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World Neurosurgery: X Apr 2024While previous studies have assessed patient reported quality of life (QOL) of various vestibular schwannoma (VS) treatment modalities, few studies have assessed QOL as...
BACKGROUND
While previous studies have assessed patient reported quality of life (QOL) of various vestibular schwannoma (VS) treatment modalities, few studies have assessed QOL as related to the amount of residual tumor and need for retreatment in a large series of patients. Objective: To assess patient reported QOL outcomes following VS resection with a focus on extent of resection and retreatment.
METHODS
A retrospective chart review was performed using single-center institutional data of adult patients who underwent VS resection by the senior authors between 1989-2018 at Loyola University Medical Center. The Penn Acoustic Neuroma Quality of Life (PANQOL) survey was sent to all patients via postal mail.
RESULTS
Fifty-five percent of 367 total patients were female with a mean age of 61.6 years (SD 12.63). The mean period between surgery and PANQOL response was 11.4 years (IQR: 4.74-7.37). The median tumor size was 2 cm (IQR: 1.5-2.8). The mean total PANQOL score was 70 (SD 19). Patients who required retreatment reported lower overall scores (μdiff = -10.11, 95% CI: -19.48 to -0.74; p = 0.03) and face domain scores (μdiff = -20.34, 95% CI: -29.78 to -10.91; p < .001). There was no association between extent of resection and PANQOL scores in any domain.
CONCLUSION
In an analysis of 367 patients who underwent microsurgical resection of VS, extent of resection did not affect PANQOL scores in contrast to previous reports in the literature, while the need for retreatment and facial function had a significant impact on patient-reported outcomes.
PubMed: 38450247
DOI: 10.1016/j.wnsx.2024.100294 -
Neurology India Jan 2024
Topics: Humans; Male; Neuroma, Acoustic
PubMed: 38443054
DOI: 10.4103/neurol-india.Neurol-India-D-23-00693 -
Neurology India Jan 2024
Topics: Humans; Neuroma, Acoustic; X-Rays; Radiography; Dextrocardia
PubMed: 38443041
DOI: 10.4103/neurol-india.Neurol-India-D-24-00057 -
Neurology India Jan 2024The literature contains several reports of herpes recrudescence after neurosurgery. We analyze our experience by vindicating or refuting the existing plausible...
BACKGROUND
The literature contains several reports of herpes recrudescence after neurosurgery. We analyze our experience by vindicating or refuting the existing plausible hypotheses.
MATERIAL AND METHODS
This is a retrospective review of all neurosurgical cases that developed postoperative herpes infection between January 2016 and June 2020.
RESULTS
Six patients developed herpes infection after vestibular schwannoma (VS) surgery. Other neurosurgical cases did not develop herpes infection. There were five females and one male, with a mean age of 44.1 years. Four out of six patients developed delayed facial palsy (DFP) and did not improve after antiviral treatment. Postoperative herpes infections were 0.2% among all operated patients, 3.07% among all cerebellopontine (CP) angle surgeries, and 5.6% among VS surgeries.
CONCLUSIONS
To date, none of the plausible hypotheses satisfactorily addresses all aspects of viral recrudescence. The etiology may be multi-factorial, and in all cases of unexplained clinical deterioration, herpes infection needs consideration in the differential diagnosis.
Topics: Female; Humans; Male; Adult; Neurosurgery; Neurosurgical Procedures; Cerebellopontine Angle; Neuroma, Acoustic; Postoperative Complications; Recurrence; Virus Diseases
PubMed: 38443000
DOI: 10.4103/neuroindia.NI_1599_20 -
Journal of Neuroscience Methods May 2024Our goal was to develop a 3D tumor slice model, replicating the individual tumor microenvironment and for individual pharmaceutical testing in vestibular schwannomas...
BACKGROUND
Our goal was to develop a 3D tumor slice model, replicating the individual tumor microenvironment and for individual pharmaceutical testing in vestibular schwannomas with and without relation to NF2.
METHODS
Tissue samples from 16 VS patients (14 sporadic, 2 NF2-related) were prospectively analyzed. Slices of 350 µm thickness were cultured in vitro, and the 3D tumor slice model underwent thorough evaluation for culturing time, microenvironment characteristics, morphology, apoptosis, and proliferation rates. Common drugs - Lapatinib (10 µM), Nilotinib (20 µM), and Bevacizumab (10 µg/ml) - known for their responses in VS were used for treatment. Treatment responses were assessed using CC3 as an apoptosis marker and Ki67 as a proliferation marker. Standard 2D cell culture models of the same tumors served as controls.
