Prognostic Factors for Survival in Patients with High-Grade Meningioma and Recurrence-Risk Stratification for Application of Radiotherapy

Yamaguchi, Shigeru; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Asaoka, Katsuyuki; Motegi, Hiroaki; Nishihara, Hiroshi; Kanno, Hiromi; Onimaru, Rikiya; Ito, Yoichi M.; Shirato, Hiroki; Houkin, Kiyohiro

doi:10.1371/journal.pone.0097108

Cited by 20 publications

(8 citation statements)

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“…Considering the results of similar studies, a change in a patient’s mean age at the time of surgery could be observed over the last decades. While the average age a few decades ago was just over 50 years [ 20 , 22 ], meningioma patients who undergo surgery today are approximately 60 years old, similar to this study [ 9 , 21 , 23 , 24 ]. This is not surprising, since the ongoing advances in medicine mean that people are living longer and, consequently, also in the case of patients undergoing surgery.…”

Section: Resultssupporting

confidence: 77%

Prognostic factors of microsurgical treatment of intracranial meningiomas – A multivariate analysis

Kreßner

Arlt

Riepl³

et al. 2018

PLoS ONE

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ObjectivePeri- and postoperative time course of meningioma patients who had undergone surgical treatment was evaluated to determine prognostic factors of neurological outcome by focusing on preoperative parameters.Material and methodsA retrospective monocenter analysis was performed including patients who were operated in the Department of Neurosurgery, University Hospital Leipzig, from 2009 to 2015. Data from all patients with histologically confirmed diagnosis of intracranial meningioma treated microsurgically were included in the study. The individual characteristics of the patients, meningiomas and Karnofsky Performance scores (KPS) were analyzed by multivariate tests.ResultsTwo hundred ninety-four patients with a median age of 61 years (range: 17–89) were included. Preoperative KPS (p < 0.001), skull base as tumor origin and tumor size (p < 0.05) proved to be significantly strong prognostic factors of KPS deterioration one year postoperative by multivariate analysis. According to uni- and bivariate analysis, the following prognostic factors could also be found: preoperative mass displacement, preexisting recurrence and presence of preoperative symptoms. In this study, age had no significant influence on deterioration in patient health state, measured by KPS, one year postoperative.ConclusionPatients generally obtained an improvement in KPS score after microsurgical treatment. The knowledge of prognostic factors can be very helpful in the decision-making process for meningioma treatment of the elderly, particularly to estimate the postoperative outcome and quality of life.

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Section: Resultssupporting

confidence: 77%

Prognostic factors of microsurgical treatment of intracranial meningiomas – A multivariate analysis

Kreßner

Arlt

Riepl³

et al. 2018

PLoS ONE

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“…While MIB-1 has been correlated with outcomes in some studies, 3,4,31,34,36,[40][41][42]44,45,52,55 this correlation has not been seen in other studies. 1,21,28,48,51 Various cutoff values for MIB-1 in predicting disease grade and progression have been suggested, including 15%, 55 4.2%, 45 3%, 3,31,42,44 2.6%, 52 and 2%. 41 Our results suggest that a value of 3% shows 82.5% specificity in predicting disease progression but only 36% sensitivity.…”

Section: Practical Mib-1 Threshold For Clinical Usementioning

confidence: 87%

Microvascularization of Grade I meningiomas: effect on tumor volume, blood loss, and patient outcome

