TY - JOUR
T1 - International Validation of the Immunoscore Biopsy in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy
AU - El Sissy, Carine
AU - Kirilovsky, Amos
AU - Lagorce Pagès, Christine
AU - Marliot, Florence
AU - Custers, Petra A.
AU - Dizdarevic, Edina
AU - Sroussi, Marine
AU - Castillo-Martin, Mireia
AU - Haicheur, Nacilla
AU - Dermani, Mohamed
AU - Loche, Nicolas
AU - Buttard, Bénedicte
AU - Musina, Ana Maria
AU - Anitei, Maria Gabriela
AU - Van Den Berg, José G.
AU - Broeks, Annegien
AU - Iseas, Soledad
AU - Coraglio, Mariana
AU - Loria, Fernando Sanchez
AU - Romero, Alfredo
AU - Laurent-Puig, Pierre
AU - De Reyniès, Aurélien
AU - Fernandez, Laura M.
AU - Karoui, Mehdi
AU - Tougeron, David
AU - Vaccaro, Carlos A.
AU - Santino, Juan P.
AU - Poulsen, Laurids Østergaard
AU - Lindebjerg, Jan
AU - O'Connor, Juan Manuel
AU - Scripcariu, Viorel
AU - Dimofte, Mihail Gabriel
AU - Gérard, Jean Pierre
AU - Chalabi, Myriam
AU - Figueiredo, Nuno
AU - Perez, Rodrigo O.
AU - Habr-Gama, Angelita
AU - Galon, Jérôme
AU - Hansen, Torben Frøstrup
AU - Jensen, Lars Henrik
AU - Beets, Geerard
AU - Zeitoun, Guy
AU - Pagès, Franck
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
U2 - 10.1200/JCO.23.00586
DO - 10.1200/JCO.23.00586
M3 - Journal article
C2 - 37788410
AN - SCOPUS:85180564660
SN - 0732-183X
VL - 42
SP - 70
EP - 80
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 1
ER -