The clinical implication of dynamic neutrophil to lymphocyte ratio and D-dimer in COVID-19: A retrospective study in Suzhou China.

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

The emergence of immunotherapy has dramatically changed how non-small cell lung cancer is treated, and longer survival is now possible for some patients, even those with advanced disease. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Given this, biomarkers that predict response to therapy are essential, and testing for tumor programmed death ligand 1(PD-L1) expression is the current standard. The extent of PD-L1 expression determined by immunohistochemistry (IHC) has demonstrated a correlation with treatment response, although limitations with this marker exist. Recently, tumor mutational burden has emerged as an alternative biomarker, and studies have demonstrated its utility, irrespective of the PD-L1 level of a tumor. Gene expression signatures, tumor genotype (such as the presence of an oncogenic driver mutation), as well as the density of tumor-infiltrating lymphocytes in the tumor microenvironment also seem to affect response to immunotherapy and are being researched. Peripheral serum markers are being studied, and some have demonstrated predictive ability, although most are still investigational and need prospective validation. In the current article, the authors review the biomarker PD-L1 as well as other emerging and investigational tissue-based and serum-based markers that have potential to better predict responders to immunotherapy.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.32468

Biomarkers for immune checkpoint inhibition in non–small cell lung cancer (NSCLC)

Background Explore markers to predict the clinical outcomes of checkpoint inhibitors have high unmet needs The following study investigates whether hematologic parameter such as systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) is associated with nivolumab efficacy in advanced non-small-cell lung cancer (NSCLC) Methods Advanced/metastatic NSCLC patients treated with nivolumab monotherapy for second-line or further-line treatment at Jilin Cancer Hospital between March 2016 and July 2018 were enrolled in this retrospective study The optimal cutoff values of SII, NLR, and PLR for predicting efficacy and prognosis were determined according to receiver operating characteristic (ROC) curve and the areas under the ROC curve Progression-free survival (PFS) and overall survival (OS) were calculated and compared using Kaplan-Meier method and log-rank test Prognostic values of each variable were evaluated with univariate and multivariate Cox proportional hazard regression (PHR) analyses Results A total of 44 patients with advanced NSCLC were included; the median age was 60 (range: 43-74) The optimal cutoff value of SII/NLR/PLR predicted PFS and OS was 6035, 307, and 144 Low SII, NLR, and PLR were associated with longer PFS (HR for SII = 034, 95%CI 015-076, P = 0006; HR for NLR = 046, 95%CI 022-099, P = 0048; HR for PLR = 039, 95%CI 017-094, P = 0025) and OS (HR for SII = 016, 95%CI 005-051, P = 0005; HR for NLR = 020, 95%CI 006-062, P = 0002; HR for PLR = 020, 95%CI 006-073, P = 0008) NLR ≤ 307, PLR ≤ 144, SII ≤ 6035 were independently associated with longer PFS and OS Conclusion The SII, NLR, and PLR are promising prognostic predictor for patients with metastatic NSCLC patients

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcla.22964

Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio can predict clinical outcomes in patients with metastatic non-small-cell lung cancer treated with nivolumab.

In cancer patients, a high pre-treatment neutrophil-to-lymphocyte ratio (NLR) is associated with poorer survival outcomes. Significant variation in the magnitude of this association has been observed between studies, but sources of this variation are poorly understood. Here, we explore differences in the prognostic potential of NLR between patient subgroups stratified by demographic and clinical characteristics using a retrospective cohort of 5,363 patients treated at Moffitt Cancer Center (Tampa, FL). We identify patients for whom NLR has maximum prognostic potential via adjusted hazard ratios (HRs) calculated using multivariable Cox proportional hazards models and area under the curve analysis. NLR demonstrates stronger associations (HRs > 2) with survival among African-American patients, patients receiving radiation therapy, stage IV patients, and melanoma patients when compared with the overall study population (HR = 1.58). Sensitivity and specificity of NLR as a prognostic marker are also higher in these patient subgroups, and increase further with combinations of multiple “high-risk” demographic or clinical characteristics. In summary, NLR may have greater prognostic value in patients with certain demographic and clinical features. Future prospective studies could validate this hypothesis, after further characterization of populations in which NLR has maximum prognostic potential and the identification of meaningful thresholds for risk stratification.

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Exploring the prognostic value of the neutrophil-to-lymphocyte ratio in cancer

Prognostic role of pretreatment blood neutrophil-to-lymphocyte ratio in advanced cancer survivors: A systematic review and meta-analysis of 66 cohort studies

Bo Wang

Papers

Prognostic role of pretreatment blood neutrophil-to-lymphocyte ratio in advanced cancer survivors: A systematic review and meta-analysis of 66 cohort studies