Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies

Abstract

Background 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. Methods 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. Results 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. Conclusion 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. Trial registration PROSPERO CRD42017069131.

Assessing inflammatory status in COVID-19: a role in the pandemic?

“…Among the biomarkers investigated, leukocytosis, lymphopenia, and several blood cell count ratios (including NLR) were associated with 28 day mortality. These results are consistent with findings already reported in the literature: NLR, which may reflect the balance between systemic inflammation and immunity, has been already described as a prognostic biomarker in other scenarios, including cardiovascular disease and cancer [12,13]. Consistently, a meta-analysis confirmed its association with mortality in patients with COVID-19 [14]; this also applies to lymphocyte count [15].…”

Artificial Intelligence in Differential Diagnostics of Meningitis: A Nationwide Study

“…Although the followed forward stepwise scheme gave a limited combination of predictors, our results demonstrated the important role of NLR when it is used as a predictor in ML algorithms for the differential diagnosis between viral and bacterial meningitis, building upon previous studies on NLR’s validity in different diseases, even chronic ones such as cancer [ 20 ]. Furthermore, our results highlight the emerging applications of ML approaches in medicine, in a whole spectrum from diabetes and cancer to infectious diseases and sepsis-associated events [ 21 , 22 , 23 ].…”

Links between Inflammation and Postoperative Cancer Recurrence

“…Some interleukins (IL-1β/IL-4/IL-6/IL-13) may correlate with the recurrence of gastric cancer [ 82 ]. Several immune- and inflammation-based prognostic scores, such as MLR and NLR, have been developed as predictors of survival and recurrence across various cancer types, including gastric cancer [ 83 , 84 , 85 ]. However, integrated indices based on peripheral lymphocyte, neutrophil, and monocyte counts that may better reflect the balance between the host’s immune and inflammatory statuses have not yet been reported for gastric cancer.…”