Atypical Meningioma Research Articles

Combining FORGE Score and Histopathological Diagnostic Criteria of Atypical Meningioma Enables Risk Stratification of Tumor Progression.

More than 50% of atypical meningiomas regrow within 5 years after surgery. FORGE score is a newly created tool to estimate the MIB-1 index in cranial meningiomas. In this investigation, we aimed to assess the predictive value of the FORGE score in combination with major diagnostic criteria of atypical meningioma (brain invasion, mitotic count ≥ 4) regarding recurrence in atypical meningiomas. We included patients operated on primary atypical meningiomas in our center from 2011 to 2019. The study included 71 patients (58% women, median age 63 years). ROC curves revealed a superiority of FORGE score combined with histopathological diagnostic criteria of atypical meningioma (AT-FORGE) in the prediction of tumor progression compared to FORGE score only (AUC: 0.72; 95% CI: 0.54–0.91, cut-off: ≥5/<5, sensitivity: 75%, specificity: 78%). Patients with an AT-FORGE score ≥ 5 had a shorter time to tumor progression (32.8 vs. 71.4 months, p < 0.001) in the univariable analysis. Multivariable cox regression analysis revealed significant predictive value of Simpson grade > II, presence of multiple meningiomas and AT-FORGE score ≥ 5 for tumor progression. The combination of histopathological diagnostic criteria for atypical meningioma with FORGE score might facilitate an effective identification of patients with an atypical meningioma who have an increased risk of tumor progression.

The role of single-fraction stereotactic radiosurgery for atypical meningiomas (WHO grade II): treatment results based on a 25-year experience.

To clarify the role of stereotactic radiosurgery (SRS) for atypical meningiomas (AM). A retrospective analysis of 68 patients with AM having SRS from 1995 until 2019. Nineteen patients (28%) had undergone prior external beam radiation therapy (EBRT) (median dose, 54Gy). The median follow-up period was 52months. Eighteen (26%), 17 (25%), and 33 (49%) patients received SRS as an upfront adjuvant (≤ 6months), early salvage (7-18months), or late salvage treatment (> 18months), respectively. The 3-, 5-, and 10-year progression-free survivals (PFSs) were 52%, 35%, and 25%, respectively. The 3-, 5-, and 10-year disease-specific survivals were 85%, 78%, and 61%, respectively. Adverse radiation events (AREs) were observed in 12 patients (18%), with increased or new seizures being the most frequent complication (n = 7). Prior EBRT was associated with reduced PFS (HR 5.92, P < 0.01), reduced DSS (HR 5.84, P < 0.01), and an increased risk of ARE (HR 3.31, P = 0.04). Timing of SRS was correlated with reduced PFS for patients having early salvage treatment compared to upfront adjuvant (HR 3.17, P = 0.01) or late salvage treatment (HR 4.39, P < 0.01). PFS for patients with residual/recurrent AM remains poor despite SRS. Prior EBRT was associated with worse tumor control, higher tumor-related mortality, and an increased risk of ARE. Further study on the timing of SRS is needed to determine if upfront adjunctive SRS improves tumor control compared to salvage SRS.

Should Adjuvant Radiotherapy be Used in Atypical Meningioma (WHO Grade II) Following Gross Total Resection? A Systematic Review and Meta-Analysis

