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Quantification of Epstein-Barr virus (EBV) cell-free DNA (cfDNA) is commonly used in clinical settings as a circulating biomarker in nasopharyngeal carcinoma (NPC), but there has been no comparison with circulating tumour cells (CTCs).Our study aims to compare the performance of CTC enumeration against EBV cfDNA quantitation through digital PCR (dPCR) and quantitative PCR. 74 plasma samples from 46 NPC patients at baseline and one month after radiotherapy with or without concurrent chemotherapy were analysed. CTCs were captured by microsieve technology and enumerated, while three different methods of EBV cfDNA quantification were applied, including an in-house qPCR assay for BamHI-W fragment, a CE-IVD qPCR assay (Sentosa ® ) and a dPCR (Clarity ™ ) assay for Epstein-Barr nuclear antigen 1 (EBNA1). EBV cfDNA quantitation by all workflows showed stronger correlation with clinical stage, radiological response and overall survival in comparison with CTC enumeration. The highest detection rate of EBV cfDNA in pre-treatment samples was seen with the BamHI-W qPCR assay (89%), followed by EBNA1-dPCR (85%) and EBNA1-qPCR (67%) assays. Overall, we show that EBV cfDNA outperforms CTC enumeration in correlation with clinical outcomes of NPC patients undergoing treatment. Techniques such as dPCR and target selection of BamHI-W may improve sensitivity for EBV cfDNA detection.Nasopharyngeal carcinoma (NPC) is a malignant cancer of the nasopharynx, which is particularly common in parts of Southern China, South East Asia and North Africa 1 . Due to high rates of Epstein-Barr virus (EBV) nucleic acid detection in NPC, non-invasive approaches to diagnosis have focused on EBV as a target [2][3][4] . Post-treatment Epstein-Barr virus (EBV) cell-free DNA (cfDNA) levels have been demonstrated to correlate with NPC prognosis and recurrence 5,6 . EBV cfDNA can be quantified in the form of EBV single-copy genes; EBNA1, LMP2 and Pol-1, or multiple-repeat fragments; BamHI-W 7 . As there are six to twenty copies of BamHI-W per EBV genome 8 , higher sensitivity is expected in BamHI-W quantification assays. However, the variability of BamHI-W copy numbers in different EBV isolates has been considered a challenges in assay comparison and standardization between laboratories 7, 8 . CTCs represent a circulating biomarker which has been extensively studied in many cancer types including breast, lung and colorectal cancer [9][10][11][12] . Due to challenges including platform costs and standardization, much

BACKGROUND Patients with nasopharyngeal carcinoma (NPC) are treated primarily with radiotherapy. In the disseminated state, platinum‐based, 2‐drug combination regimens yielded response rates of 55–75%, achieving a median survival of 10–12 months. With the proven efficacy of second‐generation cytotoxics like paclitaxel and gemcitabine in patients with metastatic NPC, the authors hypothesized that a triplet combination incorporating these newer cytotoxics may improve treatment results. METHODS Thirty‐two patients with metastatic NPC were treated with combination chemotherapy that included paclitaxel 70 mg/m2 on Days 1 and 8, carboplatin dosed to area under curve of 5 on Day 1, and gemcitabine 1000 mg/m2 on Days 1 and 8 every 21 days for a maximum of 8 cycles. RESULTS Two patients achieved a complete response, and 23 patients achieved a partial response, for an overall response rate of 78%. The main toxicities were hematologic, with 41% of patients experiencing Grade 3 or 4 anemia, 41% of patients experiencing Grade 3 or 4 thrombocytopenia, and 78% of patients experiencing Grade 3 or 4 neutropenia. The median time to disease progression was 8.1 months, and the median overall survival was 18.6 months. CONCLUSIONS The combination of paclitaxel, carboplatin, and gemcitabine showed promising efficacy against metastatic NPC but at the expense of considerable toxicity. Cancer 2005. © 2004 American Cancer Society.