Vestibular Schwannoma Growth Research Articles

The study of predictive factors for the evolution of vestibular schwannomas.

The primary objective was to determine whether the analysis of textural heterogeneity of vestibular schwannomas on MRI at diagnosis was predictive of their radiological evolutivity. The secondary objective was to determine whether some clinical or radiological factors could also be predictive of growth. We conducted a pilot, observational and retrospective study of patients with a vestibular schwannoma, initially monitored, between April 2001 and November 2019 within the Oto-Neurosurgical Institute of Champagne Ardenne, Texture analysis was performed on gadolinium injected T1 and CISS T2 MRI sequences and six parameters were extracted: mean greyscale intensity, standard deviation of the greyscale histogram distribution, entropy, mean positive pixels, skewness and kurtosis, which were analysed by the Lasso method, using statistically penalised Cox models. Extrameatal location, tumour necrosis, perceived hearing loss < 2years with objectified tone audiometry asymmetry, tinnitus at diagnosis, were investigated by the Log-Rank test to obtain univariate survival analyses. 78 patients were included and divided into 2 groups: group A comprising 39 "stable patients", and B comprising the remaining 39 "progressive patients". Independent analysis of the texture factors did not predict the growth potential of vestibular schwannomas. Among the clinical or radiological signs of interest, hearing loss < 2years was identified as a prognostic factor for tumour progression with a significant trend (p = 0.05). This study did not identify an association between texture analysis and vestibular schwannomas growth. Decreased hearing in the 2 years prior to diagnosis appears to predict potential radiological progression.

Machine Learning for Automated Calculation of Vestibular Schwannoma Volumes.

Machine learning-derived algorithms are capable of automated calculation of vestibular schwannoma tumor volumes without operator input. Volumetric measurements are most sensitive for detection of vestibular schwannoma growth and important for patient counseling and management decisions. Yet, manually measuring volume is logistically challenging and time-consuming. We developed a deep learning framework fusing transformers and convolutional neural networks to calculate vestibular schwannoma volumes without operator input. The algorithm was trained, validated, and tested on an external, publicly available data set consisting of magnetic resonance imaging images of medium and large tumors (178-9,598 mm 3 ) with uniform acquisition protocols. The algorithm was then trained, validated, and tested on an internal data set of variable size tumors (5-6,126 mm 3 ) with variable acquisition protocols. The externally trained algorithm yielded 87% voxel overlap (Dice score) with manually segmented tumors on the external data set. The same algorithm failed to translate to accurate tumor detection when tested on the internal data set, with Dice score of 36%. Retraining on the internal data set yielded Dice score of 82% when compared with manually segmented images, and 85% when only considering tumors of similar size as the external data set (>178 mm 3 ). Manual segmentation by two experts demonstrated high intraclass correlation coefficient (0.999). Sophisticated machine learning algorithms delineate vestibular schwannomas with an accuracy exceeding established norms of up to 20% error for repeated manual volumetric measurements-87% accuracy on a homogeneous data set, and 82% to 85% accuracy on a more varied data set mirroring real world neurotology practice. This technology has promise for clinical applicability and time savings.

Reduction of sporadic and neurofibromatosis type 2-associated vestibular schwannoma growth in vitro and in vivo after treatment with the c-Jun N-terminal kinase inhibitor AS602801.

