Publications by authors named "Farshad Nassiri"

74 Publications

Clinical significance of checkpoint regulator "Programmed death ligand-1 (PD-L1)" expression in meningioma: review of the current status.

J Neurooncol 2021 Feb 21;151(3):443-449. Epub 2021 Feb 21.

MacFeeters-Hamilton Center for Neuro-Oncology Research, Princess Margaret Cancer Center, 14-701, Toronto Medical Discovery Tower (TMDT), 101 College St, Toronto, ON, M5G 1L7, Canada.

Introduction: Meningioma is the most common primary brain tumor. Most meningiomas are benign; however, a subset of these tumors can be aggressive, presenting with early or multiple tumor recurrences that are refractory to neurosurgical resection and radiotherapy. There is no standard systemic therapy for these patients, and post-surgical management of these patients is usually complicated due to lack of accurate prediction for tumor progression.

Methods: In this review, we summarise the crucial immunosuppressive role of checkpoint regulators, including PD-1 and PD-L1 interacting in the tumor microenvironment, which has led to efforts aimed at targeting this axis.

Results: Since their discovery, checkpoint inhibitors have significantly improved the outcome in many types of cancers. Currently, targeted therapy for PD-1 and PD-L1 proteins are being tested in several ongoing clinical trials for brain tumors such as glioblastoma. More recently, there have been some reports implicating increased PD-L1 expression in high-grade (WHO grades II and III) meningiomas. Several clinical trials are underway to assess the efficacy of checkpoint inhibitors in the therapeutic management of patients with aggressive meningiomas. Here, we review the immune suppressive microenvironment in meningiomas, and then focus on clinical and pathological characterization and tumor heterogeneity with respect to PD-L1 expression as well as challenges associated with the assessment of PD-L1 expression in meningioma.

Conclusion: We conclude with a brief review of ongoing clinical trials using checkpoint inhibitors for the treatment of high-grade and refractory meningiomas.
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http://dx.doi.org/10.1007/s11060-020-03584-8DOI Listing
February 2021

In-Hospital Course and Complications of Laminectomy alone Versus Laminectomy plus Instrumented Posterolateral Fusion for Lumbar Degenerative Spondylolisthesis: A Retrospective Analysis of 1,804 Patients from the NSQIP Database.

Spine (Phila Pa 1976) 2020 Dec 7. Epub 2020 Dec 7.

Division of Neurosurgery and Spinal Program, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Study Design: Retrospective analysis of data from the National Surgical Quality Improvement Program (NSQIP).

Objective: We sought to compare the short-term outcomes of laminectomy with/without fusion for single-level lumbar degenerative spondylolisthesis (DS).

Summary Of Background Data: Lumbar DS is a common cause of low back and radicular pain. Controversy remains over the safety and efficacy of fusion in addition to standard decompressive surgery.

Methods: Patients with lumbar DS who underwent laminectomy alone or laminectomy plus posterolateral fusion at a single level were identified from the 2012-2017 NSQIP database. Outcomes included 30-day mortality, major complication, reoperation, readmission, as well as operative duration, need for blood transfusion, length of stay (LOS), and discharge destination. Outcomes were compared between treatment groups by multivariable regression, adjusting for age, sex, and comorbidities (modified Frailty Index). Effect sizes were reported by adjusted odds ratio (aOR) or mean difference (aMD).

Results: The study cohort consisted of 1,804 patients; of these, 802 underwent laminectomy alone and 1,002 laminectomy plus fusion. On both unadjusted and adjusted analyses, there was no difference in 30-day mortality, major complications, reoperation, or readmission. However, laminectomy plus fusion was associated with longer operative time (170.0 vs. 152.7 min; aMD 16.00 min, P < 0.001), longer hospital LOS (3.2 vs. 2.5 days; aMD 0.68, P < 0.001), more frequent need for intra- or post-operative blood transfusion (6.8% vs. 3.1%; aOR 2.24, P=0.001), and less frequent discharge home (80.7% vs. 89.2%; aOR 0.46, P < 0.001).

Conclusions: We found single-level laminectomy plus fusion for lumbar DS to have a comparable short-term safety profile to laminectomy alone. However, fusion was associated with longer operative time and LOS, higher risk of blood transfusion, and greater need for inpatient rehabilitation. These factors should be recognized by clinicians and discussed with patients in the context of their values when weighing surgical treatment of lumbar DS.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003858DOI Listing
December 2020

Correction to: Epigenomic, genomic, and transcriptomic landscape of schwannomatosis.

Acta Neuropathol 2021 Jan;141(1):117

Princess Margaret Cancer Center and MacFeeters-Hamilton Center for Neuro-Oncology Research, University Health Network, Wilkins Family Chair in Brain Tumor Research, 14-701 PMCRT, 101 College St, Toronto, ON, M5G 1L7, Canada.

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http://dx.doi.org/10.1007/s00401-020-02241-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852885PMC
January 2021

Epigenomic, genomic, and transcriptomic landscape of schwannomatosis.

Acta Neuropathol 2021 01 6;141(1):101-116. Epub 2020 Oct 6.

Princess Margaret Cancer Center and MacFeeters-Hamilton Center for Neuro-Oncology Research, University Health Network, Wilkins Family Chair in Brain Tumor Research, 14-701 PMCRT, 101 College St, Toronto, ON, M5G 1L7, Canada.

