Background We investigated the clinical significance of plasmaconcentrations of Epstein–Barr virus (EBV) DNA in patientswith advanced nasopharyngeal carcinoma.
Methods Ninety-nine patients with biopsy-proven stage III orIV nasopharyngeal carcinoma and no evidence of metastasis (M0)received 10 weekly chemotherapy treatments followed by radiotherapy.Plasma samples from the patients were subjected to a real-timequantitative polymerase-chain-reaction assay. EBV genotypesof paired samples from plasma and primary tumor were compared.
Results Plasma EBV DNA was detectable before treatment in 94of the 99 patients, but not in 40 healthy controls or 20 curedpatients. The median concentrations of plasma EBV DNA were 681copies per milliliter among 25 patients with stage III disease,1703 copies per milliliter among 74 patients with stage IV disease,and 291,940 copies per milliliter among 19 control patientswith distant metastasis (P<0.001). Patients with relapsehad a significantly higher plasma EBV DNA concentration beforetreatment than those who did not have a relapse (median, 3035vs. 1202 copies per milliliter; P=0.02). The consistent genotypingof EBV DNA between paired samples of plasma and primary tumorsuggested that the circulating cell-free EBV DNA may originatefrom the primary tumor. Unlike the rebound of plasma EBV DNAconcentrations in the patients who had a relapse, the plasmaEBV DNA concentration was persistently low or undetectable inpatients with a complete clinical remission. Overall survival(P<0.001) and relapse-free survival (P=0.02) were significantlylower among patients with pretreatment plasma EBV DNA concentrationsof at least 1500 copies per milliliter than among those withconcentrations of less than 1500 copies per milliliter. Patientswith persistently detectable plasma EBV DNA had significantlyworse overall survival (P<0.001) and relapse-free survival(P<0.001) than patients with undetectable EBV DNA one weekafter the completion of radiotherapy.
Conclusions Quantification of plasma EBV DNA is useful for monitoringpatients with nasopharyngeal carcinoma and predicting the outcomeof treatment.
Source Information
From the Department of Radiation Oncology (J.-C.L., J.-S.J.) and the Department of Otorhinolaryngology (R.-S.J.), Taichung Veterans General Hospital, Taichung; the Department of Medicine, School of Medicine (J.-C.L.), and the Department of Biochemistry and Center for Cellular and Molecular Biology, School of Life Science (Y.-H.W.), National Yang-Ming University, Taipei; the Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan (J.-C.L.); the Department of Medicine, School of Medicine (J.-C.L.), and the Department of Public Health (W.-M.L.), China Medical University, Taichung; the Department of Basic Medicine, Hung Kuang University, Taichung (W.-Y.W.); and the Cancer Center, Taipei Veterans General Hospital, Taipei (K.Y.C.) — all in Taiwan.
Address reprint requests to Dr. Lin at the Department of Radiation Oncology, Taichung Veterans General Hospital, Taiwan No. 160, Sec. 3, Taichung-Kang Rd., Taichung 407, Taiwan, or at jclin{at}vghtc.gov.tw.
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