Skull Base Location Research Articles

NCMP-03. ASSOCIATION OF PROGESTERONE CONTRACEPTION WITH TUMOR-RELATED VISUAL IMPAIRMENT IN PREMENOPAUSAL WOMEN WITH MENINGIOMA REFERRED FOR RADIATION

Abstract BACKGROUND Meningiomas express ER/PR, but hormonal risk is poorly characterized and not always considered. We hypothesized that hormonal contraceptives lead to tumor-related visual deficits in premenopausal women referred for radiation. METHODS We conducted a retrospective case-control study with primary endpoint visual deficit prior to radiation for meningioma in women age ≤55. Key risk factors determined included age, grade, skull base location, hormonal supplementation / contraception, and neurofibromatosis / prior radiation (NF/priorRT). Univariate and multivariate (including factors with p<0.05 on univariate) logistic regression was performed to analyze associations with visual deficit. RESULTS 64 women (median age 46) receiving RT from 2012-2024 at a single academic institution were included. 45 (70%) had skull base tumors, 33 (52%) used estrogen or progesterone, and 23 (36%) used unopposed progesterone only, 15 specifically medroxyprogesterone acetate (Provera). Visual deficit was present in 35 patients (55%) and was independently associated with both skull base location (p=0.002, OR 11.5) and unopposed progesterone only use (p=0.008, OR 12) but not estrogen or progesterone use on multivariate analysis. Proportion with progesterone only use was 57% vs. 11% in patients with vs. without visual deficit (chi-sq p<0.001). In 5 with ER/PR testing, 3 were PR+ (all with visual deficits and history of medroxyprogesterone acetate) and 2 were PR- (neither with visual deficits nor hormone use). 13 women (20%) were actively using progesterone during RT. 17 women have been contacted at time of analysis, and 4 discontinued progesterone. CONCLUSIONS Progesterone increases risk for meningioma-related visual deficits in premenopausal women referred for radiotherapy, with a disproportionate number on Provera specifically. These data highlight the importance of age-appropriate counseling, consistent pathologic assessment of ER/PR status, and greater awareness of this issue amongst neurosurgeons and radiation oncologists.

Preoperative Radiographic Features Independently Predict High Blood Loss During Intracranial Meningioma Resection: A Case-Control Study

Surgical resection of intracranial meningioma carries the risk of several complications, including intraoperative blood loss. The objective of this study was to investigate preoperative clinical and radiographic factors predictive of intraoperative estimated blood loss (EBL). This case-control study evaluated EBL for all adults who underwent intracranial meningioma resection from January, 2010 to December, 2021 at our institution. Fifty cases of high EBL (i.e., ≥500mL) and 75 instances of low EBL (i.e., <500mL) were randomly selected. Patients were excluded if they had a recurrent meningioma, preoperative embolization, or lack of imaging data. A multivariable logistic regression model of high EBL likelihood was created. A total of 92 patients met eligibility criteria, with 48 (52%) cases of high EBL. Bivariable analyses identified maximal tumor diameter, intratumoral flow voids, skull base location, and dural venous sinus invasion as potential predictors of high EBL. Multivariable regression found intratumoral flow voids (adjusted odds ratio [aOR]= 5.68 [1.52-21.23], P= 0.009), maximal tumor diameter (aOR= 1.58 [1.11-2.25] per 1-cm increase, P= 0.01), and skull base location (aOR= 3.35 [1.19-9.41], P= 0.02) to be independent predictors of high EBL. Intratumoral flow voids, larger maximal tumor diameter, and skull base location were independently predictive of EBL ≥500mL. Intratumoral flow void presence was the strongest predictor, with 5.68 times the odds of high EBL. Each 1-cm increase in tumor diameter had 58% greater odds of high EBL. Skull base location was associated with 3.35 times the odds of high EBL. These results can inform preoperative patient counseling and blood management preparation.