Schwannomatosis (SWNTS) is a genetic cancer predisposition syndrome that manifests as multiple and often painful neuronal tumors called schwannomas (SWNs). While germline mutations in SMARCB1 or LZTR1, plus somatic mutations in NF2 and loss of heterozygosity in chromosome 22q have been identified in a subset of patients, little is known about the epigenomic and genomic alterations that drive SWNTS-related SWNs (SWNTS-SWNs) in a majority of the cases. We performed multiplatform genomic analysis and established the molecular signature of SWNTS-SWNs. We show that SWNTS-SWNs harbor distinct genomic features relative to the histologically identical non-syndromic sporadic SWNs (NS-SWNS). We demonstrate the existence of four distinct DNA methylation subgroups of SWNTS-SWNs that are associated with specific transcriptional programs and tumor location. We show several novel recurrent non-22q deletions and structural rearrangements. We detected the SH3PXD2A-HTRA1 gene fusion in SWNTS-SWNs, with predominance in LZTR1-mutant tumors. In addition, we identified specific genetic, epigenetic, and actionable transcriptional programs associated with painful SWNTS-SWNs including PIGF, VEGF, MEK, and MTOR pathways, which may be harnessed for management of this syndrome.
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http://dx.doi.org/10.1007/s00401-020-02230-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785562PMC
January 2021

Programmed death ligand-1 (PD-L1) expression in meningioma; prognostic significance and its association with hypoxia and NFKB2 expression.

Sci Rep 2020 08 24;10(1):14115. Epub 2020 Aug 24.

Princess Margaret Cancer Center, MacFeeters-Hamilton Center for Neuro-Oncology Research, 14-701, Toronto Medical Discovery Tower (TMDT), 101 College St, Toronto, ON, M5G 1L7, Canada.

Management of clinically aggressive meningiomas is a considerable challenge. PD-L1 induced immune suppression has increasingly gained attention in clinical management of cancer; however, to date, the clinical significance and regulatory mechanisms of PD-L1 in meningioma is not yet fully characterized. We sought to characterize PD-L1 expression in meningioma and elucidate its regulatory mechanisms. Immunohistochemical staining of PD-L1 expression in meningiomas showed 43% positivity in both tumor and immune cells and we observed intra and inter tumoral heterogeneity. Univariate and multivariate analyses confirmed that PD-L1 protein expression is an independent prognostic marker for worse recurrence free survival in meningioma. Furthermore, our transcriptomic analysis revealed a strong association between PD-L1 expression and that of NFKB2 and carbonic anhydrase 9 (CA9). We also demonstrated that both of these markers, when co-expressed with PD-L1, predict tumor progression. Our studies on several meningioma cell lines cultured in hypoxic conditions validated the association of CA9 and PD-L1 expression. Here we show the clinical significance of PD-L1 in meningioma as a marker that can predict tumor recurrence. We also show an association PD-L1 expression with NFKB2 expression and its induction under hypoxic conditions. These findings may open new avenues of molecular investigation in pathogenesis of meningioma.
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http://dx.doi.org/10.1038/s41598-020-70514-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445252PMC
August 2020

How to live with a meningioma: experiences, symptoms, and challenges reported by patients.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa086. Epub 2020 Jul 10.

Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada.

Background: We aimed to explore gaps in the care of meningioma patients that could improve quality of care by better understanding symptoms experienced by patients at various stages of treatment, and afterwards.

Methods: A novel 19-item self-administered questionnaire was provided for patients with meningiomas to complete by the American Brain Tumor Association (ABTA) over a 3-month period.

Results: A total of 1852 unique respondents were included. Nearly one-third of all respondents felt they received insufficient information about meningiomas at initial diagnosis ( = 607, 32.9%) and 28.8% ( = 530) believed they received insufficient information about treatment options. In fact, 34.5% of respondents received the majority of their information from the internet and nonhealthcare professionals. The most common concerns after initial diagnosis were risks associated with surgery and/or treatment (36.5%) followed by how the tumor would impact daily life (25%) and the risk of tumor recurrence (12.4%). Respondents indicated that a list of resources available for patients with meningiomas ( = 597, 32.3%) would have been most beneficial in regards to their disease experience after their initial diagnosis. Moreover, we found that a substantial proportion of patients continued to report symptoms long after treatment, with fatigue being the most common compared to before treatment (38.2% vs. 57.7%, = 128, < .001).

Conclusions: Patients with meningiomas exhibit symptoms that continue well after treatment with fatigue and cognitive impairments as the most bothersome. Moreover, patients report key communication gaps that can be addressed to improve their disease experience and care.
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http://dx.doi.org/10.1093/noajnl/vdaa086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415257PMC
July 2020

Clinical value of methylation testing: a case report of intraventricular schwannomas with associated molecular findings.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa029. Epub 2020 Mar 26.

Division of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1093/noajnl/vdaa029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212842PMC
March 2020

Highlights of the inaugural ten - the launch of Neuro-Oncology Advances.

Neurooncol Adv 2019 May-Dec;1(1):vdz016. Epub 2019 Aug 28.

Division of Neurosurgery, University Health Network and MacFeeters-Hamilton Neuro-Oncology Program, Princess Margaret Hospital, University of Toronto, Toronto, Canada.

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http://dx.doi.org/10.1093/noajnl/vdz016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212904PMC
August 2019

Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes.

Nat Med 2020 07 22;26(7):1044-1047. Epub 2020 Jun 22.

Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

Definitive diagnosis of intracranial tumors relies on tissue specimens obtained by invasive surgery. Noninvasive diagnostic approaches provide an opportunity to avoid surgery and mitigate unnecessary risk to patients. In the present study, we show that DNA-methylation profiles from plasma reveal highly specific signatures to detect and accurately discriminate common primary intracranial tumors that share cell-of-origin lineages and can be challenging to distinguish using standard-of-care imaging.
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http://dx.doi.org/10.1038/s41591-020-0932-2DOI Listing
July 2020

A comparison of the perioperative outcomes of anterior surgical techniques for the treatment of multilevel degenerative cervical myelopathy.

J Neurosurg Spine 2020 Jun 12:1-8. Epub 2020 Jun 12.

