Vestibular Schwannoma Growth Research Articles

Single Institutional Experience With Observing 564 Vestibular Schwannomas: Factors Associated With Tumor Growth.

To characterize the risk and predictors of growth during observation of vestibular schwannomas (VS). Retrospective case series. Single academic, tertiary care center. Five hundred sixty-four consecutive VS patients who underwent at least two magnetic resonance imaging (MRI) studies before intervention. Serial MRI studies. Tumor growth, defined as a ≥2 mm increase in the maximum tumor diameter between consecutive MRI studies, or between the first and last study. A total of 1296 patients (1995-2015) with VS were identified. Of those, 564 patients (median age 59.2 years; 53.5% female) were initially observed and underwent multiple MRI studies (median follow-up 22.9 months, interquartile range [IQR] 11.7-42.7). The median maximum tumor diameter at presentation was 1.00 cm (IQR 0.6-1.51 cm). In all, 40.8% of tumors demonstrated growth and 32.1% underwent intervention (21.5% microsurgery, 10.5% radiation) during the surveillance period. Multivariable Cox regression analysis showed that for each tumor, the risk of growth or intervention was significantly increased for larger initial VS diameters (HR = 2.22; 95% CI: 1.90-2.61) and when disequilibrium was a presenting symptom (HR = 1.70; 95% CI: 1.30-2.23). Patient age, sex, aspirin use, and presenting symptoms of asymmetric hearing loss, tinnitus, and vertigo were not associated with tumor growth. To date, this is the largest series of observed VS reported in the literature. Risk of VS growth is significantly increased among patients who present with larger tumors and who have concomitant disequilibrium.IRB:: 151481. No cohort with this sample size has assessed vestibular schwannoma growth rates in conjunction with this number of variables. To characterize vestibular schwannoma growth rates and predictors of growth.

Gene expression, signal transduction pathways and functional networks associated with growth of sporadic vestibular schwannomas

The objective of this study was to determine global gene expression in relation to Vestibular schwannomas (VS) growth rate and to identify signal transduction pathways and functional molecular networks associated with growth. Repeated magnetic resonance imaging (MRI) prior to surgery determined tumor growth rate. Following tissue sampling during surgery, mRNA was extracted from 16 sporadic VS. Double stranded cDNA was synthesized from the mRNA and used as template for in vitro transcription reaction to synthesize biotin-labeled antisense cRNA, which was hybridized to Affymetrix HG-U133A arrays and analyzed by dChip software. Differential gene expression was defined as a 1.5-fold difference between fast and slow growing tumors (><0.5ccm/year), employing a p-value <0.01. Deregulated transcripts were matched against established gene ontology. Ingenuity Pathway Analysis was used for identification of signal transduction pathways and functional molecular networks associated with tumor growth. In total 109 genes were deregulated in relation to tumor growth rate. Genes associated with apoptosis, growth and cell proliferation were deregulated. Gene ontology included regulation of the cell cycle, cell differentiation and proliferation, among other functions. Fourteen pathways were associated with tumor growth. Five functional molecular networks were generated. This first study on global gene expression in relation to vestibular schwannoma growth rate identified several genes, signal transduction pathways and functional networks associated with tumor progression. Specific genes involved in apoptosis, cell growth and proliferation were deregulated in fast growing tumors. Fourteen pathways were associated with tumor growth. Generated functional networks underlined the importance of the PI3K family, among others.