Hyperostosis in meningioma: a retrospective exploration of histological correlates

Purpose Meningiomas are the most common type of primary brain tumour. Hyperostosis is commonly associated but remains incompletely understood. This study aimed to evaluate the relationship between meningioma-associated hyperostosis and other tumour variables. Materials and Methods We retrospectively analysed 245 patients with 263 cranial meningiomas (202 CNS WHO grade 1, 53 grade 2, and 8 grade 3) who underwent surgery over a three-year period. Meningiomas adjacent to the skull were included. Demographic, radiological, and tumour characteristics were analysed using standard statistical methods. Results Hyperostosis was evident in 99 (38%) of meningiomas. The most common subtypes were meningothelial, transitional, fibrous, atypical, and anaplastic. There were no statistically significant relationships between hyperostosis and bone invasion, and CNS WHO grade and histological subtype. Hyperostosis was more common in skull base meningiomas than in convexity meningiomas (p = 0.001). Ki-67 index was significantly related to CNS WHO grade but not histological subtype when grade was considered. Mean Ki-67 index was higher in meningiomas without hyperostosis (p = 0.03). There was no such relationship with bone invasion (p = 0.29). Univariate and multivariate analysis revealed that Ki-67 index was negatively correlated with hyperostosis (p = 0.03), while bone invasion (p < 0.001) and skull base location (p = 0.03) were positively correlated with hyperostosis. Conclusions Hyperostosis did not appear to be related to CNS WHO grade or histological subtype. Proliferative activity appeared to be higher in meningiomas without hyperostosis and hyperostosis was associated with evidence of bone invasion and skull base location.

Proton therapy for intracranial meningioma: a single-institution retrospective analysis of efficacy, survival and toxicity outcomes.

To report the outcomes of a large series of intracranial meningiomas (IMs) submitted to proton therapy (PT) with curative intent. We conducted a retrospective analysis on all consecutive IM patients treated between 2014 and 2021. The median PT prescription dose was 55.8Gy relative biological effectiveness (RBE) and 66 GyRBE for benign/radiologically diagnosed and atypical/anaplastic IMs, respectively. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), overall survival (OS), and radionecrosis-free survival (RNFS) were evaluated with the Kaplan-Meier method. Univariable analysis was performed to identify potential prognostic factors for clinical outcomes. Toxicity was reported according to the latest Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Overall, 167 patients were included. With a median follow-up of 41 months (range, 6-99), twelve patients (7%) developed tumor local recurrence after a median time of 39 months. The 5-year LRFS was 88% for the entire cohort, with a significant difference between benign/radiologically diagnosed and atypical/anaplastic IMs (98% vs. 47%, p < 0.001); this significant difference was maintained also for the 5-year OS and the 5-year DRFS rates. Patients aged ≤ 56 years reported significantly better outcomes, whereas lower prescription doses and skull base location were associated with better RNFS rates. Two patients experienced G3 acute toxicities (1.2%), and three patients G3 late toxicities (1.8%). There were no G4-G5 adverse events. PT proved to be effective with an acceptable toxicity profile. To the best of our knowledge this is one of the largest series including IM patients submitted to PT.

Surgical Outcomes following Reoperation for Recurrent Intracranial Meningiomas.

Background: We sometimes encounter refractory meningioma cases that are difficult to control, even after achieving a high resection rate or following radiation therapy (RT). In such cases, additional surgical resection might be attempted, but reports regarding outcomes of re-do surgery for recurrent meningiomas are scarce. Methods: This study was a retrospective review of patients who underwent re-do surgery for recurrent meningiomas. The risks of re-doing surgery were statistically analyzed. A comparative analysis between the patients who underwent primary surgery for intracranial meningiomas was also performed. Twenty-six patients underwent re-do surgeries for recurrent meningiomas. Results: At first re-do surgery, gross total resection was achieved in 20 patients (77%). The disease-free survival rate after the first re-do surgery was calculated as 73/58/44% at 1, 2, and 5 years, respectively. A significant factor affecting longer disease-free survival was WHO Grade 1 diagnosis at first re-do surgery (p = 0.02). Surgery-related risks were observed in 10 patients presenting a significant risk factor for skull base location (p = 0.04). When comparing with the risk at primary surgery, the risks of surgical site infection (p = 0.04) and significant vessel injury (p < 0.01) were significantly higher for the re-do surgery. Conclusions: Re-do surgery could increase surgery-related risks compared to the primary surgery; however, it could remain a crucial option, while the indication should be carefully examined in each case.

Is location more determining than WHO grade for long-term clinical outcome in patients with meningioma in the first two decades of life?

