Thalamic glioma treatment

Thalamic glioma treatment

Deep-seated astrocytomas within the basal ganglia and the thalamus are considered unfavourable for microsurgical removal since the circumferential neighbourhood of critical structures limits radical resection. On closer assessment, the thalamus has a unique configuration within the basal ganglia.

Its tetrahedric shape has 3 free surfaces and only the ventrolateral border is in contact with vital and critical functional structures, e.g. the subthalamic nuclei and the internal capsule.

see Transcallosal approach.

Tumors here are usually treated with biopsy and adjuvant therapy with relatively poor results. Rarely do patients undergo extensive surgical intervention. It seems reasonable to suggest that successful cytoreduction may help these patients. However, this hypothesis has not been studied due to the general view that it is not possible to remove deep-seated brain tumors with acceptable outcomes.

Through retrospective data collection, Briggs et al., described a small case series undergoing awake contralateral, transcallosal approach surgery for deep-seated brain tumors affecting the basal ganglia. They described the patient cohort, report on patient outcomes, and described the surgical technique.

Four patients underwent awake contralateral, transcallosal surgery for glioblastoma invading the basal ganglia. All four patients demonstrated hemibody weakness contralateral to the side of their tumor, with three patients confined to wheelchairs at presentation. Ages ranged from 25-64 years. Tumor volumes ranged from 14-93 cm3. Greater than 50% resection of each tumor was achieved during surgery. In two cases, approximately 90% resection was achieved. Motor strength improved in one patient who presented with hemiplegia. Two patients required ventriculoperitoneal shunting for complications related to hydrocephalus. When writing this manuscript, two of our patients were still alive, functional, and free of tumor progression.

They presented results attempting to resect large gliomas infiltrating the basal ganglia in four patients. This technique combined a contralateral, transcallosal approach with awake neuromonitoring. The results suggest it is possible to remove these tumors with reasonable outcomes 1).

From May 2011 to Aug 2015, 49 patients with thalamic gliomas underwent microsurgical resection, and received chemotherapy and radiotherapy postoperatively. The postoperative symptoms and complications were documented, and the overall survival (OS) and the progression-free survival (PFS) data were collected. The prognostic factors were evaluated by univariate and multivariate analyses. Finally, there was no perioperative death. Twenty cases, 24 cases and 5 cases were achieved subtotal resection (>90%), partial resection (70-90%) and less than partial resection (<70%) respectively. All patients’ pathological diagnosis was confirmed. The symptoms were improved in 32 cases, unchanged in 11 cases, and worsen in 6 cases. Postoperative complications were absent in 9 cases. The 6-month, 12-month, and 24-month OS were 71.4%, 38.9%, and 12.1% respectively; corresponding PFS were 66.6%, 27.1%, and 10.2% respectively. The median OS time and PFS time were 9.0 months (95% CI 6.9-11.1) and 9.0 months (95% CI 6.6-11.4) respectively. Multivariate analysis revealed extent of resection were independent prognostic factors for OS (p < .05), patients with postoperative adjuvant chemotherapy and radiotherapy had a significant prolonged OS (p < .001) and PFS (p < .001). The study shows that the short-term efficacy of microsurgery for high-grade thalamic gliomas is satisfactory. Microsurgery can effectively alleviate patients’ symptoms and improve life quality. Postoperative adjuvant chemotherapy and radiotherapy are helpful for prolonging the survival time 2).

Series demonstrated the feasibility of the microsurgical concept. Comparison with other treatment modalities, such as brachytherapy, requires future consideration 3).



Briggs RG, Nix CE, Conner AK, Palejwala AH, Smitherman AD, Teo C, Sughrue ME. An Awake, Contralateral, Transcallosal Approach for Deep-Seated Gliomas of the Basal Ganglia. World Neurosurg. 2019 Jul 10. pii: S1878-8750(19)31937-0. doi: 10.1016/j.wneu.2019.07.031. [Epub ahead of print] PubMed PMID: 31301441.

Wu B, Tang C, Wang Y, Li Z, Hu S, Hua W, Li W, Huang S, Ma J, Zhang Y. High-grade thalamic gliomas: Microsurgical treatment and prognosis analysis. J Clin Neurosci. 2018 Mar;49:56-61. doi: 10.1016/j.jocn.2017.12.008. Epub 2017 Dec 14. PubMed PMID: 29248381.

Steiger HJ, Götz C, Schmid-Elsaesser R, Stummer W. Thalamic astrocytomas: surgical anatomy and results of a pilot series using maximum microsurgical removal. Acta Neurochir (Wien). 2000;142(12):1327-36; discussion 1336-7. PubMed PMID: 11214625.

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).


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.

