Skull Base Location Research Articles

Distinct clinical outcome of microcystic meningioma as a WHO grade 1 meningioma subtype.

To evaluate the clinicopathological characteristics, radiology, and long-term outcomes of microcystic meningiomas (MM) and compare it with other subtypes of meningiomas managed at a single neurosurgical center. A total of 87 consecutive patients who underwent surgical resection and were diagnosed as MM between 2005 and 2016 were enrolled for analysis. Clinicopathological, radiology, and prognostic information was collected and analyzed. Progression free survival (PFS) was compared with 659 patients with other subtypes of WHO grade 1 meningiomas and 167 patients with atypical meningiomas treated during the same period. Fifty six females and 31 males with MM were analyzed. Peri-tumor brain edema was frequent on T2 WI (85%).12 patients (13.8%) experienced tumor progression during the mean follow-up of 101.66 ± 40.92months. The median PFS was unavailable, and the 5, 10, and 15year progression-free rates were 96.9%, 84.0%, and 73.9%, respectively. Univariate COX analysis demonstrated skull base location and higher Ki-67 index as significant negative prognostic factors for PFS (P < 0.05); multivariate analysis identified tumor location and Ki-67 index as independent factors (P < 0.01), as well. Of note, the PFS of MM was worse than other WHO grade 1 subtypes (P < 0.001), but better than atypical meningiomas (P < 0.001), and the PFS differences were retained even when the analysis was limited to the patients receiving GTR (P < 0.05). The PFS of MM was worse than other WHO grade 1 subtypes and better than atypical meningiomas. Skull base location and higher Ki-67 index were independent negative prognostic factors in MM.

Microsurgical resection of a large petroclival meningioma via translabyrinthine approach combined with middle fossa craniotomy.

Petroclival meningiomas arise from the upper two-thirds of the clivus at the petroclival junction and are reached via various approaches. As petroclival meningiomas expand, they displace the brainstem and basilar artery toward the contralateral side. Because of their proximity to critical structures and deep skull base location, surgical treatment is challenging. Although several approaches have been introduced, their rationales vary. Herein, the authors demonstrate microsurgical resection of a large petroclival meningioma via a translabyrinthine approach combined with middle fossa craniotomy. For each approach, the pros and cons should be carefully evaluated based on the patient’s presentation and lesion characteristics.The video can be found here: https://stream.cadmore.media/r10.3171/2022.1.FOCVID21253

Risk Stratification to Define the Role of Radiotherapy for Benign and Atypical Meningioma: A Recursive Partitioning Analysis.

The role of adjuvant radiotherapy (RT) for benign or atypical meningioma is controversial. To identify prognostic factors and a subgroup that could be potentially indicated for adjuvant RT. A total of 336 patients with benign and 157 patients with atypical meningioma underwent surgical resection between January 2015 and December 2019. We retrospectively analyzed 407 patients who did not receive adjuvant RT to stratify risk groups for recurrence. A recursive partitioning analysis (RPA) with the prognostic factors for their failure-free survival (FFS) divided the patients into risk groups. The 3-year FFS with surgical resection only was 76.5%. Identified prognostic factors for FFS were skull base location, tumor size, brain invasion, a Ki-67 proliferation index of ≥5%, and subtotal resection. The RPA-classified patients were divided into 4 risk groups: very low, low, intermediate, and high, and their 3-year FFS were 98.9%, 78.5%, 59.8%, and 34.2%, respectively. Intermediate-risk and high-risk groups comprise the patients with meningioma of sizes ≥2 cm after subtotal resection or meningioma of sizes >3 cm, located in the skull base or with brain invasion, respectively. After combining with patients treated with adjuvant RT, no FFS benefit was found in the very low-risk and low-risk groups after adjuvant RT, whereas significantly improved FFS was found in the intermediate-risk and high-risk groups (P < .05). The RPA classification revealed a subgroup of patients who could be potentially indicated for adjuvant RT even after gross total resection or for whom adjuvant RT could be deferred.