Correlation Between Aspirin Intake and Reduced Growth of Human Vestibular Schwannoma

To determine whether people with sporadic vestibular schwannoma (VS) who take aspirin for unrelated medical reasons exhibit less tumor growth than nonaspirin users. We previously demonstrated the efficacy of salicylates in inhibiting VS growth in vitro, corroborating the results of our retrospective clinical study, which found halted VS growth (based on linear tumor measurements) in aspirin users. The current study evaluates this association using more accurate tumor volumetric measurements, and quantifies the degree of frequency-specific, VS-induced hearing loss. Retrospective analysis. Tertiary care hospital. Diagnosed with VS between 1980 and 2012, followed by serial magnetic resonance imaging for at least 1 year. Patient history of aspirin intake; change in VS volume over time of observation; frequency-specific, VS-induced audiometric threshold shifts. Of the 347 patients followed by serial magnetic resonance imaging scans, 86 had sequential scans available for 3D-segmented volumetric analysis for up to 11 years of follow-up (median 53 mo). Twenty-five (29%) had documented history of aspirin intake; 8 (32%) of these demonstrated VS growth. Of the 61 (71%) nonusers, 36 (59%) demonstrated growth. A significant inverse association was found among aspirin users and VS growth: odds ratio 0.32, 95% confidence interval 0.11 to 0.91. VS-induced audiometric thresholds shifts were larger above than below 2000 Hz. Our volumetric analysis of VS growth reaffirms the results of our linear analysis and suggests that aspirin may inhibit VS growth. The audiometric findings are consistent with the previously reported VS-induced predominantly high-frequency sensorineural hearing loss.

Neutrophil to Lymphocyte Ratio as a Predictive Marker of Vestibular Schwannoma Growth.

To examine the predictive value of neutrophil to lymphocyte ratio (NLR) for vestibular schwannoma (VS) growth. Retrospective case-control study. Tertiary, referral center. Patients with sporadic VS and available NLR obtained within 1 year from the diagnosis were divided into two groups with growing or non-growing tumor. Patients with known conditions affecting NLR were excluded. NLR and tumor growth as determined by linear measurements on serial magnetic resonance imaging. VS growth, demographic factors, and NLR were compared using multi-variant logistic regression and Receiver Operating Characteristic (ROC) curve analysis. A total of 161 patients fulfilled the inclusion criteria, 79 with growing VS (men:women ratio = 43:36, mean age, 61.8 years) and 82 with non-growing tumors (men:women ratio = 37:45, mean age, 64.9 years). Mean NLR for the group with growing VS was 3.34 (SD [standard deviation] = 1.5) and 2.31 (SD = 0.76) for the group with non-growing VS (p = 0.001; 0.03 when adjusted for all parameters). The optimal cut-off point was NLR = 3.05 with positive predictive value 83.8% and 100% for NLR greater than 5.3. ROC analysis of the adjusted data for age, sex, and side, gave an area under the curve of 0.768, indicating NLR as a good independent predictive marker. Interestingly, the size of tumor was statistically significantly higher for the growing VS group (p = 0.001). Despite the low specificity of low NLR, our results indicate high NLR as a good predictive marker for VS growth. Confirmation by prospective studies will have a significant impact on patients' management.

An allograft mouse model for the study of hearing loss secondary to vestibular schwannoma growth.

Vestibular schwannoma is a benign neoplasm arising from the Schwann cell sheath of the auditory-vestibular nerve. It most commonly affects both sides in the genetic condition Neurofibromatosis type 2, causing progressive high frequency sensorineural hearing loss. Here, we describe a microsurgical technique and stereotactic coordinates for schwannoma cell grafting in the vestibular nerve region that recapitulates local tumor growth in the cerebellopontine angle and inner auditory canal with resulting hearing loss. Tumor growth was monitored by bioluminescence and MRI in vivo imaging, and hearing assessed by auditory brainstem responses. These techniques, by potentially enabling orthotopic grafting of a variety of cell lines will allow studies on the pathogenesis of tumor-related hearing loss and preclinical drug evaluation, including hearing endpoints, for NF2-related and sporadic schwannomas.

Mechanism-based modeling of the clinical effects of bevacizumab and everolimus on vestibular schwannomas of patients with neurofibromatosis type 2.