Vestibular schwannomas (VSs) are benign nerve sheath tumors that result from mutation in the tumor suppressor gene NF2, with functional loss of the protein merlin. The authors have previously shown that c-Jun N-terminal kinase (JNK) is constitutively active in human VS cells and plays a central role in their survival by suppressing accumulation of mitochondrial superoxides, implicating JNK inhibitors as a potential systemic treatment for VS. Thus, the authors hypothesized that the adenosine 5'-triphosphate-competitive JNK inhibitor AS602801 would demonstrate antitumor activity in multiple VS models. Treatment with AS602801 was tested in primary human VS cultures, human VS xenografts, and a genetic mouse model of schwannoma (Postn-Cre;Nf2flox/flox). Primary human VS cell cultures were established from freshly obtained surgical tumor specimens; treatment group media was enriched with AS602801. VS xenograft tumors were established in male athymic nude mice from freshly collected human tumor. Four weeks postimplantation, a pretreatment MRI scan was obtained, followed by 65 days of AS602801 (n = 18) or vehicle control (n = 19) treatment. Posttreatment MRI scans were used to measure final tumor volume. Tumors were then harvested. Finally, Postn-Cre;Nf2flox/flox mice were treated with AS602801 (n = 10) or a vehicle (n = 13) for 65 days. Posttreatment auditory brainstem responses were obtained. Dorsal root ganglia from Postn-Cre;Nf2flox/flox mice were then harvested. In all models, schwannoma identity was confirmed with anti-S100 staining, cell proliferation was measured with the EdU assay, and cell death was measured with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. All protocols were approved by the local institutional review board and Institutional Animal Care and Use Committees. Treatment with AS602801 decreased cell proliferation and increased apoptosis in primary human VS cultures. The systemic administration of AS602801 in mice with human VS xenografts reduced tumor volume and cell proliferation. Last, the AS602801-treated Postn-Cre;Nf2flox/flox mice demonstrated decreased cell proliferation in glial cells in the dorsal root ganglia. However, AS602801 did not significantly delay hearing loss in Postn-Cre;Nf2flox/flox mice up to 3 months posttreatment. The data suggest that JNK inhibition with AS602801 suppresses growth of sporadic and neurofibromatosis type 2-associated VSs. As such, AS602801 is a potential systemic therapy for VS and warrants further investigation.

β 2 -Microglobulin Participates in the Development of Vestibular Schwannoma by Regulating Nuclear Factor-κB.

Vestibular schwannoma (VS), the most common intercranial schwannoma, originates from the sheath of the vestibular nerve. The growth rate of VS varies greatly, with the tumor enlarging gradually, which can compress the peripheral nerve tissue and reveal corresponding symptoms. This study was aimed to elucidate the growth mechanism of VS by analyzing cellular changes at protein, messenger ribonucleic acid (mRNA), and other molecular levels. We determined mRNA and protein levels of β 2 -microglobulin (β 2 -M) and nuclear factor κB (NF-κB) in tumors of different sizes using the real-time polymerase chain reaction and Western blotting, respectively. The relationship between these factors was verified in VS primary cells cultured in vitro, and the potential role of β 2 -M and NF-κB in VS growth was elucidated. In the secretions of freshly isolated tumor tissue cultured for 72 h, the concentration of β 2 -M was positively correlated with the tumor diameter. Furthermore, tumors with larger diameter showed higher expressions of β 2 -M and NF-κB at protein and mRNA level. β 2 -M treatment resulted in elevated protein expression of NF-κB and also its phosphorylated form in vitro. β 2 -M may participate in VS growth by regulating NF-κB and act as a key regulatory molecule in VS tumor growth.

Spontaneous Volumetric Tumor Regression During Wait-and-Scan Management of 952 Sporadic Vestibular Schwannomas.

