A diagnostic biopsy-adapted immunoscore predicts response to neoadjuvant treatment and selects patients with rectal cancer eligible for a watch-and-wait strategy.
(2020) Clinical cancer research — Vol. 26, n° 19, p. 5198-5207 (2020)
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- Authors
El Sissy, Carine 
Kirilovsky, Amos Mușină, Ana-Maria Mourin, Anne Leonard, Daniel Scripcariu, Viorel
- Abstract
- (en) PURPOSE: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy ("Watch-and-Wait"). EXPERIMENTAL DESIGN: Biopsies from two independent cohorts (n 1 = 131, n 2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait. RESULTS: ISB positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06-0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the "Watch-and-Wait" cohort (n = 73), no relapse was observed in patients with ISB high (23.3%). CONCLUSIONS: ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.
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Citations
El Sissy, C., Kirilovsky, A., Van den Eynde, M., Mușină, A.-M., Anitei, M.-G., Romero, A. M. S., Marliot, F., Haicheur, N., Junca, A., Doyen, J., Mlecnik, B., Fredriksen, T., Lagorce-Pages, C., Mourin, A., Leonard, D., Bibeau, F., Iseas, S., Roca, E. L., Cabanne, A., et al. (2020). A diagnostic biopsy-adapted immunoscore predicts response to neoadjuvant treatment and selects patients with rectal cancer eligible for a watch-and-wait strategy. Clinical cancer research, 26(19), 5198-5207. https://doi.org/10.1158/1078-0432.CCR-20-0337 (Original work published 2020)