To identify factors for tumor relapse and poor outcome in patients with meningiomas in the first two decades of life. All patients ≤ 21years of age who underwent resection of ameningioma at the department of neurosurgery, Medical University of Vienna between 1989 and 2022 were included in this retrospective study. Clinical and radiological data were extracted from the medical records. Outcome and tumor relapse were analyzed for tumor location, histological findings and extent of resection. In this study 18 patients were included, 6 meningiomas were located in the skull base, 5 in the convexity and 7 in other locations including intraventricular and spine (2 patients each), falx, intraparenchymal and optic nerve sheath. Most frequent symptoms were seizures and cranial nerve palsy. In total 56% of the meningiomas were World Health organization (WHO) grade1, 39% grade2 and 5% grade3. Gross total resection was achieved in 67%. The overall relapse rate was 61% and 50% underwent repeat surgery. All patients with convexity meningiomas became seizure free and had afavorable outcome. Relapse and clinical outcome were independent of WHO grade among the whole cohort but the outcome significantly depended on the WHO grade when patients with skull base meningiomas were analyzed as asubgroup. The relapse rate was significantly higher in cases of skull base location (100% vs. 42%, p = 0.038) and after subtotal resection (100% vs. 42%, p = 0.038). Clinical outcome was also significantly worse and the rate of complications was higher in patients with skull base meningiomas. Patients with convexity meningiomas in the first two decades of life have agood outcome due to high chance of gross total resection. Patients with skull base meningioma are at high risk of relapse and poor outcome, particularly those with WHO grades2 and 3. Subtotal resection in patients with skull base location is probably the main reason for this difference.

Epidemiology, Genetics, and DNA Methylation Grouping of Hyperostotic Meningiomas.

Meningiomas are the most common primary intracranial tumors and are among the only tumors that can form lamellar, hyperostotic bone in the tumor microenvironment. Little is known about the epidemiology or molecular features of hyperostotic meningiomas. Using a retrospective database of 342 meningiomas treated with surgery at a single institution, we correlated clinical, tumor-related, targeted next-generation DNA sequencing (n = 39 total, 16 meningioma-induced hyperostosis [MIH]), and surgical variables with the presence of MIH using generalized linear models. Meningioma DNA methylation grouping was analyzed on a separate population of patients from the same institution with preoperative imaging studies sufficient for identification of MIH (n = 200). MIH was significantly correlated with anterior fossa (44.3% of MIH vs 17.5% of non-MIH were in the anterior fossa P < .001, c2) or skull base location (62.5% vs 38.3%, P < .001, c2) and lower MIB-1 labeling index. Gross total resection was accomplished in 27.3% of tumors with MIH and 45.5% of nonhyperostotic meningiomas (P < .05, t test). There was no association between MIH and histological World Health Organization grade (P = .32, c2). MIH was significantly more frequent in meningiomas from the Merlin-intact DNA methylation group (P < .05). Somatic missense mutations in the WD-repeat-containing domain of the TRAF7 gene were the most common genetic alteration associated with MIH (n = 12 of 15, 80%, P < .01, c2). In this article, we show that MIH has a predilection for the anterior skull base and affected tumors are less amenable to gross total resection. We find no association between MIH and histological World Health Organization grade, but show that MIH is more common in the Merlin-intact DNA methylation group and is significantly associated with TRAF7 somatic missense mutations. These data provide a framework for future investigation of biological mechanisms underlying MIH.

A systematic review and individual participant data meta-analysis of gonadal steroid hormone receptors in meningioma.

