Abstract
BackgroundThe efficacy of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal cancer (LA-NPC) is controversial. In this paper, we conduct a meta-analysis based on relevant studies to provide strong evidence for clinical strategies.Materials and MethodsWe searched the MEDLINE, Embase, Cochrane, PubMed, and Web of Science databases for studies that stratified patients based on a high or low plasma Epstein–Barr virus deoxyribonucleic acid (EBV-DNA) load before treatment and compared the clinical efficacy of IC+CCRT vs. CCRT alone in LA-NPC. We tested for heterogeneity of studies and conducted sensitivity analysis. Subgroup analysis was performed for overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS).ResultsSeven studies with a total of 5289 cases were finally included in the meta-analysis. The heterogeneity test revealed the homogeneity of OS (I 2 = 0.0%, p=0.794), PFS (I 2 = 0.0%, p=0.778), DMFS (I 2 = 0.0%, p=0.997), and LRFS (I 2 = 0.0%, p=0.697) in patients with EBV-DNA loads of ≥4000 copies/ml in both the IC+CCRT and CCRT groups. The results reveal that IC+CCRT significantly extended the OS (HR 0.70 [95% CI 0.58-0.83], p=0.000), PFS (HR 0.83 [95% CI 0.70-0.99], p=0.033), and DMFS (HR 0.79 [95% CI 0.69-0.9], p=0.000) of patients compared with the CCRT group, but there were no beneficial effects on LRFS (HR 1.07 [95% CI 0.80-1.42], p=0.647). The heterogeneity test found that there was no significant heterogeneity of PFS (I 2 = 0.0%, p=0.564), DMFS (I 2 = 0.0%, p=0.648), LRFS (I 2 = 22.3%, p=0.257), and OS (I 2 = 44.6%, p=0.164) in patients with EBV-DNA loads of <4000 copies/ml. The results show that IC+CCRT prolonged DMFS (HR 0.57 [95% CI 0.39-0.85], p=0.006) of patients without significant improvements in OS (HR 0.88 [95% CI 0.55-1.26], p=0.240), PFS (HR 0.98 [95% CI 0.74-1.31], p=0.908), and LRFS (HR 0.98 [95% CI 0.54-1.77], p=0.943).ConclusionsPretreatment plasma EBV-DNA can be considered a promising effective marker for the use of IC in LA-NPC patients. The addition of IC could improve the OS and PFS of patients with EBV-DNA load ≥4000 copies/ml, but we saw no efficacy in patients with EBV-DNA load <4000 copies/ml. Moreover, regardless of the EBV-DNA load, IC could improve DMFS, but there was no effect on LRFS.
Highlights
Nasopharyngeal cancer (NPC) is an epithelial malignancy featuring a regional incidence as evidenced by the prevalence in Guangdong and Guangxi provinces in South China, Southeast Asia, and North Africa [1, 2]
The results reveal that intensive chemotherapy (IC)+concurrent chemoradiotherapy (CCRT) significantly extended the overall survival (OS) (HR 0.70 [95% confidence intervals (CIs) 0.58-0.83], p=0.000), progression-free survival (PFS) (HR 0.83 [95% CI 0.70-0.99], p=0.033), and distant metastasisfree survival (DMFS) (HR 0.79 [95% CI 0.69-0.9], p=0.000) of patients compared with the CCRT group, but there were no beneficial effects on locoregional relapse-free survival (LRFS) (HR 1.07 [95% CI 0.80-1.42], p=0.647)
The results show that IC+CCRT prolonged DMFS (HR 0.57 [95% CI 0.39-0.85], p=0.006) of patients without significant
Summary
Nasopharyngeal cancer (NPC) is an epithelial malignancy featuring a regional incidence as evidenced by the prevalence in Guangdong and Guangxi provinces in South China, Southeast Asia, and North Africa [1, 2]. Non-keratinizing NPC is the main pathological type in high-incidence areas, and almost all patients have been infected with Epstein–Barr virus (EBV). Because of its high radiosensitivity, intensity modulated radiation therapy (IMRT)-based concurrent chemoradiotherapy is confirmed as the main treatment for locoregionally advanced NPC (LA-NPC), providing 3- and 5year overall survival (OS) rates of 76% and 72.3%, respectively [8,9,10]. Concurrent chemoradiotherapy (CCRT)-based intensive chemotherapy (IC) is regarded as an effective method to lengthen the OS and to reduce progression risks for these patients [12, 13]. The efficacy of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal cancer (LANPC) is controversial. We conduct a meta-analysis based on relevant studies to provide strong evidence for clinical strategies
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