Refining the predictive value of preoperative apparent diffusion coefficient (ADC) by whole-tumor analysis for facial nerve outcomes in vestibular schwannomas.

BACKGROUND: Apparent diffusion coefficient (ADC) in MRI has been shown to correlate with postoperative House-Brackmann (HB) scores in patients with vestibular schwannoma despite limited methodology. To rectify limitations of single region of interest (ROI) sampling, we hypothesize that whole-tumor ADC histogram analysis will refine the predictive value of this preoperative biomarker related to postoperative facial nerve function. METHODS: Of 155 patients who underwent resection of vestibular schwannoma (2014-2020), 125 patients were included with requisite clinical and radiographic data. After volumetric analysis and whole-tumor ADC histogram, regression tree analysis identified ADC cutoff for significant differences in HB grade. Outcomes were extent of resection, facial nerve function, hospital length of stay (LOS), and complications. RESULTS: Regression tree analysis defined three quantitative ADC groups (× 10-6 mm2/s) as high (> 2248.77; HB 1.7), mid (1468.44-2248.77; HB 3.1), and low (< 1468.44; HB 2.3) range (p 0.04). The mid-range ADC group had significantly worse postoperative HB scores and longer hospital LOS. Large tumor volume was independently predictive of lower rates of gross total resection (p <0.0001), higher postoperative HB score (p 0.002), higher rate of complications (p 0.04), and longer LOS (p 0.003). CONCLUSIONS: Whole-tumor histogram yielded a robust regression tree analysis that defined three ADC groups with significantly different facial nerve outcomes. This likely reflects tumor heterogeneity better than solid-tumor ROI sampling. Whole-tumor ADC warrants further study as a useful radiographic biomarker in patients with vestibular schwannoma who are considering surgical resection.

Novel classification of foramen magnum meningiomas predicted by topographic position relative to neurovascular bundle.

PURPOSE: Proximity to critical neurovascular structures can create significant obstacles during surgical resection of foramen magnum meningiomas (FMMs) to the detriment of treatment outcomes. We propose a new classification that defines the tumor's relationship to neurovascular structures and assess correlation with postoperative outcomes. METHODS: In this retrospective review, 41 consecutive patients underwent primary resection of FMMs through a far lateral approach. Groups defined based on tumor-neurovascular bundle configuration included Type 1, bundle ventral to tumor; Type 2a-c, bundle superior, inferior, or splayed, respectively; Type 3, bundle dorsal; and Type 4, nerves and/or vertebral artery encased by tumor. RESULTS: The 41 patients (range 29-81 years old) had maximal tumor diameter averaging 30.1 mm (range 12.7-56 mm). Preoperatively, 17 (41%) patients had cranial nerve (CN) dysfunction, 12 (29%) had motor weakness and/or myelopathy, and 9 (22%) had sensory deficits. Tumor type was relevant to surgical outcomes: specifically, Type 4 demonstrated lower rates of gross total resection (65%) and worse immediate postoperative CN outcomes. Long-term findings showed Types 2, 3, and 4 demonstrated higher rates of permanent cranial neuropathy. Although patients with Type 4 tumors had overall higher ICU and hospital length of stay, there was no difference in tumor configuration and rates of postoperative complications or 30-day readmission. CONCLUSION: The four main types of FMMs in this proposed classification reflected a gradual increase in surgical difficulty and worse outcomes. Further studies are warranted in larger cohorts to confirm its reliability in predicting postoperative outcomes and possibly directing management decisions.

How I do it: hearing preservation in large vestibular schwannomas using vestibular nerve fiber preservation technique.

BACKGROUND: To improve hearing function after resection of large vestibular schwannomas, we describe a strategy of vestibular-nerve-fiber preservation. Anatomical considerations and stepwise dissection are described. METHOD: Steps include locating the vestibular nerve at the brainstem and identifying a dissection plane between nerve fibers and tumor capsule. Using this plane to mobilize and resect tumor reduced manipulation and maintained vascularity of underlying cochlear and facial nerves. CONCLUSION: Preservation of hearing function is feasible in large vestibular schwannomas with vestibular-nerve-fiber preservation. Reducing manipulation and ischemic injury of underlying cochlear and facial nerves thereby helped facilitate hearing preservation, even in large tumors.

