Long-term outcomes of multimodality management for parasagittal meningiomas.

PURPOSE: The aim of this study was to systematically analyze the clinical characteristics of a large cohort of parasagittal meningioma (PM) and to evaluate the patients' outcomes and best treatment strategies based on tumor features. METHODS: To minimize selection bias we performed a single-institutional review of PM with restricted criteria. One hundred and ninety-two consecutive patients who met criteria for inclusion were reviewed from 2003 to 2011 in our general hospital. RESULTS: A total of 131 cases (68.2%) were with WHO grade I, while grade II and grade III PMs constituted 40 (20.8%) and 21 cases (10.9%). Higher histological grade was associated with loss of trimethylation of H3K27 (P = 0.000). For WHO grade I PMs, GTR was significantly associated with a better PFS (P = 0.023); however, adjuvant radiotherapy did not benefit patients with STR (P = 0.215). For de novo high-grade (WHO grade II and III) PMs (n = 37), adjuvant radiotherapy was associated with a significantly longer OS (P = 0.013), while no difference was observed between GTR and STR (P = 0.654). In recurrent high-grade PM patients (n = 24), GTR combined with adjuvant radiotherapy increased PFS (P = 0.005). CONCLUSIONS: This study demonstrated that PMs were a heterogeneous group of tumors with a high proportion of high-grade tumors that often displayed aggressive clinical behaviors. Low-grade PM benefited from radical resection, whereas high-grade de novo PM did not. Adjuvant radiotherapy significantly prolonged OS for high-grade primary PM, but did not impact survival of patients with subtotally resected low-grade tumors. Long-term outcome of high-grade recurrent PMs was dismal. We thus show that extent of tumor resection, tumor grade and tumor recurrent status inform therapeutic decisions for PMs.

The diagnostic value of texture analysis in predicting WHO grades of meningiomas based on ADC maps: an attempt using decision tree and decision forest.

OBJECTIVES: The preoperative prediction of the WHO grade of a meningioma is important for further treatment plans. This study aimed to assess whether texture analysis (TA) based on apparent diffusion coefficient (ADC) maps could non-invasively classify meningiomas accurately using tree classifiers. METHODS: A pathology database was reviewed to identify meningioma patients who underwent tumour resection in our hospital with preoperative routine MRI scanning and diffusion-weighted imaging (DWI) between January 2011 and August 2017. A total of 152 meningioma patients with 421 preoperative ADC maps were included. Four categories of features, namely, clinical features, morphological features, average ADC values and texture features, were extracted. Three machine learning classifiers, namely, classic decision tree, conditional inference tree and decision forest, were built on these features from the training dataset. Then the performance of each classifier was evaluated and compared with the diagnosis made by two neuro-radiologists. RESULTS: The ADC value alone was unable to distinguish three WHO grades of meningiomas. The machine learning classifiers based on clinical, morphological features and ADC value could achieve equivalent diagnostic performance (accuracy = 62.96%) compared to two experienced neuro-radiologists (accuracy = 61.11% and 62.04%). Upon analysis, the decision forest that was built with 23 selected texture features and the ADC value from the training dataset achieved the best diagnostic performance in the testing dataset (kappa = 0.64, accuracy = 79.51%). CONCLUSIONS: Decision forest with the ADC value and ADC map-based texture features is a promising multiclass classifier that could potentially provide more precise diagnosis and aid diagnosis in the near future. KEY POINTS: • A precise preoperative prediction of the WHO grade of a meningioma brings benefits to further treatment plans. • Machine learning models based on clinical, morphological features and ADC value could achieve equivalent diagnostic performance compared to experienced neuroradiologists. • The decision forest model built with 23 selected texture features and the ADC value achieved the best diagnostic performance (kappa = 0.64, accuracy = 79.51%).

Clinical and prognostic features of spinal meningioma: a thorough analysis from a single neurosurgical center.

