Plasma EBV DNA as a prognostic factor in EBV associated gastric cancer: a multicenter, prospective study (EBV PRESAGE study)

Andrea Alberti; Gertraud Stocker; Florian Lordick; Ulrich T Hacker; Benjamin Kobitzsch; Ivonne Haffner; Gian Luca Baiocchi; Manuel Zamparini; Guido A M Tiberio; Carla Baronchelli; Arnaldo Caruso; Paolo Bossi; Alfredo Berruti

doi:10.3389/fonc.2023.1276138

Plasma EBV DNA as a prognostic factor in EBV associated gastric cancer: a multicenter, prospective study (EBV PRESAGE study)

Front Oncol. 2023 Oct 24:13:1276138. doi: 10.3389/fonc.2023.1276138. eCollection 2023.

Affiliations

¹ Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia at the Azienda Socio Sanitaria Territoriale (ASST)-Spedali Civili, Brescia, Italy.
² Department of Medicine II (Oncology, Gastroenterology, Hepatology and Pulmonology), University Cancer Center Leipzig (UCCL), University of Leipzig Medical Center, Leipzig, Germany.
³ Surgical Unit, Department of Clinical and Experimental Sciences, University of Brescia at the Azienda Socio Sanitaria Territoriale (ASST), Cremona, Italy.
⁴ Surgical Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia at the Azienda Socio Sanitaria Territoriale (ASST)-Spedali Civili, Brescia, Italy.
⁵ Pathology Unit, Azienda Socio Sanitaria Territoriale (ASST)-Spedali Civili, Brescia, Italy.
⁶ Microbiology Unit, Department of Molecular and Translational Medicine, University of Brescia-Spedali Civili at the Azienda Socio Sanitaria Territoriale (ASST) - Spedali Civili, Brescia, Italy.
⁷ Medical Oncology and Hematology Unit, Humanitas University, IRCCS Humanitas Research Hospital, Milan, Italy.

Abstract

Purpose: The Cancer Genome Atlas Research Network identified Epstein-Barr-Virus (EBV)-positive gastric cancer as a distinct molecular subtype. The prevalence is 8-9% and the histological examination shows pronounced lymphocytic infiltration, elevated levels of IFN-γ and consequently overexpression of PD-L1. The role of plasma EBV DNA load as a prognostic factor in patients with this cancer subtype is still to be defined.

Methods and analysis: The present multicenter prospective observational study "EBV PRESAGE", involving German and Italian cancer centers, aims to evaluate the prognostic role of plasma EBV DNA in EBV-related gastric cancer (GC). The objective is to study the association between plasma EBV DNA load at different consecutive time points and the patient's prognosis. Every patient with a new diagnosis of gastric cancer (including gastroesophageal junction adenocarcinoma) will be screened for Epstein-Barr encoded small Region (EBER) on tissue biopsies using in situ hybridization (ISH). If EBER ISH is positive, blood analysis for plasma EBV DNA will be conducted. The plasma EBV quantitative analysis will be centralized, and extraction, detection, and quantification of EBV DNA in plasma samples will be performed using real-time PCR.

Discussion: We hypothesized that plasma EBV DNA represents a non-invasive tool for monitoring EBV-related GC and might be valuable as a prognostic marker.

Keywords: disease-free survival; epstein barr virus DNA; gastric and gastroesophageal junction adenocarcinoma; prognostic factor; prospective multicenter study.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project is supported by the nonprofit foundation RicerChiAmo Onlus.