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Meningiomas and Low Grade Gliomas

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

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 28552

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Prof. Dr. Giuseppe Lombardi

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Department of Oncology, Oncology 1, Veneto Institute of Oncology-IRCCS, 35128 Padua, Italy
Interests: neuro-oncology; glioblastoma; gliomas; targeted therapy; brain tumors; immunotherapy; quality of life
Special Issues, Collections and Topics in MDPI journals

Dr. Leonardo Gorgoglione

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Director of Neurosurgery Unit, Casa Sollievo della Sofferenza-IRCCS, San Giovanni Rotondo (FG), Italy
Interests: brain tumors; glioblastoma; meningiomas; low grade gliomas; high-grade gliomas; brain vascular disease; neuro-oncology research

Dr. Alba Fiorentino

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Chief Radiation Oncology Department, General Regional Hospital F. Miulli, Acquaviva delle Fonti (BA), Italy
Interests: brain tumors; glioblastoma; meningiomas; low grade gliomas; high-grade gliomas; neuro-oncology research

Dr. Tamara Ius

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Neurosurgery Unit, Head-Neck and NeuroScience Department, University Hospital of Udine, 33100 Udine, Italy
Interests: neurosurgery; glioma; meningioma; glioblastoma; brain mapping; real-time neuropsychological testing; brain tractography
Special Issues, Collections and Topics in MDPI journals

Dr. Michele Longhi

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Radiosurgery and Stereotactic Neurosurgery Unit, Neurochirurgia B, Department of Neurosurgery, AOUI VERONA, Stefani Square, 1, 37126 Verona, Italy
Interests: gamma knife radiosurgery; neuro-oncology; functional neurosurgery; stereotactic neurosurgery; deep brain stimulation

Prof. Pasquale De Bonis

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1. Neurosurgery, S. Anna University Hospital, v.le A Moro 8 44124 Ferrara, Italy
2. Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
Interests: traslational neurosurgery; neuro-oncology; intraoperative monitoring, functional neuro-oncology

Special Issue Information

Dear colleagues,

Meningioma represents the most frequent primary brain tumor in adults, while low-grade gliomas are rarer tumors. Despite growing knowledge of the molecular changes responsible for tumor development, atypical, anaplastic meningiomas and low-grade gliomas still need optimal treatment, more prognostic and predictive factors, and better molecular knowledge. Therefore, it appears very important to understand the role of surgery, characterize these tumors with advanced imaging, such as MR and positron emission tomography, and analyze their molecular alterations. It is noteworthy that molecular alterations in these tumors could represent important prognostic factors and specific targets for precision medicine trials. In the last few years, many translational and clinical studies have been performed, and new treatments based on re-surgery, re-irradiation, targeted therapy, and immunotherapy have been designed and are being administered.

This Special Issue will cover all aspects of meningiomas and low-grade gliomas, including original researches on advanced imaging, molecular characteristics, current and experimental treatment options, supportive care, neurocognitive functions, and quality of life. Expert opinions, systematic reviews, and meta-analyses are also welcome.

Dr. Giuseppe Lombardi
Dr. Leonardo Gorgoglione
Dr. Alba Fiorentino
Dr. Tamara Ius
Prof. Pasquale De Bonis
Dr. Michele Longhi MD; Ph.D
Guest Editors

Manuscript Submission Information

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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.

Published Papers (10 papers)

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Research

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10 pages, 1450 KiB

Open AccessArticle

Dynamic Interplay between Lower-Grade Glioma Instability and Brain Metaplasticity: Proposal of an Original Model to Guide the Therapeutic Strategy

by Hugues Duffau

Cancers 2021, 13(19), 4759; https://doi.org/10.3390/cancers13194759 - 23 Sep 2021

Cited by 15 | Viewed by 2224

Abstract

The behavior of lower-grade glioma (LGG) is changing over time, spontaneously, and in reaction to treatments. First, due to genomic instability and clonal expansion, although LGG progresses slowly during the early period of the disease, its growth velocity will accelerate when this tumor will transform to a higher grade of malignancy. Furthermore, its pattern of progression may change following therapy, e.g., by switching from a proliferative towards a more diffuse profile, in particular after surgical resection. In parallel to this plasticity of the neoplasm, the brain itself is constantly adapting to the tumor and possible treatment(s) thanks to reconfiguration within and between neural networks. Furthermore, the pattern of reallocation can also change, especially by switching from a perilesional to a contrahemispheric functional reorganization. Such a reorientation of mechanisms of cerebral reshaping, related to metaplasticity, consists of optimizing the efficiency of neural delocalization in order to allow functional compensation by adapting over time the profile of circuits redistribution to the behavioral modifications of the glioma. This interplay between LGG mutations and reactional connectomal instability leads to perpetual modulations in the glioma–neural equilibrium, both at ultrastructural and macroscopic levels, explaining the possible preservation of quality of life despite tumor progression. Here, an original model of these dynamic interactions across LGG plasticity and the brain metanetwork is proposed to guide a tailored step-by-step individualized therapeutic strategy over years. Integration of these new parameters, not yet considered in the current guidelines, might improve management of LGG patients. Full article