The role of adjuvant radiotherapy (RT) following gross total resection (GTR) in atypical meningioma (AM) is not well established. Non-randomized prospective trials, such as RTOG 0539, suggest to treat this group with adjuvant RT. However, it remains unclear if there is any improvement in progression free survival (PFS) and overall survival (OS) with this approach. We aim to evaluate the survival benefit of adjuvant RT in AM following GTR.We performed a systematic review and meta-analysis to aggregate the clinical outcomes of patients with AM who had undergone GTR, treated with and without adjuvant RT. We searched biomedical databases, such as Medline, EMBASE and CENTRAL, for studies published between January 1964 and February 2021. Both prospective and retrospective studies which reported the primary outcomes of 5-year PFS and 5-year OS were included. Extracted data was analyzed using random-effects meta-analysis of time to event using the DerSimonian and Laird methods.Thirteen studies, involving 1124 patients, were included in our meta-analysis. 832 (74.0%) patients were treated with GTR alone and 302 (26.9%) patients had GTR followed by adjuvant RT. Adjuvant RT was delivered as external beam RT (3D conformal RT, intensity modulated RT, fractionated stereotactic radiotherapy) in 10 (76.9%) studies. Three (23.1%) studies also included patients treated with stereotactic radiosurgery in addition to fractionated RT. Median RT dose was 59.4 Gy. Adjuvant RT resulted in an increase of 3.9 months for restricted mean PFS truncated at 60 months (95% confidence interval (CI) 0.23-7.72; P = 0.037) and a non-statistically significant 22% reduction in the hazard of disease progression or death (hazards ratio 0.78; 95% CI 0.46-1.33; P = 0.370). Restricted mean OS, truncated at 60 months, was improved with adjuvant RT by 1.1 months (95% CI 0.37-1.81; P = 0.003) and a non-significant 21% reduction in the hazard of death from any cause (HR 0.79; 95% CI 0.51-1.24; P = 0.310).The use of adjuvant RT in patients with AM who have undergone GTR improved restricted mean PFS and OS. While we await the results from ongoing randomized controlled trials, adjuvant RT should be recommended.C. Wujanto: None. Y. Soon: None. T.Y. Chan: None. B. Vellayappan: None.

Salvage Resection and Intracranial Cesium-131 Brachytherapy for Brain Tumors

Management of progressive brain tumors following high dose radiotherapy is controversial. In select cases, surgical resection can provide rapid relief of regional mass effect and edema, and highly focal adjuvant re-irradiation can be administered in the form of brachytherapy. Permanent low-dose rate cesium-131 brachytherapy may offer dosimetric and radiobiologic advantages over other isotopes. The purpose of this study was to examine the safety and efficacy of intracranial cesium-131 brachytherapy after surgical resection in a heavily pre-treated patient cohort.A retrospective chart review was conducted of all patients treated with intraoperative intracranial cesium-131 brachytherapy from an institutional database. Treatment consisted of maximal safe resection followed by implantation of suture-stranded cesium-131 seeds, maintaining approximately 10mm spacing between seeds, with a planned target dose of 80 Gy to 5mm depth. Local failure was defined as recurrence in or contacting the resection cavity after salvage resection and brachytherapy. Regional failure was defined as recurrence within 10mm of the resection cavity. Recurrence was defined as a new lesion or growth of ≥25% in any axial dimension on interval MRI. Toxicity was collected based on CTCAE 4.0.A total of 35 patients with a median imaging follow up of 17.0 months (interquartile range [IQR] 9.7-25.9) underwent 41 consecutive cesium-131 implants between 2016 and 2020. 20 patients (59%; N = 22 implants) were treated for recurrent brain metastasis, 12 patients (34%; N = 16 implants) were treated for recurrent atypical (N = 8) or anaplastic meningioma (N = 4), and 3 patients (9%) were treated for recurrent glioma (N = 2) or hemangiopericytoma (N = 1). A majority of lesions had received prior surgery (N = 28, 66.7%, range 0-3 prior surgeries) and 34 patients had received prior high dose radiation. 34 of 41 (82.9%) tumors had received prior radiosurgery, and 12 (29.2%) had undergone prior external beam radiation (range 50-60 Gy). 17 of 41 lesions (41.5%) had radiologic evidence of adverse radiation/treatment effect (ARE) prior to salvage therapy. Median tumor size was 3.0cm (IQR 2.3-3.7). Overall actuarial local/loco-regional control at 1-year was 91.6%/84.7% (89.8%/88.9% for metastases and 100%/82.5% for meningiomas). Crude loco-regional control was 86.3% for metastases, 75% for meningiomas, and 66.7% for other lesions. Symptomatic ARE following treatment was observed in 9.8% (N = 4) resection cavities. The surgical complication rate was 14.6% (N = 6 total, N = 3 [7.3%] grade 3-5) including 1 peri-operative death.Cesium-131 brachytherapy in this heavily pre-treated cohort resulted in good local control and an acceptable rate of symptomatic adverse radiation effect and toxicity and may be a reasonable treatment option for this select population.W.C. Chen: None. M. Lafreniere: None. C. Phuong: None. M. Lometti: None. O. Morin: None. B.P. Ziemer: None. H. Vasudevan: Research Grant; Children's Tumor Foundation. Patent/License Fees/Copyright; Genentech, Eli Lilly. S. Hervey-Jumper: None. P.V. Theodosopoulos: None. S. Magill: None. S.E. Fogh: Independent Contractor; Accuray. J.L. Nakamura: None. L. Boreta: None. P.K. Sneed: None. M.W. McDermott: Chair; Miami Baptist. D. Raleigh: None. S.E. Braunstein: Advisory Board; Radiation Oncology Questions, LLC.

