Dynamic changes in plasma Epstein–Barr virus DNA load during treatment have prognostic value in nasopharyngeal carcinoma: a retrospective study

Abstract

Circulating plasma Epstein–Barr virus DNA (EBV DNA) is related to tumor recurrence and metastasis and has potential as a dynamic, sensitive, and specific marker in nasopharyngeal carcinoma (NPC). We investigated the clinical significance of assessing plasma EBV DNA load at various time points during treatment. Patients with NPC (n = 949) for whom plasma EBV DNA load was measured by real‐time quantitative polymerase chain reaction (RT‐qPCR) before treatment (pre‐EBV) and at midtreatment (mid‐EBV), end of treatment (end‐EBV), and 3 months after completing treatment (3 m‐EBV) were retrospectively assessed. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal EBV DNA cutoff point for each time point. Overall survival (OS), distant metastasis‐free survival (DMFS), and progression‐free survival (PFS) were compared using Kaplan–Meier estimates. High pre‐EBV, high mid‐EBV, high end‐EBV, and high 3 m‐EBV were all associated with significantly poorer OS, DMFS, and PFS in the entire cohort. Detectable end‐EBV and 3 m‐EBV was associated with significantly poorer OS, DMFS, and PFS. Among patients with detectable end‐EBV, adjuvant therapy significantly improved OS (HR 2.419; 95% CI 1.297–4.51, P = 0.03) and DMFS (HR 2.45; 95% CI 1.243–4.828, P = 0.04), but not PFS (P = 0.17). EBV DNA represents a dynamic biomarker for monitoring treatment and predicting survival in NPC. Assessing plasma EBV DNA before, during, and after chemoradiotherapy could be clinically valuable and enable selection of patients most likely to benefit from additional therapy and improve assessment of treatment response and disease surveillance. Further multicenter prospective investigations are warranted.

Long-Term Monitoring of Dynamic Changes in Plasma EBV DNA For Improved Prognosis Prediction of Nasopharyngeal Carcinoma

“…Based on this dynamic change, we divided 252 patients into 5 subgroups/patterns and performed survival analysis. This was different from the previous reports [20][21][22][23][24][25][26], which mainly focused on the following time points primarily from pre-treatment to 3 months post-treatment.…”

“…Many studies have reported that plasma EBV DNA loads and its dynamic changes could be used as a predictive marker for NPC prognosis at limited time points [20][21][22][23][24][25][26], such as pre-treatment and 3 months post-treatment, however, the prognostic value and dynamic changes of plasma EBV DNA at other time points, such as more than 3 months post-treatment, are not be fully understood yet. Notably, in this study, we enrolled 252 NPC patients who received plasma EBV DNA tests at 4 time points (pre-treatment, 3, 12, and 24 months post-treatment).…”

“…In addition, dynamic changes of plasma EBV DNA pre-and post-treatment may also be useful for prognosis prediction and treatment evaluation. Recently, several studies have reported the potential prognostic value of dynamic changes in plasma EBV DNA in NPC patients at different time points, including during treatment [20,21], pre-and early post-treatment [22,23], and within 3 months posttreatment [24][25][26]. However, long-term monitoring of dynamic changes in plasma EBV DNA after 3 months post-treatment might also provide prognostic value.…”

Prognostic value of gross tumor regression and plasma Epstein Barr Virus DNA levels at the end of intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma

“…In the study by He et al, detectable EBV DNA at the end of treatment was also associated with significantly poorer OS, DMFS, and progression-free survival (PFS). Among patients with detectable EBV DNA at the end of treatment, adjuvant therapy significantly improved OS (P = 0.03) and DMFS (P = 0.04) [36]. Adjuvant therapy might bring survival benefit to these patients with positive plasma EBV DNA at the end of RT, but it needs to be confirmed by prospective clinical trials.…”

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

“…We have previously reported the potential bene ts of adjuvant treatment for patients with detectable Epstein Barr virus DNA (EBV DNA) load at the end of treatment [10] in addition to the prognostic value of EBV DNA concentrations during treatment [11]. Tumor response and patient survival can also be predicted based on the clearance rates of plasma EBV DNA during the rst month of chemotherapy.…”