517 Metastasis in High-Grade Meningioma: A Systematic Review of Incidence and Risk Factors

INTRODUCTION: Meningioma is the most common primary tumor of the central nervous system and has relatively good outcomes. Rarely, meningiomas metastasize and greatly reduce the likelihood of survival. Due to its infrequency, there is little information available to inform physicians whether a meningioma patient is at-risk for experiencing metastasis. METHODS: We searched PubMed, Scopus, Embase, and Ovid for studies with intracranial meningiomas metastasizing to non-CNS locations. Case reports and studies with metastasis to the spinal cord were excluded. Primary tumors were characterized based on location, recurrence, histological grade, patient sex, and overall survival. RESULTS: Our database search yielded 1,002 unique articles, of which 5 were included in the final review. The studies yielded a total of 480 patients with high-grade meningioma. Overall, there were 21 patients from this cohort that suffered metastasis of their primary tumor (4.38%). The majority of metastatic patients were female (61.1%), and 18 of the 21 patients experienced recurrence of their primary tumor, along with metastasis (85.7%). Multiple risk factors were individually analyzed by studies, including skull base location, sinus invasion, and molecular characteristics. CONCLUSION: Metastatic meningioma is a rare occurrence but greatly reduces the survival of meningioma patients. Due to its infrequent incidence, there is a paucity of literature comparing risk factors for metastasis to guide clinical decision-making. Our study summarizes the current literature available on the overall incidence of metastasis in high-grade meningiomas and highlights multiple risk factors that future studies should characterize to provide a more comprehensive understanding of this rare pathology.

The applicability of established clinical and histopathological risk factors for tumor recurrence during long-term postoperative care in meningioma patients

Risk factors to predict late-onset tumor recurrence in meningioma patients are urgently needed to schedule control intervals during long-term follow-up. We therefore analyzed the value of established risk factors for postoperative meningioma recurrence for the prediction of long-term prognosis. Correlations of clinical and histopathological variables with tumor relapse after 3, 5, and 10 years following microsurgery were analyzed in uni- and multivariate analyses, and compared to findings in the entire cohort. In the entire cohort (N = 1218), skull base location (HR: 1.51, 95%CI 1.05–2.16; p = .026), Simpson ≥ IV resections (HR: 2.41, 95%CI 1.52–3.84; p < .001), high-grade histology (HR: 3.70, 95%CI 2.50–5.47; p < .001), and male gender (HR: 1.46, 95%CI 1.01–2.11; p = .042) were independent risk factors for recurrence. Skull base location (HR: 1.92, 95%CI 1.17–3.17; p = .010 and HR: 2.02, 95%CI 1.04–3.95; p = .038) and high-grade histology (HR: 1.87, 95%CI 1.04–3.38; p = .038 and HR: 2.29, 95%CI 1.07–4.01; p = .034) but not subtotal resection (HR: 1.53, 95%CI .68–3.45; p = .303 and HR: 1.75, 95%CI .52–5.96; p = .369) remained correlated with recurrence after a recurrence-free follow-up of ≥ 3 and ≥ 5 years, respectively. Postoperative tumor volume was related with recurrence in general (p < .001) but not beyond a follow-up of ≥ 3 years (p > .05). In 147 patients with a follow-up of ≥ 10 years, ten recurrences occurred and were not correlated with any of the analyzed variables. Skull base tumor location and high-grade histology but not the extent of resection should be considered when scheduling the long-term follow-up after meningioma surgery. Recurrences ≥ 10 years after surgery are rare, and predictors are lacking.

Osteological studies of skull base neurovascular area in reference to infratemporal approach to skull basec