Establishment and Validation of an Integrated Model to Predict Postoperative Recurrence in Patients With Atypical Meningioma.

BackgroundThis study aims to establish an integrated model based on clinical, laboratory, radiological, and pathological factors to predict the postoperative recurrence of atypical meningioma (AM).Materials and MethodsA retrospective study of 183 patients with AM was conducted. Patients were randomly divided into a training cohort (n = 128) and an external validation cohort (n = 55). Univariable and multivariable Cox regression analyses, the least absolute shrinkage and selection operator (LASSO) regression analysis, time-dependent receiver operating characteristic (ROC) curve analysis, and evaluation of clinical usage were used to select variables for the final nomogram model.ResultsAfter multivariable Cox analysis, serum fibrinogen >2.95 g/L (hazard ratio (HR), 2.43; 95% confidence interval (CI), 1.05–5.63; p = 0.039), tumor located in skull base (HR, 6.59; 95% CI, 2.46-17.68; p < 0.001), Simpson grades III–IV (HR, 2.73; 95% CI, 1.01–7.34; p = 0.047), tumor diameter >4.91 cm (HR, 7.10; 95% CI, 2.52–19.95; p < 0.001), and mitotic level ≥4/high power field (HR, 2.80; 95% CI, 1.16–6.74; p = 0.021) were independently associated with AM recurrence. Mitotic level was excluded after LASSO analysis, and it did not improve the predictive performance and clinical usage of the model. Therefore, the other four factors were integrated into the nomogram model, which showed good discrimination abilities in training cohort (C-index, 0.822; 95% CI, 0.759–0.885) and validation cohort (C-index, 0.817; 95% CI, 0.716–0.918) and good match between the predicted and observed probability of recurrence-free survival.ConclusionOur study established an integrated model to predict the postoperative recurrence of AM.

Pediatric meningioma with rhabdoid features developed at the site of skull fracture: illustrative case.

BACKGROUNDPediatric meningiomas are rare, and only a few cases attributed to trauma and characterized by development at the site of bone fracture have been reported. Both pediatric and traumatic meningiomas have aggressive characteristics.OBSERVATIONSAn 11-year-old boy who sustained a head injury resulting from a left frontal skull fracture 8 years previously experienced a convulsive attack. Imaging revealed a meningioma in the left frontal convexity. Total removal of the tumor with a hyperostotic section was successfully achieved. Intraoperative investigation showed tumor invasion into the adjacent frontal cortex. Histologically, the surgical specimen revealed a transitional meningioma with brain invasion and a small cluster of rhabdoid cells. This led to a final pathological diagnosis of an atypical meningioma with rhabdoid features. The postoperative course was uneventful, and no recurrence of the tumor was found after 2 years without adjuvant therapy.LESSONSThis is the first report of a pediatric meningioma with rhabdoid features occurring at the site of a skull fracture. Meningiomas that contain rhabdoid cells without malignant features are not considered to be as aggressive as rhabdoid meningiomas. However, the clinical course must be carefully observed for possible long-term tumor recurrence.

