Prognostic Value of Regression Rate of Plasma EBV DNA After Induction Chemotherapy for Stage II-IVA Nasopharyngeal Carcinoma

BACKGROUND/OBJECTIVE: We aimed to explore the prognostic value of regression rate (RR) of plasma Epstein–Barr virus (EBV) DNA after induction chemotherapy (IC) in patients with stages II–IVA nasopharyngeal carcinoma (NPC). METHODS: Eligible patients receiving IC followed by concurrent chemoradiotherapy were included. The cut-off value of pre-treatment EBV DNA (pre-IC DNA) and RR were identified by receiver operating curve (ROC). Recursive partitioning analysis (RPA) was applied to create new staging. Harrell’s c-index and time-independent ROC were employed to compare different RPA staging. RESULTS: In total, 1,184 patients were included. The cut-off values of pre-IC DNA and RR were 16,200 copies/ml and 95.127% for patients receiving two cycles, and 5,520 copies/ml and 99.994% for those receiving three cycles. Notably, we only focused on patients receiving two cycles of IC. Patients with a RR >95.127% had significantly better 5-year overall survival (OS) than those with a RR ≤95.127% (86.2% vs. 54.3%, P <0.001). Then, RPA1 (pre-IC DNA + TNM staging + RR) and RPA2 (pre-IC DNA + TNM staging + post-IC EBV DNA [post-IC DNA]) staging systems were created. RPA1 staging achieved stronger power in OS prediction than RPA2 staging and TNM staging (c-index: 0.763 [0.714–0.812] vs. 0.735 [0.684–0.786] vs. 0.677 [0.604–0.749]; AUC: 0.736 vs. 0.714 vs. 0.628), indicating that RR had stronger prognostic power than post-IC DNA. Moreover, patients with stages III–IV(RPA1) could benefit from high concurrent cumulative platinum dose (≥160 mg/m(2)). CONCLUSION: RR in conjunction with current TNM staging could better conduct risk stratification, prognosis prediction and help to guide precise concurrent chemotherapy.