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Brazilian Journal of Otorhinolaryngology 2023To review the literature on the diagnosis and treatment of vestibular schwannoma. (Review)
Review
OBJECTIVE
To review the literature on the diagnosis and treatment of vestibular schwannoma.
METHODS
Task force members were educated on knowledge synthesis methods, including electronic database search, review and selection of relevant citations, and critical appraisal of selected studies. Articles written in English or Portuguese on vestibular schwannoma were eligible for inclusion. The American College of Physicians' guideline grading system and the American Thyroid Association's guideline criteria were used for critical appraisal of evidence and recommendations for therapeutic interventions.
RESULTS
The topics were divided into 2 parts: (1) Diagnosis - audiologic, electrophysiologic tests, and imaging; (2) Treatment - wait and scan protocols, surgery, radiosurgery/radiotherapy, and systemic therapy.
CONCLUSIONS
Decision making in VS treatment has become more challenging. MRI can diagnose increasingly smaller tumors, which has disastrous consequences for the patients and their families. It is important to develop an individualized approach for each case, which highly depends on the experience of each surgical team.
Topics: Humans; Neuroma, Acoustic; Brazil; Societies, Medical; Advisory Committees; Otolaryngology; Radiosurgery; Magnetic Resonance Imaging
PubMed: 37813009
DOI: 10.1016/j.bjorl.2023.101313 -
Journal of Neurosurgery Apr 2024The objective was to assess the performance of a context-enriched large language model (LLM) compared with international neurosurgical experts on questions related to...
OBJECTIVE
The objective was to assess the performance of a context-enriched large language model (LLM) compared with international neurosurgical experts on questions related to the management of vestibular schwannoma. Furthermore, another objective was to develop a chat-based platform incorporating in-text citations, references, and memory to enable accurate, relevant, and reliable information in real time.
METHODS
The analysis involved 1) creating a data set through web scraping, 2) developing a chat-based platform called neuroGPT-X, 3) enlisting 8 expert neurosurgeons across international centers to independently create questions (n = 1) and to answer (n = 4) and evaluate responses (n = 3) while blinded, and 4) analyzing the evaluation results on the management of vestibular schwannoma. In the blinded phase, all answers were assessed for accuracy, coherence, relevance, thoroughness, speed, and overall rating. All experts were unblinded and provided their thoughts on the utility and limitations of the tool. In the unblinded phase, all neurosurgeons provided answers to a Likert scale survey and long-answer questions regarding the clinical utility, likelihood of use, and limitations of the tool. The tool was then evaluated on the basis of a set of 103 consensus statements on vestibular schwannoma care from the 8th Quadrennial International Conference on Vestibular Schwannoma.
RESULTS
Responses from the naive and context-enriched Generative Pretrained Transformer (GPT) models were consistently rated not significantly different in terms of accuracy, coherence, relevance, thoroughness, and overall performance, and they were often rated significantly higher than expert responses. Both the naive and content-enriched GPT models provided faster responses to the standardized question set than expert neurosurgeon respondents (p < 0.01). The context-enriched GPT model agreed with 98 of the 103 (95%) consensus statements. Of interest, all expert surgeons expressed concerns about the reliability of GPT in accurately addressing the nuances and controversies surrounding the management of vestibular schwannoma. Furthermore, the authors developed neuroGPT-X, a chat-based platform designed to provide point-of-care clinical support and mitigate the limitations of human memory. neuroGPT-X incorporates features such as in-text citations and references to enable accurate, relevant, and reliable information in real time.
CONCLUSIONS
The present study, with its subspecialist-level performance in generating written responses to complex neurosurgical problems for which evidence-based consensus for management is lacking, suggests that context-enriched LLMs show promise as a point-of-care medical resource. The authors anticipate that this work will be a springboard for expansion into more medical specialties, incorporating evidence-based clinical information and developing expert-level dialogue surrounding LLMs in healthcare.