High-Throughput Screening of Epigenetic Inhibitors in Meningiomas Identifies HDAC, G9a, and Jumonji-Domain Inhibition as Potential Therapies.

Background Epigenetics may predict treatment sensitivity and clinical course for patients with meningiomas more accurately than histopathology. Nonetheless, targeting epigenetic mechanisms is understudied for pharmacotherapeutic development for these tumors. The bio-molecular insights and potential therapeutic development of meningioma epigenetics led us to investigate epigenetic inhibition in meningiomas. Methods We screened a 43-tumor cohort using a 139-compound epigenetic inhibitor library to assess sensitivity of relevant meningioma subgroups to epigenetic inhibition. The cohort was composed of 5 cell lines and 38 tumors cultured directly from surgery; mean patient age was 56.6 years ± 13.9 standard deviation. Tumor categories: 38 primary tumors, 5 recurrent; 33 from females, 10 from males; 32 = grade 1; 10 = grade 2; 1 = grade 3. Results Consistent with our previous results, histone deacetylase inhibitors (HDACi) were the most efficacious class. Panobinostat significantly reduced cell viability in 36 of 43 tumors; 41 tumors had significant sensitivity to some HDACi. G9a inhibition and Jumonji-domain inhibition also significantly reduced cell viability across the cohort; tumors that lost sensitivity to panobinostat maintained sensitivity to either G9a or Jumonji-domain inhibition. Sensitivity to G9a and HDAC inhibition increased with tumor grade; tumor responses did not separate by gender. Few differences were found between recurrent and primary tumors, or between those with prior radiation versus those without. Conclusions Few efforts have investigated the efficacy of targeting epigenetic mechanisms to treat meningiomas, making the clinical utility of epigenetic inhibition largely unknown. Our results suggest that epigenetic inhibition is a targetable area for meningioma pharmacotherapy.

Surgical outcomes in large vestibular schwannomas: should cerebellopontine edema be considered in the grading systems?

PURPOSE: Large (> 3 cm) vestibular schwannomas pose complexity in surgical management because of narrow working corridors and proximity to the cranial nerves, brainstem, and inner ear structures. With current vestibular schwannoma classifications limited in information regarding cerebellopontine edema, our retrospective series examined this radiographic feature relative to clinical outcomes and its possible role in preoperative scoring. METHODS: Of 230 patients who underwent surgical resection of vestibular schwannoma (2014-2020), we identified 107 patients with Koos grades 3 or 4 tumors for radiographic assessment of edema in the middle cerebellar peduncle (MCP), brainstem, or both. Radiographic images were graded and patients grouped into Koos grades 3 or 4 or our proposed grade 5 with edema. Tumor volumes, radiographic features, clinical presentations, and clinical outcomes were evaluated. RESULTS: The 107 patients included 22 patients with grade 3 tumors, 39 with grade 4, and 46 with grade 5. No statistical differences were noted among groups for demographic data or complication rates. Unlike grades 3 and 4 patients, grade 5 patients presented with worse hearing (p < 0.001), larger tumors (p < 0.001), lower rates of gross total resection (GTR), longer hospital stays, and higher rates of balance dysfunction. CONCLUSION: With edema detected in 43% of this cohort, special considerations are warranted for grade 5 vestibular schwannomas given the preoperative findings of worse hearing, lower GTR rates, longer hospital stays, and 96% who pursued postoperative balance therapy. We propose that grade 5 with edema offers a more nuanced interpretation of a radiographic feature that holds relevance to treatment selection and patient outcomes.

Phenotype and Neuronal Cytotoxic Function of Glioblastoma Extracellular Vesicles.

