Faculty Bibliography

PURPOSE/OBJECTIVE:Although ongoing studies are assessing the efficacy of new systemic therapies for patients with triple negative breast cancer (TNBC), the overwhelming majority have excluded patients with brain metastases (BM). Therefore, we aim to characterize systemic therapies and outcomes in a cohort of patients with TNBC and BM managed with stereotactic radiosurgery (SRS) and delineate predictors of increased survival. METHODS:We used our prospective patient registry to evaluate data from 2012 to 2023. We included patients who received SRS for TNBC-BM. A competing risk analysis was conducted to assess local and distant control. RESULTS:Forty-three patients with 262 tumors were included. The median overall survival (OS) was 16 months (95% CI 13-19 months). Predictors of increased OS after initial SRS include Breast GPA score > 1 (p < 0.001) and use of immunotherapy such as pembrolizumab (p = 0.011). The median time on immunotherapy was 8 months (IQR 4.4, 11.2). The median time to new CNS lesions after the first SRS treatment was 17 months (95% CI 12-22). The cumulative rate for development of new CNS metastases after initial SRS at 6 months, 1 year, and 2 years was 23%, 40%, and 70%, respectively. Thirty patients (70%) underwent multiple SRS treatments, with a median time of 5 months (95% CI 0.59-9.4 months) for the appearance of new CNS metastases after second SRS treatment. CONCLUSIONS:TNBC patients with BM can achieve longer survival than might have been previously anticipated with median survival now surpassing one year. The use of immunotherapy is associated with increased median OS of 23 months.

UNLABELLED:DNA methylation is an essential molecular assay for central nervous system (CNS) tumor diagnostics. While some fusions define specific brain tumors, others occur across many different diagnoses. We performed a retrospective analysis of 219 primary CNS tumors with whole genome DNA methylation and RNA next-generation sequencing. DNA methylation profiling results were compared with RNAseq detected gene fusions. We detected 105 rare fusions involving 31 driver genes, including 23 fusions previously not implicated in brain tumors. In addition, we identified 6 multi-fusion tumors. Rare fusions and multi-fusion events can impact the diagnostic accuracy of DNA methylation by decreasing confidence in the result, such as BRAF, RAF, or FGFR1 fusions, or result in a complete mismatch, such as NTRK, EWSR1, FGFR, and ALK fusions. IMPLICATIONS/UNASSIGNED:DNA methylation signatures need to be interpreted in the context of pathology and discordant results warrant testing for novel and rare gene fusions.

OBJECTIVE:The focus of this modified Delphi study was to investigate and build consensus regarding the medical management of children with moderate and severe acute spinal cord injury (SCI) during their initial inpatient hospitalization. This impetus for the study was based on the AANS/CNS guidelines for pediatric SCI published in 2013, which indicated that there was no consensus provided in the literature describing the medical management of pediatric patients with SCIs. METHODS:An international, multidisciplinary group of 19 physicians, including pediatric neurosurgeons, orthopedic surgeons, and intensivists, were asked to participate. The authors chose to include both complete and incomplete injuries with traumatic as well as iatrogenic etiologies (e.g., spinal deformity surgery, spinal traction, intradural spinal surgery, etc.) due to the overall low incidence of pediatric SCI, potentially similar pathophysiology, and scarce literature exploring whether different etiologies of SCI should be managed differently. An initial survey of current practices was administered, and based on the responses, a follow-up survey of potential consensus statements was distributed. Consensus was defined as ≥ 80% of participants reaching agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree). A final meeting was held virtually to generate final consensus statements. RESULTS:Following the final Delphi round, 35 statements reached consensus after modification and consolidation of previous statements. Statements were categorized into the following eight sections: inpatient care unit, spinal immobilization, pharmacological management, cardiopulmonary management, venous thromboembolism prophylaxis, genitourinary management, gastrointestinal/nutritional management, and pressure ulcer prophylaxis. All participants stated that they would be willing or somewhat willing to change their practices based on consensus guidelines. CONCLUSIONS:General management strategies were similar for both iatrogenic (e.g., spinal deformity, traction, etc.) and traumatic SCIs. Steroids were recommended only for injury after intradural surgery, not after acute traumatic or iatrogenic extradural surgery. Consensus was reached that mean arterial pressure ranges are preferred for blood pressure targets following SCI, with goals between 80 and 90 mm Hg for children at least 6 years of age. Further multicenter study of steroid use following acute neuromonitoring changes was recommended.

