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Meningioma: From Bench to Bedside
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Meningioma: From Bench to Bedside

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 20799

Special Issue Editor

Dr. Adriana Olar

E-Mail Website
Guest Editor
NOMIX Laboratories, Denver, CO 80218, USA
Interests: brain tumor neuropathology; molecular pathology; bioinformatics and statistics; oncology; drug development and clinical trials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Meningioma is the most common primary brain tumor in adults and is rare in children and adolescents. Per the World Health Organization (WHO), it is classified into three grades that are predictive of tumor recurrence based on histological and, recently, molecular features. Despite significant advances in the past few years there are still many questions to be answered in order to provide the best care for patients with meningioma. The current WHO grading system is not an accurate predictor of tumor recurrence despite recent refinement and additions of molecular biomarkers. Moreover, many aggressive, highly recurrent tumors lack the previously described molecular markers of recurrence and some bland tumors cause severe morbidity because of their location (for example at the skull base) with impossibility for gross total resection. Special histological subtypes of meningioma classified as aggressive (such as chordoid meningioma or rhabdoid meningioma) do not always portend a poor prognosis. Biological heterogeneity within subtype is likely.

Surgery is the best therapeutic modality to date and the extent of resection is an excellent indicator of recurrence. The decision for radiation therapy for grade 2 tumors is not yet resolved as this category of tumors is most unpredictable. Chemotherapies are toxic and usually detrimental to patient’s overall health with no or minimal effects on tumor shrinkage.

While most studies focus on bulk tissue non-randomized genomics with minimal clinical correlation it is easy to forget that meningioma, just as any other disease, is a multifactorial disease of sex, age, race, socioeconomic status, genetic predisposition, and environmental factors. Each patient is different and should receive personalized care.

I am pleased to invite you to contribute to a Special Issue on meningioma with the goal to address pertinent unanswered questions and offer ideas for the fast implementation of novel findings into clinical practice. This issue aims to offer an overview of the current advances in meningioma as well as to clarify yet-unanswered questions about this complex disease. I am pleased to invite experts to share their innovative findings, hypothesize novel mechanisms of this disease or expand upon current knowledge, propose novel tumor classification schemes, and propose drug targets or targets for genetic therapy.

Original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: epidemiology and populational studies, models of disease, pathological mechanisms, omics, innovations in surgery and surgical approaches, radiation therapy, targeted therapies, and immunotherapy.

I look forward to receiving your contributions.

Dr. Adriana Olar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • meningioma
  • pathobiology
  • omics
  • epidemiology
  • molecular pathology
  • targeted therapies

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Published Papers (7 papers)