Glioblastoma (GBM) is the most aggressive and lethal form of brain tumor. Extracellular vesicles (EVs) released by tumor cells play a critical role in cellular communication in the tumor microenvironment promoting tumor progression and invasion. We hypothesized that GBM EVs possess unique characteristics which exert effects on endogenous CNS cells including neurons, producing dose-dependent neuronal cytotoxicity. We purified EVs from the plasma of 20 GBM patients, 20 meningioma patients, and 21 healthy controls, and characterized EV phenotypes by electron microscopy, nanoparticle tracking analysis, protein concentration, and proteomics. We evaluated GBM EV functions by determining their cytotoxicity in primary neurons and the neuroblastoma cell line SH-SY5Y. In addition, we determined levels of IgG antibodies in the plasma in GBM (n = 82), MMA (n = 83), and controls (non-tumor CNS disorders and healthy donors, n = 50) with capture ELISA. We discovered that GBM plasma EVs are smaller in size and had no relationship between size and concentration. Importantly, GBM EVs purified from both plasma and tumor cell lines produced IgG-mediated, complement-dependent apoptosis and necrosis in primary human neurons, mouse brain slices, and neuroblastoma cells. The unique phenotype of GBM EVs may contribute to its neuronal cytotoxicity, providing insight into its role in tumor pathogenesis.

Recurrent Sphenocavernous Meningioma.

A case of a recurrent sphenocavernous meningioma is presented. The patient is a 42-year-old male who presented with an episode of transient right-sided numbness. A magnetic resonance imaging (MRI) revealed a large left sphenocavernous meningioma. The patient underwent a frontotemporal craniotomy for tumor resection. Near total resection was achieved with minimal residual in the left cavernous sinus (CS) and orbital apex. The pathology was consistent with meningioma, World Health Organization (WHO) grade I. A follow-up MRI was done 9 months after surgery and showed a growth of the residual tumor, which was treated with intensity modulated radiotherapy. Tumor growth was detected on serial imaging over a 4-year period. Surgical resection was offered. A left frontotemporal craniotomy with pretemporal transcavernous approach was performed. The bone flap was reopened and the dura was opened in a Y-shaped fashion. The roof of the optic canal was drilled off, and the falciform ligament was opened to decompress the optic nerve. The tumor was disconnected from the anterior clinoid region (the anterior clinoid process was eroded by the tumor) and reflected off the wall of the lateral CS. Tumor was adherent to the V2 fascicles (the lateral CS wall was resected in the first surgery) and was sharply dissected off. Gross total resection was achieved. The pathology was consistent with meningioma, WHO grade I. The patient had an unremarkable postoperative course without any new neurological deficits. The link to the video can be found at: https://youtu.be/KVBVw_86JqM .

A two-stage combined anterolateral and endoscopic endonasal approach to the petroclival region: an anatomical study and clinical application.

OBJECT: The pretemporal transcavernous anterior petrosal (PTAP) approach and the combined petrosal (CP) approach have been used to resect petroclival meningiomas (PCMs). In this cadaveric anatomical study, a two-stage combined PTAP and endoscopic endonasal far medial (EEFM) approach (the PTAPE approach) was compared morphometrically to the CP approach. A case study provides a clinical example of using the PTAPE approach to treat a patient with a PCM. The key elements of the approach selection process are outlined. METHODS: Five cadaveric specimens underwent a CP approach and 5 underwent a PTAPE approach. The area of drilled clivus, length of multiple cranial nerves (CNs), and the area of brain stem exposure were measured, reported as means (standard deviations) by group, and compared. RESULTS: The total area of the clivus drilled in the PTAPE group (695.3 [121.7] mm2) was greater than in the CP group (88.7 [17.06] mm2, P < 0.01). Longer segments of CN VI were exposed via the PTAPE than the CP approach (35.6 [9.07] vs. 16.3 [6.02] mm, P < 0.01). CN XII (8.8 [1.06] mm) was exposed only in the PTAPE group. Above the pontomedullary sulcus, the total area of brain stem exposed was greater with the PTAPE than the CP approach (1003.4 [219.5] mm2 vs. 437.6 [83.7] mm2, P < 0.01). Similarly, the total exposure of the medulla was greater after the PTAPE than the CP exposure (240.2 [57.06] mm2 vs. 48.1 [19.9] mm2, P < 0.01). CONCLUSION: A combined open-endoscopic paradigm is proposed for managing large PCMs. This approach incorporates the EEFM approach to address the limitations of the PTAP and the CP approach in a systematic fashion. Understanding the anatomical findings of this study will aid in tailoring surgical approaches to patients with these complex lesions.

