Detecting plasma Epstein-Barr virus DNA to diagnose postradiation nasopharyngeal skull base lesions in nasopharyngeal carcinoma patients: a prospective study

Abstract

The diagnosis of postradiation nasopharyngeal skull base lesions in petients with nasopharyngeal carcinoma (NPC) is still a tough problem in clinical practice. An early and accurate diagnosis is important for subsequent management. We prospectively evaluated the diagnostic value of plasma Epstein-Barr virus(EBV) DNA in detecting postradiation nasopharyngeal skull base lesions in NPC patients. From July 2006 to September 2010, 90 patients with postradiation NPC (34 women and 56 men; median age: 42 years) met the selection criteria and were recruited in this study. All postradiation nasopharyngeal skull base lesions were found in the latest magnetic resonance imaging (MRI) examinations before endoscopic surgery, and the nasopharyngeal cavity was normal under flexible nasopharyngoscopy. Plasma EBV DNA detection was performed within 2 weeks before endoscopic surgery. A total of 90 endoscopic operations were successfully performed without any postoperative complications. Recurrences confirmed by postoperative pathology were found in 30 patients. The specificity, positive and negative predictive values of plasma EBV DNA detection were better than those of MRI. In addition, combining plasma EBV DNA detection with MRI improved the specificity and positive predictive values of MRI. Plasma EBV DNA detection followed by MRI would help to diagnose recurrence whereas MRI was unable. These results indicate that plasma EBV DNA is an effective and feasible biomarker for detecting postradiation nasopharyngeal skull base lesions in NPC patients.

Figure 1.. Preoperative examination, operation, and postoperative follow-up in a nasopharyngeal carcinoma (NPC) patient with a postradiation nasopharyngeal skull base lesion.

This NPC patient was a 59-year-old man who underwent one course of radiotherapy. The 1-year follow-up MRI shows signals indicating probable malignancy. Postoperative pathology showed osteoradionecrosis. A, T2-weighted image on the axial plane shows normal marrow signal in the right clivus changed to heterogeneous slightly hypointense signal with a patchy, slightly hyperintense signal inside (yellow arrow). B, enhanced T1-weighted image on the sagittal plane shows heterogeneous enhancement in the right clivus lesion with patchy, non-enhanced areas inside (yellow arrow). C, the nasopharynx cavity is normal and there are no signs of recurrence under flexible nasopharyngoscope. D, the right clivus is exposed and abraded for biopsy via transnasal approach (black arrow). E, at the 2-month follow-up after surgery, the endoscopic examination shows the biopsied region covered by a scab (black arrow). F, at the 6-month follow-up after surgery, the endoscopic examination shows mucosal epithelialization and no signs of recurrence in the biopsied region (black arrow). S, sphenoid sinus; NP, nasopharynx.

Figure 2.. Detection of plasma Epstein-Barr virus (EBV) DNA by real-time polymerase chain reaction (PCR).

A, amplification plot of fluorescence intensity against the PCR cycle. Each plot corresponds to a particular input target quantity marked by a corresponding symbol. The X-axis denotes the cycle number of a quantitative PCR reaction. The Y-axis denotes the Rn, which is the fluorescence intensity over the background. B, a plot of the threshold cycle against the input target quantity. The input target quantity is expressed as copies of EBV DNA.

Figure 3.. Plasma EBV DNA levels in patients with and without recurrent NPC.

Scatter diagram shows that the preoperative plasma EBV DNA levels in the recurrent NPC group was significantly higher than that in the non-recurrent group (P = 0.03).