Objective: Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction in adults. Multilevel ventral compressive pathology is routinely managed through anterior decompression and reconstruction, but there remains uncertainty regarding the relative safety and efficacy of multiple discectomies, multiple corpectomies, or hybrid corpectomy-discectomy. To that end, using a large national administrative healthcare data set, the authors sought to compare the perioperative outcomes of anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), and hybrid corpectomy-discectomy for multilevel DCM.

Methods: Patients with a primary diagnosis of DCM who underwent an elective anterior cervical decompression and reconstruction operation over 3 cervical spinal segments were identified from the 2012-2017 National Surgical Quality Improvement Program database. Patients were separated into those undergoing 3-level discectomy, 2-level corpectomy, or a hybrid procedure (single-level corpectomy plus additional single-level discectomy). Outcomes included 30-day mortality, major complication, reoperation, and readmission, as well as operative duration, length of stay (LOS), and routine discharge home. Outcomes were compared between treatment groups by multivariable regression, adjusting for age and comorbidities (modified Frailty Index). Effect sizes were reported by adjusted odds ratio (aOR) or mean difference (aMD) and associated 95% confidence interval.

Results: The study cohort consisted of 1298 patients; of these, 713 underwent 3-level ACDF, 314 2-level ACCF, and 271 hybrid corpectomy-discectomy. There was no difference in 30-day mortality, reoperation, or readmission among the 3 procedures. However, on both univariate and adjusted analyses, compared to 3-level ACDF, 2-level ACCF was associated with significantly greater risk of major complication (aOR 2.82, p = 0.005), longer hospital LOS (aMD 0.8 days, p = 0.002), and less frequent discharge home (aOR 0.59, p = 0.046). In contrast, hybrid corpectomy-discectomy had comparable outcomes to 3-level ACDF but was associated with significantly shorter operative duration (aMD -16.9 minutes, p = 0.002).

Conclusions: The authors found multiple discectomies and hybrid corpectomy-discectomy to have a comparable safety profile in treating multilevel DCM. In contrast, multiple corpectomies were associated with a higher complication rate, longer hospital LOS, and lower likelihood of being discharged directly home from the hospital, and may therefore be a higher-risk operation.
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http://dx.doi.org/10.3171/2020.4.SPINE191094DOI Listing
June 2020

Degenerative cervical myelopathy - update and future directions.

Nat Rev Neurol 2020 02 23;16(2):108-124. Epub 2020 Jan 23.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults worldwide. DCM encompasses various acquired (age-related) and congenital pathologies related to degeneration of the cervical spinal column, including hypertrophy and/or calcification of the ligaments, intervertebral discs and osseous tissues. These pathologies narrow the spinal canal, leading to chronic spinal cord compression and disability. Owing to the ageing population, rates of DCM are increasing. Expeditious diagnosis and treatment of DCM are needed to avoid permanent disability. Over the past 10 years, advances in basic science and in translational and clinical research have improved our understanding of the pathophysiology of DCM and helped delineate evidence-based practices for diagnosis and treatment. Surgical decompression is recommended for moderate and severe DCM; the best strategy for mild myelopathy remains unclear. Next-generation quantitative microstructural MRI and neurophysiological recordings promise to enable quantification of spinal cord tissue damage and help predict clinical outcomes. Here, we provide a comprehensive, evidence-based review of DCM, including its definition, epidemiology, pathophysiology, clinical presentation, diagnosis and differential diagnosis, and non-operative and operative management. With this Review, we aim to equip physicians across broad disciplines with the knowledge necessary to make a timely diagnosis of DCM, recognize the clinical features that influence management and identify when urgent surgical intervention is warranted.
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http://dx.doi.org/10.1038/s41582-019-0303-0DOI Listing
February 2020

Determining the Optimal Adjuvant Therapy for Improving Survival in Elderly Patients with Glioblastoma: A Systematic Review and Network Meta-analysis.

Clin Cancer Res 2020 06 17;26(11):2664-2672. Epub 2020 Jan 17.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada.

Purpose: Older patients with glioblastoma (GBM) are underrepresented in clinical trials. Several abbreviated and standard chemoradiotherapy regimens are advocated with no consensus on the optimal approach. Our objective was to quantitatively evaluate which of these regimens would provide the most favorable survival outcomes in older patients with GBM using a network meta-analysis.

Experimental Design: MEDLINE, Embase, Google Scholar, and the Cochrane Library were searched. Patients >60 years of age with histologically confirmed GBM were included. Primary outcome of interest was the pooled HR from randomized controlled trials (RCTs). Secondary outcomes of interest included pooled HR from studies controlling for MGMT promoter methylation status, and safety.

Results: Fourteen studies, including 5 RCTs, reporting 4,561 patients were included. Using highest quality data from RCTs, our network-based approach demonstrated that standard radiotherapy (SRT) and temozolomide (TMZ) provided similar survival benefit when compared with hypofractionated radiotherapy (HRT) and TMZ [HR = 0.90; 95% confidence interval (CI), 0.43-1.87], TMZ alone (HR 1.25; 95% CI, 0.69-2.26), HRT alone (HR = 1.34; 95% CI, 0.73-2.45), or SRT alone (HR = 1.43; 95% CI, 0.87-2.36). HRT-TMZ had the highest probability (85%) of improving survival in older patients with GBM followed by SRT-TMZ (72%). Pooled analysis of trials controlling for promoter methylation status demonstrated that TMZ monotherapy confers similar survival benefit to combined chemoradiotherapy.

Conclusions: Statistical comparisons using a network approach demonstrates that the common treatment regimens for older patients with GBM in previous RCTs confer similar survival benefits. Adjustments for MGMT promoter methylation status demonstrated that radiotherapy alone was inferior to TMZ-based approaches. Head-to-head comparison of TMZ monotherapy to combined TMZ and radiation is warranted.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3359DOI Listing
June 2020

How should we manage incidental meningiomas?

