Predictors of postoperative seizure outcome in supratentorial meningioma

OBJECTIVE Meningiomas are the most common primary intracranial tumor. Seizures are common sequelae of meningioma development. Meningioma patients with seizures can be effectively treated with resection, with reports of seizure freedom of 60%–90%. Still, many patients manifest persistent epilepsy. Determining factors associated with worsened seizure outcomes remains critical in improving the quality of life for these patients. The authors sought to identify clinical, radiological, and histological factors associated with worse seizure outcomes in patients with supratentorial meningioma and preoperative seizures. METHODS The authors retrospectively reviewed the charts of 384 patients who underwent meningioma resection from 2008 to 2020. The charts of patients with a documented history of preoperative seizures were further reviewed for clinical, radiological, operative, perioperative, histological, and postoperative factors associated with seizures. Engel class at last follow-up was retrospectively assigned by the authors and further grouped into favorable (class I) and worse (class II–IV) outcomes. Factors were subsequently compared by group using comparative statistics. Univariable and multivariable regression models were utilized to identify independent predictors of worse seizure outcome. RESULTS Fifty-nine patients (15.4%) were found to have preoperative seizures, of whom 57 had sufficient postoperative data to determine Engel class outcome. Forty-two patients (74%) had Engel class I outcomes. The median follow-up was 17 months. Distinct margins on preoperative imaging (p = 0.012), Simpson grade I resection (p = 0.004), postresection ischemia (p = 0.019), WHO grade (p = 0.019), and recurrent disease (p = 0.015) were found to be the strongest predictors of Engel class outcome in univariable logistic regression. MIB-1 index (p = 0.001) and residual volume (p = 0.014) at last follow-up were found to be the strongest predictors of Engel class outcome in univariable generalized linear regression. Postresection ischemia (p = 0.012), WHO grade (p = 0.022), recurrent disease (p = 0.038), and MIB-1 index (p = 0.002) were found to be the strongest independent predictors of Engel class outcomes in multivariable analysis. CONCLUSIONS Postresection ischemia, higher WHO grade, elevated MIB-1 index, and disease recurrence independently predict postresection seizure persistence in patients with supratentorial meningioma. Further understanding of the etiology of these markers may aid in elucidation of this complex disease process and guide management to prevent worse outcomes.

COT-9 Prognostic impact of hypercoagulation in glioblastoma and molecular mechanism thereof

Introduction: Pathological features of glioblastoma include intravascular thrombosis, suggesting that the thrombus formation in tumor microenvironment contributes to progression of gliomas. Meanwhile, glioblastoma has been known to be high risk malignant tumor for venous thromboembolism, however, it remains unclear how the coagulation-fibrinolysis system is disrupted, which essentially grow within the cranium in a localized manner, and how the disruption contributes to the malignant transformation. Methods: Total 64 patients with glioblastoma between January 2014 and April 2021 who underwent a D-dimer test before the therapeutic intervention were divided into two groups: the high D-dimer group (D-dimer level >3.0μg/ml) and the low D-dimer group (D-dimer level <3.0μg/ml). We compared the two groups in the maximum gadolinium-enhanced MRI lesions, MIB-1 index, and gene abnormalities (IDH mutation, TERT promoter mutation, and MGMT promotor methylation). The progression-free survival (PFS) and overall survival were analyzed using the Kaplan-Meier method. Furthermore, in 23 patients who underwent a D-dimer test at recurrence, the time to death after recurrence was analyzed. Results: The PFS in high D-dimer group was significantly shorter than that in the low D-dimer group (log-rank p = 0.0075). The D-dimer increase at the time of recurrence significantly correlated with the decrease in post-recurrence survival duration (log-rank p = 0.0226). Moreover, the gadolinium-enhanced lesions in the high D-dimer group were significantly larger. Conclusion: The Pre-intervention D-dimer levels and PFS suggest that glioblastoma-induced systemic enhancement of the coagulation-fibrinolysis system plays a role in the malignant transformation. The D-dimer increase during the treatment was found to be a predictor of poor prognosis after recurrence. Furthermore, the MRI findings revealed a correlation between the D-dimer increase and the size of intratumoral necrosis. Meanwhile, no correlation with the MIB-1 index was found, suggesting that the mechanism of malignant transformation by hypercoagulation differ from enhanced cell proliferation.