Topics: Humans; Language; Medicine; Neuroma, Acoustic; Neurosurgeons; Reproducibility of Results; Artificial Intelligence
PubMed: 38564804
DOI: 10.3171/2023.7.JNS23573 -
Clinical Trials (London, England) Feb 2024Neurofibromatosis 1 and schwannomatosis are characterized by potential lifelong morbidity and life-threatening complications. To date, however, diagnostic and predictive... (Review)
Review
INTRODUCTION
Neurofibromatosis 1 and schwannomatosis are characterized by potential lifelong morbidity and life-threatening complications. To date, however, diagnostic and predictive biomarkers are an unmet need in this patient population. The inclusion of biomarker discovery correlatives in neurofibromatosis 1/schwannomatosis clinical trials enables study of low-incidence disease. The implementation of a common data model would further enhance biomarker discovery by enabling effective concatenation of data from multiple studies.
METHODS
The Response Evaluation in Neurofibromatosis and Schwannomatosis biomarker working group reviewed published data on emerging trends in neurofibromatosis 1 and schwannomatosis biomarker research and developed recommendations in a series of consensus meetings.
RESULTS
Liquid biopsy has emerged as a promising assay for neurofibromatosis 1/schwannomatosis biomarker discovery and validation. In addition, we review recommendations for a range of biomarkers in clinical trials, neurofibromatosis 1/schwannomatosis-specific data annotations, and common data models for data integration.
CONCLUSION
These Response Evaluation in Neurofibromatosis and Schwannomatosis consensus guidelines are intended to provide best practices for the inclusion of biomarker studies in neurofibromatosis 1/schwannomatosis clinical trials, data, and sample annotation and to lay a framework for data harmonization and concatenation between trials.
Topics: Humans; Neurofibromatosis 1; Neurofibromatosis 2; Neurofibromatoses; Biomarkers; Neurilemmoma; Skin Neoplasms
PubMed: 37904489
DOI: 10.1177/17407745231203330 -
Neurocirugia (English Edition) 2023To evaluate the efficacy of treatment with linear accelerator-based stereotactic radiosurgery (LINAC) in cerebellopontine angle meningiomas.
OBJECTIVES
To evaluate the efficacy of treatment with linear accelerator-based stereotactic radiosurgery (LINAC) in cerebellopontine angle meningiomas.
METHODS
We analyzed 80 patients diagnosed with cerebellopontine angle meningiomas between 2001 and 2014, treated with stereotactic radiosurgery (SRS), of whom 81.9% (n=68) were women, with an average age of 59.1 years (32-79). SRS was applied as primary treatment in 83.7% (n=67) and in 16.3% (n=13) as an adjuvant treatment to surgery. SRS treatment was provided using LINAC (Varian 600, 6MeV) with M3 micromultilamines (brainLab) and stereotactic frame. The average tumor volume was 3.12cm (0.34-10.36cm) and the coverage dose was 14Gy (12-16Gy). We performed a retrospective descriptive analysis and survival analysis was performed with the Kaplan-Meier method and multivariate analysis to determine those factors predictive of tumor progression or clinical improvement.
RESULTS
After an average follow-up period of 86.9 months (12-184), the tumor control rate was 92.8% (n=77). At the end of the study, there was an overall reduction in tumor volume of 32.8%, with an average final volume of 2.11cm (0-10.35cm). The progression-free survival rate at 5, 10 and 12 years was 98%, 95% and 83.3% respectively. The higher tumor volume (p=0.047) was associated with progression. There was clinical improvement in 26.5% (n=21) of cases and clinical worsening in 16.2% (n=13). Worsening is related to the radiation dose received by the brainstem (p=0.02). Complications were 8.7% (7 cases) of hearing loss, 5% (4 cases) of brain radionecrosis, and 3.7% (3 cases) of cranial nerve V neuropathy. Hearing loss was related to initial tumor size (p=0.033) and maximum dose (p=0.037). The occurrence of radionecrosis with the maximum dose (p=0.037).