Spontaneous tumor shrinkage during wait-and-scan management of sporadic vestibular schwannoma is generally considered an uncommon phenomenon. However, most data informing this understanding stem from single-slice linear tumor measurements taken in the axial imaging plane. The objective of the current work was to characterize the regression capacity of sporadic vestibular schwannomas using volumetric tumor measurements. Retrospective cohort study using slice-by-slice, three-dimensional volumetric tumor measurements. Three tertiary referral centers. Patients with sporadic vestibular schwannoma. Wait-and-scan. Regression-free survival rates with regression defined as a decrease of at least 20% of the tumor volume. Among 952 patients undergoing a total of 3,505 magnetic resonance imaging studies during observation, 123 experienced volumetric tumor regression after diagnosis at a median of 1.2 years (interquartile range, 0.6-2.9 yr). Volumetric regression-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after diagnosis were 94% (92-95%; 662), 86% (83-89%; 275), and 78% (73-82%; 132), respectively. Among 405 patients who demonstrated an initial period of tumor growth but continued wait-and-scan management, 48 experienced volumetric regression at a median of 1.2 years (interquartile range, 0.8-2.6 yr) after initial growth. Volumetric regression-free survival rates at 1, 3, and 5 years after initial growth were 94% (92-97%; 260), 84% (79-89%; 99), and 75% (67-83%; 43), respectively. Ultimately, only 82 of the 952 patients studied showed exclusively volumetric tumor regression (i.e., without any periods of tumor growth) by the time of last follow-up. Spontaneous volumetric tumor shrinkage during wait-and-scan management occurs more frequently than suggested by previous studies using linear tumor measurements and can even occur after previous episodes of documented tumor growth. These data further highlight the dynamic nature of vestibular schwannoma growth. To this end, the application of natural history data to patient management requires a nuanced approach that parallels the complex tumor behavior of vestibular schwannoma.

Whole Tumor Radiomics Analysis for Risk Factors Associated With Rapid Growth of Vestibular Schwannoma in Contrast-Enhanced T1-Weighted Images

To investigate the features associated with rapid growth of vestibular schwannoma using radiomics analysis on magnetic resonance imaging (MRI) together with clinical factors. From August 2005 to February 2019, 67 patients with vestibular schwannoma underwent contrast-enhanced T1-weighted MRI at least twice as part of their diagnosis. After excluding 3 cases with an extremely short follow-up period of 15 days or less, 64 patients were finally enrolled in this study. Ninety-three texture features were extracted from the tumor image data using 3D Slicer software (http://www.slicer.org/). We determined the texture features that significantly affected maximal tumor diameter growth of more than 2 mm/year using Random Forest and Bounty. We also analyzed age and tumor size as clinical factors. We calculated the areas under the curve (AUCs) using receiver operating characteristic analysis for prediction models using texture, clinical, and mixed factors by Random Forest and 5-fold cross-validation. Two texture features, low minimum signal and high inverse difference moment normalized (Idmn), were significantly associated with rapid growth of vestibular schwannoma. The mixed model of texture features and clinical factors offered the highest AUC (0.69), followed by the pure texture (0.67), and pure clinical (0.63) models. The minimum signal was the most important variable followed by tumor size, Idmn, and age. Our radiomics analysis found that texture features were significantly associated with the rapid growth of vestibular schwannoma in contrast-enhanced T1-weighted images. The mixed model offered a higher diagnostic performance than the pure texture or clinical models.

Evaluating growth trends of residual sporadic vestibular schwannomas: a systematic review and meta-analysis.

Gross total resection remains the gold-standard approach for vestibular schwannomas (VS) when surgery is indicated. In select cases, incomplete resection (IR) becomes a desired alternative to preserve the facial nerve function and the patient's quality of life. While a lot of earlier studies described incompletely resected sporadic VSs as dormant, more recent studies reported a higher growth rate following IR, therefore an evaluation of the residual VS growth rates could have important implications for the follow-up treatment protocols and provide relevant information for neurosurgeons, neuro-otologists, neuropathologists, and radiologists. Although prognostic factors predicting preoperative VS growth have been previously investigated, these factors have not been investigated following IR. Our review aims to examine the growth rate of residual sporadic VS following IR and to examine variables associated with the regrowth of residual VS. The review was conducted in accordance with the PRISMA guidelines. Six databases (MEDLINE (Ovid), Embase (Ovid), CINAHL Plus (EBSCO), Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform and UK Clinical Trials Gateway (WHO ICTRP) were searched. Full-text articles analysing growth rates in at least ten patients who had residual VS after IR were assessed. We conducted a meta-analysis using a random-effects model via RevMan. 14 studies totalling 849 patients were included in the analysis. The mean planimetric growth rate was 1.57mm/year (range 0.16-3.81mm/year). The mean volumetric growth rate was 281.725 mm3/year (range 17.9-530.0 mm3/year). Age, sex, pre-operative tumour size/volume, cystic tumour sub-type, MIB-1 index, and intracanalicular tumour location were not associated with residual growth. Residual tumour size/volume was statistically significant to growth (OR = 0.65, 95% CI 0.47-0.90, p = 0.01). Radiological re-growth occurred in an average of 26.6% of cases (range 0-54.5%). From our analysis, only the residual tumour volume/size was associated with residual VS growth. Therefore, close postoperative surveillance for the first year, followed by an annual MRI scan for at least 5years, and subsequently extended interval surveillance remains of utmost importance to monitor disease progression and provide timely surgical and adjuvant interventions. Our study shows that future work should be aimed at molecular and histological characteristics of residual VSs to aid prognostic understanding of growth.

