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

Jean François Emile; Catherine Julié; Karine Le Malicot; Come Lepage; Josep Tabernero; Enrico Mini; Gunnar Folprecht; Jean Luc Van Laethem; Stéphanie Dimet; Camille Boulagnon-Rombi; Marc Antoine Allard; Frédérique Penault-Llorca; Jaafar Bennouna; Pierre Laurent-Puig; Julien Taieb; Josef Thaler; Richard Greil; Johannes Gaenzer; Wolfgang Eisterer; Joerg Tschmelitsch; Felix Keil; Hellmut Samonigg; August Zabernigg; Franz Schmid; Günther Steger; Robert Steinacher; Johannes Andel; Björn Jagdt; Alois Lang; Michael Fridrik; Reinhold Függer; Friedrich Hofbauer; Ewald Woell; Dietmar Geissler; Alfred Lenauer; Manfred Prager; Geert D'Haens; Gauthier Demolin; Joseph Kerger; Guido Deboever; Gilbert Ghillebert; Marc Polus; Eric Van Cutsem; Hassan Rezaie Kalantari; Thierry Delaunoit; Jean Charles Goeminne; Marc Peeters; Philippe Vergauwe; Ghislain Houbiers; Yves Humblet; Jos Janssens; Dirk Schrijvers; Erik Vanderstraeten; Jean Luc Van Laethem; Jan Vermorken; Daniel Van Daele; Michel Ferrante; Frederic Forget; Alain Hendlisz; Mette Yilmaz; Svend Erik Nielsen; Lene Vestermark; Jim Larsen; Mohamed Ayman Zawadi; Olivier Bouche; Laurent Mineur; Jaafar Bennouna-Louridi; Louis Marie Dourthe; Marc Ychou; Eveline Boucher; Julien Taieb; Denis Pezet; Francoise Desseigne; Michel Ducreux; Patrick Texereau; Laurent Miglianico; Philippe Rougier; Serge Fratte; Charles Briac Levache; Yacine Merrouche; Stephen Ellis; Christophe Locher; Jean Francois Ramee; Claire Garnier; Frederic Viret; Bruno Chauffert; Isabelle Cojean-Zelek; Pierre Michel; Cedric Lecaille; Christian Borel; Jean Francois Seitz; Denis Smith; Catherine Lombard-Bohas; Thierry Andre; Jean Marc Gornet; Francine Fein; Marie Aude Coulon-Sfairi; Marie Christine Kaminsky; Jean Paul Lagasse; Dominique Luet

doi:10.1016/j.ejca.2017.04.025

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

Jean François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean Luc Van Laethem, Stéphanie Dimet, Camille Boulagnon-Rombi, Marc Antoine Allard, Frédérique Penault-Llorca, Jaafar Bennouna, Pierre Laurent-Puig, Julien Taieb, Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg TschmelitschFelix Keil, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Björn Jagdt, Alois Lang, Michael Fridrik, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Eric Van Cutsem, Hassan Rezaie Kalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jean Luc Van Laethem, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Mohamed Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Marc Ychou, Eveline Boucher, Julien Taieb, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean Marc Gornet, Francine Fein, Marie Aude Coulon-Sfairi, Marie Christine Kaminsky, Jean Paul Lagasse, Dominique Luet

Department of Medicine

Research output: Contribution to journal › Article › Research › peer-review

33 Citations (Scopus)

Abstract

© 2017 Elsevier Ltd 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.

Original language	English
Pages (from-to)	16-24
Journal	European Journal of Cancer
Volume	82
DOIs	https://doi.org/10.1016/j.ejca.2017.04.025
Publication status	Published - 1 Sep 2017

Keywords

Biomarker
Colorectal carcinoma
Immune response
Prospective cohort study

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ejca.2017.04.025

Cite this

Emile, J. F., Julié, C., Le Malicot, K., Lepage, C., Tabernero, J., Mini, E., Folprecht, G., Van Laethem, J. L., Dimet, S., Boulagnon-Rombi, C., Allard, M. A., Penault-Llorca, F., Bennouna, J., Laurent-Puig, P., Taieb, J., Thaler, J., Greil, R., Gaenzer, J., Eisterer, W., ... Luet, D. (2017). Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX. European Journal of Cancer, 82, 16-24. https://doi.org/10.1016/j.ejca.2017.04.025

