Abstract
Differential overall survival of nasopharyngeal carcinoma (NPC) with different organ site metastases has been documented. Here, we attempted to determine the underlying mechanisms by assessing plasma and tumor tissue markers in relation to patient survival. Pretreatment plasma Epstein-Barr virus (EBV) DNA concentrations, cytokines and tissue macrophages, proliferation and apoptosis markers were determined in 178 patients with metastatic NPC. The median overall survival (OS) was 19 months. Patients with single organ metastases had better outcomes than those with multiple organ metastases (median OS: 26 months vs. 16 months), with statistical significance. Among the single organ involvement cases, patients with lung metastasis only showed longer survival than those with bone or liver involvement (median OS: 50 months vs. 21 months vs. 18 months; P < 0.001). Pretreatment plasma EBV DNA concentrations were lower in patients with lung metastasis than bone or liver metastasis among single organ site groups. Plasma interferon-γ-inducible protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1) expression levels were correlated with differential single organ site metastasis OS and EBV DNA load. Liver metastatic tissue had higher density of infiltrating macrophages and proliferative index than the lung metastatic group. Low pretreatment plasma EBV DNA load, expression of cytokines, such as IP-10 and MCP-1, tissue macrophage infiltration, and proliferative index may contribute to the differences in overall survival.
Highlights
Nasopharyngeal carcinoma (NPC) is a commonly diagnosed disease in southeastern Asia
Consistent with previous findings, we confirmed that independent significant factors predictive of reduced survival include poor performance status, high plasma Epstein-Barr virus (EBV) load and multiple organ involvement whereas single organ metastasis is a factor predictive of increased overall survival (OS) [6, 9, 27]
Lower pretreatment EBV DNA concentration is a significant predictor of better treatment response and longer OS [15, 16]
Summary
Improvements in diagnostic techniques, including use of positron emission tomography-computed tomography (PET-CT) scanning, have facilitated early detection of distant metastases (DM) in patients [1]. Outcomes of salvage treatment are currently poor and disease content at the time of recurrence plays a pivotal role in patient survival. Aggressive multimodal therapy may facilitate long-term patient survival [5,6,7]. Distinct outcomes have been reported in patients with DM in different organs. Patients with lung metastases have a good prognosis and longer survival [6, 8], whereas liver metastases are associated with dismal prognosis and shorter survival [9]. Better outcomes have been documented for patients with solitary nodule metastases than those with multiple nodules/sites of metastases [7]. The underlying reasons for differences in outcomes are yet to be established
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