PRE-SURGERY BLOOD CELL RATIOS AND SURVIVAL IN PATIENTS WITH MALIGNANT GLIOMAS
DOI:
https://doi.org/10.15407/exp-oncology.2025.03.321Keywords:
diffuse glioma, high-grade astrocytoma, glioblastoma, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, overall survivalAbstract
Background. Malignant diffuse gliomas (MG) of the brain (WHO grade 3—4) are highly aggressive primary tumors of central nervous system (CNS), spreading rapidly by infiltrating healthy brain tissue. In the majority of cases, tumor relapse occurs. The prognostic significance of pre-surgery factors, such as inflammatory markers, particularly, the peripheral blood counts in patients with MG is discussed and remains controversial. The aim of this study was to assess the relationship between the blood cell ratios and overall survival (OS) and relapse-free survival (RFS) in MG patients. Materials and Methods. The data on 59 MG patients were analyzed: 41 cases of primary (newly diagnosed) MG (astrocytoma (A-III, WHO grade 3, n = 8) and glioblastoma (GB, WHO grade 4, n = 33)) and 18 cases of recurrent MG (recurrent A-III (WHO grade 3, n = 7) and recurrent GB (WHO grade 4, n = 11)). Blood cell counts (peripheral blood leukocytes (PBL), platelets (Pt), neutrophils (Neu), lymphocytes (Ly), monocytes (Mo)) and NLR (Neu/Ly ratio), PLR (Pt/Ly ratio), MLR (Mo/Ly ratio), and systemic immune-inflammation index (SII)) in the preoperative period (prior to re-resection in cases of recurrent MG) were evaluated. The Kaplan — Meier and Cox regression analyses of OS/RFS were performed. The potential association between the blood counts and ratios PLR (≤146 vs. >146), NLR (≤4 vs. >4), MLR (≤0.27 vs. >0.27), SII (≤906 vs. >906), as well as sex (female vs. male) and age (≤60 vs. >61) with OS and RFS were analyzed. Results. PBL and Neu counts, as well as NLR and SII indices, in patients with primary and recurrent GB in the pre-operative period significantly exceeded the reference values (p < 0.02). PBL, Neu, and SII significantly correlated with tumor grade. In patients with primary A-III and GB, longer OS tended to be associated with high PLR, NLR, MLR, and SII values, while in patients with recurrent GB, longer OS tended to be associated with low values of these ratios. Patients with recurrent A-III and GB showed a significant association between low pre-surgery NLR, SII and better RFS while patients with recurrent GB — significant association between low pre-surgery MLR and better RFS. Significant association between OS and sex of patients with both primary and recurrent GB was shown. Conclusions. The results obtained suggest the possible prognostic significance of PLR, NLR, MLR, and SII values in the treatment outcomes of MG patients.
References
Ostrom QT, Price M, Neff C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2016—2020. Neuro Oncol. 2023;25(Suppl 4):iv1-iv99. https://doi.org/10.1093/ neuonc/noad149
Price M, Ballard Ch, Benedetti J, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2017—2021. Neuro Oncol. 2024;26(Suppl 6):vi1-vi85. https://doi.org/10.1093/ neuonc/noae145
fedorenko Z, Goulak L, Gorokh y, et al. Cancer in Ukraine, 2021-2022: Incidence, mortality, prevalence and other relevant statistics. Bull Nat Cancer Reg Ukraine. 2023;24. Available at: http://ncru.inf.ua/publications/BULL_24/ Pdf_E/bull_eng_24.pdf
fedorenko Z, Goulak L, Gorokh y, et al. Cancer in Ukraine, 2022-2023: Incidence, mortality, prevalence and other relevant statistics. Bull Nat Cancer Reg Ukraine. 2024;25. Available at: http://www.ncru.inf.ua/publications/ BULL_25/Pdf_E/Bull_Eng_25.pdf
Ostrom QT, Cioffi G, Waite K, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2014—2018. Neuro Oncol. 2021;23 (12 Suppl 2):iii1-iii105. https://doi.org/10.1093/neuonc/noab200
Low JT, Ostrom QT, Cioffi G, et al. Primary brain and other central nervous system tumors in the United States (2014—2018): A summary of the CBTRUS statistical report for clinicians. Neurooncol Pract. 2022;9(3):165-182. https://doi.org/10.1093/nop/npac015
yang C, Lan T, Wang y, et al. Cumulative scoring systems and nomograms for predicating survival in patients with glioblastomas: A study based on peripheral inflammatory markers. Front Oncol. 2022;12:716295. https://doi.org/10.3389/fonc.2022.716295
Bao y, yang M, Jin C, et al. Preoperative hematologic inflammatory markers as prognostic factors in patients with glioma. World Neurosurg. 2018;119:e710-e716. https://doi.org/10.1016/j.wneu.2018.07.252
Saito T, Sugiyama K, hama S, et al. Prognostic importance of temozolomide-induced neutropenia in glioblastoma, Idh-wildtype patients. Neurosurg Rev. 2018;41(2):621-628. https://doi.org/10.1007/s10143-017-0903-3
Liu y, Li Q, Li Z, et al. Pre-treatment neutrophil-to-lymphocyte ratio is associated with neutrophil and T-cell infiltration and predicts clinical outcome in patients with glioblastoma. BMC Cancer. 2015;15:617. https://doi.org/10.1186/ s12885-015-1629-7
Ali h, harting R, de Vries R, et al. Blood-based biomarkers for glioma in the context of gliomagenesis: A systematic review. Front Oncol. 2021;11:665235. https://doi.org/10.3389/fonc.2021.665235