(This article belongs to the Special Issue Meningiomas and Low Grade Gliomas)

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19 pages, 3672 KiB

Open AccessArticle

MPscore: A Novel Predictive and Prognostic Scoring for Progressive Meningioma

by Feili Liu, Jin Qian and Chenkai Ma

Cancers 2021, 13(5), 1113; https://doi.org/10.3390/cancers13051113 - 05 Mar 2021

Cited by 14 | Viewed by 2420

Abstract

Meningioma is the most common tumor in central nervous system (CNS). Although most cases of meningioma are benign (WHO grade I) and curable by surgical resection, a few tumors remain diagnostically and therapeutically challenging due to the frequent recurrence and progression. The heterogeneity of meningioma revealed by DNA methylation profiling suggests the demand of subtyping for meningioma. Therefore, we performed a clustering analyses to characterize the progressive features of meningioma and constructed a meningioma progression score to predict the risk of the recurrence. A total of 179 meningioma transcriptome from RNA sequencing was included for progression subtype clustering. Four biologically distinct subtypes (subtype 1, subtype 2, subtype 3 and subtype 4) were identified. Copy number alternation and genomewide DNA methylation of each subtype was also characterized. Immune cell infiltration was examined by the microenvironment cell populations counter. All anaplastic meningiomas (7/7) and most atypical meningiomas (24/32) are enriched in subtype 3 while no WHO II or III meningioma presents in subtype 1, suggesting subtype 3 meningioma is a progressive subtype. Stemness index and immune response are also heterogeneous across four subtypes. Monocytic lineage is the most immune cell type in all meningiomas, except for subtype 1. CD8 positive T cells are predominantly observed in subtype 3. To extend the clinical utility of progressive meningioma subtyping, we constructed the meningioma progression score (MPscore) by the signature genes in subtype 3. The predictive accuracy and prognostic capacity of MPscore has also been validated in three independent cohort. Our study uncovers four biologically distinct subtypes in meningioma and the MPscore is potentially helpful in the recurrence risk prediction and response to treatments stratification in meningioma. Full article

(This article belongs to the Special Issue Meningiomas and Low Grade Gliomas)

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14 pages, 1004 KiB

Open AccessArticle

Molecular Profiling of 22 Primary Atypical Meningiomas Shows the Prognostic Significance of 18q Heterozygous Loss and CDKN2A/B Homozygous Deletion on Recurrence-Free Survival

by Valeria Barresi, Michele Simbolo, Adele Fioravanzo, Maria Liliana Piredda, Maria Caffo, Claudio Ghimenton, Giampietro Pinna, Michele Longhi, Antonio Nicolato and Aldo Scarpa

Cancers 2021, 13(4), 903; https://doi.org/10.3390/cancers13040903 - 21 Feb 2021

Cited by 23 | Viewed by 2656

Abstract

The use of adjuvant therapy is controversial in atypical meningiomas with gross total resection. Predictors of recurrence risk could be useful in selecting patients for additional treatments. The aim of this study was to investigate whether molecular features are associated with recurrence risk of atypical meningiomas. According to WHO classification, the diagnosis of atypical meningioma was based on the presence of one major criteria (mitotic activity, brain invasion) or three or more minor criteria. The molecular profile of 22 cases (eight mitotically active, eight brain-invasive, and six with minor criteria) was assessed exploring the mutational status and copy number variation of 409 genes using next generation sequencing. Of the 22 patients with a median follow up of 53.5 months, 13 had recurrence of disease within 68 months. NF2 mutation was the only recurrent alteration (11/22) and was unrelated to clinical-pathological features. Recurring meningiomas featured a significantly higher proportion of copy number losses than non-recurring ones (p = 0.027). Chromosome 18q heterozygous loss or CDKN2A/B homozygous deletion was significantly associated with shorter recurrence-free survival (p = 0.008; hazard ratio: 5.3). Atypical meningiomas could be tested routinely for these genetic alterations to identify cases for adjuvant treatment. Full article

