Pretreatment Alkaline Phosphatase and Epstein-Barr Virus DNA Predict Poor Prognosis and Response to Salvage Radiotherapy in Patients with Nasopharyngeal Carcinoma and Metachronous Bone-Only Metastasis

Abstract

Background : The bones are the most common site of distant metastasis in nasopharyngeal carcinoma (NPC). Few prognostic markers are available to guide treatment and sub-classify patients with bone metastasis. We aimed to identify the prognostic value of pretreatment serum alkaline phosphatase (ALP) and plasma Epstein-Barr virus DNA (EBV DNA) in patients with bone-only metastasis. Methods : A total of 272 patients who developed bone-only metastases after therapy were retrospectively analyzed. Patients were categorized according to pretreatment serum ALP (< or ≥ 110 U/L) and pretreatment plasma EBV DNA (< or ≥ 6,750 copies ml^-1). Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test. Results : Median OS for the cohort was 34.06 months (range, 2.53-143.87 months). Multivariate Cox proportional hazard analysis verified pretreatment serum ALP and pretreatment plasma EBV DNA were independent prognostic factors for OS. In stratified survival analysis of patients with elevated pretreatment serum ALP and/or plasma EBV DNA, delivery of radiotherapy (RT) to bone metastases provided a significant OS benefit compared to other therapeutic methods (P < 0.05). Conclusions : This study demonstrates two important points: firstly, pretreatment serum ALP and plasma EBV DNA have prognostic value at the first diagnosis of bone-only metastasis in NPC. Secondly, radiotherapy of bone metastasis improves the prognosis of patients with elevated pretreatment serum ALP and plasma EBV DNA.

Keywords: Epstein-Barr virus DNA; Nasopharyngeal carcinoma; alkaline phosphatase; bone metastasis; prognosis..

Figure 1

Kaplan-Meier overall survival curves for the 272 patients with nasopharyngeal cancer stratified by (A) pretreatment serum ALP and (B) pretreatment plasma EBV DNA.

Figure 2

Kaplan-Meier overall survival curves. (A) Overall survival curves for the 272 patients with nasopharyngeal cancer stratified by the disease-free interval (DFI) to bone-only metastasis. (B) Overall survival curves for the 272 patients with nasopharyngeal cancer stratified as group A, non-elevated ALP (NE-ALP) and low EBV DNA; group B, NE-ALP and high EBV DNA or elevated ALP (E-ALP) and low EBV DNA; and group C, E-ALP and high EBV DNA. (C) Overall survival curves for group A stratified by radiotherapy after metastasis; (D) group B stratified by radiotherapy after metastasis; (E) group C stratified by radiotherapy after metastasis; and (F) the entire cohort of 272 patients stratified by radiotherapy after metastasis.