scholarly journals Clinical Behavior and Treatment Response of Epstein‐Barr Virus‐Positive Metastatic Gastric Cancer: Implications for the Development of Future Trials

2020 ◽  
Vol 25 (9) ◽  
pp. 780-786 ◽  
Author(s):  
Salvatore Corallo ◽  
Giovanni Fucà ◽  
Federica Morano ◽  
Massimiliano Salati ◽  
Andrea Spallanzani ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Treatment Response ◽  
Epstein Barr Virus ◽  
Metastatic Gastric Cancer ◽  
Clinical Behavior ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Efficacy of Immune Checkpoint Inhibitors in Metastatic Epstein-Barr Virus Associated Gastric Cancer (EBVaGC): A Case Series and Review of Literature

2021 ◽  
Author(s):  
Shimeng Liang ◽  
Weibing Leng ◽  
Dan Jiang ◽  
Ming Liu ◽  
Dan Cao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Immune Checkpoint Inhibitors ◽  
Epstein Barr Virus ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Metastatic Gastric Cancer ◽  
Pooled Analysis ◽  
Barr Virus ◽  
Epstein Barr

Abstract Background Immunotherapy has revolutionized the treatment of malignant tumors. However, limited clinical data are available to report the efficacy of immune checkpoint inhibitors (ICIs) on Epstein-Barr virus-associated gastric carcinoma. Methods In this study, we report a case series of five patients with metastatic Epstein-Barr virus-associated gastric carcinoma who were treated with ICIs and to perform a pooled analysis of published cases to investigate the efficacy of ICIs in Epstein-Barr virus-associated gastric carcinoma patients. Results Between 2018 and 2020, five metastatic gastric cancer patients with EBV positivity who received PD-1 antibodies treatment were included in the analysis at the authors’ institution. Furthermore, we performed a pooled analysis of the contemporary literature. In our case series, two patients experienced partial response (PR); one patient achieved complete response (CR), whereas two patients had progression disease (PD), resulting an ORR of 60%. In the pooled analysis of all 36 patients, ORR was 48.6% (17/35). For the first line and later lines, it was 75% (3/4) and 45.2% (14/31) respectively. The ORR was 46.7% (14/30) for ICIs monotherapy and improved to 60% (3/5) by combination with chemotherapy. Conclusions These results demonstrated that an EBV-positive status was a reliable biomarker for immunotherapy in metastatic gastric cancer, especially for monotherapy. Immunotherapy combined with chemotherapy may be a better strategy, warranting further large-scale clinical trials for validation.

Clinicopathological features of program death ligand-1 expression with mismatch repair, Epstein-Barr virus status, and cancer genome alterations in metastatic gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4040-4040 ◽  
Author(s):  
Akihito Kawazoe ◽  
Kohei Shitara ◽  
Yasutoshi Kuboki ◽  
Hideaki Bando ◽  
Takashi Kojima ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mismatch Repair ◽  
Epstein Barr Virus ◽  
Metastatic Gastric Cancer ◽  
Cancer Genome ◽  
Clinicopathological Features ◽  
Barr Virus ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Epstein Barr

4040 Background: Recently, anti-programmed death 1 (PD-1) or its ligand (PD-L1) antibodies have shown promising activities in metastatic gastric cancer (MGC). However, little is known about detailed clinicopathological features of PD-L1 expression in patients (pts) with MGC. Methods: Pts with histologically confirmed MGC were eligible for this prospective observational study. PD-L1 expression on tumor cell (TC) or inflammatory cell (IC) and mismatch repair (MMR) were analyzed by immunohistochemistry (IHC). Epstein–Barr virus (EBV) was detected by in situ hybridization. The expressions of tyrosine kinase receptors (RTKs) such as HER2, EGFR and MET and cancer genome alterations were also evaluated by IHC or next generation sequencing. Results: A total of 237 pts were enrolled from September 2015 to December 2016. Samples of 199 (84.0%) pts were obtained from biopsy. PD-L1 expression on TC and IC was positive in 27 (11.4%) and 167 pts (70.5%), respectively. One hundred and seventy-one pts (72.2%) had positive PD-L1 expression on either TC or IC. MMR deficient (D-MMR) and EBV was detected in 14 (6.9%, n = 203) and 14 pts (5.9%, n = 237), respectively. PD-L1 expression on TC was more frequently observed in pts with D-MMR (P < 0.001) and KRAS mutation (P < 0.001), while that on IC was more frequently observed in pts with EBV+ (P = 0.045), lymph node metastasis (P = 0.001), and lung metastasis (P = 0.045). In contrast, pts with peritoneal metastasis were associated with less frequent PD-L1 expression in IC (P = 0.003). A significant association was not observed between PD-L1 expression and RTKs expression or presence of other gene alterations. D-MMR was significantly associated with intestinal type (P = 0.026) and absence of liver metastasis (P = 0.022). PD-L1 expression on either TC or IC was not prognostic factor (hazard ratio; 0.92, P = 0.741). Seven pts with D-MMR and seven pts with EBV+ MGC were enrolled in clinical trials of anti-PD-1/PD-L1 antibodies. Conclusions: PD-L1 expression in MGC was associated with some clinicopathological features. Impact of these characteristics on efficacy of anti-PD-1/PD-L1 antibody warrants further evaluation.

scholarly journals The Right Treatment of the Right Patient: Integrating Genetic Profiling Into Clinical Decision Making in Advanced Gastric Cancer in Asia

2021 ◽  
pp. 1-8
Author(s):  
Yoshiaki Nakamura ◽  
Kohei Shitara ◽  
Jeeyun Lee
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Mismatch Repair ◽  
Epstein Barr Virus ◽  
Clinical Decision Making ◽  
Palliative Chemotherapy ◽  
Metastatic Gastric Cancer ◽  
Barr Virus ◽  
Epstein Barr ◽  
The Right