Surgical approaches to the lateral skull base often lead to tearing of vessels and piecemeal removal of the tumour. This study is aimed to delineate exact relationship of the various foramina at the lateral skull base. The coronal dimensions of the jugular foramina are larger as compared to sagittal with right sided dominance also noticed in the case of carotid canal. The width of “Keel” separating the carotid and jugular foramina normally varies from 0.4 to1.4 centimetres and may not always suggest the erosion of the foramen of skull base scans, unless the erosion is associated with irregularity or demineralization the thickness of this keel really depends upon relative size of the vessels and location of foramina. Area between stylomastoid foramen, carotid canal and jugular foramen is roughly wedge shaped. The angle subtended by carotid and jugular at the stylomastoid foramen is about 36.84whereas the location of stylomastoid foramen and internal carotid axis pose an angle of 83:16. The angle subtended by stylomastoid and jugular at carotid on an average 59:31. The space between these structures is measured to be 0.642centimetres which can be verified on tomograms. By using these measurements, the precise location of the upper end of the vessels could be predicted, whereas the superior stump could be clamped with minimal exposure of the skull base and identification and location of the last four cranial nerves is found out. This could avoid injuries and subsequent morbidity while carrying out surgery in this region.

Preliminary report of patients with meningiomas exposed to Cyproterone Acetate, Nomegestrol Acetate and Chlormadinone Acetate – Monocentric ongoing study on progestin related meningiomas

IntroductionThe relationship between meningioma and progestins has not been elucidated. Meningioma regression after acetate cyproterone (CA) withdrawal has been reported. Our purpose was to evaluate the meningioma evolution after withdrawal of progestins in patients who underwent long-term exposure to CA, nomegestrol acetate (NA), chlormadinone acetate (ChlA). MethodsOur study retrospectively included 69 patients with intracranial meningioma and exposed to one of these 3 progestins between December 2006 and March 2019. In each patient, clinico-radiological (MRI) follow-up was performed every 6 months after diagnosis and treatment withdrawal recommendation. Statistical analyses were applied to compare tumor location and respect of prescription rules between the 3 groups. ResultsThe mean hormonal exposure was 16 years in CA group (n = 46), 16 years in NA group (n = 12) and 9.7 years in ChlA group (n = 11). A higher rate of “out of label” use was observed in the CA group (p = 0.003). Multiple meningiomas were demonstrated in more than 60% of cases in each group. Anterior skull base location was noted in 60.5% of cases in CA group, 25% of cases in NA group and 36.7% of cases in ChlA group (p = 0.05). Incomplete tumor regression was recorded in 11 cases of CA group and in 2 cases of ChlA group. ConclusionIn CA group, our results suggest a strong relationship between this treatment and development of intracranial meningioma. In presence of voluminous asymptomatic meningioma, treatment can be delayed due to the potential regression after withdrawal. On the contrary in NA and ChlA groups, further studies are needed.

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.

P14.02 The Natural History of a Residual Intracranial Meningioma- Volumetric Growth and Predictors of Progression

Abstract BACKGROUND Resection of meningioma leaves residual solid tumour in ~25% of patients. Selection for further treatment and follow-up strategy may benefit from knowledge of volumetric growth and associated prognostic factors. MATERIAL AND METHODS Growth rates were assessed using a linear mixed effects model, in a retrospective adult cohort that underwent subtotal resection of meningioma (2004–2018). Endpoints were re-treatment, end of follow-up or death. Cox regression analysis was used to identify prognostic factors for progression, defined using the Response Assessment in Neuro-Oncology (RANO) volumetric criteria. RESULTS 236 patients were included. Mean age at surgery was 56.3 years (SD=13.7) and 73.7% were female. WHO grades were 1 (n=195, 82.6%), 2 (n=40, 16.9%) and 3 (n=1, 0.5%). Adjuvant fractionated radiotherapy (fRT) was administered to 34 patients (14.4%), with no propensity towards higher WHO grade or residual volume. Median pre-operative meningioma and post-operative residual volumes were 34.0cm3 (IQR 16.0–63.0) and 2.0cm3 (IQR 0.8–5.2), respectively. Median follow-up was 64 months (IQR 42–104). Median absolute growth rate (AGR) and relative growth rate (RGR) were 0.1cm3/year and 4.3%/year, respectively. According to RANO criteria, 132 (55.9%) patients progressed, of which 13 (9.8%) developed symptoms. Median progression-free survival was 56 months (95% CI 43.1–69.0). Multivariable analysis identified adjuvant fRT (HR 1.7, [95% CI 1.0–2.8], P=0.046), skull base location (HR 1.5, [95% CI 1.0–2.4], P=0.047) and Ki-67 index (HR 3.7 [95% CI 1.3–10.8], P=0.017) as prognostic factors for volumetric progression. WHO grade was not significant (HR 1.0, [95% CI 0.5–1.7], P=0.905). Forty-nine patients who progressed (37.1%) underwent further treatment: fRT (n=19), re-operation (n=15), Stereotactic radiosurgery (SRS) (n=10) and surgery+adjuvant fRT (n=5). Of those, 8 (16.3%) progressed further (after re-operation [n=6] and SRS [n=2]). Seven were treated with a 2nd re-operation (n=3), fRT (n=3), and SRS (n=1). One patient progressed after a 2nd reoperation and was treated with SRS, after which they remained stable. Median survival was not reached. 5- and 10-year overall survival (OS) was 96% and 86% respectively. CONCLUSION Growth rates of a residual meningioma vary with a dichotomy observed in progression rates. Half of patients with a residual meningioma showed radiological progression requiring multiple treatment to control the tumour. The other half demonstrate a more indolent course. Skull base location and higher Ki67 are important prognostic factors for progression and therefore, should be considered to stratify patients for adjuvant radiotherapy.