@article{eb0ff5b4f89f4a8d976666c5a3f916a7,

title = "Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX",

abstract = "{\textcopyright} 2017 Elsevier Ltd 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.",

keywords = "Biomarker, Colorectal carcinoma, Immune response, Prospective cohort study",

author = "Emile, {Jean Fran{\c c}ois} and Catherine Juli{\'e} and {Le Malicot}, Karine and Come Lepage and Josep Tabernero and Enrico Mini and Gunnar Folprecht and {Van Laethem}, {Jean Luc} and St{\'e}phanie Dimet and Camille Boulagnon-Rombi and Allard, {Marc Antoine} and Fr{\'e}d{\'e}rique Penault-Llorca and Jaafar Bennouna and Pierre Laurent-Puig and Julien Taieb and Josef Thaler and Richard Greil and Johannes Gaenzer and Wolfgang Eisterer and Joerg Tschmelitsch and Felix Keil and Hellmut Samonigg and August Zabernigg and Franz Schmid and G{\"u}nther Steger and Robert Steinacher and Johannes Andel and Bj{\"o}rn Jagdt and Alois Lang and Michael Fridrik and Reinhold F{\"u}gger and Friedrich Hofbauer and Ewald Woell and Dietmar Geissler and Alfred Lenauer and Manfred Prager and Geert D'Haens and Gauthier Demolin and Joseph Kerger and Guido Deboever and Gilbert Ghillebert and Marc Polus and {Van Cutsem}, Eric and Kalantari, {Hassan Rezaie} and Thierry Delaunoit and Goeminne, {Jean Charles} and Marc Peeters and Philippe Vergauwe and Ghislain Houbiers and Yves Humblet and Jos Janssens and Dirk Schrijvers and Erik Vanderstraeten and {Van Laethem}, {Jean Luc} and Jan Vermorken and {Van Daele}, Daniel and Michel Ferrante and Frederic Forget and Alain Hendlisz and Mette Yilmaz and Nielsen, {Svend Erik} and Lene Vestermark and Jim Larsen and Zawadi, {Mohamed Ayman} and Olivier Bouche and Laurent Mineur and Jaafar Bennouna-Louridi and Dourthe, {Louis Marie} and Marc Ychou and Eveline Boucher and Julien Taieb and Denis Pezet and Francoise Desseigne and Michel Ducreux and Patrick Texereau and Laurent Miglianico and Philippe Rougier and Serge Fratte and Levache, {Charles Briac} and Yacine Merrouche and Stephen Ellis and Christophe Locher and Ramee, {Jean Francois} and Claire Garnier and Frederic Viret and Bruno Chauffert and Isabelle Cojean-Zelek and Pierre Michel and Cedric Lecaille and Christian Borel and Seitz, {Jean Francois} and Denis Smith and Catherine Lombard-Bohas and Thierry Andre and Gornet, {Jean Marc} and Francine Fein and Coulon-Sfairi, {Marie Aude} and Kaminsky, {Marie Christine} and Lagasse, {Jean Paul} and Dominique Luet",

year = "2017",

month = sep,

day = "1",

doi = "10.1016/j.ejca.2017.04.025",

language = "English",

volume = "82",

pages = "16--24",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Limited",

}

Emile, JF, Julié, C, Le Malicot, K, Lepage, C, Tabernero, J, Mini, E, Folprecht, G, Van Laethem, JL, Dimet, S, Boulagnon-Rombi, C, Allard, MA, Penault-Llorca, F, Bennouna, J, Laurent-Puig, P, Taieb, J, Thaler, J, Greil, R, Gaenzer, J, Eisterer, W, Tschmelitsch, J, Keil, F, Samonigg, H, Zabernigg, A, Schmid, F, Steger, G, Steinacher, R, Andel, J, Jagdt, B, Lang, A, Fridrik, M, Függer, R, Hofbauer, F, Woell, E, Geissler, D, Lenauer, A, Prager, M, D'Haens, G, Demolin, G, Kerger, J, Deboever, G, Ghillebert, G, Polus, M, Van Cutsem, E, Kalantari, HR, Delaunoit, T, Goeminne, JC, Peeters, M, Vergauwe, P, Houbiers, G, Humblet, Y, Janssens, J, Schrijvers, D, Vanderstraeten, E, Van Laethem, JL, Vermorken, J, Van Daele, D, Ferrante, M, Forget, F, Hendlisz, A, Yilmaz, M, Nielsen, SE, Vestermark, L, Larsen, J, Zawadi, MA, Bouche, O, Mineur, L, Bennouna-Louridi, J, Dourthe, LM, Ychou, M, Boucher, E, Taieb, J, Pezet, D, Desseigne, F, Ducreux, M, Texereau, P, Miglianico, L, Rougier, P, Fratte, S, Levache, CB, Merrouche, Y, Ellis, S, Locher, C, Ramee, JF, Garnier, C, Viret, F, Chauffert, B, Cojean-Zelek, I, Michel, P, Lecaille, C, Borel, C, Seitz, JF, Smith, D, Lombard-Bohas, C, Andre, T, Gornet, JM, Fein, F, Coulon-Sfairi, MA, Kaminsky, MC, Lagasse, JP & Luet, D 2017, 'Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX', European Journal of Cancer, vol. 82, pp. 16-24. https://doi.org/10.1016/j.ejca.2017.04.025

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

PY - 2017/9/1

Y1 - 2017/9/1

N2 - © 2017 Elsevier Ltd 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 - © 2017 Elsevier Ltd 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

U2 - 10.1016/j.ejca.2017.04.025

DO - 10.1016/j.ejca.2017.04.025

M3 - Article

VL - 82

SP - 16

EP - 24

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this