Electrical stimulation of the cochlea for treatment of chronic disabling tinnitus: an open-label trial towards the development of an implantable device.

BACKGROUND: Chronic tinnitus affects millions of people globally and constitutes the most commonly compensated disability among military service members in the United States. Existing treatment options largely surround helping patients cope with their disease as opposed to directly suppressing tinnitus perception. The current study investigated the efficacy of electrical stimulation of the cochlea on chronic disabling tinnitus. METHODS: In this single-arm, open-label clinical trial, 22 adult subjects with severe-range asymmetric or unilateral non-pulsatile tinnitus underwent electrical stimulation of the cochlea through use of an extra-cochlear electrode positioned on the cochlear promontory. Each subject underwent 3 stimulation treatments over 3 weeks at 7-day intervals. Tinnitus severity was determined by Tinnitus Handicap Inventory (THI), Tinnitus Functional Index (TFI), and Tinnitus Visual Analog Scale (VAS). Inclusion criteria required subjects have no worse than moderate sensorineural hearing loss determined by pre-enrollment audiometric testing. The primary outcome was nadir post-treatment THI scores, obtained at seven timepoints following electrical stimulation, with clinically significant improvement defined as a decrease of ≥ 7. RESULTS: All 22 (100%) subjects experienced clinically significant improvement in the THI during the study period with a mean decrease in scores of - 31 (95% CI - 38 to - 25) from a baseline of 48. Twenty (91%) experienced clinically significant improvement detectable on at least two of the three tinnitus survey instruments and 17 (77%) experienced clinically significant improvement detectable on all three survey instruments (i.e., THI, TFI, and VAS). Eight (36%) subjects reported either complete (THI of 0; n = 3) or near-complete (THI 1-4; n = 5) suppression of their tinnitus following a stimulation session. Thirteen (59%) subjects reported a nadir following stimulation at or below the threshold for "no or slight handicap" on the THI (≤ 16). No adverse events were observed. CONCLUSIONS: These findings establish the foundation for the development of an extra-cochlear implantable device that delivers electrical stimulation to the cochlea for the treatment of disabling tinnitus. For patients considering device implantation, trans-tympanic cochlear promontory stimulation can facilitate patient selection. Trial Registration ClinicalTrials.gov Identifier: NCT03759834. URL: https://clinicaltrials.gov/ct2/show/NCT03759834.

Whole genome sequencing reveals complexity in both HPV sequences present and HPV integrations in HPV-positive oropharyngeal squamous cell carcinomas.

BACKGROUND: High risk human papillomaviruses (HPV) plays important roles in the development of cervical cancer, a number of other anogenital cancer and they are increasingly found in oropharyngeal squamous cell carcinoma (OPSCC), however there has not been comprehensive analysis about the role how these viruses play in the development of OPSCC. METHODS: To characterize the physical status of HPV within OPSCC and to determine the effect this has throughout the host genome, we have performed 30-40X whole genome sequencing (WGS) on the BGI sequencing platform on 34 OPSCCs: 28 of which were HPV positive. We then examined the sequencing data to characterize the HPV copy number and HPV physical status to determine what effect they have on both HPV and human genome structural changes. RESULTS: WGS determined the HPV copy number across the viral genome. HPV copy number ranged from 1 copy to as high as 150 copies in each individual OPSCC. Independent of HPV copy number, most tumors had either a small or a very large deletion in the viral genome. We discovered that these deletions were the result of either HPV integration into the human genome or HPV-HPV sequence junctions. WGS revealed that ~ 70% of these tumors had HPV integrations within the human genome and HPV integration occurred independent of HPV copy number. Individual HPV integrations were found to be highly disruptive resulting in structural variations and copy number changes at or around the integration sites. CONCLUSIONS: WGS reveals that there is a great complexity in both HPV sequences present and the HPV integrations events in HPV positive OPSCCs tumors. Thus HPV may be playing different roles in the development of different OPSCCs and this further challenge the HPV-driven carcinogenesis model first proposed for cervical cancer.

Common fragile sites (CFS) and extremely large CFS genes are targets for human papillomavirus integrations and chromosome rearrangements in oropharyngeal squamous cell carcinoma.

