-
Head and Neck Pathology Dec 2020Vestibular schwannoma (VS) is a Schwann cell-derived tumour arising from the vestibulocochlear nerve. Although benign, it represents a threat to intracranial structures... (Review)
Review
Vestibular schwannoma (VS) is a Schwann cell-derived tumour arising from the vestibulocochlear nerve. Although benign, it represents a threat to intracranial structures due to mass effect and carries a small risk of malignant transformation. VS therefore represents an important healthcare burden. We review the literature regarding pathogenesis, risk factors, and diagnosis of VS. The current and future potential management strategies are also discussed. A narrative review of all relevant papers known to the authors was conducted. The majority of VS remain clinically stable and do not require interventional procedures. Nevertheless, various surgical techniques exist for removing VS, the most common of which are translabyrinthine and retrosigmoid approaches. Due to surgical risks such as hearing loss, facial nerve dysfunction, post-operative headache, and cerebrospinal fluid leakage, a "watch and rescan" approach is adopted for most patients. Radiotherapy is a useful alternative and has been shown to have a similar response for growth restriction. Due to the heterogeneous nature of VS, there is a lack of consensus regarding management of tumours that are too large for conservative management but too small to indicate surgery. Emerging biologic therapies, such as Bevacizumab, Everolimus, and Lapatinib, as well as anti-inflammatories like aspirin are promising potential treatments; however, long-term evidence of their efficacy is required. The knowledge base regarding VS continues to improve. With increased understanding of the pathogenesis of these tumors, we believe future work should focus on pharmacologic intervention. Biologic therapies aimed toward improved patient outcomes are particularly promising.
Topics: Humans; Neuroma, Acoustic; Risk Factors
PubMed: 32232723
DOI: 10.1007/s12105-020-01155-x -
Neuro-oncology Jan 2020The level of evidence to provide treatment recommendations for vestibular schwannoma is low compared with other intracranial neoplasms. Therefore, the vestibular...
The level of evidence to provide treatment recommendations for vestibular schwannoma is low compared with other intracranial neoplasms. Therefore, the vestibular schwannoma task force of the European Association of Neuro-Oncology assessed the data available in the literature and composed a set of recommendations for health care professionals. The radiological diagnosis of vestibular schwannoma is made by magnetic resonance imaging. Histological verification of the diagnosis is not always required. Current treatment options include observation, surgical resection, fractionated radiotherapy, and radiosurgery. The choice of treatment depends on clinical presentation, tumor size, and expertise of the treating center. In small tumors, observation has to be weighed against radiosurgery, in large tumors surgical decompression is mandatory, potentially followed by fractionated radiotherapy or radiosurgery. Except for bevacizumab in neurofibromatosis type 2, there is no role for pharmacotherapy.
Topics: Humans; Neuroma, Acoustic
PubMed: 31504802
DOI: 10.1093/neuonc/noz153 -
International Journal of Molecular... Jan 2021Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common... (Review)
Review
Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common primary brain tumor; many NF2 patients suffer from multiple meningiomas. In NF2, patients have mutations in the gene, specifically with loss of function in a tumor-suppressor protein that has a number of synonymous names, including: Merlin, Neurofibromin 2, and schwannomin. Merlin is a 70 kDa protein that has 10 different isoforms. The Hippo Tumor Suppressor pathway is regulated upstream by Merlin. This pathway is critical in regulating cell proliferation and apoptosis, characteristics that are important for tumor progression. Mutations of the NF2 gene are strongly associated with NF2 diagnosis, leading to benign proliferative conditions such as vestibular schwannomas and meningiomas. Unfortunately, even though these tumors are benign, they are associated with significant morbidity and the potential for early mortality. In this review, we aim to encompass meningiomas and vestibular schwannomas as they pertain to NF2 by assessing molecular genetics, common tumor types, and tumor pathogenesis.
Topics: Animals; Apoptosis; Brain Neoplasms; Cell Proliferation; Humans; Meningeal Neoplasms; Meningioma; Mutation; Neurofibromatosis 2; Neuroma, Acoustic
PubMed: 33445724
DOI: 10.3390/ijms22020690 -
JAMA Aug 2023Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been detected radiographically.
OBJECTIVE
To determine whether upfront radiosurgery provides superior tumor volume reduction to a wait-and-scan approach for small- to medium-sized vestibular schwannoma.
DESIGN, SETTING, AND PARTICIPANTS
Randomized clinical trial of 100 patients with a newly diagnosed (<6 months) unilateral vestibular schwannoma and a maximal tumor diameter of less than 2 cm in the cerebellopontine angle as measured on magnetic resonance imaging. Participants were enrolled at the Norwegian National Unit for Vestibular Schwannoma from October 28, 2014, through October 3, 2017; 4-year follow-up ended on October 20, 2021.
