Optimization of radiotherapy for neck carcinoma metastasis from unknown primary sites: a meta-analysis

This meta-analysis was designed to evaluate radiotherapy (RT) options preferable for neck cancer metastases from unknown primary sites (NCUP). Relevant articles published up through September 2015 were selected from EMBASE, Cochrane, PubMed and Web of Science. Thirty-three articles were identified, and relative risks (RRs) and 95% CIs for all pre-specified endpoints were calculated. Surgery plus RT showed an advantage for 5-year overall survival (OS) (RR 0.66, 95% CI 0.52–0.83, p = 0.0004) and neck recurrence (NR) (RR = 0.74, 95% CI 0.59–0.92, p = 0.008) compared to RT alone. The RRs for NR, primary tumor emergence (PTE), and 5-year disease free survival (DFS) for bilateral neck compared to ipsilateral neck irradiation were 0.61 (95% CI 0.41–0.91, p = 0.01), 0.44(95% CI 0.26–0.77, p = 0.004), and 0.81 (95% CI 0.64–1.03, p = 0.09), respectively. Irradiation of the neck plus potential primary tumor sites (PPTS) showed a benefit for 5-year DFS (RR 0.75, 95% CI 0.61–0.92, p = 0.005), NR (RR = 0.72, 95% CI 0.56–0.92, p = 0.009), and PTE (RR = 0.23, 95% CI 0.12–0.45, p < 0.0001) compared to neck-only irradiation. Adverse events occurred more frequently with bilateral neck plus PPTS irradiation. For NCUP, surgery plus RT of the bilateral neck and PPTS was associated with greater improvement of clinical outcomes.