The Clinical Utility of Plasma Epstein–Barr Virus DNA Assays in Nasopharyngeal Carcinoma: The Dawn of a New Era?: A Systematic Review and Meta-Analysis of 7836 Cases

In this study, we assessed the potential of plasma Epstein–Barr virus (EBV) DNA assays to predict clinical outcomes in a large sample of nasopharyngeal carcinoma (NPC) patients and proposed a risk stratification model based on standardized EBV DNA load monitoring. We conducted a meta-analysis of 14 prospective and retrospective comparative studies (n = 7 836 patients) to evaluate the correlation between pretreatment plasma EBV DNA (pre-DNA), midtreatment plasma EBV DNA (mid-DNA), posttreatment plasma EBV DNA (post-DNA), the half-life value of plasma EBV DNA clearance rate (t(1/2)), and clinical outcomes. Our primary endpoint was overall survival (OS). Our secondary endpoints were progression-free survival (PFS), distant-metastasis-free survival (DMFS), and local-regional-failure-free survival (LRFS). High pre-DNA, detectable mid-DNA, detectable post-DNA, and slow EBV DNA clearance rates were all significantly associated with poorer OS, with hazard radios (HRs) equal to 2.81, 3.29, 4.26, and 3.58, respectively. Pre-DNA, mid-DNA, and post-DNA had the same effects on PFS, DMFS, and LRFS. Plasma EBV DNA assays are highly prognostic of long-term survival and distant metastasis in NPC patients. Based on the results of this meta-analysis, we propose a 4-grade systematic risk stratification model. Given the inherent limitations of the included studies, future well-designed randomized clinical trials are required to confirm to the findings of this analysis and to contribute to the development of individualized treatment strategies for NPC patients.