PURPOSE: The aim of this study was to thoroughly analyze the clinical characteristics of a large cohort of spinal meningioma (SM) from a single neurological center and identify risk factors associated with worse progression free survival and neurological function outcome. METHODS: Clinical information was retrieved from 483 SM and 9806 cranial meningioma cases who were operated in our center between 2003 and 2013. 194 SM patients who were followed at the main branch were used for prognostic analyses that included both recurrence free survival and neurological functions based on Modified McCormick scale (MMS). RESULTS: Females were predominant (P < 0.001). High grade tumors were not common (WHO grade II, 2.9%; grade III, 1.7%), while the clear cell subtype was frequent within grade II SMs (6/14, 42.9%). Macroscopic total resection was achieved in all SMs (Simpson grade I, 30.9%; grade II, 65.5%; grade III, 3.6%) with a low complications rate (4.6%) and provided neurological improvement in 80 patients (41.2%). Recurrence was seen in 9 cases (4.6%) and associated with high WHO grade, male, prior recurrence, and Simpson grade III. High WHO grade and high Ki-67 index were identified to be independent factors predictive of both neurological function deterioration and impaired post-operative neurological status. CONCLUSIONS: Our analysis of the largest SM cohort in scale from a single institution offers a comprehensive view of the clinical characteristics of surgically treated SM, revealing the distinct biology of SM in comparison to its cranial counterparts, and providing guidance to improve surgical management of SM.

Evaluation of the applicability of territorial arterial spin labeling in meningiomas for presurgical assessments compared with 3-dimensional time-of-flight magnetic resonance angiography.

OBJECTIVES: To prospectively evaluate the application of territorial arterial spin labelling (t-ASL) in comparison with unenhanced three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) in the identification of the feeding vasculature of meningiomas. METHODS: Thirty consecutive patients with suspected meningiomas underwent conventional MR imaging, unenhanced 3D-TOF-MRA and t-ASL scanning. Four experienced neuro-radiologists assessed the feeding vessels with different techniques separately. RESULTS: For the identification of the origin of the feeding arteries on t-ASL, the inter-observer agreement was excellent (к = 0.913), while the inter-observer agreement of 3D-TOF-MRA was good (к = 0.653). The inter-modality agreement between t-ASL and 3D-TOF-MRA for the feeding arteries was moderate (к = 0.514). All 8 patients with motor or sensory disorders proved to have meningiomas supplied completely or partially by the internal carotid arteries, while all 14 patients with meningiomas supplied by the external carotid arteries or basilar arteries didn't show any symptoms concerning motor or sensory disorders (p = 0.003). CONCLUSION: T-ASL could complement unenhanced 3D-TOF-MRA and increase accuracy in the identification of the supplying arteries of meningiomas in a safe, intuitive, non-radioactive manner. The information about feeding arteries was potentially related to patients' symptoms and pathology, making it more crucial for neurosurgeons in planning surgery as well as evaluating prognosis. KEY POINTS: • A comprehensive understanding of feeding vasculature is helpful for optimized treatment decisions. • T-ASL could identify main supplying arteries of meningiomas with excellent inter-observer agreement. • The inter-modality agreement for identification of the main feeding arteries was moderate. • Blood supply from ICAs was related to motor or sensory disorders. • High-level meningiomas were found to have double main supplying arteries.

Combination of Contrast-enhanced FlAIR and Contrast-enhanced T1WI: A Quick and Efficient Method in Detecting Brain Metastases of Lung Cancers.