The risks factor of recurrence after skull base hemangiopericytoma management: A retrospective case series and review of literature

ObjectivesSkull base hemangiopericytomas are rare malignant meningothelial tumors involving anterior, middle, and posterior cranial fossa. The outcome of these tumors is inferior due to aggressive behavior and local recurrence. The study aimed to find out the factors affecting the early recurrence and the late recurrence. MethodologyA retrospective study was performed over 15 years, and patients were included from a single neurosurgical unit. A total of 35 patients were recruited for analysis. ResultsTwenty-five (71.4%) cases were in the posterior fossa, four (11.4%) cases in the middle cranial fossa, and three (8.6%) patients in the anterior cranial fossa. Fourteen (40%) cases underwent gross total excision, 21(60%) cases subtotal excision. Follow up available for 32 patients, and the median follow -up duration was 64 months (6–240 months). Progression-free survival for the gross total resection group was 104 months compared to 60 months for subtotal resection (p = 0.07). Nineteen (54.3%) cases had recurrence during follow- up period. Six (17.1%) cases recurrence at 1-year time, five (14.3%) cases at 3-year time, three (8.6%) at 5-yr time, four (11.4%) cases at 10- year time. Seventeen (48.6%) cases received radiotherapy, and 13 cases underwent re-exploration and excision of the tumor. Univariate ordinal logistic regression showed that the extent of resection was associated with 1-year, 3-year and 5-year recurrence. Multivariate ordinal logistic regression showed that only extent of resection (STR) was associated with both early and late recurrence. ConclusionsThe extent of resection is the main predictor of early and delayed recurrence. Upfront radiation therapy has superior tumor control in skull base location.

Prognostic value of the Simpson grading scale in modern meningioma surgery: Barrow Neurological Institute experience.