To describe the natural growth of vestibular schwannoma in patients with neurofibromatosis type 2 and to predict tumor volume evolution in patients treated with bevacizumab and everolimus. Clinical data, including longitudinal tumor volumes in patients treated by bevacizumab (n=13), everolimus (n=7) or both (n=2), were analyzed by means of mathematical modeling techniques. Together with clinical data, data from the literature were also integrated to account for drugs mechanisms of action. We developed a model of vestibular schwannoma growth that takes into account the effect of vascular endothelial growth factors and mammalian target of rapamycin complex 1 on tumor growth. Behaviors, such as tumor growth rebound following everolimus treatment stops, was correctly described with the model. Preliminary results indicate that the model can be used to predict, based on early tumor volume dynamic, tumor response to variation in treatment dose and regimen. The developed model successfully describes tumor volume growth before and during bevacizumab and/or everolimus treatment. It might constitute a rational tool to predict patients' response to these drugs, thus potentially improving management of this disease.

Vestibular schwannoma growth after stereotactic radiosurgery

Vestibular schwannoma growth after stereotactic radiosurgery

Long-term growth rate of vestibular schwannoma in neurofibromatosis 2: A volumetric consideration

To determine the long-term growth rate of vestibular schwannoma (VS) in neurofibromatosis type 2 (NF2) patients based on volumetric measurements. Retrospective review. We retrospectively reviewed magnetic resonance imaging (MRI) scans acquired from patients with NF2 from 1999 to 2013. Patients with an annual radiologic follow-up over at least 3 consecutive years were included. Volumetric VS growth was prospectively measured using a three-dimensional imaging workstation and through manual contouring of the lesion. Time to tumor progression was assessed according to the Response Evaluation in Neurofibromatosis and Schwannomatosis Tumor Measurement Group. Eighteen patients presenting with a total of 26 VSs were included. The mean age at diagnosis was 26.1 years (range, 7 to 49 years). One hundred five MRI scans were analyzed during a median radiological follow-up of 5.6 years (range, 3 to 12 years). The annual volume and diameter growth rates were respectively 218.3 mm(3) /yr (range, -10 to 1,250 mm(3) /yr) and 0.9 mm/yr (range, -0.5 to 4.5 mm/yr). Time to tumor progression was 3 years (median survival). There was a weak correlation between volumetric and linear measurements (P < .0001, linear regression, n = 26, r(2) = 0.58). Among the 26 VSs, 76.9% (20/26) showed progression (VS growth more than 20%), 19.2% were stable, and 3.9% (1/26) exhibited shrinkage (spontaneous regression of more than 20% of the initial volume). This study helps to assess the long-term growth profile of VS in a population of NF2 patients with untreated VS. These data could help to better acknowledge VS natural growth history. 4 Laryngoscope, 126:2358-2362, 2016.

Delayed Vestibular Schwannoma Growth following Steretoatactic Radiosurgery

Vestibular Schwannomas have unpredictable growth patterns. Stereotactic RadioSurgery (SRS) is a well recognized treatment for Vestibular Schwannomas (VS). Previous studies have shown positive outcomes from SRS with the growth of most tumors being well controlled. Long term outcomes however remain uncertain. The aim of this study was to examine for any patients with a VS which initially regressed or stopped growing post SRS and then starting growing again after an interval period.

Bevacizumab in neurofibromatosis type 2 (NF2) related vestibular schwannomas: a nationally coordinated approach to delivery and prospective evaluation.

