU - Geissler, Dietmar
AU - Lenauer, Alfred
AU - Prager, Manfred
AU - D'Haens, Geert
AU - Demolin, Gauthier
AU - Kerger, Joseph
AU - Deboever, Guido
AU - Ghillebert, Gilbert
AU - Polus, Marc
AU - Van Cutsem, Eric
AU - Kalantari, Hassan Rezaie
AU - Delaunoit, Thierry
AU - Goeminne, Jean Charles
AU - Peeters, Marc
AU - Vergauwe, Philippe
AU - Houbiers, Ghislain
AU - Humblet, Yves
AU - Janssens, Jos
AU - Schrijvers, Dirk
AU - Vanderstraeten, Erik
AU - Van Laethem, Jean Luc
AU - Vermorken, Jan
AU - Van Daele, Daniel
AU - Ferrante, Michel
AU - Forget, Frederic
AU - Hendlisz, Alain
AU - Yilmaz, Mette
AU - Nielsen, Svend Erik
AU - Vestermark, Lene
AU - Larsen, Jim
AU - Zawadi, Mohamed Ayman
AU - Bouche, Olivier
AU - Mineur, Laurent
AU - Bennouna-Louridi, Jaafar
AU - Dourthe, Louis Marie
AU - Ychou, Marc
AU - Boucher, Eveline
AU - Taieb, Julien
AU - Pezet, Denis
AU - Desseigne, Francoise
AU - Ducreux, Michel
AU - Texereau, Patrick
AU - Miglianico, Laurent
AU - Rougier, Philippe
AU - Fratte, Serge
AU - Levache, Charles Briac
AU - Merrouche, Yacine
AU - Ellis, Stephen
AU - Locher, Christophe
AU - Ramee, Jean Francois
AU - Garnier, Claire
AU - Viret, Frederic
AU - Chauffert, Bruno
AU - Cojean-Zelek, Isabelle
AU - Michel, Pierre
AU - Lecaille, Cedric
AU - Borel, Christian
AU - Seitz, Jean Francois
AU - Smith, Denis
AU - Lombard-Bohas, Catherine
AU - Andre, Thierry
AU - Gornet, Jean Marc
AU - Fein, Francine
AU - Coulon-Sfairi, Marie Aude
AU - Kaminsky, Marie Christine
AU - Lagasse, Jean Paul
AU - Luet, Dominique
AU - Etienne, Pierre Luc
AU - Gasmi, Mohamed
AU - Vanoli, Andre
AU - Nguyen, Suzanne
AU - Aparicio, Thomas
AU - Perrier, Hervé
AU - Stremsdoerfer, Noel
AU - Laplaige, Philippe
AU - Arsene, Dominique
AU - Auby, Dominique
AU - Bedenne, Laurent
AU - Coriat, Romain
AU - Denis, Bernard
AU - Geoffroy, Patrick
AU - Piot, Gilles
AU - Becouarn, Yves
AU - Bordes, Gilbert
AU - Deplanque, Gael
AU - Dupuis, Olivier
AU - Fruge, Frederic
AU - Guimbaud, Rosine
AU - Lecomte, Thierry
AU - Lledo, Gérard
AU - Sobhani, Iradej
AU - Asnacios, Amani
AU - Azzedine, Ahmed
AU - Desauw, Christophe
AU - Galais, Marie Pierre
AU - Gargot, Dany
AU - Lam, You Heng
AU - Abakar-Mahamat, Abakar
AU - Berdah, Jean Francois
AU - Catteau, Sylviane
AU - Clavero-Fabri, Marie Christine
AU - Codoul, Jean Francois
AU - Legoux, Jean Louis
AU - Goldfain, Denis
AU - Guichard, Pierre
AU - Verge, Denis Pere
AU - Provencal, Jocelyne
AU - Vedrenne, Bruno
AU - Brezault-Bonnet, Catherine
AU - Cleau, Denis
AU - Desir, Jean Paul
AU - Fallik, David
AU - Garcia, Bruno
