Prognostic impact of the number and total tumor burden of secondary cerebral lesions in patients with resected brain metastases of non-small cell lung cancers.

OBJECTIVE: Systemic therapeutic advancements have improved the prognosis of cancer patients, leading to surgery more frequently being carried out for patients with multiple brain metastases (BM). The underlying evidence for the strategy is currently lacking. This study aimed to evaluate the prognostic significance of the number of BM and total tumor burden (TTB) on the overall survival (OS) of patients with resected BM of non-small cell lung cancer (NSCLC) in a modern series. METHODS: In this monocentric retrospective series, patients who underwent resection of BM of NSCLC between 2015 and 2021 were included. Demographic, clinical, and histological parameters were collected, and formal radiological volumetric analyses were performed. Prognostic biomarkers for cerebral progression-free survival (C-PFS) and OS were analyzed with univariate and multivariate Cox proportional hazards analysis. RESULTS: One hundred eighty-four patients were included in the study. Among these, 108 patients (58.7%) presented with a single brain metastasis, 36 patients (19.6%) with 2 BM, 22 patients (11.9%) with 3 BM, and 18 patients (9.8%) with more than 3 BM (maximum 15 BM). The mean ± SD (range) preoperative tumor burden was 23.1 ± 25.3 (1.1-145.3) cm3. The mean residual tumor burden after surgery was 0.3 ± 0.8 (0.0-6.3) cm3. By the time of the analysis, 128 patients (69.6%) had died. The median follow-up duration was 49.0 months (95% CI 39.6-63.6). The median OS was 19.2 months (95% CI 13.2-24.0), and the survival rates at 6 months, 1 year, and 2 years were 76% (95% CI 69%-82%), 61% (95% CI 53%-67%), and 43% (95% CI 35%-50%), respectively. The median C-PFS was 8.4 months (95% CI 7.2-12.0). In the Cox multivariate regression model, younger age (< 65 years), single brain metastasis, adjuvant brain radiation therapy, adjuvant use of targeted therapy, and TTB < 7 cm3 were all independent predictors of longer OS. CONCLUSIONS: In this era of modern systemic treatments for cancer, the number of BM and total cerebral tumor burden remain significant prognostic factors of OS. However, resection should be considered as an option even in those patients with multiple BM in order to enhance patient clinical status, enable further local and systemic treatment delivery, and improve their survival and quality of life.

Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas.

Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin interactions between super-enhancers within DIRC3 and a locus containing IHH. Our work expands the landscape of meningioma molecular drivers and demonstrates enhancer hijacking of Hedgehog ligands as a route to activate this pathway  in neoplasia.

Respective roles of Pik3ca mutations and cyproterone acetate impregnation in mouse meningioma tumorigenesis.

Despite their rarity, PIK3CA mutations in meningiomas have raised interest as potentially targetable, ubiquitous mutations owing to their presence in sporadic benign and malignant tumors but also in hormone-related cases. Using new genetically engineered mouse models, we here demonstrate that Pik3ca mutations in postnatal meningeal cells are sufficient to promote meningioma formation but also tumor progression in mice. Conversely, hormone impregnation, whether alone or in association with Pik3ca and Nf2 mutations, fails to induce meningioma tumorigenesis while promoting breast tumor formation. We then confirm in vitro the effect of Pik3ca mutations but not hormone impregnation on the proliferation of primary cultures of mouse meningeal cells. Finally, we show by exome analysis of breast tumors and meninges that hormone impregnation promotes breast tumor formation without additional somatic oncogenic mutation but is associated with an increased mutational burden on Pik3ca-mutant background. Taken together, these results tend to suggest a prominent role of Pik3ca mutations over hormone impregnation in meningioma tumorigenesis, the exact effect of the latter is still to be discovered.

Surgical, functional, and oncological considerations regarding awake resection for giant diffuse lower-grade glioma of more than 100 cm3.