INTRAMEDULLARY THORACIC MENINGIOMA: A RARE CASE REPORT AND REVIEW OF THE LITERATURE

Only a few cases of intramedullary meningiomas in the cervical and thoracic region have been reported in the literature. We present a rare case of intramedullary meningioma in the lower thoracic region. A 68-year-old woman with complaints of back pain, gait disturbance, and paresthesias in both lower extremities for 4 months was admitted to our institution. Initially, she presented with weakness in her legs that gradually deteriorated over time. The patient had been operated on for breast cancer 2 years prior to the onset of current complaints. The neurological examination revealed spastic inferior paraparesis (McCormick grade IV), hypoesthesia below Th10 dermatome, bowel and bladder disturbances. Magnetic resonance imaging of the thoracic spine demonstrated intramedullary tumor that was hypointense on T1 and T2-weighted images but showed homogenous enhancement after gadolinium administration. After gross total resection, the histopathological examination confirmed the diagnosis of atypical intramedullary meningioma. CONCLUSION: The intramedullary meningiomas are extremely rare, but they should not be excluded from the differential diagnosis, especially in cases of intramedullary tumors with homogenous enhancement on magnetic resonance imaging. The best treatment strategy is gross total removal of the tumor.

Exploring the role of epidermal growth factor receptor variant III in meningeal tumors.

Meningioma is the second most common type of intracranial brain tumor. Immunohistochemical techniques have shown prodigious results in the role of epidermal growth factor receptor variant III (EGFR vIII) in glioma and other cancers. However, the role of EGFR vIII in meningioma is still in question. This study attempt the confer searches for the position attained by EGFR vIII in progression and expression of meningioma. Immunohistochemistry technique showed that EGFR vIII is highly expressed in benign tumors as compared to the atypical meningioma with a highly significant p-value (p<0.05). Further analysis by flow cytometry results supported these findings thus presented high intensity of EGFR vIII in low grades of meningioma. The study revealed that the significant Ki 67 values, to predictor marker for survival and prognosis of the patients. Higher expression of EGFR vIII in low grades meningiomas as compared to high-grade tumors indicate towards its oncogenic properties. To our knowledge, limited studies reported in literature expressing the EGFR vIII in meningioma tumors. Hence, Opinions regarding the role that EGFR vIII in tumorigenesis and tumor progression are clearly conflicting and, therefore, it is crucial not only to find out its mechanism of action, but also to definitely identify its role in meningioma.

Adjuvant Radiotherapy in Grade II, Atypical Meningioma of the Skull Base.

Introduction Atypical meningiomas (AM) are meningiomas that are more aggressive than their grade-I counterparts and have a higher rate of recurrence. The effect of adjuvant radiotherapy (ART) on AM of the skull base is not defined. Methods A retrospective review of all AM's of the skull base primarily resected at our institution from 1996 to 2018 was completed. ART was defined as radiotherapy (RT) that occurred within 6 months of initial resection, regardless of Simpson's grade. Minimum time length of follow-up after resection was 2 years. Statistical analysis was performed using SAS. Results There were a total of 59 skull base-located (SBL) AMs resected at our institution from 1996 to 2018. The average age of our cohort was 53.2 years. Gross total resection, defined as Simpson's grades I to III resection, was achieved in 36 (61%) of cases. Thirty-five of 59 (59%) patients received ART. Recurrence was observed in 14 patients (24%), and mean time to recurrence was 63.8 months. Patients who received ART had a lower observed rate of recurrence (8 vs. 46%); however, time to recurrence was not significantly different between the two populations. Conclusion We observe that AM in the skull base location have higher recurrence rates than we would expect from grade-I meningioma. These data suggest that ART may offer benefit to the overall observed frequency of recurrence of SBL AM; however, the time to recurrence between patients who received ART and those who did not was not statistically significant in survival analysis.

