TY - JOUR
T1 - 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
AU - Mlecnik, Bernhard
AU - Bifulco, Carlo
AU - Bindea, Gabriela
AU - Marliot, Florence
AU - Lugli, Alessandro
AU - Lee, J. Jack
AU - Zlobec, Inti
AU - Rau, Tilman T.
AU - Berger, Martin D.
AU - Nagtegaal, Iris D.
AU - Vink-Börger, Elisa
AU - Hartmann, Arndt
AU - Geppert, Carol
AU - Kolwelter, Julie
AU - Merkel, Susanne
AU - Gru tzmann, Robert
AU - Van den Eynde, Marc
AU - Jouret-Mourin, Anne
AU - Kartheuser, Alex
AU - Léonard, Daniel
AU - Remue, Christophe
AU - Wang, Julia Y.
AU - Bavi, Prashant
AU - Roehrl, Michael H.A.
AU - Ohashi, Pamela S.
AU - Nguyen, Linh T.
AU - Han, Seong Jun
AU - MacGregor, Heather L.
AU - Hafezi-Bakhtiari, Sara
AU - Wouters, Bradly G.
AU - Masucci, Giuseppe V.
AU - Andersson, Emilia K.
AU - Zavadova, Eva
AU - Vocka, Michal
AU - Spacek, Jan
AU - Petruzelka, Lubos
AU - Konopasek, Bohuslav
AU - Dundr, Pavel
AU - Skalova, Helena
AU - Nemejcova, Kristyna
AU - Botti, Gerardo
AU - Tatangelo, Fabiana
AU - Delrio, Paolo
AU - Ciliberto, Gennaro
AU - Maio, Michele
AU - Laghi, Luigi
AU - Grizzi, Fabio
AU - Fredriksen, Tessa
AU - Buttard, Béńedicte
AU - Lafontaine, Lucie
AU - Bruni, Daniela
AU - Lanzi, Anastasia
AU - El Sissy, Carine
AU - Haicheur, Nacilla
AU - Kirilovsky, Amos
AU - Berger, Anne
AU - Lagorce, Christine
AU - Paustian, Christopher
AU - Ballesteros-Merino, Carmen
AU - Dijkstra, Jeroen
AU - Van De Water, Carlijn
AU - Van Lent-Van Vliet, Shannon
AU - Knijn, Nikki
AU - Muşinǎ, Ana Maria
AU - Scripcariu, Dragos Viorel
AU - Popivanova, Boryana
AU - Xu, Mingli
AU - Fujita, Tomonobu
AU - Hazama, Shoichi
AU - Suzuki, Nobuaki
AU - Nagano, Hiroaki
AU - Okuno, Kiyotaka
AU - Torigoe, Toshihiko
AU - Sato, Noriyuki
AU - Furuhata, Tomohisa
AU - Takemasa, Ichiro
AU - Itoh, Kyogo
AU - Patel, Prabhu S.
AU - Vora, Hemangini H.
AU - Shah, Birva
AU - Patel, Jayendrakumar B.
AU - Rajvik, Kruti N.
AU - Pandya, Shashank J.
AU - Shukla, Shilin N.
AU - Wang, Yili
AU - Zhang, Guanjun
AU - Kawakami, Yutaka
AU - Marincola, Francesco M.
AU - Ascierto, Paolo A.
AU - Fox, Bernard A.
AU - Pagès, Franck
AU - Galon, Jérome
N1 - Funding Information:
Supported and led by the Society for Immunotherapy of Cancer (SITC), which provided organizational and financial support, and the steering committee that oversaw the performance of this study and managed potential conflicts of interest. This work was also supported by grants from INSERM, the LabEx Immuno-oncology, the Transcan ERAnet European Project, Association pour la Recherche contre le Cancer (ARC), CARPEM, AP-HP, INCA Translationnel, Italian Association for Cancer Research (AIRC), Japan-AMED (P-DIRECT, P-CREATE) and MEXT (Grants-in-aid for Scientific Research-S), Ministry of Health of the Czech Republic Grant No. AZV CR 15-28188A, Progres Q25-LF1, League against Cancer, Czech Republic, and by support from PathForce and Definiens. Also supported by the European Academy of Tumor Immunology (EATI), La Fondazione Melanoma Onlus, US National Cancer Institute (NCI), Biotherapy Development Association (BDA), Canadian Cancer Immunotherapy Consortium (CCIC), Cancer Immunotherapy Consortium (CIC), Cancer Research Institute (CRI), Association for Cancer Immunotherapy (CIMT), Committee for Tumor Immunology and Bio-therapy (TIBT), European Society for Cancer Immunology and Immunotherapy (ESCII), Italian Network for Tumor
Publisher Copyright:
© 2020 by American Society of Clinical Oncology.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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 CD81 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 5 .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.
AB - 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 CD81 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 5 .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.
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U2 - 10.1200/JCO.19.03205
DO - 10.1200/JCO.19.03205
M3 - Article
C2 - 32897827
AN - SCOPUS:85092566575
SN - 0732-183X
VL - 38
SP - 3638
EP - 3651
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 31
ER -