Clinical outcomes of Epstein–Barr virus (EBV)-associated metastatic and locally advanced unresectable gastric cancers (GCs) in patients receiving first-line fluoropyrimidine and platinum (FP) doublet chemotherapy

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association Vol. 27; no. 1; pp. 146 - 154
• Main Authors: Kim, Eo Jin, Chae, Heejung, Park, Young-Soo, Ryu, Min-Hee, Kim, Hyung-Don, Shin, Junyoung, Park, Yang Soon, Moon, Mee Sun, Kang, Yoon-Koo
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 2024; Springer Nature B.V
• Subjects: Abdominal Surgery; Cancer Research; Chemotherapy; Clinical outcomes; Cytotoxicity; Epstein-Barr virus; Epstein-Barr Virus Infections - complications; Female; Gastric cancer; Gastroenterology; Herpesvirus 4, Human - genetics; Humans; Hybridization; Immune checkpoint inhibitors; Immunogenicity; Leukocytes (neutrophilic); Lymphocytes; Male; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Metastasis; Oncology; Original Article; Palliation; Patients; Platinum; Response rates; Retrospective Studies; Stomach Neoplasms - pathology; Surgical Oncology; Survival analysis; Trastuzumab; Viruses; Stomach neoplasms; Epstein–Barr virus; Palliative chemotherapy
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-023-01445-7

Background Epstein–Barr virus-associated gastric cancer (EBVaGC) is a distinct molecular subgroup showing excellent outcomes after surgery for localized disease. Prominent immune cell infiltration in EBVaGC reflects the immunogenicity of Epstein–Barr virus (EBV) and, as suggested by some investigators, responsiveness to immune checkpoint inhibitors in the palliative setting. However, few data are available on the prevalence, clinical characteristics, and prognosis of EBVaGC patients receiving palliative cytotoxic chemotherapy. Methods In this retrospective study, we identified 1061 patients with metastatic, recurrent, or locally advanced unresectable gastric cancer (GC) who started first-line fluoropyrimidine/platinum (FP) doublet chemotherapy with or without trastuzumab from January 2015 to August 2018. For 766 patients with available tumor tissue, the presence of EBV in cancer cells was evaluated by EBV-encoded RNA in situ hybridization and correlated with clinical characteristics and treatment outcomes. Results Among the patients evaluated ( n  = 766), 40 (5.0%) were EBV-positive. EBVaGC was associated with male sex ( p  = 0.009) and lower neutrophil–lymphocyte ratio (NLR < 2.46, p  = 0.03). Efficacy of first-line FP chemotherapy, in terms of response rate ad progression-free survival (PFS), did not differ between EBVaGC and EBV-negative GC (overall response rate: 53.8% vs. 51.8%, p  = 0.99; median PFS: 6.4 vs. 6.7 months, p  = 0.90). However, overall survival tended to be better with EBVaGC than EBV-negative GC (16.4 vs. 14.0 months, p  = 0.07). Conclusions EBVaGC accounted for 5% of metastatic/unresectable GCs. While EBVaGC was not associated with better response to or PFS following first-line cytotoxic chemotherapy, it showed a trend toward better overall survival.