Neuro Oncol 2020 02;22(2):173-174

Division of Neurosurgery, University Health Network, University of Toronto, and MacFeeters-Hamilton Center for Neuro-Oncology, Princess Margaret Cancer Center, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1093/neuonc/noz237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032628PMC
February 2020

Reinitiation of Anticoagulation After Surgical Evacuation of Subdural Hematomas.

World Neurosurg 2020 Mar 23;135:e616-e622. Epub 2019 Dec 23.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Neurosurgery, Sunnybrook Health Science Centre, Toronto, Canada. Electronic address:

Background: Chronic subdural hematoma (cSDH) is an increasingly common condition due to the growing use of anticoagulation. Currently, there remains a lack of evidence to guide the optimal timing of anticoagulant reinitiation for stroke prevention in atrial fibrillation after cSDH evacuation. We aimed to better understand the perceived risks of hemorrhagic and embolic complications along with current practice patterns on restarting anticoagulation after surgical evacuation of cSDH.

Methods: We conducted a survey of Canadian neurosurgeons and stroke neurologists using a novel self-administered questionnaire using clinical cases that included questions on clinical experience, practice setting, practice patterns, and perceptions on stroke/bleeding risk with anticoagulation reinitiation after cSDH evacuation. The instrument was evaluated for clinical sensibility by 5 neurosurgeons, neurologists, and intensivists.

Results: The response rate after 4 mailings was 40% for neurosurgeons (55/136) and 21% for stroke neurologists (26/122). Almost all participants would restart anticoagulation for stroke prevention in atrial fibrillation after cSDH evacuation (91.8% in low-risk patients, 98.6% in high-risk patients). Time to reinitiation of anticoagulation varied considerably, particularly for high-risk patients where 36% of participants would restart anticoagulation within 1 week of surgery, 44% between 1 and 4 weeks after surgery, and 19% after 4 weeks postoperatively. The perceived risk of stroke and SDH reaccumulation varied considerably among participants and was dependent on timing of anticoagulation reinitiation.

Conclusions: There is considerable variation in current practice patterns and perceived risks of embolic and hemorrhagic complications with anticoagulation reinitiation after cSDH evacuation. These results demonstrate clinical equipoise that warrant further targeted investigation in large-scale randomized controlled trials.
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http://dx.doi.org/10.1016/j.wneu.2019.12.080DOI Listing
March 2020

The central nervous system tumor methylation classifier changes neuro-oncology practice for challenging brain tumor diagnoses and directly impacts patient care.

Clin Epigenetics 2019 12 5;11(1):185. Epub 2019 Dec 5.

Division of Neurosurgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Background: Molecular signatures are being increasingly incorporated into cancer classification systems. DNA methylation-based central nervous system (CNS) tumor classification is being recognized as having the potential to aid in cases of difficult histopathological diagnoses. Here, we present our institutional clinical experience in integrating a DNA-methylation-based classifier into clinical practice and report its impact on CNS tumor patient diagnosis and treatment.

Methods: Prospective case review was undertaken at CNS tumor board discussions over a 3-year period and 55 tumors with a diagnosis that was not certain to two senior neuropathologists were recommended for methylation profiling based on diagnostic needs. Tumor classification, calibrated scores, and copy number variant (CNV) plots were obtained for all 55 cases. These results were integrated with histopathological findings to reach a final diagnosis. We retrospectively reviewed each patient's clinical course to determine final neuro-pathology diagnoses and the impact of methylation profiling on their clinical management, with a focus on changes that were made to treatment decisions.

Results: Following methylation profiling, 46 of the 55 (84%) challenging cases received a clinically relevant diagnostic alteration, with two-thirds having a change in the histopathological diagnosis and the other one-third obtaining clinically important molecular diagnostic or subtyping alterations. WHO grading changed by 27% with two-thirds receiving a higher grade. Patient care was directly changed in 15% of all cases with major changes in clinical decision-making being made for these patients to avoid unnecessary or insufficient treatment.

Conclusions: The integration of methylation-based CNS tumor classification into diagnostics has a substantial clinical benefit for patients with challenging CNS tumors while also avoiding unnecessary health care costs. The clinical impact shown here may prompt the expanded use of DNA methylation profiling for CNS tumor diagnostics within prominent neuro-oncology centers globally.
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http://dx.doi.org/10.1186/s13148-019-0766-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896594PMC
December 2019

Bedside Optic Nerve Ultrasonography for Diagnosing Increased Intracranial Pressure: A Systematic Review and Meta-analysis.

Ann Intern Med 2019 12 19;171(12):896-905. Epub 2019 Nov 19.

McMaster University, Hamilton, Ontario, Canada (N.S., K.Y., Q.Z., T.R., S.F., E.P., A.H., L.B., S.A.A.).

Background: Optic nerve ultrasonography (optic nerve sheath diameter sonography) has been proposed as a noninvasive, quick method for diagnosing increased intracranial pressure.

Purpose: To examine the accuracy of optic nerve ultrasonography for diagnosing increased intracranial pressure in children and adults.

Data Sources: 13 databases from inception through May 2019, reference lists, and meeting proceedings.

Study Selection: Prospective optic nerve ultrasonography diagnostic accuracy studies, published in any language, involving any age group or reference standard.

Data Extraction: 3 reviewers independently abstracted data and performed quality assessment.

Data Synthesis: Of 71 eligible studies involving 4551 patients, 61 included adults, and 35 were rated as having low risk of bias. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of optic nerve ultrasonography in patients with traumatic brain injury were 97% (95% CI, 92% to 99%), 86% (CI, 74% to 93%), 6.93 (CI, 3.55 to 13.54), and 0.04 (CI, 0.02 to 0.10), respectively. Respective estimates in patients with nontraumatic brain injury were 92% (CI, 86% to 96%), 86% (CI, 77% to 92%), 6.39 (CI, 3.77 to 10.84), and 0.09 (CI, 0.05 to 0.17). Accuracy estimates were similar among studies stratified by patient age, operator specialty and training level, reference standard, sonographer blinding status, and cutoff value. The optimal cutoff for optic nerve sheath dilatation on ultrasonography was 5.0 mm.

