// Lu Zhang 1, 2, * , Lin-Quan Tang 1, 2, * , Qiu-Yan Chen 1, 2 , Huai Liu 4, 5, 6 , Shan-Shan Guo 1, 2 , Li-Ting Liu 1, 2 , Ling Guo 1, 2 , Hao-Yuan Mo 1, 2 , Chong Zhao 1, 2 , Xiang Guo 1, 2 , Ka-Jia Cao 1, 2 , Chao-Nan Qian 1, 2 , Mu-Sheng Zeng 1 , Jian-Yong Shao 1, 7 , Ying Sun 1, 8 , Jun Ma 1, 8 , Ming-Huang Hong 1, 3 , Hai-Qiang Mai 1, 2 1 Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China 2 Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 3 GCP Center, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 4 Department of Radiotherapy, Hunan Cancer Hospital, Changsha, P. R. China 5 Department of Radiotherapy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P. R. China 6 Key Laboratory of Translational Radiation Oncology, Changsha, P. R. China 7 Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 8 Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China * These authors contributed equally to this work Correspondence to: Hai-Qiang Mai, e-mail: maihq@sysucc.org.cn Ming-Huang Hong, e-mail: hongmh@sysucc.org.cn Keywords: nasopharyngeal carcinoma, Epstein-Barr viral DNA, TNM staging, intensity-modulated radiotherapy, prognosis Received: July 31, 2015 Accepted: November 26, 2015 Published: December 24, 2015 ABSTRACT Background: The objective of this study is to verify the prognostic value of pretreatment plasma Epstein-Barr viral deoxyribonucleic acid (pEBV DNA) levels in nasopharyngeal carcinoma (NPC) patients to complement TNM classification based on the application of the intensity-modulated radiotherapy (IMRT) technique. Methods: In total, 1467 patients staged at I–IVa–b (M0) and treated with IMRT were retrospectively analyzed at our cancer center from January 2007 to December 2010. Patient survival among different stages and EBV DNA levels were compared. Results: Outcome analyses of different stages and EBV DNA levels revealed that patients in stages II–III with low EBV DNA levels had similar survival as that of patients in stages IVa–b with low EBV DNA (5-yr overall survival (OS), 94.7% vs. 92.9% ( P = 0.141), progression failure-free survival (PFS), 87.2% vs. 89.0% ( P = 0.685), distant metastasis failure-free survival (DMFS), 93.5% vs. 92.4% ( P = 0.394) and locoregional failure-free survival (LRFS), 93.8% vs. 96.3% ( P = 0.523)). Conversely, patients in stages II–III with high EBV DNA had better survival than patients in stages IVa–b with high EBV DNA (5-yr OS, 82.7% vs. 71.7% ( P = 0.001), PFS, 70.7% vs. 66.2% ( P = 0.047), DMFS, 79.6% vs. 74.8% ( P = 0.066) and LRFS, 89.3% vs. 87.6% ( P = 0.425)) but poorer survival than patients in stages IVa–b with low EBV DNA (5-yr OS, 82.7% vs. 92.9% ( P = 0.025), PFS, 70.7% vs. 89.0, ( P < 0.001), DMFS, 79.6% vs. 92.4%, ( P = 0.001), LRFS, 89.3% vs. 96.3%, ( P = 0.022)). Conclusion: pEBV DNA is a strong prognostic factor for patients with NPC when complemented with TNM staging in the era of IMRT application.