INTERVENTIONS
Participants were randomized to receive either upfront radiosurgery (n = 50) or to undergo a wait-and-scan protocol, for which treatment was given only upon radiographically documented tumor growth (n = 50). Participants underwent 5 annual study visits consisting of clinical assessment, radiological examination, audiovestibular tests, and questionnaires.
MAIN OUTCOMES AND MEASURES
The primary outcome was the ratio between tumor volume at the trial end at 4 years and baseline (V4:V0). There were 26 prespecified secondary outcomes, including patient-reported symptoms, clinical examinations, audiovestibular tests, and quality-of-life outcomes. Safety outcomes were the risk of salvage microsurgery and radiation-associated complications.
RESULTS
Of the 100 randomized patients, 98 completed the trial and were included in the primary analysis (mean age, 54 years; 42% female). In the upfront radiosurgery group, 1 participant (2%) received repeated radiosurgery upon tumor growth, 2 (4%) needed salvage microsurgery, and 45 (94%) had no additional treatment. In the wait-and-scan group, 21 patients (42%) received radiosurgery upon tumor growth, 1 (2%) underwent salvage microsurgery, and 28 (56%) remained untreated. For the primary outcome of the ratio of tumor volume at the trial end to baseline, the geometric mean V4:V0 was 0.87 (95% CI, 0.66-1.15) in the upfront radiosurgery group and 1.51 (95% CI, 1.23-1.84) in the wait-and-scan group, showing a significantly greater tumor volume reduction in patients treated with upfront radiosurgery (wait-and-scan to upfront radiosurgery ratio, 1.73; 95% CI, 1.23-2.44; P = .002). Of 26 secondary outcomes, 25 showed no significant difference. No radiation-associated complications were observed.
CONCLUSION AND RELEVANCE
Among patients with newly diagnosed small- and medium-sized vestibular schwannoma, upfront radiosurgery demonstrated a significantly greater tumor volume reduction at 4 years than a wait-and-scan approach with treatment upon tumor growth. These findings may help inform treatment decisions for patients with vestibular schwannoma, and further investigation of long-term clinical outcomes is needed.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02249572.
Topics: Female; Humans; Male; Middle Aged; Neuroma, Acoustic; Radiosurgery; Retrospective Studies; Treatment Outcome; Watchful Waiting; Magnetic Resonance Imaging; Cerebellopontine Angle; Salvage Therapy; Microsurgery
PubMed: 37526718
DOI: 10.1001/jama.2023.12222 -
International Journal of Molecular... May 2022Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined over the... (Review)
Review
Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined over the past few decades, especially for small tumors. Gamma knife radiosurgery has become an accepted treatment for VS, with a high rate of tumor control. For neurofibromatosis type 2 (NF2)-associated VS resistant to radiotherapy, vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR)-targeted therapy (e.g., bevacizumab) may become the first-line therapy. Recently, a clinical trial using a VEGFR1/2 peptide vaccine was also conducted in patients with progressive NF2-associated schwannomas, which was the first immunotherapeutic approach for NF2 patients. Targeted therapies for the gene product of SH3PXD2A-HTRA1 fusion may be effective for sporadic VS. Several protein kinase inhibitors could be supportive to prevent tumor progression because merlin inhibits signaling by tyrosine receptor kinases and the activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Tumor-microenvironment-targeted therapy may be supportive for the mainstays of management. The tumor-associated macrophage is the major component of immunosuppressive cells in schwannomas. Here, we present a critical overview of targeted therapies for VS. Multimodal therapy is required to manage patients with refractory VS.
Topics: High-Temperature Requirement A Serine Peptidase 1; Humans; Neurilemmoma; Neurofibromatosis 2; Neuroma, Acoustic; Phosphatidylinositol 3-Kinases; Tumor Microenvironment; Vascular Endothelial Growth Factor A
PubMed: 35628268
DOI: 10.3390/ijms23105462 -
Environment International May 2024Some have looked forward to the publication of the results of the COSMOS study on brain tumors, because the potential biases from retrospective investigations...
Some have looked forward to the publication of the results of the COSMOS study on brain tumors, because the potential biases from retrospective investigations predominating the search for brain tumor risks of mobile phone use since the late 1990 s were deemed unresolvable by further investigations of that type. Indeed, prospective cohort studies typically have the advantage of being not or less affected by differential exposure misclassification, recall and selection bias, and, as they proceed in the direction of the time arrow, results are more easily interpreted in terms of causation. However, results of the COSMOS study published now in this journal are not of help for the risk assessment of mobile phone use and do not support the conclusions of the authors that their findings "suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma".