Targeting DNA Methyl Transferases with Decitabine in Cultured Meningiomas.

OBJECTIVE: Meningiomas are a common primary central nervous system tumor that lack a U.S. Food and Drug Administration-approved pharmacotherapy. Approximately 20%-35% of meningiomas are classified as higher grade with poor outcome, whereas patients with lower-grade meningiomas are known to have long-term neurologic deficits and reduced overall survival. Recent efforts to understand the epigenetic landscape of meningiomas have highlighted the importance of DNA methylation for predicting tumor outcomes and prognosis; therefore, inhibition of these pathways may present a viable therapy for these tumors. METHODS: In this study, we perform dose-response curves of decitabine, a DNA methyltransferase inhibitor, on patient-cultured tumors and meningioma cell lines. RESULTS: Thirty total samples were evaluated, including 24 patient-cultured tumors and 6 established meningioma cell lines. Meningiomas were found to have a significant reduction in cell viability after decitabine treatment in a dose dependent manner. The effect was primarily driven by 11 of the 30 tumors in our cohort, or 36.7%. Decitabine significantly reduced cell viability across all grades, tumors from different sexes, recurrent and primary tumors, as well as tumors without a history of previous radiation. Surprisingly, our single radiation-induced tumor did demonstrate greater viability after decitabine treatment. CONCLUSIONS: Our work has identified a potential drug candidate in decitabine for the treatment of meningiomas regardless of clinical subgroup. These data require further evaluation in preclinical models, and the conclusions based on clinical subgroups need to be evaluated in a larger cohort to achieve appropriate statistical power.

Endocrinological outcomes after transcranial resection of tuberculum sellae meningiomas: a systematic review and meta-analysis.

Tuberculum sellae meningiomas (TSMs) arise from the anterior skull base. Endocrine status after TSM resection is an important determinant of quality of life. We sought to better characterize the risk of postoperative endocrinopathy for patients with TSM undergoing open transcranial approach (TCA) microsurgical resection. A systematic review was conducted following MOOSE and PRISMA guidelines. Results were screened against predefined criteria, which included studies evaluating endocrinopathy rates after open transcranial microsurgery for TSM. Outcome incidence was calculated using random-effect meta-analysis of proportions. Eight studies met the inclusion criteria, comprising 406 patients. The average age of the cohort was 52.2 years, and a majority (70%) of the patients were female. The pooled incidence of postoperative transient diabetes insipidus (DI) was 7.5% (95% CI 2.9-12%; p = 0.001; I2 = 75.9%) and permanent DI was 1.6% (95% CI 0.3-2.7%; p = 0.01; I2 = 0%). The pooled rate of postoperative hypopituitarism was 3.6% (95% CI 1.6-5.7%; p < 0.001; I2 = 22.2%), while the incidence of hyperprolactinemia was 1.3% (95% CI 0.1 = 2.6%; p = 0.036; I2 = 8.74%). The incidence of SIADH was 4% in one study but was not included in the meta-analysis. Endocrinopathy after TSM microsurgical resection is rare, but the available studies' poor quality of evidence and inconsistent methodology may reflect that it is underreported in the literature. Nevertheless, clinicians should consider the risk of hormonal impairment and counsel their patients accordingly when selecting a TCA for these lesions.

Nervus Intermedius Outcomes After Vestibular Schwannoma Surgery and Radiosurgery: A Single-Institution Experience.

