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Neurosurgical Review Mar 2023The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Despite advances in... (Meta-Analysis)
Meta-Analysis Review
Efficacy of radiotherapy and stereotactic radiosurgery as adjuvant or salvage treatment in atypical and anaplastic (WHO grade II and III) meningiomas: a systematic review and meta-analysis.
The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Despite advances in modern neuro-oncology, HGM (WHO grade II and III) remains refractory to multimodal therapies. Published reports present aggregated data and are extremely varied in population size, exclusion criteria, selection bias, and inclusion of mixed histologic grades, making it extremely difficult to draw conclusions when taken individually. This current work aims to gather the existing evidence on RT and SRS as adjuvants following surgery or salvage treatment at recurrence after multimodality therapy failure and to conduct a systematic comparison between these two modalities. An extensive systematic literature review and meta-analysis were performed. A total of 42 papers were eligible for final analysis (RT n = 27; SRS n = 15) after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases. Adjuvant regimens were addressed in 37 papers (RT n = 26; SRS n = 11); salvage regimens were described in 5 articles (RT n = 1; SRS n = 4). The primary outcomes of the study were the overall recurrence rate and mortality. Other actuarial rates (local and distant control, OS, PFS, and complications) were retrieved and analyzed as secondary outcomes. A total of 2853 patients harboring 3077 HGM were included. The majority were grade II (87%) with a mean pre-radiation volume of 8.7 cc. Adjuvant regimen: 2742 patients (76.4% RT; 23.6% SRS) with an overall grade II/III rate of 6.6/1. Lesions treated adjSRS were more frequently grade III (17 vs 12%, p < 0.001), and received subtotal resection (57 vs 27%, p = 0.001) compared to the RT cohort. AdjSRS cohort had a significantly shorter mean follow-up than adjRT (36.7 vs 50.3 months, p = 0.01). The overall recurrence rate was 38% in adjRT vs 25% in adjSRS (p = 0.01), while mortality did not differ between the groups (20% vs 23%, respectively; p = 0.80). The median time to recurrence was 1.5 times longer in the RT group (p = 0.30). Five-year local control was 55% in adjRT and 26% in adjSRS (p = 0.01), while 5-year OS was 73% and 78% (p = 0.62), and 5-year PFS was 62% and 40% in adjRT and adjSRS (p = 0.008). No difference in the incidence of complications (24% vs 14%, p = 0.53). Salvage regimen: 110 patients (37.3% RT; 62.7% SRS) with a grade II/III rate of 8.6/1. The recurrence rate was 46% in salRT vs 24% in salSRS (p = 0.39), time to recurrence was 1.8 times longer in the salRT group (35 vs 18.5 months, p = 0.74). Mortality was slightly yet not significantly higher in salRT (34% vs 12%, p = 0.54). Data on local and distant control were only available for salSRS. The 5-year OS was 49% and 83% (p = 0.90), and the 5-year PFS was 39% and 50% in salRT and salSRS (p = 0.66), respectively. High-grade meningiomas (WHO grade II and III) receiving adjuvant RT showed a higher overall recurrence rate than meningiomas receiving adjuvant SRS. The adjRT cohort, however, achieved higher 5-year LC and PFS rates, thus suggesting a potentially longer time to recurrence compared to adjSRS patients, who, meanwhile, experienced a significantly shorter follow-up. This result must also consider the higher number of grade III lesions and the smaller extent of resection achieved in the adjSRS group. Overall mortality did not differ between the two groups. No differences in outcome measures were observed in salvage regimens.
Topics: Humans; Meningioma; Radiosurgery; Treatment Outcome; Salvage Therapy; Retrospective Studies; Meningeal Neoplasms; World Health Organization; Neoplasm Recurrence, Local; Follow-Up Studies
PubMed: 36928326
DOI: 10.1007/s10143-023-01969-7 -
Current Neurology and Neuroscience... Nov 2020Meningioma is a common intracranial neoplasm currently classified in 15 histologic subtypes across 3 grades of malignancy. First-choice therapy for meningioma is maximum... (Review)
Review
PURPOSE OF REVIEW
Meningioma is a common intracranial neoplasm currently classified in 15 histologic subtypes across 3 grades of malignancy. First-choice therapy for meningioma is maximum safe resection for grade I tumors, and surgery plus optional and mandatory adjuvant radiotherapy for grade II and III, respectively, given the increased rate of recurrence even in the event of complete resection. The WHO 2016 histopathologic grading of meningioma has been questioned due to subjectivity and its controversial predictive power for recurrence.