Molecular profiling of pediatric meningiomas shows tumor characteristics distinct from adult meningiomas

In contrast to adults, meningiomas are uncommon tumors in childhood and adolescence. Whether adult and pediatric meningiomas differ on a molecular level is unclear. Here we report detailed genomic analyses of 37 pediatric meningiomas by sequencing and DNA methylation profiling. Histologically, the series was dominated by meningioma subtypes with aggressive behavior, with 70% of patients suffering from WHO grade II or III meningiomas. The most frequent cytogenetic aberrations were loss of chromosomes 22 (23/37 [62%]), 1 (9/37 [24%]), 18 (7/37 [19%]), and 14 (5/37 [14%]). Tumors with NF2 alterations exhibited overall increased chromosomal instability. Unsupervised clustering of DNA methylation profiles revealed separation into three groups: designated group 1 composed of clear cell and papillary meningiomas, whereas group 2A comprised predominantly atypical meningiomas and group 2B enriched for rare high-grade subtypes (rhabdoid, chordoid). Meningiomas from NF2 patients clustered exclusively within groups 1 and 2A. When compared with a dataset of 105 adult meningiomas, the pediatric meningiomas largely grouped separately. Targeted panel DNA sequencing of 34 tumors revealed frequent NF2 alterations, while other typical alterations found in adult non-NF2 tumors were absent. These data demonstrate that pediatric meningiomas are characterized by molecular features distinct from adult tumors.

Human TERT Promoter Mutations in Atypical and Anaplastic Meningiomas.

Background: The role of telomerase reverse transcriptase (TERT) gene promoter mutations (pTERT) in atypical and anaplastic meningiomas remains controversial. This study aimed to evaluate their impact on the histologic diagnosis and prognosis in a retrospective series of 74 patients with atypical and anaplastic meningioma, including disease progression and relapse. A supplementary panel of 21 benign tumours was used as a control cohort. Materials and Methods: The mutation rate of the pTERT gene was assessed by Sanger sequencing. ATRX protein expression was detected by immunohistochemistry. The phenotypic and genotypic intra-tumour heterogeneity was studied in a sub-group of 12 cases using a Molecular Machines & Industries (MMI) CellCut laser microdissection (LMD) system. Results: pTERT mutations were detected in 12/74 (17.6%) malignant meningiomas. The mutation rate was significantly higher in anaplastic meningiomas (7/23, 30.4%) compared to atypical tumours (5/48, 10.4%) (p = 0.0443). In contrast, the mutation rate was < 5% in benign tumours. All pTERT mutant cases retained nuclear ATRX immunoreactivity. pTERT mutations were significantly associated with the histologic grade (p = 0.0443) and were adverse prognostic factors for anaplastic tumours (p = 0.06). Conclusion: We reported on the pTERT mutation spectrum in malignant meningiomas, supporting their use in the prognostic classification.

Immunohistochemical Expression of EGFR and ErbB2/ HER2 in Human Meningioma. A Clinicopathological Study

Background: meningioma is considered a common benign tumor and more frequent happen, they are slow growing primary tumors that originate from meningothelial cells of the arachnoid and spinal cord. The histological grade of the WHO and the extension of the initial surgical resection are determining prognostic factors in these tumors. Aim of the study: To investigate the expression of EGFR and ErbB2 / HER2 in human meningiomas, to correlate this expression with various clinic pathological parameters (age, gender, tumor type, tumor grade), and to study the correlation between these two markers. Methods: this is a retrospective study including 30 cases of human meningiomas. Clinical data collected from patient's files. Immunohistochemical study of EGFR and ErbB2/HER2 performed along with scoring. Results: this study included 30 cases of meningioma. There was a significant statistical correlation between tumor grade and tumor histological type, as 100% of grade II were atypical meningiomas, and 77.8% of grade I were meningiothelial meningiomas, with a P value 0.0001. 25/30 cases showed positive immunohistochemical expression of EGFR, 24/25 (96%) cases were grade I, 1/25 (4%), 16/25(72%) cases were meningiothelial, 1/25 (4%) case angiomatous, 1/25 (4%) case atypical, 5/25 (20%) cases were fibroblastic. only 4/30 cases showed expression of HER 2/ neu, 3/4(75%) cases were female, all cases were above 30 years of age, all cases were grade I, 2/4 (50%) cases were fibroblastic and the other two cases were meningiothelial type. Conclusions: EGFR is frequently over expressed in meningiomas, there was a significant difference between mean of EGFR and HER 2, EGFR have more positive results than HER 2.

