Subdivision of de novo metastatic nasopharyngeal carcinoma based on tumor burden and pretreatment Epstein-Barr virus DNA for therapeutic guidance of primary tumor radiotherapy

Purpose: To improve individualized treatment of de novo metastatic nasopharyngeal carcinoma (dmNPC) patients by investigating prognostic factors and identifying patients who achieved better survival outcomes after locoregional radiotherapy (LRRT).Materials and methods: Our study included a cohort of 498 dmNPC patients. Overall survival (OS) was the primary endpoint. We analyzed the correlation of all potential prognostic factors and survival outcomes by Kaplan-Meier survival curves using log-rank test and Cox proportional hazards regression model.Results: Multivariate analysis identified three independent prognostic factors: Epstein-Barr virus (EBV) DNA, number of metastatic lesions, and number of metastatic organs. Through these factors, we successfully divided all patients into 3 subgroups: low-risk (single metastatic organ, EBV DNA ≤ 25,000 copies/ml, and ≤ 5 metastatic lesions), intermediate-risk (single metastatic organ, EBV DNA > 25,000 copies/ml, and ≤ 5 metastatic lesions), and high-risk (multiple metastatic organs or > 5 metastatic lesions or both). By comparing LRRT and non-RT groups, we found statistical differences in OS in the low-risk and intermediate-risk subgroups (p = 0.039 and p = 0.010, respectively) but no significant difference in OS in the high-risk subgroup (p = 0.076). Further multivariate analysis of different risk stratifications revealed that LRRT was a protective factor only for the low- and intermediate-risk subgroups.Conclusions: The risk stratification of dmNPC may be used as a new prognostic factor to help clinicians organize individualized LRRT treatment to improve the survival outcomes of dmNPC patients.