Zemskova O, yu Ny, Löser A, et al. Prognostic role of platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios in patients irradiated for glioblastoma multiforme. Cancer Diagn Progn. 2024;4(4):408-415. https://doi. org/10.21873/cdp.10340
Bambury RM, Teo My, Power dG, et al. The association of pre-treatment neutrophil to lymphocyte ratio with over-all survival in patients with glioblastoma multiforme. J Neurooncol. 2013;114(1):149-154. https://doi.org/10.1007/ s11060-013-1164-9
Han S, Liu y, Li Q, et al. Pre-treatment neutrophil-to-lymphocyte ratio is associated with neutrophil and T-cell infiltration and predicts clinical outcome in patients with glioblastoma. BMC Cancer. 2015;15:617. https://doi.org/10.1186/s12885-015-1629-7
Wang Pf, Song hW, Cai hQ, et al. Preoperative inflammation markers and Idh mutation status predict glioblas-toma patient survival. Oncotarget. 2017;8(30):50117-50123. https://doi.org/10.18632/oncotarget.15235
Yersal Ö, Odabaşi E, Özdemir Ö, et al. Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with glioblastoma. Mol Clin Oncol. 2018;9(4):453-458. https://doi.org/ 10.3892/mco.2018.1695
Lv y, Zhang S, Liu Z, et al. Prognostic value of preoperative neutrophil to lymphocyte ratio is superior to systemic immune inflammation index for survival in patients with glioblastoma. Clin Neurol Neurosurg. 2019;181:24-27. https://doi.org/10.1016/j.clineuro.2019.03.017
Marini A, dobran M, Aiudi d, et al. Pre-operative hematological markers as predictive factors for overall survival and progression free survival in glioblastomas. Clin Neurol Neurosurg. 2020;197:106162. https://doi.org/10.1016/j. clineuro.2020.106162
Madhugiri VS, Subeikshanan V, dutt A, et al. Biomarkers of systemic inflammation in patients with glioblastoma: an analysis of correlation with tumour-related factors and survival. Neurol India. 2021;69:894-901.
yang C, Wen hB, Zhao yh, et al. Systemic inflammatory indicators as prognosticators in glioblastoma patients: A comprehensive meta-analysis. Front Neurol. 2020;11:580101. https://doi.org/10.3389/fneur.2020.580101
Guo X, Jiao h, Zhang T, et al. Pre-treatment and preoperative neutrophil-to-lymphocyte ratio predicts prognostic value of glioblastoma: A meta-analysis. Brain Sci. 2022;12(5):675. https://doi.org/10.3390/brainsci12050675
Bispo RG, Bastos Siqueira If, de Oliveira BfS, et al. Prognostic value of the platelet-lymphocyte ratio for glioblas- toma: A systematic review. World Neurosurg. 2023;175:137-141. https://doi.org/10.1016/j.wneu.2023.04.086
Duan X, Yang B, Zhao C, et al. Prognostic value of preoperative hematological markers in patients with glioblas- toma multiforme and construction of random survival forest model. BMC Cancer. 2023;23(1):432. https://doi. org/10.1186/s12885-023-10889-0
Gurrieri L, Mercatali L, Ibrahim T, et al. Immuno markers in newly diagnosed glioblastoma patients underwent Stupp protocol after neurosurgery: a retrospective series. J Neurooncol. 2023;164(1):55-64. https://doi.org/10.1007/ s11060-023-04357-9
Serban GM, Tamas CI, Tamas f, et al. Preoperative immune-inflammatory status of the patients with newly-diagnosed glioblastoma – could it genuinely predict their survival? Cureus. 2023;15(8):e43802. https://doi.org/10.7759/cureus.43802
Jarmuzek P, Kozlowska K, defort P, et al. Prognostic values of systemic inflammatory immunological markers in glioblastoma: A systematic review and meta-analysis. Cancers (Basel). 2023;15(13):3339. https://doi.org/10.3390/can- cers15133339
McNamara MG, Lwin Z, Jiang h, et al. factors impacting survival following second surgery in patients with glio- blastoma in the temozolomide treatment era, incorporating neutrophil/lymphocyte ratio and time to first progression. J Neurooncol. 2014;117(1):147-152. https://doi.org/10.1007/s11060-014-1366-9
Haksoyler V, A Besen A, Koseci T, et al. Neutrophil-to-lymphocyte ratio is prognostic in recurrent glioblastoma multiforme treated with bevacizumab plus irinotecan. Biomark Med. 2021;15(11):851-859. https://doi.org/10.2217/ bmm-2021-0271
Deng D, Hammoudeh L, Youssef G, et al. Evaluating hematologic parameters in newly diagnosed and recurrent glio-blastoma: Prognostic utility and clinical trial implications of myelosuppression. Neurooncol Adv. 2023;5(1):vdad083. https://doi.org/10.1093/noajnl/vdad083
Zemskova O, yu Ny, Leppert J, et al. Can platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) help predict outcomes of patients with recurrent glioblastoma? In Vivo. 2024;38(5):2341-2348.
Yan P, Li JW, Mo LG, et al. A nomogram combining inflammatory markers and clinical factors predicts survival in patients with diffuse glioma. Med (Baltimore). 2021;100:e27972. https://doi.org/10.1097/Md.0000000000027972
Best MG, Wesseling P, Wurdinger T. Tumor-educated platelets as a noninvasive biomarker source for cancer detection and progression monitoring. Cancer Res. 2018;78(13):3407-3412. https://doi.org/10.1158/0008-5472.CAN-18-0887
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