OBJECTIVE: Surgery for giant diffuse lower-grade gliomas (LGGs) is challenging, and very few data have been reported on this topic in the literature. In this article, the authors investigated surgical, functional, and oncological aspects in patients who underwent awake resection for large LGGs with a volume > 100 cm3. METHODS: The authors retrospectively reviewed a consecutive cohort of patients who underwent surgery in an awake condition for an LGG (WHO grade 2 with possible foci of grade 3 transformation) with a volume > 100 cm3. RESULTS: A total of 108 patients were included, with a mean age of 36.1 ± 8.5 years. The mean presurgical LGG volume was 136.7 ± 34.5 cm3. In all but 2 patients a disconnection resective surgery up to functional boundaries was possible thanks to active patient collaboration during the awake period. At 3 months of follow-up, all but 1 patient had a normal neurological examination, with a mean Karnofsky Performance Status (KPS) score of 89.8 ± 10.36. In all patients with preoperative epilepsy, there was postoperative control or significant reduction of seizure events. Moreover, 85.1% of patients returned to work. The mean extent of resection (EOR) was 88.9% ± 7.0%, with a mean residual tumor volume (RTV) of 16.3 ± 12.0 cm3 (median RTV 15 cm3). Pathological examination revealed 73 grade 2 gliomas (67.6%; 26 oligodendrogliomas and 47 astrocytomas) and 35 gliomas with foci of grade 3 (32.4%; 19 oligodendrogliomas and 16 astrocytomas). During the postoperative period, 93.6% of patients underwent adjuvant chemotherapy with a median interval between surgery and first chemotherapy of 14 months (IQR 2-26 months), and 55% of patients had radiotherapy with a median interval of 38.5 months (IQR 18-59.8 months). At the last follow-up, 69.7% of patients were still alive with a median follow-up of 62 months (IQR 36-99 months). Overall survival (OS) rates at 1, 5, and 10 years were 100% (95% CI 0.99-1), 80% (95% CI 0.72-0.9), and 58% (95% CI 0.45-0.73), respectively. The median OS was 138 months. In multivariable Cox regression analysis, RTV was established as the only independent prognostic factor for survival. CONCLUSIONS: With the application of rigorous surgical methodology based on functional-guided resection, resection of giant LGGs (volume > 100 cm3) can be reproducibly achieved during surgery with patients under awake mapping with both favorable functional results (< 1% permanent neurological worsening) and favorable long-term oncological outcomes (median OS > 11 years, with a more significant benefit when the RTV is < 15 cm3).

GAB1 as a Marker of Recurrence in Anterior Skull Base Meningioma.

BACKGROUND: About one-third of anterior skull base meningiomas show Hedgehog pathway activation. We have recently identified GAB1 as a surrogate marker for Hedgehog pathway-activated meningiomas. OBJECTIVE: To determine the reproducibility and prognostic value of GAB1 marker in anterior skull base meningiomas. METHODS: A retrospective bicentric cohort of anterior skull base meningiomas, operated from 2005 to 2015, was constituted. GAB1 immunohistochemistry was performed in 2 centers, and the GAB1 score was assessed. Clinical and pathological data were reviewed to determine the prognostic value of the GAB1 score, along with classical factors of recurrence. RESULTS: One hundred forty-eight patients were included (median follow-up of 72 ± 46 months). 78% of patients had gross total resection. Eighty-four percentage of patients harbored grade 1 meningiomas. GAB1 immunohistochemistry was positive (ie, GAB1 staining score was >250) in 53 cases (35%). GAB1-positive cases were mainly at olfactory groove, of meningothelial grade 1 subtype, and showed greater recurrence (36% vs 14%, P = .002), greater requirement for multiple surgeries (17% vs 4.2%, P = .014), and more likely evolution toward diffuse skull base infiltration (15% vs 3%, P = .0017). By multivariable Cox regression analysis, incomplete surgical resection (hazard ratios [HR] = 8.3, 95% IC [3.7-18.2], P < .001), male sex (HR = 5.4, 95% IC [2.2-13.5], P < .001), GAB1 positivity (HR = 3.2, 95% CI [1.5-6.9], P = .004), and Ki67 index >4 (HR = 2.2, 95% IC [1.2-4.6], P = .035) were independent prognostic factors for recurrence. CONCLUSION: GAB1 marker is an independent prognostic factor for anterior skull base meningioma and could be useful for both prognostic evaluation and identification of Hedgehog-activated meningiomas.