Predictors of progression in radiation-induced versus nonradiation-induced pediatric meningiomas: a large single-institution surgical experience.

The goal in this study was to outline unique differences between radiation-induced and nonradiation-induced pediatric meningiomas and to identify independent risk factors of tumor recurrence/progression. This is a retrospective cohort study of all pediatric meningiomas diagnosed and surgically treated at the authors' institution between 1993 and 2017. Multivariable Cox regression was applied to identify independent risk factors for tumor recurrence/progression. Thirty-five patients were identified. The primary etiology was nonradiation-induced (n = 24: n = 3 with neurofibromatosis type 2) or radiation-induced (n = 11: acute lymphoblastic leukemia [n = 5], medulloblastoma [n = 4], germ cell tumor [n = 1], and primitive neuroectodermal tumor [n = 1]) meningioma. The mean age at time of diagnosis was 10.7 ± 5.7 years for nonradiation-induced and 17.3 ± 3.5 years for radiation-induced meningiomas. Overall, 8/24 patients with nonradiation-induced meningioma experienced either recurrence or progression of the tumor. Of the 8 patients with tumor recurrence or progression, the pathological diagnosis was clear cell meningioma (n = 3: 2 recurrent and 1 progressive); grade I (n = 2 progressive); grade I with atypical features (n = 2: 1 recurrent and 1 progressive); or atypical meningioma (n = 1 recurrent). None of the patients with radiation-induced meningioma experienced recurrence or progression. Predictors of tumor recurrence/progression by univariate analysis included age at time of diagnosis ≤ 10 years (p = 0.002), histological subtype clear cell meningioma (p = 0.003), and primary etiology nonradiation-induced meningioma (p = 0.04), and there was a notable trend with elevated MIB-1 staining index (SI) (p = 0.09). There was no significant difference between nonradiation-induced and radiation-induced meningiomas (p = 0.258), although there was a trend between recurrent and nonrecurrent meningiomas (p = 0.09). Multivariate Cox regression, adjusted for length of follow-up, identified younger age at diagnosis (p = 0.004) and a higher MIB-1 SI (p = 0.044) as independent risk factors for recurrence. Elevated MIB-1 SI statistically correlated with atypia (p < 0.001). However, there was no significant statistical correlation between tumor recurrence/progression and atypia (p = 0.2). Younger patient age and higher MIB-1 SI are independent risk factors for recurrence. Atypia was not a predictor of recurrence.

Adjuvant radiotherapy for atypical meningiomas is associated with improved progression free survival

PurposeTo assess the progression-free survival benefits of adjuvant radiotherapy (ART) following surgical resection compared to surgery alone in high-grade meningioma patients. MethodsWe retrospectively identified 43 patients with atypical meningiomas, who underwent either radiotherapy post-surgical resection (Surgery+ART) or surgery alone (Surgery alone) at our institution between February 2007 to March 2019. GTR was achieved in 28 patients, and STR, in 11. Patient, meningioma, and treatment data were extracted from records and compared using Kaplan-Meier methodology, log-rank tests, and Cox proportional hazard models. Radiation complications were also evaluated. ResultsOverall 32.6% (n = 14) of patients, 6 patients in the Surgery+ART group and 8 in the Surgery alone group, experienced recurrence. In the Surgery+ART group, the median PFS time was 46.5 months (CI: [35.8–50.6]), compared to 24.5 months (CI: [18.3–32.9]) in the Surgery alone group. 2-year PFS for Surgery+ART was 100% vs. 69.0% for Surgery alone, and the 5-year PFS rate was 70.6% and 39.2%, respectively (log-rank p-value = .004). ConclusionsOur data revealed a significant PFS increase for those treated with adjuvant radiotherapy following surgery compared to surgery alone. Future prospective studies evaluating differing radiation modalities and dosages should be conducted.