Defining clinically significant tumor size in vestibular schwannoma to inform timing of microsurgery during wait-and-scan management: moving beyond minimum detectable growth.

Detection of vestibular schwannoma (VS) growth during observation leads to definitive treatment at most centers globally. Although ≥ 2 mm represents an established benchmark of tumor growth on serial MRI studies, 2 mm of linear tumor growth is unlikely to significantly alter microsurgical outcomes. The objective of the current work was to ascertain where the magnitude of change in clinical outcome is the greatest based on size. A single-institution retrospective review of a consecutive series of patients with sporadic VS who underwent microsurgical resection between January 2000 and May 2020 was performed. Preoperative tumor size cutpoints were defined in 1-mm increments and used to identify optimal size thresholds for three primary outcomes: 1) the ability to achieve gross-total resection (GTR); 2) maintenance of normal House-Brackmann (HB) grade I facial nerve function; and 3) preservation of serviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery class A/B). Optimal size thresholds were obtained by maximizing c-indices from logistic regression models. Of 603 patients meeting inclusion criteria, 502 (83%) had tumors with cerebellopontine angle (CPA) extension. CPA tumor size was significantly associated with achieving GTR, postoperative HB grade I facial nerve function, and maintenance of serviceable hearing (all p < 0.001). The optimal tumor size threshold to distinguish between GTR and less than GTR was 17 mm of CPA extension (c-index 0.73). In the immediate postoperative period, the size threshold between HB grade I and HB grade > I was 17 mm of CPA extension (c-index 0.65). At the most recent evaluation, the size threshold between HB grade I and HB grade > I was 23 mm (c-index 0.68) and between class A/B and C/D hearing was 18 mm (c-index 0.68). Tumors within 3 mm of the 17-mm CPA threshold displayed similarly strong c-indices. Among purely intracanalicular tumors, linear size was not found to portend worse outcomes for all measures. The probability of incurring less optimal microsurgical outcomes begins to significantly increase at 14-20 mm of CPA extension. Although many factors ultimately influence decision-making, when considering timing of microsurgical resection, using a size threshold range as depicted in this study offers an evidence-based approach that moves beyond reflexively recommending treatment for all tumors after detecting ≥ 2 mm of tumor growth on serial MRI studies.

Celastrol suppresses the growth of vestibular schwannoma in mice by promoting the degradation of β-catenin.

