Faculty Bibliography

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.

OBJECTIVES/HYPOTHESIS: In pediatric patients with congenital malformations of the inner ear, anomalies within the anatomy may facilitate unintentional insertion of the cochlear implant electrode into the internal auditory canal. Revision procedures for removal and replacement of cochlear implant electrodes following internal auditory canal insertion are fraught with potential danger, including the theoretical risk of injury to vasculature within the internal auditory canal, repeat insertion within the internal auditory canal, and cerebrospinal fluid leak. The objective of this presentation is to describe a technique for revision cochlear implantation following internal auditory canal insertion to minimize the potential associated risks. STUDY DESIGN: Case series. METHODS: A retrospective chart review was performed on all patients at a tertiary care facility who underwent revision cochlear implantation for internal auditory canal insertion between January 1999 and July 2011. RESULTS: A total of four patients referred from outside institutions have undergone revision cochlear implantation for internal auditory canal insertion. The records from these patients were reviewed. Electrodes were safely removed in all cases without injury to the anterior inferior cerebellar artery or its branches (i.e., labyrinthine artery). Complete insertion was accomplished on reimplantation. Neural response telemetry was performed in all cases, and responses were noted. Fluoroscopy was utilized to visualize electrode progression during insertion. A detailed description of the operative technique is provided. CONCLUSIONS: This case series describes a technique for revision cochlear implantation that appears to be safe and effective in preventing potential associated complications. Laryngoscope, 2013.