A persistently detectable post-treatment pEBV DNA level was identified as the most important prognostic factor for both OS (hazard ratio, 4.61; 95% confidence interval, 2.74-7.76; www.selleckchem.com
P < .001) and RFS (hazard ratio, 7.55; 95% confidence interval, 4.35-13.12; P < .001) after adjustment for other variables. A high pretreatment pEBV DNA (��1500 copies/mL) also was identified as a significant predictor for OS (hazard ratio, 1.76; 95% confidence interval, 1.11-2.80; P = .017) and RFS (hazard ratio, 1.95; 95% confidence interval, 1.16-3.28; P = .012). Other variables that had a significant effect on survival were pathologic type for OS and pathologic type, N-classification, and sex for RFS. We replicated the subsequent relapse rate calculation Alpelisib
according to pEBV DNA levels using the same cutoff values (1500 copies/mL pretreatment and 0 copies/mL post-treatment) in the validating set and confirmed that both high pretreatment levels and persistently detectable post-treatment levels were correlated with significantly higher relapse rates (39.3% vs 20% [P = .0439] and 73.7% vs 20.7% [P < .0001], respectively). Similarly, updated follow-up for the training set continued to reveal a positive association between pEBV DNA and the occurrence of treatment failure (53.2% vs 23.1% [P = .0039] and 81.8% vs 31.8% [P = .0020], respectively). In the combined data set, we observed that 47 of 103 patients (45.6%) who had Ibrutinib mw
high pretreatment pEBV DNA levels (��1500 copies/mL) developed recurrent tumors later, whereas 23 of 107 patients (21.5%) who had low pretreatment pEBV DNA levels (<1500 copies/mL) developed recurrent tumors (P = .0037) (Fig. 4A). Patients who had persistently detectable post-treatment pEBV DNA levels (>0 copies/mL) had a significantly higher relapse rate than those who had undetectable levels (76.7% vs 26.1%; P < .0001) (Fig. 4B). The recent development of a real-time quantitative polymerase chain reaction assay has allowed us to detect circulating EBV DNA fragments in most patients with newly diagnosed NPC.18-28 In addition, pEBV DNA has rarely been detected in healthy individuals or in long-term survivors of NPC without relapse.18,24 Lin et al demonstrated that circulating, cell-free EBV DNA may originate from the primary tumor according to their observations of a concordant pattern of decrease in EBV DNA levels in both primary tumor cells and plasma samples after treatment along with consistent genotyping of EBV DNA between paired samples of plasma and primary tumor.24 Several studies have demonstrated a positive correlation between pretreatment pEBV DNA levels and clinical stages of NPC.18,24-28 On the basis of these data, we believe that the quantification of pEBV DNA reflects tumor load in NPC. Recent studies have consistently indicated that the pEBV DNA assay is a useful test in the management of patients with NPC.