Study On The Prognostic Value Of Monitoring The Dynamic Changes In Plasma Epstein-Barr Virus DNA In Nasopharyngeal Carcinoma

BackgroundPlasma EBV DNA has been proved to be a reliable molecular marker of nasopharyngeal carcinoma(NPC),and it has important prognostic value.However,the plasma EBV DNA data included in previous studies were mostly focused on the time points pre-treatment to three months post-treatment,but the research on monitoring the dynamic changes of plasma EBV DNA more than 3 months post-treatment and long-term follow-up is very limited,so the prognostic value of dynamic monitoring of plasma EBV DNA in long-term follow-up before and after treatment for NPC is still unclear.Therefore,this paper intends to retrospectively study the prognostic value of monitoring the dynamic changes in plasma Epstein-Barr virus DNA in nasopharyngeal carcinoma by examining long-term follow-up clinical database with a large sample size.MethodThe first part analyzed the prognostic value of plasma EBV DNA load prior and 3 months,12 months 24 months and 36 months subsequent to treatment on 1077 patients with non-metastatic NPC first diagnosised in our hospital from January 2005 to December 2015.in the second part,we selected 543 patients to explore the relationship between the changes in plasma EBV DNA pre-treatment and 3 months post-treatment and the prognosis of NPC.The third part was to study the effect of dynamic changes of plasma EBV DNA load at four time points which include pre-treatment and 3 months,12 months,24 months post-treatment on the prognosis of 252 patients with NPC.The prognostic differences between the two groups were compared by survival analysis and chi-square test.Cox proportional hazard model was used for multivariate analysis.ROC curve analysis was used to determine the cutoff value of plasma EBV DNA,and compare the differenceprognostic values between the change in plasma EBV DNA pre-treatment and 3 months post-treatment,the dynamic changes of plasma EBV DNA at 4 time points at four time points pre-and post-treatment and single time point EBV DNA in predicting the prognosis of NPC.Results(1)There was a certain dynamic change trend of plasma EBV DNA before and after treatment,and the positive rate and load of plasma EBV DNA decreased significantly after treatment,but rose again slowly over time,peaking again at 24 months post-treatment,and then decreased at 36 monthspost-treatment.Except for the limited study on the value of plasma EBV DNA 36 months post-treatment in predicting the mortality of NPC patients,the 5-year progression-free survival(PFS),distant metastasis-free survival(DMFS),locoregional relapse-free survival(LRFS),and overall survival(OS)of NPC patients with plasma EBV DNA higher than cutoff value at each time point prior and subsequent to treatment were significantly worse than those with lower cutoff value(P<0.001).(2)There were significant differences in the prognosis among the four subgroups patients with NPC stratified by the change in plasma EBV DNA pre-treatment and 3 months post-treatment(P<0.001).the combination of pre-treatment and 3 months post-treatmentplasma EBV DNA was an independent prognostic factor of NPC,which was more valuable than pre-treatment plasma EBV DNA or 3 months post-treatmentplasma EBV DNA alone.(3)There were significant differences in 3-year PFS,DMFS,LRFS and OS among the five subgroups patients with NPC stratified by the dynamic changes in plasma EBV DNA at four time points pre-and post-treatment(P<0.001).Multivariate analysis confirmed that the dynamic changes of plasma EBV DNA at four time points pre-and post-treatment was a powerful prognostic factor for patients with NPC(P<0.001).ROC curve analysis also confirmed that the dynamic changes in plasma EBV DNA at four time points pre-and post-treatment was more sensitive than single time point EBV DNA in predicting the prognosis of NPC.ConclusionsThis study confirmed that plasma EBV DNA has a certain dynamic trend in long-term follow-up monitoring pre-and post-treatment,which has important predictive value for the prognosis of patients with nasopharyngeal carcinoma,and can provide more comprehensive and in-depth disease risk stratification information.It has important clinical reference significance for the clinical diagnosis and treatment of NPC patients,especially in the formulation and implementation of individualized follow-up management plan.