Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer.

Authors

Bernhard Mlecnik
Carlo Bifulco, Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, Portland, ORFollow
Gabriela Bindea
Florence Marliot
Alessandro Lugli
J Jack Lee
Inti Zlobec
Tilman T Rau
Martin D Berger
Iris D Nagtegaal
Elisa Vink-Börger
Arndt Hartmann
Carol Geppert
Julie Kolwelter
Susanne Merkel
Robert Grützmann
Marc Van den Eynde
Anne Jouret-Mourin
Alex Kartheuser
Daniel Léonard
Christophe Remue
Julia Y Wang
Prashant Bavi
Michael H A Roehrl
Pamela S Ohashi
Linh T Nguyen
SeongJun Han
Heather L MacGregor
Sara Hafezi-Bakhtiari
Bradly G Wouters
Giuseppe V Masucci
Emilia K Andersson
Eva Zavadova
Michal Vocka
Jan Spacek
Lubos Petruzelka
Bohuslav Konopasek
Pavel Dundr
Helena Skalova
Kristyna Nemejcova
Gerardo Botti
Fabiana Tatangelo
Paolo Delrio
Gennaro Ciliberto
Michele Maio
Luigi Laghi
Fabio Grizzi
Tessa Fredriksen
Bénédicte Buttard
Lucie Lafontaine
Daniela Bruni
Anastasia Lanzi
Carine El Sissy
Nacilla Haicheur
Amos Kirilovsky
Anne Berger
Christine Lagorce
Christopher Paustian
Carmen Ballesteros-Merino
Jeroen Dijkstra
Carlijn van de Water
Shannon van Lent-van Vliet
Nikki Knijn
Ana-Maria Muşină
Dragos-Viorel Scripcariu
Boryana Popivanova
Mingli Xu
Tomonobu Fujita
Shoichi Hazama
Nobuaki Suzuki
Hiroaki Nagano
Kiyotaka Okuno
Toshihiko Torigoe
Noriyuki Sato
Tomohisa Furuhata
Ichiro Takemasa
Kyogo Itoh
Prabhu S Patel
Hemangini H Vora
Birva Shah
Jayendrakumar B Patel
Kruti N Rajvik
Shashank J Pandya
Shilin N Shukla
Yili Wang
Guanjun Zhang
Yutaka Kawakami
Francesco M Marincola
Paolo A Ascierto
Bernard A Fox, Chiles Research Institute Providence Portland Medical CenterFollow
Franck Pagès
Jérôme Galon

Document Type

Article

Publication Date

9-8-2020

Publication Title

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Abstract

PURPOSE: The purpose of this study was to evaluate the prognostic value of Immunoscore in patients with stage III colon cancer (CC) and to analyze its association with the effect of chemotherapy on time to recurrence (TTR).

METHODS: An international study led by the Society for Immunotherapy of Cancer evaluated the predefined consensus Immunoscore in 763 patients with American Joint Committee on Cancer/Union for International Cancer Control TNM stage III CC from cohort 1 (Canada/United States) and cohort 2 (Europe/Asia). CD3+ and cytotoxic CD8+ T lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The primary end point was TTR. Secondary end points were overall survival (OS), disease-free survival (DFS), prognosis in microsatellite stable (MSS) status, and predictive value of efficacy of chemotherapy.

RESULTS: Patients with a high Immunoscore presented with the lowest risk of recurrence, in both cohorts. Recurrence-free rates at 3 years were 56.9% (95% CI, 50.3% to 64.4%), 65.9% (95% CI, 60.8% to 71.4%), and 76.4% (95% CI, 69.3% to 84.3%) in patients with low, intermediate, and high immunoscores, respectively (hazard ratio [HR; high v low], 0.48; 95% CI, 0.32 to 0.71; P = .0003). Patients with high Immunoscore showed significant association with prolonged TTR, OS, and DFS (all P < .001). In Cox multivariable analysis stratified by participating center, Immunoscore association with TTR was independent (HR [high v low], 0.41; 95% CI, 0.25 to 0.67; P = .0003) of patient's sex, T stage, N stage, sidedness, and microsatellite instability status. Significant association of a high Immunoscore with prolonged TTR was also found among MSS patients (HR [high v low], 0.36; 95% CI, 0.21 to 0.62; P = .0003). Immunoscore had the strongest contribution χ2 proportion for influencing survival (TTR and OS). Chemotherapy was significantly associated with survival in the high-Immunoscore group for both low-risk (HR [chemotherapy v no chemotherapy], 0.42; 95% CI, 0.25 to 0.71; P = .0011) and high-risk (HR [chemotherapy v no chemotherapy], 0.5; 95% CI, 0.33 to 0.77; P = .0015) patients, in contrast to the low-Immunoscore group (P > .12).

CONCLUSION: This study shows that a high Immunoscore significantly associated with prolonged survival in stage III CC. Our findings suggest that patients with a high Immunoscore will benefit the most from chemotherapy in terms of recurrence risk.

Clinical Institute

Cancer

Clinical Institute

Digestive Health

Department

Oncology

Department

Pathology & Laboratory Medicine

Department

Earle A. Chiles Research Institute

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