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

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.

Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinoma

“…We also examined the baseline tumor size, blood CD8+ and CD4+ T cells proportions, and plasma IFN-γ levels in different response groups and did not observe a significant difference ( Figures 2C–F ; Supplementary Table S2 ). However, we found that plasma EBV DNA load was weakly related to tumor size (n=46, r=0.41, P = 0.0042) ( Figure 2G ), which was consistent with a previous study ( 35 ). However, we did not detect any correlations between plasma EBV DNA load and blood CD8+ T cell proportion, CD4+ T cell proportion, or TMB, using Spearman coefficient analysis ( Figures 2H, I ).…”

“…Regarding environmental factors, we found that higher blood EBV DNA load was significantly related to poor clinical prognosis, as previously reported ( 41 ). Blood EBV load is often found to correlate positively with tumor size, reflecting that the cell-free EBV DNA likely originates from the tumor mass ( 35 ). Other than tumor size, the plasma EBV DNA load did not show correlation with the other identified markers (TMB, peripheral blood T helper cells and cytotoxic T cells, or IFN-γ levels).…”

Early change of plasma Epstein-Barr virus DNA load and the viral lytic genome level could positively predict clinical outcome in recurrent or metastatic nasopharyngeal carcinoma receiving anti-programmed cell death 1 monotherapy

“…In POLARIS-02 study, the association of baseline EBV DNA titers with ORR was not statistically different but patients with RM-NPC with low baseline EBV copy number had a significantly higher DCB rate and improved survival [ 5 , 20 ]. In our study, the baseline EBV load was positively correlated with tumor size and patients with PR and SD had significantly lower baseline EBV load than patients with PD, indicating that the blood EBV DNA might be derived from the tumor mass and could serve as an indicator of the tumor burden [ 29 ]. Previous studies have reported that large baseline tumor size was an independent prognostic marker of unfavorable efficacy in patients treated with pembrolizumab monotherapy [ 30 , 31 ].…”