AU - Gaspard, Marie Hélène
AU - Genet, Dominique
AU - Hartwig, Johannes
AU - Krummel, Yves
AU - Budnik, Tamara Matysiak
AU - Palascak-Juif, Vanessa
AU - Randrianarivelo, Harizo
AU - Rinaldi, Yves
AU - Aleba, Albert
AU - Darut-Jouve, Ariane
AU - de Gramont, Aimery
AU - Hamon, Herve
AU - Wendehenne, Frederic
AU - Matzdorff, Axel
AU - Stahl, Michael Konrad
AU - Schepp, Wolfgang
AU - Burk, Martin
AU - Mueller, Lothar
AU - Folprecht, Gunnar
AU - Geissler, Michael
AU - Mantovani-Loeffler, Luisa
AU - Hoehler, Thomas
AU - Asperger, Walter
AU - Kroening, Hendrik
AU - von Weikersthal, Ludwig Fischer
AU - Fuxius, Stefan
AU - Groschek, Matthias
AU - Meiler, Johannes
AU - Trarbach, Tanja
AU - Rauh, Jacqueline
AU - Ziegenhagen, Nicolas
AU - Kretzschmar, Albrecht
AU - Graeven, Ullrich
AU - Nusch, Arnd
AU - von Wichert, Goetz
AU - Hofheinz, Ralf Dieter
AU - Kleber, Gerhard
AU - Schmidt, Karl Heinz
AU - Vehling-Kaiser, Ursula
AU - Baum, Claudia
AU - Schuette, Jochen
AU - Haag, Georg Martin
AU - Holtkamp, Wilhelm
AU - Potenberg, Jochen
AU - Reiber, Tobias
AU - Schliesser, Georg
AU - Schmoll, Hans Joachim
AU - Schneider-Kappus, Wolfgang
AU - Abenhardt, Wolfgang
AU - Denzlinger, Claudio
AU - Henning, Jan
AU - Marxsen, Bartscht
AU - Derigs, Hans Guenter
AU - Lambertz, Helmut
AU - Becker-Boost, Ingulf
AU - Caca, Karel
AU - Constantin, Christian
AU - Decker, Thomas
AU - Eschenburg, Henning
AU - Gabius, Sigrun
AU - Hebart, Holger
AU - Hoffmeister, Albrecht
AU - Horst, Heinz August
AU - Kremers, Stephan
AU - Leithaeuser, Malte
AU - Mueller, Sebastian
AU - Wagner, Siegfried
AU - Daum, Severin
AU - Schlegel, Frank
AU - Stauch, Martina
AU - Heinemann, Volker
AU - Maiello, Evaristo
AU - Latini, Luciano
AU - Zaniboni, Alberto
AU - Amadori, Dino
AU - Aprile, Giuseppe
AU - Barni, Sandro
AU - Mattioli, Rodolfo
AU - Martoni, Andrea
AU - Passalacqua, Rodolfo
AU - Nicolini, Mario
AU - Pasquini, Enzo
AU - Rabbi, Carla
AU - Aitini, Enrico
AU - Ravaioli, Alberto
AU - Barone, Carlo
AU - Biasco, Guido
AU - Tamberi, Stefano
AU - Gambi, Angelo
AU - Verusio, Claudio
AU - Marzola, Marina
AU - Lelli, Giorgio
AU - Boni, Corrado
AU - Cascinu, Stefano
AU - Bidoli, Paolo
AU - Vaghi, Massimo
AU - Cruciani, Giorgio
AU - Di Costanzo, Francesco
AU - Sobrero, Alberto
AU - Mini, Enrico
AU - Petrioli, Roberto
AU - Aglietta, Massimo
AU - Alabiso, Oscar
AU - Capuzzo, Federico
AU - Falcone, Alfredo
AU - Corsi, Domenico Cristi
AU - Labianca, Roberto
AU - Salvagni, Stefania
AU - Chiara, Silvana
AU - Ciuffreda, Libero
AU - Ferraù, Francesco
AU - Giuliani, Francesco
AU - Lonardi, Sara