OBJECTIVE: Nervus intermedius (NI) dysfunction after the management of vestibular schwannoma (VS) is underreported and is experienced by patients undergoing stereotactic radiosurgery and surgical resection. The aim of this study was to present NI outcomes in a series of patients who underwent all treatment modalities for VS and to review the existing literature. METHODS: We performed a retrospective review of all patients with VS who were treated at our institution between January 1, 2008, and December 31, 2018. Demographic data, tumor size, Koos grade, treatment modality, extent of resection, postoperative facial nerve function, and hearing function were collected. NI outcomes were determined from phone interview using a previously published functional questionnaire. RESULTS: Of 222 patients who were reviewed, 98 patients responded to the questionnaire. Patients were stratified into 3 groups: group 1, 54 patients who underwent radiation; group 2, 27 patients who underwent surgical treatment; group 3, 17 patients who underwent both radiation and surgery. Of patients, 28% presented with preoperative NI dysfunction, most commonly dry eye followed by taste dysfunction and lacrimation dysfunction. Following treatment, 79% of patients experienced NI dysfunction, most commonly dry eye. Statistical differences in dry eye and taste dysfunction were observed when comparing the treatment groups. CONCLUSIONS: NI dysfunction is common following treatment for VS and should be included in pretreatment counseling of patients, as it may impact treatment choice and quality of life. Additional studies are warranted to fully characterize NI dysfunction after treatment.

Comparative analysis of the combined petrosal and the pretemporal transcavernous anterior petrosal approach to the petroclival region.

OBJECTIVE: The combined petrosal (CP) approach has been traditionally used to resect petroclival meningioma (PCM). The pretemporal transcavernous anterior petrosal (PTAP) approach has emerged as an alternative. A quantitative comparison of both approaches has not been made. This anatomical study compared the surgical corridors afforded by both approaches and identified key elements of the approach selection process. METHODS: Twelve cadaveric specimens were dissected, and 10 were used for morphometric analysis. Groups A and B (n = 5 in each) underwent the CP and PTAP approaches, respectively. The area of drilled clivus, lengths of cranial nerves (CNs) II-X, length of posterior circulation vessels, surgical area of exposure of the brainstem, and angles of attack anterior and posterior to a common target were measured and compared. RESULTS: The area of drilled clivus was significantly greater in group A than group B (mean ± SD 88.7 ± 17.1 mm2 vs 48.4 ± 17.9 mm2, p < 0.01). Longer segments of ipsilateral CN IV (52.4 ± 2.33 mm vs 46.5 ± 3.71 mm, p < 0.02), CN IX, and CN X (9.91 ± 3.21 mm vs 0.00 ± 0.00 mm, p < 0.01) were exposed in group A than group B. Shorter portions of CN II (9.31 ± 1.28 mm vs 17.6 ± 6.89 mm, p < 0.02) and V1 (26.9 ± 4.62 mm vs 32.4 ± 1.93 mm, p < 0.03) were exposed in group A than group B. Longer segments of ipsilateral superior cerebellar artery (SCA) were exposed in group A than group B (36.0 ± 4.91 mm vs 25.8 ± 3.55 mm, p < 0.02), but there was less exposure of contralateral SCA (0.00 ± 0.00 mm vs 7.95 ± 3.33 mm, p < 0.01). There was no statistically significant difference between groups with regard to the combined area of the exposed cerebral peduncles and pons (p = 0.75). Although exposure of the medulla was limited, group A had significantly greater exposure of the medulla than group B (p < 0.01). Finally, group A had a smaller anterior angle of attack than group B (24.1° ± 5.62° vs 34.8° ± 7.51°, p < 0.03). CONCLUSIONS: This is the first study to quantitatively identify the advantages and limitations of the CP and PTAP approaches from an anatomical perspective. Understanding these data will aid in designing maximally effective yet minimally invasive approaches to PCM.

Hydroxyapatite cement cranioplasty for reconstruction of translabyrinthine approach: aesthetic results, long-term satisfaction, quality of life, and complications.

