Download PDF
J Neurol Surg B Skull Base
DOI: 10.1055/s-0044-1779050
Original Article

Prediction of Survival in the Elderly Patients with Glioblastoma using Cumulative Inflammatory Markers Score

Kun Song   #
1   Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
,
Chunjui Chen   #
1   Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
,
Hao Xu
1   Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
,
Lingchao Chen
1   Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
,
Hongzhi Xu
1   Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
,
Xi Han
1   Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
,
Hong Chen
2   Department of Neuropathology, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
,
Zhiyong Qin
1   Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
› Author Affiliations Funding This work was supported by Development Center for Medical Science and Technology National Health and Family Planning Commission of the People Republic of China (W2012FZ003).
› Further Information
    Permissions and Reprints

Abstract

Objectives This retrospective study aimed to explore the prognostic effect of cumulative score based on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and fibrinogen in older adults diagnosed with glioblastoma (GBM).

Design Retrospective study.

Setting Huashan Hospital.

Participants Patients aged over 60 years and diagnosed with GBM between 2010 and 2017.

Main Outcome Measures Results of preoperative routine biochemistry and coagulation blood examinations were reviewed from medical records. Overall survival (OS) was considered a period from first resection surgery until death. Progression-free survival (PFS) was considered a period from initial operation until the date of tumor progression demonstrated in brain magnetic resonance imaging or death from any cause. If no event occurred, the last follow-up appointment was the end of the observation for OS or PFS. The Kaplan–Meier method was used to evaluate survival curves, and prognostic factors were analyzed by the Cox proportional hazards model.

Results A total of 289 patients were included. Patients with higher levels of fibrinogen, NLR, and PLR had significantly shorter median OS (p = 0.001, p = 0.016, and p = 0.002, respectively) and PFS (p = 0.004, p = 0.022, and p = 0.009, respectively) compared with those with lower levels. Multivariate analyses showed a significant association between higher F-NLR-PLR score and reduced OS (adjusted hazard ratios [aHRs]: 1.356, 95% confidence interval [CI] 1.009–1.822 for scores 1–2 compared with 0; 5.974, 95% CI 2.811–12.698 for score 3 compared with 0). Similarly, a significant association between higher F-NLR-PLR score and reduced PFS was observed (aHR: 1.428, 95% CI 1.066–1.912 for scores 1–2 compared with 0; aHR: 2.860, 95% CI 1.315–6.223 for score 3 compared with 0).

Conclusion Higher F-NLR-PLR score is associated with reduced OS and PFS in older adults with GBM, which helps identify patients at high risk and guide the individualized treatment in clinical practice.

Keywords

glioblastoma - fibrinogen - neutrophil–lymphocyte ratio - platelet–lymphocyte ratio

Availability of Data and Materials

All data analyzed during this study are included in this published article.


