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// Wen-Yi Wang 1, 2, * , Tian-Yun Lin 3, * , Chih-Wen Twu 4, 5 , Hsiao-Hui Tsou 6, 7 , Po-Ju Lin 8 , Yi-Chun Liu 8 , Jing-Wen Huang 8 , He-Yuan Hsieh 8 , Jin-Ching Lin 5, 8, 9, 10 1 Department of Nursing, Hung Kuang University, Taichung, Taiwan 2 Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan 3 Department of Otorhinolaryngology, Taipei Veterans General Hospital, Taipei, Taiwan 4 Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan 5 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan 6 Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan 7 Graduate Institute of Biostatistics, College of Public Health, China Medical University, Taichung, Taiwan 8 Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan 9 Institute of Clinical Medicine,School of Medicine, National Yang Ming University, Taipei, Taiwan 10 Department of Medicine, China Medical University, Taichung, Taiwan * These authors contributed equally to this work Correspondence to: Jin-Ching Lin, email: jclin@vghtc.gov.tw Keywords: nasopharyngeal carcinoma, radiotherapy, plasma Epstein-Barr virus DNA, quantitative polymerase chain reaction Received: October 25, 2015 Accepted: April 18, 2016 Published: May 12, 2016 ABSTRACT Purpose: To investigate the long-term clinical outcome of nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma EBV (pEBV) DNA after curative radiotherapy (RT). Results: The post-RT pEBV DNA levels were very lower copy number (median 21, interquartile range 8–206 copies/ml). After long-term follow-up, the relapse rate was 64.8%, the median time to progression 20 months, and 5-year overall survival (OS) 49.6%. Thirty-two of 39 (82.1%) patients with high viral load (≥ 100 copies/ ml) developed tumor relapse, whereas 57.0% (49/86) patients with low viral load (< 100 copies/ml) had tumor relapse ( P = 0.0065). The 5-year OS rates were 20.5% and 62.9% for patients with viral load ≥ and < 100 copies/ml (median survival, 20 vs. 100 months; P < 0.0001). Patients who received adjuvant chemotherapy (AdjCT) experienced significant reduction in distant failures (66.2% vs. 31.6%; P = 0.0001) but similar locoregional recurrences ( P = 0.2337). The 5-year OS rates were 69.4% for patients who received AdjCT compared with 33.2% for those of without AdjCT (median survival, 111 vs. 32 months; P < 0.0001). Methods: We screened 931 newly diagnosed NPC patients who finished curative RT and found 125 patients (13.4%) with detectable pEBV DNA one week after RT. The clinical characteristics, treatment modality, subsequent failure patterns and survivals were analyzed. Conclusions: NPC patients with persistently detectable pEBV DNA after curative RT have a higher rate of treatment failure and poor survivals. Levels of the post-RT pEBV DNA and administration of AdjCT affect the final outcome significantly.