RECENT FINDINGS
Novel DNA methylation profiling has simplified classification into six classes that seem to improve prognostic accuracy. We review five main topics of molecular biology research regarding tumorigenesis and natural history of meningioma from the clinician's perspective: the histopathologic diagnostic features and pitfalls of the current tumor classification; the molecular integrated diagnosis supported by identification of genetic alterations and DNA methylation profiling; the general landscape of the various signaling pathways involved in meningioma formation; the pathogenic theories of the peri-tumoral edema present in meningioma and its therapy implications; and a summarized review on the current treatments and plausible targeted therapies directed to meningioma. It seems likely that molecular assessment will be introduced within the next update of the WHO classification of meningiomas, acknowledging the promising value of DNA methylation profiling. This integrated diagnostic protocol will simplify tumor subtype categorization and provide improved accuracy in predicting recurrence and outcome. Although much effort is being done in identifying key gene mutations, and elucidating specific intracellular signaling pathways involved in meningioma tumorigenesis, effective targeted therapies for recurrent meningiomas are still lacking.
Topics: Humans; Meningeal Neoplasms; Meningioma; Molecular Biology; Neoplasm Grading; Neoplasm Recurrence, Local; Prognosis
PubMed: 33136206
DOI: 10.1007/s11910-020-01084-w -
Current Opinion in Neurology Dec 2021Although most meningiomas are slow growing tumors mainly controlled by surgery with or without radiotherapy, aggressive meningiomas that fail these conventional... (Review)
Review
PURPOSE OF REVIEW
Although most meningiomas are slow growing tumors mainly controlled by surgery with or without radiotherapy, aggressive meningiomas that fail these conventional treatments constitute a rare situation, a therapeutic challenge and an unmet need in neuro-oncology.
RECENT FINDING
Mutational landscape in recurrent high-grade meningiomas includes mainly NF2 mutation or 22q chromosomal deletion, whereas telomerase reverse transcriptase promoter, BAP-1 and CDK2NA mutations were also found in aggressive meningiomas. Pi3K-Akt-mTOR pathway is currently the most relevant intracellular signaling pathway target in meningiomas with preliminary clinical activity observed. Assessment of drug activity with progression free survival rate at 6 months is challenging in regard to meningioma growth rate heterogeneity, so that 3-dimensional growth rate before and during treatment could be considered in the future to selected new active drugs.
SUMMARY
Despite a low evidence level, some systemic therapies may be considered for patients with recurrent meningioma not amenable to further surgery or radiotherapy. In recurrent high-grade meningioma, everolimus-octreotide combination, bevacizumab, sunitinib and peptide receptor radionuclide therapy exhibit a signal of activity that may justify their clinical use. Despite a lack of clear signal of activity to date, immunotherapy may offer new perspectives in the treatment of these refractory tumors.
Topics: Humans; Meningeal Neoplasms; Meningioma; Neoplasm Recurrence, Local; Octreotide; Phosphatidylinositol 3-Kinases
PubMed: 34629433
DOI: 10.1097/WCO.0000000000001002 -
Folia Medica Feb 2021Spinal meningiomas are found in all age groups, predominantly in women aged over 50 years. The clinical symptoms of this condition may range from mild to significant... (Review)
Review
Spinal meningiomas are found in all age groups, predominantly in women aged over 50 years. The clinical symptoms of this condition may range from mild to significant neurological deficit, varying widely depending on the location, position in relation to the spinal cord, size and histological type of the tumor. Magnetic resonance imaging is the diagnostic tool of choice because it shows the location, size, the axial position of the tumor, and the presence of concomitant conditions such as spinal malformations, edema or syringomyelia. According to the degree of malignancy, the World Health Organization divides meningiomas into three grades: grade I - benign; grade II - atypical, and grade III - malignant. The goal of the surgery is total resection which is achievable in 82%-98% of cases. Advances in radiosurgery have led to its increased use as primary or adjunct therapy. The current paper aims to review the fundamental clinical as-pects of spinal meningiomas such as their epidemiology, clinical presentation, histological characteristics, diagnostics, and management.