Endoscopic transsphenoidal surgery for non-functioning pituitary adenoma: Learning curve and surgical results in a prospective series during initial experience.

Background: To report the initial experience of surgery for non-functioning pituitary adenoma (NFPA) from a neurosurgeon in a dedicated residency training endoscopic transsphenoidal (ETS) program, and detail the surgical and clinical outcomes during this period. Methods: A prospective series of all patients operated for NFPA, using an ETS approach, during the three first years of experience of a newly board-certified neurosurgeon was analysed. Clinical, radiological and peri-operative data were collected. Extent of resection (EOR) was determined by formal volumetric analysis. Impact of the learning curve and predictive factors of gross total resection (GTR) were determined. Results: Fifty-three patients with NFPA were included in this prospective cohort which was divided in two periods of time ("First period": 30 first cases, and "second period": 23 following cases). Baseline characteristics of the patients in the two periods were similar. Overall occurrence of complication was 22% and was not significantly different in the two periods of time. No patient had severe neurological complication. Gross total resection was achieved in 70% of patients. Mean Extent of resection was 96%. In a multiple linear regression model, a higher EOR was positively correlated with experience (p = 0.018) and negatively correlated with Knosp Score equal to 4 (p < 0.001). Predictive factors for GTR were Higher Knosp grade (p = 0,01), higher pre-operative volume (p = 0.03), and second period of time (p = 0.01). Conclusion: NFPA surgery can be safe and efficient during the learning period. Dedicated intensive learning, careful patient selection and multidisciplinary work are key to shorten the learning curve and achieve satisfactory results.

Somatic PIK3CA Mutations in Sporadic Cerebral Cavernous Malformations.

BACKGROUND: Cerebral cavernous malformations (CCMs) are common sporadic and inherited vascular malformations of the central nervous system. Although familial CCMs are linked to loss-of-function mutations in KRIT1 (CCM1), CCM2, or PDCD10 (CCM3), the genetic cause of sporadic CCMs, representing 80% of cases, remains incompletely understood. METHODS: We developed two mouse models harboring mutations identified in human meningiomas with the use of the prostaglandin D2 synthase (PGDS) promoter. We performed targeted DNA sequencing of surgically resected CCMs from patients and confirmed our findings by droplet digital polymerase-chain-reaction analysis. RESULTS: We found that in mice expressing one of two common genetic drivers of meningioma - Pik3ca H1047R or AKT1 E17K - in PGDS-positive cells, a spectrum of typical CCMs develops (in 22% and 11% of the mice, respectively) instead of meningiomas, which prompted us to analyze tissue samples from sporadic CCMs from 88 patients. We detected somatic activating PIK3CA and AKT1 mutations in 39% and 1%, respectively, of lesion tissue from the patients. Only 10% of lesions harbored mutations in the CCM genes. We analyzed lesions induced by the activating mutations Pik3ca H1074R and AKT1 E17K in mice and identified the PGDS-expressing pericyte as the probable cell of origin. CONCLUSIONS: In tissue samples from sporadic CCMs, mutations in PIK3CA were represented to a greater extent than mutations in any other gene. The contribution of somatic mutations in the genes that cause familial CCMs was comparatively small. (Funded by the Fondation ARC pour la Recherche contre le Cancer and others.).

