International validation of the Immunoscore-biopsy (IS B ) to guide selection and monitoring of patients treated with watch-and-wait (WW) strategy for rectal cancer.

Franck Pages, Carine El Sissy, Amos Kirilovsky, Petra Custers, Edina Dizdarevic, Christine Lagorce, Mireia Castillo-Martin, José van den Berg, Soledad Iseas, Fernando Sanchez Loria, Jean-Pierre Gerard, Gabriel Dimofte, Rodrigo O Perez, Angelita Habr-Gama, Nuno Figueiredo, Torben Hansen, Myriam Chalabi, Jerome Galon, Geerard Beets, Guy Zeitoun

Research output: Contribution to journalConference abstract in journalResearchpeer-review

Abstract

Background: The WW strategy for patients with rectal cancer who achieved a clinical complete response (cCR) after neoadjuvant therapy (nT) allows to avoid major resection and the associated morbidity and mortality. Standardized criteria to select and monitor WW patients, including biomarkers predicting recurrence after nT, are lacking. The prognostic impact of the immune infiltrate in colorectal cancers is now demonstrated and has been implemented into clinics through the Immunoscore, the first standardized digital-pathology-based assay, recommended by academic institutions. We evidenced that an Immunoscore adapted to biopsies (IS B ) performed at diagnosis, predicts the response to nT and the risk of recurrence after nT. Its clinical utility was suggested in a test cohort of WW patients (El Sissy et al., Clin Cancer Res 2020). The aim of this study was to confirm the ability of the IS B to predict clinical outcomes, improve patients’ eligibility for the WW strategy, and optimize a follow-up schedule. Methods: A total of 304 WW patients from 10 centers across 7 countries were included. Tumor biopsies before treatment were immunostained for CD3+ and CD8+ T-cells and converted to IS B using the pre-defined cut-off. The primary endpoint was time-to-recurrence (TTR). Secondary endpoint was disease-free-survival (DFS). As immune response originates in draining lymph nodes, signs of immune activation were carried out in lymph nodes of additional patients managed by radical surgery with complete pathological response (pCR; n = 12) or non-pCR (n = 12) by 3' RNA-Seq and immunofluorescence technologies. Results: High-IS B patients presented with the lowest risk of recurrence after WW. 5-year recurrence-free rates were 97% (92%-100%), 61% (49%-76%), and 56% (44%-73%) with IS B High, Intermediate, and Low, respectively (HR [Low-vs-High] = 14.3, 95% CI 1.8-100). In patients with cCR after nT (n = 209), High-IS B showed a significant association with prolonged TTR and DFS (Logrank P = 0.005 and P = 0.006, respectively). When IS B was evaluated as a continuous variable, the risk of recurrence was increasing along with decreasing IS B (Wald tests, all P < 0.005). In multivariate analyses, IS B was independent of age, sex, location, and cTNM stage and was the single parameter correlated with TTR (HR [IS B High-vs-Low] = 0.08, 95% CI 0.01-0.6; P = 0.015) and DFS (P = 0.013). Unlike for patients with cCR, no difference according to IS B was observed for those with incomplete response (n = 41) or treated with brachytherapy (n = 34). Finally, intranodal signs of T-cell and B-cell activation were only evidenced in patients with pCR. Conclusions: IS B provides a reliable biomarker to predict clinical outcomes, improve eligibility, and optimize patients’ follow-up. Intranodal T-cell and B-cell activation further supports the immune benefit of both organ and lymph node preservation.
Original languageEnglish
Article number3517
JournalJournal of Clinical Oncology
Volume40
Issue number16. suppl.
Pages (from-to)3517
Number of pages1
ISSN0732-183X
DOIs
Publication statusPublished - 2022
Event2022 ASCO annual meeting - McCormick Place, Chicago, United States
Duration: 3. Jun 20227. Jun 2022

Conference

Conference2022 ASCO annual meeting
LocationMcCormick Place
Country/TerritoryUnited States
CityChicago
Period03/06/202207/06/2022

Cite this