AU - Gebbia, Nicola
AU - Mantovani, Giovanni
AU - Sanches, Evaristo
AU - Mellidez, Juan Carlos
AU - Santos, Pedro
AU - Freire, Joao
AU - Sarmento, Cristina
AU - Costa, Luis
AU - Pinto, Antonio Moreira
AU - Barroso, Sergio
AU - Santo, Jorge Espirito
AU - Guedes, Fátima
AU - Monteiro, Amélia
AU - Sa, Anabela
AU - Furtado, Irene
AU - Salazar, Ramon
AU - Aguilar, Enrique Aranda
AU - Herrero, Fernando Rivera
AU - Valera, Javier Sastre
AU - Ayerbes, Manuel Valladares
AU - Batlle, Jaime Feliu
AU - Gil, Silvia
AU - Esteve, Albert Abad
AU - Garcia-Giron, Carlos
AU - Vivanco, Guillermo Lopez
AU - Salvia, Antonia Salud
AU - Orduña, Vicente Alonso
AU - Garcia, Ruth Vera
AU - Gallego, Javier
AU - Sureda, Bartomeu Massuti
AU - Remon, Jordi
AU - Safont Aguilera, Maria Jose
AU - Nogueras, Luis Cirera
AU - Merino, Bernado Queralt
AU - Castro, Cristina Gravalos
AU - de Prado, Purificacion Martinez
AU - Pericay, Carlos Pijaume
AU - Figueiras, Manuel Constenla
AU - Jordan, Inmaculada Guasch
AU - Gome Reina, Maria Jose
AU - Garcia, Amelia Lopez Ladron
AU - Garcia-Ramos, Antonio Arrivi
AU - Cervantes, Andres
AU - Martos, Carlos Fernandez
AU - Gaspar, Eugenio Marcuello
AU - Montero, Ines Cabezas
AU - Emperador, Pilar Escudero
AU - Carbonero, Ana Leon
AU - Castillo, Manuel Gallen
AU - Garcia, Teresa Garcia
AU - Lopez, Jose Garcia
AU - Flores, Encarnacion Gonzalez
AU - Morales, Monica Guillot
AU - Muñoz, Marta Llanos
AU - Martín, Ana López
AU - Maurel, Joan
AU - Camara, Juan Carlos
AU - Garcia, Rosario Dueñas
AU - Salgado, Mercedes
AU - Busquier, Isabel Hernandez
AU - Ruiz, Teresa Checa
AU - Muñoa, Adelaida Lacasta
AU - Aliguer, Miquel Nogue
AU - de Taranco, Amalia Velasco Ortiz
AU - Ureña, Miguel Mendez
AU - Gaspa, Ferran Losa
AU - Ponce, Jose Juan
AU - Roig, Carlos Bosch
AU - Jimenez, Pedro Valero
AU - Brotons, Antonio Galan
AU - Rodriguez, Santiago Albiol
AU - Martinez, Jose Ales
AU - Ruiz, Liliana Canosa
AU - Ruiz, Margarita Centelles
AU - Bridgewater, John
AU - Glynne-Jones, Rob
AU - Tahir, Saad
AU - Hickish, Tamas
AU - Cassidy, Jim
AU - Samuel, Leslie
N1 - Publisher Copyright: © 2017 Elsevier Ltd
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
KW - Biomarker
KW - Colorectal carcinoma
KW - Immune response
KW - Prospective cohort study
UR - http://www.scopus.com/inward/record.url?scp=85021288157&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2017.04.025
DO - 10.1016/j.ejca.2017.04.025
M3 - Article
C2 - 28651158
AN - SCOPUS:85021288157
SN - 0959-8049
VL - 82
SP - 16
EP - 24
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -