The optimum number of induction chemotherapy cycles for N3M0 stage nasopharyngeal carcinoma based on pre-treatment plasma EBV DNA

Background: The objective of this study was to examine the significance of pre-treatment Epstein-Barr virus DNA (pre-DNA) in determining the optimal number of induction chemotherapy cycles (ICC) prior to concurrent chemoradiotherapy (CCRT) in patients with stage N3M0 nasopharyngeal carcinoma (NPC). Methods In this research, we used propensity score matching to divide enrolled patients into 3 cycles (IC = 3) or 4 cycles (IC = 4) group based on the number of ICC. To assess the disparity in survival and toxicities, the log-rank and chi-squared tests were employed, respectively. The main endpoint was distant metastasis-free survival (DMFS). Additional endpoints included overall survival (OS), progression-free survival (PFS), and locoregional relapse-free survival (LRRFS). Multivariate cox proportional hazard analysis identified potential independent prognostic factors. Results Of 369 patients, 194 were enrolled, with 97 and 97 included in IC = 3 and IC = 4 group respectively. The IC = 4 group exhibited markedly superior 3-year OS, PFS, DMFS, and LRRFS compared to the IC = 3 group (all p < 0.05), while experiencing higher adverse reactions, although not statistically significant. Based on DMFS, the cut-off value of pre-DNA was 8700 copies/ml (area under curve, 0.593; sensitivity, 0.794; specificity, 0.481). For low-risk patients with pre-DNA < 8700 copies/ml, both groups demonstrated comparable survival results. Nonetheless, the IC = 4 group exhibited better survival in 3-year OS, PFS, DMFS, and LRRFS compared to the IC = 3 group among high-risk patients with pre-DNA ≥ 8700 copies/ml (78.2% vs 49.1%, 69.1% vs 40.0%, 74.5% vs 40.0%, 70.9% vs 47.3%, all p < 0.05). Additionally, in high-risk group, ICC was considered as a protective element for OS and DMFS according to multivariate analysis. Conclusions For N3M0 stage NPC, pre-DNA could be a powerful predictor to guide the optimum number of ICC. IC = 4 was recommended for high-risk patients due to superior survival, while for low-risk patients, IC = 3 might be sufficient.