BACKGROUND: Some patients with suspected brain metastases (BM) could not tolerate longer scanning examinations according to the standardized MRI protocol. OBJECTIVE: The purpose of this study was to evaluate the clinical value of contrast-enhanced fast fluid-attenuated inversion recovery (CE FLAIR) imaging in combination with contrast-enhanced T1 weighted imaging (CE T1WI) in detecting BM of lung cancer and explore a quick and effective MRI protocol. MATERIAL AND METHODS: In 201 patients with lung cancers and suspected BM, T1WI and FLAIR were performed before and after administration of gadopentetate dimeglumine. Two radiologists reviewed pre- and post-contrast images to determine the presence of abnormal contrast enhancement or signal intensity and decided whether it was metastatic or not on CE T1WI (Group 1) and CE FLAIR (Group 2). The number, locations and features of abnormal findings in two groups were recorded. Receiver Operating Characteristic (ROC) analyses were conducted in three groups: Group 1, 2 and 3(combination of CE FLAIR and CE T1WI). RESULTS: A total of 714 abnormal findings were revealed, of which 672 were considered as BM and 42 nonmetastatic. Superficial and small metastases(≤10mm) in parenchyma and ependyma, leptomeningeal and non-expansive skull metastases were typically better seen on CE FLAIR. The areas under ROC in the three groups were 0.720,0.887 and 0.973, respectively. Group 3 was significantly better in diagnostic efficiency of BMs than Group 1 (p<0.0001) or Group 2 (p=0.0006). CONCLUSION: The combination of CE T1WI and CE FLAIR promotes diagnostic performance and results in better observation and characterization of BM in patients with lung cancers. It provides a quick and efficient way of detecting BM.

CBX7 reprograms metabolic flux to protect against meningioma progression by modulating the USP44/c-MYC/LDHA axis.

Meningioma is one of the most common primary neoplasms in the central nervous system, whereas there is still no specific molecularly targeted therapy that has been approved for the clinical treatment of aggressive meningiomas. There is therefore an urgent demand to decrypt the biological and molecular landscape of malignant meningioma. Here, through the in-silica prescreening and 10-year follow-up of 445 meningioma patients, we uncovered that CBX7 is progressively decreased with malignancy grade and neoplasia stage in meningioma and a high CBX7 expression level predicts a favorable prognosis in meningioma patients. CBX7 restoration significantly induces cell cycle arrest and inhibits meningioma cell proliferation. iTRAQ-based proteomics analysis indicated that CBX7 restoration triggers the metabolic shift from glycolysis to oxidative phosphorylation. The mechanistic study demonstrated that CBX7 promotes the proteasome-dependent degradation of c-MYC proteins by transcriptionally inhibiting the expression of a c-MYC deubiquitinase, USP44, which attenuates c-MYC-mediated transactivation of LDHA transcripts and further inhibits glycolysis and subsequent cellular proliferation. More importantly, the functional role of CBX7 was further confirmed in both subcutaneous and orthotopic meningioma xenografts mouse models and human meningioma patients. Together, our results shed light on the critical role of CBX7 during meningioma malignancy progression and identified the CBX7/USP44/c-MYC/LDHA axis as a promising therapeutic target against meningioma progression.

TMZ-induced PrPc/par-4 interaction promotes the survival of human glioma cells.

Malignant gliomas recur even after extensive surgery and chemo-radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ), has demonstrated promising activity against gliomas, the effects last only a few months and drug resistance develops thereafter in many cases. It has been acknowledged that glioma cells respond to TMZ treatment by undergoing G2/M arrest, but not apoptosis. Here we demonstrate a phase-specific chemotherapy resistance due to cellular prion protein (PrPc) in human glioma cells upon TMZ treatment. TMZ-induced G2/M-arrested cultures show an upregulation of PrPc expression and are more resistant, whereas G1/S-phase cells that show decreased levels of PrPc are more sensitive to apoptosis. Furthermore, an investigation into the biological significance of PrPc association with par-4 provided the first evidence of a relationship between the endogenous levels of PrPc and the resistance of glioma cells to the apoptotic effects of TMZ. Upon TMZ treatment, PrPc exerts its antiapoptotic activity by inhibiting PKA-mediated par-4 phosphorylation that are important for par-4 activation, nuclear entry and initiation of apoptosis. In context with cell cycle-dependent responses to chemotherapy, the data from this study suggest the possibility of exploiting the PrPc-dependent pathway to improve the efficacy of TMZ-based regimen for patients with gliomas.