Karsy¹,

Burnett

Ieva

et al. 2018

Journal of Neurosurgery

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OBJECTIVE Quantitative assessment of tumor microvascularity has the potential to improve prognostication, advance understanding of tumor biology, and help narrow potential molecular therapies. While the role of tumor microvascularity has been widely studied in meningiomas, this study examines both the role of automated measurements and the impact on surgical outcome. METHODS Two hundred seven patients with Grade I meningiomas underwent surgery between 1996 and 2011. Tissue samples from each patient were retrospectively evaluated for histopathological measures of microvascularity, including staining for von Willebrand factor (vWF), CD31, CD105, hypoxia-inducible factor 1 (HIF-1), vascular endothelial growth factor, glucose transporter 1, and carbonic anhydrase IX. Manual methods of assessing microvascularity were supplemented by a computational analysis of the microvascular patterns by means of fractal analysis. MIB-1 proliferation staining was also performed on the same tumors. These measures were compared with various patient characteristics, tumor volume, estimated blood loss (EBL) during surgery, progression-free survival (PFS), and overall survival (OS). RESULTS The mean patient age was 55.4 ± 14.8 years, and 63 (30.4%) patients were male. Patients harboring tumors ≥ 3 cm were significantly older (56.9 ± 15.2 years vs 53.1 ± 13.6 years; p = 0.07), more frequently male (40.8% vs 14.6%; p = 0.0001), and had greater EBL (446.5 ± 532.2 ml vs 185.4 ± 197.2 ml; p = 0.0001), greater tumor volume (33.9 ± 38.1 ml vs 29.4 ± 23.5 ml; p = 0.0001), higher MIB-1 index values (3.0% ± 5.4% vs 1.7% ± 1.7%; p = 0.03), higher vWF levels (85.6% ± 76.9% vs 54.1% ± 52.4%; p = 0.001), lower HIF-1 expression (1.4 ± 1.3 vs 2.2 ± 1.4; p = 0.004), and worse OS (199.9 ± 7.6 months vs 180.8 ± 8.1 months; p = 0.05) than patients with tumors < 3 cm. In the multivariate logistic regression, MIB-1 (OR 1.14; p = 0.05), vWF (OR 1.01; p = 0.01), and HIF-1 (OR 1.54; p = 0.0001) significantly predicted tumor size. Although multiple factors were predictive of EBL in the univariate linear regression, only vWF remained significant in the multivariate analysis (β = 0.39; p = 0.004). Lastly, MIB-1 was useful via Kaplan-Meier survival analysis for predicting patients with disease progression, whereby an MIB-1 cutoff value of ≥ 3% conferred a 36% sensitivity and 82.5% specificity in predicting disease progression; an MIB-1 value ≥ 3% showed significantly shorter mean PFS (140.1 ± 11.7 months vs 179.5 ± 7.0 months; log-rank test, p = 0.05). The Cox proportional hazards model showed a trend for MIB-1 in predicting disease progression in a hazards model (OR 1.08; 95% CI 0.99-1.19; p = 0.08). CONCLUSIONS These results support the importance of various microvascularity measures in predicting preoperative (e.g., tumor size), intraoperative (e.g., EBL), and postoperative (e.g., PFS and OS) outcomes in patients with Grade I meningiomas. An MIB-1 cutoff value of 3% showed good specificity for predicting tumor progression. The predictive ability of various measur...

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“…Here we revealed that genotype was associated with recurrence independently from the degree of surgical resection completeness (Simpson grade) and histological malignancy (Ki-67 LI and WHO grade), which is known as prognostic factors in meningioma. [32][33][34] TRAKLS type was the most favorable genotype, so in addition to evaluating NF2 status, identifying this genotype from non-NF2 meningioma may help the accurate assessment of the recurrent risk. More recently, TERT promoter and PIK3CA mutations were reported to be associated with highly aggressive behavior or tumorigenesis in meningioma.…”

Section: Discussionmentioning

confidence: 99%

Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system

et al. 2016

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Recent genetic analyses using next-generation sequencers have revealed numerous genetic alterations in various tumors including meningioma, which is the most common primary brain tumor. However, their use as routine laboratory examinations in clinical applications for tumor genotyping is not cost effective. To establish a clinical sequencing system for meningioma and investigate the clinical significance of genotype, we retrospectively performed targeted amplicon sequencing on 103 meningiomas and evaluated the association with clinicopathological features. We designed amplicon-sequencing panels targeting eight genes including NF2 (neurofibromin 2), TRAF7, KLF4, AKT1, and SMO. Libraries prepared with genomic DNA extracted from PAXgenefixed paraffin-embedded tissues of 103 meningioma specimens were sequenced using the Illumina MiSeq. NF2 loss in some cases was also confirmed by interphase-fluorescent in situ hybridization. We identified NF2 loss and/or at least one mutation in NF2, TRAF7, KLF4, AKT1, and SMO in 81 out of 103 cases (79%) by targeted amplicon sequencing. On the basis of genetic status, we categorized meningiomas into three genotype groups: NF2 type, TRAKLS type harboring mutation in TRAF7, AKT1, KLF4, and/or SMO, and 'not otherwise classified' type. Genotype significantly correlated with tumor volume, tumor location, and magnetic resonance imaging findings such as adjacent bone change and heterogeneous gadolinium enhancement, as well as histopathological subtypes. In addition, multivariate analysis revealed that genotype was independently associated with risk of recurrence. In conclusion, we established a rapid clinical sequencing system that enables final confirmation of meningioma genotype within 7 days turnaround time. Our method will bring multiple benefits to neuropathologists and neurosurgeons for accurate diagnosis and appropriate postoperative management.

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Prognostic Factors for Survival in Patients with High-Grade Meningioma and Recurrence-Risk Stratification for Application of Radiotherapy

Cited by 20 publications

References 20 publications

Prognostic factors of microsurgical treatment of intracranial meningiomas – A multivariate analysis

Prognostic factors of microsurgical treatment of intracranial meningiomas – A multivariate analysis

Microvascularization of Grade I meningiomas: effect on tumor volume, blood loss, and patient outcome

Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system

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