Mouse Models in Meningioma Research: A Systematic Review.

Meningiomas are the most frequent primitive central nervous system tumors found in adults. Mouse models of cancer have been instrumental in understanding disease mechanisms and establishing preclinical drug testing. Various mouse models of meningioma have been developed over time, evolving in light of new discoveries in our comprehension of meningioma biology and with improvements in genetic engineering techniques. We reviewed all mouse models of meningioma described in the literature, including xenograft models (orthotopic or heterotopic) with human cell lines or patient derived tumors, and genetically engineered mouse models (GEMMs). Xenograft models provided useful tools for preclinical testing of a huge range of innovative drugs and therapeutic options, which are summarized in this review. GEMMs offer the possibility of mimicking human meningiomas at the histological, anatomical, and genetic level and have been invaluable in enabling tumorigenesis mechanisms, including initiation and progression, to be dissected. Currently, researchers have a range of different mouse models that can be used depending on the scientific question to be answered.

GAB1 overexpression identifies hedgehog-activated anterior skull base meningiomas.

AIMS: Mutations activating the hedgehog (Hh) signalling pathway have been described in anterior skull base meningiomas, raising hope for the use of targeted therapies. However, identification of Hh-activated tumours is hampered by the lack of a reliable immunohistochemical marker. We report the evaluation of GAB1, an immunohistochemical marker used to detect Hh pathway activation in medulloblastoma, as a potential marker of Hh-activated meningiomas. METHODS: GAB1 staining was compared to SMO mutation detection with Sanger and NGS techniques as well as Hh pathway activation study through mRNA expression level analyses in a discovery set of 110 anterior skull base meningiomas and in a prospective validation set of 21 meningiomas. RESULTS: Using an expression score ranging from 0 to 400, we show that a cut-off score of 250 lead to excellent detection of Hh pathway mutations (sensitivity 100%, specificity 86%). The prospective validation set confirmed the excellent negative predictive value of GAB1 to exclude Hh-independent meningiomas. We describe a large series of 32 SMO-mutant meningiomas and define multiple ways of Hh activation, either through somatic mutations or associated with mutually co-exclusive sonic hedgehog (SHH) or Indian hedgehog (IHH) overexpression independent of the mutations. CONCLUSION: The assessment of GAB1 expression by an immunohistochemical score is a fast and cost-efficient tool to screen anterior skull base meningiomas for activation of the Hh pathway. It could facilitate the identification of selected cases amenable to sequencing for Hh pathway genes as predictive markers for targeted therapy.

Multimodal management of surgery- and radiation-refractory meningiomas: an analysis of the French national tumor board meeting on meningiomas cohort.

PURPOSE: Meningiomas represent the most frequent tumor of the central nervous system in adults. While most meningiomas are efficiently treated by surgery and radiotherapy/radiosurgery, there is a small portion of radiation- and surgery-refractory tumors for which there is no clear recommendation for optimal management. The French National Tumor Board Meeting on Meningiomas (NTBM) offers a glimpse on the current management of such patients. METHODS: We retrospectively reviewed the charts of patients presented to the multidisciplinary Meeting between 2016 and 2019. We selected patients with a progressive disease after at least two treatments, including surgery and radiotherapy. RESULTS: In this multicentric cohort of 86 cases, patients harbored 17 (19.8%) WHO Grade I, 48 (55.8%) WHO Grade II and 21 (24.4%) WHO Grade III tumors. The median number of treatments received before inclusion was 3 (range: 2 - 11). Following the Board Meeting, 32 patients (37.2%) received chemotherapy, 11 (12.8%) surgery, 17 (19.8%) radiotherapy, 14 (16.3%) watchful observation and 12 (13.9%) palliative care. After a mean follow-up of 13 months post-inclusion, 32 patients (37.2%) had died from their disease. The mean progression free survival was 27 months after radiotherapy, 10 months after surgery, 8.5 months after chemotherapy (Bevacizumab: 9 months - Octreotide/Everolimus: 8 months). CONCLUSIONS: Surgery- and radiation-refractory meningiomas represent a heterogeneous group of tumors with a majority of WHO Grade II cases. If re-irradiation and redo-surgery are not possible, bevacizumab and octreotide-everolimus appear as a valuable option in heavily pre-treated patients considering the current EANO guidelines.

