Relationship of circulating tumor cells and Epstein–Barr virus DNA to progression‐free survival and overall survival in metastatic nasopharyngeal carcinoma patients

PURPOSE Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, –4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

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The impact of Epstein-Barr virus status on clinical outcome in diffuse large B-cell lymphoma

Blood ◽

10.1182/blood-2007-01-067769 ◽

2007 ◽

Vol 110 (3) ◽

pp. 972-978 ◽

Cited By ~ 220

Author(s):

Sarah Park ◽

Jeeyun Lee ◽

Young Hyeh Ko ◽

Arum Han ◽

Hyun Jung Jun ◽

...

Keyword(s):

In Situ Hybridization ◽

B Cell ◽

Epstein Barr Virus ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Free Survival ◽

Barr Virus ◽

Large B Cell Lymphoma ◽

Epstein Barr

AbstractTo define prognostic impact of Epstein-Barr virus (EBV) infection in diffuse large B-cell lymphoma (DLBCL), we investigated EBV status in patients with DLBCL. In all, 380 slides from paraffin-embedded tissue were available for analysis by EBV-encoded RNA-1 (EBER) in situ hybridization, and 34 cases (9.0%) were identified as EBER-positive. EBER positivity was significantly associated with age greater than 60 years (P = .005), more advanced stage (P < .001), more than one extranodal involvement (P = .009), higher International Prognostic Index (IPI) risk group (P = .015), presence of B symptom (P = .004), and poorer outcome to initial treatment (P = .006). The EBER+ patients with DLBCL demonstrated substantially poorer overall survival (EBER+ vs EBER− 35.8 months [95% confidence interval (CI), 0-114.1 months] vs not reached, P = .026) and progression-free survival (EBER+ vs EBER− 12.8 months [95% CI, 0-31.8 months] vs 35.8 months [95% CI, 0-114.1 months], respectively (P = .018). In nongerminal center B-cell–like subtype, EBER in situ hybridization positivity retained its statistical significance at the multivariate level (P = .045). Nongerminal center B-cell–like patients with DLBCL with EBER positivity showed substantially poorer overall survival with 2.9-fold (95% CI, 1.1-8.1) risk for death. Taken together, DLBCL patients with EBER in situ hybridization+ pursued more rapidly deteriorating clinical course with poorer treatment response, survival, and progression-free survival.

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Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742)

Journal of Clinical Oncology ◽

10.1200/jco.2017.77.0388 ◽

2018 ◽

Vol 36 (14) ◽

pp. 1412-1418 ◽

Cited By ~ 94

Author(s):

Brigette B.Y. Ma ◽

Wan-Teck Lim ◽

Boon-Cher Goh ◽

Edwin P. Hui ◽

Kwok-Wai Lo ◽

...

Keyword(s):

Overall Survival ◽

Survival Rate ◽

Nasopharyngeal Carcinoma ◽

Antitumor Activity ◽

Epstein Barr Virus ◽

Objective Response ◽

Human Leukocyte ◽

Overall Survival Rate ◽

Barr Virus ◽

Epstein Barr

Purpose This multinational study evaluated the antitumor activity of nivolumab in nasopharyngeal carcinoma (NPC). Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Patients and Methods Patients with multiply pretreated recurrent or metastatic NPC were treated with nivolumab until disease progression. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity. The expression of programmed death-ligand 1 (PD-L1) and human leukocyte antigens A and B in archived tumors and plasma clearance of Epstein-Barr virus DNA were correlated with ORR and survival. Results A total of 44 patients were evaluated and the overall ORR was 20.5% (complete response, n = 1; partial response, n = 8). Nine patients received nivolumab for > 12 months (20%). The 1-year overall survival rate was 59% (95% CI, 44.3% to 78.5%) and 1-year progression-free survival (PFS) rate was 19.3% (95% CI, 10.1% to 37.2%). There was no statistical correlation between ORR and the biomarkers; however, a descriptive analysis showed that the proportion of patients who responded was higher among those with PD-L1 positive tumors (> 1% expression) than those with PD-L1-negative tumors. The loss of expression of one or both human leukocyte antigen class 1 proteins was associated with better PFS than when both proteins were expressed (1-year PFS, 30.9% v 5.6%; log-rank P = .01). There was no association between survival and PD-L1 expression or plasma Epstein-Barr virus DNA clearance. There was no unexpected toxicity to nivolumab. Conclusion Nivolumab has promising activity in NPC and the 1-year overall survival rate compares favorably with historic data in similar populations. Additional evaluation in a randomized setting is warranted. The biomarker results were hypothesis generating and validation in larger cohorts is needed.