Vestibular schwannoma (VS), one of characteristic tumors of neurofibromatosis type 2 (NF2), is an intracranial tumor that arises from Schwann cells of the vestibular nerve. VS results in hearing loss, tinnitus, dizziness, and even death, but there are currently no FDA-approved drugs for treatment. In this study, we established a high-throughput screening to discover effective compounds that could inhibit the viability of VS cells. Among 1019 natural products from the Korea Chemical Bank screened, we found that celastrol, a pentacyclic triterpene derived from a Tripterygium Wilfordi plant, exerted potent inhibitory effect on the viability of VS cells with an IC50 value of 0.5 µM. Celastrol (0.5, 1 µM) dose-dependently inhibited the proliferation of primary VS cells derived from VS patients. Celastrol also inhibited the growth, and induced apoptosis of two other VS cell lines (HEI-193 and SC4). Aberrant activation of Wnt/β-catenin signaling has been found in VS isolated from clinically defined NF2 patients. In HEI-193 and SC4 cells, we demonstrated that celastrol (0.1, 0.5 μM) dose-dependently inhibited TOPFlash reporter activity and protein expression of β-catenin, but not mRNA level of β-catenin. Furthermore, celastrol accelerated the degradation of β-catenin by promoting the formation of the β-catenin destruction complex. In nude mice bearing VS cell line SC4 allografts, administration of celastrol (1.25 mg · kg-1 · d-1, i.p. once every 3 days for 2 weeks) significantly suppressed the tumor growth without showing toxicity. Collectively, this study demonstrates that celastrol can inhibit Wnt/β-catenin signaling by promoting the degradation of β-catenin, consequently inhibiting the growth of VS.

Hemorrhagic vestibular schwannoma: a case example of vestibular apoplexy syndrome. Illustrative case.

BACKGROUNDAcute intratumoral hemorrhage within a vestibular schwannoma, or vestibular apoplexy, is a rare condition. Unlike the typical insidious vestibulopathy typically caused by vestibular schwannoma growth, patients with vestibular apoplexy have an acute and severe presentation with nausea and emesis in addition to severe vertigo and hearing loss. Here, the authors present an illustrative case demonstrating this rare clinical condition and an operative video detailing the surgical management.OBSERVATIONSA 76-year-old man presented to the emergency department with acute-onset dizziness, left-ear fullness, double vision, gait ataxia, emesis, and facial numbness. Imaging revealed a 2.8-cm hemorrhagic left cerebellopontine angle lesion extending into the left internal auditory canal, consistent with hemorrhagic vestibular schwannoma. The patient subsequently underwent a retrosigmoid craniotomy for resection of the hemorrhagic mass, and by 1 month after surgery, all his presenting symptoms had resolved, allowing his return to daily activities.LESSONSVestibular schwannomas typically present with decreased hearing and chronic vestibulopathy. Acute presentation should raise the suspicion for an apoplectic event, and surgical debulking may lead to improvement in most vestibular symptoms.

How many growing vestibular schwannomas tend to stop growing without any treatment?

To determine the long-term, spontaneous growth arrest rates in a large cohort of vestibular schwannoma patients. This paper describes a retrospective case series of 735 vestibular schwannoma patients organised into four groups: group A patients showed tumour growth which then stopped without any treatment; group B patients showed tumour growth which continued, but were managed conservatively; group C patients had a growing vestibular schwannoma and received active treatment; and group D patients had a stable, non-growing vestibular schwannoma. Demographics, tumour size and vestibular schwannoma growth rate (mm/month) were recorded. A total of 288 patients (39.2 per cent) had growing vestibular schwannomas. Of the patients, 103 (35.8 per cent) were managed conservatively, with 52 patients (50.5 per cent of the conservative management group, 18 per cent of the total growing vestibular schwannoma group) showing growth arrest, which occurred on average at four years following the diagnosis. Eighty-two per cent of vestibular schwannomas stopped growing within five years. Only differences between age (p = 0.016) and vestibular schwannoma size (p = 0.0008) were significant. Approximately 20 per cent of growing vestibular schwannomas spontaneously stop growing, predominantly within the first five years; this is important for long-term management.

A Subset of Intracanalicular Vestibular Schwannomas Demonstrates Minimal Growth Over a 10-Year Period.