(This article belongs to the Special Issue Meningiomas and Low Grade Gliomas)

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13 pages, 558 KiB

Open AccessArticle

Psychological Burden in Meningioma Patients under a Wait-and-Watch Strategy and after Complete Resection Is High—Results of a Prospective Single Center Study

by Darius Kalasauskas, Naureen Keric, Salman Abu Ajaj, Leoni von Cube, Florian Ringel and Mirjam Renovanz

Cancers 2020, 12(12), 3503; https://doi.org/10.3390/cancers12123503 - 25 Nov 2020

Cited by 14 | Viewed by 2612

Abstract

The diagnosis of intracranial meningiomas as incidental findings is increasing by growing availability of MRI diagnostics. However, the psychological distress of patients with incidental meningiomas under a wait-and-watch strategy is unknown. Therefore, we aimed to compare the psychosocial situation of meningioma patients under wait-and-watch to patients after complete resection to bridge this gap. The inclusion criteria for the prospective monocenter study were either an incidental meningioma under a wait-and-watch strategy or no neurologic deficits after complete resection. Sociodemographic, clinical, and health-related quality of life and clinical data were assessed. Psychosocial factors were measured by the Distress Thermometer (DT), Hospital Anxiety and Depression Scale (HADS), Brief Fatigue Inventory (BFI), and the Short Form (SF-36). A total of 62 patients were included (n = 51 female, mean age 61 (SD 13) years). According to HADS, the prevalence of anxiety was 45% in the postoperative and 42% in the wait-and-watch group (p = 0.60), and depression was 61% and 87%, respectively (p = 0.005). In total, 43% of patients under wait-and-watch and 37% of patients in the postoperative group scored ≥6 on the DT scale. SF-36 scores were similar in all categories except general health (p = 0.005) and physical component aggregate score (43.7 (13.6) vs. 50.5 (9.5), (p = 0.03), both lower in the wait-and-watch group. Multivariate analysis revealed the wait-and-watch strategy was associated with a 4.26-fold higher risk of a pathological depression score based on HADS (p = 0.03). This study demonstrates a high prevalence of psychological distress in meningioma patients. Further evaluation is necessary to identify the patients in need of psychooncological support. Full article

(This article belongs to the Special Issue Meningiomas and Low Grade Gliomas)

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11 pages, 2127 KiB

Open AccessArticle

Identification of High-Risk Atypical Meningiomas According to Semantic and Radiomic Features

by Darius Kalasauskas, Andrea Kronfeld, Mirjam Renovanz, Elena Kurz, Petra Leukel, Harald Krenzlin, Marc A. Brockmann, Clemens J. Sommer, Florian Ringel and Naureen Keric

Cancers 2020, 12(10), 2942; https://doi.org/10.3390/cancers12102942 - 12 Oct 2020

Cited by 17 | Viewed by 2293

Abstract

Up to 60% of atypical meningiomas (World Health Organization (WHO) grade II) reoccur within 5 years after resection. However, no clear radiological criteria exist to identify tumors with higher risk of relapse. In this study, we aimed to assess the association of certain radiomic and semantic features of atypical meningiomas in MRI with tumor recurrence. We identified patients operated on primary atypical meningiomas in our department from 2007 to 2017. An analysis of 13 quantitatively defined radiomic and 11 qualitatively defined semantic criteria was performed based on preoperative MRI scans. Imaging characteristics were assessed along with clinical and survival data. The analysis included 76 patients (59% women, mean age 59 years). Complete tumor resection was achieved in 65 (86%) cases, and tumor relapse occurred in 17 (22%) cases. Mean follow-up time was 41.6 (range 3–168) months. Cystic component was significantly associated with tumor recurrence (odds ratio (OR) 21.7, 95% confidence interval (CI) 3.8–124.5) and shorter progression-free survival (33.2 vs. 80.7 months, p < 0.001), whereas radiomic characteristics had no predictive value in univariate analysis. However, multivariate analysis demonstrated significant predictive value of high cluster prominence (hazard ratio (HR) 5.89 (1.03–33.73) and cystic component (HR 20.21 (2.46–166.02)) for tumor recurrence. The combination of radiomic and semantic features might be an effective tool for identifying patients with high-risk atypical meningiomas. The presence of a cystic component in these tumors is associated with a high risk of tumor recurrence. Full article

(This article belongs to the Special Issue Meningiomas and Low Grade Gliomas)

