911P Post-radiotherapy (RT) Epstein-Barr virus (EBV) DNA dynamics identifies optimal timepoint for stratification of high-risk nasopharyngeal carcinoma (NPC)

Detectable plasma EBV DNA post-RT portends for a poor prognosis in NPC patients. Adjuvant chemotherapy (AC) trials however failed to yield a survival benefit in these high-risk patients. Studies have shown that post-RT EBV DNA levels and kinetics could further stratify NPC patients into risk-groups with disparate survival. There is thus a need to correctly identify patients who benefit from AC. Here, we investigated whether an early (0-2 w) or delayed (8-12 w) measure of plasma EBV DNA better predicts for disease relapse. We curated a prospective single institution NPC registry for patients with a plasma EBV DNA result at 0-2 w post-RT and a minimum follow-up of 2 years. A subset of patients had a duplicate test done at 8-12 w post-RT. Plasma EBV DNA was quantified using the international harmonised BamH1 PCR-based assay. Primary clinical endpoint was disease-free survival (DFS). 297 patients with an EBV DNA result at 0-2 w post-RT were analysed. Median follow up was 51 (IQR: 47-55) mo. 71% (210/297) had TNM-stage III-IVA NPC; and 41% (122/297) reported pre-RT EBV DNA of ≥4000 copies/mL. At 0-2 w post-RT, 82% (243/297) had 0 EBV DNA copy/mL, while 16% (14/297) and 2% (7/297) had 1-264 copies/mL and ≥265 copies/mL, respectively. Using different EBV DNA level cut-offs of 0, 1-499, and ≥500 copies/mL, we validated the RPA model by Hui et al. with the high-risk group (≥500 copies/mL) yielding the worst HR of 4.9 (95%CI: 1.9-12.5) relative to the low-risk group. Next, we observed substantial EBV DNA changes in 109 patients with a repeat EBV DNA at 8-12 w. Specifically, 65% (22/34) with a detectable EBV DNA at 0-2 w had 0 copy/mL subsequently. We found that a detectable EBV DNA at 8-12 w was a stronger predictor of relapse than a positive result at 0-2 w; AUCROC for DFS was 0.806 (95%CI: 0.727-0.886) for stage+EBV DNA8-12w versus 0.679 (95% CI: 0.576-0.783) for stage+EBV DNA0-2w. Our findings revealed that post-RT EBV DNA levels are dynamic, and an EBV DNA test at 8-12 w more accurately identifies high-risk patients than a test at 0-2 w post-RT. This has potential implications on AC trials that adopt an early EBV DNA result for treatment stratification.