Limitation: Small studies, imprecise summary estimates, possible publication bias, and no evaluation of effect on clinical outcomes.

Conclusion: Optic nerve ultrasonography can help diagnose increased intracranial pressure. A normal sheath diameter measurement has high sensitivity and a low negative likelihood ratio that may rule out increased intracranial pressure, whereas an elevated measurement, characterized by a high specificity and positive likelihood ratio, may indicate increased intracranial pressure and the need for additional confirmatory tests.

Primary Funding Source: None. (PROSPERO: CRD42017055485).
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http://dx.doi.org/10.7326/M19-0812DOI Listing
December 2019

A Phase II Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases: Clinical Trial Protocol.

Neurosurgery 2020 08;87(2):403-407

Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada.

Background: Brain metastases which require resection are treated with surgery followed by whole brain radiation therapy or postoperative cavity boost stereotactic radiosurgery (POCBS). Recently a novel strategy using neoadjuvant stereotactic radiosurgery (NaSRS) followed by resection was reported, demonstrating lower rates of postoperative leptomeningeal dissemination (LMD) and symptomatic radiation toxicity compared to a comparative cohort of patients treated with postoperative SRS.

Objective: To determine if the rate of symptomatic radiation toxicity at 1 yr in patients who receive NaSRS differs significantly from historical rates for patients treated with POCBS.

Methods: This is a multi-center, non-randomized, open phase II clinical trial. A total of 30 patients with up to 10 brain metastases, at least 1 of which is appropriate for surgical resection, will be enrolled for over 4 yr. All enrolled patients will be assigned to receive NaSRS followed by surgery.

Expected Outcome: This study will clarify whether symptomatic radiation toxicity caused by NaSRS is significantly decreased compared to historical rates associated with POCBS. Secondary endpoints will include 1-yr local control (LC) of the treated lesion, 1-yr rates of LMD, median survival and 2-yr rates of progression-free and overall survival. Tertiary analyses will include correlation between LC and radiation toxicity with pretreatment clinical factors, serum markers, radiomic features, and molecular assessments of the resected tumors.

Discussion: This prospective study will determine the toxicity associated with NaSRS and provide additional quantitative metrics of efficacy for future comparative trials.
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http://dx.doi.org/10.1093/neuros/nyz442DOI Listing
August 2020

The Effect of Older Age on the Perioperative Outcomes of Spinal Fusion Surgery in Patients With Lumbar Degenerative Disc Disease With Spondylolisthesis: A Propensity Score-Matched Analysis.

Neurosurgery 2020 09;87(4):672-678

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada.

Background: Degenerative spondylolisthesis (DS) is often treated with lumbar spinal fusion (LSF). However, there is concern that the morbidity of LSF may be prohibitively high in older adults.

Objective: To evaluate the impact of advanced age on the safety of LSF for DS.

Methods: Patients who underwent LSF for DS were retrospectively identified from National Surgical Quality Improvement Program datasets for 2011 to 2015 using Current Procedural Terminology codes. Data on demographic characteristics, comorbidities, surgical factors, and 30-d morbidity and mortality were collected. Propensity score matching (nearest neighbor) was performed with age (<70 vs ≥70 yr) as the dependent variable and sex, type of fusion procedure, number of levels fused, diabetes, smoking, hypertension, and chronic steroid use as covariates. Outcomes were compared between age <70 and ≥70 groups.

Results: The study cohort consisted of 2238 patients (n = 1119, age <70; n = 1119, age ≥70). The 2 age groups were balanced for key covariates including sex, race, diabetes, hypertension, CHF, smoking, chronic steroid use, type of fusion, and number of levels. Rates of all complications were similar between younger and older age groups, except urinary tract infection, which was more frequent among the ≥70 age group (OR 2.32, P = .009). Further, patients in the older age group were more likely to be discharged to a rehabilitation (OR 2.94, P < .001) or skilled care (OR 3.66, P < .001) facility, rather than directly home (OR 0.25, P < .001).

Conclusion: LSF may be performed safely in older adults with DS. Our results suggest older age alone should not exclude a patient from undergoing lumbar fusion for DS.
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http://dx.doi.org/10.1093/neuros/nyz444DOI Listing
September 2020

Integrated models incorporating radiologic and radiomic features predict meningioma grade, local failure, and overall survival.

Neurooncol Adv 2019 May-Dec;1(1):vdz011. Epub 2019 Aug 28.

Department of Radiation Oncology, University of California San Francisco, California.

Background: We investigated prognostic models based on clinical, radiologic, and radiomic feature to preoperatively identify meningiomas at risk for poor outcomes.

Methods: Retrospective review was performed for 303 patients who underwent resection of 314 meningiomas (57% World Health Organization grade I, 35% grade II, and 8% grade III) at two independent institutions, which comprised primary and external datasets. For each patient in the primary dataset, 16 radiologic and 172 radiomic features were extracted from preoperative magnetic resonance images, and prognostic features for grade, local failure (LF) or overall survival (OS) were identified using the Kaplan-Meier method, log-rank tests and recursive partitioning analysis. Regressions and random forests were used to generate and test prognostic models, which were validated using the external dataset.