Vestibular schwannomas (VS) commonly undergo magnetic resonance imaging (MRI) surveillance, but long-term data to support the ideal frequency is limited. Herein, we aim to investigate intracanalicular VS growth predictors and long-term growth rates (GR). Retrospective chart review. Two tertiary care centers. Sporadic intracanalicular VS with initial conservative management and at least two sequential MRIs. Serial MRI. VS were categorized by baseline internal auditory canal tertile sublocalization (fundus, midpoint, porus) and size (≤100, 100-200, >200 mm3). Throughout follow-up, volumetric GR (mm3/yr) were determined (baseline-3 yrs, 3-5 yrs, 5-10 yrs) and treatment rates were assessed. Ninety-nine intracanalicular VS were identified (mean follow-up of 6.1 ± 4.5 yrs). Mean GR before 5-year follow-up were comparable for baseline tertile involvement and size. After 5-year follow-up, mean GR of VS involving the fundus at baseline were lower than those involving the midpoint and fundus (6.17 ± 21.16 and 119.74 ± 117.57 mm3/yr, respectively; p = 0.034). Mean GR of VS with less than or equal to 100 mm3 at baseline (-7.29 ± 25.44 mm3/yr) were lower than those with 100 to 200 mm3 (86.55 ± 103.99 mm3/yr; p = 0.011) and more than 200 mm3 (45.70 ± 35.71 mm3/yr; p = 0.031). Vestibular schwannomas involving the midpoint and fundus had greater treatment rates compared with VS involving only the fundus (p < 0.001). Baseline tertile involvement and size may predict long-term intracanalicular VS growth where fundal tumors or those less than or equal to 100 mm3 exhibit little long-term growth. Extending surveillance after 5-year follow-up may be reasonable for fundal VS.

Long-term natural history and patterns of sporadic vestibular schwannoma growth: A multi-institutional volumetric analysis of 952 patients.

The current study aims to characterize the natural history of sporadic vestibular schwannoma volumetric tumor growth, including long-term growth patterns following initial detection of growth. Volumetric tumor measurements from 3505 serial MRI studies were analyzed from unselected consecutive patients undergoing wait-and-scan management at three tertiary referral centers between 1998 and 2018. Volumetric tumor growth was defined as a change in volume ≥20%. Among 952 patients undergoing observation, 622 experienced tumor growth with initial growth-free survival rates (95% CI) at 1, 3, and 5 years following diagnosis of 66% (63-69), 30% (27-34), and 20% (17-24). Among 405 patients who continued to be observed despite demonstrating initial growth, 210 experienced subsequent tumor growth with subsequent growth-free survival rates at 1, 3, and 5 years following initial growth of 77% (72-81), 37% (31-43), and 24% (18-31). Larger tumor volume at initial growth (HR 1.13, P = .02) and increasing tumor growth rate (HR 1.31; P < .001) were significantly associated with an increased likelihood of subsequent growth, whereas a longer duration of time between diagnosis and detection of initial growth was protective (HR 0.69; P < .001). While most vestibular schwannomas exhibit an overall propensity for volumetric growth following diagnosis, prior tumor growth does not perfectly predict future growth. Tumors can subsequently grow faster, slower, or demonstrate quiescence and stability. Larger tumor size and increasing tumor growth rate portend a higher likelihood of continued growth. These findings can inform timing of intervention: whether upfront at initial diagnosis, after detection of initial growth, or only after continued growth is observed.

Elevated baseline C-reactive protein levels predict poor progression-free survival in sporadic vestibular schwannoma

BackgroundRecent investigations showed emerging evidence of the role of inflammation in the growth of sporadic vestibular schwannoma (VS). The present retrospective study investigated the impact of systemic inflammation on tumor progression using serum C-reactive protein (CRP) levels in a series of 87 surgically treated sporadic VS patients.MethodsThe optimal cut-off value for CRP was defined as 3.14 mg/dl according to the receiver operating characteristic curve (AUC: 0.70, 95% CI 0.47–0.92). Patient cohort was dichotomized into normal (n = 66; < 3.14 mg/dl) and high baseline (n = 21; ≥ 3.14 mg/dl) CRP groups.ResultsNo significant differences in age, sex, comorbidities influencing the systemic inflammatory state, Karnofsky performance status (KPS), tumor size, extent of resection, or MIB-1 index were identified between the two groups defined by the baseline CRP levels. Univariable analysis demonstrated that a high CRP level (≥ 3.14 mg/dl) is significantly associated with a shortened progression-free survival (PFS) (hazard ratio (HR): 6.05, 95% CI 1.15–31.95, p = 0.03). Multivariable Cox regression analysis considering age, extent of resection, KPS, tumor size, and baseline CRP confirmed that an elevated CRP level (≥ 3.14 mg/dl) is an independent predictor of shortened PFS (HR: 7.20, 95% CI 1.08–48.14, p = 0.04).ConclusionsThe baseline CRP level thus serves as an independent predictor of PFS. Further investigations of the role of inflammation and tumor inflammatory microenvironment in the prediction of prognosis in sporadic VS are needed.Graphical abstract

