Neutrophil to lymphocyte ratio for glioma

Neutrophil to lymphocyte ratio for glioma

Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, the systemic immune inflammation index (SII), and red blood cell distribution width (RDW), have been recognized as promising predictors for histological grade and prognosis in multiple cancer types.

It is a simple, low-cost and easily measured inflammation marker.

Studies have shown that the peripheral blood pretreatment Neutrophil to lymphocyte ratio(NLR) is a prognostic measure in various cancers. The few studies evaluating NLR in glioblastoma multiforme (GBM) patients yielded inconsistent results.

In the cohort of Brenner et al., 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 1).

For Weng et al., the preoperative NLR was correlated with glioma grading, and the elevated NLR was an independent predictive factor for poor outcome of glioblastoma patients 2).

For Bao et al., NLR was an independent prognostic factor for overall survival in glioma 3).

For Zadora et al., preoperative NLCR measurement corresponds with a glial brain tumor grading 4).

Case series

Brenner et al., 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 O6-methylguanine-DNA methyltransferase (MGMT) promoter was not determined.

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 (p = 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; p = 0.035). There were no treatment-related deaths. The most common grade III-IV toxicities were thrombocytopenia, 12.4%, and fatigue, 13.5%.

In this 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 5).


The preoperative NLR was analyzed retrospectively in 239 gliomas of different grades, and receiver operating characteristic (ROC) curve analysis was adopted to investigate the prediction of glioma grading. Univariate and multivariate analyses were performed to analyze the variables of overall survival (OS) of glioblastoma patients.

There were significant differences in the preoperative NLR values among the four glioma groups, with the highest values observed in the glioblastoma group (p < 0.05). ROC curve analysis showed the NLR value of 2.36 was a cutoff point for predicting glioblastoma. The OS of patients with high NLR (≥ 4.0) was shorter compared with that with low NLR (< 4.0) (mean 11.23 vs. 18.56 months, p < 0.05). Univariate analysis and multivariate analysis indicated age≥ 60, NLR≥ 4.0, Karnofsky Performance Scores (KPS) ≤ 70, incomplete tumor resection, incomplete Stupp protocol accomplishment and the isocitrate dehydrogenase 1 (IDH1) wild-type as independent prognostic indicators for poor outcome (each p < 0.05).

The preoperative NLR was correlated with glioma grading, and the elevated NLR was an independent predictive factor for poor outcome of glioblastoma patients 6).


A retrospective chart review study was conducted for 219 glioma patients between January 2012 and January 2017. The values of the NLR, PLR, MLR and RDW on the prognosis were evaluated. And correlations between these hematologic inflammatory markers were examined.

Patients were divided into high and low groups according to cutoff points from the receiver operating characteristic curve. The high NLR groups were associated with tumor grade (p = 0.000). Kaplan-Meier survival analyses shown that the high NLR group experienced inferior median survival compared with the low NLR group (11 vs. 32 months; p = 0.000). The high PLR group experienced inferior median survival compared with the low PLR group (12 vs. 21 months; p = 0.001). The high MLR group experienced inferior median survival compared with the low MLR group (12 vs. 22 months; p = 0.006). However, there was no significant difference in median survival between the high and low RDW groups (15 vs. 23 months; p = 0.184). Multivariate analysis demonstrated that NLR was an independent predictor for overall survival (OS) (HR 1.758; p = 0.008).

High preoperative NLR, PLR, MLR were predictors of poor prognosis for patients with glioma. NLR was an independent prognostic factor for OS in glioma 7).


A retrospective analysis of NLCR was performed in neurosurgical patients treated for glial brain tumors. The preoperative NLCR was analyzed in accordance with WHO glial tumors’ classification, which distinguishes G1, G2, G3 and G4 (glioblastoma) tumors.

The analysis of NLCR was performed in 424 patients (258 males and 166 females) aged 53 ± 16 years who underwent either an open surgery or stereotactic biopsy for a glial brain tumor. G1 was diagnosed in 22 patients, G2 – in 71 patients, G3 – in 63 patients and G4 – in 268 patients. The highest value of NLCR was noted in G4 patients (5.08 [3.1; 8.7] – median [quartiles 1 and 3, respectively]) and was significantly higher compared to G3 (p<0.01), G2 (p<0.001) and G1 (p<0.01) groups. Moreover, NLCR was significantly higher in group G3 than G2 (p<0.05). ROC curve analysis showed 2.579 as a cut-off point for prediction of glioblastoma.

Preoperative NLCR measurement corresponds with a glial brain tumor grading 8).