NF2 patients develop multiple nervous system tumors including bilateral vestibular schwannomas (VS). The tumors and their surgical treatment are associated with deafness, neurological disability, and mortality.Medical treatment with bevacizumab has been reported to reduce VS growth and to improve hearing. In addition to evaluating these effects, this study also aimed to determine other important consequences of treatment including patient-reported quality of life and the impact of treatment on surgical VS rates. Patients treated with bevacizumab underwent serial prospective MRI, audiology, clinical, CTCAE-4.0 adverse events, and NFTI-QOL quality-of-life assessments. Tumor volumetrics were classified according to the REiNs criteria and annual VS surgical rates reviewed. Sixty-one patients (59% male), median age 25 years (range, 10-57), were reviewed. Median follow-up was 23 months (range, 3-53). Partial volumetric tumor response (all tumors) was seen in 39% and 51% had stabilization of previously growing tumors. Age and pretreatment growth rate were predictors of response. Hearing was maintained or improved in 86% of assessable patients. Mean NFTI-QOL scores improved from 12.0 to 10.7 (P < .05). Hypertension was observed in 30% and proteinuria in 16%. Twelve treatment breaks occurred due to adverse events. The rates of VS surgery decreased after the introduction of bevacizumab. Treatment with bevacizumab in this large, UK-wide cohort decreased VS growth rates and improved hearing and quality of life. The potential risk of surgical iatrogenic damage was also reduced due to an associated reduction in VS surgical rates. Ongoing follow-up of this cohort will determine the long-term benefits and risks of bevacizumab treatment.

MiR-1 association with cell proliferation inhibition and apoptosis in vestibular schwannoma by targeting VEGFA.

A growing body of research has demonstrated the tumor suppressive function of microRNA (miR)-1 in many cancers. Our study aimed to investigate its role in vestibular schwannoma (VS). We examined miR-1 expression in 95 VS specimens and 79 normal vestibular nerves using quantitative real-time polymerase chain reaction. Moreover, miR-1 mimics, miR-1 inhibitors, and negative control oligonucleotides were transfected into HEI-193 human VS cells to investigate the functional significance of miR-1 expression in this condition at a cellular level. Finally, the role of vascular endothelial growth factor A (VEGFA) in miR-1-mediated HEI-193 cell growth was confirmed. miR-1 levels were significantly reduced in VS specimens compared with normal vestibular nerve tissues (P < 0.001). In addition, low levels of miR-1 were associated with larger tumor volumes. In functional assays, miR-1 suppressed HEI-193 cell proliferation and colony formation, and enhanced apoptosis. VEGFA was verified as a target gene of miR-1, and VEGFA overexpression partially negated the effects of miR-1 on HEI-193 cells. These findings suggest that miR-1 suppresses VS growth by targeting VEGFA, and should be considered as a potential therapeutic target for treatment of this condition.

Factors influencing the growth rate of vestibular schwannoma in patients with neurofibromatosis type 2.

Neurofibromatosis type 2 (NF2) is a devastating disease with no well-accepted management guidelines. Better understanding of the disease process provides the basis for how or when to initiate treatment. Only few studies have addressed the factors influencing the growth rate of NF2-related vestibular schwannomas (VSs), and these studies have reported variable results. This study aimed to assess the clinical factors influencing the growth rate of NF2-related VSs. The medical records of 66 patients (totalling 74 VSs) were retrospectively analysed. The tumours were measured according to a two-component box model. The tumour growth rate was estimated by linear regression analysis of the changes in VS volumes over time. The clinical characteristics of all the patients were recorded. The relationship between the tumour growth rate and clinical factors were analysed. Linear regression, Pearson's correlation and Student's t-test were conducted using the SPSS 19.0 statistical package. The median follow-up duration was 4.9 years. The VSs growth rate was highly correlated with the initial VS volume (r = 0.97, p < 0.01). However, it was inversely correlated with the age at symptom onset (r = -0.41, p < 0.01). The average VS growth rate in patients with spinal tumours was 13.18 cm(3)/year compared with 0.19 cm(3)/year in patients without spinal tumours (p < 0.01). The VS growth rate in patients who had resection of a contralateral VS was slightly higher than that of patients with untreated VSs (p < 0.01). Other factors including sex, vestibular symptom, presence of other cranial schwannomas, family history and dermal abnormalities did not affect the VS growth rate. The potential clinical factors influencing the VS growth rate are the age at symptom onset, initial tumour volume and presence of spinal tumours. Surgical resection of VSs might accelerate the growth rate of contralateral tumours. The effects of these factors require further experimental confirmation.

