Epstein-Barr Virus-Associated Lymphoepithelioma-Like Gastric Carcinoma Presenting as a Submucosal Mass: CT Findings with Pathologic Correlation

Background: Epstein-Barr virus associated gastric carcinoma (EBVaGC) is considered a distinct GC disease entity, with the virus persisting in a latent phase. Treatment with Epirubicin, Capecitabine and Cisplatin (ECC combination) showed survival benefit in patients with GC in clinical trials (MAGIC study and CRITICS study) when compared to chemotherapy with Capecitabine and Cisplatin (GCb/Cis). Current treatment protocols for GC do not consider virus involvement. Methods: In this study, we tested a CytoLytic Virus Activation (CLVA) strategy consisting of the ECC combination or GCb/Cis together with the HDAC inhibitor Valproic acid (VPA) to define whether EBV reactivation and subsequent antiviral treatment with Ganciclovir (GCV) could be used as virus-targeted therapy for EBVaGC. Drug combinations with VPA and GCV were evaluated in multiple cell lines and in an EBVaGC mouse model based on human naturally EBV-infected SNU-719 cells. Results: EBV reactivation was demonstrated by lytic mRNA transcripts and proteins in treated cells, and the virus-reactivating capacity of different CLVA drug combinations was compared in C666.1, AGS-BX1 and SNU-719 cell lines. In an EBVaGC mouse model, GCb/Cis with VPA and GCV strongly reduced tumor volume and showed the highest potential for EBV-reactivation. Upon a single round of CLVA treatment, EBV DNA levels in circulation decreased, and loss of EBV-positive cells in treated tumors was observed. In vivo EBV-reactivation was revealed by the presence of lytic gene transcripts and proteins in tumor tissues 6 days after treatment. Conclusion: In EBVaGC model systems, CLVA treatment showed a more potent virus reactivation and killing of tumor cells when compared to standard chemotherapy alone, suggesting that addition of VPA plus GCV to the ECC or GCb/Cis combination should be considered in future clinical studies.

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Determination and genome-wide analysis of Epstein-Barr virus (EBV) sequences in EBV-associated gastric carcinoma from Guangdong, an endemic area of nasopharyngeal carcinoma

Journal of Medical Microbiology ◽

10.1099/jmm.0.000839 ◽

2018 ◽

Vol 67 (11) ◽

pp. 1614-1627 ◽

Cited By ~ 3

Author(s):

Jian-ning Chen ◽

Lu Zhou ◽

Xin-min Qiu ◽

Ri-hong Yang ◽

Jing Liang ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Gastric Carcinoma ◽

Endemic Area ◽

Epstein Barr Virus ◽

Genome Wide Analysis ◽

Barr Virus ◽

Genome Wide ◽

Epstein Barr

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

10.21203/rs.3.rs-967167/v1 ◽

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.

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