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Updated: Sep 19, 2026
Establishment and Evaluation of a Risk Prediction Model for Pathological Escalation of Gastric Low-Grade Intraepithelial Neoplasia
Published on: February 16, 2024
Clinicopathologic Features, Treatment Patterns, and Outcomes of Microsatellite Instability-High Gastric and
Dani Castillo1, Pranati Shah2, Natasha Setia1
1Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA.
Purpose:
Microsatellite instability-high (MSI-H) and deficient mismatch repair (dMMR) gastric or gastroesophageal junction (GEJ) adenocarcinomas are biologically distinct tumors with established sensitivity to immune checkpoint inhibitors (ICIs). However, real-world treatment patterns, response heterogeneity, and predictors of durable benefit remain poorly defined.
Methods:
We retrospectively analyzed patients with biopsy-confirmed MSI-H/dMMR gastric/GEJ adenocarcinoma treated at a single center. Clinicopathologic, genomic, treatment, and outcome data were collected. Molecular profiling included ARID1A, RNF43, TP53, PIK3CA, KRAS, TGFBR2, and human epidermal growth factor 2 (HER2). ICIs-treated patients were classified as achieving clinical benefit (complete response, partial response, or durable stable disease ≥16 weeks) or no clinical benefit using iRECIST v1.1 and clinical assessment. Overall survival (OS) was estimated by using the Kaplan-Meier method.
Results:
Thirty-four patients were identified (median age, 66 years; 53% male), including 21 with stage IV disease. Tumors were predominantly poorly differentiated (65%) and HER2-negative (94%), and 18% of patients had Lynch syndrome. Among 22 ICI-treated patients, 55% achieved clinical benefit, which was strongly associated with prolonged OS (P < .01). Most responses occurred at the first radiographic assessment (approximately 12 weeks). Elevated tumor mutational burden (TMB; ≥20 mutations/Mb) was present in 56% of patients but was not associated with clinical benefit (P = .40), and no individual genomic alteration significantly correlated with treatment outcome. Exploratory analyses suggested longer OS among patients with liver versus peritoneal metastases. Treatment was well tolerated, with predominantly low-grade immune-related adverse events. Baseline Eastern Cooperative Oncology Group performance status (0-1 v ≥ 2) was associated with clinical benefit (P = .049).
Conclusion:
Approximately half of the patients with MSI-H/dMMR gastric/GEJ adenocarcinoma cancers derived durable clinical benefit from ICIs, and treatment response was strongly associated with survival. Conventional genomic features, including TMB, did not predict clinical benefit, highlighting the need for additional biomarkers.