BACKGROUND: Translabyrinthine approaches (TLAs) for resection of skull base neoplasms are complex with variable reconstruction techniques. Fat grafts in conjunction with hydroxyapatite bone cement techniques have seldom been described in terms of possible superiority to other skull base reconstruction techniques. We sought to determine the impact of this skull base reconstruction technique on clinical outcomes and patient's satisfaction. METHOD: We performed a retrospective analysis of all patients who underwent translabyrinthine approaches for resection of CPA lesions over a 5-year period. Both post-op objective and subjective markers of reconstruction, as well as postoperative complications, were collected and analyzed. RESULTS: Sixty-nine patients were included, 34 underwent reconstruction with hydroxyapatite and fat (rHAC) and 35 with fat alone (rF). rHAC was associated with fewer cranial wound superficial infection/dehiscence (0% vs 14.3%; p = 0.029) and shorter length of stay (mean ± standard deviation) (6.9 ± 7.4 vs 4.4 ± 3.7 days, p = 0.008). Postoperative subjective characterization of rHAC demonstrated improved satisfaction scores (1.38 ± 0.5 vs 1.83 ± 1; p = 0.049) and fewer reports of post-operative irregularities (11.5% vs 37.5%; p = 0.017). CONCLUSION: The use of hydroxyapatite for cranial reconstruction after translabyrinthine approaches has improved patient satisfaction and decreased cranial defects in our small series. Postoperative complications are consistent with other described methods, but with shorter hospital stay, decreased risk of superficial wound dehiscence/infection, and a perceived superiority in preventing percutaneous post-op CSF leaks.

Acute Sigmoid Sinus Compromise Following Skull Base Procedures: Is a "Laissez-Faire" Approach Best?

Objective Venous sinus compromise (VSC) of the sigmoid sinus can manifest as either venous sinus thrombosis, stenosis, or a combination of the two. It may occur following retro and presigmoid craniotomy, even in the absence of overt intraoperative sinus injury. Currently, the optimal management of VSC in the perioperative period is not well established. We report our incidence and management of VSC following skull base surgery around the sigmoid sinus. Patients and Methods A retrospective chart review of all patients undergoing presigmoid, retrosigmoid, or combined approach by the senior author from 2014 to 2019 was performed. Main Outcome Measures Charts were reviewed for patient demographics, surgical details, details of venous sinus compromise, and patient outcomes. Statistical analyses were performed using R 3.6.0 (R Project). Results A 115 surgeries were found with a total of 13 cases of VSC (overall incidence of 11.3%). Nine cases exhibited thrombosis and four stenosis. There were no statistically significant differences between the groups with (group 1) or without (group 2) VSC. Operation on the side of the dominant sinus did not predispose to postoperative VSC. Five patients received antiplatelet medication in the perioperative period. There was no difference in outcomes in the group that did not receive antiplatelet medication versus those who did. Conclusion Acute iatrogenic sigmoid sinus compromise can be managed expectantly. We believe that the treatment for each instance of VSC must be individualized, considering the symptoms of the patient, rather than applying a universal algorithm.

Combined biportal unilateral endoscopic endonasal and endoscopic anterior transmaxillary approach for resection of lesions involving the infratemporal fossa.

BACKGROUND: Approaching tumors involving the infratemporal fossa (ITF) is technically challenging due to the complex relationships between several neurovascular structures and the deep-seated location of these lesions. METHODS: The authors describe in detail a minimally invasive approach to the ITF, consisting on a single-nostril endoscopic endonasal transmaxillary approach aided by an anterior transmaxillary port (EEA-ATMa). Anatomical landmarks and surgical tenets of this approach are highlighted and reviewed with the goal to guarantee successful tumor resection and avoid operative complications. CONCLUSION: The EEA-ATMa is technically feasible and offers excellent surgical exposure to the anterior and lateral aspect of ITF, without the need of transecting the Vidian nerve or performing a wide septectomy.

Clinical Features of Pineal Parenchymal Tumors of Intermediate Differentiation (PPTID): A Single-Institution Series.

