Abstract 354: Mucinous phenotype is associated with response to neoadjuvant chemotherapy in microsatellite instable resectable gastric cancer
Authors: Biesma H.D. , Soeratram A.T.T.D. , Sikorska K. , Caspers I.A. , van Essen H.F. , Egthuijsen J.M.P. , Mookhoek A. , Hoek D.M. , Vos W. , van Laarhoven H.W.M. , Nordsmark M. , van der Peet D.L. , Warmerdam F.A.R.M. , Geenen M.M. , Loosveld O.J.L. , Portielje J.E.A. , Los M. , Kranenbarg E. Meershoek - Klein , Hartgrink H.H. , van Sandick J. , van de Velde C.J.H. , Verheij M. , Cats A. , Ylstra B. , van Grieken N.C.T. ,   On behalf of the CRITICS investigators
Published: July 2021

Abstract
Background: Epstein-Barr virus positivity (EBV+) and microsatellite instability (MSI-high) have been shown to be positive prognostic factors for long term survival in resectable gastric cancer (GC) in several studies. However, the benefit of perioperative treatment in patients with MSI-high tumors remains topic of discussion. Here, we present the clinicopathological outcome of patients with EBV+ and MSI-high GCs treated with surgery only in the Dutch D1/D2 trial, and treated with chemotherapy or chemoradiotherapy after preoperative chemotherapy and surgery in the CRITICS trial.
Patients and methods: EBV was determined in tumor tissue using EBV-encoded RNA in situ hybridization (EBER-ISH). PCR and/or immunohistochemistry were performed to determine MSI status. Results were correlated to histopathological response, morphological tumor characteristics and survival.
Results: In the Dutch D1/D2 trial 10.5% (47/447) of tumors were EBV+ and 10.5% (47/447) were MSI-high. In the CRITICS trial 5.5% (25/451) of tumors were EBV+ and 5.5% (25/451) were MSI-high tumors. In the Dutch D1/D2 trial, five-year overall survival probability was 51.1% for EBV+, 46.8% for MSI-high, and 42.5% for EBV-/MSS (P=0.19). In the CRITICS trial, five-year overall survival was 56.0% for EBV+, 47.3% for MSI-high, and 36.5% for EBV-/MSS (P=0.22). In the CRITICS trial, 3 (12.5%) MSI-high tumors showed moderate to complete histopathological response. Interestingly, all three showed a mucinous phenotype. Eight (36.4%) EBV+ and 114 (29.9%) EBV-/MSS tumors showed moderate to complete histopathological response. None of the EBV+ GCs showed mucinous differentiation.
Conclusions: The favorable outcome of GC patients with resectable EBV+ or MSI-high tumors compared to EBV-/MSS tumors remains after perioperative chemotherapy. In MSI-high tumors significant histopathological response to neoadjuvant chemotherapy was found only in those with a mucinous phenotype.
Citation Format: H.D. Biesma, A.T.T.D. Soeratram, K. Sikorska, I.A. Caspers, H.F. van Essen, J.M.P. Egthuijsen, A. Mookhoek, D.M. Hoek, W. Vos, H.W.M. van Laarhoven, M. Nordsmark, D.L. van der Peet, F.A.R.M. Warmerdam, M.M. Geenen, O.J.L. Loosveld, J.E.A. Portielje, M. Los, E. Meershoek - Klein Kranenbarg, H.H. Hartgrink, J. van Sandick, C.J.H. van de Velde, M. Verheij, A. Cats, B. Ylstra, N.C.T. van Grieken, On behalf of the CRITICS investigators. Mucinous phenotype is associated with response to neoadjuvant chemotherapy in microsatellite instable resectable gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 354.