LncRNA-IMAT1 Promotes Invasion of Meningiomas by Suppressing KLF4/hsa-miR22-3p/Snai1 Pathway.

Malignant meningiomas often show invasive growth that makes complete tumor resection challenging, and they are more prone to recur after radical resection. Invasive meningioma associated transcript 1 (IMAT1) is a long noncoding RNA located on Homo sapiens chromosome 17 that was identified by our team based on absolute expression differences in invasive and non-invasive meningiomas. Our studies indicated that IMAT1 was highly expressed in invasive meningiomas compared with non-invasive meningiomas. In vitro studies showed that IMAT1 promoted meningioma cell invasion through the inactivation of the Krüppel-like factor 4 (KLF4)/hsa-miR22-3p/Snai1 pathway by acting as a sponge for hsa-miR22-3p, and IMAT1 knockdown effectively restored the tumor suppressive properties of KLF4 by preserving its tumor suppressor pathway. In vivo experiments confirmed that IMAT1 silencing could significantly inhibit the growth of subcutaneous tumors and prolong the survival period of tumor-bearing mice. Our findings demonstrated that the high expression of IMAT1 is the inherent reason for the loss of the tumor suppressive properties of KLF4 during meningioma progression. Therefore, we believe that IMAT1 may be a potential biological marker and treatment target for meningiomas.

Supratentorial hemangioblastoma.

Hemangioblastomas are extremely rare in supratentorial locations, and to date, approximately 128 cases of supratentorial hemangioblastoma have been reported in the literature. Here, we report a female case of supratentorial hemangioblastoma, not associated with von Hippel-Lindau disease. We describe its clinical, neuropathological, and neuroradiological characteristics, elaborate the surgical protocols, and follow-up methods, and review the pertinent literature.

Frontal intraparenchymal schwannoma.

A 39-year-old female had been subject to headache, and intermittent seizures for 9 years and decreasing memory for one year, without obvious neurological signs. An MRI revealed a 2x2 cm contrast-enhanced lesion in the frontal lobe, with a cyst and peritumoral edema, which was not attached to the dura or falx. Preoperatively, it was diagnosed as a glioma. Total surgical removal of the lesion led to a favorable result. Post-operative histo-pathological examination showed characteristic Antoni A and B areas consistent with intraparenchymal schwannoma. Intraparenchymal schwannoma is an extremely uncommon lesion, which is seen mostly in young adults and children. The main clinical symptoms include rising-intracranial-pressure-related manifestations and associated seizure disorders. The possible developmental origins, histological, imaging features, and protocols of treatment for this entity are discussed.

Prognostic Model That Predicts Benefits of Adjuvant Radiotherapy in Patients With High Grade Meningioma.

OBJECTIVE: Adjuvant radiotherapy is the main treatment modality for high grade meningioma after surgical resection; however, recurrence and survival outcomes vary. The aim of this study was to create a new "prognostic score" that allows personalized recommendations for post-operative adjuvant radiotherapy in patients with high grade meningioma. METHODS: Clinical data were collected from 115 patients with high grade meningioma treated with surgical resection and adjuvant radiotherapy. A prognostic model was built based on the hazards ratios of independent prognostic factors yielded by multivariate cox proportional analysis. Calibration and discrimination of the prognostic score was evaluated using good of fit test and Harrel's C index, respectively. RESULTS: A total of 115 high grade meningioma patients (72 atypical and 43 anaplastic meningiomas) were enrolled. Three factors were independently associated with progression-free survival (PFS): extent of resection (GTR vs. STR), recurrent status (de novo vs. recurrent), and Ki-67 labeling index (<5% vs. ≥ 5%). The respective ß-coefficients were used to generate the "prognostic score". The cohort was divided into low-risk and high-risk groups based on the median prognostic score. Good of fit test showed strong calibration (P = 0.7133) and Harrel's C index 0.766 indicated a strong discrimination capability of the prognostic score. The Harrel's C index for OS was 0.60. CONCLUSIONS: Our prognostic model using three basic clinical parameters robustly separated high grade meningioma patients who benefit vs. do not benefit from adjuvant radiotherapy. External validation of our model is warranted to help improve patient selection suitable for adjuvant radiotherapy.

