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Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer

Mlecnik, B (author)
Lugli, A (author)
Bindea, G (author)
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Marliot, F (author)
Bifulco, C (author)
Lee, JKJ (author)
Zlobec, I (author)
Rau, TT (author)
Berger, MD (author)
Nagtegaal, ID (author)
Vink-Borger, E (author)
Hartmann, A (author)
Geppert, C (author)
Kolwelter, J (author)
Merkel, S (author)
Grutzmann, R (author)
Van den Eynde, M (author)
Jouret-Mourin, A (author)
Kartheuser, A (author)
Leonard, D (author)
Remue, C (author)
Wang, J (author)
Bavi, P (author)
Roehrl, MHA (author)
Ohashi, PS (author)
Nguyen, LT (author)
Han, S (author)
MacGregor, HL (author)
Hafezi-Bakhtiari, S (author)
Wouters, BG (author)
Masucci, G (author)
Karolinska Institutet
Andersson, EK (author)
Zavadova, E (author)
Vocka, M (author)
Spacek, J (author)
Petruzelka, L (author)
Konopasek, B (author)
Dundr, P (author)
Skalova, H (author)
Nemejcova, K (author)
Botti, G (author)
Tatangelo, F (author)
Delrio, P (author)
Ciliberto, G (author)
Maio, M (author)
Laghi, L (author)
Grizzi, F (author)
Fredriksen, T (author)
Buttard, B (author)
Lafontaine, L (author)
Maby, P (author)
Majdi, A (author)
Hijazi, A (author)
El Sissy, C (author)
Kirilovsky, A (author)
Berger, A (author)
Lagorce, C (author)
Paustian, C (author)
Ballesteros-Merino, C (author)
Dijkstra, J (author)
van de Water, C (author)
Van Lent-van Vliet, S (author)
Knijn, N (author)
Musing, AM (author)
Scripcariu, DV (author)
Popivanova, B (author)
Xu, ML (author)
Fujita, T (author)
Hazama, S (author)
Suzuki, N (author)
Nagano, H (author)
Okuno, K (author)
Torigoe, T (author)
Sato, N (author)
Furuhata, T (author)
Takemasa, I (author)
Patel, P (author)
Vora, HH (author)
Shah, B (author)
Patel, JB (author)
Rajvik, KN (author)
Pandya, SJ (author)
Shukla, SN (author)
Wang, YL (author)
Zhang, GJ (author)
Kawakami, Y (author)
Marincola, FM (author)
Ascierto, PA (author)
Fox, BA (author)
Pages, F (author)
Galon, J (author)
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 (creator_code:org_t)
2023-01-08
2023
English.
In: Cancers. - : MDPI AG. - 2072-6694. ; 15:2
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4–82.6), 88.1% (95%-CI, 85.7–90.4), 93.4% (95%-CI, 91.1–95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi vs. Lo) = 0.27 (95%-CI, 0.18–0.41); p < 0.0001). In Cox multivariable analysis, the association of Immunoscore to outcome was independent (TTR: HR (Hi vs. Lo) = 0.29, (95%-CI, 0.17–0.50); p < 0.0001) of the patient’s gender, T-stage, sidedness, and microsatellite instability-status (MSI). A significant association of Immunoscore with survival was found for Stage II, high-risk Stage II, T4N0 and MSS patients. The Immunoscore also showed significant association with TTR in Stage-I (HR (Hi vs. Lo) = 0.07 (95%-CI, 0.01–0.61); P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ2 for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered.

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