Corticosteroids as an Adjuvant Treatment to Surgery in Chronic Subdural Hematomas: A Multi-Center Double-Blind Randomized Placebo-Controlled Trial.

Chronic subdural hematoma (CSDH) is a common condition necessitating surgery; however, recurrence occurs in 15-25% of cases despite surgical management. The HEMACORT trial was a prospective randomized, double-blind, placebo-controlled, multi-centric study (NCT01380028). The aim of this trial was to determine the effect of corticosteroids as an adjuvant treatment to surgery on CSDH recurrence at 6 months. After surgery, participants were assigned by block-randomization to receive either placebo or oral prednisone at a dose of 1 mg/kg/day followed by weekly stepwise tapering in steps of 10 mg/day. The primary outcome was CSDH recurrence, defined by the need for reoperation and/or radiological progression of CSDH. Secondary outcomes were one-year death, radiological changes, safety, neurological status, and quality of life. The trial was discontinued at midpoint of expected inclusions: 78 participants received prednisone and 77 received placebo controls. In an intention-to-treat analysis, CSDH clinicoradiological recurrence was not different between prednisone and placebo groups (21.8% vs. 35.1%, respectively; hazard ratio 0.56; 95% confidence interval 0.30-1.02; p = 0.06), although post hoc analyses concluded to statistical significance (p = 0.02). Earlier radiological resolution was observed after prednisone administration, but reoperation rates (reaching 5.8% overall) and functional outcomes were not different at 6 months. Among adverse events, sleep disorders occurred more often in the prednisone group (26.1% vs. 9.1%, p = 0.02). The HEMACORT trial data suggest that prednisone, as an adjuvant treatment to surgery, may reduce early radiological recurrence of CSDH, although clinical benefits are unclear. In view of these findings, the authors suggest that shorter treatment duration should be assessed for safety and efficacy in future trials.

Associations of meningioma molecular subgroup and tumor recurrence.

BACKGROUND: We and others have identified mutually exclusive molecular subgroups of meningiomas; however, the implications of this classification for clinical prognostication remain unclear. Integrated genomic and epigenomic analyses implicate unique oncogenic processes associated with each subgroup, suggesting the potential for divergent clinical courses. The aim of this study was to understand the associated clinical outcomes of each subgroup, as this could optimize treatment for patients. METHODS: We analyzed outcome data for 469 meningiomas of known molecular subgroup, including extent of resection, postoperative radiation, surveillance imaging, and time to recurrence, when applicable. Statistical relationships between outcome variables and subgroup were assessed. Features previously associated with recurrence were further investigated after stratification by subgroup. We used Kaplan-Meier analyses to compare progression-free survival, and identified factors significantly associated with recurrence using Cox proportional hazards modeling. RESULTS: Meningioma molecular subgroups exhibited divergent clinical courses at 2 years of follow-up, with several aggressive subgroups (NF2, PI3K, HH, tumor necrosis factor receptor-associated factor 7 [TRAF7]) recurring at an average rate of 22 times higher than others (KLF4, POLR2A, SMARCB1). PI3K-activated tumors recurred earlier than other subgroups but had intermediate long-term outcome. Among low-grade tumors, HH and TRAF7 meningiomas exhibited elevated recurrence compared with other subgroups. Recurrence of NF2 tumors was associated with male sex, high grade, and elevated Ki-67. Multivariate analysis identified molecular subgroup as an independent predictor of recurrence, along with grade and previous recurrence. CONCLUSION: We describe distinct clinical outcomes and recurrence rates associated with meningioma molecular subgroups. Our findings emphasize the importance of genomic characterization to guide postoperative management decisions for meningiomas.