The Diagnostic Value Of Using 18F-Fluorodeoxyglucose Positron Emission Tomography To Differentiate Between Low- And High-Grade Meningioma.

OBJECTIVE: This study aims to evaluate the potential role of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in detecting high-grade meningiomas and predicting the prognosis of patients after meningioma surgery. PATIENTS AND METHODS: A total of 124 patients met the final inclusion criterion. Tumor to gray ratio (TGR) was compared with Ki-67 labeling index, and its correlations with pre-operative neurological function and treatment status were also evaluated. Receiver-operating characteristic (ROC) curve was drawn to determine a cut-off value which could discriminate meningioma of different grades. Prognostic factors including TGR were analyzed using Kaplan-Meier survival curve and cox proportional model. RESULTS: The TGR of higher World Health Organization (WHO) grade meningioma was significantly higher than that in lower grade (p < 0.001), and it was correlated with the Ki-67 labeling index (p < 0.001, r = 0.1545). The TGR of 1.30 was the best cutoff value for the detection of high grade (WHO grade II&III) meningioma from low grade (WHO grade I) according to ROC analysis, with a sensitivity of 61.5%, the specificity of 86.7%, and accuracy of 81.5%. The TGR (p < 0.001), treatment status (p = 0.035), tumor grade (p < 0.001) and Ki-67 labeling index (p < 0.001) were significantly associated with progression-free survival (PFS). Cox proportional hazards model demonstrated that TGR (p = 0.013) was an independent prognostic factor for PFS. CONCLUSION: A high uptake of FDG was correlated with a more proliferative biological behavior and is a risk factor for tumor recurrence.

Angiomatous Meningiomas Have a Very Benign Outcome Despite Frequent Peritumoral Edema at Onset.

OBJECTIVE: Angiomatous meningioma (AM) is a rare subtype of meningioma characterized by highly vascular tumor tissue comprising predominantly variable sized hyalinized blood vessels. The aim of this study is to evaluate the clinical radiologic features of AM and the long-term prognosis in a single neurosurgical center. METHODS: A total of 93 patients who underwent surgical resection of AMs between 2003 and 2008 were enrolled for analysis. Clinical information, treatment, and radiologic images were collected and analyzed; follow-up was carried out as well. Expression of estrogen receptor, progesterone receptor, and vascular endothelial growth factor was analyzed by immunohistochemistry. RESULTS: Forty-eight females and 45 males were identified. Forty-four patients (47.31%) manifested as hypersignal in T1-weighted imaging sequences and 68 (73.12%) as hypersignal in T2-weighted imaging, and a characteristic ringlike signal was observed in 28 patients (30.11%). Eighty-one cases (87.10%) showed different degrees of peritumor brain edema and it was significantly correlated with the vascular endothelial growth factor expression (P < 0.001). Simpson I resection was achieved in 63 patients (67.74%), grade II in 27 patients (29.03%), and grade III in 3 patients (3.23%). The extent of resection was not associated with the postoperative neurologic function (P = 0.546). Only 4 patients experienced recurrences during the follow-up and these 4 patients were stable until the last follow-up. CONCLUSIONS: AMs were a special subtype of meningioma with distinctive radiologic features. AMs manifest benign behavior with a satisfying outcome, which makes Simpson grade II resection an option.

Cognitive deficits in patients with brain tumor.