Retrosigmoid Craniotomy for Auditory Brainstem Implantation in Adult Patients with Neurofibromatosis Type 2.

Objective To report our technique and experience using a retrosigmoid craniotomy approach for auditory brainstem implantation (ABI) placement in adult neurofibromatosis type 2 (NF2) patients. Design Retrospective case series. Setting Single-center study, Boston, Massachusetts, United States. Participants All NF2 patients who underwent evaluation at Massachusetts Eye and Ear Infirmary and surgery at Massachusetts General Hospital from 2009 to 2013 were reviewed. Six cases of retrosigmoid craniotomy for ABI surgery in five adult NF2 patients were identified. The clinical history, operative course, and outcomes in these patients were reviewed. Main Outcome Measures Postoperative complications and audiological outcomes. Results Indications for ABI surgery were profound hearing loss associated with growth or treatment of bilateral vestibular schwannomas. In all cases, a retrosigmoid craniotomy was performed for tumor resection and ABI placement without complication. Electrode placement was confirmed intraoperatively using electrical-evoked auditory brainstem responses. The ABI was activated in the awake patient 4 to 6 weeks postoperatively. Audiological testing was used to evaluate sound detection and speech perception with the ABI. There were no cases of cerebrospinal fluid leak. Conclusion Retrosigmoid craniotomy is a safe and effective means to provide access to the cochlear nucleus for ABI placement following tumor resection in the adult NF2 patient. Preliminary data indicate that this approach has few complications while offering benefits for hearing. The retrosigmoid craniotomy should be considered a reasonable alternative to the traditional translabyrinthine approach for placement of the ABI in deaf patients who are not candidates for the cochlear implant.

Bevacizumab decreases vestibular schwannomas growth rate in children and teenagers with neurofibromatosis type 2.

Vestibular schwannoma (VS) growth in neurofibromatosis type 2 (NF2) can be responsible for brainstem compression and hearing loss. Surgical removal remains the standard therapy despite potential morbidity. Previous studies suggested that the inhibition of the VEGF-pathway with bevacizumab could result in hearing improvement, reduction of the tumor volume or both in adults. We retrospectively describe the French experience of bevacizumab treatment delivered for progressive VS in pediatric NF2 patients. Patients received Bevacizumab 5 or 10mg/kg every 2weeks according to the physician's choice. Follow-up included clinical assessment, audiometry and volumetric MRI every 3-6months. Seven patients harboring 11 VS were included. The median age at inclusion was 15years (11.4-18.8), and the median treatment duration was 11.3months (3.2-55.6). At baseline, the median tumor volume was 1.2cm(3) (0.52-13.5) and the median word recognition score was 90% (0-100). We observed one major response, two minor responses and a decrease in the rate of tumor growth for the 4 other patients. The median annual growth rate before treatment was significantly higher than after 1year of treatment (138 vs. 36%, n=5, p=0.043). We noted one hearing improvement over the course of 1year under treatment (hearing response rate was 14%). Overall, the treatment was well tolerated. Our study supports that bevacizumab is an attractive therapeutic option for pediatric NF2 patients with growing VS. Thorough multidisciplinary evaluation is necessary to identify the best candidates prior to treatment. It is likely that a better functional outcome would be expected if targeted therapies were discussed early in the management of the disease.

Preclinical validation of anti-nuclear factor-kappa B therapy to inhibit human vestibular schwannoma growth