References

1) , 5)

Brenner A, Friger M, Geffen DB, Kaisman-Elbaz T, Lavrenkov K. 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. Oncology. 2019 Jul 9:1-9. doi: 10.1159/000500926. [Epub ahead of print] PubMed PMID: 31288238.
2) , 6)

Weng W, Chen X, Gong S, Guo L, Zhang X. Preoperative neutrophil-lymphocyte ratio correlated with glioma grading and glioblastoma survival. Neurol Res. 2018 Aug 3:1-6. doi: 10.1080/01616412.2018.1497271. [Epub ahead of print] PubMed PMID: 30074469.
3) , 7)

Bao Y, Yang M, Jin C, Hou S, Shi B, Shi J, Lin N. Preoperative hematologic inflammatory markers as prognostic factors in patients with glioma. World Neurosurg. 2018 Aug 6. pii: S1878-8750(18)31732-7. doi: 10.1016/j.wneu.2018.07.252. [Epub ahead of print] PubMed PMID: 30092479.
4) , 8)

Zadora P, Dabrowski W, Czarko K, Smolen A, Kotlinska-Hasiec E, Wiorkowski K, Sikora A, Jarosz B, Kura K, Rola R, Trojanowski T. Preoperative neutrophil-lymphocyte count ratio helps predict the grade of glial tumor – a pilot study. Neurol Neurochir Pol. 2015;49(1):41-4. doi: 10.1016/j.pjnns.2014.12.006. Epub 2015 Jan 6. PubMed PMID: 25666772.

Neutrophil to lymphocyte ratio for intracerebral hemorrhage

Inflammatory response plays a vital role in the pathological mechanism of intracerebral hemorrhage. It has been recently reported that neutrophil to lymphocyte ratio (NLR) could represent a novel composite inflammatory marker for predicting the prognosis of intracranial hemorrhage (ICH).


The clinical data of 558 consecutive patients from the Ulanqab Central Hospital, with intracerebral hemorrhage (ICH) were retrospectively analyzed. Neutrophil to lymphocyte ratio is calculated by absolute lymphocyte count divided by absolute monocyte count.

Of these patients, 166 patients experienced neurological deterioration (ND) during the first week after admission and 72 patients died within 90 days. Multivariate analysis indicated that white blood cells (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), LMR were significantly associated with ND during the initial week after ICH onset and also were associated with 90-day mortality. Moreover, NLR and LMR showed a higher predictive ability in ND during the initial week after ICH onset than 90-day mortality in receiver operating characteristic analysis. The best cut-off points of NLR and LMR in predicting ND and 90-day mortality were 10.24 and 2.21 and 16.81 and 2.19, respectively.

The results suggest that LMR on admission is a predictive factor for ND during the initial week after ICH onset, as well as 90-day mortality 1).


104 patients with acute ICH admitted to West China Hospital, Sichuan University, ChengduChina, from October 2016 to January 2018 were retrospectively enrolled. Admission absolute neutrophil count, lymphocyte count and white blood count were extracted from electronic medical records of patents with ICH. The associations between outcome and laboratory biomarkers were assessed by multivariable logistic regression analysis. The comparison of predictive power of independent predictors was evaluated by receiver operating characteristic curves (ROC).

59 ICH patients with surgical treatment exhibited unfavorable outcome, which associated with higher admission NLR (OR 0.692, 95%CI 0.518-0.925, P=0.01; OR 1.148, 95%CI 1.078-1.222, P<0.01; OR 1.215, 95%CI 1.015-1.454, P=0.03), lower GCS and larger hematoma. NLR showed the best predictive power by comparing with other laboratorial variables (area under the curve [AUC] 0.668, 95%CI 0.569-0.757, P<0.01), and was also found to linearly correlate with GCS at admission, hematoma volume, ANC, ALC and hydrocephalus. Meanwhile, the best predictive cutoff point of 6.46 for NLR was also identified.

Other than the association of prognosis of ICH patients, NLR exhibited potential independently predictive ability for 90-day functional outcome of ICH patients after surgery 2).

1)

Qi H, Wang D, Deng X, Pang X. Lymphocyte-to-Monocyte Ratio Is an Independent Predictor for Neurological Deterioration and 90-Day Mortality in Spontaneous Intracerebral Hemorrhage. Med Sci Monit. 2018 Dec 20;24:9282-9291. doi: 10.12659/MSM.911645. PubMed PMID: 30572340.
2)

F Z, C T, X H, J Q, X L, C Y, Y J, M Y. Association of neutrophil to lymphocyte ratio on 90-day functional outcome in intracerebral hemorrhage patients undergoing surgical treatment. World Neurosurg. 2018 Aug 10. pii: S1878-8750(18)31791-1. doi: 10.1016/j.wneu.2018.08.010. [Epub ahead of print] PubMed PMID: 30103056.

Moderate elevations in international normalized ratio should not lead to delays in neurosurgical intervention in patients with traumatic brain injury

Intracranial procedures are often deferred until an international normalized ratio (INR) of less than 1.4 is achieved. There is no evidence that a moderately elevated INR is associated with increased risk of bleeding in neurosurgical intervention (NI). Thromboelastography (TEG) provides a functional assessment of clotting and has been shown to better predict clinically relevant coagulopathy compared with INR.
Traumatic brain injury (TBI) patients with an admission INR of greater than 1.4 had a longer time to NI. The use of plasma transfusion to decrease the INR may have contributed to this delay. A moderately elevated INR was not associated with coagulopathy based on TEG. Routine plasma transfusion to correct a moderately elevated INR before NI should be reexamined
Rowell SE, Barbosa RR, Lennox TC, Fair KA, Rao AJ, Underwood SJ, Schreiber MA. Moderate elevations in international normalized ratio should not lead to delays in neurosurgical intervention in patients with traumatic brain injury. J Trauma Acute Care Surg. 2014 Dec;77(6):846-851. PubMed PMID: 25423533.

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