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

Abstract

BackgroundPretreatment 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 MethodsPretreatment 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.ResultsTwo 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.ConclusionThis 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.

Usefulness of Hybrid PET/MRI in Clinical Evaluation of Head and Neck Cancer Patients

“…Some studies have demonstrated that EBV status and primary tumor volume can be utilized in the prognostic stratification of NPC patients [48,49]. On the other hand, data confirming correlations between primary tumor volume and EBV-positivity is limited [50,51].…”

Association of Epstein-Barr virus infection with peripheral immune parameters and clinical outcome in advanced nasopharyngeal carcinoma

“…However, in the current study, we only found that EBV positive patients had more chance to have lower CD8% and higher NK%, no significant association of EBV positive with other peripheral immune parameters in advanced NPC was found. Previous studies reported that EBV DNA titers correlated with tumor burden, remission, and recurrence and could precede tumor development of NPC [32][33][34][35] . Thus, we further analyzed the association of the concentration of plasma EBV DNA with immune parameters.…”

A comparison of EBV serology and serum cell‐free DNA as screening tools for nasopharyngeal cancer: Results of the Singapore NPC screening cohort

“…However, our observations here in an actual screening scenario, suggest that serum EBV DNA performed more poorly in a setting where the disease identified is at a very early stage, as none of the NPC cases identified had levels >100 copies/ml. This may be because cell‐free EBV DNA is a reflection of tumor burden; the early‐stage NPC cases in our screen cohort had very limited disease and thus did not have significantly elevated levels. We also recognize that plasma‐based assays for cell‐free EBV DNA have a better sensitivity and specificity profile compared to serum‐based assays and our serum results here may not reflect the better accuracy profile reported in plasma‐based studies.…”