NIMG-29. ELEVATION OF GLUTAMINE AND CITRATE BY MR SPECTROSCOPY IS AN IMAGING BIOMARKER OF RAPID CELL PROLIFERATION IN GLIOMAS

Prior studies suggested glutamine metabolism in cancers may be altered to meet the high demands of nucleotide biosynthesis in cancers. We conducted 1H MR spectroscopy in 18 glioma patients and analyzed the metabolic data together with post-gadolinium MRI and cell proliferation rate (MIB-1 label index). The optimized MRS (TE 97 ms PRESS) provided well discernible signal of glutamine at 2.45 ppm and a negative-polarity signal of citrate at 2.6 ppm, without considerable overlaps with neighboring signals. The 18 patients had biopsy-proven anaplastic gliomas or glioblastomas. Concurrent elevation of glutamine and citrate was identified in 15 gliomas. These gliomas presented with enhancement in post-gadolinium MRI, indicative of broken blood-brain barrier (BBB). The 15 gliomas were grouped as subset-1 while the other 3 gliomas that had elevated citrate without elevation of glutamine were grouped as subset-2. Citrate level was significantly different between the two subsets of gliomas (1.4+/-0.5 vs. 1.6+/-0.4 mM). However, subst-1 had significantly higher choline (4.7+/-1.8 vs. 1.6+/-0.3 mM, p< 0.01) and higher MIB-1 compared with subset-2. Given that choline is a cellularity marker, a finding of high choline and high MIB-1 with elevation of glutamine and citrate suggests that the tumors have high tumor cellularity and cell multiplication competence. Of the 18 gliomas, 13 were IDH mutated with elevated 2HG. The glutamine and citrate levels in IDH-mutant gliomas were not significantly different from those in IDH wildtype gliomas. In conclusion, high-grade gliomas undergo a metabolic rearrangement of concurrent elevation of glutamine and citrate to attain malignant characters such as high cellularity, rapid cell proliferation, and BBB breakdown. IDH mutant and IDH wildtype gliomas may share a common metabolic rearrangement of glutamine-mediated citrate elevation to attain malignancy. Measurements of glutamine and citrate may serve a potential imaging biomarker for aggressive gliomas.

Ki-67/MIB-1 and Recurrence in Pituitary Adenoma

Objectives Ki-67/MIB-1 is a marker of cellular proliferation used as a pathological parameter in the clinical assessment of pituitary adenomas, where its expression has shown utility in predicting the invasiveness of these tumors. However, studies have shown variable results when using Ki-67/MIB-1 association with recurrence. The purpose of this study is to determine if a high Ki-67/MIB-1 labeling index (LI) is predictive of recurrence in pituitary adenomas. Methods A retrospective chart review was performed for patients undergoing pituitary adenoma resection with at least 1 year of follow-up. Additionally, systematic data searches were performed and included studies that correlated recurrence rate to Ki-67/MIB-1 LI. Our institutional data were included in a synthesis with previously published data. Results Our institutional review included 79 patients with a recurrence rate of 26.6%. We found that 8.8% of our patients had a high Ki-67/MIB-1 LI (>3%); however, high Ki-67/MIB-1 was not associated with recurrence. The systematic review identified 244 articles and 49 full-text articles that were assessed for eligibility. Quantitative analysis was performed on 30 articles including our institutional data and 18 studies reported recurrence by level of Ki-67/MIB-1 LI. Among studies that compared Ki-67/MIB-1 ≥3 vs. <3%, 10 studies reported odds ratios (OR) greater than 1 of which 6 were statistically significant. A high Ki-67/MIB-1 had higher odds of recurrence via the pooled odds ratio (OR = 4.15, 95% confidence interval [CI]: 2.31–7.42). Conclusion This systematic review suggests that a high Ki-67/MIB-1 should prompt an increased duration of follow-up due to the higher odds of recurrence of pituitary adenoma.