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Establishing M1 stage subdivisions by incorporating radiological features and Epstein-Barr virus DNA for metastatic nasopharyngeal carcinoma

Annals of Translational Medicine ◽

10.21037/atm.2020.01.13 ◽

2020 ◽

Vol 8 (4) ◽

pp. 83-83

Author(s):

Wei-Hong Zheng ◽

Xiao-Jun He ◽

Fo-Ping Chen ◽

Li Lin ◽

Xiao-Dan Huang ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Epstein Barr Virus ◽

Barr Virus ◽

Radiological Features ◽

Metastatic Nasopharyngeal Carcinoma ◽

Epstein Barr

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Detection of Epstein-Barr Virus DNA in the Peripheral-Blood Cells of Patients With Nasopharyngeal Carcinoma: Relationship to Distant Metastasis and Survival

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.10.2607 ◽

2001 ◽

Vol 19 (10) ◽

pp. 2607-2615 ◽

Cited By ~ 79

Author(s):

Jin-Ching Lin ◽

Kuang Y. Chen ◽

Wen-Yi Wang ◽

Jian-Sheng Jan ◽

Wen-Miin Liang ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Distant Metastasis ◽

Peripheral Blood ◽

Blood Cells ◽

Epstein Barr Virus ◽

Peripheral Blood Cells ◽

Free Survival ◽

Barr Virus ◽

Kaplan Meier ◽

Epstein Barr

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proved to be an Epstein-Barr virus (EBV)-associated cancer. By use of nested polymerase chain reactions (PCRs), we examined whether the presence of EBV DNA in the peripheral-blood cells (PBC) can serve as a prognostic indicator for NPC.PATIENTS AND METHODS: Peripheral blood from 124 patients with NPC who had no evidence of distant metastasis and 114 healthy volunteers with serologically positive findings for EBV infection was collected prospectively. Plasma and erythrocytes were separated. DNA was extracted from PBCs and analyzed by a nested PCR using primers specific to Epstein-Barr virus nuclear antigen 1 (EBNA-1). All patients were treated by radiotherapy with or without chemotherapy. Clinical parameters and status of EBNA-1 in PBCs were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards model.RESULTS: Positive rates of EBNA-1 DNA in PBCs of NPC patients and healthy volunteers are 71% and 14%, respectively (P = .001). No significant difference was observed with regard to the clinical characteristics of patients who were EBNA-1–positive (n = 88) and those who were EBNA-1–negative (n = 36). After a median follow-up period of 38 months (range, 24 to 56 months), 29 of 88 EBNA-1–positive patients and only one of 36 EBNA-1–negative patients developed distant metastases (P = .00015). Kaplan-Meier estimates of overall survival (P = .0010), metastasis-free survival (P = .0004), and progression-free survival (P = .0004) were significantly lower for the patients in the EBNA-1–positive group than for those in the EBNA-1–negative group. Multivariate Cox analysis confirmed the same results.CONCLUSION: The presence of EBNA-1 DNA in PBCs is a novel, important risk factor for patients with NPC that indicates a significantly higher risk of developing distant metastasis as well as a lower survival rate.

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The impact of Epstein-Barr virus status on primary CNS lymphoma survival.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13528 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13528-e13528

Author(s):

Isabel P Prado ◽

Frank Barbiero ◽

Joachim M. Baehring ◽

Kevin Becker ◽

Zachary Corbin

Keyword(s):

