J Cancer 2016; 7(6):664-670. doi:10.7150/jca.14183

Research Paper

Circulating EBV DNA, Globulin and Nodal Size Predict Distant Metastasis after Intensity-Modulated Radiotherapy in Stage II Nasopharyngeal Carcinoma

Xiao-Jing Du1, Ling-Long Tang1, Yan-Ping Mao1, Rui Guo1, Ying Sun1, Ai-Hua Lin2, Jun Ma1✉

1. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Guangzhou 510060, China;
2. Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road, Guangzhou 510060, China.

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Du XJ, Tang LL, Mao YP, Guo R, Sun Y, Lin AH, Ma J. Circulating EBV DNA, Globulin and Nodal Size Predict Distant Metastasis after Intensity-Modulated Radiotherapy in Stage II Nasopharyngeal Carcinoma. J Cancer 2016; 7(6):664-670. doi:10.7150/jca.14183. Available from http://www.jcancer.org/v07p0664.htm

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Background: The optimal treatment for early-stage nasopharyngeal carcinoma (NPC) remains controversial. Identification of prognostic factors for metastasis and tumor progression is urgently required to improve clinical decision-making for patients with American Joint Committee on Cancer (AJCC) 2009 stage II NPC from the endemic area.

Methods: Consecutive newly-diagnosed patients (n=296) with non-disseminated, biopsy-proven stage II NPC were retrospectively reviewed; all patients received intensity-modulated radiotherapy and MRI follow-up. Plasma EBV DNA level, serum lactate dehydrogenase, serum albumin, serum globulin and leukocyte counts were measured before therapy. Survival rates were analyzed using the Kaplan-Meier method and log-rank test and multivariate Cox proportional hazards model.

Results: Median follow-up was 50.2 months (range, 8-69.5 months). Multivariate analysis demonstrated a plasma Epstein-Barr virus (EBV) DNA level ≥ 4000 copies/mL, maximal axial diameter (MAD) of the cervical lymph nodes ≥ 30 mm and serum globulin level < 29.5 g/L were independent predictors of poor DMFS (P = 0.018; P = 0.019; P = 0.006, respectively). On the basis of these parameters, a prognostic model was developed as follows: 1) patients with no risk factors; 2) one risk factor; and 3) two or three risk factors. The 3-year distant metastasis-free survival rates for groups 1, 2 and 3 were 100%, 94.6% and 84.3%, respectively (P = 0.001).

Conclusion: The prognostic model based on EBV DNA, serum globulin and nodal size may facilitate individualized treatment of patients with stage II NPC at high risk of distant metastasis.

Keywords: prognostic model, Epstein-Barr virus DNA, serum globulin, nodal size, metastasis, nasopharyngeal carcinoma.