Recently, the prognostic value of the Simpson resection grading scale has been called into question for modern meningioma surgery. In this study, the authors analyzed the relationship between Simpson resection grade and meningioma recurrence in their institutional experience. This study is a retrospective review of all patients who underwent resection of a WHO grade I intracranial meningioma at the authors' institution from 2007 to 2017. Binary logistic regression analysis was used to assess for predictors of Simpson grade IV resection and postoperative neurological morbidity. Cox multivariate analysis was used to assess for predictors of tumor recurrence. Kaplan-Meier analysis and log-rank tests were used to assess and compare recurrence-free survival (RFS) of Simpson resection grades, respectively. A total of 492 patients with evaluable data were included for analysis, including 394 women (80.1%) and 98 men (19.9%) with a mean (SD) age of 58.7 (12.8) years. The tumors were most commonly located at the skull base (n = 302; 61.4%) or the convexity/parasagittal region (n = 139; 28.3%). The median (IQR) tumor volume was 6.8 (14.3) cm3. Simpson grade I, II, III, or IV resection was achieved in 105 (21.3%), 155 (31.5%), 52 (10.6%), and 180 (36.6%) patients, respectively. Sixty-three of 180 patients (35.0%) with Simpson grade IV resection were treated with adjuvant radiosurgery. In the multivariate analysis, increasing largest tumor dimension (p < 0.01) and sinus invasion (p < 0.01) predicted Simpson grade IV resection, whereas skull base location predicted neurological morbidity (p = 0.02). Tumor recurrence occurred in 63 patients (12.8%) at a median (IQR) of 36 (40.3) months from surgery. Simpson grade I resection resulted in superior RFS compared with Simpson grade II resection (p = 0.02), Simpson grade III resection (p = 0.01), and Simpson grade IV resection with adjuvant radiosurgery (p = 0.01) or without adjuvant radiosurgery (p < 0.01). In the multivariate analysis, Simpson grade I resection was independently associated with no tumor recurrence (p = 0.04). Simpson grade II and III resections resulted in superior RFS compared with Simpson grade IV resection without adjuvant radiosurgery (p < 0.01) but similar RFS compared with Simpson grade IV resection with adjuvant radiosurgery (p = 0.82). Simpson grade IV resection with adjuvant radiosurgery resulted in superior RFS compared with Simpson grade IV resection without adjuvant radiosurgery (p < 0.01). The Simpson resection grading scale continues to hold substantial prognostic value in the modern neurosurgical era. When feasible, Simpson grade I resection should remain the goal of intracranial meningioma surgery. Simpson grade IV resection with adjuvant radiosurgery resulted in similar RFS compared with Simpson grade II and III resections.

Clinical application of 3D virtual and printed models for cerebrovascular diseases

ObjectiveThree-dimensional (3D) printing techniques are rapidly advancing in the medical industry and in clinical practice. We aimed to evaluate the usefulness of 3D virtual and printed models of 6 representative cerebrovascular diseases using the software we developed. MethodsSix cases consisted of 4 intracranial aneurysms (IAs) including complex ones with intrasaccular thrombosis, large size and a skull base location; 1 cavernous malformation in the pons; and 1 arteriovenous malformation in the parietal lobe. The 3D modeling process was performed retrospectively in 3 cases and prospectively in 1 IA. Segmentation of raw data and rendering and modification for 3D virtual models were processed mostly automatically. ResultsMost intracranial structures were satisfactorily made, including the skull, brain, vessels, thrombus, tentorium and major cranial nerves. Based on 3D modeling, surgical plan was changed in 1 prospective IA case. However, it was still difficult to discriminate small vessels and cranial nerves, to feel a realistic tactile sense and to directly perform presurgical simulations, such as dissection, removal, clipping and microanastomosis. ConclusionsThe 3D modeling was thought to be very helpful in experiencing the operative views from various directions in advance, in selecting an appropriate surgical approach, and in educating physicians and patients. With advancements in radiological resolution, processing techniques and material properties, 3D modeling is expected to simulate real brain tissues more closely.

Meningiomas in patients with long-term exposition to progestins: Characteristics and outcome

ObjectiveThe aim of this study was to describe progestin-associated meningiomas’ characteristics, outcome and management. Material and methodsWe included 53 patients operated on and/or followed in the department for meningioma with progestin intake longer than one year and with recent drug discontinuation. ResultsCyproterone acetate (CPA), nomegestrol acetate (NomA), and chlormadinone acetate (ChlA) were involved in most cases. Mean duration of progestin drugs intake was 17.5 years. Tumors were multiple in 66% of cases and were located in the anterior and the medial skull base in 71% of cases. Transitional subtype represented 16/25 tumors; 19 meningiomas were WHO grade I and 6 were grade II. The rate of transitional subtype and skull base location was significantly higher compared to matched operated meningioma general population. No difference was observed given WHO classification. But Ki67 proliferation index tends to be lower and 5/6 of the WHO grade II meningiomas were classified as WHO grade II because of brain invasion. Strong progesterone receptors expression was observed in most cases. After progestin discontinuation, a spontaneous visual recovery was observed in 6/10 patients. Under CPA (n=24) and ChlA/NomA (n=11), tumor volume decreased in 71% and 18% of patients, was stabilized in 25% and 64% of patients, and increased in 4% and 18% of patients, respectively. Volume outcome was related to meningioma location. ConclusionsOutcome at progestins discontinuation is favorable but different comparing CPA versus ChlA-NomA and comparing tumor location. Long-term follow-up is required. In most cases, simple observation is recommended and surgery should be avoided.