Gastric cancer is a major global health burden, especially when patients are diagnosed with recurrent or metastatic gastric cancer. Despite recent advances in treatment options with palliative chemotherapy, the median overall survival of patients with gastric cancer remains within 1 or 2 years after the diagnosis of metastatic disease. Gastric cancer is significantly more prevalent in eastern Asia (e.g., Japan and Korea). Next-generation sequencing (NGS) is rapidly being adopted as part of clinical practice in Korea and Japan, especially in patients with gastric cancer. Approximately 10% to 15% of the patients with gastric cancer who undergo NGS of their tumor specimen are allocated to target-matched clinical trials in Japan and Korea. In Japan and Korea, a cell-free DNA NGS panel is also actively being investigated as an alternative NGS test for patients with gastric cancer, which may reflect the tumor heterogeneity of gastric cancer. In Japan and Korea, multiple biomarkers, such as HER2, mismatch repair, Epstein-Barr virus, PD-L1 (combined positive score), EGFR, FGFR2, and CLDN18.2, are routinely assessed through immunohistochemistry or in situ hybridization before initiation of the first-line treatment in all patients with gastric cancer. Most tertiary cancer centers in Korea routinely perform HER2, mismatch repair, Epstein-Barr virus, and PD-L1 NGS before palliative chemotherapy in patients with gastric cancer. Biomarker evaluation for all patients with metastatic gastric cancer enables clinicians to identify available biomarker-based clinical trials early during the course of treatment, which expands treatment opportunities while patients are medically fit for clinical trials, if available. Comprehensive genomic profiling using a tissue or circulating tumor DNA NGS panel is considered necessary during second-line or subsequent treatment. It is hoped that a comprehensive molecular profiling strategy will facilitate greater use of precision medicine through molecularly targeted therapies for patients with gastric cancer in the near future.

scholarly journals Intratumoral CXCR5+CD8+T associates with favorable clinical outcomes and immunogenic contexture in gastric cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jieti Wang ◽  
Ruochen Li ◽  
Yifan Cao ◽  
Yun Gu ◽  
Hanji Fang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Epstein Barr Virus ◽  
Effector Memory ◽  
Feature Identification ◽  
Barr Virus ◽  
T Cell Infiltration ◽  
Epstein Barr ◽  
Gastric Cancer Patients

AbstractStudies that examined an association between CD8+T and prognosis in gastric cancer are inconsistent, and a distinct population of CXCR5+CD8+T associated with better overall survival has been reported among various malignancies. Here, we show that the abundance of intratumoral CXCR5+CD8+T cells is associated with better overall survival in patients with gastric cancer. Patients with TNM II + III gastric cancer with higher intratumoral CXCR5+CD8+T cell infiltration are more likely to benefit from adjuvant chemotherapy. Microsatellite-unstable and Epstein–Barr virus positive tumors are enriched with CXCR5+CD8+T cells. Gastric cancer infiltrating CXCR5+CD8+T cells represent a specific subtype of stem-like CD8+T with effector memory feature. Identification of the clinical significance and phenotype of gastric cancer infiltrating CXCR5+CD8+T provides a roadmap for patient stratification and trials of targeted therapies.

scholarly journals Identification of differential proteomics in Epstein-Barr virus-associated gastric cancer and related functional analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zeyang Wang ◽  
Zhi Lv ◽  
Qian Xu ◽  
Liping Sun ◽  
Yuan Yuan
Keyword(s):  
Gastric Cancer ◽  
Functional Analysis ◽  
Protein Expression ◽  
Epstein Barr Virus ◽  
Protein Profile ◽  
Expression Patterns ◽  
Clinicopathological Parameters ◽  
Differential Proteomics ◽  
Barr Virus ◽  
Epstein Barr

Abstract Background Epstein-Barr virus-associated gastric cancer (EBVaGC) is the most common EBV-related malignancy. A comprehensive research for the protein expression patterns in EBVaGC established by high-throughput assay remains lacking. In the present study, the protein profile in EBVaGC tissue was explored and related functional analysis was performed. Methods Epstein-Barr virus-encoded RNA (EBER) in situ hybridization (ISH) was applied to EBV detection in GC cases. Data-independent acquisition (DIA) mass spectrometry (MS) was performed for proteomics assay of EBVaGC. Functional analysis of identified proteins was conducted with bioinformatics methods. Immunohistochemistry (IHC) staining was employed to detect protein expression in tissue. Results The proteomics study for EBVaGC was conducted with 7 pairs of GC cases. A total of 137 differentially expressed proteins in EBV-positive GC group were identified compared with EBV-negative GC group. A PPI network was constructed for all of them, and several proteins with relatively high interaction degrees could be the hub genes in EBVaGC. Gene enrichment analysis showed they might be involved in the biological pathways related to energy and biochemical metabolism. Combined with GEO datasets, a highly associated protein (GBP5) with EBVaGC was screened out and validated with IHC staining. Further analyses demonstrated that GBP5 protein might be associated with clinicopathological parameters and EBV infection in GC. Conclusions The newly identified proteins with significant differences and potential central roles could be applied as diagnostic markers of EBVaGC. Our study would provide research clues for EBVaGC pathogenesis as well as novel targets for the molecular-targeted therapy of EBVaGC.

Persistence of Epstein—Barr virus antigens in gastric cancer: characteristic of inflammatory cellular reactions in tumor

2021 ◽  
Vol 83 (1) ◽  
pp. 18
Author(s):  
N.V. Danilova ◽  
I.A. Mikhailov ◽  
N.A. Oleynikova ◽  
P.G. Malkov ◽  
A.V. Chayka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Virus Antigens ◽  
Epstein Barr
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