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

BackgroundAtypical 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.MethodsThe 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.ConclusionsThe 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.

Rhabdoid meningiomas: Clinicopathological analysis of a rare variant of meningioma

IntroductionRhabdoid Meningiomas (RM) are rare malignant type of meningiomas, classified as grade III in the WHO classification. Only a few case series have been reported, and factors affecting prognosis are still unclear. MethodsWe did a retrospective chart review of all the RMs diagnosed in our institute between 2007 and 2019. Demographic profile, clinical status, imaging, surgical procedures used, post-operative course, adjuvant therapy and follow-ups were reviewed. Histopathological slides were also reviewed. ResultsThere were 11 patients with RM who underwent 17 surgical procedures between them. Median age was 26 years. On imaging, four had lesions in skull base, three in convexity and four in parasagittal region. Five patients had lesions which had bled and two had leptomeningeal dissemination. Two patients underwent Simpson’s grade 1 excision, seven underwent grade 2 and one patient each underwent grade 3 and 5 excisions. One patient presented with poor sensorium and underwent surgery but ultimately succumbed. All reported patients had Rhabdoid features (>50%). Features of anaplasia were seen in four cases and atypical meningioma in others. The median progression-free-survival and overall survival was 6 months and 9 months, respectively. Female gender (n = 5; p = 0.032) and patients who received radiotherapy (p = 0.030) had a survival advantage. Location of the tumor (p = 0.43), presence of hemorrhage in the lesion (p = 0.49), grade of excision (p = 0.40) and WHO pathological grade (p = 0.11) did not have a statistically significant survival benefit. ConclusionFemale gender and adjuvant radiotherapy were associated with survival advantage in our sample. Large studies are required to establish the factors associated with survival.

Metastatic mediastinal atypical meningioma: a case report

Meningiomas are common neoplasms arising from the central nervous system meninges. Extracranial metastasis of meningiomas are rare and are usually found in less than 0.1–0.2% of cases, though isolated metastasis to the liver and lung have been reported. Because of its rarity and intriguing pathogenesis, we reported here a case of metastatic mediastinal atypical meningioma. 1.Ostrom QT, Cioffi G, Gittleman H, et al. Primary brain and other central nervous system tumours diagnosed in the US in 2012-2016. Neuro Oncol 2019; 21 (Suppl 5): v1–100.2.Miller DC, Ojemann RG, Proppe KH, et al. Benign metastasizing meningioma. Case report. J Neurosurg 1985; 62: 763–6.

Meningioma in shape

Objective: The aim of this study was to evaluate the possible relationship between the appearance of tumour margins of atypical meningiomas and the risk of tumour recurrence, as well as progression-free survival. We also evaluated the correlations between the tumour margins and the neuroimaging characteristics (e.g. brain oedema and contrast enhancement) along with pathological features (e.g. brain invasion and mean value of Ki-67 LI).&#x0D; Material and methods: In our study, we included 81 patients diagnosed with atypical meningioma (grade II meningioma), who have undergone surgery at the "Prof. Dr N. Oblu" Emergency Clinical Hospital Iasi, between January 1, 2010, and December 31, 2019. We followed the MRI imaging characteristics (e.g. tumour margins patterns, contrast enhancement, oedema grading and tumour volume), but also the pathological characteristics such as brain invasion and the mean value of the Ki-67 labelling index. The assessment of tumour recurrence was made using MRI imaging (T1+ contrast), over a follow-up period of 5 years after the surgery.&#x0D; Results: In our study, we observed that 59.3% (n=48) of meningiomas had an irregular appearance. The irregular margins predominated in the male population (65.1%) and were statistically significantly correlated with brain oedema (p&lt;0.001), contrast enhancement (p&lt;0.01), anatomical location (p&lt;0.014) and the mean value of the Ki-67 labelling index (p&lt;0.01). The tumour margins were not correlated with brain invasion or volume of meningiomas.&#x0D; Conclusion: In our series of patients we found that the irregular margin was not a prognostic factor for tumour recurrence over a period of 5 years or for progression-free survival.