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11 pages, 235 KiB

Open AccessArticle

Intracranial Meningiomas in the Elderly: Clinical, Surgical and Economic Evaluation. A Multicentric Experience

by Delia Cannizzaro, Maria Pia Tropeano, Ismail Zaed, Mario De Robertis, Simone Olei, Marco Vindigni, Enrico Pegolo, Daniele Bagatto, Andrea Cardia, Giulio Maira, Maurizio Fornari, Miran Skrap and Tamara Ius

Cancers 2020, 12(9), 2685; https://doi.org/10.3390/cancers12092685 - 20 Sep 2020

Cited by 2 | Viewed by 2060

Abstract

Meningioma is one of the most common intracranial tumors. It is benign and slow growing in the majority of cases. Given the increase in life expectancy and the number of radiological tests performed, the incidence in the elderly population (≥65 years) is continuously increasing. The surgical outcomes and prognostic factors in this age group are unclear. A retrospective analysis of all the patients treated for intracranial meningiomas in two different Italian institutions was performed. The clinical, radiological, surgical and follow-up data were retrospectively reviewed. Statistical analyses were performed to identify relationships between factors and outcomes. We also carried out an economic analysis. We analyzed 321 patients with intracranial meningioma. The mean age was 72.6 years (range, 65–90), with a female predominance (F/M, 1.41). Pre-operative deficits, cognitive impairment and seizures (p < 0.001) were associated with a worse post-operative Karnofsky performance scale (KPS) score (<80). A high pre-operative KPS score was associated with a good clinical and neurological outcome (p < 0.001). Being aged between 65 and 74 years, low surgical timing and Simpson removal grades of I and II were associated with a good outcome (p < 0.001). The length of hospitalization was significantly related to the outcome (p < 0.001). The complication rate was 14.3%. At 6-month follow-up, the mortality rate was 2.5%. The average cost was higher in patients with a pre-operative KPS score lower than 80. The outcome of intracranial-meningioma resection in elderly individuals is favorable when the pre-operative KPS score is >80. Treatment should be patient-specific, and additional factors should be considered. Patients with poor pre-operative clinical conditions might benefit from a combined strategy with partial resection and radiosurgery in order to reduce surgical timing and the complication rate. Full article

(This article belongs to the Special Issue Meningiomas and Low Grade Gliomas)

Review

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23 pages, 2595 KiB

Open AccessReview

Precision Oncology in Lower-Grade Gliomas: Promises and Pitfalls of Therapeutic Strategies Targeting IDH-Mutations

by Pasquale Persico, Elena Lorenzi, Agnese Losurdo, Angelo Dipasquale, Antonio Di Muzio, Pierina Navarria, Federico Pessina, Letterio Salvatore Politi, Giuseppe Lombardi, Armando Santoro and Matteo Simonelli

Cancers 2022, 14(5), 1125; https://doi.org/10.3390/cancers14051125 - 22 Feb 2022

Cited by 10 | Viewed by 3045

Abstract

Mutations in isocitrate dehydrogenase (IDH)1 and its homolog IDH2 are considered an earliest “driver” genetic event during gliomagenesis, representing now the molecular hallmark of lower-grade gliomas (LGGs). IDH-mutated genes encode for a neomorphic enzyme that converts α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate (2-HG), which accumulates to high concentrations and alters cellular epigenetics and metabolism. Targeting IDH mutations is the first attempt to apply “precision oncology” in LGGs. Two distinct strategies have been proposed so far and are under intense clinical investigation: (i) reducing the amount of intratumoral 2-HG by directly blocking the function of mutant IDH enzyme; (ii) exploiting the selective epigenetic and metabolic cellular vulnerabilities as a consequence of 2-HG accumulation. The present review describes the physiopathological mechanisms by which IDH mutations lead to tumorigenesis, discussing their prognostic significance and pivotal role in the gliomas diagnostic classification system. We critically review preclinical evidence and available clinical data of first-generation mutant-selective IDH inhibitors and novel IDH-targeted vaccines. Finally, as an alternative and attractive approach, we present the rationale to take advantage of selective 2-HG related epigenetic and metabolic weaknesses. The results of ongoing clinical trials will help us clarify the complex scenario of IDH-targeted therapeutic approaches in gliomas. Full article

(This article belongs to the Special Issue Meningiomas and Low Grade Gliomas)

