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Quantitative measurement of plasma Epstein–Barr virus (EBV) DNA by real-time PCR at the end of primary treatment is a robust prognostic marker for nasopharyngeal carcinoma (NPC) patients. However, up to 40% of patients who would later develop disease recurrence had undetectable post-treatment plasma EBV DNA. Targeted sequencing for the entire EBV genome potentially allows a more comprehensive and unbiased detection of plasma EBV DNA and enables the use of other parameters such as fragment size as biomarkers. Hence, we explored if plasma EBV DNA sequencing might allow more accurate prognostication of NPC patients. Plasma samples collected from 769 patients with stage IIB-IVB NPC at 6-8 weeks after radiotherapy were analysed using targeted sequencing for EBV DNA. The sensitivities of the PCR-based analysis, at a cut-off of any detectable levels of plasma EBV DNA, for prediction of local and distant recurrences were 42.3% and 85.3%, respectively. The sequencing-based analysis (involving quantitation and size profiling) achieved better performance for both local and distant recurrences than PCR. Using a cut-off of the proportion of plasma EBV DNA deduced by sequencing at 0.01%, the sensitivities of the sequencing-based analysis for local and distant recurrences were 88.5% and 97.1%, with the resultant negative predictive values of 99.1% and 99.4%, respectively. Among patients with undetectable EBV DNA on quantitative PCR, sequencing could further define a subgroup that enjoyed superior survival outcomes based on the proportion of plasma EBV DNA, with a 5-year progression-free survival (PFS) approaching 90%. On multivariate analysis, sequencing-based quantitative level of plasma EBV DNA was the independent prognostic factor with the highest hazard ratio for prediction of overall survival and PFS. NPC prognostication using post-treatment plasma EBV DNA could be enhanced through sequencing. • PCR-based analysis of plasma EBV DNA has limited sensitivity in predicting recurrences of NPC. • Sequencing analysis of post-treatment plasma EBV DNA improves the sensitivity for both local and distant relapses of NPC. • Sequencing analysis of post-treatment plasma EBV DNA could better stratify the mortality risk of NPC patients than PCR. [ABSTRACT FROM AUTHOR]

Unfavorable EBV DNA response at mid-course of radiotherapy/ chemoradiotherapy for nasopharyngeal carcinoma is an adverse prognosticator for treatment outcome, and is linked to majority of failures. The data provides a basis for design of biomarker-driven trials that address alteration of therapy intensity during the latter phase of chemoradiotherapy, and adjuvant therapy.Background To test the hypothesis that prognostication of treatment outcome is feasible by biomarker response at midcourse of chemoradiotherapy (CRT)/radiotherapy (RT), with respect to the plasma load of Epstein–Barr viral (EBV) DNA in nasopharyngeal carcinoma (NPC). Patients and methods One hundred seven patients with stage IIB–IV NPC were prospectively studied. Plasma EBV DNA load was measured by quantitative PCR before therapy (pre-DNA), at completion of 4 weeks of CRT/RT (mid-DNA), and within 3 months of completion of therapy (post-DNA). The end points are post-DNA load, a recognized surrogate of survival, and clinical outcome. Results Ninety-three percent of patients had detectable EBV DNA before therapy (median load = 972 copies/ml). EBV DNA became undetectable in 55 (51%) patients at the end of week 4 of therapy. Detectable mid-DNA was associated with worse clinical outcome (median follow-up time, 6.2 years), for distant failure [hazard ratio (HR) 12.02, 95% confidence interval (CI) 2.78–51.93; P < 0.0001], progression-free survival (PFS; HR 4.05, 95% CI 1.89–8.67, P < 0.0001), and overall survival (OS; HR 3.29, 95% CI 1.37–7.90, P = 0.0077). Seventy-four percent of all failures were associated with detectable mid-DNA, whereas 34% of all failures were associated with detectable post-DNA. Stratification by tumor stage (IIB, III, IV) has no significant prognostic effect. Conclusions Unfavorable EBV DNA response at midcourse of RT/CRT is an adverse prognosticator for treatment outcome, is linked to majority of all failures, and discriminates outcome better than tumor stage. The data could provide a basis for trial design that addresses alteration of therapy intensity during the latter phase of CRT, and adjuvant therapy. Validation studies are awaited. [ABSTRACT FROM PUBLISHER]

Background: We aimed to evaluate the safety and efficacy of single-agent sunitinib in nasopharyngeal carcinoma (NPC).Methods: Eligible patients had progressive disease after prior platinum-based chemotherapy. Sunitinib was given as continuous once-daily dosing of 37.5 mg in 4-week cycles until progression.Results: Thirteen patients were enrolled. Recruitment was stopped after two patients died of hemorrhagic events. All patients had previously received curative radiotherapy (RT) to nasopharynx/neck (including nine patients who had chemoradiotherapy). Patients received a median of three cycles of sunitinib. One patient was still on sunitinib with stable disease after 24 cycles. Hemorrhagic events occurred in nine patients (64%), including epistaxis in six, hemoptyses in three and hematemesis in two patients. Prior RT to thorax was significantly associated with hemoptyses (P = 0.03). Two patients with local tumor invasion into the carotid sheath developed fatal epistaxis/hematemesis within the first cycle of sunitinib, likely due to internal carotid blowout after tumor shrinkage.Conclusions: Sunitinib demonstrated modest clinical activity in heavily pretreated NPC patients. However, the high incidence of hemorrhage from the upper aerodigestive tract in NPC patients who received prior high-dose RT to the region is of concern. Direct vascular invasion by tumors appeared to increase the risk of serious bleeding. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is a platinum-sensitive cancer and excision repair cross-complementing group 1 (ERCC1) polymorphisms have been shown to predict survival in several cancers following platinum therapy. [ABSTRACT FROM PUBLISHER]