Meningioma: International Consortium on Meningiomas (ICOM) consensus review on scientific advances & treatment paradigms for clinicians, researchers, and patients.

Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and the rising availability of neuroimaging. While most exhibit non-malignant behaviour, a subset of meningiomas are biologically aggressive and lead to significant neurological morbidity and mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW) working group. There also remains clinical equipoise on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas (ICOM) including field-leading experts, have prepared a comprehensive consensus narrative review directed towards clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality of life studies, and management strategies for unique meningioma patient populations. In each section we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.

Corrigendum: Grade 3 Meningioma Survival and Recurrence Outcomes in an International Multicenter Cohort.

[This corrects the article DOI: 10.1055/s-0044-1779888.].

Grade 3 meningioma survival and recurrence outcomes in an international multicenter cohort.

OBJECTIVE: Grade 3 meningioma represents a rare meningioma subtype, for which limited natural history data are available. The objective of this study was to identify demographics and pathologic characteristics, clinical and functional status outcomes, and prognostic factors in an international cohort of grade 3 meningioma patients. METHODS: Clinical and histopathological data were collected for patients treated at 7 sites across North America and Europe between 1991 and 2022. RESULTS: A total of 103 patients (54% female, median age 65 [IQR 52, 72] years) were included. Sixty-seven (65%) patients had de novo grade 3 lesions, whereas 29 (28%) had malignant transformations of lower-grade meningiomas. All patients underwent initial resection of their tumor. Patients were followed for a median of 46 (IQR 24, 108) months, during which time there were 65 (73%) recurrences and 50 (49%) deaths. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 66% (95% CI 56%-77%) and 37% (95% CI 28%-48%), respectively. Age ≥ 65 years and male sex were independent predictors of worse OS and PFS in multivariate regression analysis, while postoperative radiotherapy was independently associated with improved OS. Karnofsky Performance Status (KPS) remained stable relative to baseline over 5 years postdiagnosis among participants who were alive at the end of the follow-up period. CONCLUSIONS: This large multicenter study provides insight into the longitudinal outcomes of grade 3 meningioma, with respect to recurrence, survival, and functional status. This study affirms the survival benefit conferred by radiotherapy in this population and suggests good functional status outcomes for patients surviving to 5 years postoperatively.

Delayed neurological improvement in a patient with Duret hemorrhage secondary to an acute subdural hematoma: illustrative case.

BACKGROUND: Duret hemorrhage is a rare phenomenon wherein rapid transtentorial herniation results in brainstem injury and hemorrhage. It is usually regarded as a poor prognostic factor representing irreversible and often catastrophic brain injury. The authors report an unusual case of Duret hemorrhage with spontaneous delayed neurological recovery postoperatively after surgical treatment of an acute subdural hematoma (SDH). OBSERVATIONS: The authors present the case of a 65-year-old male who initially presented to the hospital with a large acute left-sided SDH causing 1.3 cm of midline shift. He was taken urgently for a craniotomy, with no significant intraoperative swelling or visible contusions. Postoperative imaging revealed an unexpected pontine hyperdensity concerning for a Duret hemorrhage. He initially had no neurological improvement; however, at 3 weeks postoperatively, he gradually recovered and was able to follow commands and was extubated. At 10 weeks after surgery, his Glasgow Coma Scale score improved to 15, with mild residual left hemiparesis. LESSONS: This case challenges a classic dogma that Duret hemorrhage carries a universally poor outcome. In select cases, patients can make meaningful recoveries in a delayed fashion. The lack of intraoperative contusions and swelling may have contributed to this patient's recovery.

Reoperation in adult patients with recurrent glioblastoma: A matched cohort analysis.

Background: Despite maximal safe cytoreductive surgery and postoperative adjuvant therapies, glioblastoma (GBM) inevitably recurs and leads to deterioration of neurological status and eventual death. There is no consensus regarding the benefit of repeat resection for enhancing survival or quality of life in patients with recurrent GBM. We aimed to examine if reoperation for GBM recurrence incurs a survival benefit as well as examine its complication profile. Methods: We performed a single-center retrospective chart review on all adult patients who underwent resection of supratentorial GBM between January 1, 2008 and December 1, 2013 at our center. Patients with repeat resection were manually matched for age, sex, tumor location, and Karnofsky Performance Status (KPS) with patients who underwent single resection to compare overall survival (OS), and postoperative morbidity. Results: Of 237 patients operated with GBM, 204 underwent single resection and 33 were selected for repeat surgical resections. In a matched analysis there was no difference in the OS between groups (17.8 ± 17.6 months vs 17 ± 13.5 months, P = .221). In addition, repeat surgical resection had a higher rate of postoperative neurological complications compared to the initial surgery. Conclusions: When compared with matched patients who underwent a single surgical resection, patients undergoing repeat surgical resection did not show significant increase in OS and may have incurred more neurological complications related to the repeat resection. Further studies are required to assess which patients would benefit from repeat surgical resection and optimize timing of the repeat resection in selected patients.