Predictive Evolution Factors of Incidentally Discovered Suspected Low-Grade Gliomas: Results From a Consecutive Series of 101 Patients.

BACKGROUND: Incidentally discovered suspected diffuse low-grade gliomas (LGGs) on brain imaging pose a challenge to neurosurgeons. Modern surgical series of LGGs favor early prophylactic surgery with a maximal extent of resection. However, some nonevolutive lesions may mimic LGGs on magnetic resonance imaging (MRI). OBJECTIVE: To determine objective criteria to advocate surgical resection of an incidentally discovered suspected LGG based upon MRI findings. METHODS: The prospective cohort of patients referred to our institution for an incidental finding suggestive of LGG was retrospectively reviewed. Stable lesions underwent systematic serial MRI follow-up, while evolutive lesions underwent prophylactic surgery under awake conditions. Initial clinico-radiological features were compared between stable and evolutive lesions in order to determine predictive criteria of further evolution. RESULTS: Among 101 patients referred for surgical resection of incidentally discovered suspected LGG in our center, 19 patients (18.8%) had nonevolutive MRI lesions after a mean follow-up of 46.9 ± 34.9 mo. Insular topography (P = .003), higher mean volume at discovery (19.2 vs 5.2 cm3, P < .001), and adjacent sulcal effacement (P = .001) were associated with evolutive lesions. Histopathological diagnosis of LGG was confirmed in all surgical cases. CONCLUSION: Increasing volume is an effective predictor of LGG diagnosis in incidental MRI findings, as all patients who subsequently underwent surgery had confirmed histopathological diagnosis of diffuse glioma. Approximately 18.8% of incidental findings were stable over time. Insular topography, adjacent sulcal effacement, and volume greater than 4.5 cm3 were predictive of further radiological progression. These significant elements will help neurosurgeons to define personalized strategies in this complex setting of incidental discovery.

Meningiomas from a developmental perspective: exploring the crossroads between meningeal embryology and tumorigenesis.

Meningiomas are tumors arising from the meninges and represent the most frequent central nervous system tumors in adults. Recent large-scale genetic studies and preclinical meningioma mouse modelling led to a better comprehension of meningioma development and suggested evidences of close relationships between meningeal embryology and tumorigenesis. In this non-systematic review, we summarize the current knowledge on meningeal embryology and developmental biology, and illustrate how meningioma tumorigenesis is deeply related to meningeal embryology, concerning the potential cell of origin, the role of reactivation of embryonic stem cells, the influence of the embryonic tissue of origin, and the parallelism between topography-dependant molecular pathways involved in normal meninges and in meningioma development. Our study emphasizes why future studies on meningeal embryology are mandatory to affine our comprehension of mechanisms underlying meningioma initiation and development.

Endoscopic subperichondrial transseptal transsphenoidal approach is safe and efficient for non-extended pituitary surgery.

PURPOSE: To report the results of a series of patients undergoing the endoscopic subperichondrial transseptal (STRAS) approach for pituitary surgery and to evaluate the efficiency and the safety of this approach. METHODS: This is a single-centre retrospective study including all patients undergoing pituitary lesion resection through the STRAS approach from January 2002 to December 2017 by a multidisciplinary surgical team (ENT and neurosurgeon). Demographic data, tumour type, complication rate and pre- and post-operative visual, endocrine and tumour status were retrospectively analysed. RESULTS: 119 patients were included in the study, 80 (67%) presenting macroadenoma, 24 (20%) microadenoma (20%) and 6 (5%) giant adenoma. 61 (51%) patients had secreting adenoma and 51 (42%) patient had non-functioning adenoma. The STRAS approach allowed a good visualization of intrasphenoidal and intrasellar anatomical landmarks in all cases and no patient needed turbinate resection. No patient died or had neurological deficit. Endocrine remission or control was achieved in 90.5% of hormone-secreting microadenomas and in 84.2% of hormone-secreting macroadenomas. Gross-total resection was achieved for 39 patients (48.8%) of the 80 macroadenomas. Nasal complication rate was very low, with no septal perforation and two epistaxis (1.7%) medically treated. CONCLUSION: The STRAS approach is an elegant approach to the sphenoid sinus that enables a good exposure of the intrasphenoidal anatomical landmarks with a maximal preservation of the nasal mucosa. This approach allows an intrasellar work with great comfort and safety for the surgeon using a two-hand or a four-hand technique.