Common fragile sites (CFS) are chromosome regions that are prone to form gaps or breaks in response to DNA replication stress. They are often found as hotspots for sister chromatid exchanges, deletions, and amplifications in different cancers. Many of the CFS regions are found to span genes whose genomic sequence is greater than 1 Mb, some of which have been demonstrated to function as important tumor suppressors. CFS regions are also hotspots for human papillomavirus (HPV) integrations in cervical cancer. We used mate-pair sequencing to examine HPV integration events and chromosomal structural variations in 34 oropharyngeal squamous cell carcinoma (OPSCC). We used endpoint PCR and Sanger sequencing to validate each HPV integration event and found HPV integrations preferentially occurred within CFS regions similar to what is observed in cervical cancer. We also found that many of the chromosomal alterations detected also occurred at or near the cytogenetic location of CFSs. Several large genes were also found to be recurrent targets of rearrangements, independent of HPV integrations, including CSMD1 (2.1Mb), LRP1B (1.9Mb), and LARGE1 (0.7Mb). Sanger sequencing revealed that the nucleotide sequences near to identified junction sites contained repetitive and AT-rich sequences that were shown to have the potential to form stem-loop DNA secondary structures that might stall DNA replication fork progression during replication stress. This could then cause increased instability in these regions which could lead to cancer development in human cells. Our findings suggest that CFSs and some specific large genes appear to play important roles in OPSCC. © 2016 Wiley Periodicals, Inc.

A selected group of large common fragile site genes have decreased expression in oropharyngeal squamous cell carcinomas.

The common fragile sites (CFSs) are large regions of profound genomic instability found in all individuals. The frequent deletions and other alterations in these regions in multiple cancers has led to the discovery of a number of extremely large genes contained within these regions and several of the large CFS genes have already been demonstrated to function as tumor suppressors involved in the formation of many different cancers. To study the large CFS genes in oropharyngeal squamous cell carcinoma (OPSCC), we did RNA seq analysis from 11 head and neck cancer patients. This revealed that there are six large CFS genes which consistently had decreased expression in the tumor samples compared to their matched normal tissues. These six genes are PARK2, DLG2, NBEA, CTNNA3, DMD, and FHIT. PARK2 and FHIT are located within the two most frequently expressed CFSs and both have been demonstrated to function as tumor suppressors, while the other large genes are found to have frequent alterations in multiple cancers. Validation experiments using real time PCR indicated that over 60% of OPSCC tumors showed decreased expression for all six genes. Both HPV-positive and HPV-negative OPSCCs had similar proportions with loss of expression of these genes. Our results suggest that this selected group of large genes might serve as potential tumor suppressors involved in the development of OPSCCs. Further studies are needed to investigate whether the decreased expression observed is due to genomic instability within the CFS regions or the selection for alterations of specific large CFS genes.

Comparing Patient Satisfaction After Upfront Treatment Versus Wait-and-Scan for Small Sporadic Vestibular Schwannoma.

OBJECTIVE: Management of small vestibular schwannoma (VS) remains controversial, as patients are typically candidates for all three management options including microsurgery, stereotactic radiosurgery, or wait-and-scan. This study compares patient satisfaction across treatment modalities in patients with small VS. STUDY DESIGN: Cross-sectional study. SETTING: Survey distributed to members of the Acoustic Neuroma Association and Mayo Clinic patients. METHODS: Patients with small (<1 cm in any location) sporadic VS who completed at least one survey regarding treatment history and patient satisfaction were included. RESULTS: Among 346 patients with small VS, 106 (31%) underwent microsurgery, 78 (23%) radiosurgery, 152 (44%) wait-and-scan, and 10 (3%) multimodal treatment. Collectively, 307 (89%) patients indicated "Yes, I am happy with my treatment type and in hindsight I would not change anything," and 39 (11%) indicated "No, in hindsight I would have chosen a different treatment type." Satisfaction differed significantly by treatment group with 85, 86, 96, and 40% of patients in the microsurgery, radiosurgery, wait-and-scan, and multimodal groups reporting that they were satisfied with treatment, respectively ( p < 0.001). Satisfaction also differed significantly among those undergoing upfront treatment with microsurgery or radiosurgery (81%), initial wait-and-scan followed by treatment (88%), and wait-and-scan only groups (96%; p = 0.001). Specifically, the wait-and-scan only group demonstrated greater satisfaction compared with the other two treatment strategies ( p < 0.05 for both). CONCLUSIONS: Patient satisfaction with the management of small VS is generally high. Management with wait-and-scan, even if treatment is eventually pursued, may offer higher patient satisfaction compared with upfront treatment.

Development and validation of a new disease-specific quality of life instrument for sporadic vestibular schwannoma: the Mayo Clinic Vestibular Schwannoma Quality of Life Index.

