Department of Epidemiology & Biostatistics, MRC Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, W21PG, UK.
Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
BMC Med. 2020 Nov 20;18(1):360. doi: 10.1186/s12916-020-01817-1.
Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis.
We searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria.
A total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence.
In total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility.
PROSPERO CRD42017069131 .
尽管中性粒细胞与癌症的进展有关，但根据所考虑的部位、结果和治疗方法，其与癌症结果的关联存在不确定性。我们旨在评估中性粒细胞与淋巴细胞比值（NLR）或肿瘤相关中性粒细胞（TAN）与癌症预后之间关联的证据强度和有效性。
我们从 MEDLINE、Embase 和 Cochrane 系统评价数据库中检索了从建库到 2020 年 5 月 29 日的关于中性粒细胞计数（即 NLR 或 TAN）与疾病进展或生存相关的特定癌症结局的观察性研究的系统评价和荟萃分析。通过应用预先设定的 GRADE 标准，将现有证据评为强、高度提示、提示、弱或不确定。
共有 86 项研究的 204 项荟萃分析符合纳入标准，这些研究调查了 NLR 或 TAN 与癌症结局之间的关联。除了一项荟萃分析外，其余所有荟萃分析均发现风险比（HR）增加了风险（HR>1）。我们没有发现足够的荟萃分析来评估 TAN 与癌症结局（N=9）。当评估与异质性和小样本效应相关的效应大小、显著性和偏倚时，在复合癌症终点（综合分析）、免疫治疗治疗的癌症和一些特定部位的癌症（泌尿、鼻咽、胃、乳腺、子宫内膜、软组织肉瘤和肝细胞癌）中，NLR 与结局之间的 18 项（9%）关联得到了强有力的证据支持。
总的来说，有 60 项（29%）荟萃分析提供了强有力或高度提示性的证据。尽管 NLR 和 TAN 在与不良癌症预后的关联中具有临床应用前景，但仍需要进一步的研究提供强有力的证据，评估因果关系并测试临床实用性。
PROSPERO CRD42017069131。
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