Comparative Efficacy of Treatments for Brain Metastases from Non-Small Cell Lung Cancer without an EGFR-Mutation/ALK-Rearrangement: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: As many as 30% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases (BMs) over the course of their illness. Here, we quantitatively compare the efficacy of the various emerging regimens for NSCLC BMs without a definitive targetable epidermal growth factor receptor mutation/ALK rearrangement. METHODS: We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL, and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs that included ≥10 patients were included. We used a frequentist fixed or random-effects model for network meta-analysis. The outcomes of interest included intracranial progression-free survival (iPFS), overall survival (OS), and overall progression-free survival. RESULTS: In total, 18 studies representing 17 trials (n = 2726 patients) were identified. Immune checkpoint inhibitor regimens showed significant improvement in OS compared with chemotherapy alone, including pembrolizumab and chemotherapy (6 studies, hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.21-0.62), atezolizumab alone (HR 0.54, 95% CI 0.33-0.89), and nivolumab and ipilimumab (HR 0.64, 95% CI 0.42-0.97). An improvement in overall PFS was seen with use of pembrolizumab and chemotherapy compared with chemotherapy alone (3 studies, HR 0.42, 95% CI 0.26-0.68). Studies evaluating checkpoint inhibitors did not report iPFS data, and we did not find improvement in iPFS or OS with the addition of any chemotherapy regimen to whole-brain radiation therapy. CONCLUSIONS: In this network meta-analysis, we demonstrate the promising survival benefit with use of checkpoint inhibitor-based regimens in NSCLC BMs without a targetable epidermal growth factor receptor mutation/ALK rearrangement. Moving forward, large-scale BM-focused RCTs are necessary to establish the iPFS benefit of immune checkpoint inhibitor-based immunotherapy in this patient population.

Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Brain metastases (BM) from non-small-cell lung cancer (NSCLC) are frequent and carry significant morbidity, and current management options include varying local and systemic therapies. Here, we performed a systematic review and network meta-analysis to determine the ideal treatment regimen for NSCLC BMs with targetable EGFR-mutations/ALK-rearrangements. METHODS: We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs including ≥10 patients were selected. We used a frequentist random-effects model for network meta-analysis (NMA) and assessed the certainty of evidence using the GRADE approach. Our primary outcome of interest was intracranial progression-free survival (iPFS). RESULTS: We included 24 studies representing 19 trials with 1623 total patients. Targeted tyrosine kinase inhibitors (TKIs) significantly improved iPFS, with second-and third- generation TKIs showing the greatest benefit (HR=0.25, 95%CI 0.15-0.40). Overall PFS was also improved compared to conventional chemotherapy (HR=0.47, 95%CI 0.36-0.61). In EGFR-mutant patients, osimertinib showed the greatest benefit in iPFS (HR=0.32, 95%CI 0.15-0.69) compared to conventional chemotherapy, while gefitinib + chemotherapy showed the greatest overall PFS benefit (HR=0.26, 95%CI 0.10-0.70). All ALKi improved overall PFS compared to conventional chemotherapy, with alectinib having the greatest benefit (HR=0.13, 95%CI 0.07-0.24). CONCLUSIONS: In patients with NSCLC BMs and EGFR/ALK mutations, targeted TKIs improve intracranial and overall PFS compared to conventional modalities such as chemotherapy, with greater efficacy seen using newer generations of TKIs. This data is important for treatment selection and patient counseling, and highlights areas for future RCT research. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=179060.

Pharmacoprophylaxis for Venous Thromboembolism in Spinal Surgery: A Systematic Review and Meta-analysis.