OBJECTIVE: Facial nerve function, hearing preservation, and tumor control have been the primary benchmarks used to assess vestibular schwannoma (VS) outcomes. Acknowledging the frequent discrepancy between what physicians prioritize and what patients value, there has been increasing prioritization of patient-reported outcome measures when evaluating the impact of VS diagnosis and its treatment. Motivated by reported limitations of prior instruments used to assess quality of life (QOL) in patients with VS, the authors describe the development and validation of a new disease-specific QOL measure: the Vestibular Schwannoma Quality of Life (VSQOL) Index. METHODS: The content development phase comprised identification of clinically important domains and prioritization of feelings or concerns individuals with VS may have. The validation phase encompassed determining how items were grouped into domains and eliminating redundant items. Both phases leveraged data from cross-sectional and longitudinal surveys, expertise from a multidisciplinary working group, and patients with a broad range of experiences with VS (n = 42 during content development and n = 263 during validation). Domain scores from the new instrument were assessed for reliability and correlation with other measures of similar constructs. RESULTS: The VSQOL Index consists of 40 items that evaluate the impact of VS diagnosis and its management on QOL, treatment satisfaction, and employment and is estimated to take 8-10 minutes to complete. Domain scores range from 0 (worst) to 100 (best) and demonstrate excellent psychometric properties, including content, construct, and convergent validity and both internal consistency (Cronbach's alphas 0.83 to 0.91) and test-retest reliability (reliability coefficients 0.86 to 0.96). CONCLUSIONS: The VSQOL Index is a valid and reliable measure that overcomes several limitations of prior instruments, including omission or underrepresentation of domains that frequently impact well-being, such as pain, cognition, satisfaction or regret surrounding treatment decisions, and occupational limitations, to comprehensively evaluate the impact of VS diagnosis or its treatment on QOL.

Implementation Strategy for Highly-Coordinated Cochlear Implant Care With Remote Programming: The Complete Cochlear Implant Care Model.

OBJECTIVE: To introduce and discuss implementation strategy for the Complete Cochlear Implant Care (CCIC) model, a highly-coordinated cochlear implant (CI) care delivery model requiring a single on-site visit for preoperative workup, surgery, and postoperative programming. STUDY DESIGN: Prospective, nonrandomized, two-arm clinical trial. SETTING: Tertiary referral CI center. PATIENTS: Adults who meet audiologic criteria for cochlear implantation. INTERVENTIONS: Cochlear implantation, coordinated care delivery, including remote programming. MAIN OUTCOME MEASURES: Care delivery model feasibility and process implementation. RESULTS: Patients determined to be likely CI candidates based on routine audiometry are eligible for enrollment. The CCIC model uses telemedicine and electronic educational materials to prepare patients for same-day on-site consultation with CI surgery, same or next-day activation, and postoperative remote programming for 12 months. Implementation challenges include overcoming inertia related to the implementation of a new clinical workflow, whereas scalability of the CCIC model is limited by current hardware requirements for remote programming technology. A dedicated CCIC process coordinator is critical for overcoming obstacles in implementation and process improvement through feedback and iterative changes. Team and patient-facing materials are included and should be tailored to fit each unique CI program looking to implement CCIC. CONCLUSION: The CCIC model has the potential to dramatically streamline hearing healthcare delivery. Implementation requires an adaptive approach, as obstacles may vary according to institutional infrastructure and policies.

Disease-Specific Quality of Life in Vestibular Schwannoma: A National Cross-sectional Study Comparing Microsurgery, Radiosurgery, and Observation.

OBJECTIVE: To examine the impact of treatment on disease-specific health-related quality of life (HRQOL) among patients with sporadic vestibular schwannoma (VS). STUDY DESIGN: National cross-sectional study. SETTING: Tertiary referral center and the Acoustic Neuroma Association. SUBJECTS AND METHODS: Adult patients with VS who completed the Penn Acoustic Neuroma Quality of Life (PANQOL) survey. Patients were classified by treatment at the most recent survey as microsurgery, radiosurgery, observation, or recently diagnosed (RD). PANQOL scores were compared among VS treatment groups and with nontumor controls using analysis of covariance. RESULTS: A total of 1362 respondents with VS were analyzed. Total PANQOL scores differed significantly by treatment (P = .024) with adjusted means of 60, 63, 65, and 62 for the microsurgery, radiosurgery, observation, and RD groups, respectively. Subdomain scores for facial function, balance, hearing loss, and pain differed significantly (P < .05) by treatment. Comparisons that surpassed thresholds for clinical significance included microsurgery compared to radiosurgery and observation for facial function, microsurgery compared to observation and RD for hearing loss, and microsurgery compared to radiosurgery and observation for pain. Subdomain scores for anxiety, facial function, balance, hearing loss, energy, and pain and total PANQOL scores for nontumor controls were significantly higher (ie, more favorable) compared to the VS groups (P < .05). General health scores did not differ significantly between the nontumor controls and the VS groups (P = .19). CONCLUSION: Differences in HRQOL among treatment modalities are small and variably exceed the minimal clinically important difference. The impact of a VS diagnosis on HRQOL supersedes that of the treatment type.

Impact of Treatment on Vestibular Schwannoma-Associated Symptoms: A Prospective Study Comparing Treatment Modalities.

