Faculty Bibliography

BACKGROUND:Late pathology after vestibular schwannoma radiosurgery is uncommon. The authors presented a case of a resected hemorrhagic mass 13 years after radiosurgery, when no residual tumor was found. OBSERVATIONS/METHODS:A 56-year-old man with multiple comorbidities, including myelodysplastic syndrome cirrhosis, received Gamma Knife surgery for a left vestibular schwannoma. After 11 years of stable imaging assessments, the lesion showed gradual growth until a syncopal event occurred 2 years later, accompanied by progressive facial weakness and evidence of intralesional hemorrhage, which led to resection. However, histopathological analysis of the resected specimen showed hemorrhage and reactive tissue but no definitive residual tumor. LESSONS/CONCLUSIONS:This case demonstrated histopathological evidence for the role of radiosurgery in complete elimination of tumor tissue. Radiosurgery for vestibular schwannoma carries a rare risk for intralesional hemorrhage in select patients.

BACKGROUND/UNASSIGNED:Hyperglycemia has been associated with worse survival in glioblastoma. Attempts to lower glucose yielded mixed responses which could be due to molecularly distinct GBM subclasses. METHODS/UNASSIGNED:Clinical, laboratory, and molecular data on 89 IDH-wt GBMs profiled by clinical next-generation sequencing and treated with Stupp protocol were reviewed. IDH-wt GBMs were sub-classified into RTK I (Proneural), RTK II (Classical) and Mesenchymal subtypes using whole-genome DNA methylation. Average glucose was calculated by time-weighting glucose measurements between diagnosis and last follow-up. RESULTS/UNASSIGNED:= .02). Methylation clustering did not identify unique signatures associated with high or low glucose levels. Metabolomic analysis of 23 tumors showed minimal variation across metabolites without differences between molecular subclasses. CONCLUSION/UNASSIGNED:Higher average glucose values were associated with poorer OS in RTKI and Mesenchymal IDH-wt GBM, but not RTKII. There were no discernible epigenetic or metabolomic differences between tumors in different glucose environments, suggesting a potential survival benefit to lowering systemic glucose in selected molecular subtypes.

OBJECTIVE:Patients with non-small cell lung cancer (NSCLC) metastatic to the brain are living longer. The risk of new brain metastases when these patients stop systemic therapy is unknown. The authors hypothesized that the risk of new brain metastases remains constant for as long as patients are off systemic therapy. METHODS:A prospectively collected registry of patients undergoing radiosurgery for brain metastases was analyzed. Of 606 patients with NSCLC, 63 met the inclusion criteria of discontinuing systemic therapy for at least 90 days and undergoing active surveillance. The risk factors for the development of new tumors were determined using Cox proportional hazards and recurrent events models. RESULTS:The median duration to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase (RTK) pathways (e.g., KRAS, EGFR) were more likely to develop new tumors (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33-3.81, p = 2.5 × 10-3; HR 2.51, 95% CI 1.45-4.34, p = 9.8 × 10-4, respectively). CONCLUSIONS:The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or RTK pathway mutations have a higher rate of new metastases and should be followed more closely.

PURPOSE:), whereas no molecularly based stratification exists for the broad spectrum of patients with low- and intermediate-risk meningioma. METHODS:DNA methylation data and copy-number information were generated for 3,031 meningiomas (2,868 patients), and mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNVs), mutations, and WHO grading were analyzed. Prediction power for outcome was assessed in a retrospective cohort of 514 patients, validated on a retrospective cohort of 184, and on a prospective cohort of 287 multicenter cases. RESULTS:= .005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (hazard ratio 4.34 [2.48-7.57] and 3.34 [1.28-8.72] retrospective and prospective validation cohorts, respectively). CONCLUSION:Merging these layers of histologic and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision making for patients with meningioma on the basis of robust outcome prediction.