Prognostic value of proliferation, PD-L1 and nuclear size in patients with superior sulcus tumours treated with chemoradiotherapy and surgery

AimsThe aim of this study was to determine the relationship between proliferative activity, PD-L1 status and nuclear size changes after preoperative chemoradiotherapy (CRT) and the clinical outcome in patients with superior sulcus tumours.MethodsProliferative activity (MIB-1) and PD-L1 status were estimated by immunohistochemistry in the tumour cells of resection specimen in a series of 33 patients with residual tumour after trimodality therapy for a sulcus superior tumour between 2005 and 2014. A morphometric analysis of both pretreatment and post-treatment tumour materials was also performed. Results were related to disease-free survival and overall survival.ResultsLow proliferative activity (<20% MIB-1) was associated with better overall survival: 2-year overall survival of 73% compared with 43% and 25%, respectively, for moderate (MIB-1 20%–50%) and high (MIB-1 >50%) proliferative activity (p=0.016). A negative PD-L1 status (<1% positive tumour cells) was also associated with better overall survival (p=0.021). The mean nuclear size of normal lung tissue pneumocytes was significantly smaller compared with the mean nuclear size of tumour cells of the resection specimens (median difference −38.1; range −115.2 to 16.0; p<0.001). The mean nuclear size of tumour cells did not differ between pretreatment biopsies and resection specimens (median difference −4.6; range −75.2 to 86.7; p=0.14). Nuclear size was not associated with survival (p=0.82).ConclusionsLow proliferative activity determined by MIB-1 as well as a negative PD-L1 expression are significantly associated with better overall survival in patients with residual tumour after CRT for superior sulcus tumour.

To study histopathological features, GFAP staining and Ki 67/ MIB-1 labelling index in diagnoses and histological grading of gliomas

: A group of tumors that develops in the brain and spinal cord is called glioma. Histologically gliomas are classified into astrocytoma, ependymoma, oligodendroglioma, brain stem glioma and oligoastrocytoma. The present study was conducted to study histological grading of gliomas and correlate it with patient’s age, sex, GFAP staining, role of the Ki-67/MIB-1 labelling indices (PIs). The present retrospective study was conducted on 50 biopsies received. All specimens were subjected to immunohistochemistory for GFAP and MIB-1 and correlated with WHO grading for glioma.: High incidence of glial tumours was seen in the 3 and 4 decade with slight male predominance (60%), with commonest site being frontal lobe. Glioblastomas (Grade IV) constitute the most common glial tumour. A statistically significant correlation was observed between GFAP staining and Ki-67/MIB-1 with histological grading.: The study can prove helpful in diagnosis and histological grading of gliomas and in planning treatment protocols and strategies.

Retrospective analysis of recurrence patterns and clinical outcome of grade II meningiomas following postoperative radiotherapy

Background Atypical meningiomas exhibit a high tendency for tumor recurrence even after multimodal therapy. Information regarding recurrence patterns after additive radiotherapy is scarce but could improve radiotherapy planning and therapy decision. We conducted an analysis of recurrence patterns with regard to target volumes and dose coverage assessing target volume definition and postulated areas of tumor re-growth origin. Prognostic factors contributing to relapse were evaluated. Methods The clinical outcome of patients who had completed additive, somatostatin receptor (SSTR)-PET/CT-based fractionated intensity-modulated radiotherapy for atypical meningioma between 2007 and 2017 was analyzed. In case of tumor recurrence/progression, treatment planning was evaluated for coverage of the initial target volumes and the recurrent tumor tissue. We proposed a model evaluating the dose distribution in postulated areas of tumor re-growth origin. The median of proliferation marker MIB-1 was assessed as a prognostic factor for local progression and new distant tumor lesions. Results Data from 31 patients who had received adjuvant (n = 11) or salvage radiotherapy (n = 20) were evaluated. Prescribed dose ranged from 54.0 to 60.0 Gy. Local control at five years was 67.9%. Analysis of treatment plans of the eight patients experiencing local failure proved sufficient extent of target volumes and coverage of the prescribed dose of at least 50.0 Gy as determined by mean dose, D98, D2, and equivalent uniform dose (EUD) of all initial target volumes, postulated growth-areas, and areas of recurrent tumor tissue. In all cases, local failure occurred in high-dose volumes. Tumors with a MIB-1 expression above the median (8%) showed a higher tendency for re-growth. Conclusions The model showed adequate target volume and relative dose distribution but absolute dose appears lower in recurrent tumors without reaching statistical significance. This might provide a rationale for dose escalation studies. Biological factors such as MIB-1 might aid patients’ stratification for dose escalation.

