1. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study
- Author
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Pages, F., Mlecnik, B., Marliot, F., Bindea, G., Ou, F.S., Bifulco, C., Lugli, A., Zlobec, I., Rau, T.T., Berger, M.D., Nagtegaal, I.D., Vink-Borger, E., Hartmann, A., Geppert, C., Kolwelter, J., Merkel, S., Grutzmann, R., Eynde, M. Van den, Jouret-Mourin, A., Kartheuser, A., Leonard, D., Remue, C., Wang, J.Y., 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., Angelova, M., Vasaturo, A., Maby, P., Church, S.E., Angell, H.K., Lafontaine, L., Bruni, D., Sissy, C. El, Haicheur, N., Kirilovsky, A., Berger, A., Lagorce, C., Meyers, J.P., Paustian, C., Feng, Z., Ballesteros-Merino, C., Dijkstra, J., Water, C. van de, Vliet, S. van, Knijn, N., Musina, 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., Itoh, K., Patel, P.S., 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., Sargent, D.J., Fox, B.A., Galon, J., Pages, F., Mlecnik, B., Marliot, F., Bindea, G., Ou, F.S., Bifulco, C., Lugli, A., Zlobec, I., Rau, T.T., Berger, M.D., Nagtegaal, I.D., Vink-Borger, E., Hartmann, A., Geppert, C., Kolwelter, J., Merkel, S., Grutzmann, R., Eynde, M. Van den, Jouret-Mourin, A., Kartheuser, A., Leonard, D., Remue, C., Wang, J.Y., 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., Angelova, M., Vasaturo, A., Maby, P., Church, S.E., Angell, H.K., Lafontaine, L., Bruni, D., Sissy, C. El, Haicheur, N., Kirilovsky, A., Berger, A., Lagorce, C., Meyers, J.P., Paustian, C., Feng, Z., Ballesteros-Merino, C., Dijkstra, J., Water, C. van de, Vliet, S. van, Knijn, N., Musina, 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., Itoh, K., Patel, P.S., 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., Sargent, D.J., Fox, B.A., and Galon, J.
- Abstract
Contains fulltext : 193579.pdf (publisher's version ) (Closed access), BACKGROUND: The estimation of risk of recurrence for patients with colon carcinoma must be improved. A robust immune score quantification is needed to introduce immune parameters into cancer classification. The aim of the study was to assess the prognostic value of total tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts with the consensus Immunoscore assay in patients with stage I-III colon cancer. METHODS: An international consortium of 14 centres in 13 countries, led by the Society for Immunotherapy of Cancer, assessed the Immunoscore assay in patients with TNM stage I-III colon cancer. Patients were randomly assigned to a training set, an internal validation set, or an external validation set. Paraffin sections of the colon tumour and invasive margin from each patient were processed by immunohistochemistry, and the densities of CD3+ and cytotoxic CD8+ T cells in the tumour and in the invasive margin were quantified by digital pathology. An Immunoscore for each patient was derived from the mean of four density percentiles. The primary endpoint was to evaluate the prognostic value of the Immunoscore for time to recurrence, defined as time from surgery to disease recurrence. Stratified multivariable Cox models were used to assess the associations between Immunoscore and outcomes, adjusting for potential confounders. Harrell's C-statistics was used to assess model performance. FINDINGS: Tissue samples from 3539 patients were processed, and samples from 2681 patients were included in the analyses after quality controls (700 patients in the training set, 636 patients in the internal validation set, and 1345 patients in the external validation set). The Immunoscore assay showed a high level of reproducibility between observers and centres (r=0.97 for colon tumour; r=0.97 for invasive margin; p<0.0001). In the training set, patients with a high Immunoscore had the lowest risk of recurrence at 5 years (14 [8%] patients with a high Immunosc
- Published
- 2018