Susceptibility weighted imaging for glioma

Susceptibility weighted imaging for glioma

Gradient echo T2WI MRI is the 3–4 × more sensitive test than FLAIR for demonstrating intraparenchymablood (which appears dark) due to high sensitivity to paramagnetic artifact. It is not as sensitive as SWI.

Susceptibility weighted imaging (SWI) of brain tumors provides information about neoplastic vasculature and intratumoral micro- and macrobleedings. Low- and high-grade gliomas can be distinguished by SWI due to their different vascular characteristics. Fractal analysis allows for quantification of these radiological differences by a computer-based morphological assessment of SWI patterns.

SWI and CE-SWI are indispensable tools for diagnosis, preoperative grading, posttherapy surveillance, and assessment of glioma 1).

The theory that susceptibility signals show microvasculature that correlates with tumor grade has been well validated with the help of various studies. However, the cons of SWI lie within the technique itself. Small tweaks made in imaging parameters lead to varying subjective results. This lack of standardization of the SWI technique remains an obstacle in its integration into mainstream grading of gliomas. SWI for now plays an important role in detecting gliomas and guiding biopsies. The goal of noninvasive accurate grading of tumors is yet to be realized. Further studies with greater sample size and better collaborations are warranted in this regard 2).

Eighteen GBM patients were retrospectively analyzed. After completion of therapy, imaging was performed every 3 months. MRI was analyzed at the following time points: after the third and sixth cycle of adjuvant temozolomide chemotherapy, thereafter in 3 month intervals and at recurrence. The number of SWI positive tumor pixels was quantified and compared with progression as defined by the RANO criteria on T2- and contrast-enhanced T1-weighted MRI sequences (T1-CE).

The MRI interval between completion of the sixth chemotherapy cycle and last MRI before progression was 390 ± 292 days. Between the last MRI before progression and at progression a significant increase in SWI positive tumor pixels was observed (P = .012), whereas tumor size remained unchanged (RANO T2: P = .385; RANO T1-CE: P = .165). The number of SWI positive pixels remained unchanged between last MRI before progression until progression (P = .149), whereas RANO T2 and T1-CE showed tumor progression (interval 128 ± 69 days).

SWI positive pixel count increases significantly prior to changes in tumor size (RANO). The findings may be explained by microbleeds compatible with stimulation of angiogenesis and possibly serve as an early biomarker of tumor progression 3).

Seventy-eight patients affected by brain tumors of different histopathology (low- and high-grade gliomas, metastases, meningiomas, lymphomas) were included. All patients underwent preoperative 3-T magnetic resonance imaging including SWI, on which the lesions were contoured. The images underwent automated computation, extracting 2 quantitative parameters: the volume fraction of SWI signals within the tumors (signal ratio) and the morphological self-similar features (fractal dimension [FD]). The results were then correlated with each histopathological type of tumor.

Signal ratio and FD were able to differentiate low-grade gliomas from grade III and IV gliomas, metastases, and meningiomas (P < .05). FD was statistically different between lymphomas and high-grade gliomas (P < .05). A receiver-operating characteristic analysis showed that the optimal cutoff value for differentiating low- from high-grade gliomas was 1.75 for FD (sensitivity, 81%; specificity, 89%) and 0.03 for signal ratio (sensitivity, 80%; specificity, 86%).

FD of SWI on 3-T magnetic resonance imaging is a novel image biomarker for glioma grading and brain tumor characterization. Computational models offer promising results that may improve diagnosis and open perspectives in the radiological assessment of brain tumors 4).



Hsu CC, Watkins TW, Kwan GN, Haacke EM. Susceptibility-Weighted Imaging of Glioma: Update on Current Imaging Status and Future Directions. J Neuroimaging. 2016 Jul;26(4):383-90. doi: 10.1111/jon.12360. Epub 2016 May 26. Review. PubMed PMID: 27227542.

Mohammed W, Xunning H, Haibin S, Jingzhi M. Clinical applications of susceptibility-weighted imaging in detecting and grading intracranial gliomas: a review. Cancer Imaging. 2013 Apr 24;13:186-95. doi: 10.1102/1470-7330.2013.0020. Review. PubMed PMID: 23618919; PubMed Central PMCID: PMC3636597.

van Leyen K, Roelcke U, Gruber P, Remonda L, Berberat J. Susceptibility and Tumor Size Changes During the Time Course of Standard Treatment in Recurrent Glioblastoma. J Neuroimaging. 2019 May 21. doi: 10.1111/jon.12631. [Epub ahead of print] PubMed PMID: 31112344.

Di Ieva A, Le Reste PJ, Carsin-Nicol B, Ferre JC, Cusimano MD. Diagnostic Value of Fractal Analysis for the Differentiation of Brain Tumors Using 3-Tesla Magnetic Resonance Susceptibility-Weighted Imaging. Neurosurgery. 2016 Dec;79(6):839-846. PubMed PMID: 27332779.
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