Atypical Histological Features as Risk Factors for Recurrence in Newly Diagnosed WHO Grade I Meningioma.

The significance of atypical histological features (AHF) as risk factors for recurrence in benign meningioma is not well understood. This study examined risk factors of World Health Organization (WHO) Grade I meningioma (GIM) recurrence, focusing on AHF. We investigated 150 consecutive newly diagnosed GIM patients who had more than one year of follow-up after resection in our hospital between January 2007 and March 2018. The following factors were reviewed retrospectively: age, sex, tumor location, extent of resection, MIB-1 index, mitotic figures, number and distribution of AHF, and recurrence. The patients were grouped according to the presence or absence of recurrence and comparatively examined. Recurrence was observed in 10 cases (6.7%). Univariate analysis showed that patients with recurrence had a significantly higher MIB-1 index (2.0 vs. 4.3; p = 0.006) and a significantly higher proportion of male patients (21.4% vs. 70.0%; p = 0.002) and patients with sheet-like growth (6.42% vs. 30.0%; p = 0.04). In multivariate analysis, skull base location (odds ratio [OR] 31.424; 95% confidence interval [CI] 1.74–569), gross total resection (OR 0.130; 95% CI 0.0189–0.897), and MIB-1 index (OR 1.939; 95% CI 1.19–3.15) were significantly associated with recurrence. Our study revealed that skull base location, subtotal resection, and high MIB-1 index were independent risk factors for recurrence. Only the presence of sheet-like growth had a significantly higher incidence in patients with recurrence in univariate analysis of AHF. Multivariate analysis found no significant association. Sheet-like growth may be involved in malignancy and recurrence of benign meningioma.

Histological transformation in recurrent WHO grade I meningiomas

Atypical or malignant transformation (AT/MT) has been described in WHO grade I meningiomas. Our aim was to identify predictive factors of AT/MT at recurrence. A total of N = 15 WHO grade increases were observed in N = 13 patients (0.96% of the study population, risk of transformation of 0.12% per patient-year follow-up). Patients with and without progression at recurrence were similar regarding age, gender distribution, skull-base location, bone infiltration, and Simpson grades. Recurrence-free survival was lower in patients with transformation (5 ± 4.06 years versus 7.3 ± 5.4 years; p = 0.03). Among patient age, gender, skull base location, extent of resection or post-operative RT, no predictor of AT/MT was identified, despite a follow-up of 10,524 patient-years. The annual risk of transformation of WHO grade I meningiomas was 0.12% per patient-year follow-up. Despite the important number of patients included and their extended follow-up, we did not identify any risk factor for transformation. A total of 1,352 patients with surgically managed WHO grade I meningioma from a mixed retro-and prospective database with mean follow-up of 9.2 years ± 5.7 years (0.3–20.9 years) were reviewed. Recurring tumors at the site of initial surgery were considered as recurrence.

