Background & objective: Distant metastasis is one of the main causes of treatment failure in nasopharyngeal carcinoma (NPC). Trials of combined modality treatment could not demonstrate obvious decrease of the rate of distant metastasis and survival rate, therefore eligible individualized and best combined modality treatment has not been established. Plasma Epstein-Barr virus (EBV) DNA is a sensitive and specific molecular marker, which may reflect the stage, response to treatments and prognosis of NPC. This prospective study was to investigate whether the plasma EBV DNA concentration could be used to predict distant metastasis in NPC, and thus to provide us a molecular marker for individualized combined modality treatment.
Methods: Blood samples from 69 patients with primary NPC were collected before and after radiotherapy. The content of EBV DNA in the plasma samples was detected by real-time quantitative PCR. All patients received consequent follow up and long-term efficacy and survival assessment. The correlation of pre/post treatment EBV DNA concentrations to survival was analyzed by Kaplan-Meier method. The prognostic factors were evaluated by Cox proportional hazards model.
Results: Both pretreatment EBV DNA median concentration (27,000 copies/ml) and post-treatment EBV DNA detecting rate (55.56%) in patients with distant metastasis were higher than those with continuous remission (4,000 copies/ml, 5.56%) and those with local relapse (3,850 copies/ml, 0%)(P = 0.039 and 0.001, respectively). With a cut-off value of 20,000 copies/ml and 0 copies/ml respectively for pretreatment and post-treatment EBV DNA concentration, patients with lower EBV DNA concentration had statistically preferable progression-free survival (PFS), metastasis-free survival(MFS) and overall survival (OS) than those with higher EBV DNA concentration. Cox regression analysis demonstrated that both pretreatment EBV DNA (P = 0.050; RR = 3.95) and post-treatment EBV DNA (P = 0.001; RR = 11.74) were risk factors for MFS. Further analysis of pretreatment and post-treatment EBV DNA concentration revealed that whether EBV DNA concentration could be decreased to 0 after treatment dominated metastasis-free survival (P = 0.000).
Conclusion: Plasma EBV DNA concentration before and after treatment, especially whether post-treatment concentration could be decreased to 0 may predict distant metastasis, which helps to select patients with high risks and determine the combined modality treatment.