Pre-Treatment and Preoperative Neutrophil-to-Lymphocyte Ratio Predicts Prognostic Value of Glioblastoma: A Meta-Analysis

Guo, Xin; Jiao, Hengxing; Zhang, Tiantian; Zhang, Yuelin

doi:10.3390/brainsci12050675

Cited by 8 publications

(5 citation statements)

References 57 publications

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“…Finally, there is increasing evidence, based on studies using large sample sizes, that suggests that both a high pre-treatment and preoperative NLR are correlated with poor overall survival in GBM patients. This aligns with the conclusions from our results [11,12].…”

Section: Discussionsupporting

confidence: 93%

“…Recent studies corroborate the prognostic significance of elevated levels of the NLR and PLR before surgery [10][11][12]. Conversely, the role of the RDW as a prognostic indicator has been a subject of divergence.…”

Section: Discussionmentioning

confidence: 89%

“…The PLR may be suggestive of a prothrombotic state often associated with tumor growth and metastasis. Platelets can shield tumor cells from immune detection and destruction, promoting dissemination [11,12,15,16].…”

Section: Discussionmentioning

confidence: 99%

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Sequential Evaluation of Hematology Markers as a Prognostic Factor in Glioblastoma Patients

Gonçalves,

Carvalho,

Tuna

et al. 2024

Biomedicines

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In our study, we investigated the prognostic significance of hematological markers—NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width—Coefficient of Variation)—in 117 glioblastoma patients. The data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment regimens. Unlike previous research, which often examined these markers solely before surgery, our unique approach analyzed them at multiple stages: preoperative, postoperative, and before adjuvant therapies. We correlated these markers with the overall survival (OS) and progression-free survival (PFS) using statistical tools, including ANOVA, Cox regression, and Kaplan–Meier survival analyses, employing SPSS version 29.0. Our findings revealed notable variations in the NLR, PLR, and RDW-CV across different treatment stages. The NLR and PLR decreased after surgery, with some stabilization post-STUPP phase (NLR: p = 0.007, η2p = 0.06; PLR: p = 0.001, η2p = 0.23), while the RDW-CV increased post-surgery and during subsequent treatments (RDW-CV: p < 0.001, η2p = 0.67). Importantly, we observed significant differences between the preoperative phase and other treatment phases. Additionally, a higher NLR and RDW-CV at the second-line treatment and disease progression were associated with an increased risk of death (NLR at 2nd line: HR = 1.03, p = 0.029; RDW-CV at progression: HR = 1.14, p = 0.004). We proposed specific marker cut-offs that demonstrated significant associations with survival outcomes when applied to Kaplan–Meier survival curves (NLR at 2nd line < 5: p < 0.017; RDW-CV at progression < 15: p = 0.007). An elevated NLR and RDW-CV at later treatment stages correlated with poorer OS and PFS. No significant preoperative differences were detected. These biomarkers may serve as non-invasive tools for glioblastoma management.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 89%

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Sequential Evaluation of Hematology Markers as a Prognostic Factor in Glioblastoma Patients

Gonçalves,

Carvalho,

Tuna

et al. 2024

Biomedicines

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“…High baseline (preoperative/pretreatment) NLR was established as an independent predictor of shorter overall survival in patients with glioblastoma/gliomas (Table 1) (51, 52, 54, 56-59, 85, 90-92, 112, 114, 119-128), and this was confirmed by meta-analyses (131)(132)(133). However, the independent prognostic significance of NLR remains debatable (55).…”

Section: A High Neutrophil-to-lymphocyte Ratio Is a Prognostic Factor...mentioning

confidence: 92%

Systemic and local immunosuppression in glioblastoma and its prognostic significance

Stepanenko,

Sosnovtseva,

Valikhov

et al. 2024

Front. Immunol.