CONCLUSIONS
Treatment of cerebellopontine angle meningiomas with single-dose SRS using LINAC is effective in the long term. Better tumor control rates were obtained in patients with small lesions.
Topics: Humans; Female; Middle Aged; Male; Meningioma; Radiosurgery; Treatment Outcome; Meningeal Neoplasms; Retrospective Studies; Cerebellopontine Angle; Follow-Up Studies; Hearing Loss; Neuroma, Acoustic
PubMed: 36842609
DOI: 10.1016/j.neucie.2023.02.001 -
The Laryngoscope Nov 2023Exclusive endoscopic (EETTA) and expanded (ExpTTA) transcanal transpromontorial approaches have shown promising results for treating internal auditory canal (IAC)... (Review)
Review
OBJECTIVE
Exclusive endoscopic (EETTA) and expanded (ExpTTA) transcanal transpromontorial approaches have shown promising results for treating internal auditory canal (IAC) lesions. We reviewed the literature to answer the question: "Do EETTA and ExpTTA achieve high rates of complete resection and low rates of complications in treating patients with IAC pathologies?"
DATA SOURCES
PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched.
REVIEW METHODS
Studies reporting EETTA/ExpTTA for IAC pathologies were included. Indications and techniques were discussed and meta-analyzed rates of outcomes and complications were obtained with random-effect model meta-analyses.
RESULTS
We included 16 studies comprising 173 patients, all with non-serviceable hearing. Baseline FN function was mostly House-Brackmann-I (96.5%; 95% CI: 94.9-98.1%). Most lesions were vestibular/cochlear schwannomas (98.3%; 95% CI: 96.7-99.8%) of Koos-I (45.9%; 95% CI: 41.3-50.3%) or II (47.1%; 95% CI: 43-51.1%). EETTA was performed in 101 patients (58.4%; 95% CI: 52.4-64.3%) and ExpTTA in 72 (41.6%; 95% CI: 35.6-47.6%), achieving gross-total resection in all cases. Transient complications occurred in 30 patients (17.3%; 95% CI: 13.9-20.5%), with meta-analyzed rates of 9% (95% CI: 4-15%), comprising FN palsy with spontaneous resolution (10.4%; 95% CI: 7.7-13.1%). Persistent complications occurred in 34 patients (19.6%; 95% CI: 17.1-22.2%), with meta-analyzed rates of 12% (95% CI: 7-19%), comprising persistent FN palsy in 22 patients (12.7%; 95% CI: 10.2-15.2%). Mean follow-up was 16 months (range, 1-69; 95% CI: 14.7-17.4). Post-surgery FN function was stable in 131 patients (75.8%; 95% CI: 72.1-79.5%), worsened in 38 (21.9%; 95% CI: 18.8-25%), and improved in 4 (2.3%; 95% CI: 0.7-3.9%), with meta-analyzed rates of improved/stable response of 84% (95% CI: 76-90%).
CONCLUSION
Transpromontorial approaches offer newer routes for IAC surgery, but their restricted indications and unfavorable FN outcomes currently limit their use. Laryngoscope, 133:2856-2867, 2023.
Topics: Humans; Retrospective Studies; Ear, Inner; Neuroma, Acoustic; Endoscopy; Paralysis
PubMed: 37078512
DOI: 10.1002/lary.30703 -
JAMA Otolaryngology-- Head & Neck... Apr 2024Management of sporadic vestibular schwannoma with radiosurgery is becoming increasingly common globally; however, limited data currently characterize patient outcomes in...
IMPORTANCE
Management of sporadic vestibular schwannoma with radiosurgery is becoming increasingly common globally; however, limited data currently characterize patient outcomes in the setting of microsurgical salvage for radiosurgical failure.
OBJECTIVE
To describe the clinical outcomes of salvage microsurgery following failed primary stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) among patients with sporadic vestibular schwannoma.
