Faculty Bibliography

PURPOSE OF REVIEW: To summarize the recent medical literature related to the feasibility of hearing preservation after cochlear implantation and to identify variables that may influence hearing preservation in the implanted ear as well as the hearing perception outcomes. RECENT FINDINGS: The published data provide evidence that hearing preservation in the implanted ear yields significantly higher levels of speech recognition in complex listening environments than having just monaural acoustic hearing. There is ample evidence that hearing preservation is feasible and the reported rate is 50-89% in the low frequencies. This rate tends to be stable over time, except for a small percentage that diminishes around 3 months of follow-up. However, factors or variables which influence hearing preservation are yet unknown. Variables such as patient age, degree of residual hearing, insertion depth, insertion speed, duration of profound high frequency deafness and electrode design have been proposed. SUMMARY: Much attention has been focused on hearing preservation in the implanted ear. Thus, investigations into electrode array design, surgical technique and pharmacological management have been undertaken. Minimizing damage in the inner ear not only enhances the possibility for hearing preservation and better performance in complex listening scenarios but also conserves inner ear structures for future treatments.

Background Activation of the mammalian target of rapamycin (mTOR) signaling pathway is thought to be a key driver of tumor growth in Merlin (NF2)-deficient tumors. Everolimus is an oral inhibitor of mTOR complex 1 (mTORC1) with antitumor activity in a variety of cancers. Methods We conducted a single-institution, prospective, 2-stage, open-label phase II study to estimate the response rate to everolimus in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannoma (VS). Ten eligible patients were enrolled, including 2 pediatric patients. Everolimus was administered at a daily dose of 10 mg (adults) or 5 mg/m(2)/day (children <18 y) orally in continuous 28-day courses, for up to 12 courses. Response was assessed every 3 months with MRI, using 3-dimensional volumetric tumor analysis, and audiograms. Nine patients were evaluable for the primary response, defined as >/=15% decrease in VS volume. Hearing response was evaluable as a secondary endpoint in 8 patients. Results None of the 9 patients with evaluable disease experienced a clinical or MRI response. No objective imaging or hearing responses were observed in stage 1 of the trial, and the study was closed according to predefined stopping rules. Conclusion Everolimus is ineffective for the treatment of progressive VS in NF2 patients. We are currently conducting a pharmacokinetic/pharmacodynamic ("phase 0") study of everolimus in presurgical VS patients to elucidate the biological basis for apparent treatment resistance to mTORC1 inhibition in these tumors.