Meningioma: not always a benign tumor. A review of advances in the treatment of meningiomas.
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ABSTRACT:
SUBMITTER: Maggio I
PROVIDER: S-EPMC8162186 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Nineteen benign [World Health Organization (WHO) grade I; MI], 21 atypical (WHO grade II; MII), and 19 anaplastic (WHO grade III; MIII) sporadic meningiomas were screened for chromosomal imbalances by comparative genomic hybridization (CGH). These data were supplemented by molecular genetic analyses of selected chromosomal regions and genes. With increasing malignancy grade, a marked accumulation of genomic aberrations was observed; i.e., the numbers (mean +/- SEM) of total alterations detected per tumor were 2.9 +/- 0.7 for MI, 9.2 +/- 1.2 for MII, and 13.3 +/- 1.9 for MIII. The most frequent alteration detected in MI was loss on 22q (58%). In MII, aberrations most commonly identified were losses on 1p (76%), 22q (71%), 14q (43%), 18q (43%), 10 (38%), and 6q (33%), as well as gains on 20q (48%), 12q (43%), 15q (43%), 1q (33%), 9q (33%), and 17q (33%). In MIII, most of these alterations were found at similar frequencies. However, an increase in losses on 6q (53%), 10 (68%), and 14q (63%) was observed. In addition, 32% of MIII demonstrated loss on 9p. Homozygous deletions in the CDKN2A gene at 9p21 were found in 4 of 16 MIII (25%). Highly amplified DNA sequences were mapped to 12q13-q15 by CGH in 1 MII. Southern blot analysis of this tumor revealed amplification of CDK4 and MDM2. By CGH, DNA sequences from 17q were found to be amplified in 1 MII and 8 MIII, involving 17q23 in all cases. Despite the high frequency of chromosomal aberrations in the MII and MIII investigated, none of these tumors showed mutations in exons 5-8 of the TP53 gene. On the basis of the most common aberrations identified in the various malignancy grades, a model for the genomic alterations associated with meningioma progression is proposed.
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Project description:Around 20% of meningiomas histologically benign may be clinically aggressive and recur. This strongly affects management of meningioma patients. There is a need to evaluate the potential aggressiveness of an individual meningioma. Additional criteria for better classification of meningiomas will improve clinical decisions as well as patient follow up strategy after surgery. The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. Forty benign and fourteen atypical meningioma tissue samples were included in the study. We obtained metabolic profiles by NMR and recurrence after surgery information for all of them. We measured gene expression by oligonucleotide microarray measurements on 19 of them. To our knowledge, this is the first time that distinct gene expression profiles are reported for benign meningioma molecular subgroups with clinical correlation. Our results show that metabolic aggressiveness in otherwise histological benign meningioma proceeds mostly through alterations in the expression of genes involved in the regulation of transcription, mainly the LMO3 gene. Genes involved in tumor metabolism, like IGF1R, are also differentially expressed in those meningioma subgroups with higher rates of membrane turnover, higher energy demand and increased resistance to apoptosis. These new subgroups of benign meningiomas exhibit different rates of recurrence. This work shows that benign meningioma with metabolic aggressiveness constitute a subgroup of potentially recurrent tumors in which alterations in genes regulating critical features of aggressiveness, like increased angiogenesis or cell invasion, are still no predominant. The determination of these gene expression biosignatures may allow the early detection of clinically aggressive tumors.
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Project description:Meningiomas are relatively common, and typically benign intracranial tumors, which in many cases can be cured by surgical resection. However, less prevalent, high grade meningiomas, grow quickly, and recur frequently despite treatment, leading to poor patient outcomes. Across tumor grades, subjective guidelines for histological analysis can preclude accurate diagnosis, and an insufficient understanding of recurrence risk can cloud the choice of optimal treatment. Improved diagnostic and prognostic markers capable of discerning between the 15 heterogeneous WHO recognized meningioma subtypes are necessary to improve disease management and identify new targeted drug treatments. In this review, we show the advances in molecular profiling and immunophenotyping of meningiomas, which may lead to the development of new personalized therapeutic strategies.
