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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 -
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 -
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 -
Neuro-oncology Dec 2023Schwannomas are common peripheral nerve sheath tumors that can cause severe morbidity given their stereotypic intracranial and paraspinal locations. Similar to many...
BACKGROUND
Schwannomas are common peripheral nerve sheath tumors that can cause severe morbidity given their stereotypic intracranial and paraspinal locations. Similar to many solid tumors, schwannomas and other nerve sheath tumors are primarily thought to arise due to aberrant hyperactivation of the RAS growth factor signaling pathway. Here, we sought to further define the molecular pathogenesis of schwannomas.
METHODS
We performed comprehensive genomic profiling on a cohort of 96 human schwannomas, as well as DNA methylation profiling on a subset. Functional studies including RNA sequencing, chromatin immunoprecipitation-DNA sequencing, electrophoretic mobility shift assay, and luciferase reporter assays were performed in a fetal glial cell model following transduction with wildtype and tumor-derived mutant isoforms of SOX10.
RESULTS
We identified that nearly one-third of sporadic schwannomas lack alterations in known nerve sheath tumor genes and instead harbor novel recurrent in-frame insertion/deletion mutations in SOX10, which encodes a transcription factor responsible for controlling Schwann cell differentiation and myelination. SOX10 indel mutations were highly enriched in schwannomas arising from nonvestibular cranial nerves (eg facial, trigeminal, vagus) and were absent from vestibular nerve schwannomas driven by NF2 mutation. Functional studies revealed these SOX10 indel mutations have retained DNA binding capacity but impaired transactivation of glial differentiation and myelination gene programs.
CONCLUSIONS
We thus speculate that SOX10 indel mutations drive a unique subtype of schwannomas by impeding proper differentiation of immature Schwann cells.
Topics: Humans; INDEL Mutation; Transcriptional Activation; Neurilemmoma; Neuroma, Acoustic; Mutation; Nerve Sheath Neoplasms; SOXE Transcription Factors
PubMed: 37436963
DOI: 10.1093/neuonc/noad121 -
Environment International Mar 2024Each new generation of mobile phone technology has triggered discussions about potential carcinogenicity from exposure to radiofrequency electromagnetic fields (RF-EMF)....
BACKGROUND
Each new generation of mobile phone technology has triggered discussions about potential carcinogenicity from exposure to radiofrequency electromagnetic fields (RF-EMF). Available evidence has been insufficient to conclude about long-term and heavy mobile phone use, limited by differential recall and selection bias, or crude exposure assessment. The Cohort Study on Mobile Phones and Health (COSMOS) was specifically designed to overcome these shortcomings.
METHODS
We recruited participants in Denmark, Finland, the Netherlands, Sweden, and the UK 2007-2012. The baseline questionnaire assessed lifetime history of mobile phone use. Participants were followed through population-based cancer registers to identify glioma, meningioma, and acoustic neuroma cases during follow-up. Non-differential exposure misclassification was reduced by adjusting estimates of mobile phone call-time through regression calibration methods based on self-reported data and objective operator-recorded information at baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for glioma, meningioma, and acoustic neuroma in relation to lifetime history of mobile phone use were estimated with Cox regression models with attained age as the underlying time-scale, adjusted for country, sex, educational level, and marital status.
RESULTS
264,574 participants accrued 1,836,479 person-years. During a median follow-up of 7.12 years, 149 glioma, 89 meningioma, and 29 incident cases of acoustic neuroma were diagnosed. The adjusted HR per 100 regression-calibrated cumulative hours of mobile phone call-time was 1.00 (95 % CI 0.98-1.02) for glioma, 1.01 (95 % CI 0.96-1.06) for meningioma, and 1.02 (95 % CI 0.99-1.06) for acoustic neuroma. For glioma, the HR for ≥ 1908 regression-calibrated cumulative hours (90th percentile cut-point) was 1.07 (95 % CI 0.62-1.86). Over 15 years of mobile phone use was not associated with an increased tumour risk; for glioma the HR was 0.97 (95 % CI 0.62-1.52).
CONCLUSIONS
Our findings suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma.
Topics: Humans; Meningioma; Cohort Studies; Neuroma, Acoustic; Prospective Studies; Cell Phone Use; Brain Neoplasms; Glioma; Electromagnetic Fields; Cell Phone; Surveys and Questionnaires; Meningeal Neoplasms; Case-Control Studies
PubMed: 38458118
DOI: 10.1016/j.envint.2024.108552 -
Frontiers in Neurology 2023Brain tumors, especially gliomas, are known for high lethality. It is currently understood that the correlations of tumors with coagulation and inflammation have been...
BACKGROUND
Brain tumors, especially gliomas, are known for high lethality. It is currently understood that the correlations of tumors with coagulation and inflammation have been gradually revealed.
OBJECTIVE
This study aimed to explore the potential value of several reported peripheral blood parameters as comprehensively as possible, with preoperative diagnosis and identification of brain tumors (focus on gliomas).