OBJECTIVE:Miscommunication and poor coordination among surgical teams are known causes of preventable medical harms and operating room inefficiencies and inhibit surgical training. Technology may help overcome these challenges. This study used the personal experience of one of the authors as a former Air Force F-15 pilot to design a combat aviation pre- and postoperative communication workflow in the neurosurgery department and tested its effect on safety, efficiency, and education. The authors hypothesized that the adoption of this workflow through a tailored technological platform will increase compliance and improve the chances of sustainability. METHODS:Data were prospectively collected from neurosurgery cases before (January-May 2020) and after (June-October 2020) implementation of this workflow. Briefing and debriefing were executed using a custom mobile platform and were defined as nonmandatory for all participants. All faculty and residents who operated at NYU Langone Medical Center (Tisch campus) during the intervention period were enrolled on the platform. Primary outcomes were morbidity and mortality per the department's criteria, and intraoperative last-minute requests as reported by operating room staff in a double-blinded fashion. Secondary outcomes were user responses on the subjective questionnaires. RESULTS:Data were collected from 637 and 893 cases during the preintervention and intervention periods, respectively. The average briefing rates for residents and surgeons were 71% and 81%, respectively, and the average debriefing rates for residents and surgeons were 67% and 88%. There was no significant difference in preoperative risk score between the preintervention and intervention patient populations (p = 0.24). The rate of intraoperative last-minute requests significantly decreased from 16.6% (35/211) to 10.5% (35/334, p = 0.048). There was no significant change in morbidity and mortality between the preintervention and intervention periods. On subjective questionnaires there was a statistically significant improvement in safety, efficiency, and educational aspects of the cases during the intervention period. CONCLUSIONS:Implementation of aviation-like structured team communication practices in the neurosurgery department through a technological platform improved education and communication between surgical teams and led to a reduction in last-minute surgical requests that could impact costs.

OBJECTIVE:To evaluate outcomes following salvage microsurgery (MS) and salvage stereotactic radiosurgery (SRS) after failure of primary treatment for vestibular schwannomas (VS). STUDY DESIGN/METHODS:Retrospective chart review. SETTING/METHODS:Tertiary referral center. METHODS:Patients with more than 1 intervention for their VS were divided into 4 groups: MS followed by SRS (n = 61), MS followed by MS (n = 9), SRS followed by MS (n = 7), and SRS followed by SRS (n = 7), and outcomes were evaluated. RESULTS:A total of 77 patients were included (84 procedures). In group 1 (MS then SRS), 3% developed a decline in facial function, 3% developed trigeminal sensory loss, and 13% patients had gradual improvement of facial nerve function following SRS. Group 2 (MS then MS) had the highest rates of facial nerve deterioration, although all but 1 patient achieved a House-Brackmann score of II or III. Gross-total resection (GTR) was achieved in 56% of patients. When a different approach was used for salvage resection, GTR occurred more commonly, and facial nerve outcomes were similar. In group 3 (SRS then MS), GTR occurred in 43% of cases, and 2 of 7 patients developed worsened facial function. In group 4 (SRS then SRS), no patient developed facial weakness after reirradiation, and 1 developed a trigeminal nerve deficit. CONCLUSIONS:For MS recurrences/residuals, SRS is the mainstay of treatment and does not preclude facial function recovery. If salvage microsurgery is required, an alternate approach should be considered. For SRS failures, when MS is required, less-than GTR may be preferable, and reirradiation is a potential safe alternative.

Inhibition of mTORC1 signaling has been shown to diminish growth of meningiomas and schwannomas in preclinical studies, and clinical data suggest that everolimus, an orally administered mTORC1 inhibitor, may slow tumor progression in a subset of NF2 patients with vestibular schwannoma (VS). To assess the pharmacokinetics, pharmacodynamics and potential mechanisms of treatment resistance, we performed a pre-surgical (phase 0) clinical trial of everolimus in patients undergoing elective surgery for VS or meningiomas. Eligible patients with meningioma or VS requiring tumor resection enrolled on study received everolimus 10 mg daily for 10 days immediately prior to surgery. Everolimus blood levels were determined immediately prior to and after surgery. Tumor samples were collected intraoperatively. Ten patients completed protocol therapy. Median pre- and post-operative blood levels of everolimus were found to be in a high therapeutic range (17.4 ng/ml and 9.4 ng/ml, respectively). Median tumor tissue drug concentration determined by mass spectrometry was 24.3 pg/mg (range 9.2-169.2). We observed only partial inhibition of phospho-S6 in the treated tumors, indicating incomplete target inhibition compared to control tissues from untreated patients (p=0.025). Everolimus led to incomplete inhibition of mTORC1 and downstream signaling. These data may explain the limited anti-tumor effect of everolimus observed in clinical studies for NF2 patients and will inform the design of future pre-clinical and clinical studies targeting mTORC1 in meningiomas and schwannomas.