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

SIMPLE SUMMARY: The authors report the most up-to-date review and a thorough meta-analysis of inflammatory, immunological markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII) and systemic inflammation response index (SIRI) as prognostic factors in patients with glioblastoma. A number of studies showed the important prognostic value of inflammatory immune markers. Similarly, some studies reported on the potential benefits of the measurements of small cell-free DNA fragments (cfDNA) released into the bloodstream as the biomarker of early diagnosis or/and prognosis. Twenty-one studies met our meta-analysis criteria assessing the prognostic significance of NLR, PLR, SII, SIRI, and cfDNA. According to our findings, NLR, PLR, and cfDNA fare significantly better than SII and SIRI in the evaluation of prognosis in glioblastoma patients. NLR and PLR calculated from routine blood tests, potentially in combination with measurements of cfDNA, can help assess disease progression and optimize treatment and follow-up. 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.