OBJECTIVE: Venous thromboembolism (VTE) is a significant contributor to postoperative morbidity and mortality. Prophylactic regimens for VTE involve mechanical prophylaxis and pharmacoprophylaxis. This systematic review and meta-analysis aimed to determine the efficacy and safety of pharmacoprophylaxis in comparison with any nonpharmacoprophylaxis regimen for the prevention of postoperative VTE in patients undergoing spinal surgery. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and ICRCTN were searched for comparative studies including both pharmacoprophylaxis and nonpharmacoprophylaxis post spinal surgery. The primary outcome was the incidence of VTE within the postoperative hospitalized period. Secondary outcomes included the incidence of spinal epidural hematoma, significant bleeding events, and other adverse events associated with VTE. The data was pooled using random-effects models of meta-analysis and relative risk (RR) was calculated. RESULTS: Four retrospective and 3 randomized controlled trials representing a total of 8373 patients were included. Overall, there was a significant decrease in postoperative deep venous thrombosis with pharmacoprophylaxis versus nonpharmacoprophylaxis (RR 0.42, 95% confidence interval 0.21-0.86, P = 0.02, I2 = 0%); however, there were no significant differences between the groups in the incidences of VTE (RR 0.31, 95% confidence interval 0.12-0.81, P = 0.02, I2 = 0%). The incidences of spinal epidural hematoma and significant bleeding events were rare and comparable in both groups. CONCLUSIONS: This systematic review and meta-analysis found a potential benefit with pharmacoprophylaxis post spinal surgery in the prevention of deep venous thrombosis. However, there is a need for future randomized controlled trials to investigate the efficacy and safety of pharmacoprophylaxis in spinal surgery across various spinal procedures.

Safety of Early Mobilization in Patients With Intraoperative Cerebrospinal Fluid Leak in Minimally Invasive Spine Surgery: A Case Series.

BACKGROUND: Cerebrospinal fluid (CSF) leak is a common complication in spine surgery. Repairing durotomy is more difficult in the setting of minimally invasive spine surgery (MISS). Efficacy of postoperative bed rest in case of dural tear in MISS is not clear. OBJECTIVE: To assess the safety and efficacy of our protocol of dura closure without changing access, early mobilization, and discharge in cases of intraoperative CSF leak in MISS. METHODS: A retrospective review from 2006 to 2018 of patients who underwent MISS for degenerative and neoplastic diseases with documented accidental or intentional durotomy was conducted. The primary outcome of interest was readmission rate for repair of persistent CSF leak. Secondary outcomes captured included development of pseudomeningocele, positional headache, and subdural hematoma. RESULTS: A total of 80 patients were identified out of 527 patients. Of these, intentional durotomy was performed in 28 patients and unintentional durotomy occurred in 52 patients. Mean follow-up period was 80.6 mo. Most of the patients were discharged on postoperative day 0 (within 4 h of surgery) without activity restrictions. A total of 2 (2.5%) patients required readmission and dural repair for continuous CSF leak and 3 patients (3.75%) developed pseudomeningocele. No lumbar drain insertion, meningitis, or subdural hematoma was reported. CONCLUSION: Early mobilization and discharge in cases of intraoperative CSF leak in MISS appear to be safe and not associated with higher rate of complications than that of reported literature.

Outcomes of civilian pediatric craniocerebral gunshot wounds: A systematic review.

BACKGROUND: Pediatric craniocerebral gunshot injuries (CGIs) occur both in the context of accidental and intentional trauma. The incidence and physiology of pediatric CGIs merit reexamination of prognostic factors and treatment priorities. This study characterizes the current understanding of mortality and prognostic factors in this patient population. METHODS: A systematic search was conducted. Selection criteria included all studies published since 2000, which described civilian isolated CGIs in pediatric patients. Data were analyzed qualitatively and quantitatively to identify factors prognostic for the primary outcome of mortality. Secondary outcomes included functional outcome status, requirement for surgery, and injury complications. Study quality was assessed with the Newcastle-Ottawa Scale. This study was registered with PROSPERO (CRD42019134231). RESULTS: Initial search revealed 349 unique studies. Forty underwent full text screening, and eight studies were included in the final synthesis. The overall mortality rate was 44.8%. Most CGIs occurred in older teenagers. Aggressive surgical treatment was recommended by one author, while remaining studies emphasized clinical judgment. Reported prognostic factors include initial Glasgow Coma Scale, pupil reactivity, involvement of multiple lobes or deep nuclei, and bihemispheric injuries. Reported complications from CGIs included seizure, meningitis, abscess, cerebrospinal fluid leak, bullet migration, focal neurological deficits, endocrine abnormalities, cognitive deficits, and neuropsychological deficits. The Glasgow Outcome Scale was the predominant measure of function and demonstrated a moderate recovery in 17.4% and a good recovery in 27.3% of patients. CONCLUSION: This systematic review analyzed the existing evidence for prognostic factors in the context of pediatric CGIs. Significant long-term clinical improvement is possible with interventions including urgent surgical therapy. Fixed bilateral pupils and low initial Glasgow Coma Scale correlate with mortality but do not predict all patient outcomes. Patients younger than 15 years are underreported and may have differences in outcome. The literature on pediatric CGIs is limited and requires further characterization. LEVEL OF EVIDENCE: Systematic Review, level IV.

