Shorter Half-Life Clearance of Plasma EBV DNA Is a Significant Prognostic Factor of Non-Metastatic Nasopharyngeal Carcinoma Treated with Radical Intensity-Modulated Radiation Therapy

Abstract

Plasma Epstein-Barr virus (EBV) DNA has been adopted widely in diagnosis, treatment monitoring and post-treatment surveillance of nasopharyngeal carcinoma (NPC). However, the prognostic role of its plasma clearance in the modern era when intensity-modulated radiotherapy (IMRT) and the 8th edition of AJCC/UICC TNM Staging Classification are fully implemented. We investigated if the half-life clearance of plasma EBV DNA could be an early prognosticator of survival during radical IMRT with or without chemotherapy for previously untreated non-metastatic NPC. Forty-four patients with previously untreated non-metastatic NPC were prospectively recruited and treated with radical IMRT and concurrent chemotherapy +/- induction/adjuvant chemotherapy from 2014 to 2018. All had their plasma EBV DNA measured immediately before treatment followed by weekly schedules until it was undetectable in two consecutive measurements (i.e. 0 copies/ml), as determined by real-time quantitative polymerase chain reaction. Cox regression models were employed to identify prognostic factors of survival. The overall stage distribution was: stage II in 9 (20.4%); stage III in 21 (47.7%) and stage IVA in 14 (31.8%) patients. After a median follow-up of 18.4 months (range 3.4–57.1 months), 2 patients (4.5%), 1 (2.3%) and 4 (9.1%) experienced local recurrences, regional recurrence and distant metastases respectively. Four patients (9.1%) died and all were related to NPC progression. The mean half-life of plasma EBV DNA clearance was 9.82 days. Patients were dichotomized according to the half-life clearance: those with half-life of >15 days had a significantly worse 2-year progression-free survival (PFS) (84.2% vs. 60.0%; p=0.001) and distant metastasis-free survival (DMFS) (94.7% vs. 60.0%; p<0.001) when compared to those with a shorter half-life. Univariable and multivariable analyses demonstrated that age (HR 1.10; 95% CI 1.01–1.19; p=0.026) and half-life (>15 days) were prognostic of PFS (HR 11.13; 95% CI, 2.13–58.11; p=0.007), while half-time (>15 days) was the only prognostic factor of DMFS (HR 14.24; 95% CI, 2.53–79.80; p=0.003). The half-life clearance of plasma EBV DNA was a significant prognostic factor in patients with non-metastatic NPC treated in the modern era. Earlier active surveillance with this relatively non-invasive plasma monitoring tool should be adopted, leading to more prompt subsequent imaging and intensified treatment especially for those who have a suboptimal clearance during their radical treatment.