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Project description: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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Project description: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.
| S-EPMC6347080 | biostudies-literature
Project description:Meningiomas are the most common adult primary intracranial tumor. Despite their higher incidence, there have not-until recently-been as many advances in understanding and managing meningiomas. Thus far, two broad classes of meningiomas have emerged on the basis of their mutational profile: those driven by neurofibromatosis 2 (NF2) inactivation and those with non-NF2 driver gene alterations, such as mammalian target of rapamycin and Hedgehog, Wingless/b-catenin, Notch, transforming growth factor-b receptor, mitogen-activated protein kinase, and phospholipase C pathway alterations. In addition to improvements in molecular diagnostics, advances in imaging are being studied to better predict tumor behavior, stratify risk, and potentially monitor for disease response. Management consists primarily of surgery and radiation therapy and there has been limited success from medical therapies, although novel targeted agents are now in clinical trials. Advances in imaging and understanding of the genetic makeup of meningiomas demonstrate the huge potential in revolutionizing the classification, diagnosis, management, and prognosis of meningiomas..
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Project description: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.
| S-EPMC6347083 | biostudies-literature
Project description: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.
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Project description:The current analysis follows the implementation of Public Law 107-260, the Benign Brain Tumor Cancer Registries Amendment Act, which mandated the collection of nonmalignant brain tumors.Meningiomas were selected from the Surveillance, Epidemiology, and End Results (SEER) Program database for the years 2004 to 2011. Demographic and clinical characteristics, initial treatment patterns, and survival outcomes were evaluated using surveillance epidemiology statistical methods.The average annual age-adjusted incidence rate per 100,000 population was 7.62 (95 % confidence interval [CI], 7.55-7.68) for all meningiomas, 7.18 (95% CI, 7.12-7.25) for benign meningiomas, 0.32 (95% CI, 0.31-0.33) for borderline malignant meningiomas, and 0.12 (95% CI, 0.11-0.12) for malignant meningiomas. The annual rates increased for benign and borderline malignant tumors but decreased for malignant tumors. The rates for women exceeded those for men, especially for those with benign meningiomas. Black race was associated with significantly higher rates as was advancing age. Greater than 80% of tumors were located in cerebral meninges. Diagnostic confirmation through pathology occurred for approximately 50% of benign tumors, 90% of borderline malignant tumors, and 80% of malignant tumors. No initial treatment was reported for greater than 60% of benign tumors, 29% of borderline malignant tumors, or 31% of malignant tumors. The 5-year relative survival estimates for benign tumors, borderline malignant tumors, and malignant tumors were 85.6% (95% confidence interval [CI], 85%-86.2%), 82.3% (95% CI, 79.3%-84.8%), and 66% (95% CI, 60.6%-70.9%), respectively. Predictors of poorer survival were advanced age, being male gender, black race, no initial treatment, and malignant tumor behavior.The current analysis demonstrates that there is an increasing incidence of nonmalignant meningiomas, probably because of reporting learning curves associated with the implementation of Public Law 107-260. The high proportion of cases who receive no initial treatment is a survival outcome concern, especially for patients with malignant meningiomas.
| S-EPMC5549267 | biostudies-other
Project description:Meningioma is the most common primary neoplasm of the central nervous system (CNS). Generally, these tumors are benign and have a good prognosis. However, treatment can be challenging in cases with aggressive variants and poor prognoses. Among various prognostic factors that have been clinically investigated, bone invasion remains controversial owing to a limited number of assessments. Recent study reported that bone invasion was not associated with WHO grades, progression, or recurrence. Whereas, patients with longer-recurrence tended to have a higher incidence of bone invasion. Furthermore, bone invasion may be a primary preoperative predictor of the extent of surgical resection. Increasing such evidence highlights the potential of translational studies to understand bone invasion as a prognostic factor of meningiomas. Therefore, this mini-review summarizes recent advances in pathophysiology and diagnostic modalities and discusses future research directions and therapeutic strategies for meningiomas with bone invasion.
| S-EPMC9280135 | biostudies-literature