OBJECTIVE: To discuss the present status and progress of clinical research on the cognitive effects caused by different types of brain tumors and common treatments. DATA SOURCES: The data used in this review were mainly from PubMed articles published in English from 1990 to Febuary 2012. Research terms were "cognitive deficits" or "cognitive dysfunction". STUDY SELECTION: Articals including any information about brain tumor related cognitive deficits were selected. RESULTS: It is widely accepted that brain tumors and related treatments can impair cognitive function across many domains, and can impact on patients' quality of life. Tumor localization, lateralization, surgery, drugs, radiotherapy and chemotherapy are all thought to be important factors in this process. However, some conflicting findings regarding brain tumor-related cognitive deficits have been reported. It can be difficult to determine the mechanism of these treatments, such as chemotherapy, antibiotics, antiepileptics, and steroids. Future research is needed to clarify these potential treatment effects. CONCLUSIONS: Cognitive function is important for patients with brain tumor. Much more focus has been paid on this field. It should be regarded as an important prognostic index for the patients with brain tumor, and neuropsychological tests should be used in regular examinations.

MicroRNA-34a: a novel tumor suppressor in p53-mutant glioma cell line U251.

BACKGROUND AND AIMS: Previous studies showed that microRNA-34 (miR-34a) family was found to be a direct target of p53, functioning downstream of the p53 pathway as tumor suppressors. MiR-34a was identified to represent the status of p53 and participate in initiation and progress of cancers. We undertook this study to investigate the role of miR-34a in glioma cells. METHODS: Expression levels of miR-34a in glioma cell lines and normal brains were detected using qRT-PCR. Human U251 glioma cells were transfected with miR-34a mimics, and the effects of miR-34a restoration were assessed by MTT assays, cell cycle analysis, caspase-3 activation, and in vitro migration and invasion assays. A computational search revealed a conserved target site of miR-34a within the 3'-untranslated region of SIRT1. Luciferase reporter assay was performed to examine the effects of miR-34a on expression of potential target gene SIRT1, and mRNA and protein expression of SIRT1 after miR-34a transfection were detected by qRT-PCR and Western blot analysis. RESULTS: MiR-34a expression was markedly reduced in p53-mutant cells U251 compared with A172 and SHG-44 cells expressing wild-type p53 and normal brains. Overexpression of miR-34a in U251 cells resulted in inhibition of cell growth and arrest in G0-G1 phase and induced apoptosis. Also, restoration of miR-34a significantly reduced in vitro migration and invasion capabilities. Reporter assays indicated that SIRT1 was a direct target of miR-34a. In U251 cells, overexpression of miR-34a decreased SIRT1 protein levels but not mRNA expressions, which demonstrated miR-34a-induced SIRT1 inhibition occurred at the posttranscriptional level. CONCLUSIONS: Our results demonstrate that miR-34a acts as a tumor suppressor in p53-mutant glioma cells U251, partially through regulating SIRT1.

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle: Case report and review of literature.

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle has been identified as a novel and distinctive type of primary central nervous system neoplasm. In this report, we present a case with RGNT arising from the right cerebellar hemisphere. A 30-year-old female patient complained of headache for a five-year duration. Preoperative MRI revealed a well-circumscribed, cystic-solid lesion with hypo-intensity on T1-weighted image, hyper-intensity on T2-weighted image, and significant dot-like enhancement after IV contrast. Gross total resection was achieved in this case via suboccipital retro-sigmoidal approach, and RGNT was confirmed in the final histopathological diagnosis. RGNT of the fourth ventricle is a rare, benign tumor with an excellent prognosis. Operation is recommended as the prior protocol of treatment, and the follow-up MRI is necessary to evaluate the long-term prognostic effects. Currently, only one case of progression or recurrence has been reported in the postoperative course.

Impaired vision associated with a solitary intracranial plasmacytoma.

Solitary intracranial plasmacytomas (SICPs) are extremely uncommon tumors in the central nervous system, and are often misdiagnosed pre-operatively. We report a patient with SICP, describe the neuroradiological and neurosurgical features and the clinical management of this patient, and review the pertinent literature.