Overall Survival ◽

Epstein Barr Virus ◽

Primary Cns Lymphoma ◽

Cns Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Barr Virus ◽

Immunohistochemical Markers ◽

Epstein Barr ◽

The Impact

e13528 Background: Primary CNS lymphoma (PCNSL) incidence is increasing among the elderly and immunocompromised. Especially for these vulnerable populations, a deeper understanding of the prognostic value of tumor biomarkers is necessary to recommend more targeted therapies. Our primary objective is to evaluate the predictive strength of immunohistochemical markers on PCNSL overall survival. Secondary objectives include estimating the impact of these biomarkers on event-free survival. Methods: We retrospectively analyzed PCNSL patients treated at Yale between 2000 and 2018. The primary endpoint is overall survival. Event-free survival, measured by time to relapse or death, is the secondary endpoint. Kaplan-Meier survival curves with log-log confidence intervals were used to estimate survival outcomes. Cox proportional hazards regression models were used to evaluate the statistical significance (at alpha = 0.05) of immunohistochemical markers. Results: One hundred ten subjects were analyzed. Not all biomarkers were available for every subject. The median age of the cohort is 64 years. Sixty-three patients died, and seventy-six experienced an event (progression or death). Surviving patients had a median follow-up of 4.36 years. The median overall survival is 2.63 years (95% confidence interval (CI): 1.13 to 5.98 years). Epstein-Barr virus (EBV) status by immunohistochemistry significantly impacted overall survival. Adjusting for age and immunocompromised status, EBV-positive patients had a higher risk of death than EBV-negative patients (n = 13, hazard ratio (HR) = 33.75, 95% CI: 1.61-708.68). Other significant biomarkers include the GFAP and S100 proteins. The median event-free survival is 1.13 years (95% CI: 0.66 to 2.12 years), and EBV-positive patients had an increased risk of event (HR = 38.23, 95% CI: 2.32-630.88). CD10, BCL2, BCL6, and MUM1 were not significant to predict either survival outcome. Conclusions: We describe a large cohort of PCNSL patients treated at a single institution with comparable survival outcomes to similar research yet conflicting evidence of biomarker significance. Multi-institutional studies may further clarify the prognostic role of immunohistochemistry for improved PCNSL patient survival.

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Impact of Donor Epstein-Barr Virus Serostatus on the Incidence of Graft-Versus-Host Disease in Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation: A Study From the Acute Leukemia and Infectious Diseases Working Parties of the European Society for Blood and Marrow Transplantation

Journal of Clinical Oncology ◽

10.1200/jco.2015.64.2405 ◽

2016 ◽

Vol 34 (19) ◽

pp. 2212-2220 ◽

Cited By ~ 19

Author(s):

Jan Styczynski ◽

Gloria Tridello ◽

Lidia Gil ◽

Per Ljungman ◽

Jennifer Hoek ◽

...

Keyword(s):

Overall Survival ◽

Acute Leukemia ◽

Epstein Barr Virus ◽

Chronic Gvhd ◽

Relapse Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Graft Versus Host ◽

Barr Virus ◽

Epstein Barr

Purpose We investigated the effect of Epstein-Barr virus (EBV) serostatus on the overall outcome of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Patients and Methods The study included 11,364 patients who underwent allogeneic peripheral-blood or bone marrow transplantation for acute leukemia between 1997 and 2012. We analyzed the impact of donor and recipient EBV serologic status on overall survival, relapse-free survival, relapse incidence, nonrelapse mortality, and incidence of graft-versus-host disease (GVHD) after allo-HSCT. Results Patients receiving grafts from EBV-seropositive donors had the same overall survival as patients who received grafts from EBV-seronegative donors (hazard ratio [HR], 1.05; 95% CI, 0.97 to 1.12; P = .23). Seropositive donors also had no influence on relapse-free survival (HR, 1.04; 95% CI, 0.97 to 1.11; P = 0.31), relapse incidence (HR, 1.03; 95% CI, 0.94 to 1.12; P = .58), and nonrelapse mortality (HR, 1.05; 95% CI, 0.94 to 1.17; P = .37). However, in univariate analysis, recipients receiving grafts from seropositive donors had a higher risk of chronic GVHD than those with seronegative donors (40.8% v 31.0%, respectively; P < .001; HR, 1.42; 95% CI, 1.30 to 1.56). When adjusting for confounders, higher risk was identified for both acute and chronic GVHD. In seronegative patients with seropositive donors, the HR for chronic GVHD was 1.30 (95% CI, 1.06 to 1.59; P = .039). In seropositive patients with seropositive donors, the HR was 1.24 (95% CI, 1.07 to 1.45; P = .016) for acute GVHD and 1.43 (95% CI, 1.23 to 1.67; P < .001) for chronic GVHD. Seropositive patients with seronegative donors did not have an increased risk of GVHD. Conclusion Our data suggest that donor EBV status significantly influences development of acute and chronic GVHD after allo-HSCT.

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