DESIGN, SETTING, AND PARTICIPANTS
This was a cohort study of adults (≥18 years old) with sporadic vestibular schwannoma who underwent salvage microsurgery following failed primary SRS/FSRT in 7 vestibular schwannoma treatment centers across the US and Norway. Data collection was performed between July 2022 and January 2023, with data analysis performed between January and July 2023.
EXPOSURE
Salvage microsurgical tumor resection.
MAIN OUTCOMES AND MEASURES
Composite outcome of undergoing less than gross total resection (GTR) or experiencing long-term facial paresis.
RESULTS
Among 126 patients, the median (IQR) age at time of salvage microsurgery was 62 (53-70) years, 69 (55%) were female, and 113 of 117 (97%) had tumors that extended into the cerebellopontine angle at time of salvage. Of 125 patients, 96 (76%) underwent primary gamma knife SRS, while 24 (19%) underwent linear accelerator-based SRS; the remaining patients underwent FSRT using other modalities. Postoperative cerebrospinal fluid leak was seen in 15 of 126 patients (12%), hydrocephalus in 8 (6%), symptomatic stroke in 7 (6%), and meningitis in 2 (2%). Each 1-mm increase in cerebellopontine angle tumor size was associated with a 13% increased likelihood of foregoing GTR (64 of 102 patients [63%]) or long-term postoperative House-Brackmann grade higher than I (48 of 102 patients [47%]) (odds ratio, 1.13; 95% CI, 1.04-1.23). Following salvage microsurgery, tumor growth-free survival rates at 1, 3, and 5 years were 97% (95% CI, 94%-100%), 93% (95% CI, 87%-99%), and 91% (95% CI, 84%-98%), respectively.
CONCLUSIONS
In this cohort study, more than half of patients who received salvage microsurgery following primary SRS/FSRT underwent less than GTR or experienced some degree of facial paresis long term. These data suggest that the cumulative risk of developing facial paresis following primary SRS/FSRT by the end of the patient's journey with treatment approximates 2.5% to 7.5% when using published primary SRS/FSRT long-term tumor control rates.
Topics: Adult; Humans; Female; Adolescent; Male; Radiosurgery; Neuroma, Acoustic; Cohort Studies; Treatment Outcome; Microsurgery; Facial Paralysis; Retrospective Studies
PubMed: 38358763
DOI: 10.1001/jamaoto.2023.4474 -
Brain : a Journal of Neurology Jul 2023Vestibular schwannomas are benign nerve sheath tumours that arise on the vestibulocochlear nerves. Vestibular schwannomas are known to occur in the context of tumour...
Vestibular schwannomas are benign nerve sheath tumours that arise on the vestibulocochlear nerves. Vestibular schwannomas are known to occur in the context of tumour predisposition syndromes NF2-related and LZTR1-related schwannomatosis. However, the majority of vestibular schwannomas present sporadically without identification of germline pathogenic variants. To identify novel genetic associations with risk of vestibular schwannoma development, we conducted a genome-wide association study in a cohort of 911 sporadic vestibular schwannoma cases collated from the neurofibromatosis type 2 genetic testing service in the north-west of England, UK and 5500 control samples from the UK Biobank resource. One risk locus reached genome-wide significance in our association analysis (9p21.3, rs1556516, P = 1.47 × 10-13, odds ratio = 0.67, allele frequency = 0.52). 9p21.3 is a genome-wide association study association hotspot, and a number of genes are localized to this region, notably CDKN2B-AS1 and CDKN2A/B, also referred to as the INK4 locus. Dysregulation of gene products within the INK4 locus have been associated with multiple pathologies and the genes in this region have been observed to directly impact the expression of one another. Recurrent associations of the INK4 locus with components of well-described oncogenic pathways provides compelling evidence that the 9p21.3 region is truly associated with risk of vestibular schwannoma tumorigenesis.