Clear cell meningioma in a child: Case report and systematic literature review

Antecedentes: El meningioma de células claras (MCC) consiste en una variante poco común de meningiomas que generalmente ocurren en niños. Este tumor poco común se comporta de manera agresiva y las tasas de recurrencia son altas. Las manifestaciones clínicas son atípicas y el tratamiento generalmente implica cirugía. Métodos y Objetivos: Realizamos una revisión sistemática con el fin de definir las características más comunes de este raro tumor. Pubmed y LILACS fueron las bases de datos utilizadas para la búsqueda bibliográfica. Se incluyeron 17 estudios que cumplieron con nuestros criterios. Para avanzar en nuestra investigación, incluimos el caso clínico de una niña de 3 años con CCM operada en nuestro servicio. Resultados: Los MCC fueron más frecuentes en la población pediátrica que en la adulta, especialmente en el sexo femenino. La resección macroscópica del tumor y el índice MIB-1 < 3 fueron los parámetros relacionados con una menor tasa de recurrencia. La resección subtotal del tumor fue seguida de radioterapia en la mayoría de los casos de adultos. La mutación SMARCE-1 se pudo encontrar en varios pacientes. Conclusión: Los MCC son meningiomas raros que ocurren especialmente en niños. La agresividad y las altas tasas de recurrencia dificultan el manejo de esta enfermedad. Aún queda mucho por discutir sobre estos tumores raros, lo que exige más investigación.

Facial Nerve Outcome and Results in Hypervascular Large Vestibular Schwannomas: Our Personal Experience in A Series of 32 Cases.

BackgroundVestibular schwannomas (VS) are usually hypovascularized. Large VS with unusual vascular architecture are defined hyper-vascular (HVVS); excessive bleeding during microsurgery has negative impact on results. Methods Thirty-two consecutive patients were operated on for HVVS (Group-A). Results were compared with those of 25 patients (Group-B) operated on for large low-bleeding VS. Tendency to bleed and adherence of capsule to nervous structures were evaluated by reviewing video records. Cisternal facial nerve (FN) position was reported. Microsurgical removal was classified as total, near-total, subtotal or partial and MIB-1 index evaluated in all. FN results were classified according the House-Brackmann scale.Results Mean tumor diameter was 3,99cm in Group-A and 3,67 in Group-B; mean age was 42,3 and 58,1 years, respectively. Mean ASA class of Group-A was 1,72 versus 2,48 of Group-B (p<0,001). Total-NT resection was accomplished in 71,9% of HVVS versus 80,0% of Group-B. Tight capsule adhesion was observed in 68,7% HVVS versus 56,0% low-bleeding ones. Mean MIB-1 was 1,25% and 1,08%, respectively.Anterior-superior position of FN was observed in 48,6% of HVVS versus 32,0% of low-bleeding tumors (p<0,05). FN anatomical preservation was possible in 81,2% of Group-A versus 100% of Group-B (p<0,05); 62,5% of HVVS had HBI-II FN outcome versus 96,0% of low-bleeding (p<0,01). In Group-A 25,0% experienced postoperative complications versus 8,0% of Group-B (p<0,05). Recurrence/re-growth was observed in 7 HVVS versus 1 low-bleeding (p<0,05).Conclusions Microsurgery of large HVVS was associated with higher complication and recurrence/re-growth rate and poorer FN outcome, especially in cases with tight capsule adhesion.