Prognostic significance of plasma Epstein-Barr virus (EBV) DNA level in patients with locally advanced head and neck carcinoma treated with concurrent cisplatin and concomitant boost radiotherapy (CBRT)

Abstract

20003 Background: EBV DNA is detectable in the plasma in most patients (Pts) with lymphoepithelial carcinoma (LECA) and in some Pts with squamous cell carcinoma (SCC) of the HN. We investigated the prognostic significance of plasma EBV DNA level in a prospective phase II trial of concurrent cisplatin and CBRT for locally advanced HN carcinomas. Methods: Eligibility criteria included newly-diagnosed SCC or LECA of non-nasopharyngeal HN sites; stage III or IV disease; ECOG performance status ≤ 1; and age ≤ 70 years. Plasma EBV DNA levels were measured by real-time quantitative polymerase chain reaction (PCR) before treatment and at 6 weeks post-treatment. Pre-treatment gross tumor volume (GTV) was measured on CT, and invasion of bone and cartilage was assessed on CT and MRI. Cisplatin 40–50 mg/m2 was given on days 1, 8, 15 and 22 of CBRT. Radiotherapy consisted of 54 Gy/30 fractions/6 weeks and a concomitant boost (18 Gy/12 fractions) in the last 12 treatment days. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). Survival curves were compared by the log-rank test and multivariate analysis was performed with Cox regression. Results: Between March 2001 and January 2005, 46 Pts were recruited (36 with SCC and 10 with LECA). Thirty-four Pts had stage III and 12 had stage IV disease. Pre-treatment plasma EBV DNA level was > 0 copy/ml in all Pts with LECA (range, 37 - 211737 copies/ml) and in 8 Pts with SCC (range, 10 - 48734 copies/ml). Ten Pts had plasma EBV DNA level > 0 copy/ml at 6 weeks post-treatment. With a median follow-up of 1.6 years, the 1-year OS rate was 87.7 % and 1-year PFS rate was 68.3%. On multivariate analysis, plasma EBV DNA > 0 copy/ml at 6 weeks post-treatment was the only independent predictive factor of decreased OS [hazard ratio (HR) 3.59, p = 0.04] for the entire group. In the subgroup of Pts with SCC, pre-treatment EBV DNA > 0 copy/ml was the only independent predictive factor of decreased locoregional PFS (HR 7.08, p = 0.03). Conclusions: Plasma EBV DNA level is a prognostic factor in Pts with locally advanced HN SCC and LECA. Further studies are warranted to confirm the finding and to elucidate its biological basis. No significant financial relationships to disclose.