Incorporating early cfEBV DNA clearance into clinical risk stratification to tailor induction chemotherapy cycles for locoregionally advanced nasopharyngeal carcinoma

BACKGROUND: The optimal number of induction chemotherapy (IC) cycles for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is debated. This study investigates if early cell-free Epstein-Barr virus (cfEBV) DNA clearance can personalise treatment. METHODS: We included 1590 LA-NPC patients treated with IC+ chemoradiotherapy (2010-2023) with complete early cfEBV DNA data. COX regression identified independent prognostic factors, and receiver operating characteristic curves assessed predictive accuracy. Propensity score matching (PSM) balanced covariates between groups receiving different IC cycles. The primary outcome, progression-free survival (PFS) was analysed using Kaplan-Meier and log-rank tests. RESULTS: After the first IC cycle, 45.5% of patients had undetectable cfEBV DNA. Combining cfEBV DNA clearance, N-stage, and overall stage yielded the highest AUC for 5-year PFS (0.632). Patients were stratified into high- and low-risk groups (p < 0.001). Post-matching, low-risk patients receiving three IC cycles had better 5-year PFS than those receiving two (85.2% vs. 76.0%, p = 0.024), with no significant increase in grade 3-4 toxicities (30.36% vs. 24.29%, p = 0.157). High-risk patients showed no PFS benefit from additional cycles (63.2% vs. 61.0%, p = 0.960). DISCUSSION: Early cfEBV DNA clearance predicts LA-NPC outcomes. Low-risk patients may benefit from an additional cycle of IC, while high-risk patients may require alternative strategies like immunotherapy or earlier chemoradiotherapy.