Jean-François Emile1, Catherine Julié2, Karine Le Malicot3, Come Lepage4, Josep Tabernero5, Enrico Mini6, Gunnar Folprecht7, Jean-Luc Van Laethem8, Stéphanie Dimet9, Camille Boulagnon-Rombi10, Marc-Antoine Allard11, Frédérique Penault-Llorca12, Jaafar Bennouna13, Pierre Laurent-Puig14, Julien Taieb15. 1. EA4340, Versailles University, Paris-Saclay University, Boulogne, France; Assistance Publique Hôpitaux de Paris, Hopital Ambroise Paré, Boulogne, France. Electronic address: jean-francois.emile@uvsq.fr. 2. EA4340, Versailles University, Paris-Saclay University, Boulogne, France; Assistance Publique Hôpitaux de Paris, Hopital Ambroise Paré, Boulogne, France. 3. Fédération Francophone de Cancérologie Digestive (FFCD), Dijon, France. 4. Fédération Francophone de Cancérologie Digestive (FFCD), Dijon, France; Department of Hepato-Gastroenterology, Dijon University Hospital, Dijon, France; UMR 866, INSERM, Dijon, France. 5. Vall D'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain. 6. Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. 7. Medical Department I, University Hospital Carl Gustav Carus, Dresden, Germany. 8. Department of Gastroenterology, Erasme Hospital University, Brussels, Belgium. 9. Department of Pathology, Hospital of La Roche sur Yon, La Roche sur Yon, France. 10. Department of Pathology, University Hospital of Reims, Reims, France. 11. EA4340, Versailles University, Paris-Saclay University, Boulogne, France. 12. Department of Pathology, Centre Jean Perrin, Clermont-Ferrand, France. 13. Department of Gastroenterology, Centre Rene Gauducheau, Saint-Herblain, France. 14. Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique Hôpitaux de Paris, Department of Biology, Hôpital Européen Georges Pompidou, Paris, France; INSERM UMR-S1147 Centre Universitaire des Saints Pères, Paris, France. 15. Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Paris Descartes University, Paris Sorbonne cité, Department of Digestive Oncology, HEGP, Paris, France.
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.
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 cancerpatients.
Authors: Keisuke Kosumi; Tsuyoshi Hamada; Sui Zhang; Li Liu; Annacarolina da Silva; Hideo Koh; Tyler S Twombly; Kosuke Mima; Teppei Morikawa; Mingyang Song; Jonathan A Nowak; Reiko Nishihara; Leonard B Saltz; Donna Niedzwiecki; Fang-Shu Ou; Tyler Zemla; Robert J Mayer; Hideo Baba; Kimmie Ng; Marios Giannakis; Xuehong Zhang; Kana Wu; Edward L Giovannucci; Andrew T Chan; Charles S Fuchs; Jeffrey A Meyerhardt; Shuji Ogino Journal: Eur J Cancer Date: 2019-03-01 Impact factor: 9.162
Authors: Douglas J Hartman; Madison Frank; Lindsey Seigh; Haroon Choudry; James Pingpank; Matthew Holtzman; David Bartlett; Nathan Bahary; Liron Pantanowitz; Reetesh K Pai Journal: Am J Surg Pathol Date: 2020-07 Impact factor: 6.298
Authors: Yong Joon Lee; Sat Byol Lee; Suk Kyung Beak; Yoon Dae Han; Min Soo Cho; Hyuk Hur; Kang Young Lee; Nam Kyu Kim; Byung Soh Min Journal: Sci Rep Date: 2018-05-15 Impact factor: 4.379