# These authors contributed equally to this study and share first authorship.




Publication History

Received: 04 August 2023

Accepted: 21 December 2023

Article published online:
12 February 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Ostrom QT, Gittleman H, Farah P. et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol 2013; 15 (Suppl 2) ii1-ii56
    Google Scholar
  • 2 Darefsky AS, King Jr JT, Dubrow R. Adult glioblastoma multiforme survival in the temozolomide era: a population-based analysis of Surveillance, Epidemiology, and End Results registries. Cancer 2012; 118 (08) 2163-2172
    Google Scholar
  • 3 Guedes de Castro D, Matiello J, Roa W. et al. Survival outcomes with short-course radiation therapy in elderly patients with glioblastoma: data from a randomized Phase 3 trial. Int J Radiat Oncol Biol Phys 2017; 98 (04) 931-938
    Google Scholar
  • 4 Keime-Guibert F, Chinot O, Taillandier L. et al; Association of French-Speaking Neuro-Oncologists. Radiotherapy for glioblastoma in the elderly. N Engl J Med 2007; 356 (15) 1527-1535
    Google Scholar
  • 5 Malmström A, Grønberg BH, Marosi C. et al; Nordic Clinical Brain Tumour Study Group (NCBTSG). Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 2012; 13 (09) 916-926
    Google Scholar
  • 6 Bauchet L, Zouaoui S, Darlix A. et al. Assessment and treatment relevance in elderly glioblastoma patients. Neuro-oncol 2014; 16 (11) 1459-1468
    Google Scholar
  • 7 Straube C, Kessel KA, Antoni S. et al. A balanced score to predict survival of elderly patients newly diagnosed with glioblastoma. Radiat Oncol 2020; 15 (01) 97
    Google Scholar
  • 8 Heiland DH, Haaker G, Watzlawick R. et al. Correction to: One decade of glioblastoma multiforme surgery in 342 elderly patients: what have we learned?. J Neurooncol 2018; 140 (02) 393
    Google Scholar
  • 9 Paszat L, Laperriere N, Groome P, Schulze K, Mackillop W, Holowaty E. A population-based study of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 2001; 51 (01) 100-107
    Google Scholar
  • 10 Chaichana KL, Chaichana KK, Olivi A. et al. Surgical outcomes for older patients with glioblastoma multiforme: preoperative factors associated with decreased survival. Clinical article. J Neurosurg 2011; 114 (03) 587-594
    Google Scholar
  • 11 Ewelt C, Goeppert M, Rapp M, Steiger HJ, Stummer W, Sabel M. Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival. J Neurooncol 2011; 103 (03) 611-618
    Google Scholar
  • 12 Noorbakhsh A, Tang JA, Marcus LP. et al. Gross-total resection outcomes in an elderly population with glioblastoma: a SEER-based analysis. J Neurosurg 2014; 120 (01) 31-39
    Google Scholar
  • 13 Stupp R, Mason WP, van den Bent MJ. et al; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, ; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352 (10) 987-996
    Google Scholar
  • 14 Perry JR, Laperriere N, O'Callaghan CJ. et al; Trial Investigators. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med 2017; 376 (11) 1027-1037
    Google Scholar
  • 15 Perisanidis C, Psyrri A, Cohen EE. et al. Prognostic role of pretreatment plasma fibrinogen in patients with solid tumors: a systematic review and meta-analysis. Cancer Treat Rev 2015; 41 (10) 960-970
    Google Scholar
  • 16 García-Ortega DY, Álvarez-Cano A, Sánchez-Llamas LA. et al. Neutrophil/lymphocyte ratio is associated with survival in synovial sarcoma. Surg Oncol 2018; 27 (03) 551-555
    Google Scholar
  • 17 Kijima T, Arigami T, Uchikado Y. et al. Combined fibrinogen and neutrophil-lymphocyte ratio as a prognostic marker of advanced esophageal squamous cell carcinoma. Cancer Sci 2017; 108 (02) 193-199
    Google Scholar
  • 18 Shimizu T, Ishizuka M, Shibuya N. et al. Preoperative globulin-to-albumin ratio predicts outcome after curative resection in patients with gastric cancer. Ann Gastroenterol Surg 2018; 2 (05) 367-375
    Google Scholar
  • 19 Wang J, Xiao W, Chen W, Hu Y. Prognostic significance of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with glioma. EXCLI J 2018; 17: 505-512
    Google Scholar
  • 20 Arigami T, Uenosono Y, Ishigami S. et al. A novel scoring system based on fibrinogen and the neutrophil-lymphocyte ratio as a predictor of chemotherapy response and prognosis in patients with advanced gastric cancer. Oncology 2016; 90 (04) 186-192
    Google Scholar
  • 21 Gan Y, Zhou X, Niu X. et al. Neutrophil/lymphocyte ratio is an independent prognostic factor in elderly patients with high-grade gliomas. World Neurosurg 2019; 127: e261-e267
    Google Scholar
  • 22 Tang L, Liu K, Wang J, Wang C, Zhao P, Liu J. High preoperative plasma fibrinogen levels are associated with distant metastases and impaired prognosis after curative resection in patients with colorectal cancer. J Surg Oncol 2010; 102 (05) 428-432
    Google Scholar
  • 23 Du J, Zheng JH, Chen XS. et al. High preoperative plasma fibrinogen is an independent predictor of distant metastasis and poor prognosis in renal cell carcinoma. Int J Clin Oncol 2013; 18 (03) 517-523
    Google Scholar
  • 24 Wang PF, Meng Z, Song HW. et al. Preoperative changes in hematological markers and predictors of glioma grade and survival. Front Pharmacol 2018; 9: 886
    Google Scholar
  • 25 Han S, Liu Y, Li Q, Li Z, Hou H, Wu A. 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
    Google Scholar
  • 26 Alexiou GA, Vartholomatos E, Voulgaris S. Prognostic value of neutrophil-to-lymphocyte ratio in patients with glioblastoma. J Neurooncol 2013; 115 (03) 521-522
    Google Scholar
  • 27 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 (01) 01-10
    Google Scholar
  • 28 Wang PF, Song HW, Cai HQ. et al. Preoperative inflammation markers and IDH mutation status predict glioblastoma patient survival. Oncotarget 2017; 8 (30) 50117-50123
    Google Scholar
  • 29 Hartmann C, Hentschel B, Wick W. et al. Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol 2010; 120 (06) 707-718
    Google Scholar
  • 30 Akamine T, Takada K, Toyokawa G. et al. Association of preoperative serum CRP with PD-L1 expression in 508 patients with non-small cell lung cancer: a comprehensive analysis of systemic inflammatory markers. Surg Oncol 2018; 27 (01) 88-94
    Google Scholar
  • 31 Wainwright DA, Chang AL, Dey M. et al. Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4, and PD-L1 in mice with brain tumors. Clin Cancer Res 2014; 20 (20) 5290-5301
    Google Scholar
  • 32 Akamine T., Takada K, Toyokawa G. et al. Association of preoperative serum CRP with PD-L1 expression in 508 patients with non-small cell lung cancer: A comprehensive analysis of systemic inflammatory markers. Surg Oncol 2018; 27 (01) 88-94
    Google Scholar
  • 33 Zadora P, Dabrowski W, Czarko K. et al. Preoperative neutrophil-lymphocyte count ratio helps predict the grade of glial tumor - a pilot study. Neurol Neurochir Pol 2015; 49 (01) 41-44
    Google Scholar
  • 34 Malaguarnera L, Ferlito L, Imbesi RM. et al. Immunosenescence: a review. Arch Gerontol Geriatr 2001; 32 (01) 1-14
    Google Scholar
  • 35 Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer 2009; 9 (04) 239-252
    Google Scholar
  • 36 Lopes M, Carvalho B, Vaz R, Linhares P. Influence of neutrophil-lymphocyte ratio in prognosis of glioblastoma multiforme. J Neurooncol 2018; 136 (01) 173-180
    Google Scholar
  • 37 Linhares P, Carvalho B, Vaz R, Costa BM. Glioblastoma: is there any blood biomarker with true clinical relevance?. Int J Mol Sci 2020; 21 (16) 5809
    Google Scholar