Plasma EBV DNA in Nasopharyngeal Cancer (NPC) Treated with Definitive Radiotherapy (RT)

Abstract

EBV DNA has well-studied roles in NPC including early detection and surveillance. There are limited North American data on EBV DNA testing. Our center has used EBV DNA testing since 2010. We hypothesized: (1) higher first post-RT EBV DNA level is associated with worse prognosis, and (2) surveillance EBV DNA is specific for recurrence at a low detection threshold. We retrospectively reviewed all patients with non-metastatic (TNM-7 stage I-IVB) NPC treated with definitive RT/chemoRT (CRT) ± adjuvant chemotherapy (AC) between 2010-2017. EBV DNA was assayed by quantitative PCR in a CAP/CLIA-certified laboratory and reported in copies/mL of plasma. Pre-RT is defined as 0-90 days before the first RT fraction and post-RT within one year after RT. We report log odds ratios (LOR) from a linear model of T- and N-category with log-adjusted EBV DNA as the response variable. Survival outcomes were analyzed with log-rank tests and Cox multivariate analyses (MVA) adjusted for age, stage, and treatment, reporting hazard ratios (HR). A total of 95% confidence intervals of LOR and HR are reported. The detection threshold that maximized the F1 accuracy score was considered optimal. Of 271 patients in the study window, 179 had pre-RT +/- post-RT EBV DNA testing. Six received RT, 43 CRT, and 130 CRT+AC. With 7-yr median follow-up, 37 recurred and 37 died. Detectable pre-RT EBV DNA was found in 154 (86%) with a median of 928 copies/mL (range: 1-239214). EBV DNA level correlated with higher N category (LOR: 0.28, 0.15-0.42, p<0.001), but not T category (0.04, -0.06-0.13, p = 0.5). Above-median pre-RT EBV DNA was associated with worse recurrence-free survival (RFS) by log-rank test (p = 0.016) and Cox MVA (HR: 2.2, 1.1-4.8, p = 0.03) along with N category, age, and no AC. Post-RT EBV DNA was available in 99 patients at a median of 54 days. RFS, progression-free survival (PFS), and overall survival (OS) were worse in patients with detectable post-RT EBV DNA (Table). RFS and PFS drop further to 20% if EBV DNA was detectable after the full treatment (RT±AC, n = 71). In Cox MVA, post-RT EBV DNA remained independently prognostic (Table). EBV DNA was performed within 30 days of recurrence in 30 patients, and 24 were detectable (80% sensitivity). Conversely, of 152 patients without recurrence and at least 3-yr follow-up, 95 had post-RT EBV DNA testing and 84 were undetectable (88% specificity). An EBV DNA threshold of 31 copies maximized F1 accuracy metric, yielding 74% sensitivity and 97% specificity. Pre-RT EBV DNA is prognostic and associated with higher N-category. Post-RT EBV DNA is a strong, independent predictor of RFS, PFS, and OS; 31 copies/mL may be a useful threshold to detect recurrence.