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Background: Salvage surgery for progressive symptoms or recurrent growth of vestibular schwannoma (VS) after stereotactic radiosurgery (SRS) is uncommon. It has been reported to be more difficult, the same or easier than expected compared with microsurgical resection (MS) of treatment-naive VS, with variable facial nerve outcomes. We conducted a matched cohort analysis to evaluate facial nerve outcomes for patients undergoing MS for progressive symptoms or recurrent growth of VS after SRS compared with MS for treatment-naive VS. Methods: We evaluated the records of 365 non-NF2 VS patients treated with MS from 2001 to 2014. All patients who had postoperative notes were considered to have "adequate follow-up" and included in the study. Nine patients underwent resection for VS after prior SRS (MS-POST SRS) with no prior intervention, 7 of which had adequate follow-up, and 331 patients that underwent MS for treatment naive VS (MS-NO SRS), 317 of which had adequate follow-up. From this dataset, we created propensity score matched cohorts to retrospectively compare facial nerve preservation and clinical outcomes. The propensity score model incorporated age at surgery, tumor size, and pre-operative HB grade, and cases were matched at a ratio of 4:1 MS-NO SRS to MS-POST SRS cases. Results: The MS-POST SRS (n = 7) and MS-NO SRS (n = 28) groups differed only in preoperative hearing status (p < 0.01). Preoperative HB grades were similar between MS-POST SRS and MS-NO SRS groups (p>0.3). The average time-to-intervention after SRS in the MS-POST SRS group was 44.4 months. The indication for MS after SRS was symptom progression with tumor growth in 4 cases, and only tumor growth in the remaining 3. Postoperatively, 3 cases in the MS-POST SRS group demonstrated improvement in HB grade and none became worse whereas 3 of 28 cases in the MS-NO SRS group demonstrated improvement and 12 cases had decrement in HB grade relative to baseline (p < 0.05). There was no significant difference in the extent of resection with both cohorts (MS-POST SRS and MS-NO SRS) attaining gross total resection in 85.7% of cases. Subsequent intervention was not required for any case in the MS-POST SRS group and 2 cases in the MS-NO SRS group, although this difference was not significant. Both cases requiring subsequent intervention in the MS-POST SRS group were gross total resections via the translabyrinthine approach, with subsequent intervention required at 62 and 48 months. There were no significant differences in the complication rate for individual complications or the overall complication rate between cohorts. Conclusions: At a center with high clinical volume, microsurgical resection of VS after prior SRS was associated with good postoperative facial nerve preservation and low morbidity, comparable to those observed in resection of treatment-naive VS. In addition there were similar outcomes in terms of extent of resection between the two groups. The good outcomes reported here may reflect a confluence of factors which include patient selection, the experience of the attending surgeons, the use of more contemporary SRS dosing protocols during initial treatment for these patients, and divergent goals of therapy between cohorts

OBJECTIVE Off-label therapies are widely used in clinical practice by spinal surgeons. Some patients and practitioners have advocated for increased regulation of their use, and payers have increasingly questioned reimbursment for off-label therapies. In this study, the authors applied a model that quantifies publication data to analyze the developmental process from initial on-label use to off-label innovation, using as an example recombinant human bone morphogenetic protein 2 (rhBMP-2) because of its wide off-label use. METHODS As a case study of off-label innovation, the developmental patterns of rhBMP-2 from FDA-approved use for anterior lumbar interbody fusion to several of its off-label uses, including posterolateral lumbar fusion, anterior cervical discectomy and fusion, and posterior lumbar interbody fusion/transforaminal lumbar interbody fusion, were evaluated using the "progressive scholarly acceptance" (PSA) model. In this model, PSA is used as an end point indicating acceptance of a therapy or procedure by the relevant scientific community and is reached when the total number of peer-reviewed studies devoted to refinement or improvement of a therapy surpasses the total number assessing initial efficacy. Report characteristics, including the number of patients studied and study design, were assessed in addition to the time to and pattern of community acceptance, and results compared with previous developmental study findings. Disclosures and reported conflicts of interest for all articles were reviewed, and these data were also used in the analysis. RESULTS Publication data indicated that the acceptance of rhBMP-2 off-label therapies occurred more rapidly and with less evidence than previously studied on-label therapies. Additionally, the community appeared to respond more robustly (by rapidly changing publication patterns) to reports of adverse events than to new questions of efficacy. CONCLUSIONS The development of off-label therapies, including the influence of investigative methods, regulation, and changing perspectives, can be characterized on the basis of publication patterns. The approach and findings in this report could inform future off-label development of therapies and procedures as well as attempts to regulate off-label use.

OBJECTIVE A randomized trial that compares clinical outcomes following microsurgery (MS) or stereotactic radiosurgery (SRS) for patients with small- and medium-sized vestibular schwannomas (VSs) is impractical, but would have important implications for clinical decision making. A matched cohort analysis was conducted to evaluate clinical outcomes in patients treated with MS or SRS. METHODS The records of 399 VS patients who were cared for by 2 neurosurgeons and 1 neurotologist between 2001 and 2014 were evaluated. From this data set, 3 retrospective matched cohorts were created to compare hearing preservation (21 matched pairs), facial nerve preservation (83 matched pairs), intervention-free survival, and complication rates (85 matched pairs) between cases managed with SRS and patients managed with MS. Cases were matched for age at surgery (+/- 10 years) and lesion size (+/- 0.1 cm). To compare hearing outcomes, cases were additionally matched for preoperative Class A hearing according to the American Academy of Otolaryngology-Head and Neck Surgery guidelines. To compare facial nerve (i.e., cranial nerve [CN] VII) outcomes, cases were additionally matched for preoperative House-Brackmann (HB) score. Investigators who were not involved with patient care reviewed the clinical and imaging records. The reported outcomes were as assessed at the time of the last follow-up, unless otherwise stated. RESULTS The preservation of preoperative Class A hearing status was achieved in 14.3% of MS cases compared with 42.9% of SRS cases (OR 4.5; p < 0.05) after an average follow-up interval of 43.7 months and 30.3 months, respectively. Serviceable hearing was preserved in 42.8% of MS cases compared with 85.7% of SRS cases (OR 8.0; p < 0.01). The rates of postoperative CN VII dysfunction were low for both groups, although significantly higher in the MS group (HB III-IV 11% vs 0% for SRS; OR 21.3; p < 0.01) at a median follow-up interval of 35.7 and 19.0 months for MS and SRS, respectively. There was no difference in the need for subsequent intervention (2 MS patients and 2 SRS patients). CONCLUSIONS At this high-volume center, VS resection or radiosurgery for tumors