Comparison of endoscopic third ventriculostomy with or without choroid plexus cauterization in pediatric hydrocephalus: a systematic review and meta-analysis.

OBJECTIVE: Pediatric hydrocephalus is a significant contributor to infant morbidity and mortality, particularly in developing countries. The mainstay of treatment has long been shunt placement for CSF diversion, but recent years have seen the rise of alternative procedures such as endoscopic third ventriculostomy (ETV), which provides similar efficacy in selected patients. The addition of choroid plexus cauterization (CPC) to ETV has been proposed to increase efficacy, but the evidence of its utility is limited. This systematic review and meta-analysis aimed to determine the efficacy and safety of ETV+CPC in comparison to ETV alone for the treatment of pediatric all-cause hydrocephalus. METHODS: MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov, and ICRCTN databases were searched from conception through to October 2018 for comparative studies including both ETV+CPC and ETV in a pediatric population. The primary outcome was success rate, defined as no secondary procedure required for CSF diversion; secondary outcomes included time to failure, mortality, and complications. Data were pooled using random-effects models of meta-analysis, and relative risk (RR) was calculated. RESULTS: Five studies were included for final qualitative and quantitative analysis, including 2 prospective and 3 retrospective studies representing a total of 963 patients. Overall, there was no significant difference in success rates between ETV and ETV+CPC (RR 1.24, 95% CI 0.88-1.75, p = 0.21). However, a subgroup analysis including the 4 studies focusing on African cohorts demonstrated a significant benefit of ETV+CPC (RR 1.38, 95% CI 1.08-1.78, p = 0.01). There were no notable differences in complication rates among studies. CONCLUSIONS: This systematic review and meta-analysis failed to find an overall benefit to the addition of CPC to ETV; however, a subgroup analysis showed efficacy in sub-Saharan African populations. This points to the need for future randomized clinical trials investigating the efficacy of ETV+CPC versus ETV in varied patient populations and geographic locales.

Visual Outcomes After Endoscopic Endonasal Resection of Orbital Lesions.

BACKGROUND: The endoscopic endonasal approach (EEA) has been increasing in popularity as an alternative to traditional transcranial and transorbital approaches in the treatment of orbital pathological entities. The purpose of the present study was to examine the outcomes of patients who had undergone EEA resection of orbital lesions at our center. METHODS: We performed a retrospective medical record review of patients who had undergone the EEA for resection of orbital lesions and orbital apex decompression from January 1, 2006 to December 1, 2019. For all the patients, the demographic data, presenting symptoms, symptom duration, imaging data, operative details, and postoperative outcomes were collected and reviewed. RESULTS: Nine patients underwent endoscopic endonasal resection of orbital lesions and orbital apex decompression at our center, including 6 male patients and 3 female patients. The mean age was 49.4 years, and the mean follow-up period was 3.8 years (range, 1-13.5 years). The orbital pathological lesions that were treated included nasopharyngeal carcinoma, hemangioma, fibrous dysplasia, IgG4 pseudotumor, inverted papilloma, angioleiomyoma, adenocarcinoma, and neuroendocrine paraganglioma metastasis. All the patients presented with exophthalmos of the affected orbit. Of the 9 patients, 5 presented with decreased visual acuity on examination. Postoperatively, 1 of these 5 patients had improved to baseline visual acuity, 3 had stable vision, and 1 had brief improvement before experiencing progressive visual decline 1 month postoperatively. Two patients presented with diplopia, and both improved postoperatively. Three patients experienced new, transient, and self-limiting postoperative diplopia. CONCLUSIONS: For patients with orbital lesions causing compressive optic neuropathy, the endoscopic endonasal approach can be used as an alternative strategy in appropriately selected patients.

Skull Base Calcifying Pseudoneoplasms of the Neuraxis: Two Case Reports and a Systematic Review of the Literature.