OBJECTIVE: The degree to which various treatment modalities modify vestibular schwannoma (VS)-associated symptoms has received limited attention. The purpose of this study was to determine how different treatment modalities affect subjective symptoms in those presenting with VS. STUDY DESIGN: Prospective survey. SETTING: Tertiary neurotology referral center. METHODS: Patients with sporadic VS who received treatment at our institution were prospectively surveyed with a VS symptom questionnaire. Those who completed a baseline survey prior to treatment and at least 1 posttreatment survey were included. The prospective survey evaluated the severity of self-reported symptoms (Likert scale, 1-10), including tinnitus, dizziness or imbalance, headaches, and hearing loss. RESULTS: A total of 244 patients were included (mean age, 57 years). The mean duration of follow-up was 2.1 years, and the median number of surveys completed was 2 (interquartile range, 1-3). Seventy-eight (32%) cases were managed with observation, 118 (48%) with microsurgery, and 48 (20%) with radiosurgery. Multivariable analyses revealed no statistically significant difference in the change in tinnitus (P = .15), dizziness or imbalance (P = 0.66), or headaches (P = .24) among treatment groups. Evaluation of clinically important differences demonstrated that microsurgery leads to significant bidirectional changes in headaches. CONCLUSIONS: Limited prospective data exist regarding the progression or resolution of subjective symptoms in those presenting with VS. This study suggests that tinnitus, dizziness or imbalance, and headaches are unlikely to be significantly modified by treatment modality and generally should not be used to direct treatment choice.

Prospective Study of Disease-Specific Quality-of-Life in Sporadic Vestibular Schwannoma Comparing Observation, Radiosurgery, and Microsurgery.

BACKGROUND: Previous cross-sectional studies analyzing quality of life (QOL) outcomes in patients with sporadic vestibular schwannoma (VS) have shown surprisingly little difference among treatment modalities. To date, there is limited prospective QOL outcome data available comparing baseline to posttreatment scores. STUDY DESIGN: Prospective longitudinal study using the disease-specific Penn Acoustic Neuroma Quality of Life (PANQOL) scale. SETTING: Large academic skull base center. PATIENTS: Patients diagnosed with unilateral VS who completed a baseline survey before treatment and at least one posttreatment survey. MAIN OUTCOME MEASURES: Change in PANQOL scores from baseline to most recent survey. RESULTS: A total of 244 patients were studied, including 78 (32%) who elected observation, 118 (48%) microsurgery, and 48 (20%) stereotactic radiosurgery. Patients who underwent microsurgery were younger (p < 0.001) and had larger tumors (p < 0.001) than those who underwent observation or radiosurgery; there was no significant difference in duration of follow-up among management groups (mean 2.1 yrs; p = 0.28). When comparing the total PANQOL score at baseline to the most recent survey, the net change was only -1.1, -0.1, and 0.3 points on a 100-point scale for observation, microsurgery, and radiosurgery, respectively (p = 0.89). After multivariable adjustment for baseline features, there were no statistically significant changes when comparing baseline to most recent scores within each management group for facial function, general health, balance, hearing loss, energy, and pain domains or total score. However, the microsurgical group experienced a 10.8-point improvement (p = 0.002) in anxiety following treatment, compared with 1.5 (p = 0.73) and 5.3 (p = 0.31) for observation and radiosurgery, respectively. CONCLUSIONS: In this prospective longitudinal study investigating differences in QOL outcomes among VS treatment groups using the disease-specific PANQOL instrument, treatment did not modify QOL in most domains. Microsurgery may confer an advantage with regard to patient anxiety, presumably relating to the psychological benefit of "cure" from having the tumor removed.

The Influence of Vestibular Schwannoma Tumor Volume and Growth on Hearing Loss.

OBJECTIVE: To ascertain the relationship among vestibular schwannoma (VS) tumor volume, growth, and hearing loss. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary center. SUBJECTS AND METHODS: Adults with observed VS and serviceable hearing at diagnosis were included. The primary outcome was the development of nonserviceable hearing as estimated using the Kaplan-Meier method. Associations of tumor volume with baseline hearing were assessed using Spearman rank correlation coefficients. Associations of volume and growth with the development of nonserviceable hearing over time were assessed using Cox proportional hazards models and summarized with hazard ratios (HRs). RESULTS: Of 230 patients with VS and serviceable hearing at diagnosis, 213 had serial volumetric tumor data for analysis. Larger tumor volume at diagnosis was associated with increased pure-tone average (PTA) (P < .001) and decreased word recognition score (WRS) (P = .014). Estimated rates of maintaining serviceable hearing at 6 and 10 years following diagnosis were 67% and 49%, respectively. Larger initial tumor volume was associated with development of nonserviceable hearing in a univariable setting (HR for 1-cm3 increase: 1.36, P = .040) but not after adjusting for PTA and WRS. Tumor growth was not significantly associated with time to nonserviceable hearing (HR, 1.57; P = .14), although estimated rates of maintaining serviceable hearing during observation were poorer in the group that experienced growth. CONCLUSION: Larger initial VS tumor volume was associated with poorer hearing at baseline. Larger initial tumor volume was also associated with the development of nonserviceable hearing during observation in a univariable setting; however, this association was not statistically significant after adjusting for baseline hearing status.

