Pretreatment Epstein-Barr Virus DNA Load and Cumulative Cisplatin Dose Intensity Affect Long-Term Outcome of Nasopharyngeal Carcinoma Treated with Concurrent Chemotherapy: Experience of an Institute in an Endemic Area

Abstract

Background: We retrospectively compared the long-term efficacy of concurrent chemoradiotherapy (CCRT) regimens (docetaxel vs. cisplatin), total dose intensity of cisplatin (> 200 vs. ≤ 200 mg/m²) and pretreatment plasma levels of Epstein-Barr virus (EBV) DNA for nasopharyngeal carcinoma (NPC), and investigated the prognostic factors. Methods: We enrolled 214 patients diagnosed with NPC and treated with CCRT. 41 patients received weekly docetaxel and 173 weekly cisplatin. 62 received cumulative cisplatin of ≤ 200 mg/m² and 111, > 200 mg/m². Pretreatment levels of EBV DNA were available for 155 patients. Results: Patients receiving concurrent weekly docetaxel and cisplatin had similar 5-year rates for overall survival (OS) (p = 0.306), progression-free survival (PFS) (p = 0.133), distant failure-free survival (DFS) (p = 0.110), and locoregional failure-free survival (LFS) (p = 0.452). Cumulative cisplatin of > 200 mg/m² improved the 5-year rates of PFS (p = 0.018) and DFS (p = 0.042) significantly in comparison with cumulative cisplatin of ≤ 200 mg/m². EBV DNA levels of ≥ 1,500 copies/ml was closely associated with poor DFS (p = 0.011), PFS (p = 0.006), and OS (p = 0.004). Conclusions: Weekly cisplatin was well tolerated in CCRT, during which cumulative cisplatin of > 200 mg/m² improved PFS and DFS. The long-term efficacy of concurrent docetaxel was similar to that of concurrent cisplatin. The EBV DNA level was the most significant prognostic factor.

Clinical implications of hepatitis B viral infection in Epstein–Barr virus-associated nasopharyngeal carcinoma

“…The pretreatment work-up has previously been described in detail [20,21]. All patients were routinely screened for hepatitis B at the time of diagnosis using the serologic markers HBsAg, hepatitis B surface antibody (anti-HBs), hepatitis B e antigen (HBeAg), hepatitis B e antibody (anti-HBe) and hepatitis B core antibody (anti-HBc).…”

Prognostic role of plasma Epstein-Barr virus DNA load for nasopharyngeal carcinoma: a meta-analysis

“…The meta-analysis found that high pre-treatment levels of EBV DNA had good value as a prognostic indicator of survival and disease outcomes in patients with NPC. Most of the studies included in this meta-analysis found that increased levels of EBV DNA prior to treatment was associated with poor overall survival [13,[28][29][30][32][33][34][35][36][37]39,40]. Of the studies that evaluated the other outcomes, high pre-treatment EBV DNA levels was also associated with increased risk for disease progression, relapse, recurrence, and distant metastasis.…”

“…The remaining 57 were fully evaluated for inclusion and 41 were eliminated for not reporting the outcomes of interest, reporting data that could not be pooled for a meta-analysis, not being relevant or reporting findings from a study that was already included. Sixteen studies were included in the study with a total of 7698 patients [12,13,[28][29][30][31][32][33][34][35][36][37][38][39][40][41]. Three of the studies were retrospective in design and the remaining 13 studies were prospective (Table 1).…”

The Biology and Clinical Utility of EBV Monitoring in Blood

“…In several series, median plasma EBV DNA copy number for untreated NPC patients with stage II-IV disease ranges from a few hundred to a few thousand copies/mL Leung et al 2014;Tan et al 2006). Pre-treatment plasma EBV DNA levels of >1500 copies/mL have been associated with inferior progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS) in many studies including prospective cohorts (Wei et al 2014;Wang et al 2013;Lin et al 2004Lin et al , 2007. The association between high pretreatment plasma EBV DNA levels and inferior OS has also been demonstrated in NPC cohorts using other cutoffs (Chai et al 2012).…”