A prognostic model, including the EBV status of tumor cells, for primary gastric diffuse large B-cell lymphoma in the rituximab era

Eri Ishikawa, Tsutomu Tanaka, Kazuyuki Shimada, Kei Kohno, Akira Satou, Ahmed E. Eladl, Ayako Sakakibara, Kazuhiro Furukawa, Kohei Funasaka, Ryoji Miyahara, Masanao Nakamura, Hidemi Goto, Shigeo Nakamura, Seiichi Kato, Yoshiki Hirooka

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Abstract

EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), often affects the gastrointestinal tract. However, the prognostic significance of EBV associated with primary gastric DLBCL (gDLBCL) has not been established. This retrospective study included 240 patients with primary gDLBCL, diagnosed between 1995 and 2015. Tumor specimens were analyzed with EBER in situ hybridization. In 25 (10%) cases, tumor cells harbored EBV. The EBV+ group more frequently exhibited programmed death-ligand 1 (PD-L1) expression in microenvironment immune cells, but not tumor cells, compared to the EBV group (86% vs 43%, P =.006). Among 156 patients that received rituximab-containing chemotherapy, the EBV+ group had a significantly worse overall survival (OS) than the EBV group (P =.0029). Multivariate analyses identified 3 independent adverse prognostic factors of OS: multiple gastric lesions (P =.002), EBER positivity (P =.003), and B symptoms (P =.018). These factors were combined to develop a gDLBCL prognostic (gDLP) model that significantly stratified the patients into 3 distinct risk groups (Scores: good = 0, intermediate = 1, and poor = 2/3, P <.0001) with 5-year OS rates of 100%, 81%, and 39%, respectively. Patients with EBV+ gDLBCL commonly exhibited microenvironmental PD-L1 expression and showed a significantly worse prognosis than subjects with EBV gDLBCL. Our gDLP model, which included EBV+ tumor cells, provided good predictions of clinical outcome and may be useful for selecting patients in trials in the immune-oncology era.

Original languageEnglish
Pages (from-to)3510-3520
Number of pages11
JournalCancer Medicine
Volume7
Issue number7
DOIs
Publication statusPublished - 07-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Ishikawa, E., Tanaka, T., Shimada, K., Kohno, K., Satou, A., Eladl, A. E., Sakakibara, A., Furukawa, K., Funasaka, K., Miyahara, R., Nakamura, M., Goto, H., Nakamura, S., Kato, S., & Hirooka, Y. (2018). A prognostic model, including the EBV status of tumor cells, for primary gastric diffuse large B-cell lymphoma in the rituximab era. Cancer Medicine, 7(7), 3510-3520. https://doi.org/10.1002/cam4.1595