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

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.

SUBMITTER: Ishikawa E

PROVIDER: S-EPMC6051208 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Ishikawa Eri E Tanaka Tsutomu T Shimada Kazuyuki K Kohno Kei K Satou Akira A Eladl Ahmed E AE Sakakibara Ayako A Furukawa Kazuhiro K Funasaka Kohei K Miyahara Ryoji R Nakamura Masanao M Goto Hidemi H Nakamura Shigeo S Kato Seiichi S Hirooka Yoshiki Y

Cancer medicine 20180601 7

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<sup>+</sup> group more frequently exhibit ...[more]

PMID: 29856127

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Project description:BackgroundPatients with diffuse large B-cell lymphoma (DLBCL) with concurrent hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection have distinct clinical features. Nevertheless, the prognostic value of HBsAg in DLBCL in the rituximab era remains unclear.Materials and methodsWe conducted a retrospective cohort study to investigate the clinical relevance of HBsAg in immunocompetent patients with DLBCL treated with homogeneous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone between 2002 and 2016.ResultsAmong 416 analyzed patients, 98 (23.6%) were HBsAg positive. HBsAg positivity was associated with a younger age and more advanced stage at diagnosis, more frequent hepatic impairment during perichemotherapy, and a trend of higher National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score at diagnosis. Compared with the HBsAg-negative patients, the HBsAg-positive patients had a lower overall response rate (76.5% vs. 85.5%, p = .043), poorer 5-year overall survival (OS) rate (57.2% vs. 73.5%, p < .001), and shorter 5-year progression-free survival (PFS) rate (47.2% vs. 60.7%, p = .013). Multivariate analyses showed that HBsAg positivity was an independent unfavorable prognostic indicator for OS and PFS. A scoring system incorporating HBsAg positivity, the NCCN-IPI score, and serum albumin levels proved to be useful for stratifying prognostically relevant subgroups of patients with DLBCL.ConclusionThis study demonstrated that HBV infection is uniquely relevant to DLBCL. HBsAg might serve as a novel biomarker to improve clinical risk stratification of patients with DLBCL in areas with high prevalence of HBV infection. Further research investigating the etiopathogenesis of HBV infection in DLBCL is imperative.Implications for practiceA considerable disparity exists regarding the prognostic relevance of hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection in patients with diffuse large B-cell lymphoma (DLBCL). In this large, retrospective cohort study from an area with high prevalence of HBV infection, the authors demonstrated that HBsAg was an independent unfavorable factor significantly associated with survival, highlighting its potential as a novel prognostic indicator to improve the risk stratification of patients with DLBCL in the rituximab era.

Dataset Information

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

Publications

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

Similar Datasets

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