Translabyrinthine resection of NF2 associated vestibular schwannoma with cochlear implant insertion.

The authors present the case of a 24-year-old female with neurofibromatosis type 2. Growth of the left vestibular schwannoma and progressive hearing loss prompted the decision to proceed to translabyrinthine resection with cochlear nerve preservation and cochlear implant insertion. Complete resection with preservation of the facial and cochlear nerves was achieved. The patient had grade 1 facial function and was discharged on postoperative day 4 following suturing of a minor CSF leak. This case highlights the feasibility of cochlear nerve preservation and cochlear implant insertion in appropriately selected patients, offering a combination of effective tumor control and hearing rehabilitation.The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID21122

Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects.

Vestibular schwannomas (VSs, also known as acoustic neuromas) are relatively rare benign brain tumors stem from the Schwann cells of the eighth cranial nerve. Tumor growth is the paramount factor for neurosurgeons to decide whether to choose aggressive treatment approach or careful follow-up with regular magnetic resonance imaging (MRI), as surgery and radiation can introduce significant trauma and affect neurological function, while tumor enlargement during long-term follow-up will compress the adjacent nerves and tissues, causing progressive hearing loss, tinnitus and vertigo. Recently, with the deepening research of VS biology, some proteins that regulate merlin conformation changes, inflammatory cytokines, miRNAs, tissue proteins and cerebrospinal fluid (CSF) components have been proposed to be closely related to tumor volume increase. In this review, we discuss advances in the study of biomarkers that associated with VS growth, providing a reference for exploring the growth course of VS and determining the optimal treatment strategy for each patient.

Growth of vestibular schwannoma: long-term follow-up study using survival analysis.

A vestibular schwannoma (VS) is a benign nerve sheath tumor derived from the vestibular nerves. The growth rate of VS during long-term follow-up has not yet been fully evaluated. We aimed to investigate the growth rate of newly diagnosed VS and the related predictive factors for tumor growth. A retrospective review was performed using VS patients who underwent at least two magnetic resonance imaging (MRI) scans before tumor growth was observed. Tumor growth was defined as a size increase of more than 2mm in the longest diameter of the tumor. To assess the growth rate of VS and related factors, we assessed tumor growth using survival analysis. Survival analysis to assess the growth rate and Cox regression analysis were performed to find related factors. The study included 118 patients. The mean age of patients was 57.0 ± 12.9years. During the observation period, the 5-year cumulative growth incidence rate was 41.3% by survival analysis. Extrameatal tumor location and hearing loss were found to be associated with an increased hazard ratio (HR) for tumor growth. After long-term observation of VS, 41.3% of VS patients presented cumulative growth incidence rate in the first 5years after diagnosis. Extrameatal tumor location and hearing changes were related to subsequent tumor growth.

Association of Metformin With Volumetric Tumor Growth of Sporadic Vestibular Schwannomas.