The relationship between patient and meningioma characteristics and hormone receptors (HRs) of progesterone, estrogen, and androgen remains poorly defined despite literature suggesting that meningiomas are sensitive to gonadal steroid hormones. Therefore, the authors sought to collect and compare data on this topic by performing a systematic review and meta-analysis of reported studies of HR status in meningiomas. A MEDLINE PubMed literature review conducted for articles published between January 1, 1951, and December 31, 2020, resulted in 634 unduplicated articles concerning meningiomas and HRs. There were 114 articles that met the criteria of detailed detection protocols for progesterone receptor (PR), estrogen receptor (ER), and/or androgen receptor (AR) using immunohistochemistry (IHC) or ligand-binding (LB) assays and simultaneous reporting of HR status with at least one variable among age, sex, histology, location, grade, or recurrence. Between-study heterogeneity and risk of bias were evaluated using graphical and statistical methods. The authors performed a multilevel meta-analysis using random-effects modeling on aggregated data (n = 4447) and individual participant data (n = 1363) with subgroup results summarized as pooled effects. A mixed-effects meta-regression using individual participant data was performed to analyze independently associated variables. The 114 selected articles included data for 5810 patients with 6092 tumors analyzed to determine the expression of three HRs in human meningiomas: PRs, ARs, and ERs. The proportions of HR+ meningiomas were estimated to be 0.76 (95% CI 0.72-0.80) for PR+ and 0.50 (95% CI 0.33-0.66) for AR+ meningiomas. ER+ meningioma detection varied depending on the measurement method used and was 0.06 (95% CI 0.03-0.10) with IHC and 0.11 (95% CI 0.06-0.20) with LB assays. There were associations between age and PR and ER expression that varied between male and female patients. PR+ and AR+ were more common in female patients (OR 1.84, 95% CI 1.47-2.29 for PR and OR 4.16, 95% CI 1.62-10.68 for AR). Additionally, PR+ meningiomas were enriched in skull base locations (OR 1.89, 95% CI 1.03-3.48) and meningothelial histology (OR 1.86, 95% CI 1.23-2.81). A meta-regression showed that PR+ was independently associated with age (OR 1.11 95% CI 1.09-1.13; p < 0.0001) and WHO grade I tumors (OR 8.09, 95% CI 3.55-18.44; p < 0.0001). ER+ was negatively associated with meningothelial histology (OR 0.94, 95% CI 0.86-0.98; p = 0.044) and positively associated with convexity location (OR 1.12, 95% CI 1.05-1.18; p = 0.0003). The association between HRs and meningioma features has been investigated but unexplained for decades. In this study the authors demonstrated that HR status has a strong association with known meningioma features, including WHO grade, age, female sex, histology, and anatomical location. Identifying these independent associations allows for a better understanding of meningioma heterogeneity and provides a foundation for revisiting targeted hormonal therapy in meningioma on the basis of proper patient stratification according to HR status.

MODL-24. NEUROIMMUNE-COMPETENT HUMAN BRAIN ORGANOID MODEL FOR STUDYING BRAIN TUMOR INVASION

Abstract INTRODUCTION Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brain tumor with a very poor prognosis (&amp;lt; 12 months survival). There is currently no effective treatment for DIPG. Complete surgical resection of DIPG is difficult due to its skull base location and infiltrative growth pattern. Gaining insights into the invasion process of the DIPG cells and their interaction with brain cells in the tumor microenvironment, such as microglia - the brain's primary immune cells, may guide the development of effective treatment strategies to halt or even reverse disease progression. To build a clinically relevant model for studying the microglia/tumor interaction in a 3D human tissue context, we developed a neuroimmune-competent brain organoid/DIPG fusion model system. METHODS Human embryonic stem cell derived-neural progenitor cells (NPCs) and -GFP-labelled human myeloid precursor cells were combined to form microglia-containing organoids (MiCBOs) through self-assembly and co-development over two months. Using two-photon live imaging, we characterized the distribution and motility of microglia in MiCBOs and corroborated these results with immunofluorescence staining and single-cell RNA-Sequencing (scRNA-Seq). Tumor cell invasion and interaction with microglia in the brain organoids were assessed by confocal microscopy as well as immunofluorescence stainings. RESULTS The human microglia in MiCBOs are viable, widely distributed, actively motile, and highly resemble those in the human brain. Confrontation experiments of the MiCBO with DIPG spheroids enable quantitative characterization of the invasion patterns for different cell lines under various conditions. CONCLUSION Our MiCBOs represent a valuable model for studying tumor cell invasion within a neuroimmune-competent human tissue context. Ongoing experiments with different primary DIPG cell lines as well as genetically engineered microglia will deliver more detailed insights into the invasion patterns of tumor cells into brain tissue and shed light on tumor cell/microglia interplay during the DIPG invasion process.

An unusual ectopic thyroid tissue location & review of literature

Ectopic thyroid is well-known pathology for several decades. Many locations have been described. Nowadays, only three cases of skull base location have been described in literature. In our case, we reported a single case of a 39-year-old male presenting with a supra-sellar and suprachiasmatic location. He presented no clinical symptoms, no endocrine alteration on biology and no skull base invasion which make this case unique compared to actual literature. Such diagnosis should always be an exclusion diagnosis as secondary neoplastic should be first ruled out.

Rare case of extra nasopharyngeal angiofibroma arising from tonsil-case report

Angiofibroma is a highly vascular tumour. It occurs in adolescent males mainly in nasopharynx. Due to aggressive local growth, skull base location and risk of profound haemorrhage, management is challenging. Angiofibromas have been sporadically described in extra nasopharyngeal locations. Presentation varies depending upon the location of origin. Here we present a case of 7 year old boy presenting with difficulty in breathing with lump in the throat for 3 years, which has progressively increased in 4 months period with recurrent chocking while sleeping. Initially he was diagnosed with polyp arising from the tonsil. Polyp along with tonsil excised completely. Histopathology confirmed extra nasopharyngeal angiofibroma (ENA). To the best of our knowledge, only 3 cases arising from tonsil had been reported in English literature.