Main Symptom that Led to Medical Evaluation and Diagnosis of Vestibular Schwannoma and Patient-Reported Tumor Size: Cross-sectional Study in 1,304 Patients.

Objectives Although vestibular schwannomas (VS) are known to cause cranial nerve deficits, cerebellar symptoms, and hydrocephalus, the role of these symptoms as the key driver of presentation from the patient's perspective has not been described. Our objective was to survey a large, retrospective VS cohort to document the patient-reported principal initial symptom, and self-reported tumor size, and to study trends in VS patient presentation. Methods Patients diagnosed with VS at our tertiary referral center and belonging to the Acoustic Neuroma Association (ANA) answered a questionnaire between 2015 and 2017. Demographic data, self-reported tumor size, and symptomatology were analyzed. Results 1,304 patients completed the questionnaire. Tumors were diagnosed from 1966 to 2017 at a mean 51.8 years (range: 8-86 years); 66% were female, and 1.1% had confirmed neurofibromatosis type 2 (NF2). Tumor size was reported using a 6-point scale: 0 to 1 cm (22.9%), 1 to 2 cm (28.7%), 2 to 3 cm (20.5%), 3 to 4 cm (10%), greater than 4 cm (7.2%), and unknown (10.6%). Hearing loss was the most common symptom that led to diagnosis (51.5%), followed by dizziness (17%), tinnitus (11.2%), and incidental diagnosis (10.2%); a fraction that has increased significantly in the last decade ( p = 0.022). Larger tumors and NF2 were significantly associated with young age ( p < 0.001). Conclusion Our large-scale questionnaire-driven review of 1,304 patients confirms that VS presentations are stereotypical, with most individuals recalling hearing loss, dizziness, or tinnitus as their chief complaint. Many tumors were incidentally diagnosed; an expanding population, attributable to increased access to magnetic resonance imaging (MRI). Large tumors were significantly more prevalent among younger patients at diagnosis, excluding NF2 patients, suggesting a more aggressive tumor biology that remains incompletely understood.

Influence of Selection Bias in Survey Studies Derived From a Patient-Focused Organization: A Comparison of Response Data From a Single Tertiary Care Center and the Acoustic Neuroma Association.

BACKGROUND: The Acoustic Neuroma Association (ANA) is a national, nonprofit organization, focused on the education and support of patients with vestibular schwannoma (VS). The aim of the present study is to characterize the profile of ANA survey respondents and compare them with non-ANA patients evaluated at a single tertiary academic referral center to investigate the potential influence of selection bias. METHODS: A prospectively maintained VS quality-of-life (QOL) database, comprised of patients evaluated at the authors' center and members of the ANA, was queried. Demographic variables, patient-reported symptoms and tumor characteristics, as well as patient-reported outcome scores were captured. Health-related QOL was evaluated using the disease-specific Penn Acoustic Neuroma QOL (PANQOL) questionnaire. Multivariable regression models were fitted for PANQOL domain and total scores as well as satisfaction with treatment adjusting for baseline demographics, symptoms, and PANQOL scores. RESULTS: A total of 1,060 patients (802 [76%] ANA respondents) were analyzed. Overall, ANA patients were slightly younger (mean age: 59 vs 60 yr, p = 0.145), more likely to be women (72 vs 55%, p < 0.001), and had a larger tumor size (overall p < 0.001). Furthermore, a significantly higher proportion of ANA patients were more likely to undergo microsurgery (57 vs 21%) or radiation (21 vs 8%) and less likely to be managed with observation (16 vs 65%, overall p < 0.001). A significantly higher proportion of ANA patients reported hearing loss (95 vs 88%, p < 0.001), tinnitus (80 vs 73%, p = 0.034), dizziness (78 vs 64%, p < 0.001), headache (56 vs 45% p = 0.003), and facial paralysis (37 vs 12%, p < 0.001). On multivariable analysis, ANA respondents exhibited significantly lower PANQOL scores for hearing (OR: 0.47, 95% CI: 0.35-0.64, p < 0.001), balance (OR: 0.51, 95% CI: 0.38-0.70, p < 0.001), pain (OR: 0.63, 95% CI: 0.46-0.86, p = 0.004), facial function (OR: 0.58, 95% CI: 0.42-0.80, p = 0.001), energy (OR: 0.44, 95% CI: 0.32-0.59, p < 0.001), anxiety (OR: 0.54, 95% CI: 0.40-0.74, p < 0.001), general (OR: 0.72, 95% CI: 0.53-0.98, p = 0.03), and total QOL (OR: 0.40, 95% CI: 0.30-0.55, p < 0.001). No statistically significant difference was seen with regard to treatment satisfaction.To determine the true clinical relevance of these differences, the two groups were compared using the minimal clinically important difference (MCID) for each domain. MCID is defined as the smallest difference in score in the domain of interest that patients perceive as important, either beneficial or harmful. The domains for hearing, balance, energy, anxiety, and total QOL reached their respective MCID thresholds, indicating that the ANA cohort has QOL scores that are clinically, perceptually worse for these domains compared to the non-ANA group. CONCLUSION: These data help delineate some of the inherent limitations and biases associated with survey studies incorporating data from national patient support organizations. The population profile of ANA survey respondents likely differs significantly from the greater population of patients with VS that may be encountered at a tertiary referral center.

