Evaluating the Prognostic Relevance of Pre-Treatment Epstein–Barr Virus Levels in Non-Endemic Pediatric Nasopharyngeal Carcinoma

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Background/Objectives: Pediatric nasopharyngeal carcinoma (NPC) is a very rare childhood cancer strongly associated with Epstein–Barr virus (EBV) infection. We investigated the prognostic value of EBV DNA on staging and outcome in pediatric NPC from two large study centers, the Children’s Oncology Group (COG) in North America and the German Society of Pediatric Oncology and Hematology (GPOH) in Europe. Methods: Samples collected from NPC patients treated on the COG study ARAR0331 between 2006 and 2012 and the GPOH NPC protocol between 2003 and 2021 were retrospectively analyzed for the level of available plasma (P-EBV) or whole-blood EBV DNA (WB-EBV), both pre-treatment and post-induction chemotherapy. Patients were dichotomized into high and low groups based on the median pre-treatment EBV value. Results: Pre-treatment EBV DNA levels from 102 patients (50 and 23 P-EBV DNA from the COG and GPOH, respectively, and 29 WB-EBV from GPOH) and post-induction EBV DNA levels from 61 patients (31 and 12 P-EBV DNA from the COG and GPOH, respectively, and 18 WB-EBV DNA from GPOH) were evaluated. Patient characteristics, including age and disease stage, were not associated with high and low P-EBV values in any cohort. Disease stage correlated with high EBV levels in the WB-EBV GPOH cohort (p = 0.014). Pre-treatment P-EBV and WB-EBV levels showed no significant association with 5-year event-free survival (EFS: COG p = 0.65, GPOH P-EBV: p = 0.08, GPOH WB-EBV: p = 0.75) or 5-year overall survival (OS: COG p = 0.90, GPOH P-EBV p = 0.17, GPOH WB-EBV p = 0.19). Conclusions: Our study could not establish a significant correlation between outcome and pre-treatment EBV DNA in pediatric NPC patients from non-endemic areas.

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