Use of early EBV DNA clearance to select optimal induction chemotherapy cycles for locoregional advanced nasopharyngeal carcinoma.

6076 Background: Based on 3 cycles of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is the standard treatment for locoregional advanced nasopharyngeal carcinoma (LA-NPC). However, it remains unclear whether all patients benefit from 3 cycles of IC. Epstein-Barr virus (EBV) DNA is a key biomarker for NPC, and changes of cell-free EBV DNA (cfEBV DNA) may reflect tumor dynamics. This study aims to use early cfEBV DNA clearance to guide optimal IC cycle selection for LA-NPC patients. Methods: We included 1541 LA-NPC patients treated with IC+CCRT between 2010 and 2023, all with early cfEBV DNA data (pre-treatment, and after 1 st IC cycle). Independent prognostic factors were identified by COX regression, and predictive accuracy was assessed using receiver operating characteristic (ROC) curves. Propensity score matching (PSM) balanced covariates between groups receiving different IC cycles. The primary outcome, progression-free survival (PFS) was analyzed using Kaplan-Meier and log-rank tests. Results: After the 1st IC cycle, 693 (44.97%) patients had undetectable cfEBV DNA. cfEBV DNA after the 1st IC (p=0.014) and N stage (p=0.048) were significant predictors of PFS. The combination of N stage and cfEBV DNA after the 1st IC cycle had a higher AUC for 5-year PFS (0.610) compared to N stage, cfEBV DNA after 1st IC, or TNM stage alone (0.543, 0.588, 0.557). Based on these two factors, patients were divided into high-risk (N2-3 and detectable cfEBV DNA after 1st IC) and low-risk (N0-1 or undetectable cfEBV DNA after 1st IC) groups. The 5-year PFS for low-risk and high-risk groups was 81.2% vs. 65.1% (p<0.001). After PSM, low-risk patients receiving 3 cycles of IC showed significantly better PFS compared to those receiving 2 cycles (5-year PFS: 86.0% vs. 72.5%, p<0.001). However, high-risk patients showed similar PFS regardless of IC cycles (5-year PFS: 66.1% vs. 63.7%, p=0.306). Conclusions: EBV DNA clearance after the first cycle of IC is a sensitive predictor of outcomes in LA-NPC. Low-risk patients may benefit from an additional cycle of IC, while high-risk patients require alternative strategies such as immunotherapy or earlier initiation of CCRT.