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Research

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8 pages, 983 KiB  
Communication
Metastases to Meningiomas: A Comprehensive Literature Review Including Mediating Proteins
by Mahlon D. Johnson
Cancers 2022, 14(23), 5877; https://doi.org/10.3390/cancers14235877 - 29 Nov 2022
Cited by 3 | Viewed by 1712
Abstract
Approximately 5–15% of solid tumors metastasizing to the central nervous system metastasize to the leptomeninges. Less common, is metastasis to leptomeningeal meningiomas. These are primarily carcinomas of the breast and lung. Awareness of this phenomenon is critical to the evaluation of meningiomas, especially [...] Read more.
Approximately 5–15% of solid tumors metastasizing to the central nervous system metastasize to the leptomeninges. Less common, is metastasis to leptomeningeal meningiomas. These are primarily carcinomas of the breast and lung. Awareness of this phenomenon is critical to the evaluation of meningiomas, especially since the metastases may be the first indication of an occult tumor elsewhere in the body. Lack of clear demarcation between the metastasis and meningioma parenchyma, as well as histological features similar to the meningioma, may hinder recognition. The mechanisms underlying metastases anchoring and spread along the leptomeninges are not established. However, several cell adhesion molecules are thought to contribute to this phenomenon. E cadherin is a cell adhesion molecule present in meningioma cells. Binding to endothelium by adhesion molecules such as ICAM, B1 integrin, P-selectin, PECAM-1, CXCL12 and SDF-1 have also been proposed as part of the mechanisms underlying breast carcinoma metastases. In addition, the leptomeninges and meningiomas express mesothelin that acts as an anchoring protein coupling with mucin-16. Consequently, metastatic tumor cell mucin and mesothelin may also facilitate the anchoring of metastases to meningiomas. Full article
(This article belongs to the Special Issue Meningioma: From Bench to Bedside)
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15 pages, 2373 KiB  
Article
Surgical and Functional Outcome after Resection of 64 Petroclival Meningiomas
by Arthur Wagner, Marie Alraun, Victoria Kahlig, Anne-Sophie Dorier, Amir Kaywan Aftahy, Denise Bernhardt, Stephanie E. Combs, Jens Gempt, Ehab Shiban, Bernhard Meyer and Chiara Negwer
Cancers 2022, 14(18), 4517; https://doi.org/10.3390/cancers14184517 - 17 Sep 2022
Cited by 8 | Viewed by 3210
Abstract
Objective: The management of petroclival meningiomas (PCMs) remains notoriously difficult due to their close association with neurovascular structures and their complex anatomy, hence the surgical paradigm change from radical to functional resection in the past. With this study, we aimed to analyze surgical [...] Read more.
Objective: The management of petroclival meningiomas (PCMs) remains notoriously difficult due to their close association with neurovascular structures and their complex anatomy, hence the surgical paradigm change from radical to functional resection in the past. With this study, we aimed to analyze surgical and functional outcomes of a modern consecutive series of patients with PCMs. Methods: We reviewed patient charts and imaging data of 64 consecutive patients from 2006 to 2018 with a PCM resected at our institution and compared surgical and functional outcomes between subgroups stratified by surgical approach. Results: Females comprised 67.2% of patients (n = 43), with a mean age of 55 years (median 56; range 21–84). Follow-up data were available for 68.8% and reached a mean of 42.3 months (range 1–129) with a median of 28.5 months. The mean tumor diameter was 37.3 mm (standard deviation (SD) 15.4; median 37.0). Infiltration of the cavernous sinus was observed in 34 cases (53.1%), and the lesions affected the brain stem in 28 cases (43.8%). Preoperative cranial nerve palsy was observed in 73.4% of cases; trigeminal neuropathy (42.2%), hearing loss (32.8%), and impairment of vision (18.8%) were the most common. A retrosigmoid approach was employed in 47 cases (78.1%), pterional in 10 (15.6%), combined petrosal in 2 (3.1%), and transnasal and subtemporal in 1 (1.6%). Fifteen cases (23.4%) were resected in a two-staged fashion. Gross total resection (GTR) was attempted in 30 (46.9%) cases without cavernous sinus infiltration and was achieved in 21 (70.0%) of these cases. Surgical complications occurred in 13 cases (20.3%), most commonly meningitis (n = 4; 6.3%). Postoperatively, 56 patients (87.5%) developed new cranial nerve palsy, of which 36 (63.6%) had improved or resolved on last follow up. Achieving GTR was not significantly associated with higher rates of surgical complications (chi-square; p = 0.288) or postoperative cranial nerve palsy (chi-square; p = 0.842). Of all cases, 20 (31.3%) underwent postoperative radiation. Tumor progression was observed in 10 patients (15.9%) after a mean 102 months (median 124). Conclusions: Surgical resection remains the mainstay of treatment for PCMs, with perioperative cranial neuropathies exhibiting favorable recovery rates. Most essentially, the preselection of patients with hallmarks of brain stem affection and cavernous sinus infiltration should dictate whether to strive for a functionally oriented strategy in favor of radical resection. Full article
