The Role of Pre-Treatment Plasma Epstein-Barr Virus (EBV) DNA As a Predictive Biomarker of Induction Chemotherapy for Stage IVA or IVB Nasopharyngeal Carcinoma (NPC) Patients – A Subgroup Analysis on Taiwan Cooperative Oncology Group (TCOG) 1303 Study

Pre-treatment plasma EBV DNA is considered as a prognostic biomarker for NPC patients. Whether the pre-treatment EBV DNA could be a biomarker guiding the treatment for advanced NPC patients warrants investigation. TCOG 1303 was a phase III trial comparing induction chemotherapy (IC) followed by concurrent chemoradiation (CCRT) versus CCRT alone in stage IVA or IVB NPC patients. In both arms, radiotherapy would be delivered with weekly cisplatin (30mg/m2). For patients in IC arm, chemotherapy with mitomycin C, epirubicin, cisplatin, 5-fluorouracil, and leucovorin were administered for 3 cycles before the CCRT. The primary endpoint was disease free survival. Pre-treatment plasma EBV DNA was analyzed. From September 2003 to August 2009, 479 patients were enrolled. The pre-treatment plasma EBV DNA were collected from 264 patients. The median follow-up were 66 months. The median of plasma EBV DNA was 7862.5 copies/mL. 135 pts were grouped in EBV DNA < 8000 copies/mL (EBV-low) and 129 pts in EBV DNA >=8000 copies/mL (EBV-high). High plasma EBV DNA is statistically significant with larger tumor size (p < 0.0001), advanced N stage (p = 0.001) and overall stage (p = 0.0002). Between the EBV-low and EBV-high groups, there was no statistically significant difference in DFS (HR = 1.26 (95% CI: 0.85-1.87), p = 0.25) and overall survival (OS) (HR = 1.39 (0.84-2.28), p = 0.20) with Cox proportional hazard model. Between the IC-CCRT arm and CCRT arm in the EBV-low group or EBV-high group, no significant difference in characteristics was observed between two arms. By univariate Cox-regression analysis, there was no statistically significant difference on DFS and OS between IC-CCRT and CCRT in both groups (EBV-high: IC-CCRT vs CCRT, DFS: HR = 0.788 (0.46-1.37), p = 0.40, and OS: HR = 0.85 (0.43-1.69), p = 0.65; EBV-low: IC-CCRT vs CCRT: DFS: HR = 0.73 (0.41-1.28), p = 0.27, and OS: HR = 0.64 (0.32-1.27), p = 0.20). Pre-treatment plasma EBV DNA cannot be a biomarker of induction MEPFL for stage IVA or IVB NPC patients. The biology role of pre-treatment EBV DNA should be explored.