BACKGROUND: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumefactive lesion. CAPNONs can mimic calcified meningiomas at the skull base. METHODS: Here, we report two cases of CAPNON and present a systematic review of the literature on skull base CAPNONs, to compare CAPNONs with calcified meningiomas. RESULTS: Case 1: A 57-year-old man presented with right-sided lower cranial neuropathies and gait ataxia. He underwent a subtotal resection of a right cerebellopontine angle lesion, with significant improvement of his gait ataxia. However, his cranial neuropathies persisted. Pathological examination of the lesion was diagnostic of CAPNON, with the entrapped nerve fibers identified at the periphery of the lesion, correlating with the patient's cranial neuropathy. Case 2: A 70-year-old man presented with progressive headache, gait difficulty, and cognitive impairment. He underwent a frontotemporal craniotomy for a near-total resection of his right basal frontal CAPNON. He remained neurologically stable 7 years after the initial resection without evidence of disease recurrence. We analyzed 24 reported CAPNONs at the skull base in our systematic review of the literature. Cranial neuropathies were present in 11 (45.8%) patients. Outcomes regarding cranial neuropathies were documented in six patients: two had sacrifice of the nerve function with surgical approaches and four had persistent cranial neuropathies. CONCLUSION: While CAPNON can radiologically and grossly mimic calcified meningiomas, they are two distinctly different pathologies. CAPNONs located at the skull base are commonly associated with cranial neuropathies, which may be difficult to reverse despite surgical intervention.

The expanded endoscopic endonasal approach for suprasellar meningiomas: long-term outcomes in a single-center series of 27 patients.

BACKGROUND: The endoscopic endonasal approach (EEA) has become increasingly employed in the treatment of suprasellar meningiomas. These tumors often cause visual symptoms due to compression of the anterior visual pathway. We aimed to examine long-term visual outcomes after EEA for optic nerve decompression and resection of suprasellar meningioma at our center, and to identify preoperative factors predictive of postoperative visual improvement. METHODS: We performed a retrospective cohort study on 27 patients who underwent the EEA for resection of meningiomas extending into the suprasellar cistern and decompression of anterior visual pathway between January 1, 2005, and March 1, 2019. RESULTS: We treated 8 male and 19 female patients, with a mean follow-up of 7.6 years. The mean age of our patients at initial presentation was 60.1 years. Eighteen patients (66.7%) presented with visual acuity deficits, and 12 (44.4%) patients presented with visual field deficits. Postoperatively, 11 patients had improved visual acuity, 6 had stable visual acuity, and 1 patient had slow and progressive decline of visual acuity; 5 patients had improved visual field, 6 had stable visual field, and 1 patient had slow and progressive decline in visual field. Patients less likely to have postoperative improvement of visual acuity were those with longer than 6-month duration of visual symptoms (P = 0.024*) as well as patients with the presence of a relative afferent pupillary defect (RAPD) (P = 0.023*). CONCLUSION: The EEA can achieve good visual outcomes in patients harboring suprasellar meningiomas. Symptom duration of less than 6 months and lack of a RAPD were positive predictors of postoperative visual acuity.

Single- or double-anastomosis duodenal switch versus Roux-en-Y gastric bypass as a revisional procedure for sleeve gastrectomy: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is one of the most commonly performed bariatric procedure worldwide. There is currently no consensus on which revisional procedure is best after an initial SG. OBJECTIVES: To compare the efficacy and safety between single-anastomosis duodeno-ileal bypass (SADI) or biliopancreatic diversion with duodenal switch (BPD-DS) versus Roux-en-Y gastric bypass (RYGB) as a revisional procedure for SG. SETTING: University Hospital, Canada. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PubMed were searched up to August 2018. Studies were eligible for inclusion if they compared SADI or BPD-DS with RYGB as a revisional bariatric procedure for SG. Primary outcome was absolute percentage of total weight loss. Secondary outcomes were length of stay, adverse events, and improvement or resolution of co-morbidities (diabetes, hypertension, or hypercholesterolemia). Pooled mean differences were calculated using random effects meta-analysis. RESULTS: Six retrospective cohort studies involving 377 patients met the inclusion criteria. The SADI/BPD-DS group achieved a significantly higher percentage of total weight loss compared with RYGB by 10.22% (95% confidence interval, -17.46 to -2.97; P = .006). However, there was significant baseline equivalence bias with 4 studies reporting higher initial body mass index (BMI) in the SADI/BPD-DS group. There were no significant differences in length of stay, adverse events, or improvement of co-morbidities between the 2 groups. CONCLUSION: SADI, BPD-DS, and RYGB are safe and efficacious revisional surgeries for SG. Both SADI and RYGB are efficacious in lowering initial BMI but there is more evidence for excellent weight loss outcomes with the conversion to BPD-DS when the starting BMI is high. Further randomized trials are required for definitive conclusions.