Inexpensive Systemic Inflammatory Biomarkers in Ovarian Cancer: An Umbrella Systematic Review of 17 Prognostic Meta-Analyses

Abstract

The association of several inflammation-based biomarkers [lymphocyte-to-monocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios (LMR, NLR, and PLR, respectively)] with the survival of epithelial ovarian cancer (EOC) patients has been extensively investigated in several systematic reviews and meta-analyses (MAs) of observational studies. The aim of this umbrella systematic review is to appraise all available results in published MAs that explored the association between these biomarkers and EOC outcomes. An umbrella systematic review of the current evidence for systemic inflammatory biomarkers in the peripheral blood of EOC patients was performed by searching several databases including PubMed/Medline and Web of Science. The quality of the MAs was appraised using the AMSTAR-2 tool as well as other qualitative criteria. The evidence was graded from convincing (Class I) to weak (Class IV). Our umbrella review appraised 17 MAs of retrospective studies (range: 7–16) with a number of enrolled patients ranging from 1,636 to 4,910 patients in each MA. All these MAs demonstrated that pretreatment high NLR and PLR, as well as low LMR, were independent predictors of poor overall survival and progression-free survival in EOC. Nearly all published MAs were conducted by Chinese researchers (16/17) and were redundant in their character. Another issue in these MAs is the absence of prior PROSPERO database registration as well as the earlier exclusion of the gray literature. On the other hand, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses Of Observational Studies in Epidemiology (MOOSE)-based reporting guidelines were used in nine out of the 17 MAs. A good number of MAs have transparently provided funding acknowledgment. The AMSTAR-2-based assessment showed low quality in 11 out of the 17 reviewed MAs. This negative rating was largely due to the absence of critical domains. Finally, all evaluated MAs were rated as Class III or IV (suggestive and weak, respectively). Despite the power of MAs in increasing sampling and precision, the quality of the current non-randomized evidence on this topic is still weak.Systematic Review RegistrationPROSPERO, identifier CRD42020201493.

Preoperative systemic immune‐inflammation index for predicting the prognosis of thymoma with radical resection

“…According to a meta‐analysis in 2014, a high NLR was a poor predictive factor for OS among various disease subgroups and across disease stages of 100 studies comprising 40 559 patients and a high NLR was significantly associated with OS, similar to the present study. Although the role of PLR requires a meta‐analysis of randomized trials, previous studies showed that a high PLR was an independent predictor of poor OS for epithelial ovarian cancers 49 . To date, several studies focused on the role of NLR, PLR, and SII in thymic epithelial tumors 23–25,50–53 .…”

“…Although the role of PLR requires a meta‐analysis of randomized trials, previous studies showed that a high PLR was an independent predictor of poor OS for epithelial ovarian cancers. 49 To date, several studies focused on the role of NLR, PLR, and SII in thymic epithelial tumors. 23 , 24 , 25 , 50 , 51 , 52 , 53 In 2021, Huang et al established a nomogram to predict outcomes of thymomas by combining clinical features, NLR, PLR and other blood assays but PLR was not an independent prognostic factor, rather the primary outcome indicator was relapse‐free survival rather than OS.…”

Systemic inflammation factors as survival prognosis markers in ovarian neoplasm and the relationship with cancer-associated inflammatory mediators—a review

“…86,87 The involvement of lymphocytes in the defense against cancer cells, scientifically justifies their use in medical practice, the numerical value being involved in the calculation of the three ratios: NLR, MRL, and PLR. 13,71,73,88 Platelets, as a factor involved in the defense system through the development of antineoplastic inflammation. Physiopathologically, in neoplasms, the research in daily medical practice of the number of circulating platelets, their volume and the calculation of the PLR index, is supported by the involvement of these elements figured in:…”

“…Scores based on absolute values of different types of leukocytes are NLR-neutrophil-to-lymphocyte ratio, PLR-platelet-to-lymphocyte ratio, and LMR-lymphocyte-to-monocyte ratio. [11][12][13][14]…”

Integration of local and systemic immunity in ovarian cancer: Implications for immunotherapy

“…Moreover, the association of three inflammation-based parameters with the survival of OC patients has been proposed, i.e., lymphocyte/monocyte ratio (LMR) (a), neutrophil/lymphocyte ratio (NLR) (b), and platelet/lymphocyte ratio (PLR) (c). High NLR and PLR and low LMR were independent prediction factors of poor OS and PFS in OC ( 147 ).…”