The consensus Immunoscore adapted to biopsies in patients with locally advanced rectal cancer: Potential clinical significance for a “Watch and Wait” strategy.

El Sissy, Carine;Kirilovsky, Amos;Van den Eynde, Marc;Romero, Alfredo;Pages, Franck;et.al.
(2019) Meeting Abstract | 2019 ASCO Annual Meeting I - DEVELOPMENTAL IMMUNOTHERAPY AND TUMOR IMMUNOBIOLOGY

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Authors
  • El Sissy, Carine
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  • Kirilovsky, Amos
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  • Van den Eynde, MarcUCLouvain
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  • Romero, Alfredo
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  • Pages, Franck
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Abstract
Background: We investigated whether an adaptation to rectal biopsies of the recently validated consensus Immunoscore, could predict the response to neoadjuvant treatment and delineate clinical responders that could benefit from a “Watch and Wait” (W&W) strategy with acceptable outcomes. Methods: Initial biopsies from 273 patients with locally advanced rectal cancer (LARC) treated by neoadjuvant chemoradiotherapy (nCRT) followed by Total Mesorectal Excision (TME), were immunostained for CD3+ and cytotoxic CD8+ T cells and quantified by digital pathology to determine the Immunoscore within pre-treatment Biopsy (ISB). Expression level of 44 immune related genes post-neoadjuvant treatment was investigated by Nanostring technology (n = 64 patients). Results were correlated with response to neoadjuvant treatment, disease free survival (DFS) and time to recurrence (TTR). Prognostic performance of ISB was finally assessed in 73 LARC treated by W&W strategy. Results: ISB Low, Intermediate and High were respectively observed in 23.3, 50.4 and 26.3 % of the cohort. ISB was positively and significantly correlated with the response to nCRT, as evaluated by Dworak classification (P = .0034), ypTNM (P = .0003), down-staging (P = .0014), and neoadjuvant rectal (NAR) score, (P < .0001). ISB status was also positively associated with the degree of local immune activation post-neoadjuvant treatment. ISB High patients were at low risk of relapse, with 5-year DFS rates of 81.1 % (CI, 71.3-92.1 %) as compared to 57.8 % (CI, 45.9-72.9 %) in ISB low patients. In multivariate analysis, ISB was the only significant parameter at presentation associated with DFS (High vs Low: P = .001). Among W&W patients, significant difference was observed for TTR according to ISB status (High vs Low: P = .025). Conclusions: ISB could provide a reliable estimate of the response to nCRT and risk of recurrence in LARC patients' treated by TME or W&W strategy.
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El Sissy, C., Kirilovsky, A., Van den Eynde, M., Romero, A., Marliot, F., Lagorce, C., Bibeau, F., Iseas, I. S., Roca, E. L., Vaccaro, C. A., Tougeron, D., Carvalho, C. T., Figueiredo, N., Perez, R. O., Habr Gama, A., Scripcariu, V., Gerard, J.-P., Galon, J., Zeitoun, G., & Pages, F. (2019). The consensus Immunoscore adapted to biopsies in patients with locally advanced rectal cancer: Potential clinical significance for a “Watch and Wait” strategy. Journal of Clinical Oncology, 37(15_suppl), 2628. https://doi.org/10.1200/jco.2019.37.15_suppl.2628 (Original work published 2019)