Vestibular schwannomas (VSs), the most common tumors of the cerebellopontine angle, arise from Schwann cells lining the vestibular nerve. Pharmacotherapies against VS are almost non-existent. Although the therapeutic inhibition of inflammatory modulators has been established for other neoplasms, it has not been explored in VS. A bioinformatic network analysis of all genes reported to be differentially expressed in human VS revealed a pro-inflammatory transcription factor nuclear factor-kappa B (NF-κB) as a central molecule in VS pathobiology. Assessed at the transcriptional and translational level, canonical NF-κB complex was aberrantly activated in human VS and derived VS cultures in comparison to control nerves and Schwann cells, respectively. Cultured primary VS cells and VS-derived human cell line HEI-193 were treated with specific NF-κB siRNAs, experimental NF-κB inhibitor BAY11-7082 (BAY11) and clinically relevant NF-κB inhibitor curcumin. Healthy human control Schwann cells from the great auricular nerve were also treated with BAY11 and curcumin to assess toxicity. All three treatments significantly reduced proliferation in primary VS cultures and HEI-193 cells, with siRNA, 5 μM BAY11 and 50 μM curcumin reducing average proliferation (±standard error of mean) to 62.33% ± 10.59%, 14.3 ± 9.7%, and 23.0 ± 20.9% of control primary VS cells, respectively. These treatments also induced substantial cell death. Curcumin, unlike BAY11, also affected primary Schwann cells. This work highlights NF-κB as a key modulator in VS cell proliferation and survival and demonstrates therapeutic efficacy of directly targeting NF-κB in VS.

Growth of Primary and Remnant Vestibular Schwannomas: A Three-Year Follow-Up Study

Vestibular schwannomas (VSs) are benign, slowly growing tumors. The management strategy, however, remains unclear for both primary VS and remnant VS after subtotal or partial resection. In this study, we analyzed the radiographical tumor growth to elucidate factors possibly predicting growth or regrowth of their tumors. We retrospectively analyzed the data of 76 patients with diagnoses of VS at a single tertiary academic referral center. The primary VS group consisted of 43 patients with conservative management, and the remnant VS group included 33 patients with tumor remnant after surgery. All patients were followed up with serial magnetic resonance imaging without intervention. The primary end point in this study was significant tumor growth at the end of the 3-year follow-up period. Multivariate analysis revealed that remnant VS was less likely to grow than primary VS (odds ratio: 0.27, 95% confidence interval: 0.09-0.84). Tumor volume was correlated with tumor growth; larger tumors grew more frequently than small tumors in both primary and remnant VS groups with marginal (P = 0.05) and definite (P = 0.007) significance, respectively. The receiver operating characteristic curves plotted for tumor growth identified the optimum cutoff points of tumor volumes with greater sensitivity and specificity for remnant VS than for primary VS (sensitivity: 80% vs. 59%, specificity: 87% vs. 76%, respectively). Small remnant VS after surgery could be conservatively managed without additional treatment, and relatively large remnant VS should be followed up with close serial imaging or might be a possible candidate for radiosurgery during the early postoperative period.

Hearing in Static Unilateral Vestibular Schwannoma Declines More Than in the Contralateral Ear

To determine the effect of static vestibular schwannomas on hearing. Retrospective review of audiometric measures in 15 patients with documented nongrowth of internal auditory canal and cerebellopontine angle enhancing masses. Data from patients seen in an ambulatory tertiary care setting between the years of 2002 and 2012 with a diagnosis of acoustic neuroma or vestibular schwannoma were reviewed. Exclusion criteria included preexisting otologic disease, prior therapy for the schwannoma, and tumor growth. Radiology reports were reviewed to ensure nongrowth and were confirmed by taking magnetic resonance imaging (MRI) measurements ourselves. Audiologic measurements included pure tone average, enhanced pure tone average (average of .5, 1, 2, and 4 KHz thresholds), 4 KHz threshold, 8 KHz threshold, and speech discrimination. The data were analyzed using mixed effect model with unstructured variance-covariance structure. Difference in audiometric measures between ears significantly (P<.05) increased for all measures except 8 KHz. Spontaneous decline in hearing relative to time is exaggerated in the affected ear despite no vestibular schwannoma growth. This finding can be useful for patient counseling and treatment decision making.