Significance of Early Postoperative Magnetic Resonance Imaging following Intracranial Meningioma Resection.

The significance of early postoperative magnetic resonance imaging (MRI) for meningioma resection has not yet been evaluated. We retrospectively reviewed patients with intracranial meningiomas resected at our institute between 2011 and 2021. Early postoperative MRI with contrast enhancement was routinely performed within 48 h after surgery while first follow-up MRI was performed approximately after 6 months. MRI findings were reviewed, and the risk factors for postoperative infarction and early recurrence were analyzed. Among the 245 resections performed, early postoperative MRI was performed in 200 cases. Postoperative radiological and symptomatic infarctions occurred in 54 (27%) and 17 patients (9%), respectively. Diameter > 5 cm (p = 0.015) and skull base location (p = 0.010) were independent risk factors for radiological infarctions. Follow-up postoperative MRI performed in 180 patients (90%) detected early recurrence in 24 patients (13%). Non-gross total resection was an independent risk factor for early recurrence (p < 0.0001). Additionally, early recurrence after gross total resection occurred significantly more frequently in meningiomas with dural sinus involvement than in those without (8.3% vs. 0%, p = 0.018). Thus, early postoperative MRI may enable the timely assessment of postoperative neurological deficits, especially after large skull base meningioma resections along with accurate detection of early recurrence, which is critical for meningiomas with dural sinus involvement.

Beyond the Surgical Margin: Patterns of Recurrence in World Health Organization Grade 2 Intracranial Meningiomas

To characterize and classify the location of recurrence in surgically resected WHO grade 2 intracranial meningiomas that did not receive adjuvant radiation, and compare the recurrence pattern of those that underwent gross total versus subtotal resection. We performed a retrospective review of patients who underwent surgical resection of a newly diagnosed WHO grade 2 meningioma at our institution between 1996 and 2019. Patients that were observed postoperatively without adjuvant radiation and subsequently developed a recurrence were included in the study. All patients who received adjuvant therapy were excluded. Recurrence was defined as any evidence of radiographic progression on postoperative surveillance MRI. Location of recurrence were categorized as follows: (1) central - growth observed inside the area of the previously resected tumor more than 1 cm inside the original tumor margin; (2) marginal - growth observed within 1 cm (inside or outside) of the original tumor margin; and (3) remote - growth observed more than 1 cm outside of the original tumor margin. Patterns of recurrence were evaluated by two observers after co-registering pre- and post-operative MRIs, and any differences were reconciled by discussion. A total of 22 patients matched the inclusion criteria. Twelve (55%) underwent GTR while ten (45%) underwent STR. In 12 patients in whom GTR was achieved, mean preoperative tumor volume was 50.6 cm3 with 5 (41.7%) in a skull base location. The average time to recurrence for these tumors was 22.7 months, with a mean recurrent tumor volume of 9.0 cm3. Ten (83.3%) patients had central recurrence, 11 (91.7%) patients had marginal recurrence, and only 4 (33.3%) patients had remote recurrence. In 10 patients in whom STR was achieved, mean preoperative tumor volume was 44.8 cm3, with 7 (70.0%) in a skull base location. The average time to recurrence for these tumors was 23.0 months, with a mean recurrent tumor volume of 21.8 cm3. Of these 10 patients, 9 (90.0%) had central recurrence, all 10 (100.0%) had marginal recurrence, and only 4 (40.0%) patients had remote recurrence. The present study evaluating patterns of recurrence for WHO grade 2 meningiomas after surgical resection (GTR or STR) showed that recurrence occurred centrally and/or at the original tumor margin, with only a minority recurring >1cm outside the original tumor margin. The results of this study suggest that treatment, whether initial surgical resection or adjuvant radiation, may benefit from including at least a 1cm dural margin when safe, to optimize tumor control, but further clinical study is needed.