Benefits of re-do surgery for recurrent intracranial meningiomas

Meningiomas are the most common intracranial extra-axial tumor. While the literature is abundant on the therapeutic management of meningioma recurrence after the initial surgery, the natural history of repeated recurrences is poorly described, as well as and their respective management. A partly retrospective, partly prospective review was conducted in a Norwegian cohort of 1469 consecutive cases of meningioma surgically treated, totaling 11 414 patient-years of follow-up. 114 recurrences (7.7%) were treated surgically with a risk a surgical retreatment of 1% per patient-year of follow-up. 36 patients were operated on 3 times or more. The time-to-retreatment (TTR) decreased significantly and steadily between surgeries, from 4.3 ± 4 years after the first surgery to 2.4 ± 2.9 years after the third surgery. The primary driver for recurrence was the WHO grade (OR 7.13 [4.40;11.55], p < 0.001 for the first recurrence and OR 4.13 [1.49;12.15], p 0.008 for the second), the second predictive factor being a skull base location (OR 2.76 [1.95;3.99] p < 0.001 and OR 0.24 [0.09;0.65], p0.006 respectively). The rates of postoperative hematomas and infections were not influenced by the number of surgeries, whereas the rate of postoperative neurological worsening increased from 3.9% to 16.6% and 13.9%, respectively, after the first, second, and third surgeries. We observed that the TTR decreased significantly between surgeries in patients requiring repeated resections, indicating that surgical treatment of recurrences does not reset the clock but is indeed a “race against time”. This should be considered when assessing the benefit-to-risk ratio of patients undergoing repeated surgeries for a recurrent meningioma.

Hydrocephalus Following Giant Transosseous Vertex Meningioma Resection

Introduction Meningiomas are among the most common primary intracranial tumors. While well-described, there is limited information on the outcomes and consequences following treatment of giant-sized vertex-based meningiomas. These meningiomas have specific risks and potential complications due to their size, location, and involvement with extracalvarial soft tissue and dural sinuses. Herein, we present four giant-sized vertex transosseous meningioma cases with involvement and occlusion of the sagittal sinus, that postoperatively developed external hydrocephalus and ultimately required shunting. Methods A retrospective chart review identified patients with large vertex meningiomas that were: (1) large (>6 cm) with hemispheric (no skull base) location, (2) involvement of the superior sagittal sinus resulting in complete sinus occlusion, (3) involvement of dura resulting in a large duraplasty area, (4) transosseous involvement requiring a 5 cm or larger craniectomy for resection of invaded calvarial bone. Results Tumors were resected in all four cases, with all patients subsequently developing external hydrocephalus which required shunting within 2 weeks to 6 months postsurgery. Conclusion We believe this may be the first report of the development of hydrocephalus following surgical resection of these large lesions. Based on our observations, we propose that a combination of superior sagittal sinus occlusion and changes in brain elasticity and compliance affect the brain's CSF absorptive capacity, which ultimately lead to hydrocephalus development. We suggest that neurosurgeons be aware that postoperative hydrocephalus can quickly develop following treatment of giant-sized vertex-based meningiomas, and that correction of hydrocephalus with shunting can readily be achieved.

MNGI-05. COMBINED MULTIMODAL TREATMENT REGIMEN IN RECURRENT MENINGIOMAS

Abstract Meningiomas are the most common primary brain tumor, subsequent tumor progression can be problematic for surgical treatment options based upon location. Currently there is limited activity of various single agent medical therapies. We evaluated a combined treatment modality in recurrent Meningiomas. Patients were consented to NOC study protocol JWCI-17–0401 in this retrospective analysis. Treatment consisted of combination Octreotide LAR, Everolimus, Hydroxyurea, and Mifepristone. Patient characteristics in the combined treatment meningioma group (n=12) had a median age 60, 50% male, 47% WHO grade I, 37% WHO grade II, 11% WHO grade III, 67% skull base location, median number of recurrences is 2.2, with median number of surgeries of 1.7. Total comparison meningioma patients (n=19) with median age 62, 42% male, 42% WHO grade I, 50% WHO grade II, 17% WHO grade III, 58% skull base location, median number of recurrences is 2.2, with median number of surgeries of 2.2. Median PFS in recurrence prior to initiation of multimodal combined therapy, mPFS=283 days. Median PFS with subsequent multimodal combined therapy, mPFS=318 days. Multimodal therapy may prolong mPFS in recurrent meningiomas. Our pilot data supports further clinical trials in combined multimodal treatments.