Nonsteroidal anti-inflammatory medications are cytostatic against human vestibular schwannomas

Vestibular schwannomas (VSs) are the most common tumors of the cerebellopontine angle. Significant clinical need exists for pharmacotherapies against VSs. Motivated by previous findings that immunohistochemical expression of cyclooxygenase 2 (COX-2) correlates with VS growth rate, we investigated the role of COX-2 in VSs and tested COX-2 inhibiting salicylates against VSs. COX-2 was found to be aberrantly expressed in human VS and primary human VS cells in comparison with control human nerve specimens and primary Schwann cells (SCs), respectively. Furthermore, levels of prostaglandin E2, the downstream enzymatic product of COX-2, were correlated with primary VS culture proliferation rate. Because COX-2 inhibiting salicylates such as aspirin are well tolerated and frequently clinically used, we assessed their repurposing for VS. Changes in proliferation, cell death, and cell viability were analyzed in primary VS cultures treated with aspirin, sodium salicylate, or 5-aminosalicylic acid. These drugs neither increased VS cell death nor affected healthy SCs. The cytostatic effect of aspirin in vitro was in concurrence with our previous clinical finding that patients with VS taking aspirin demonstrate reduced tumor growth. Overall, this work suggests that COX-2 is a key modulator in VS cell proliferation and survival and highlights salicylates as promising pharmacotherapies against VS.

Correlation of Unilateral Sporadic Vestibular Schwannoma Growth Rates with Genetic and Immunohistochemical Abnormalities

Background: Unilateral sporadic vestibular schwannomas (USVS) are caused by inactivating somatic mutations of both alleles of the neurofibromatosis 2 (NF2) tumor suppressor gene. Unilateral sporadic vestibular schwannomas have a widely-varying growth patterns whose causes are poorly understood. Objective: We examined the relationships between an index of USVS growth, and genetic abnormalities and pathological growth indices. Subjects and Methods: Single-strand conformational polymorphism analysis and heteroduplex methods were used to screen for mutations in all 17 exons of the NF2 gene in USVS from 63 patients. Loss of heterozygosity (LOH) analyses were also carried out. An index of USVS growth (clinical growth index, CGI) was calculated as maximum tumor diameter divided by duration of symptoms. The immunohistochemical growthindices were based on monoclonal antibodies to Ki-67 and another tumor cell proliferation marker (platelet-derived growth factor (PDGF)). Results: CGI was highly variable and did not significantly decrease with increasing age at diagnosis. Either somatic NF2 mutations or LOH was found in 88% of tumors. PDGF and Ki-67 increased significantly with increasing age at diagnosis, and PDGF was lower in tumors with LOH than in those without LOH. In multiple linear regression analysis, CGI was significantly higher in people with higher PDGF, after accounting for age at diagnosis and LOH. Conclusion: An index of USVS growth increases with increasing PDGF, after accounting for age and LOH.

Progress of hearing loss in neurofibromatosis type 2: implications for future management.

The objective of this study was to describe changes in hearing over time in patients with neurofibromatosis type 2 (NF2) treated conservatively. A retrospective case review was conducted in a tertiary referral centre. Pure tone audiometry, speech discrimination scores, serviceable hearing (American Academy of Otolaryngology class A or B) and measurement of vestibular schwannoma (VS) size on magnetic resonance imaging were evaluated in 56 patients (89 ears) with NF2 with at least one conservatively managed VS. Over a mean follow-up period of 7 years (range 0.8-21 years) pure tone average thresholds increased gradually with a mean annual rate of 1.3 dB for the right ear (p = 0.0003) and 2 dB for the left ear (p = 0.0009). Speech discrimination scores dropped with an average annual rate of 1.3 and 0.34% in the right and left ear, respectively. Patients maintained serviceable hearing for an average of 7.6 years (range 2.7-19.3 years). The average annual VS growth was 0.4 mm without any correlation with hearing loss. There was a correlation between patients' age and pure tone threshold increase (p < 0.05 for both ears). In this selected population of patients with NF2, hearing threshold increases were very slow. In NF2 patients with indolently behaving tumours, serviceable hearing can be maintained for a significant length of time, making conservative management an attractive option.