RESULTS
The 3D tumor slice model accurately mimicked VS ex vivo, maintaining stability for three months. Cell count within the model was approximately tenfold higher than in standard cell culture, and the tumor microenvironment remained stable for 46 days. Pharmacological testing was feasible for up to three weeks, revealing interindividual differences in treatment response to Lapatinib and intraindividual variability in response to Lapatinib and Nilotinib. The observed effects were less pronounced in tumor slices than in standard cell culture, indicating the model's proximity to in vivo tumor biology and enhanced realism. Bevacizumab had limited impact in both models.
CONCLUSION
This study introduces a 3D tumor slice model for sporadic and NF2-related VS, demonstrating stability for up to 3 months, replication of the schwannoma microenvironment, and utility for individualized pharmacological testing.
Topics: Humans; Neuroma, Acoustic; Lapatinib; Bevacizumab; Neurilemmoma; Tumor Microenvironment
PubMed: 38387803
DOI: 10.1016/j.jneumeth.2024.110082 -
Journal of Neuro-oncology Apr 2024NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS) often causing hearing and neurologic deficits, with currently no FDA-approved...
PURPOSE
NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS) often causing hearing and neurologic deficits, with currently no FDA-approved drug treatment. Pre-clinical studies highlighted the potential of mTORC1 inhibition in delaying schwannoma progression. We conducted a prospective open-label, phase II study of everolimus for progressive VS in NF2 patients and investigated imaging as a potential biomarker predicting effects on growth trajectory.
METHODS
The trial enrolled 12 NF2 patients with progressive VS. Participants received oral everolimus daily for 52 weeks. Brain imaging was obtained quarterly. As primary endpoint, radiographic response (RR) was defined as ≥ 20% decrease in target VS volume. Secondary endpoints included other tumors RR, hearing outcomes, drug safety and quality of life (QOL).
RESULTS
Eight participants completed the trial and four discontinued the drug early due to significant volumetric VS progression. After 52 weeks of treatment, the median annual VS growth rate decreased from 77.2% at baseline to 29.4%. There was no VS RR and 3 of 8 (37.5%) participants had stable disease. Decreased or unchanged VS volume after 3 months of treatment was predictive of stabilization at 12 months. Seven of eight participants had stable hearing during treatment except one with a decline in word recognition score. Ten of twelve participants reported only minimal changes to their QOL scores.
CONCLUSIONS
Volumetric imaging at 3 months can serve as an early biomarker to predict long-term sensitivity to everolimus treatment. Everolimus may represent a safe treatment option to decrease the growth of NF2-related VS in patients who have stable hearing and neurological condition. TRN: NCT01345136 (April 29, 2011).
Topics: Humans; Biomarkers; Everolimus; Neurofibromatosis 2; Neuroma, Acoustic; Quality of Life; Treatment Outcome
PubMed: 38372904
DOI: 10.1007/s11060-024-04596-4 -
Cancer Medicine Jan 2024The mechanism of hearing loss following stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs) remains unclear. There is conflicting evidence regarding...
INTRODUCTION
The mechanism of hearing loss following stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs) remains unclear. There is conflicting evidence regarding cochlear nerve damage by transient volume expansion of VSs after radiosurgery and radiation-induced cochlear damage. This study aimed to investigate whether there is a specific patient population that can achieve definite hearing preservation after SRS for VSs.
METHODS
A total of 37 consecutive patients with sporadic unilateral intracanalicular VSs and serviceable hearing (Gardner-Roberson [G-R] class I or II) were treated with SRS from 2009 to 2023. This is a retrospective study. Survival analysis with Cox regression for hearing deterioration was performed.
RESULTS
The median age was 55 years old. The median tumor volume was 0.089 cm , and the median marginal dose was 12.0 Gy. Nonserviceable hearing deterioration occurred in 9 patients (24.3%), with a median onset of 11.9 months after SRS. The actuarial rates of serviceable hearing preservation were 86%, 82%, and 70% at 1, 2, and 3 years after SRS, respectively. In a multivariate analysis, only baseline pure tone average > 30 dB increased the risk of nonserviceable hearing deterioration with significant hazard ratio. There were 13 patients with petit VSs whose tumor volume was smaller than 0.05 cm , and 11 of them were treated by a 4-mm single shot with a marginal dose of 12 Gy. None of the 13 patients had nonserviceable hearing deterioration.