Middle meningeal artery embolization as an adjuvant treatment to surgery for symptomatic chronic subdural hematoma: a pilot study assessing hematoma volume resorption.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common condition requiring surgical treatment; however, recurrence occurs in 15% of cases at 1 year. Middle meningeal artery (MMA) embolization has recently emerged as a promising treatment to prevent CSDH recurrence. OBJECTIVE: To investigate the effect of MMA embolization on hematoma volume resorption (HVR) after surgery in symptomatic patients. METHODS: From April 2018 to October 2018, participants with CSDH requiring surgery were prospectively randomized in a pilot study, and received either surgical treatment alone (ST group) or surgery and adjuvant MMA embolization (ST+MMAE group). The primary outcome was HVR measured on the 3 month CT scan compared with the immediate pre-embolization CT scan. Secondary outcomes were clinical recurrence of CSDH and safety measures. RESULTS: 46 patients were randomized and 41 of these achieved a 3 month follow-up . Twenty-one patients received MMA embolization. At 3 months, the HVR from postsurgical level was higher in the ST+MMAE group (mean difference 17.5 mL, 95% CI 3.87 to 31.16 mL; p=0.015). Two participants presented a CSDH recurrence (one in each group). One patient died (ST group). No MMA embolization-related adverse events were reported. CONCLUSION: The addition of MMA embolization to surgery led to an increase in CSDH resorption at 3 months. One recurrence of CSDH was reported in each group, and there were no treatment-related complications.

Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas.

OBJECTIVE: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts. METHODS: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features. RESULTS: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation. CONCLUSIONS: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.

Herpes Simplex Encephalitis Shortly After Surgery for a Secondary Glioblastoma: A Case Report and Review of the Literature.

BACKGROUND: Herpes simplex encephalitis (HSE) and glioblastoma multiforme (GBM) co-occurrence has been described in few cases presenting immunocompromised status related to chemotherapy or chemoradiotherapy. Focal encephalitis over surgical edge of resection occurring shortly after GBM resection is rarely reported, and such infection has never been reported in low-grade glioma with secondary malignant transformation (i.e., secondary GBM). Here, we report a case of HSE misdiagnosed in the early postoperative course following a secondary GBM resection. We also provide a review of the literature about HSE occurring after glioma surgery. CASE DESCRIPTION: We report a case of an acute HSE with a fatal outcome occurring shortly after surgery for a secondary GBM. The patient presented with hyperthermia 12 days after the surgery and was treated with empirical antibiotics. She later suffered from seizure and neurologic deterioration, leading to death despite delayed antiviral administration. Magnetic resonance imaging revealed considerable fluid-attenuated inversion-recovery signal progression at the edge of the surgical resection and polymerase chain reaction amplification of herpes simplex virus (HSV) 1 DNA was positive. CONCLUSIONS: Clinicians should be aware of the existing co-occurrence between HSV infections and GBM during the postoperative course. Cerebrospinal fluid analysis with HSV polymerase chain reaction testing should be promptly undertaken, and some keys clinical elements should justify early empirical treatment, including acyclovir administration. The significant prognostic implication of HSE complicating GBM must raise the attention of neurosurgeon and neuro-oncologist about this entity.