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

Abstract

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.

The need for paradigm shift: prognostic significance and implications of standard therapy-related systemic immunosuppression in glioblastoma for immunotherapy and oncolytic virotherapy

“…Third, absolute/total lymphocyte counts should be monitored after radiotherapy, and appropriate effective interventions overcoming radiation-induced lymphopenia should be established and applied. Fourth, high NLR ( 31 – 33 ) and low post-treatment TLC are significant prognostic factors for shorter survival in patients with glioblastoma/gliomas. These and other cost-effective, widely and easily available clinically relevant prognostic immune variables associated with systemic inflammation and adaptive immunity (e.g., platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic immune response index (SIRI), or combinations thereof) ( 33 , 242 – 248 ) should be reported and correlated with response and survival in immunotherapy/oncolytic virotherapy studies.…”

“…Fourth, high NLR ( 31 – 33 ) and low post-treatment TLC are significant prognostic factors for shorter survival in patients with glioblastoma/gliomas. These and other cost-effective, widely and easily available clinically relevant prognostic immune variables associated with systemic inflammation and adaptive immunity (e.g., platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic immune response index (SIRI), or combinations thereof) ( 33 , 242 – 248 ) should be reported and correlated with response and survival in immunotherapy/oncolytic virotherapy studies. In addition, since the use of different time points to define treatment-related lymphopenia has been reported to modify the prognostic power of lymphocyte counts, uniform time-points in standard therapy-related lymphopenia assessment should be established.…”

The role of preoperative hematological inflammatory markers as a predictor of meningioma grade: A systematic review and meta-analysis

“…reported PLR as a marker significantly associated with glioma prognosis. [ 16 ] Whereas in the analysis reported by Wang et al ., PLR values did not have a significant association with glioma. Further studies still need to confirm the relationship between PLR values in intracranial tumors, including meningioma.…”

Diagnostic and Prognostic Value of Circulating DNA Fragments in Glioblastoma Multiforme Patients

“…Currently, circulating cfDNA and ctDNA fractions are analysed in the context of inflammation, as they appear to be promising potential biomarkers for the early diagnosis or prognosis in glioblastoma [22][23][24]. To date, only two meta-analyses have been reported by MacMahon et al [13] and Jarmuzek et al [25]. Both studies showed that cfDNA appeared to be a significantly sensitive and specific biomarker in adults with low-and high-grade gliomas; however, further studies should be conducted with glioblastoma as a target.…”