(This article belongs to the Special Issue Meningioma: From Bench to Bedside)
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18 pages, 2501 KiB  
Article
Co-Targeting MAP Kinase and Pi3K-Akt-mTOR Pathways in Meningioma: Preclinical Study of Alpelisib and Trametinib
by Gregoire Mondielli, Gregory Mougel, Florent Darriet, Catherine Roche, Adeline Querdray, Christophe Lisbonis, Romain Appay, Henry Dufour, Olivier Chinot, Thomas Graillon and Anne Barlier
Cancers 2022, 14(18), 4448; https://doi.org/10.3390/cancers14184448 - 13 Sep 2022
Cited by 7 | Viewed by 2342
Abstract
Recurrent or high-grade meningiomas are an unmet medical need. Recently, we demonstrated that targeting mTOR by everolimus was relevant both in vitro and in humans. However, everolimus induces an AKT activation that may impact the anti-proliferative effect of the drug. Moreover, the MAP [...] Read more.
Recurrent or high-grade meningiomas are an unmet medical need. Recently, we demonstrated that targeting mTOR by everolimus was relevant both in vitro and in humans. However, everolimus induces an AKT activation that may impact the anti-proliferative effect of the drug. Moreover, the MAP kinase pathway was shown to be involved in meningioma tumorigenesis. We therefore targeted both the Pi3k-AKT-mTOR and MAP kinase pathways by using combinations of the Pi3k inhibitor alpelisib and the MEK inhibitor trametinib. Our study was performed in vitro on the human meningioma cell lines and on a large series of primary cultures providing from 63 freshly operated meningiomas including 35 WHO grade 1, 23 grade 2, and five grade 3, half of which presented a NF2 genomic alteration. Alpelisib induced a higher inhibitory effect on cell viability and proliferation than everolimus in all cell lines and 32 randomly selected tumors no matter the genomic status, the histological subtype or grade. Trametinib also strongly inhibited cell proliferation and induced AKT activation. Combined treatment with alpelisib plus trametinib reversed the AKT activation induced by trametinib and induced an additive inhibitory effect irrespective of the cell lines or tumor features. Co-targeting pathways seems promising and may be considered particularly for aggressive meningioma. Full article
(This article belongs to the Special Issue Meningioma: From Bench to Bedside)
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15 pages, 1604 KiB  
Article
Low-Dose Acetylsalicylic Acid Treatment in Non-Skull-Base Meningiomas: Impact on Tumor Proliferation and Seizure Burden
by Johannes Wach, Ági Güresir, Hartmut Vatter, Ulrich Herrlinger, Albert Becker, Marieta Toma, Michael Hölzel and Erdem Güresir
Cancers 2022, 14(17), 4285; https://doi.org/10.3390/cancers14174285 - 1 Sep 2022
Cited by 1 | Viewed by 1778
Abstract
MIB-1 index is an important predictor of meningioma progression and was found to be correlated with COX-2 expression. However, the impact of low-dose acetylsalicylic acid (ASA) on MIB-1 index and clinical symptoms is unclear. Between 2009 and 2022, 710 patients with clinical data, [...] Read more.
MIB-1 index is an important predictor of meningioma progression and was found to be correlated with COX-2 expression. However, the impact of low-dose acetylsalicylic acid (ASA) on MIB-1 index and clinical symptoms is unclear. Between 2009 and 2022, 710 patients with clinical data, tumor-imaging data, inflammatory laboratory (plasma fibrinogen, serum C-reactive protein) data, and neuropathological reports underwent surgery for primary cranial WHO grade 1 and 2 meningioma. ASA intake was found to be significantly associated with a low MIB-1 labeling index in female patients ≥ 60 years. Multivariable analysis demonstrated that female patients ≥ 60 years with a non-skull-base meningioma taking ASA had a significantly lower MIB-1 index (OR: 2.6, 95%: 1.0–6.6, p = 0.04). Furthermore, the intake of ASA was independently associated with a reduced burden of symptomatic epilepsy at presentation in non-skull-base meningiomas in both genders (OR: 3.8, 95%CI: 1.3–10.6, p = 0.03). ASA intake might have an anti-proliferative effect in the subgroup of elderly female patients with non-skull-base meningiomas. Furthermore, anti-inflammatory therapy seems to reduce the burden of symptomatic epilepsy in non-skull-base meningiomas. Further research is needed to investigate the role of anti-inflammatory therapy in non-skull-base meningiomas. Full article
(This article belongs to the Special Issue Meningioma: From Bench to Bedside)
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Review