MNGI-09. MENINGIOMA WITH MULTIPLE DRIVERS: GENOMIC LANDSCAPE AND CLINICAL CORRELATIONS

Abstract BACKGROUND Previous studies have established several meningioma genomic subgroups, defined by the mutually exclusive genomic drivers. However, we distinguished a small subset of meningiomas simultaneously harboring multiple drivers from different genomic subgroups, thus referred to as “multiple-driver meningiomas”, that has not been previously investigated. We aimed to characterize the genomic landscape and clinical features of multiple-driver meningiomas. METHODS We identified 42 cases of multiple-driver meningiomas from a cohort of 3,016 cases screened for genomic drivers via molecular inversion probe sequencing (MIPS) and/or whole-exome sequencing (WES) previously in our laboratory. All driver mutations were validated via Sanger sequencing and chromosome 22 loss was accessed with qPCR. Clinical information was collected and genome-to-clinical correlations were statistically analyzed. We selected 10 multiple-driver meningioma cases for tumor-normal WES for further characterization of genomic architecture. RESULTS Multiple-driver meningiomas were significantly enriched for NF2 alteration (p&lt; 0.001), had significantly higher WHO grade (p= 0.005) and proportion of recurrent tumors (p= 0.007) when compared with “single-driver meningiomas”, i.e. harboring driver alterations from a single genomic subgroup. Among female cases, those with multiple drivers were nearly four times more likely to be high-grade (II or III) compared to single-driver female samples (48.6% vs. 12.6%, p&lt; 0.001). Among tumors harboring NF2 alteration, multiple-driver meningiomas demonstrated skull base predilection compared with single-driver meningiomas (50.0% vs. 27.9%, p= 0.005). WES analysis of 10 multiple-driver meningiomas identified 1p and/or 14q loss in 60% of cases. Clonality analysis revealed the presence of sub-clonal cell populations in 9 cases with all driver mutations clustered into the founding clone in 7 cases, suggesting their acquisition in the early phase of tumor development. CONCLUSION Multiple-driver meningiomas demonstrate distinct genomic and clinical features that distinguish them as clinically aggressive. They frequently occur in surgically challenging skull base locations, and are more prevalent among high-grade and recurrent cases.

OS8.2 Risk stratification in chordoid meningioma depends on mutation status and epithelial differentiation

Abstract BACKGROUND Meningiomas are heterogenous tumors and their pathologic classification in the WHO Classification of Tumors of the CNS comprises 13 recognized histologic variants. Chordoid meningioma is a rare and more aggressive histologic variant of meningioma. Due to paucity of cases, the molecular profiling and patient risk stratification were not addressed in this variant. MATERIAL AND METHODS We performed an integrated clinical, NHERF1 immunohistochemical (IHC) and next generation sequencing (NGS) analysis of WHO grade II chordoid meningiomas from 30 patients (35 cases), representing the largest study to date. The NGS was performed by using a custom Agilent-generated 295-gene library containing genes with recurrent mutations in adult and pediatric, primary and metastatic brain cancer. Five of these cases cases were confirmed by performing NGS at Tempus on the xT panel containing 596 genes, and an additional 10 atypical (non-chordoid) meningioma, WHO grade II, cases were sequenced at Tempus, for comparison. RESULTS The patients with chordoid meningioma have demographic characteristics different from the general population: younger age of onset (45 vs 65), skull base (SB) location for the female patients (6:1), and increased recurrence rate (25% at 5 years). NHERF1 microlumen extent directly correlated with skull base location (p=0.0002), and segregated tumors into three cell differentiation categories -fibroblastic (13.3%), epithelial/poorly-differentiated (26.7%) and epithelial/well-differentiated (60%). NGS identified NF2 and TRAF7, as the most common mutated genes, correlating with the location and epithelial differentiation of the tumors. Mutations in AKT1, KLF4 and MN1 were found in isolated well-differentiated skull base tumors. Mutations in genes not previously involved in meningioma pathogenesis were also found. CONCLUSION The integrated tumor analysis stratified the patients into: (1) HIGH RECURRENCE RISK , characterized by tumors harboring NF2 mutations and low epithelial differentiation and (2) LOW RECURRENCE RISK , characterized by tumors exhibiting either epithelial differentiation, skull base location and TRAF7/AKT1/KLF4 mutations, or fibroblastic differentiation, non-skull base location and other mutations. This is the first study of the integrated mutational landscape of chordoid meningioma with important implications for patient risk stratification and management.