Topics: Disease Management; Global Health; Humans; Magnetic Resonance Imaging; Meningeal Neoplasms; Meningioma; Morbidity; Neoplasm Staging; Radiosurgery
PubMed: 33650392
DOI: 10.3897/folmed.63.e52967 -
Romanian Journal of Morphology and... 2023Atypical meningiomas (AMs), World Health Organization (WHO) grade 2, are a group of tumors with uneven and unpredictable clinical behavior. Our aim was to analyze...
BACKGROUND AND OBJECTIVES
Atypical meningiomas (AMs), World Health Organization (WHO) grade 2, are a group of tumors with uneven and unpredictable clinical behavior. Our aim was to analyze possible tumor recurrence predictors, and to identify factors that improve progression-free survival (PFS).
PATIENTS, MATERIALS AND METHODS
Our retrospective study included 81 patients followed up in the Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iaşi, Romania, between 1 January 2010 and 31 December 2020. The histopathological specimens were reviewed according to the WHO 2021 criteria. Analyses included clinical, imaging, pathological and surgical factors.
RESULTS
The tumor recurred in 53.1% of the 81 cases within 60 months of surgery. Tumor location (p<0.000), tumor volume (p<0.010), extent of surgical resection (p<0.000) and dural sinus invasion (p<0.001) were predictive factors of recurrence. Gross total resection (Simpson grade I and II) was achieved in 59.2% of patients. Patients with the tumors located in the brain convexity and volume <26.4 cm³ had better survival rates up to recurrence. PFS showed a significant relationship between Simpson grade I-III and biopsy (p<0.000) and was statistically influenced by tumor volume and location, and dural sinus invasion.
CONCLUSIONS
AMs are a heterogeneous group of tumors, and we identified posterior fossa location, volume ≥26.4 cm³, Simpson grade III and IV resection and dural sinus invasion as predictive factors for relapse and a shorter PFS. Whereas certain characteristics provide some prognostic value, future molecular characterizations of AMs are necessary, which will support the clinical decision-making process.
Topics: Humans; Meningioma; Meningeal Neoplasms; Retrospective Studies; Neoplasm Recurrence, Local; World Health Organization; Treatment Outcome
PubMed: 37867351
DOI: 10.47162/RJME.64.3.05 -
Journal of Neuro-oncology Apr 2023Surgical resection has long been the treatment of choice for meningiomas and is considered curative in many cases. Indeed, the extent of resection (EOR) remains a... (Review)
Review
INTRODUCTION
Surgical resection has long been the treatment of choice for meningiomas and is considered curative in many cases. Indeed, the extent of resection (EOR) remains a significant factor in determining disease recurrence and outcome optimization for patients undergoing surgery. Although the Simpson Grading Scale continues to be widely accepted as the measure of EOR and is used to predict symptomatic recurrence, its utility is under increasing scrutiny. The influence of surgery in the definitive management of meningioma is being re-appraised considering the rapid evolution of our understanding of the biology of meningioma.
DISCUSSION
Although historically considered "benign" lesions, meningioma natural history can vary greatly, behaving with unexpectedly high recurrence rates and growth which do not always behave in accordance with their WHO grade. Histologically confirmed WHO grade 1 tumors may demonstrate unexpected recurrence, malignant transformation, and aggressive behavior, underscoring the molecular complexity and heterogeneity.
CONCLUSION
As our understanding of the clinical predictive power of genomic and epigenomic factors matures, we here discuss the importance of surgical decision-making paradigms in the context of our rapidly evolving understanding of these molecular features.
Topics: Humans; Meningioma; Meningeal Neoplasms; Neoplasm Recurrence, Local; Neurosurgical Procedures; Retrospective Studies
PubMed: 37010677
DOI: 10.1007/s11060-023-04272-z -
Chinese Clinical Oncology Jul 2017Meningiomas are the most frequent primary central nervous system (CNS) tumors. Although approximately 80% of the tumors are slow growing and benign, some subtypes are...
