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).

References

1)

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.
2)

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.
3)

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).

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.

Osteosarcoma

Osteosarcoma

An osteosarcoma is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma) and that exhibits osteoblastic differentiation and produces malignant osteoid.

Osteoblastoma is a rare, benign, locally recurrent tumor with a predilection for spine, that may rarely undergo sarcomatous change (to osteosarcoma, only a handful of known cases of this 1)).

Epidemiology

The most common primary bone cancer. More common in children, usually occurring near the ends of long bones, but also in the mandible, pelvis, and rarely in the spine.

Spinal osteosarcoma usually occurs in the lumbosacral region in males in their 40 s, sometimes arising from areas of osteoblastoma or Paget’s disease. If a percutaneous biopsy reveals osteosarcoma, the contaminated needle tract can increase the difficulty of subsequent surgery. Poor prognosis, median survival=10 months 2).

Diagnosis

Caution regarding needle biopsy: if the lesion turns out to be osteosarcoma, the contaminated needle tract can result in worse prognosis.


The purpose of a work was to identify and measure catecholamines, their metabolites, and the gene expression of catecholamine receptors in osteosarcoma tissue.

The levels of 3,4-dihydroxyphenylacetic acid, norepinephrine, serotonin, and 5-hydroxyindoleacetic acid in cancer tissue and in adjacent and non-oncological bone tissue were analysed by high-performance liquid chromatography, and the gene expression of catecholamine receptors and of dopamine β-hydroxylase, monoaminoxidase, ki67, and Runx2 in the osteosarcoma tissue, tissue adjacent to the tumour, non-oncological bone, and human brain tissue was analysed by RT-PCR.

Bandala et al., found significantly higher levels of 3,4-dihydroxyphenylacetic acid and norepinephrine in the cancer sample than in adjacent and non-oncological bone. We found that β-adrenergic receptors and dopaminergic receptors, dopamine β-hydroxylase, ki67, Runx2, and serotonergic receptor gene expression were significantly higher in tumour tissue than in adjacent and non-oncological bone.

Catecholamines and their receptors could be potential molecular markers for osteosarcoma progression 3).

Complications

References

1)

Amacher AL, Eltomey A. Spinal Osteoblastoma in Children and Adolescents. Childs Nerv Syst. 1985; 1:29–32
2)

Shives TC, Dahlin DC, Sim FH, Pritchard DJ, Earle JD. Osteosarcoma of the spine. J Bone Joint Surg Am. 1986; 68:660–668
3)

Bandala C, Ávila-Luna A, Gómez-López M, Estrada-Villaseñor E, Montes S, Alfaro-Rodríguez A, Miliar-García Á, Cortés-Altamirano JL, Peralta R, Ibáñez-Cervantes G, Gómez-Manzo S, Cárdenas-Rodríguez N, Lara-Padilla E. Catecholamine levels and gene expression of their receptors in tissues of adults with osteosarcoma. Arch Physiol Biochem. 2019 Jul 10:1-7. doi: 10.1080/13813455.2019.1638942. [Epub ahead of print] PubMed PMID: 31291139.
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