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The effectiveness of tumor therapy, especially immunotherapy and oncolytic virotherapy, critically depends on the activity of the host immune cells. However, various local and systemic mechanisms of immunosuppression operate in cancer patients. Tumor-associated immunosuppression involves deregulation of many components of immunity, including a decrease in the number of T lymphocytes (lymphopenia), an increase in the levels or ratios of circulating and tumor-infiltrating immunosuppressive subsets [e.g., macrophages, microglia, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs)], as well as defective functions of subsets of antigen-presenting, helper and effector immune cell due to altered expression of various soluble and membrane proteins (receptors, costimulatory molecules, and cytokines). In this review, we specifically focus on data from patients with glioblastoma/glioma before standard chemoradiotherapy. We discuss glioblastoma-related immunosuppression at baseline and the prognostic significance of different subsets of circulating and tumor-infiltrating immune cells (lymphocytes, CD4+ and CD8+ T cells, Tregs, natural killer (NK) cells, neutrophils, macrophages, MDSCs, and dendritic cells), including neutrophil-to-lymphocyte ratio (NLR), focus on the immune landscape and prognostic significance of isocitrate dehydrogenase (IDH)-mutant gliomas, proneural, classical and mesenchymal molecular subtypes, and highlight the features of immune surveillance in the brain. All attempts to identify a reliable prognostic immune marker in glioblastoma tissue have led to contradictory results, which can be explained, among other things, by the unprecedented level of spatial heterogeneity of the immune infiltrate and the significant phenotypic diversity and (dys)functional states of immune subpopulations. High NLR is one of the most repeatedly confirmed independent prognostic factors for shorter overall survival in patients with glioblastoma and carcinoma, and its combination with other markers of the immune response or systemic inflammation significantly improves the accuracy of prediction; however, more prospective studies are needed to confirm the prognostic/predictive power of NLR. We call for the inclusion of dynamic assessment of NLR and other blood inflammatory markers (e.g., absolute/total lymphocyte count, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, and systemic immune response index) in all neuro-oncology studies for rigorous evaluation and comparison of their individual and combinatorial prognostic/predictive significance and relative superiority.

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“…A comparison made between these hematological markers and traditional molecular prognostic markers demonstrated that isocitrate dehydrogenase-1 mutation in gliomas was associated with chronic low-grade inflammation, which could be associated with a better prognosis in this subgroup of patients [ 28 ]. Recently, four meta-analyses demonstrated that NLR could be considered a prognostic factor in GMB, and some modification of chemotherapy should be recommended in high-risk patients [ 29 , 30 , 31 , 32 ]. In our retrospective study, we turned our attention to systemic inflammatory-immune markers, NLR, SII, and SIRI, which are based on neutrophil counts and which all exceeded the reference values proposed by Luo et al [ 33 ] and Qui et al [ 34 ] (0.87–4.15 103/µL for NLR, 142–808 103/µL for SII and 0.41–1.42 103/µL for SIRI).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Values of Systemic Inflammatory Immunological Markers in Glioblastoma: A Systematic Review and Meta-Analysis

Jarmużek

Kozłowska

Defort

et al. 2023

Cancers

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Background. Neutrophils are an important part of the tumor microenvironment, which stimulates inflammatory processes through phagocytosis, degranulation, release of small DNA fragments (cell-free DNA), and presentation of antigens. Since neutrophils accumulate in peripheral blood in patients with advanced-stage cancer, a high neutrophil-to-lymphocyte ratio can be a biomarker of a poor prognosis in patients with glioblastoma. The present study aimed to explore the prognostic value of the preoperative levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and cell-free DNA (cfDNA) to better predict prognostic implications in the survival rate of glioblastoma patients. Methods. The meta-analysis was carried out according to the recommendations and standards established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Databases of PubMed, EBSCO, and Medline were systematically searched to select all the relevant studies published up to December 2022. Results. Poorer prognoses were recorded in patients with a high NLR or PLR when compared with the patients with a low NLR or PLR (HR 1.51, 95% CI 1.24–1.83, p < 0.0001 and HR 1.34, 95% CI 1.10–1.63, p < 0.01, respectively). Similarly, a worse prognosis was reported for patients with a higher cfDNA (HR 2.35, 95% CI 1.27–4.36, p < 0.01). The SII and SIRI values were not related to glioblastoma survival (p = 0.0533 and p = 0.482, respectively). Conclusions. Thus, NLR, PLR, and cfDNA, unlike SII and SIRI, appeared to be useful and convenient peripheral inflammatory markers to assess the prognosis in glioblastoma.

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Pre-Treatment and Preoperative Neutrophil-to-Lymphocyte Ratio Predicts Prognostic Value of Glioblastoma: A Meta-Analysis

Cited by 8 publications

References 57 publications

Sequential Evaluation of Hematology Markers as a Prognostic Factor in Glioblastoma Patients

Sequential Evaluation of Hematology Markers as a Prognostic Factor in Glioblastoma Patients

Systemic and local immunosuppression in glioblastoma and its prognostic significance

Prognostic Values of Systemic Inflammatory Immunological Markers in Glioblastoma: A Systematic Review and Meta-Analysis

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