5-Year Results of the Prognostic Roles of Serial Post-Intensity-Modulated Radiation Therapy Undetectable Plasma EBV DNA for Non-Metastatic Nasopharyngeal Carcinoma

Abstract

Purpose/Objective(s): We previously demonstrated that post-IMRT 8th week and 6th month undetectable plasma EBV DNA were significant prognostic factors of 3-year survival endpoints for non-metastatic NPC. We now presented our 5-year results. (NCT02476669).

Materials/Methods: Patients with previously untreated non-metastatic NPC confirmed by PET-CT and MRI scans were prospectively recruited from 2010 to 2016. They all had plasma EBV DNA measured at baseline, and then 8 weeks and 6 months following IMRT with/without concurrent +/- adjunct chemotherapy. They were staged and treated based on the 7th edition TNM of AJCC/UICC Staging Classification. Covariates including age, sex, ACE-27, pretreatment LDH and plasma EBV DNA were analyzed by Cox regression for prognostic factors of progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS).

Results: A total of 518 patients were prospectively recruited. 71 (13.7%) patients received IMRT alone, while 90 (17.4%) and 357 (68.9%) received concurrent chemoradiation alone and concurrent chemoradiation followed by adjunct chemotherapy respectively. The median pretreatment plasma EBV DNA titers was 494 copies/ml (range 0-175000 copies/ml). After a median follow-up of 5.2 years, 38 (7.3%) and 21 (4.1%) patients still had detectable titers at 8 weeks and 6 months following IMRT. 5-year PFS, CSS and OS in the whole study population were 77.1%, 90.4% and 84.4% respectively. Patients with post-IMRT 8th week and 6th month undetectable plasma EBV DNA titers enjoyed longer 5-year survival endpoints (PFS 79.1% vs. 40.9%; CSS 93.8% vs. 58.8%; OS 85.7% vs. 55.3%; all p<0.001), which were also lengthened for those with post-IMRT 6th month undetectable titers (PFS 78.7% vs. 19.0%; CSS 93.4% vs. 39.7%; OS 85.5% vs. 37.5%; all p<0.001), compared to those who still had detectable titers at the corresponding time points. They are also the only prognostic factors of these endpoints in multivariable analyses (all p<0.001).

Conclusion: Post-IMRT 8th week and 6th month undetectable plasma EBV DNA remained significant prognostic factors after 5 years of follow-up. Additional therapy may have to be considered for those who had persistently detectable plasma EBV DNA after IMRT.