Quality of Life in Jugular Paraganglioma Following Radiosurgery.

OBJECTIVE: The treatment paradigm for jugular paraganglioma (JP) has changed considerably over time with the wider adoption of stereotactic radiosurgery (SRS). To the best of the authors' knowledge, there are no published studies that use validated patient-reported outcome measures to ascertain quality of life (QoL) outcomes following SRS for JP when used in single or combined modality treatment regimens. STUDY DESIGN: Cross-sectional survey. SETTING: Tertiary referral center. PATIENTS: Adult patients with JP treated with primary SRS or SRS following primary surgery between 1990 and 2017. INTERVENTIONS(S): Surgery and/or Gamma Knife SRS. MAIN OUTCOME MEASURES: Global and treatment-related QoL and differences in QoL based on treatment approach. RESULTS: Sixty-nine surveys were distributed and a total of 26 completed surveys were received (38% response rate). Among respondents, the median age at SRS was 53 years and 16 of the 26 patients (62%) were female. Median follow-up was 97 months. Nineteen patients (73%) were treated with primary SRS or staged SRS following intentional subtotal resection (STR; hereafter referred to as "staged SRS"), while the remainder (n = 7, 27%) were treated with SRS for recurrent JP. Median physical and mental health QoL PROMIS-10 T-scores regardless of treatment strategy were 39.8 and 38.8, respectively, while median SF36 physical and mental component subscores were similar to national averages and non-tumor controls. When comparing general physical and mental health QoL scores, there was no significant difference between patients treated with primary or staged SRS and those treated with SRS for recurrent JP. However, age-adjusted swallowing function among patients treated with primary or staged SRS was better than in those patients treated with SRS for recurrent JP (p = 0.05). CONCLUSIONS: Patients treated with primary or staged SRS for JP tend to exhibit better swallowing outcomes than those treated with SRS for recurrent JP. However, the majority of overall and disease-specific quality of life measures were not different between groups. Based on the low incidence of new cranial neuropathy following SRS, it is likely that initial surgical morbidity is the primary contributor to this outcome. Disease-specific overall quality of life measures, akin to those already used for other benign skull base tumors, are necessary to better gauge physical and mental health outcomes following treatment for JP. Though limited by small sample size, this represents the first study to gauge QoL outcomes following treatment for JP.

A Cross-Sectional Survey of the North American Skull Base Society Part 3: The State of Lateral Skull Base Surgery Training in North America.

Introduction Optimal management of vestibular schwannoma (VS) demands involvement of an experienced multidisciplinary team. As the number of training programs in neurotology and skull base neurosurgery continues to rise, ensuring that trainees are capable of evidence-based decision-making and treatment, whether microsurgical or radiosurgical, is of paramount importance. The purpose of this study is to characterize the landscape of neurotologic and neurosurgical fellowship training programs in North America, with special reference to VS management. Methods A 64-item web-based survey assessing VS practice trends was devised by members of the North American Skull Base Society (NASBS) Research Task Force and distributed electronically to NASBS membership via SurveyMonkey as a cross-sectional study. Participation was entirely voluntary and there was no remuneration for survey completion. The survey link was active from November 29 to December 14, 2016. Results Of 719 members of the NASBS who were emailed a survey link, a total of 57 were returned (8%) completed surveys. Of all respondents, 51 (89%) claimed to have formal training in skull base neurosurgery or neurotology. Thirty-three respondents (65%) were skull base neurosurgeons while the remainder were neurotologists ( n = 18; 35%). Institutions with fellowship programs tended to have a higher surgical, radiosurgical, and overall case volume than those with a residency program alone. However, 20% of respondents at institutions with fellowship programs reported evaluating less than 50 new diagnoses of VS per year and 12% reported a surgical case volume of less than 10 cases per year. Conclusion As the number of skull base training programs expands, it is our duty to ensure that trainees gain sufficient experience to enter independent practice with the ability to exercise informed decision-making and safely perform VS surgery and radiosurgery. In the current training climate, implementing multidisciplinary care models, formalized training requirements, and emerging surgical simulators will support the development of minimum proficiencies in VS care.

