Prospective evaluation of plasma Epstein-Barr virus DNA clearance and fluorodeoxyglucose positron emission scan in assessing early response to chemotherapy in patients with advanced or recurrent nasopharyngeal carcinoma

Abstract

Background: Plasma Epstein-Barr virus (pEBV) DNA and fluorodeoxyglucose positron emission (PET) reflect tumour burden in advanced NPC. This study hypothesised that a dual endpoint based on assessing pEBV DNA clearance and PET response could predict early drug response.

Methods: Eligible patients underwent a computed tomography (CT) scan and dual PET-CT at baseline, a PET-CT at 4 weeks, and then a CT scan at 10 weeks after starting palliative or induction chemotherapy. Plasma EBV DNA clearance was determined.

Results: Fifty-eight out of 70 enrolled patients completed all imaging and 50/58 had falling pEBV DNA level, which allowed calculation of the clearance. At a median follow-up of 29.1 months, the dual endpoint (pEBV DNA clearance ≤ 10 days and > 50% drop in sum of SUVmax of target lesions) was an independent indicator of overall survival (hazard ratio (HR) = 0.135, 95% CI = 0.039 to 0.466, p = 0.0015) and progression-free survival (HR = 0.136, 95% CI = 0.048 to 0.385, p = 0002). This dual endpoint could predict subsequent response by Response Evaluation Criteria In Solid Tumours (RECIST) criteria at 10 weeks after chemotherapy.

Conclusions: Early PET-CT response and pEBV DNA clearance could predict survival and subsequent response. This dual endpoint is an innovative tool for assessing early drug response.

Trial registration: ClinicalTrials.gov NCT01365208.

Fig. 1

Overall survival (OS) curves of responders (top curve, > 50% drop in sum of SUVmax of target lesions and plasma EBV DNA clearance of ≤ 10 days, 1-year OS 100%) versus non-responders (bottom curve, ≤ 50% drop in sum of SUVmax and plasma EBV DNA clearance of > 10 days, 1-year OS 81.9%) based on the dual endpoint (log-rank, p = 0.0003). For the evaluable cohort (n = 58), the number of death and progression are 30 and 35

Fig. 2

Progression-free survival (PFS) curves of responders (top curve, > 50% drop in sum of SUVmax and plasma EBV DNA clearance of ≤ 10 days, 1-year PFS rate 86.2%) versus non-responders (bottom curve, ≤ 50% drop in SUVmax and plasma EBV DNA clearance of > 10 days, 1-year PFS 36.5%) based on the dual endpoint (log-rank p = 0.0047)