| Source: |
El Sissy, C, Kirilovsky, A, Lagorce Pagès, C, Marliot, F, Custers, P A, Dizdarevic, E, Sroussi, M, Castillo-Martin, M, Haicheur, N, Dermani, M, Loche, N, Buttard, B, Musina, A M, Anitei, M G, van den Berg, J G, Broeks, A, Iseas, S, Coraglio, M, Loria, F S, Romero, A, Laurent-Puig, P, de Reyniès, A, Fernandez, L M, Karoui, M, Tougeron, D, Vaccaro, C A, Santino, J P, Poulsen, L Ø, Lindebjerg, J, O'Connor, J M, Scripcariu, V, Dimofte, M-G, Gérard, J-P, Chalabi, M, Figueiredo, N, Perez, R O, Habr-Gama, A, Galon, J, Hansen, T F, Jensen, L H, Beets, .... |
| Description: |
PURPOSE: No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait (W&W) strategy is currently available. Prognostic performance of the Immunoscore biopsy (IS ) was recently suggested in a preliminary study. METHODS: This international validation study included 249 patients with clinical complete response (cCR) managed by W&W strategy. Intratumoral CD3+ and CD8+ T cells were quantified on pretreatment rectal biopsies by digital pathology and converted to IS . The primary end point was time to recurrence (TTR; the time from the end of neoadjuvant treatment to the date of local regrowth or distant metastasis). Associations between IS and outcomes were analyzed by stratified Cox regression adjusted for confounders. Immune status of tumor-draining lymph nodes (n = 161) of 17 additional patients treated by neoadjuvant chemoradiotherapy and surgery was investigated by 3'RNA-Seq and immunofluorescence. RESULTS: Recurrence-free rates at 5 years were 91.3% (82.4%-100.0%), 62.5% (53.2%-73.3%), and 53.1% (42.4%-66.5%) with IS High, IS Intermediate, and IS Low, respectively (hazard ratio [HR; Low High], 6.51; 95% CI, 1.99 to 21.28; log-rank = .0004). IS was also significantly associated with disease-free survival (log-rank = .0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, IS was independent of patient age, sex, tumor location, cT stage (T, primary tumor; c, clinical), cN stage (N, regional lymph node; c, clinical), and was the strongest predictor for TTR (HR [IS High Low], 6.93; 95% CI, 2.08 to 23.15; = .0017). The addition of IS to a clinical-based model significantly improved the prediction of recurrence. Finally, B-cell proliferation and memory in draining lymph nodes was evidenced in the draining lymph nodes of patients with cCR. CONCLUSION: The IS is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome. |