METHODS
Patients with central nervous system tumors (craniopharyngioma, ependymoma, spinal meningioma, acoustic neuroma, brain metastases, meningioma, and glioma) or primary trigeminal neuralgia admitted to our hospital were retrospectively analyzed. The results of the routine coagulation factor test, serum albumin test, and blood cell test in peripheral blood were recorded for each group of patients on admission. Neutrophil-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), prognostic nutritional index (PNI), the systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and their pairings were calculated. Their ability to identify brain tumors and their correlation with glioma grade were analyzed.
RESULTS
A total of 698 patients were included in this retrospective case-control study. Glioma patients had higher NLR, SII, and PIV but lower LMR. The NLR in the brain metastasis group was lower than that in the control, meningioma, and acoustic neuroma groups, but the SII and PIV were higher than those in the ependymoma group. Fibrinogen, white blood cell count, neutrophil count, NLR, SII, and PIV in the GBM group were higher than those in the control group. In all comparisons, NLR and NLR + dNLR showed the greatest accuracy, with areas under the curve (AUCs) of 0.7490 (0.6482-0.8498) and 0.7481 (0.6457-0.8505), respectively. PIV, dNLR + PIV, and LMR + PIV ranked second, with AUCs of 0.7200 (0.6551-0.7849), 0.7200 (0.6526-0.7874), 0.7204 (0.6530-0.7878) and 0.7206 (0.6536-0.7875), respectively.
CONCLUSION
NLR, PIV, and their combinations show high sensitivity and specificity in the diagnosis of brain tumors, especially gliomas. Overall, our results provide evidence for these convenient and reliable peripheral blood markers.
PubMed: 37936915
DOI: 10.3389/fneur.2023.1297835 -
Cancers Sep 2023Vestibular schwannoma (VS) are equally common in men and woman. A number of epidemiological studies have reported on sex-specific aspects of incidence, tumor size,...
Vestibular schwannoma (VS) are equally common in men and woman. A number of epidemiological studies have reported on sex-specific aspects of incidence, tumor size, tinnitus and hearing loss. However, data on sex-specific, pre- and post-surgically quality of life (QoL) are rare. The objective of the present study was to determine sex-specific aspects on QoL in VS. Health-related QoL was analyzed in 260 patients (112 male/148 female) with unilateral sporadic VS using general (SF-36: general Short-Form Health Survey), disease-specific (PANQOL: Penn Acoustic Neuroma Quality-of-Life Scale, PANQOL) and symptom-specific (DHI: Dizziness Handicap Inventory; HHI: Hearing Handicap Inventory; THI: Tinnitus Handicap Inventory; FDI: Facial Disability Index) QoL questionnaires. Sex differences were evaluated pre- and postoperative by multi- and univariate analyses based on 200 preoperative and 88 postoperative questionnaires. Female patients were significantly more affected by dizziness, headaches, reduced energy and anxiety. Energy and balance changed similarly in both sexes after surgery. However, postoperative women tended to be more affected by facial palsy and headaches than men. Despite the greater physical impairment, general health improved equivalently or even more in female patients than in males. In conclusion, self-rated QoL in VS is significantly affected by sex and surgery. This should be taken into account when counseling VS patients regarding observation, radiotherapy, and surgery.
PubMed: 37686642
DOI: 10.3390/cancers15174365 -
Scientific Reports Dec 2023It is difficult to distinguish other pathologies mimicking Ménière's disease (MD) clinically. This study aims to investigate the differences of imaging findings and...
It is difficult to distinguish other pathologies mimicking Ménière's disease (MD) clinically. This study aims to investigate the differences of imaging findings and features between MD and other menieriform diseases via intravenous gadolinium-enhanced magnetic resonance imaging (MRI). 426 patients with menieriform symptoms, including MD, vestibular migraine (VM), and vestibular schwannoma (VS), underwent 3D-FLAIR and 3D-T2WI MRI 6 h after the intravenous gadolinium injection. MR images were analyzed for inner ear morphology, perilymphatic enhancement (PE), EH and other abnormalities. EH was observed at a higher rate in MD patients (85.71%) than patients with other menieriform diseases (VM group = 14.75%, VS group = 37.50%). The prevalence of unilateral EH as well as both cochlear and vestibular EH showed significant differences between MD and VM groups. The prevalence of cochlear EH (I and II) and vestibular EH (II and III) was different between MD and VM groups. The prevalence of PE was higher in MD than VM group. The degrees of cochlear and vestibular hydrops were higher in the definite than probable MD group (P < 0.05). Using these imaging features, MRI can be used to help differentiate MD from other menieriform diseases.
Topics: Humans; Meniere Disease; Endolymphatic Hydrops; Gadolinium; Vestibule, Labyrinth; Vertigo; Magnetic Resonance Imaging; Neuroma, Acoustic; Migraine Disorders
PubMed: 38057393
DOI: 10.1038/s41598-023-49066-5