Long-term Outcomes of Non-vascularized Multilayer Fascial Closure Technique for Dural Repair in Endoscopic Transnasal Surgery: Efficacy, Durability, and Limitations

Non-vascularized multilayer fascial closure technique (NMFCT) can be used instead of nasoseptal flap reconstruction for dural repair in endoscopic transnasal surgery (ETS); however, due to the lack of blood supply, its long-term durability and possible limitations need to be clarified. This was a retrospective study on patients who underwent ETS with intraoperative cerebrospinal fluid (CSF) leakage. We assessed the postoperative and delayed CSF leakage rates and the associated risk factors. Among 200 ETSs with intraoperative CSF leakage, 148 (74.0%) ETSs were performed for skull base pathologies other than pituitary neuroendocrine tumor. The mean follow-up period was 34.4 months. Esposito grade 3 leakage was confirmed in 148 (74.0%) cases. NMFCT was used either with (67 [33.5%]) or without (133 [66.5%]) lumbar drainage. There were 10 cases (5.0%) of postoperative CSF leakage that necessitated reoperation. In 4 other cases (2.0%), CSF leakage was suspected but lumbar drainage alone successfully restored the condition. Multivariate logistic regression analyses revealed that posterior skull base location (P < 0.01, odds ratio 11.5, 95% CI 1.99-2.17× 102) and craniopharyngioma pathology (P= 0.03, odds ratio 9.4, 95% CI 1.25-1.92× 102) were significantly associated with postoperative CSF leakage. No delayed leakage occurred during the observation period except for 2 patients who underwent multiple radiotherapies. NMFCT is a reasonable alternative with long-term durability, though vascularized flap may be a better choice for cases in which vascularity of the surrounding tissues is significantly impaired due to interventions including multiple radiotherapies.

Comparative analysis of histopathological parameters, genome-wide copy number alterations, and variants in genes involved in cell cycle regulation in chordomas of the skull base and sacrum.

Chordomas are rare tumors of the axial skeleton that are refractory to conventional therapy. Few studies have compared the morphological and molecular characteristics of chordomas according to the skull base and sacral locations. Histopathological data and changes revealed by array comparative genomic hybridization (CGH) and next-generation sequencing (NGS) of cell cycle regulation genes were analyzed for 28 skull base (SBCs) and 15 sacral (SC) chordomas. All cases were conventional chordomas. SBCs were significantly more frequent in patients aged <40 years and SCs predominated in patients aged >60 years. Mitotic indices ≥2 mitoses/10 high-power fields were correlated with high degrees of nuclear atypia and Ki67 labeling indices ≥6%. We identified 321 genomic positions, and copy number variation losses were more frequent than gain. Moreover, we report a panel of 85 genetic variants of cell cycle genes and the presence of molecular clusters for chordoma as well in CGH as in NGS. These new data strengthen the view that the chordoma should not be considered as a single molecular entity.

Volumetric Growth and Growth Curve Analysis of Residual Intracranial Meningioma.

After meningioma surgery, approximately 1 in 3 patients will have residual tumor that requires ongoing imaging surveillance. The precise volumetric growth rates of these tumors are unknown. To identify the volumetric growth rates of residual meningioma, growth trajectory, and factors associated with progression. Patients with residual meningioma identified at a tertiary neurosurgery center between 2004 and 2020 were retrospectively reviewed. Tumor volume was measured using manual segmentation, after surgery and at every follow-up MRI scan. Growth rates were ascertained using a linear mixed-effects model and nonlinear regression analysis of growth trajectories. Progression was defined according to the Response Assessment in Neuro-Oncology (RANO) criteria (40% volume increase). There were 236 patients with residual meningioma. One hundred and thirty-two patients (56.0%) progressed according to the RANO criteria, with 86 patients being conservatively managed (65.2%) after progression. Thirteen patients (5.5%) developed clinical progression. Over a median follow-up of 5.3 years (interquartile range, 3.5-8.6 years), the absolute growth rate was 0.11 cm 3 per year and the relative growth rate 4.3% per year. Factors associated with residual meningioma progression in multivariable Cox regression analysis were skull base location (hazard ratio [HR] 1.60, 95% CI 1.02-2.50) and increasing Ki-67 index (HR 3.43, 95% CI 1.19-9.90). Most meningioma exhibited exponential and logistic growth patterns (median R 2 value 0.84, 95% CI 0.60-0.90). Absolute and relative growth rates of residual meningioma are low, but most meet the RANO criteria for progression. Location and Ki-67 index can be used to stratify adjuvant treatment and surveillance paradigms.