Topics: Humans; Neuroma, Acoustic; Genome-Wide Association Study; Neurilemmoma; Neurofibromatoses; Skin Neoplasms; Neurofibromatosis 2; Transcription Factors
PubMed: 36546557
DOI: 10.1093/brain/awac478 -
The Journal of Laryngology and Otology Nov 2023Stereotactic radiosurgery has been shown to be an effective method of managing vestibular schwannomas. The primary aim here is to establish the impact of pre-treatment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Stereotactic radiosurgery has been shown to be an effective method of managing vestibular schwannomas. The primary aim here is to establish the impact of pre-treatment fast-growing vestibular schwannomas on the efficacy of stereotactic radiosurgery.
METHODS
PubMed, Medline and Embase databases were used. The ROBINS-I ('Risk Of Bias In Non-randomised Studies - of Interventions') tool was utilised to assess for risk of bias. Proportionate meta-analysis and sub-analysis for fast-growing tumours were performed to explore the success rate of stereotactic radiosurgery in stabilising or decreasing the tumour burden in vestibular schwannomas.
RESULTS
Four moderate risk studies were included in the analysis. Overall, 91 per cent (95 per cent confidence interval = 0.83-0.97, < 0.01, = 80 per cent) of the tumours demonstrated successful size reduction or stabilisation following stereotactic radiosurgery. Nevertheless, the efficacy of stereotactic radiosurgery in reducing or stabilising fast-growing vestibular schwannomas decreased by 79 per cent (95 per cent confidence interval = 0.64-0.91, = 0.11, = 62 per cent).
CONCLUSION
Stereotactic radiosurgery has a statistically significant success rate in stabilising or decreasing the vestibular schwannoma size. This success rate is diminished in fast-growing vestibular schwannomas.
Topics: Humans; Neuroma, Acoustic; Radiosurgery; Microsurgery
PubMed: 37194631
DOI: 10.1017/S0022215123000786 -
Neurosurgical Review Oct 2023Pelvic schwannomas are rare tumors that may occur either sporadically or in the context of schwannomatosis. We retrospectively reviewed the charts of patients harboring...
Pelvic schwannomas are rare tumors that may occur either sporadically or in the context of schwannomatosis. We retrospectively reviewed the charts of patients harboring a pelvic schwannoma under conservative management or operated at our reference center between 2016 and 2023. All patients were operated by a multidisciplinary team, combining a vascular surgeon and a neurosurgeon. Twenty-four patients harboring 33 pelvic tumors were included in the cohort, including 12 patients with sporadic lesions, 2 patients with NF2-related schwannomatosis, and 10 patients with NF2-independent schwannomatosis. Multi-nodular tumors were more frequent in schwannomatosis compared to sporadic cases (p = 0.005). The mean age at diagnosis was 41 years old. Schwannomas were located on branches of the sciatic nerve (23/33, 70%), the femoral nerve (6/33, 18%), and the obturator nerve (4/33, 12%). Over the course of the study, 16 patients were operated, including 11 sporadic cases. The indication for surgery was pain (12/16, 75%) or tumor growth (4/16, 25%). Complete resection was achieved in 14 of 16 patients (87%). The mean post-operative follow-up was 37 months (range: 2-168 months). At last-follow-up, complete pain relief was achieved in all 12 patients with pre-operative pain. Post-operative morbidity included 3 long-term localized numbness and one MRC class 4 motor deficit in a multi-nodular tumor in a schwannomatosis patient. Despite its limited size, our series suggests that nerve-sparing resection of pelvic schwannomas offers satisfying rates of functional outcome both in sporadic and schwannomatosis cases, except for multi-nodular tumors.
Topics: Humans; Adult; Neurofibromatosis 2; Retrospective Studies; Neurilemmoma; Pain
PubMed: 37857782
DOI: 10.1007/s10143-023-02186-y -
Nature Communications Jun 2024Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some...
Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.
Topics: Humans; Transcriptome; Single-Cell Analysis; Animals; Regeneration; Mice; Saccule and Utricle; Neuroma, Acoustic; Ear, Inner; Insulin-Like Growth Factor I; Male; Hair Cells, Vestibular; Female; Gene Expression Profiling
PubMed: 38844821
DOI: 10.1038/s41467-024-48491-y