Defining the Minimal Clinically Important Difference for Patients With Vestibular Schwannoma: Are all Quality-of-Life Scores Significant?

BACKGROUND: The diagnosis of vestibular schwannomas (VS) is associated with reduced patient quality of life (QOL). Minimal clinically important difference (MCID) was introduced as the lowest improvement in a patient-reported outcome (PRO) score discerned as significant by the patient. We formerly presented an MCID for the Penn Acoustic Neuroma QOL (PANQOL) battery based on cross-sectional data from 2 tertiary referral centers. OBJECTIVE: To validate the PANQOL MCID values using prospective data. METHODS: A prospective registry capturing QOL was queried, comprising patients treated at the authors' institution and Acoustic Neuroma Association members. Anchor- and distribution-based techniques were utilized to determine the MCID for domain and total scores. We only included anchors with Spearman's correlation coefficient larger than 0.3 in the MCID threshold calculations. Most domains had multiple anchors with which to estimate the MCID. RESULTS: A total of 1254 patients (mean age: 57.4 yr, 65% females) were analyzed. Anchor-based methods produced a span of MCID values (median, 25th-75th percentile) for each PANQOL domain and the total score: hearing (13.1, 13-16 points), balance (14, 14-19 points), pain (21, 20-28 points), face (25, 16-36 points), energy (16, 15-18 points), anxiety (16 [1 estimate]), general (13 [1 estimate]), and total (12.5, 10-15 points). CONCLUSION: Current findings corroborate our formerly shared experience using multi-institutional, cross-sectional information. These MCID thresholds can serve as a pertinent outcome when deciphering the clinical magnitude of VS QOL endpoints in cross-sectional and longitudinal studies.

Impact of Aspirin and Other NSAID Use on Volumetric and Linear Growth in Vestibular Schwannoma.

OBJECTIVES: Conflicting research exists surrounding the utility of aspirin to prevent tumor growth in the medical management of vestibular schwannoma (VS). Recent studies demonstrated no association between aspirin and VS growth using linear tumor measurements. Given the heightened sensitivity of volumetric analyses to monitor tumor growth, the current study was conceived with the chief objective of assessing the association between aspirin or other nonsteroidal anti-inflammatory drug (NSAID) use and VS growth using volumetric analyses. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: A total of 361 patients totaling 1601 volumetrically analyzed magnetic resonance imaging studies who underwent initial observation since January 1, 2003. RESULTS: In total, 123 (35%) patients took 81 mg aspirin daily, 23 (7%) took 325 mg aspirin daily, and 41 (11%) reported other NSAID use. Among those taking aspirin, 112 (72%) exhibited volumetric tumor growth during observation compared to 33 (80%) among other NSAID users and 137 (67%) among nonaspirin users. Patients taking aspirin or other NSAIDs were significantly older at time of diagnosis (median, 66 vs 56 years; P < .001). Neither aspirin use (hazard ratio [HR], 0.96; P = .73) nor other NSAID use (HR, 1.39; P = .081) was significantly associated with a reduced risk of volumetric tumor growth. These results were similar following age adjustment ( P = .81 and .087, respectively). When separating aspirin users by 81-mg or 325-mg dosing, neither group exhibited a reduced risk of growth ( P = .95 and .73, respectively). CONCLUSION: Despite promising initial results, the preponderance of existing literature suggests that aspirin and other NSAID use does not prevent tumor growth in VS.

Patient Motivation and Long-Term Satisfaction with Treatment Choice in Vestibular Schwannoma.

OBJECTIVES: To ascertain primary motivation and long-term satisfaction with treatment selection in patients with vestibular schwannoma. METHODS: A multicenter, cross-sectional survey was performed. Patients with small- to medium-sized sporadic vestibular schwannoma who underwent stereotactic radiosurgery (SRS; n = 247), microsurgery (n = 144), or observation (n = 148) between 1998 and 2008 were surveyed regarding their motivation behind treatment selection and hindsight satisfaction with their choice of management. RESULTS: "Physician recommendation" was the most commonly stated reason for modality selection in all 3 groups. The second and third most common reasons for selecting SRS included "less invasive option than surgery" in 80 patients (32%) and "less recovery time than surgery" in 16 patients (6%). The second and third most common reasons for selecting observation included "to avoid side-effects of treatment" in 25 patients (17%) and "symptoms not severe enough to warrant intervention" in 22 patients (15%). The second and third most common reasons for selecting microsurgery included "do not want tumor in head" in 35 patients (24%) and "most definitive treatment" in 15 patients (10%). Overall, 232 patients (96%) treated with SRS, 141 observed patients (97%), and 121 patients (85%) who underwent microsurgical treatment were satisfied with their original decision (P < 0.001). CONCLUSIONS: Motivation behind treatment selection varies between individuals. Those who select observation and SRS commonly reference less invasiveness and lower risk, whereas those who select microsurgery are commonly motivated by having their tumor physically removed and the more definitive nature of treatment. Posttreatment satisfaction is highest in patients who undergo SRS and observation, although all 3 groups report high levels of satisfaction.

