Spontaneous remission of residual post‐therapy plasma Epstein–Barr virus DNA and its prognostic implication in nasopharyngeal carcinoma: A large‐scale, big‐data intelligence platform‐based analysis

Detectable post‐therapy plasma Epstein–Barr virus (EBV) DNA predicts poor survival in non‐metastatic nasopharyngeal carcinoma (NPC). However, some patients subsequently experience spontaneous remission of residual EBV DNA during follow‐up and it was unclear whether these patients were still at high risk of disease failure. Using the NPC database from an established big‐data intelligence platform, 3269 NPC patients who had the plasma EBV DNA load measured at the end of therapy (+ 1 week) were identified. In total, 93.0% (3031/3269) and 7.0% (238/3269) of patients had undetectable and detectable (> 0 copy/ml) plasma EBV DNA at the end of therapy (EBV DNA_end), respectively. Detectable EBV DNA_end was a prognostic factor for poorer 3‐year disease‐free survival (DFS), overall survival (OS), distant metastasis‐free survival (DMFS), and loco‐regional recurrence‐free survival (LRRFS) in both univariate and multivariate analyses. Of 238 patients with residual EBV DNA_end, 192 underwent EBV DNA assay 3 months after and spontaneous remission occurred in 72.4% (139/192). However, these patients still had poorer 3‐year DFS (55.1% vs. 89.8%), OS (79.1% vs. 96.2%), DMFS (68.4% vs. 94.1%) and LRRFS (84.5% vs. 95.0%) than patients with undetectable EBV DNA_end (all P < 0.001). And patients with persistent detectable post‐therapy EBV DNA had the worst outcomes. These results were confirmed in multivariate analysis. In conclusion, residual EBV DNA post therapy was a robust biomarker for NPC prognosis. Although residual post‐therapy EBV DNA could spontaneous remit during follow‐up, these patients were still at high risk of disease failure and such patients may benefit from adjuvant therapy.

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