CONCLUSIONS
Petit VSs that can be treated with 4-mm single or double shots with a marginal dose of 12 Gy may achieve hearing preservation after SRS.
Topics: Humans; Middle Aged; Neuroma, Acoustic; Radiosurgery; Retrospective Studies; Hearing; Hearing Loss; Treatment Outcome; Follow-Up Studies
PubMed: 38348957
DOI: 10.1002/cam4.6990 -
Scientific Reports Feb 2024The vestibulo-collic reflex generates neck motor commands to produce head-on-trunk movements that are essential for stabilizing the head relative to space. Here we...
The vestibulo-collic reflex generates neck motor commands to produce head-on-trunk movements that are essential for stabilizing the head relative to space. Here we examined the effects of vestibular loss on head-on-trunk kinematics during voluntary behavior. Head and trunk movements were measured in individuals with vestibular schwannoma before and then 6 weeks after unilateral vestibular deafferentation via surgical resection of the tumor. Movements were recorded in 6 dimensions (i.e., 3 axes of rotation and 3 axes of translation) using small light-weight inertial measurement units while participants performed balance and gait tasks. Kinematic measures differed between individuals with vestibular schwannoma (at both time points) and healthy controls for the more challenging exercises, namely those performed in tandem position or on an unstable surface without visual input. Quantitative assessment of the vestibulo-ocular reflex (VOR) revealed a reduction in VOR gain for individuals with vestibular schwannoma compared to control subjects, that was further reduced following surgery. These findings indicated that the impairment caused by either the tumor or subsequent surgical tumor resection altered head-on-trunk kinematics in a manner that is not normalized by central compensation. In contrast, we further found that head-on-trunk kinematics in individuals with vestibular schwannoma were actually comparable before and after surgery. Thus, taken together, our results indicate that vestibular loss impacts head-on-trunk kinematics during voluntary balance and gait behaviors, and suggest that the neural mechanisms mediating adaptation alter the motion strategies even before surgery in a manner that may be maladaptive for long-term compensation.
Topics: Humans; Neuroma, Acoustic; Reflex, Vestibulo-Ocular; Vestibule, Labyrinth; Neck; Gait; Head Movements
PubMed: 38347021
DOI: 10.1038/s41598-024-53512-3 -
Oncogene Mar 2024Neurofibromatosis Type 2 (NF2)-related schwannomatosis is a genetic disorder that causes development of multiple types of nervous system tumors. The primary and...
Neurofibromatosis Type 2 (NF2)-related schwannomatosis is a genetic disorder that causes development of multiple types of nervous system tumors. The primary and diagnostic tumor type is bilateral vestibular schwannoma. There is no cure or drug therapy for NF2. Recommended treatments include surgical resection and radiation, both of which can leave patients with severe neurological deficits or increase the risk of future malignant tumors. Results of our previous pilot high-throughput drug screen identified phosphoinositide 3-kinase (PI3K) inhibitors as strong candidates based on loss of viability of mouse merlin-deficient Schwann cells (MD-SCs). Here we used novel human schwannoma model cells to conduct combination drug screens. We identified a class I PI3K inhibitor, pictilisib and p21 activated kinase (PAK) inhibitor, PF-3758309 as the top combination due to high synergy in cell viability assays. Both single and combination therapies significantly reduced growth of mouse MD-SCs in an orthotopic allograft mouse model. The inhibitor combination promoted cell cycle arrest and apoptosis in mouse merlin-deficient Schwann (MD-SCs) cells and cell cycle arrest in human MD-SCs. This study identifies the PI3K and PAK pathways as potential targets for combination drug treatment of NF2-related schwannomatosis.
Topics: Humans; Animals; Mice; Neurofibromatosis 2; Neurofibromin 2; Phosphatidylinositol 3-Kinases; p21-Activated Kinases; Phosphatidylinositol 3-Kinase; Neurilemmoma; Indazoles; Skin Neoplasms; Sulfonamides; Neurofibromatoses
PubMed: 38336988
DOI: 10.1038/s41388-024-02958-w