Survey of the American Neurotology Society on Cochlear Implantation: Part 1, Candidacy Assessment and Expanding Indications.

OBJECTIVE: To examine practice variance of cochlear implant candidacy assessment and off-label indications across centers in the United States. METHODS: Cross-sectional survey of the American Neurotology Society (ANS). RESULTS: A total of 81 surveys were returned from ANS members who report regular involvement in cochlear implant care. Overall there was a broad distribution in age and clinical experience, with most respondents reporting ACGME accreditation in neurotology and employment at an academic center. The annual volume of cochlear implant surgeries varied considerably across centers.Seventy-eight percent of respondents performed cochlear implantation for at least one of the following indications within the last 2 years: profound hearing loss in children less than 12 months of age (35, 43%), children with asymmetrical hearing loss where at least one ear was better than performance cutoff for age (25, 31%), adults with asymmetrical hearing where at least one ear was better than the performance cutoff for adult criteria (49, 61%), single-sided deafness (37, 46%), and ipsilateral vestibular schwannoma (28, 35%). Centers with a higher annual implant volume more frequently performed off-label implantation in all queried populations (all, p≤0.001), and performed surgery on infants with congenital deafness at a younger age (p = 0.013), compared with centers with lower surgical volume.When surveyed regarding speech perception testing practices for adult candidacy assessment, 75 (100%) respondents who answered this question reported routine use of AzBio sentences, 42 (56%) CNC word scores, and 26 (35%) HINT testing; only 7 (9%) reported using BKB-SIN testing and 6 (8%) reported using CUNY scores. Fifty-one (68%) reported routine use of speech-in-noise testing to determine adult cochlear implant candidacy, 21 (28%) reported selective use only when patient scores were borderline in quiet, and 3 (4%) reported that their center does not currently use testing in noise for candidacy determination. Nineteen (26%) solely used +10 dB signal-to-noise ratio (SNR), 12 (16%) solely used +5 dB SNR, and 41 (55%) used both +10 and +5 dB SNR. Overall, 19% (N = 14) only perform unilateral implantation in the Medicare population, while 81% (N = 58) consider bilateral implantation. CONCLUSION: Significant variation in cochlear implant candidacy assessment and off-label implantation exists across centers and providers in the United States resulting in healthcare inequities. The high percentage of surgeons performing implantations for off-label or nontraditional indications reflects the overly restrictive and dated status of current implant guidelines. With greater adoption of more difficult speech perception testing in noise, careful clinical judgment is needed to maintain a favorable risk-benefit balance for prospective implant candidates.

Quality of Life Within the First 6 Months of Vestibular Schwannoma Diagnosis With Implications for Patient Counseling.

OBJECTIVE: To evaluate quality-of-life (QOL) in patients with sporadic vestibular schwannoma (VS) with particular focus on those recently diagnosed. STUDY DESIGN: Cross-sectional survey, Penn Acoustic Neuroma Quality of Life (PANQOL) instrument. SETTING: Acoustic Neuroma Association and a single tertiary referral center. PATIENTS: Patients with sporadic VS. MAIN OUTCOME MEASURES: Domain-specific and total PANQOL scores comparing treatment modalities after adjusting for baseline covariates of interest. RESULTS: Among all 1,288 respondents there were 229 (18%) who were recently diagnosed and had not yet selected a treatment modality, 303 (24%) who were observed, 185 (14%) who underwent radiosurgery alone, 507 (39%) who underwent microsurgery alone, and 64 (5%) who underwent radiosurgery and microsurgery. After adjusting for covariates of interest, total PANQOL scores were highest for the observation cohort (65; 95% CI 62-68), lowest for patients treated with multimodality therapy (56; 51-61) and those recently diagnosed (58; 55-62), and intermediate for those who received microsurgery alone (60; 58-62) and radiosurgery alone (61; 57-64) (global comparison, p = 0.001). When comparing groups that received single-modality therapy, there were no statistically significant differences in total PANQOL scores at short (0-5 yr), intermediate (6-10 yr), or long-term (≥11 yr) follow-up after adjusting for baseline covariates (all, p > 0.05). CONCLUSION: A new diagnosis of VS frequently imparts significant anxiety on the patient and leads to a temporary reduction in QOL. Notably, anxiety domain QOL scores among patients with newly diagnosed VS are poorer than patients who have observed their tumor for 6 months or longer. When feasible, an initial period of observation may afford patients valuable time to reconcile with the new diagnosis, to learn more about treatment options, and to discover whether there is tumor growth. In turn, this valuable information can be used to inform sound decision-making regarding tumor management.