a b s t r a c tPurpose: To assess gross tumor regression and plasma Epstein-Barr virus (EBV)-DNA levels at the end of intensity-modulated radiation therapy (IMRT) and its prognostic impact on patients with nasopharyngeal carcinoma (NPC). Participants and Methods: In total, 397 patients with non-metastatic, histologically confirmed NPC were retrospectively examined. All patients underwent magnetic resonance imaging of the nasopharynx and neck, and plasma EBV DNA assays before treatment and at the end of IMRT. Results: The estimated 5-year loco-regional, local and regional relapse-free survival rates for patients with complete response (CR) and non-CR of the total tumor, primary tumor and metastatic lymph nodes at the end of IMRT were 94.9% vs. 85.8%, 96.6% vs. 87.3%, and 98.7% vs. 89.8%, respectively (P < 0.05). The estimated 5-year loco-regional relapse-free survival (LRRFS) rates for patients with persistent tumor with and without boost irradiation were 95.3% vs. 83%, respectively (P = 0.034). The estimated 5-year overall survival (OS), failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates for patients with negative and positive plasma EBV DNA at the end of IMRT were 83.1% vs. 50.3%, 81.5% vs. 49.3%, and 87.6% vs. 61.5%, respectively (P < 0.001). Multivariate analyses indicated that regression of the total tumor and boost irradiation was an independent predictor of LRRFS, and plasma EBV DNA levels were independent predictors of OS, FFS and DMFS. Conclusions: Gross tumor regression and plasma EBV DNA levels at the end of IMRT served as predictors of poor prognosis for patients with NPC. The patients with persistent tumor and/or positive plasma EBV DNA might require timely strengthening treatment. Ó 2018 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 132 (2019) 223-229 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Radical radiotherapy (RT) is the first treatment option for nonmetastatic nasopharyngeal carcinoma (NPC). Intensity-modulated radiation therapy (IMRT) was a milestone development in RT technology, as IMRT can provide a high conformal radiation dose to the tumor target area while effectively decreasing the dose to the sur-rounding normal tissues. IMRT, instead of 2-dimensional RT (2-DRT) and 3-dimensional conformal RT (3-DCRT), is currently more commonly used to treat NPC, due to the associated better tumor control and lower RT-related toxicities [1][2][3][4][5]. The 5-year overall survival (OS), 5-year local relapse-free survival (LRFS), 5-year regional relapse-free survival (RRFS), and 5-year distant metastasis-free survival (DMFS) rates of patients with NPC treated with IMRT ranged from 74% to 84%, 83% to 95%, 91% to 97%, and 83.3% to 85.6%, respectively [6][7][8][9][10].Both loco-regional relapse and distant metastasis are the main reasons of treatment failure in patients with NPC [6-10]. Due to the poor survival of patients with loco-regional relapse and distant metastasis, some effective the...