SURG-33. RATES OF PRE-OPERATIVE SEIZURE IN PATIENTS WITH MENINGIOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Recent literature has primarily focused on the factors influencing postoperative seizures following resection of meningioma, but many patients also suffer seizures preoperatively. This meta-analysis examined patient demographics, tumor characteristics, and preoperative symptoms to determine which factors are most associated with preoperative seizures. A literature search of Pubmed, Web of Science, and Scopus was conducted. All randomized controlled trials, case-control studies, and cohort studies reporting on preoperative seizure in patients with meningioma were included for analysis. The initial search yielded 4129 total studies, 33 of which were included for quantitative analysis. A total of 8221 patients were analyzed and the rate of preoperative seizure was 26%. Patients were classified as adult vs pediatric and male vs female for analysis. Meningiomas were classified as midline/bilateral vs left-sided vs right-sided, WHO grade 1 vs grade 2-3, greater than 4 cm3 vs less than 4 cm3, and skull base vs non-skull base location. The preoperative signs and symptoms analyzed included presence of headaches, tumor-related edematous change, and neurological deficits. Preoperative seizures were more common in pediatric patients (p&amp;lt; .02) and males (p&amp;lt; .0001). Patients with tumors classified as midline (p&amp;lt; .0001), WHO grade 2-3 (p&amp;lt; .0001), larger than 4 cm3 (p&amp;lt; .0001), and skull base location (p&amp;lt; .0001) were more likely to experience preoperative seizures. Preoperative headaches (p&amp;lt; .0001) were less common in patients with preoperative seizures. Edematous change (p&amp;lt; .0001) and neurological deficits (P&amp;lt; .0001) were more common in patients with pre-operative seizures. On assessment of risk for study bias, no publication bias was detected. This meta-analysis displayed that over 20% of meningioma patients suffer from preoperative seizures. Notably, pediatric patients, patients with midline and skull base meningiomas, and males of all ages were more likely to experience preoperative seizure. Interestingly, patients with preoperative seizures were less likely to experience headaches.

P18.01.A The applicability of established clinical and histopathological risk factors for tumor recurrence during long-term perioperative care in meningioma patients

Abstract Background Risk factors for the prediction of late-onset tumor recurrence in meningioma patients are sparse but needed to estimate duration and control intervals during long-term follow-up in meningioma patients. In this study, we therefore analyzed the value of established risk factors for postoperative meningioma recurrence for the prediction of long-term prognosis in a large, single-center series. Material and methods Correlations of established clinical (age, sex, tumor location, extent of resection), radiological (postoperative tumor volume) and histopathological variables (WHO grade, brain invasion) with tumor relapse were analyzed separately after 3, 5, and 10 years following microsurgery for primary diagnosed intracranial meningioma between 1991 and 2021 in uni- and multivariate analyses. The prognostic value was compared to findings in the entire cohort. Results Within a median follow-up of 29 months (range: 0-307 months), recurrence was observed in 141 patients (12%) after a median PFS of 36 months. PFS among the entire cohort (n=1218) at 3, 5, 10 and 15 years postoperatively were 90%, 84%, 74% and 70%, respectively. Among all patients included, 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&amp;lt;.001), high-grade histology (HR: 3.70, 95%CI 2.50-5.47; p&amp;lt;.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 independently correlated with recurrence after an event-free PFS of at least three (n=485) and five years (n=346), respectively. Similarly, postoperative tumor volume was related with recurrence in the entire cohort (p&amp;lt;.001) but not beyond a follow-up of ≥ three years (p&amp;gt;.05). In 147 patients with a follow-up of ≥ ten years, ten recurrences occurred, and no correlation was found with any of the analyzed variables. Conclusion Skull base tumor location and high-grade histology but not the extent of resection should be considered when planning follow-up duration and intervals following ≥5 years after meningioma surgery. Tumor relapses following more than ten years after surgery are very rare, and corresponding predictors are lacking.

Critical appraisal of minimally invasive keyhole surgery for intracranial meningioma in a large case series.

