Relationship between pretreatment concentration of plasma Epstein‐Barr virus DNA and tumor burden in nasopharyngeal carcinoma: An updated interpretation

BACKGROUND: Pretreatment plasma Epstein‐Barr virus (EBV) DNA is an important tumor marker and prognostic factor in nasopharyngeal carcinoma (NPC). This study aimed to clarify the relationship between plasma EBV DNA level and tumor burden. MATERIALS AND METHODS: Pretreatment tumor burden was measured by radiologically delineated volumes, including nasopharynx tumor volume (GTVnx) and malignant nodes volume (GTVnd); pretreatment level of plasma EBV DNA was quantified by quantitative polymerase chain reaction. The relationship between natural logarithm of EBV DNA (ln‐DNA) and square root of tumor volume (sq‐GTV) was analyzed by Pearson correlation coefficient and partial correlation coefficient. Correlations in subgroups of tumor and nodal stages were also analyzed. A linear regression model was constructed to evaluate the contribution of tumor volumes to plasma EBV DNA. The prognostic effects of EBV DNA independent of tumor burden were evaluated. RESULTS: Two thousand two hundred and forty nine nonmetastatic NPC patients with detectable plasma EBV DNA were included in correlation analyses. Ln‐DNA showed significant correlation with sq‐GTVnx (r = 0.171) and sq‐GTVnd (r = 0.339) separately. Together, sq‐GTVnx and sq‐GTVnd could only explain 12.9% of the ln‐DNA. Tumor and nodal stages of disease could clearly influence the strength of relationship in subgroup analysis. After excluding confounding volume information, EBV DNA still can predict death and distant metastasis, but not locoregional relapse. CONCLUSION: This study suggests that plasma EBV DNA is not only an index of tumor burden, but may also reflect other tumor features, such as accessibility to circulation, angiogenesis, tumor cell kinetics, metabolic activity, and metastatic potential, among others.