Meningiomas are the most frequent primary central nervous system (CNS) tumors. Although approximately 80% of the tumors are slow growing and benign, some subtypes are associated with a less favorable outcome. An adequate classification system aims at providing a tool for estimating recurrence and overall survival of meningioma patients. The 2016 version of the World Health Organization (WHO) classification for CNS tumors constitutes a hallmark for neuropathological tumor classification since genetic alterations and histopathology are combined for a final diagnosis. Although this mainly applies to neuroepithelial tumors in meningioma research and classification the connection of histomorphological features and genetic profiles becomes more and more evident. Here we report on advances and controversies of meningioma classification in the 2016 edition of the WHO classification of CNS tumors. Furthermore we provide an outlook how a future meningioma classification system might look like.
Topics: Humans; Meningeal Neoplasms; Meningioma; Neoplasm Grading; Neoplasm Recurrence, Local; World Health Organization
PubMed: 28595423
DOI: 10.21037/cco.2017.05.02 -
Ophthalmic Plastic and Reconstructive... 2020Orbital actinomyces is a rare diagnosis with only a few cases reported in the literature. It can be difficult to diagnose due to its slow, indolent course, and...
Orbital actinomyces is a rare diagnosis with only a few cases reported in the literature. It can be difficult to diagnose due to its slow, indolent course, and nonspecific findings on imaging and clinical examination, and frequently it can masquerade as other pathologies such as neoplasm and inflammatory disease. The authors present a case of actinomyces masquerading as meningioma with findings of hyperostosis and a superior orbital roof interosseous tract on imaging.
Topics: Actinomyces; Humans; Hyperostosis; Meningeal Neoplasms; Meningioma; Orbit
PubMed: 32134768
DOI: 10.1097/IOP.0000000000001626 -
Brain Tumor Pathology Jul 2021Meningiomas are the most commonly diagnosed benign intracranial adult tumors. Subsets of meningiomas that present with extensive invasion into surrounding brain areas... (Review)
Review
Meningiomas are the most commonly diagnosed benign intracranial adult tumors. Subsets of meningiomas that present with extensive invasion into surrounding brain areas have high recurrence rates, resulting in difficulties for complete resection, substantially increased mortality of patients, and are therapeutically challenging for neurosurgeons. Exciting new data have provided insights into the understanding of the molecular machinery of invasion. Moreover, clinical trials for several novel approaches have been launched. Here, we will highlight the mechanisms which govern brain invasion and new promising therapeutic approaches for brain-invasive meningiomas, including pharmacological approaches targeting three major aspects of tumor cell invasion: extracellular matrix degradation, cell adhesion, and growth factors, as well as other innovative treatments such as immunotherapy, hormone therapy, Tumor Treating Fields, and biodegradable copolymers (wafers), impregnated chemotherapy. Those ongoing studies can offer more diversified possibilities of potential treatments for brain-invasive meningiomas, and help to increase the survival benefits for patients.
Topics: Antineoplastic Agents; Brain Neoplasms; Cell Adhesion; Disease-Free Survival; Extracellular Matrix; Humans; Immunotherapy; Intercellular Signaling Peptides and Proteins; Meningeal Neoplasms; Meningioma; Molecular Targeted Therapy; Neoplasm Invasiveness
PubMed: 33903981
DOI: 10.1007/s10014-021-00399-x -
Journal of Pediatric Hematology/oncology Jan 2022Malignant peritoneal mesothelioma (MPM) is an extremely rare entity with a poor prognosis. We report on a 16-year-old boy with ascites and abdominal distension. A...
Malignant peritoneal mesothelioma (MPM) is an extremely rare entity with a poor prognosis. We report on a 16-year-old boy with ascites and abdominal distension. A computed tomography scan showed peritoneal thickening and a mass adjacent to the transverse colon. Neither repeated cytologic testing of ascitic fluid, nor peritoneal tissue biopsy detected malignant cells. After the patient became progressively comatose, a magnetic resonance imaging scan of the brain showed leptomeningeal enhancement. An autopsy showed MPM infiltrating the pleura and the meninges. This is the first report on meningeal metastasis of MPM in a pediatric patient illustrating the enigmatic behavior of the tumor and highlighting the diagnostic pitfalls.
Topics: Adolescent; Humans; Male; Meningeal Neoplasms; Mesothelioma, Malignant; Neoplasm Metastasis; Peritoneal Neoplasms
PubMed: 33633025
DOI: 10.1097/MPH.0000000000002118