Topics: Brain Neoplasms; Humans; Cell Phone; Prospective Studies; Cohort Studies; Bias; Risk Assessment; Glioma; Meningioma; Neuroma, Acoustic; Radiation Exposure; Young Adult; Adult; Middle Aged; Aged
PubMed: 38677087
DOI: 10.1016/j.envint.2024.108665 -
Neuro-oncology Jul 2022
Topics: Glioma; Humans; Neuroma, Acoustic
PubMed: 35323960
DOI: 10.1093/neuonc/noac078 -
Yonsei Medical Journal May 2016Many epidemiological studies have investigated environmental risk factors for the development of acoustic neuroma. However, these results are controversial. We conducted... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Many epidemiological studies have investigated environmental risk factors for the development of acoustic neuroma. However, these results are controversial. We conducted a meta-analysis of case-control studies to identify any potential relationship between history of noise exposure, smoking, allergic diseases, and risk of acoustic neuroma.
MATERIALS AND METHODS
We searched PubMed to identify relevant articles. Two researchers evaluated the eligibility and extracted the data independently.
RESULTS
Eleven case-control studies were included in our meta-analysis. Acoustic neuroma was found to be associated with leisure noise exposure [odds ratio (OR)=1.33, 95% confidence interval (CI): 1.05-1.68], but not with occupational noise exposure and ever noise exposure (OR=1.20, 95% CI: 0.84-1.72 and OR=1.15, 95% CI: 0.80-1.65). The OR of acoustic neuroma for ever (versus never) smoking was 0.53 (95% CI: 0.30-0.94), while the subgroup analysis indicated ORs of 0.95 (95% CI: 0.81-1.10) and 0.49 (95% CI: 0.41-0.59) for ex-smoker and current smoker respectively. The ORs for asthma, eczema, and seasonal rhinitis were 0.98 (95% CI: 0.80-1.18), 0.91 (95% CI: 0.76-1.09), and 1.52 (95% CI: 0.90-2.54), respectively.
CONCLUSION
Our meta-analysis is suggestive of an elevated risk of acoustic neuroma among individuals who were ever exposed to leisure noise, but not to occupational noise. Our study also indicated a lower acoustic neuroma risk among ever and current cigarette smokers than never smokers, while there was no significant relationship for ex-smokers. No significant associations were found between acoustic neuroma and history of any allergic diseases, such as asthma, eczema, and seasonal rhinitis.
Topics: Adult; Asthma; Environmental Exposure; Female; Humans; Hypersensitivity; Leisure Activities; Neuroma, Acoustic; Noise; Occupational Exposure; Risk Factors; Smoking
PubMed: 26996581
DOI: 10.3349/ymj.2016.57.3.776 -
Wiener Medizinische Wochenschrift (1946) Feb 2022Vestibular schwannomas can severely impair the quality of life of patients. Next to impaired hearing function, facial palsy is perceived as particularly disturbing in...
Vestibular schwannomas can severely impair the quality of life of patients. Next to impaired hearing function, facial palsy is perceived as particularly disturbing in this context. Varying growth rates of these benign tumors complicate a prediction of functional impairment of cranial nerves. Therefore, a regular update on current therapeutic strategies and alternative treatment options is relevant for both physicians and patients.
Topics: Aftercare; Humans; Neuroma, Acoustic; Quality of Life
PubMed: 33439379
DOI: 10.1007/s10354-020-00800-y -
Cell Death & Disease Sep 2023Hearing loss (HL) is the most common and heterogeneous disorder of the sensory system, with a large morbidity in the worldwide population. Among cells of the acoustic... (Review)
Review
Hearing loss (HL) is the most common and heterogeneous disorder of the sensory system, with a large morbidity in the worldwide population. Among cells of the acoustic nerve (VIII cranial nerve), in the cochlea are present the hair cells, the spiral ganglion neurons, the glia-like supporting cells, and the Schwann cells (SCs), which alterations have been considered cause of HL. Notably, a benign SC-derived tumor of the acoustic nerve, named vestibular schwannoma (VS), has been indicated as cause of HL. Importantly, SCs are the main glial cells ensheathing axons and forming myelin in the peripheral nerves. Following an injury, the SCs reprogram, expressing some stemness features. Despite the mechanisms and factors controlling their biological processes (i.e., proliferation, migration, differentiation, and myelination) have been largely unveiled, their role in VS and HL was poorly investigated. In this review, we enlighten some of the mechanisms at the base of SCs transformation, VS development, and progression, likely leading to HL, and we pose great attention on the environmental factors that, in principle, could contribute to HL onset or progression. Combining the biomolecular bench-side approach to the clinical bedside practice may be helpful for the diagnosis, prediction, and therapeutic approach in otology.
Topics: Humans; Neuroma, Acoustic; Hearing Loss; Deafness; Schwann Cells; Neuroglia
PubMed: 37741837
DOI: 10.1038/s41419-023-06141-z