International Validation of the Immunoscore Biopsy in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy

Carine El Sissy, Amos Kirilovsky, Christine Lagorce Pagès, Florence Marliot, Petra A. Custers, Edina Dizdarevic, Marine Sroussi, Mireia Castillo-Martin, Nacilla Haicheur, Mohamed Dermani, Nicolas Loche, Bénedicte Buttard, Ana Maria Musina, Maria Gabriela Anitei, José G. Van Den Berg, Annegien Broeks, Soledad Iseas, Mariana Coraglio, Fernando Sanchez Loria, Alfredo RomeroPierre Laurent-Puig, Aurélien De Reyniès, Laura M. Fernandez, Mehdi Karoui, David Tougeron, Carlos A. Vaccaro, Juan P. Santino, Laurids Østergaard Poulsen, Jan Lindebjerg, Juan Manuel O'Connor, Viorel Scripcariu, Mihail Gabriel Dimofte, Jean Pierre Gérard, Myriam Chalabi, Nuno Figueiredo, Rodrigo O. Perez, Angelita Habr-Gama, Jérôme Galon, Torben Frøstrup Hansen, Lars Henrik Jensen, Geerard Beets, Guy Zeitoun, Franck Pagès

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

PURPOSENo 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 (ISB) was recently suggested in a preliminary study.METHODSThis 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 ISB. 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 ISB 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.RESULTSRecurrence-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 ISB High, ISB Intermediate, and ISB Low, respectively (hazard ratio [HR; Low v High], 6.51; 95% CI, 1.99 to 21.28; log-rank P =.0004). ISB was also significantly associated with disease-free survival (log-rank P =.0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, ISB 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 [ISB High v Low], 6.93; 95% CI, 2.08 to 23.15; P =.0017). The addition of ISB 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.CONCLUSIONThe ISB is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome.

Original languageEnglish
Pages (from-to)70-80
Number of pages11
JournalJournal of Clinical Oncology
Volume42
Issue number1
DOIs
StatePublished - 1 Jan 2024
Externally publishedYes

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