Interplay of Tumor Spread, Volume and Epstein-Barr Virus DNA in Nasopharyngeal Carcinoma: Feasibility of An Integrative Risk Stratification Scheme

Xin Zhou^1,2*, Youqi Yang^1,2*, Xiaomin Ou^1,2, Tingting Xu^1,2, Chunying Shen^1,2, Chaosu Hu^1,2✉

1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
*The coauthors contributed equally to the manuscript.

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Citation:
Zhou X, Yang Y, Ou X, Xu T, Shen C, Hu C. Interplay of Tumor Spread, Volume and Epstein-Barr Virus DNA in Nasopharyngeal Carcinoma: Feasibility of An Integrative Risk Stratification Scheme. J Cancer 2018; 9(22):4271-4278. doi:10.7150/jca.26777. Available from https://www.jcancer.org/v09p4271.htm

Abstract

Purpose: To investigate the inter-correlation of tumor spread, volume and quantitative plasma Epstein-Barr virus DNA level (pEBV DNA), and to further assess the prognostic efficacy of a novel risk stratification combining anatomic, volumetric and biological features in nasopharyngeal carcinoma (NPC).

Methods and Materials: One hundred and twelve patients with non-metastatic NPC were prospectively enrolled. Correlation of pEBV DNA with tumor invasiveness, lymph node (LN) metastasis, tumor volume and classification was tested by univariate and multivariate analyses. 5-year distant metastasis free survival (DMFS) was evaluated using Kaplan-Meier method and Cox proportional hazards model.

Results: Tumor volume, TNM stage and pEBV DNA were strongly inter-correlated to each other. Nodal volume, skull base invasion and LN metastasis to supraclavicular fossa were determined to be independent predictors for pEBV DNA level. To exclude collinearity, a risk stratification based on combination of EBV DNA, nodal volume and anatomic features was established, offering significant distinguishing ability in 5-year DMFS. Further multivariate Cox regression analysis found the novel stratification to be independent predictor of DMFS.

Conclusions: Both anatomic spread and tumor volume contribute to pEBV DNA level, leading to strong inter-correlation between NPC stage, volume and EBV DNA. The proposed risk stratification combining anatomic, volumetric and biological features showed potential in refining DMFS prediction.

Keywords: AJCC cancer staging, Epstein-Barr virus DNA, nasopharyngeal carcinoma, tumor burden, tumor spread