Attenzione: i dati modificati non sono ancora stati salvati. Per confermare inserimenti o cancellazioni di voci è necessario confermare con il tasto INSERISCI in fondo alla pagina
CINECA IRIS Institutional Research Information System
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.
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, Josef;Greil, Richard;Gaenzer, Johannes;Eisterer, Wolfgang;Tschmelitsch, Joerg;Keil, Felix;Samonigg, Hellmut;Zabernigg, August;Schmid, Franz;Steger, Günther;Steinacher, Robert;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, Joseph;Deboever, Guido;Ghillebert, Gilbert;Polus, Marc;Van Cutsem, Eric;Kalantari, Hassan Rezaie;Delaunoit, Thierry;Goeminne, Jean Charles;Peeters, Marc;Vergauwe, Philippe;Houbiers, Ghislain;Humblet, Yves;Janssens, Jos;Schrijvers, Dirk;Vanderstraeten, Erik;Van Laethem, Jean Luc;Vermorken, Jan;Van Daele, Daniel;Ferrante, Michel;Forget, Frederic;Hendlisz, Alain;Yilmaz, Mette;Nielsen, Svend Erik;Vestermark, Lene;Larsen, Jim;Zawadi, Mohamed Ayman;Bouche, Olivier;Mineur, Laurent;Bennouna Louridi, Jaafar;Dourthe, Louis Marie;Ychou, Marc;Boucher, Eveline;Taieb, Julien;Pezet, Denis;Desseigne, Francoise;Ducreux, Michel;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;Smith, Denis;Lombard Bohas, Catherine;Andre, Thierry;Gornet, Jean Marc;Fein, Francine;Coulon Sfairi, Marie Aude;Kaminsky, Marie Christine;Lagasse, Jean Paul;Luet, Dominique;Etienne, Pierre Luc;Gasmi, Mohamed;Vanoli, Andre;Nguyen, Suzanne;Aparicio, Thomas;Perrier, Hervé;Stremsdoerfer, Noel;Laplaige, Philippe;Arsene, Dominique;Auby, Dominique;Bedenne, Laurent;Coriat, Romain;Denis, Bernard;Geoffroy, Patrick;Piot, Gilles;Becouarn, Yves;Bordes, Gilbert;Deplanque, Gael;Dupuis, Olivier;Fruge, Frederic;Guimbaud, Rosine;Lecomte, Thierry;Lledo, Gérard;Sobhani, Iradej;Asnacios, Amani;Azzedine, Ahmed;Desauw, Christophe;Galais, Marie 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 Pere;Provencal, Jocelyne;Vedrenne, Bruno;Brezault Bonnet, Catherine;Cleau, Denis;Desir, Jean Paul;Fallik, David;Garcia, Bruno;Gaspard, 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 Konrad;Schepp, Wolfgang;Burk, Martin;Mueller, Lothar;Folprecht, Gunnar;Geissler, Michael;Mantovani Loeffler, Luisa;Hoehler, Thomas;Asperger, Walter;Kroening, Hendrik;von Weikersthal, Ludwig Fischer;Fuxius, Stefan;Groschek, Matthias;Meiler, Johannes;Trarbach, Tanja;Rauh, Jacqueline;Ziegenhagen, Nicolas;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 Martin;Holtkamp, Wilhelm;Potenberg, Jochen;Reiber, Tobias;Schliesser, Georg;Schmoll, Hans Joachim;Schneider Kappus, Wolfgang;Abenhardt, Wolfgang;Denzlinger, Claudio;Henning, Jan;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;Barni, 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;Di Costanzo, Francesco;SOBRERO, ALBERTO;Mini, Enrico;Petrioli, Roberto;AGLIETTA, Massimo;ALABISO, Oscar;Capuzzo, Federico;Falcone, Alfredo;Corsi, Domenico Cristi;Labianca, Roberto;Salvagni, Stefania;Chiara, Silvana;CIUFFREDA, LIBERO;Ferraù, Francesco;Giuliani, Francesco;Lonardi, Sara;Gebbia, Nicola;Mantovani, Giovanni;Sanches, Evaristo;Mellidez, Juan Carlos;Santos, Pedro;Freire, Joao;Sarmento, Cristina;Costa, Luis;Pinto, Antonio Moreira;Barroso, Sergio;Santo, Jorge Espirito;Guedes, Fátima;Monteiro, Amélia;Sa, Anabela;Furtado, Irene;Salazar, Ramon;Aguilar, Enrique Aranda;Herrero, Fernando Rivera;Tabernero, Josep;Valera, Javier Sastre;Ayerbes, Manuel Valladares;Batlle, Jaime Feliu;Gil, Silvia;Esteve, Albert Abad;Garcia Giron, Carlos;Vivanco, 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;de Prado, Purificacion Martinez;Pericay, Carlos Pijaume;Figueiras, Manuel Constenla;Jordan, Inmaculada Guasch;Gome Reina, Maria Jose;Garcia, Amelia Lopez Ladron;Garcia Ramos, Antonio Arrivi;Cervantes, Andres;Martos, Carlos Fernandez;Gaspar, Eugenio Marcuello;Montero, Ines Cabezas;Emperador, Pilar Escudero;Carbonero, Ana Leon;Castillo, Manuel Gallen;Garcia, Teresa Garcia;Lopez, 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, Pedro Valero;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
2017-01-01
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.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1652484
Citazioni
19
38
35
social impact
Conferma cancellazione
Sei sicuro che questo prodotto debba essere cancellato?
simulazione ASN
Il report seguente simula gli indicatori relativi alla produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione.
La simulazione si basa sui dati IRIS e presenta gli indicatori calcolati alla data indicata sul report. Si ricorda che in sede di domanda ASN presso il MIUR gli indicatori saranno invece calcolati a partire dal 1° gennaio rispettivamente del quinto/decimo/quindicesimo anno precedente la scadenza del quadrimestre di presentazione della domanda (art 2 del DM 598/2018).
In questa simulazione pertanto il valore degli indicatori potrà differire da quello conteggiato all’atto della domanda ASN effettuata presso il MIUR a seguito di:
Correzioni imputabili a eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori.
Presenza di eventuali errori di catalogazione e/o dati mancanti in IRIS
Variabilità nel tempo dei valori citazionali (per i settori bibliometrici)
Variabilità della finestra temporale considerata in funzione della sessione di domanda ASN a cui si partecipa.
La presente simulazione è stata realizzata sulla base delle regole riportate nel DM 598/2018 e dell'allegata Tabella A e delle specifiche definite all'interno del Focus Group Cineca relativo al modulo IRIS ER. Il Cineca non si assume alcuna responsabilità in merito all'uso che il diretto interessato o terzi faranno della simulazione.