Purpose: To investigate the prognostic effect of the concentrations and clearance rates of plasma EBV DNA in metastatic/recurrent nasopharyngeal carcinoma (NPC).Experimental Design: Thirty relapsed and four previously nontreated metastatic NPC patients were treated according to the consensus guidelines of the head and neck cancer team in our hospital (i.v. chemotherapy first, followed by local irradiation boost and oral maintenance chemotherapy where applicable). Multiple plasma samples were collected during the first month of chemotherapy. Circulating EBV DNA concentrations were measured by a real-time quantitative PCR. The half-life values (t 1/2 ) of plasma EBV DNA clearance were calculated. The associations between clinical outcome and plasma EBV DNA assays were analyzed.Results: Tumor response evaluated after 12 weeks of treatment showed 14 complete responses (41.2%), 12 partial responses (35.3%), 7 stable diseases (20.6%), and 1 progression disease (2.9%). The plasma EBV DNA concentrations have no significant effects on outcome prediction. The t 1/2 of plasma EBV DNA clearance ranged from 1.85 to 28.29 days (median, 3.99). Patients with a short t 1/2 of plasma EBV DNA clearance have significantly higher complete response rate and overall survival than those with long t 1/2 . Multivariate analysis revealed a significant effect of the t 1/2 of plasma EBV DNA clearance on survival.Conclusions: The clearance rates of plasma EBV DNA during the first month of chemotherapy can predict tumor response and patient survival. Early change of chemotherapy regimen may be considered for patients with slow plasma EBV DNA clearance rate. Clin Cancer Res; 16(3); 1016-24. ©2010 AACR.Nasopharyngeal carcinoma (NPC) is distinct from other cancers of the head and neck by its epidemiology, histopathology, clinical characteristics, methods of treatment, and patterns of failure. Because of the inherent anatomic constraints and a high degree of radiosensitivity, radiotherapy has been the primary treatment for NPC patients without distant metastasis. Treatment failure in the past was due to a high rate of local recurrence and/or distant metastasis. However, advances in radiation oncology have improved the locoregional control, and treatment failure is now due mainly to distant metastasis. To date, the outcome of salvage treatment for relapse is still very poor, with the 5-year survival rates after local recurrence and distant metastasis being 9.4% to 30% and <5%, respectively (1-6). Because most metastatic/recurrent patients will succumb rapidly to the disease, the development of a quick and precise marker to predict treatment response is urgently needed.NPC has been proven as an EBV-associated cancer. EBV genome is present in the cells from almost every primary and metastatic NPC, regardless of the degree of tumor differentiation or the geographic origin of the patients. Recently, the quantification of plasma EBV DNA by the real-time quantitative PCR has been shown as a useful marker in the detection, monitoring, and prognos...

BACKGROUND:The objective of this study was to confirm the relation between plasma Epstein-Barr virus (EBV) DNA (pEBV DNA) load and treatment outcomes after long-term follow-up in patients with nasopharyngeal carcinoma (NPC). METHODS: In total, 210 patients with NPC were enrolled, including 99 previously reported patients and 111 new patients. They prospectively received treatment with induction chemotherapy plus radiotherapy and were followed for at least 6 years. In these patients, pEBV DNA levels were measured before treatment and 1 week after treatment. The plasma viral load was correlated with treatment outcomes in the group of new patients and in the entire group. RESULTS: By using previously defined pEBV DNA cutoff values (1500 copies/mL pretreatment and 0 copies/mL post-treatment), there was a significant correlation between the pEBV DNA value and relapse-free survival, overall survival, and subsequent relapse rates in the new, independent patient cohort. Outcome analyses for the entire group revealed a higher relapse rate (45.6% vs 21.5% [P ¼ .0037] or 76.7% vs 26.1% [P < .0001]), a worse relapse-free survival rate (56.5% vs 79.3% [P < .0001] or 23.3% vs 75.6% [P < .0001]), and poorer overall survival (59.2% vs 86% [P ¼ .0003] or 33.3% vs 79.4% [P < .0001]) in patients who had high pretreatment or persistently detectable post-treatment pEBV DNA levels, respectively, versus their respective counterparts. Multivariate Cox analysis also confirmed these results. CONCLUSIONS: In this expanded study, the prognostic significance of pEBV DNA was confirmed using predefined cutoff values in an independent patient group, and pEBV DNA was identified as an independent prognostic marker for NPC.

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