OBJECTIVE: Pineal parenchymal tumors of intermediate differentiation (PPTID) are rare tumors of the pineal gland. Their treatment is often heterogeneous due to the lack of literature to compile standardized treatments. Although no single institution has large numbers of cases, our experience has been that the clinical course is more varied and complicated than reported. METHODS: We reviewed the clinical data for all patients with pathology found to be consistent with PPTID at our institution between the years 2006 and 2019. RESULTS: Nine patients were identified. At initial diagnosis, all were treated with surgery and 4 of 9 patients underwent gross total resection. Adjuvant radiation therapy to the resection bed was administered in 6 of 9 patients. Mean follow-up time was 95.3 months. Mean progression-free survival was 50.5 months, with a tendency to be longer for male sex and after gross total resection. Seven patients developed a recurrence. Five of 6 known locations of first recurrences had either distant metastases or dissemination of disease. First recurrences were treated with radiation alone in 5 patients, craniospinal radiation with multiagent chemotherapy in 1 patient, and surgery with radiation therapy in 1. At last follow-up, 2 patients had died. CONCLUSIONS: Herein, we report clinical patterns of disease progression and treatment patterns of PPTID. Many patients progressed during the follow-up period. Disseminated disease was the most common presentation at recurrence. Ultimately, given the risk of recurrence and dissemination at recurrence, more aggressive treatment strategies should be considered. Specifically, our series suggests a benefit of adjuvant radiation at initial diagnosis for grade II patients.

High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas.

BACKGROUND: Meningiomas are the most common primary central nervous system tumors. 20-30% of these tumors are considered high-grade and associated with poor prognosis and high recurrence rates. Despite the high occurrence of meningiomas, there are no FDA-approved compounds for the treatment of these tumors. METHODS: In this study, we screened patient-cultured meningiomas with an epigenetic compound library to identify targetable mechanisms for the potential treatment of these tumors. Meningioma cell cultures were generated directly from surgically resected patient tumors and were cultured on a neural matrix. Cells were treated with a library of compounds meant to target epigenetic functions. RESULTS: Although each tumor displayed a unique compound sensitivity profile, Panobinostat, LAQ824, and HC toxin were broadly effective across most tumors. These three compounds are broad-spectrum Histone Deacetylase (HDAC) inhibitors which target class I, IIa, and IIb HDACs. Panobinostat was identified as the most broadly effective compound, capable of significantly decreasing the average cell viability of the sample cohort, regardless of tumor grade, recurrence, radiation, and patient gender. CONCLUSIONS: These findings strongly suggest an important role of HDACs in meningioma biology and as a targetable mechanism. Additional validation studies are necessary to confirm these promising findings, as well to identify an ideal HDAC inhibitor candidate to develop for clinical use.

Long-term disease control and treatment outcomes of stereotactic radiosurgery in cavernous sinus meningiomas.

BACKGROUND: Most of the current knowledge on the clinical effects of stereotactic radiosurgery (SRS) on the treatment of cavernous sinus meningiomas (CSM) is based on series with limited follow-up. However, determining the role of radiation in a tumor with slow disease progression such as CSM necessitates long term follow up. OBJECTIVE: To review and pool metadata in the literature to determine the long-term outcomes of SRS with respect to clinical and radiographic tumor control of CSM. METHODS: A systematic search was conducted following MOOSE guidelines. Results were screened against predefined criteria, which excluded studies with a median follow-up less than 5 years. The incidences of each outcome were calculated using random-effects metanalysis of proportions. RESULTS: Seven studies met the inclusion criteria, comprising 645 patients. The median follow-up was 74 months (range 62-87). Progression-free-survival at 5, 10, and 15 years was 93.4% (95% CI 89.1-96.7%), 84.9% (95% CI 77-91.4%), and 81.3% (95% CI 74-87.7%), respectively. Clinical response to SRS at last follow-up defined as improvement of cranial nerve deficits was found in in 36.4% (95% CI 26.3-47.1%) of patients, while worsening or onset of new cranial nerve deficits was found in 11.5% (95% CI 7.9-15.7%). Radiological regression was found in 57.8% (95% CI 43-71.8%), while tumor progression was found in 8.5% (95% CI 5.2-12.6%). CONCLUSION: SRS achieves excellent disease control and radiographic response in CSM. Although the risk of long-term cranial neuropathies is minimal, it is relatively higher to what has been previously reported in early series with limited follow-up.