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14 pages, 276 KiB  
Review
Surgical Management of High-Grade Meningiomas
by Mark A. Pacult, Colin J. Przybylowski, Shaan M. Raza and Franco DeMonte
Cancers 2024, 16(11), 1978; https://doi.org/10.3390/cancers16111978 - 23 May 2024
Cited by 1 | Viewed by 990
Abstract
Maximal resection with the preservation of neurological function are the mainstays of the surgical management of high-grade meningiomas. Surgical morbidity is strongly associated with tumor size, location, and invasiveness, whereas patient survival is strongly associated with the extent of resection, tumor biology, and [...] Read more.
Maximal resection with the preservation of neurological function are the mainstays of the surgical management of high-grade meningiomas. Surgical morbidity is strongly associated with tumor size, location, and invasiveness, whereas patient survival is strongly associated with the extent of resection, tumor biology, and patient health. A versatile microsurgical skill set combined with a cogent multimodality treatment plan is critical in order to achieve optimal patient outcomes. Continued refinement in surgical techniques in conjunction with directed radiotherapeutic and medical therapies will define future treatment. Full article
(This article belongs to the Special Issue Meningioma: From Bench to Bedside)
21 pages, 4054 KiB  
Review
Spinal Meningiomas: A Comprehensive Review and Update on Advancements in Molecular Characterization, Diagnostics, Surgical Approach and Technology, and Alternative Therapies
by Danielle D. Dang, Luke A. Mugge, Omar K. Awan, Andrew D. Gong and Andrew A. Fanous
Cancers 2024, 16(7), 1426; https://doi.org/10.3390/cancers16071426 - 7 Apr 2024
Cited by 5 | Viewed by 2434
Abstract
Spinal meningiomas are the most common intradural, extramedullary tumor in adults, yet the least common entity when accounting for all meningiomas spanning the neuraxis. While traditionally considered a benign recapitulation of their intracranial counterpart, a paucity of knowledge exists regarding the differences between [...] Read more.
Spinal meningiomas are the most common intradural, extramedullary tumor in adults, yet the least common entity when accounting for all meningiomas spanning the neuraxis. While traditionally considered a benign recapitulation of their intracranial counterpart, a paucity of knowledge exists regarding the differences between meningiomas arising from these two anatomic compartments in terms of histopathologic subtypes, molecular tumor biology, surgical principles, long-term functional outcomes, and recurrence rates. To date, advancements at the bench have largely been made for intracranial meningiomas, including the discovery of novel gene targets, DNA methylation profiles, integrated diagnoses, and alternative systemic therapies, with few exceptions reserved for spinal pathology. Likewise, evolving clinical research offers significant updates to our understanding of guiding surgical principles, intraoperative technology, and perioperative patient management for intracranial meningiomas. Nonetheless, spinal meningiomas are predominantly relegated to studies considering non-specific intradural extramedullary spinal tumors of all histopathologic types. The aim of this review is to comprehensively report updates in both basic science and clinical research regarding intraspinal meningiomas and to provide illustrative case examples thereof, thereby lending a better understanding of this heterogenous class of central nervous system tumors. Full article
(This article belongs to the Special Issue Meningioma: From Bench to Bedside)
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17 pages, 1666 KiB  
Review
Clinical Management of Supratentorial Non-Skull Base Meningiomas
by Adefisayo Adekanmbi, Mark W. Youngblood, Constantine L. Karras, Ephraim A. Oyetunji, John Kalapurakal, Craig M. Horbinski, Hinda Najem, Virginia B. Hill, James P. Chandler, Amy B. Heimberger, Stephen T. Magill and Rimas V. Lukas
Cancers 2022, 14(23), 5887; https://doi.org/10.3390/cancers14235887 - 29 Nov 2022
Cited by 4 | Viewed by 7216
Abstract
Supratentorial non-skull base meningiomas are the most common primary central nervous system tumor subtype. An understanding of their pathophysiology, imaging characteristics, and clinical management options will prove of substantial value to the multi-disciplinary team which may be involved in their care. Extensive review [...] Read more.
Supratentorial non-skull base meningiomas are the most common primary central nervous system tumor subtype. An understanding of their pathophysiology, imaging characteristics, and clinical management options will prove of substantial value to the multi-disciplinary team which may be involved in their care. Extensive review of the broad literature on the topic is conducted. Narrowing the scope to meningiomas located in the supratentorial non-skull base anatomic location highlights nuances specific to this tumor subtype. Advances in our understanding of the natural history of the disease and how findings from both molecular pathology and neuroimaging have impacted our understanding are discussed. Clinical management and the rationale underlying specific approaches including observation, surgery, radiation, and investigational systemic therapies is covered in detail. Future directions for probable advances in the near and intermediate term are reviewed. Full article
(This article belongs to the Special Issue Meningioma: From Bench to Bedside)
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