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11 pages, 739 KiB

Open AccessReview

Meningiomas in Ancient Human Populations

by Della Collins Cook and Marie Elaine Danforth

Cancers 2022, 14(4), 1058; https://doi.org/10.3390/cancers14041058 - 19 Feb 2022

Cited by 2 | Viewed by 1697

Abstract

Meningiomas are the most common tumor of the central nervous system and can result in skeletal manifestations, including hyperostosis of the adjacent cranial bone, enostoses, depressions, and enhanced vascular impressions. However, their identification in the paleopathological literature has been rare and few cases have received broad acceptance of the diagnosis. A review of the literature identified some 43 cases in which individuals were argued to have suffered from meningiomas. Most were seen in older individuals but were more likely to affect males. Eleven individuals exhibited hyperostosis, the most easily recognized indicator, usually located on the parietal bone; the hyperostotic region averaged 8 cm in diameter and 3.0 cm in height. Seven displayed lytic lesions with areas much smaller in size than the hyperostosis, and many had vascular changes. The other cases had indicators that varied greatly in terms of location and expression and included both sclerotic lesions and hollow areas. Several authors also suggested other possible causes of the lesions. The findings reflect the non-pathognomonic nature of the effects of meningiomas. However, given their likely frequency and potentially severe effects in ancient people, it is argued that they should be taken into consideration more frequently when performing differential diagnoses. Full article

(This article belongs to the Special Issue Meningiomas and Low Grade Gliomas)

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24 pages, 13413 KiB

Open AccessReview

Advances in Multidisciplinary Management of Skull Base Meningiomas

by Tamara Ius, Alessandro Tel, Giuseppe Minniti, Teresa Somma, Domenico Solari, Michele Longhi, Pasquale De Bonis, Alba Scerrati, Mario Caccese, Valeria Barresi, Alba Fiorentino, Leonardo Gorgoglione, Giuseppe Lombardi and Massimo Robiony

Cancers 2021, 13(11), 2664; https://doi.org/10.3390/cancers13112664 - 28 May 2021

Cited by 11 | Viewed by 3574

Abstract

The surgical management of Skull Base Meningiomas (SBMs) has radically changed over the last two decades. Extensive surgery for patients with SBMs represents the mainstream treatment; however, it is often challenging due to narrow surgical corridors and proximity to critical neurovascular structures. Novel surgical technologies, including three-dimensional (3D) preoperative imaging, neuromonitoring, and surgical instruments, have gradually facilitated the surgical resectability of SBMs, reducing postoperative morbidity. Total removal is not always feasible considering a risky tumor location and invasion of surrounding structures and brain parenchyma. In recent years, the use of primary or adjuvant stereotactic radiosurgery (SRS) has progressively increased due to its safety and efficacy in the control of grade I and II meningiomas, especially for small to moderate size lesions. Patients with WHO grade SBMs receiving subtotal surgery can be monitored over time with surveillance imaging. Postoperative management remains highly controversial for grade II meningiomas, and depends on the presence of residual disease, with optional upfront adjuvant radiation therapy or close surveillance imaging in cases with total resection. Adjuvant radiation is strongly recommended in patients with grade III tumors. Although the currently available chemotherapy or targeted therapies available have a low efficacy, the molecular profiling of SBMs has shown genetic alterations that could be potentially targeted with novel tailored treatments. This multidisciplinary review provides an update on the advances in surgical technology, postoperative management and molecular profile of SBMs. Full article

(This article belongs to the Special Issue Meningiomas and Low Grade Gliomas)

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25 pages, 2415 KiB

Open AccessReview

Clinical Management of Diffuse Low-Grade Gliomas

by Giuseppe Lombardi, Valeria Barresi, Antonella Castellano, Emeline Tabouret, Francesco Pasqualetti, Alessandro Salvalaggio, Giulia Cerretti, Mario Caccese, Marta Padovan, Vittorina Zagonel and Tamara Ius

Cancers 2020, 12(10), 3008; https://doi.org/10.3390/cancers12103008 - 16 Oct 2020

Cited by 40 | Viewed by 4325

Abstract

Diffuse low-grade gliomas (LGG) represent a heterogeneous group of primary brain tumors arising from supporting glial cells and usually affecting young adults. Advances in the knowledge of molecular profile of these tumors, including mutations in the isocitrate dehydrogenase genes, or 1p/19q codeletion, and in neuroradiological techniques have contributed to the diagnosis, prognostic stratification, and follow-up of these tumors. Optimal post-operative management of LGG is still controversial, though radiation therapy and chemotherapy remain the optimal treatments after surgical resection in selected patients. In this review, we report the most important and recent research on clinical and molecular features, new neuroradiological techniques, the different therapeutic modalities, and new opportunities for personalized targeted therapy and supportive care. Full article

(This article belongs to the Special Issue Meningiomas and Low Grade Gliomas)

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