Results: Multivariate analysis revealed that apparent diffusion coefficient hypointensity (HR 5.56, 95% CI 2.01-16.7, = .002) was associated with high grade meningioma, and low sphericity was associated both with increased LF (HR 2.0, 95% CI 1.1-3.5, = .02) and worse OS (HR 2.94, 95% CI 1.47-5.56, = .002). Both radiologic and radiomic predictors of adverse meningioma outcomes were significantly associated with molecular markers of aggressive meningioma biology, such as somatic mutation burden, DNA methylation status, and expression. Integrated prognostic models combining clinical, radiologic, and radiomic features demonstrated improved accuracy for meningioma grade, LF, and OS (area under the curve 0.78, 0.75, and 0.78, respectively) compared to models based on clinical features alone.

Conclusions: Preoperative radiologic and radiomic features such as apparent diffusion coefficient and sphericity can predict tumor grade, LF, and OS in patients with meningioma.
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http://dx.doi.org/10.1093/noajnl/vdz011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777505PMC
August 2019

Comparison of the Inpatient Complications and Health Care Costs of Anterior versus Posterior Cervical Decompression and Fusion in Patients with Multilevel Degenerative Cervical Myelopathy: A Retrospective Propensity Score-Matched Analysis.

World Neurosurg 2020 Feb 28;134:e112-e119. Epub 2019 Sep 28.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada. Electronic address:

Background: The optimal surgical approach for multilevel degenerative cervical myelopathy (DCM) is unclear, and there is significant variation in practice patterns. We sought to compare inpatient complications and costs of anterior (ACDF) versus posterior cervical decompression and fusion (PCDF).

Methods: Patients who underwent multilevel ACDF or PCDF for DCM were identified from the National Inpatient Sample for 2004-2014 using ICD-9-CM codes. Propensity score matching was performed with age, sex, comorbidities, hospital bed size, and use of intraoperative monitoring as covariates. Hospitalization charges/costs, length of stay (LOS), discharge disposition, and inpatient morbidity/mortality were compared between matched ACDF and PCDF groups.

Results: Propensity score matching generated a cohort of 13,884 patients (n = 6,942 ACDF; n = 6,942 PCDF). PCDF was associated with greater LOS (mean difference [MD] +1.7 days, P < 0.001) and less frequent routine discharge home (odds ratio [OR] 0.26, P < 0.01). With regard to complications, PCDF had a higher rate of myocardial infarction (OR 1.6, P = 0.007), pulmonary embolism (OR 2.6, P = 0.009), deep vein thrombosis (OR 3.7, P < 0.001), neurological complications (OR 1.7, P = 0.037), hardware-related complications (OR 2.7, P < 0.001), wound infection/breakdown (OR 6.8, P < 0.001), and cerebrospinal fluid leak (OR 1.7, P = 0.011). By contrast, rates of postoperative hematoma (OR 0.61, P = 0.007), hoarseness (OR 0.13, P < 0.001), and dysphagia (OR 0.20, P < 0.001) were higher after ACDF. Mortality was comparable. Hospital charges (MD +$26,259, P < 0.001) and costs (MD +$7,728, P < 0.001) were significantly higher for PCDF.

Conclusions: At a national level, for multilevel DCM, we found PCDF to be associated with greater LOS, in-hospital costs, and general medical and surgical complications. ACDF carried higher risk of postoperative hematoma, hoarseness, and dysphagia.
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http://dx.doi.org/10.1016/j.wneu.2019.09.132DOI Listing
February 2020

Molecular and Clinical Insights into the Invasive Capacity of Glioblastoma Cells.

J Oncol 2019 29;2019:1740763. Epub 2019 Jul 29.

Genetics Unit, Hospital Universitario Marqués de Valdecilla and Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain.

The invasive capacity of GBM is one of the key tumoral features associated with treatment resistance, recurrence, and poor overall survival. The molecular machinery underlying GBM invasiveness comprises an intricate network of signaling pathways and interactions with the extracellular matrix and host cells. Among them, PI3k/Akt, Wnt, Hedgehog, and NFkB play a crucial role in the cellular processes related to invasion. A better understanding of these pathways could potentially help in developing new therapeutic approaches with better outcomes. Nevertheless, despite significant advances made over the last decade on these molecular and cellular mechanisms, they have not been translated into the clinical practice. Moreover, targeting the infiltrative tumor and its significance regarding outcome is still a major clinical challenge. For instance, the pre- and intraoperative methods used to identify the infiltrative tumor are limited when trying to accurately define the tumor boundaries and the burden of tumor cells in the infiltrated parenchyma. Besides, the impact of treating the infiltrative tumor remains unclear. Here we aim to highlight the molecular and clinical hallmarks of invasion in GBM.
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http://dx.doi.org/10.1155/2019/1740763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699388PMC
July 2019

Pituitary Apoplexy: Results of Surgical and Conservative Management Clinical Series and Review of the Literature.

World Neurosurg 2019 Oct 11;130:e988-e999. Epub 2019 Jul 11.

Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.

Objective: Pituitary apoplexy is associated with visual, cranial nerve, and endocrine dysfunction. In this article, the results of surgical and conservative management of pituitary apoplexy in a single center are evaluated and a review of the literature is presented.

Methods: A retrospective analysis was made of patients with pituitary apoplexy who underwent surgery or conservative management at our center between January 2007 and June 2017. Surgery was typically selected for patients who presented with acute deterioration of visual status and/or level of consciousness. Patients with no visual field deficit and those who had medical contraindications to undergo a surgical procedure because of previous comorbidities typically had conservative treatment. Baseline characteristics and clinical and radiologic outcomes were reviewed. A review of the literature (1990-2018) was performed according to PRISMA guidelines. Studies comparing the results of conservative and surgical management were identified. Visual, cranial nerve, and endocrine outcomes and tumor recurrence were analyzed.

