Pretreatment hematologic markers as prognostic predictors of gastroenteropancreatic neuroendocrine tumors: a systematic review and meta-analysis

Background: Systemic inflammation can be reflected by peripheral hematologic parameters and combined index like the lymphocyte count, neutrophil count, platelet count, neutrophil-to-lymphocyte (NLR), and platelet-to-lymphocyte ratio (PLR). This systematic review and meta-analysis aimed to summarize the association between the hematologic markers and prognosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods: A computerized systematic search of PubMed, Embase, and Web of Science was conducted up to August 2016. Studies evaluating prognosis value of hematologic parameters in patients with GEP-NETs were retrieved. For meta-analysis, hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and synthesized using Review Manager software. Results: We identified eight retrospective cohort studies comprising a total of 724 cases. The majority of included studies focused on pancreatic neuroendocrine tumors (PNETs). The prognostic values of NLR, PLR, and platelet count were reported in six studies, two studies, and one study, respectively. All the parameters were associated with prognostic outcomes in patients with GEP-NETs. A high NLR was significantly associated with poor prognosis in GEP-NETs (pooled HR 3.05, 95% CI 1.96-4.76, I-2 = 0%, P < 0.00001 for overall survival (OS); pooled HR 3.30, 95% CI 2.04-5.32, I-2 = 0%, P < 0.00001 for recurrence-free survival [RFS]). In PNETs, pooled-analyses also showed significant superiority of a low NLR on OS (pooled HR 4.21, 95% CI 1.95-9.13, I-2 = 0%, P = 0.0003) and RFS (pooled HR 5.37, 95% CI 2.14-13.47, I-2 = 0%, P = 0.003). Conclusions: These findings suggest that the elevated NLR could be an adverse prognosis factor for GEP-NETs. The conclusion should be mainly limited to PNETs as the majority of included cases were PNET patients. The prognostic value of other hematologic parameters deserves further investigation. We recommend that further studies should use a continuous NLR variable and adopt a prospective and matched study design.