Atypical meningioma: patterns of postradiotherapy recurrences

Purpose There is no consensus on a target definition and optimal dose in radiotherapy for atypical meningioma (AM). Insight into the postradiotherapy recurrence pattern is needed for optimal target definition and local control. The objective was to describe the patterns of recurrence after postoperative or salvage radiotherapy in patients with AM. Materials and methods A retrospective analysis was conducted of patients treated for intracranial AM with (fractionated) stereotactic radiotherapy (FSRT). The relationships between postradiotherapy recurrences, the dura and irradiated volume were established. Moreover, the dose prescriptions and fractionation schedules were converted to a reference to determine the relationship between dose and local control. Results The included patients received 57 (F)SRT treatments and 73 surgeries. Recurrent disease was found in 21 of 29 patients (72%) and after 39 of 57 (F)SRTs (68%). The median interval to first recurrence was 39.7 months. Of these recurrences, 25 were in-field, 11 were marginal, and 3 were out of field. In-field recurrence rates after biological equivalent doses < 60 Gy or 60 Gy were 50% and 21%. All recurrences were connected to the dura. Of the marginal recurrences, 64% were within 2 cm and 91% were within 3 cm of the volume receiving the prescribed dose. Conclusions AM frequently recurs after radiotherapy. All postradiotherapy recurrences were connected to the dura. Most marginal recurrences occurred within 3 cm of the irradiated abnormal dura. The lowest rate of in-field recurrences occurred after equivalent doses of least 60 Gy in 2 Gy fractions suggesting a dose–effect relationship.

High risk of recurrence for grade II meningioma: a 10-year multicenter analysis of prognosis factors.

Atypical meningioma is a variant of meningioma with a high risk of recurrence. Gross total resection is the standard of treatment, while no consensus on optimal adjuvant management has been found. Between 2008 and 2018, a retrospective search identified 216 grade II meningiomas treated in six centers. Clinical, histological, and therapeutic data were analyzed to determine the prognostic factors of recurrence and survival. In total, 216 patients underwent surgical resection. Among these, 122 patients (56%) underwent gross total resection, and 21% of the patients received adjuvant radiotherapy. Univariate analysis reported subtotal resection, high Ki-67, negative progesterone receptor (PR) and histological grade evolution as unfavorable prognosis factors. According to multivariate analysis, the Ki-67 proliferative index (cut-off value of 17.5%) was the only prognostic factor of recurrence (HR 1.1; 95% CI, 1.0-1.2, P=0.048). Gross total resection improved progression-free survival (PFS) (P=0.03) but without impact on overall survival (OS) (P=0.2). Median PFS and OS times were longer for patients receiving adjuvant radiotherapy than those who did not receive adjuvant radiotherapy. PFS (P=0.3) and OS (P=0.7) were associated with adjuvant RT by trend only. After a median follow-up time of 6.7 years, 99 (46%) patients relapsed. Median progression-free and OS rates were 4.5 (95% CI, 3.5-5.5) and 14.7 years (11.4-NA), respectively. In this study, Ki-67 proliferative index was significantly associated with recurrence. Gross total resection significantly improved PFS without impacting OS. Adjuvant radiotherapy delayed recurrence and improved OS, but a longer follow-up time is needed to distinguish a statistically significant difference. Large prospective studies are needed to determine postoperative treatment guidelines.