Results: Forty-nine patients (73.1%) were managed surgically and 18 (26.9%) conservatively. After careful case selection, patients underwent surgical or conservative treatment. Patients who underwent conservative treatment had fewer visual deficits. At diagnosis, visual deficit (38.8% vs. 75.5%; P = 0.008) and cranial nerve palsy (27.7% vs. 51%; P = 0.058) were less common in the conservative group. Conservative and surgical treatments had similar visual and cranial nerve improvement rates (75% vs. 58.3%, P = 0.63 and 75% vs. 69.2%, P = 1.0, respectively). In the conservative group, tumor shrinkage was observed in 76.4% of cases. The systematic review retrieved 11 studies. No significant difference between conservative and surgical treatment for clinical outcomes (visual field recovery, odds ratio [OR], 1.45; 95% confidence interval [CI], 0.72-2.92; cranial nerve recovery, OR, 2.30; 95% CI, 0.93-5.65; and hypopituitarism, OR, 1.05; 95% CI, 0.64-1.74) or tumor recurrence (OR, 0.68; 95% CI, 0.20-2.34) was observed.

Conclusions: A tailored approach to pituitary apoplexy, one that does not include an absolute need for surgery, is appropriate. Conservative management is appropriate in selected patients presenting without visual deficits.
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http://dx.doi.org/10.1016/j.wneu.2019.07.055DOI Listing
October 2019

Predicting Outcomes After Surgical Decompression for Mild Degenerative Cervical Myelopathy: Moving Beyond the mJOA to Identify Surgical Candidates.

Neurosurgery 2020 04;86(4):565-573

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada.

Background: Patients with mild degenerative cervical myelopathy (DCM) represent a heterogeneous population, and indications for surgical decompression remain controversial.

Objective: To dissociate patient phenotypes within the broader population of mild DCM associated with degree of impairment in baseline quality of life (QOL) and surgical outcomes.

Methods: This was a post hoc analysis of patients with mild DCM (modified Japanese Orthopedic Association [mJOA] 15-17) enrolled in the AOSpine CSM-NA/CSM-I studies. A k-means clustering algorithm was applied to baseline QOL (Short Form-36 [SF-36]) scores to separate patients into 2 clusters. Baseline variables and surgical outcomes (change in SF-36 scores at 1 yr) were compared between clusters. A k-nearest neighbors (kNN) algorithm was used to evaluate the ability to classify patients into the 2 clusters by significant baseline clinical variables.

Results: One hundred eighty-five patients were eligible. Two groups were generated by k-means clustering. Cluster 1 had a greater proportion of females (44% vs 28%, P = .029) and symptoms of neck pain (32% vs 11%, P = .001), gait difficulty (57% vs 40%, P = .025), or weakness (75% vs 59%, P = .041). Although baseline mJOA correlated with neither baseline QOL nor outcomes, cluster 1 was associated with significantly greater improvement in disability (P = .003) and QOL (P < .001) scores following surgery. A kNN algorithm could predict cluster classification with 71% accuracy by neck pain, motor symptoms, and gender alone.

Conclusion: We have dissociated a distinct patient phenotype of mild DCM, characterized by neck pain, motor symptoms, and female gender associated with greater impairment in QOL and greater response to surgery.
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http://dx.doi.org/10.1093/neuros/nyz160DOI Listing
April 2020

DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management.

Neuro Oncol 2019 07;21(7):901-910

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Background: Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma.

Methods: DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS). Subsequently, a 5-year meningioma recurrence score was generated using a nomogram that integrated the methylome model with established prognostic clinical factors. Performance of both models was evaluated and compared with standard-of-care models using multiple independent cohorts.

Results: The methylome-based predictor of 5-year RFS performed favorably compared with a grade-based predictor when tested using the 3 validation cohorts (ΔAUC = 0.10, 95% CI: 0.03-0.018) and was independently associated with RFS after adjusting for histopathologic grade, extent of resection, and burden of copy number alterations (hazard ratio 3.6, 95% CI: 1.8-7.2, P < 0.001). A nomogram combining the methylome predictor with clinical factors demonstrated greater discrimination than a nomogram using clinical factors alone in 2 independent validation cohorts (ΔAUC = 0.25, 95% CI: 0.22-0.27) and resulted in 2 groups with distinct recurrence patterns (hazard ratio 7.7, 95% CI: 5.3-11.1, P < 0.001) with clinical implications.

Conclusions: The models developed and validated in this study provide important prognostic information not captured by previously established clinical and molecular factors which could be used to individualize decisions regarding postoperative therapeutic interventions, in particular whether to treat patients with adjuvant radiotherapy versus observation alone.
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http://dx.doi.org/10.1093/neuonc/noz061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620635PMC
July 2019

Investigating the utility of intraoperative neurophysiological monitoring for anterior cervical discectomy and fusion: analysis of over 140,000 cases from the National (Nationwide) Inpatient Sample data set.

J Neurosurg Spine 2019 03;31(1):76-86

1Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario; and.

Objective: Intraoperative neurophysiological monitoring (IONM) is a useful adjunct in spine surgery, with proven benefit in scoliosis-correction surgery. However, its utility for anterior cervical discectomy and fusion (ACDF) is unclear, as there are few head-to-head comparisons of ACDF outcomes with and without the use of IONM. The authors sought to evaluate the impact of IONM on the safety and cost of ACDF.

Methods: This was a retrospective analysis of data from the National (Nationwide) Inpatient Sample of the Healthcare Cost and Utilization Project from 2009 to 2013. Patients with a primary procedure code for ACDF were identified, and diagnosis codes were searched to identify cases with postoperative neurological complications. The authors performed univariate and multivariate logistic regression for postoperative neurological complications with use of IONM as the independent variable; additional covariates included age, sex, surgical indication, multilevel fusion, Charlson Comorbidity Index (CCI) score, and admission type. They also conducted propensity score matching in a 1:1 ratio (nearest neighbor) with the use of IONM as the treatment indicator and the aforementioned variables as covariates. In the propensity score-matched cohort, they compared neurological complications, length of stay (LOS), and hospital charges (in US dollars).

