| Authors: |
Mlecnik, B.; Lugli, A.; Bindea, G.; Marliot, F.; Bifulco, C.; Lee, J. K. J.; Zlobec, I.; Rau, T. T.; Berger, M. D.; Nagtegaal, I. D.; Vink-Börger, E.; Hartmann, A.; Geppert, C. I.; Kolwelter, J.; Merkel, S.; Grützmann, R.; Van den Eynde, M.; Jouret-Mourin, A.; Kartheuser, A.; Léonard, D.; Remue, C.; Wang, J.; Bavi, P.; Roehrl, M. H. A.; Ohashi, P. S.; Nguyen, L. T.; Han, S.; MacGregor, H. L.; Hafezi-Bakhtiari, S.; Wouters, B. G.; Masucci, G. V.; Andersson, E. K.; Zavadova, E.; Vocka, M.; Spacek, J.; Petruzelka, L.; Konopasek, B.; Dundr, P.; Skalova, H.; Nemejcova, K.; Botti, G.; Tatangelo, F.; Delrio, P.; Ciliberto, G.; Maio, M.; Laghi, L.; Grizzi, F.; Fredriksen, T.; Buttard, B.; Lafontaine, L.; Maby, P.; Majdi, A.; Hijazi, A.; El Sissy, C.; Kirilovsky, A.; Berger, A.; Lagorce, C.; Paustian, C.; Ballesteros-Merino, C.; Dijkstra, J.; van de Water, C.; Vliet, S. V. L. V.; Knijn, N.; Mușină, A. M.; Scripcariu, D. V.; Popivanova, B.; Xu, M.; Fujita, T.; Hazama, S.; Suzuki, N.; Nagano, H.; Okuno, K.; Torigoe, T.; Sato, N.; Furuhata, T.; Takemasa, I.; Patel, P.; Vora, H. H.; Shah, B.; Patel, J. B.; Rajvik, K. N.; Pandya, S. J.; Shukla, S. N.; Wang, Y.; Zhang, G.; Kawakami, Y.; Marincola, F. M.; Ascierto, P. A.; Fox, B. A.; Pagès, F.; Galon, J. |
| Article Title: |
Multicenter international study of the consensus immunoscore for the prediction of relapse and survival in early-stage colon cancer |
| Abstract: |
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. © 2023 by the authors. |
| Keywords: |
adult; cancer chemotherapy; cancer survival; controlled study; aged; major clinical study; overall survival; cancer recurrence; cancer patient; cancer staging; consensus; cohort analysis; high risk patient; proportional hazards model; colon cancer; microsatellite instability; scoring system; gender; early-stage; tumor microenvironment; low risk patient; cancer prognosis; immunoscore; predictive biomarkers; prognosis; human; male; female; article; cancer free survival
|
| Journal Title: |
Cancers
|
| Volume: |
15 |
| Issue: |
2 |
| ISSN: |
2072-6694 |
| Publisher: |
MDPI
|
| Date Published: |
2023-01-02 |
| Start Page: |
418 |
| Language: |
English |
| DOI: |
10.3390/cancers15020418
|
| PROVIDER: |
scopus
|
| PMCID: |
PMC9856473
|
| PUBMED: |
36672367
|
| DOI/URL: |
|
| Notes: |
The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
