Associations of three immune inflammatory markers with the risk of brain metastasis from lung cancer: a systematic review and meta-analysis.

[OBJECTIVE] This study sought to comprehensively evaluate the associations between three immune-inflammatory markers, namely neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), and the risk of brain metastasis from lung cancer (BMLC). Through a meta-analysis, this study was expected to offer evidence-based support for early clinical identification of high-risk patients.

[METHODS] Databases including PubMed, Cochrane, EMBASE, Web of Science, and Scopus were comprehensively searched. Relevant articles published up to November 2025 were retrieved. Cohort studies investigating the associations between the above markers and BMLC were included. Two researchers independently screened the articles, extracted data, and assessed study quality. Stata 15.0 was utilized to perform the meta-analysis. A random-effects or fixed-effects model was applied to pool the effect sizes. Subgroup analyses, meta-regression, sensitivity analyses, and publication bias assessment were conducted.

[RESULTS] Fourteen retrospective cohort studies were included, involving 3,643 participants with lung cancer. Pooled multivariate analyses revealed that elevated NLR served as an independent risk factor for BMLC (odds ratio [OR]=1.61, 95% confidence interval [CI]: 1.27-2.05, P<0.05). The association of NLR with BMLC was stronger in the small cell lung cancer (SCLC) subgroup (OR = 2.36, 95% CI: 1.60-3.47, P<0.05) and the metachronous brain metastasis (MBM) subgroup (OR = 1.84, 95% CI: 1.19-2.85, P<0.05). Pooled univariate analyses revealed that low LMR was associated with an elevated risk of brain metastasis (BM) (OR = 1.24, 95% CI: 1.03-1.49, P<0.05). Multivariate analyses incorporating original studies further suggested that the association between LMR and the risk of BM was more significant only in the non-small cell lung cancer (NSCLC) subgroup and synchronous brain metastasis (SBM) subgroup. PLR showed no significant association with the risk of BM in the overall analysis.

[CONCLUSION] Existing evidence indicates that high NLR before treatment is an independent risk factor for BMLC, with a stronger association in patients with SCLC. The association between low LMR and the risk of BM is context-specific, primarily observed in patients with NSCLC and SBM. These findings provide evidence-based support for stratifying the risk of BM with routine inflammatory markers, warranting further validation in prospective studies.

[SYSTEMATIC REVIEW REGISTRATION] https://www.crd.york.ac.uk/PROSPERO/myprospero, identifier CRD420251170550.