Results: A total of 141,007 ACDF operations were identified. IONM was used in 9540 cases (6.8%). No significant association was found between neurological complications and use of IONM on univariate analysis (OR 0.80, p = 0.39) or multivariate regression (OR 0.82, p = 0.45). By contrast, age ≥ 65 years, multilevel fusion, CCI score > 0, and a nonelective admission were associated with greater incidence of neurological complication. The propensity score-matched cohort consisted of 18,760 patients who underwent ACDF with (n = 9380) or without (n = 9380) IONM. Rates of neurological complication were comparable between IONM and non-IONM (0.17% vs 0.22%, p = 0.41) groups. IONM and non-IONM groups had a comparable proportion of patients with LOS ≥ 2 days (19% vs 18%, p = 0.15). The use of IONM was associated with an additional $6843 (p < 0.01) in hospital charges.

Conclusions: The use of IONM was not associated with a reduced rate of neurological complications following ACDF. Limitations of the data source precluded a specific assessment of the effectiveness of IONM in preventing neurological complications in patients with more complex pathology (i.e., ossification of the posterior longitudinal ligament or cervical deformity).
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http://dx.doi.org/10.3171/2019.1.SPINE181110DOI Listing
March 2019

Tissue 2-Hydroxyglutarate as a Biomarker for Mutations in Gliomas.

Clin Cancer Res 2019 06 18;25(11):3366-3373. Epub 2019 Feb 18.

Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

Purpose: mutations are common in low-grade gliomas and the IDH mutation status is now integrated into the WHO classification of gliomas. IDH mutations lead to preferential accumulation of the R- relative to the S-enantiomer of 2-hydroxyglutarate (2-HG). We investigated the utility of tissue total 2-HG, R-2-HG, and the R-2-HG/S-2-HG ratio (rRS) as diagnostic and prognostic biomarkers for mutations in gliomas. Glioma tissue and blood samples from 87 patients were analyzed with HPLC-MS/MS coupled with a CHIROBIOTIC column to quantify both enantiomers of 2-HG. ROC analysis was conducted to evaluate the sensitivity and specificity of 2-HG, R-2-HG, and rRS. The feasibility of real-time determination of IDH status was evaluated in 11 patients intraoperatively. The prognostic value of rRS was evaluated using the Kaplan-Meier method.

Results: The rRS in glioma tissues clearly distinguished patients with -mutant versus wild-type tumors ( < 0.001). Sensitivity and specificity using an rRS cut-off value of 32.26 were 97% and 100%, respectively. None of total 2-HG, R-2-HG, or rRS was elevated in serum samples. Among patients with -mutant tumors, tissue rRS stratifies overall survival. The duration of tissue analysis is approximately 60 minutes.

Conclusions: Our study demonstrates that rRS is a reliable biomarker of mutation status. This technique can be used to determine mutation status intraoperatively, and to guide treatment decisions based on mutation status in real time. Finally, rRS values may provide additional prognostic information and further validation is required.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-3205DOI Listing
June 2019

Imaging and diagnostic advances for intracranial meningiomas.

Neuro Oncol 2019 01;21(Suppl 1):i44-i61

Center for Skull Base and Pituitary Surgery, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

The archetypal imaging characteristics of meningiomas are among the most stereotypic of all central nervous system (CNS) tumors. In the era of plain film and ventriculography, imaging was only performed if a mass was suspected, and their results were more suggestive than definitive. Following more than a century of technological development, we can now rely on imaging to non-invasively diagnose meningioma with great confidence and precisely delineate the locations of these tumors relative to their surrounding structures to inform treatment planning. Asymptomatic meningiomas may be identified and their growth monitored over time; moreover, imaging routinely serves as an essential tool to survey tumor burden at various stages during the course of treatment, thereby providing guidance on their effectiveness or the need for further intervention. Modern radiological techniques are expanding the power of imaging from tumor detection and monitoring to include extraction of biologic information from advanced analysis of radiological parameters. These contemporary approaches have led to promising attempts to predict tumor grade and, in turn, contribute prognostic data. In this supplement article, we review important current and future aspects of imaging in the diagnosis and management of meningioma, including conventional and advanced imaging techniques using CT, MRI, and nuclear medicine.
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http://dx.doi.org/10.1093/neuonc/noy143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347083PMC
January 2019

Molecular and translational advances in meningiomas.

Neuro Oncol 2019 01;21(Suppl 1):i4-i17

Division of Neurosurgery, University Health Network, University of Toronto, Ontario, Canada.

Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.
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http://dx.doi.org/10.1093/neuonc/noy178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347079PMC
January 2019

Advances in multidisciplinary therapy for meningiomas.

Neuro Oncol 2019 01;21(Suppl 1):i18-i31

Department of Neurological Surgery, University of California, San Francisco, California, USA.

Surgery has long been established as the first-line treatment for the majority of symptomatic and enlarging meningiomas, and evidence for its success is derived from retrospective case series. Despite surgical resection, a subset of meningiomas display aggressive behavior with early recurrences that are difficult to treat. The decision to radically resect meningiomas and involved structures is balanced against the risk for neurological injury in patients. Radiation therapy has largely been used as a complementary and safe therapeutic strategy in meningiomas with evidence primarily stemming from retrospective, single-institution reports. Two of the first cooperative group studies (RTOG 0539 and EORTC 22042) evaluating the outcomes of adjuvant radiation therapy in higher-risk meningiomas have shown promising preliminary results. Historically, systemic therapy has resulted in disappointing results in meningiomas. However, several clinical trials are under way evaluating the efficacy of chemotherapies, such as trabectedin, and novel molecular agents targeting Smoothened, AKT1, and focal adhesion kinase in patients with recurrent meningiomas.
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http://dx.doi.org/10.1093/neuonc/noy136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347080PMC
January 2019