Meningioma surgery has evolved over the last 20 years with increased use of minimally invasive approaches including the endoscopic endonasal route and endoscope-assisted and gravity-assisted transcranial approaches. As the "keyhole" concept remains controversial, we present detailed outcomes in a cohort series. Retrospective analysis was done for all patients undergoing meningioma removal at a tertiary brain tumor referral center from 2008-2021. Keyhole approaches were defined as: use of a minimally invasive "retractorless" approach for a given meningioma in which a traditional larger approach is often used instead. The surgical goal was maximal safe removal including conservative (subtotal) removal for some invasive locations. Primary outcomes were resection rates, complications, length of stay and Karnofsky Performance Scale (KPS). Secondary outcomes were endoscopy use, perioperative treatments, tumor control and acute MRI FLAIR/T2 changes to assess for brain manipulation and retraction injury. Of 329 patients, keyhole approaches were utilized in 193(59%) patients (mean age 59±13; 30 (15.5%) had prior surgery) who underwent 213 operations; 205(96%) were skull base location. Approaches included: endoscopic endonasal (n = 74,35%), supraorbital (n = 73,34%), retromastoid (n = 38,18%), mini-pterional (n = 20,9%), suboccipital (n = 4,2%), and contralateral transfalcine (n = 4,2%). Primary outcomes: Gross total/near total (>90%) resection was achieved in 125(59%) (5% for petroclival, cavernous sinus/Meckel's cave, spheno-cavernous locations vs 77% for all other locations). Major complications included: permanent neurological worsening 12(6%), CSF leak 2(1%) meningitis 2(1%). There were no DVTs, PEs, MIs or 30-day mortality. Median LOS decreased from 3 to 2 days in the last 2 years; 94% were discharged to home with favorable 90-day KPS in 176(96%) patients. Secondary outcomes: Increased FLAIR/T2 changes were noted on POD#1/2 MRI in 36/213(17%) cases, resolving in all but 11 (5.2%). Endoscopy was used in 87/139(63%) craniotomies, facilitating additional tumor removal in 55%. Tumor progression occurred in 26(13%) patients, mean follow-up 42±36 months. Our experience suggests minimally invasive keyhole transcranial and endoscopic endonasal meningioma removal is associated with comparable resection rates and low complication rates, short hospitalizations and high 90-day performance scores in comparison to prior reports using traditional skull base approaches. Subtotal removal may be appropriate for invasive/adherent meningiomas to avoid neurological deficits and other post-operative complications, although longer follow-up is needed. With careful patient selection and requisite experience, these approaches may be considered reasonable alternatives to traditional transcranial approaches.

A Frailty-Adjusted Stratification Score to Predict Surgical Risk, Post-Operative, Long-Term Functional Outcome, and Quality of Life after Surgery in Intracranial Meningiomas.

Simple SummaryMeningiomas are the most common primary brain tumour and their prevalence increases in the ageing population. Among researchers, predicting surgical outcomes, complications, and quality of life (QoL) after surgery still represents a major subject of debate. The aim of the study hereby presented was to review well known and potential new prognostic factors affecting the early and long-term functional outcomes and quality of life of patients treated for intracranial meningiomas. Our findings might help define tailored surgical and perioperative protocols to maximise the standard of care, relying on a patient-specific multi-domain surgical, biometric, and clinical assessment to be conducted during the pre-operative medical interview. This approach might be beneficial for reducing complications occurrence, predicting surgical and functional outcomes, counselling patients and caregivers on surgical indications, reducing legal issues, and providing a valuable tool to healthcare providers for resources allocation.Object: To investigate those parameters affecting early and follow-up functional outcomes in patients undergoing resection of meningiomas and to design a dedicated predictive score, the Milan Bio(metric)-Surgical Score (MBSS) is hereby presented. Methods: Patients undergoing transcranial surgery for intracranial meningiomas were included. The most significant parameters in the regression analyses were implemented in a patient stratification score and were validated by testing its classification consistency with a clinical–radiological grading scale (CRGS), Milan complexity scale (MCS), and Charlson Comorbidity Index (CCI) scores. Results: The ASA score, Frailty index, skull base and posterior cranial fossa locations, a diameter of >25 mm, and the absence of a brain–tumour interface were predictive of early post-operative deterioration and were collected in MBSS Part A (AUC: 0.965; 95%C.I. 0.890–1.022), while the frailty index, posterior cranial fossa location, a diameter of >25 mm, a edema/tumour volume index of >2, dural sinus invasion, DWI hyperintensity, and the absence of a brain–tumour interface were predictive of a long-term unfavourable outcome and were collected in MBSS Part B (AUC: 0.877; 95%C.I. 0.811–0.942). The score was consistent with CRGS, MCS, and CCI. Conclusion: Patients’ multi-domain evaluation and the implementation of frailty indexes might help predict the perioperative complexity of cases; the functional, clinical, and neurological early outcomes; survival; and overall QoL after surgery.