The Prognostic Value of the Pretreatment Neutrophil/Lymphocyte Ratio in Patients with Glioblastoma Multiforme Brain Tumors: A Retrospective Cohort Study of Patients Treated with Combined Modality Surgery, Radiation Therapy, and Temozolomide Chemotherapy

Abstract

<b><i>Background:</i></b> Recent studies have shown that the peripheral blood pretreatment neutrophil/lymphocyte ratio (NLR) is a prognostic measure in various cancers. The few studies evaluating NLR in glioblastoma multiforme (GBM) patients yielded inconsistent results. <b><i>Objectives:</i></b> The primary objective of our study was to test the ability of pretreatment NLR to predict the overall survival (OS) and progression-free survival (PFS) of patients with GBM treated by combined modality therapy (surgery, radiation, and temozolomide chemotherapy). A secondary objective was to evaluate the toxicity of the combined modality protocol in a consecutive series of patients treated in our center, in the context of a real-world universal health-care setting. <b><i>Methods:</i></b> We analyzed 89 patients with GBM in a retrospective cohort analysis who were treated in Soroka University Medical Center’s Oncology Department between the years 2005–2016. We analyzed NLR as a dichotomous variable at 3 cut-off points, 2.5, 3 and 4, as a predictor of OS and PFS. Methylation status of the O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT) promoter was not determined. <b><i>Results:</i></b> No significant correlation was found between NLR and either OS or PFS. Factors that predicted a shorter OS were age and extent of surgery. Patients over 70 years of age had a statistically significant shorter OS, 12.5 months (95% CI: 10.4–14.5 months) versus 17.6 months (95% CI: 14.2–21.1 months) in those 70 years of age and younger (<i>p</i> = 0.004). The OS of patients undergoing partial resection (12.7 months 95% CI: 8.3–17.1 months) or biopsy only (9.3 months 95% CI: 7.8–24.6 months), was significantly shorter than that of patients undergoing total resection (18.9 months, 95% CI: 11.8–26.0 months; <i>p</i> = 0.035). There were no treatment-related deaths. The most common grade III–IV toxicities were thrombocytopenia, 12.4%, and fatigue, 13.5%. <b><i>Conclusions:</i></b> In our cohort of GBM patients treated with combined modality therapy, pretreatment NLR was not prognostic. Toxicity of treatment was acceptable. Investigation of the NLR with larger groups of patients selected by MGMT status is warranted.

Systemic Inflammatory Indicators as Prognosticators in Glioblastoma Patients: A Comprehensive Meta-Analysis

“…One study by Kaya et al used 5 as the cut-off value and found that the NLR was correlated with survival (33), whereas another study by Mason et al used 7.5 as the cut-off value and found that the NLR was not correlated with survival (11), although they used postoperative samples. Notably, a recent study by Brenner et al (35) come to the result that the pretreatment NLR did not have the prognostic value in glioblastoma patients treated with combined modality surgery, radiation, and temozolomide, indicating the prognostic significance of the NLR in some designate cohort remains unclear. The NLR was also found to positively correlate with the expression of Ki-67 (34) and the glioma grade (51)(52)(53).…”

“…Likewise, one study (14) treated the lymphocyte count as a dichotomous variable, which was different from the remaining studies, and was therefore excluded in the last quantitative synthesis. Finally, there were 2 (11,12), 3 (11, 14, 28), 2 (16,29), 8 (11,(30)(31)(32)(33)(34)(35)(36), and 3 (30,31,37) included studies examining the neutrophil, lymphocyte, and platelet counts and the NLR and PLR, respectively. All the incorporated studies focused on glioblastoma patients performing the multivariate analysis.…”

“…We included eight retrospective studies (11,(30)(31)(32)(33)(34)(35)(36) published between 2013 and 2019 examining 1,225 patients to evaluate the association between the NLR and prognosis in GBM patients. There are 4 studies from China, 1 from Canada, 1 from Ireland, 1 from Turkey, and 1 from Israel.…”

Research Supporting a Pilot Study of Metronomic Dapsone during Glioblastoma Chemoirradiation

“…Relevant to this statement, empirically, remarkably fully 13 independent studies just between 2018 and 2020 reported the same findings-that a higher neutrophil to lymphocyte ratio-a relative or absolute neutrophilia-correlated with shorter survival in GB [66][67][68][69][70][71][72][73][74][75][76][77][78]. Few parameters in any cancer have been so oft confirmed.…”

The Prognostic Value of Preoperative Systemic Inflammatory Response Index (SIRI) in Patients With High-Grade Glioma and the Establishment of a Nomogram

“…However, no consensus has been reached (21)(22)(23). The prognostic value of SIRI as a new indicator was first found in patients with pancreatic cancer (24).…”