biostudies-literatureMlecnik BMEXTThe Society for Immunotherapy of Cancer (SITC)La Ligue contre le CancerJapan-AMEDNIH/NCIHalioDxNCI NIH HHS418https://www.ebi.ac.uk/biostudies/studies/S-EPMC9856473biostudies-literatureUnknown15(2)<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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); <i>p</i> &lt; 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); <i>p</i> &lt; 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); <i>P</i> = 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.<h4>Conclusion</h4>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.CancersMulticenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer.PMC9856473R21 CA251992 and R21 CA263262.P30 CA008748UMRS1138Agreement number EL2019Grants-in-aid for Scientific Research-SP-DIRECTZhang GMasucci GVGrizzi FMusina AMJouret-Mourin AOhashi PSMarincola FMWang JHazama SDundr PKirilovsky APatel PKawakami YMaby PFuruhata TFox BASkalova HLee JJKnijn NPages FBerger MDHafezi-Bakhtiari SHijazi AWang YTatangelo FMerkel SBerger ARau TTKonopasek BCiliberto GXu MWouters BGZlobec IAscierto PANguyen LTPaustian CMlecnik BBavi Pvan de Water CMarliot FNagano HTorigoe TScripcariu DVVan den Eynde MButtard BDijkstra JRajvik KNBindea GEl Sissy CBallesteros-Merino CKolwelter JLeonard DKartheuser ASuzuki NBifulco CLafontaine LVocka MSpacek JHan SGeppert CIAndersson EKNagtegaal IDPandya SJDelrio PMajdi ABotti GVliet SVLLugli AGrutzmann RRemue CMacGregor HLOkuno KPatel JBShukla SNNemejcova KLaghi LFujita THartmann AFredriksen TMaio MVora HHZavadova EVink-Borger ETakemasa IShah BSato NLagorce CRoehrl MHAGalon JPopivanova BPetruzelka LfalseMulticenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer.<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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); <i>p</i> &lt; 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); <i>p</i> &lt; 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); <i>P</i> = 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.<h4>Conclusion</h4>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.2023-01-01T00:00:00Z2023 Jan2025-04-04T11:33:10.726Z2025-04-04T11:33:10.726ZS-EPMC98564733667236710.3390/cancers15020418