Recent research demonstrates a potential association between metformin use and reduced sporadic vestibular schwannoma (VS) growth in patients undergoing conservative observation. The current study was designed to elucidate the effect of metformin on tumor growth in sporadic VS using volumetric analyses. Retrospective cohort. Tertiary referral center. Patients with sporadic VS who elected initial conservative treatment with at least two serial magnetic resonance imaging (MRI) scans were included. Metformin use among patients with observed sporadic VS. Tumor growth, defined as an increase in volume of at least 20% from the initial MRI. A total of 361 patients were evaluated. Thirty-four patients (9%) had a diagnosis of diabetes at baseline. Nineteen patients (5%) were taking metformin at the time of the initial MRI. Metformin use was not significantly associated with a reduced risk of volumetric tumor growth in a univariable analysis in all patients undergoing observation for VS (hazard ratio [HR] 0.75; 95% confidence intervals [CI] 0.40-1.42; p = 0.38) or within the diabetic subset (HR 0.79; 95% CI 0.34-1.83; p = 0.58). Additionally, diabetes status, insulin dependence, hemoglobin A1c value, and metformin dose were not significantly associated with volumetric tumor growth. Despite promising initial results in several previous studies, our data suggest that metformin use does not significantly reduce the risk of volumetric tumor growth in sporadic VS.

Vestibular Schwannoma: Results of Hypofractionated Stereotactic Radiation Therapy

PurposeOur purpose was to study the outcomes of hypofractionated stereotactic radiation therapy (HSRT) in terms of hearing and radiologic response for vestibular schwannomas. Methods and MaterialsThis was a longitudinal retrospective study at a referral center from 2011 to 2016. All treatments were performed on a Cyberknife device with a dose of 21 Gy (3 × 7 Gy) or 25 Gy (5 × 5 Gy). We assessed tumor response, neurologic outcomes (hearing and facial nerve function), and treatment toxicity. ResultsA total of 82 patients were included. Fifty-three patients were treated with the 3 × 7 Gy scheme and 29 with the 5 × 5 Gy. Sixteen patients (20%) had a previous surgery. The median follow-up was 48 months (range, 12-88 months). We noted 3 recurrences leading to a control rate of 96.3%. In our cohort, predictive factors of vestibular schwannoma growth were a tumor volume >2 mm3 and a conformal index <1.1 (P < .0001). The treatment was well tolerated with only 5 grade III acute toxicities (4 vertigo and 1 headache) and no grade IV or V. As for late toxicity, we noticed 2 cases of mild peripheral facial palsy (House and Brackman grade II) in previously operated patients. There was 46.0% hearing preservation among patients with serviceable hearing after HSRT. ConclusionsOur results suggest that HSRT using 3 or 5 fractions is a well-tolerated and effective regimen. These findings are in addition to the few previous hypofractionation studies and contribute to the validity of this treatment modality.

Identifying Factors Associated with the Growth of Vestibular Schwannomas: A Systematic Review

Surveillance imaging is a valid management option for selected vestibular schwannomas (VS). An ideal protocol for radiologic monitoring would highlight growth-related risk factors and tailor management accordingly. This study aims to identify variables associated with the growth of sporadic VS to enhance surveillance imaging, enable early intervention, and optimize outcomes. The review was conducted according to the PRISMA guidelines. A systematic review of 5 databases (PubMed, Ovid, Cochrane Library, Web of Science, and Google Scholar) was performed to identify negative and positive growth predictors of sporadic vestibular schwannomas. The search was limited to studies reported between January 2015 and January 2020. We conducted an individual patient data meta-analysis using a 1-stage multivariate mixed-effect logistic regression model. A total of 437 studies were identified, of which 25 met our criteria for full-text analysis. Articles that measured VS with comparable methods were determined eligible for meta-analysis inclusion. The selected articles were highly heterogeneous in their use of grading scales and assessment of tumor size. Our review showed that size at diagnosis (odds ratio, 1.15; 95% confidence interval, 1.11-1.18; P < 0.0001) and intracanalicular localization (odds ratio, 0.49; 95% confidence interval, 0.26-0.90; P=0.023) were associated with VS growth. The factors most frequently reported as being associated with growth within the literature were size of VS at diagnosis and localization of an intracanalicular component. Greater attention should be placed on these criteria within the surveillance imaging algorithm for VS.