Circulating Plasma Epstein-Barr Virus DNA Load During the Follow-up Periods Predicts Recurrence and Metastasis in Nasopharyngeal Carcinoma

Abstract

BackgroundEpstein-Barr virus DNA (EBV DNA) load has been identified as a prognostic factor in nasopharyngeal carcinoma (NPC), whereas the dynamic changes in the long period have not been explored. In this study, we evaluated EBV DNA kinetics and its role in the survival.MethodsWe conducted a retrospective review of 900 NPC patients. Plasma EBV DNA levels were measured at various time points after treatment. The correlations of EBV kinetics with recurrence and metastasis were analyzed. After stratifying patients according to the EBV results, survival was compared using Kaplan-Meier estimates. Twelve- and 24-month landmark analyses for overall survival (OS) data were performed according to the EBV groups.ResultsPatients with post-EBV of less than 2500 copies/mL achieved better survival than did those with higher ones. Furthermore, patients with continuously elevated EBV DNA expressed significantly poorer OS (hazard ratio [HR], 2.542, 95% confidence interval [CI], 2.077–3.111; P < 0.001), distant metastasis-free survival (HR, 2.970; 95% CI, 2.392–3.687; P < 0.001), locoregional-free survival (HR, 1.699; 95% CI, 1.072–2.692; P = 0.013), and progression-free survival (HR, 2.535; 95% CI, 1.987–3.233; P < 0.001) than did patients with continuously normal EBV or those with elevated levels at any time point. The 5-year OS with elevated EBV was lower than that of the remission group by using the 12- and 24-month landmark analysis.ConclusionsElevated EBV DNA after treatment was a better predictive indicator of survival than the baseline concentrations. Furthermore, continuously elevated EBV DNA after treatment indicated recurrence, metastasis, and unfavorable prognosis for NPC. In addition, there were consistent patterns of EBV DNA kinetics during long-term follow-up, which warrant further study.

High plasma EBV-DNA load and positive EBER status associated with viral recurrence and persistent infection in early treatment of lymphoma

“…Studies con rmed that post-treatment EBV-DNA positivity could predict early relapse and poor prognosis for patients with lymphoma [26]. Furthermore, He et al also demonstrated that elevated EBV-DNA after treatment indicated recurrence, metastasis, and unfavorable prognosis for EBV-associated nasopharyngeal carcinoma (NPC) [27]. In our study, pretreatment PEDL was compared between the TN and CP groups, we found that the median pretreatment PEDL of CP was 2.4 times higher than that of TN (P < 0.0001) (Fig.…”

Automatic tumor segmentation and metachronous single-organ metastasis prediction of nasopharyngeal carcinoma patients based on multi-sequence magnetic resonance imaging

“…Another shortcoming is that it falls short of reflecting the heterogeneity of individual tumors ( 6 ). Several studies have reported that lymph node gross tumor volume (GTVln), gross tumor volume of the nasopharynx (GTVnx), circulating CD4 T lymphocytes, lactate dehydrogenase, lactate dehydrogenase (LDH) level before treatment, hemoglobin level, and EBV DNA level were significantly associated with the distant metastases of NPC ( 6 , 39 , 40 ). Several studies have shown that the plasma EBV DNA level before treatment was related to the clinical stage and tumor burden of nasopharyngeal carcinoma, and it was currently considered to be the most important molecular marker for complementary clinical staging ( 41 , 42 ).…”

Clinical Characteristics and Predictive Outcomes of Recurrent Nasopharyngeal Carcinoma—A Lingering Pitfall of the Long Latency

“…However, MRI is expensive, while the phantom tumor phenomenon is not uncommon in MRI, particularly after completion of radiotherapy more than five years [ 60 ]. Recently the plasma EBV DNA has been regarded as a valuable tool for early detection of either primary surveillance or recurrence [ 61 , 62 , 63 ]. Xu et al found that the increased EBV DNA titer was present at a median of 2.6 months before radiographic progression [ 64 ].…”