OBJECTIVE:Cervical spine disorders in children are relatively uncommon; therefore, paradigms for surgical and nonsurgical clinical management are not well established. The purpose of this study was to bring together an international, multidisciplinary group of pediatric cervical spine experts to build consensus via a modified Delphi approach regarding the clinical management of children with cervical spine disorders and those undergoing cervical spine stabilization surgery. METHODS:A modified Delphi method was used to identify consensus statements for the management of children with cervical spine disorders requiring stabilization. A survey of current practices, supplemented by a literature review, was electronically distributed to 17 neurosurgeons and orthopedic surgeons experienced with the clinical management of pediatric cervical spine disorders. Subsequently, 52 summary statements were formulated and distributed to the group. Statements that reached near consensus or that were of particular interest were then discussed during an in-person meeting to attain further consensus. Consensus was defined as ≥ 80% agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree). RESULTS:Forty-five consensus-driven statements were identified, with all participants willing to incorporate them into their practice. For children with cervical spine disorders and/or stabilization, consensus statements were divided into the following categories: A) preoperative planning (12 statements); B) radiographic thresholds of instability (4); C) intraoperative/perioperative management (15); D) postoperative care (11); and E) nonoperative management (3). Several important statements reaching consensus included the following recommendations: 1) to obtain pre-positioning baseline signals with intraoperative neuromonitoring; 2) to use rigid instrumentation when technically feasible; 3) to provide postoperative external immobilization for 6-12 weeks with a rigid cervical collar rather than halo vest immobilization; and 4) to continue clinical postoperative follow-up at least until anatomical cervical spine maturity was reached. In addition, preoperative radiographic thresholds for instability that reached consensus included the following: 1) translational motion ≥ 5 mm at C1-2 (excluding patients with Down syndrome) or ≥ 4 mm in the subaxial spine; 2) dynamic angulation in the subaxial spine ≥ 10°; and 3) abnormal motion and T2 signal change on MRI seen at the same level. CONCLUSIONS:In this study, the authors have demonstrated that a multidisciplinary, international group of pediatric cervical spine experts was able to reach consensus on 45 statements regarding the management of pediatric cervical spine disorders and stabilization. Further study is required to determine if implementation of these practices can lead to reduced complications and improved outcomes for children.

BACKGROUND/UNASSIGNED:Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis. METHODS/UNASSIGNED:We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility. RESULTS/UNASSIGNED:Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases. CONCLUSIONS/UNASSIGNED:DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.

Diffuse spinal cord gliomas (SCGs) are rare tumors associated with a high morbidity and mortality that affect both pediatric and adult populations. In this retrospective study, we sought to characterize the clinical, pathological, and molecular features of diffuse SCG in 22 patients with histological and molecular analyses. The median age of our cohort was 23.64 years (range 1-82) and the overall median survival was 397 days. K27M mutation was significantly more prevalent in males compared to females. Gross total resection and chemotherapy were associated with improved survival, compared to biopsy and no chemotherapy. While there was no association between tumor grade, K27M status (p = 0.366) or radiation (p = 0.772), and survival, males showed a trend toward shorter survival. K27M mutant tumors showed increased chromosomal instability and a distinct DNA methylation signature.

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.

Laminectomy can be accomplished using the craniotome with a footplate attachment, and the technique has been advanced as a superior alternative to using a high-speed drill-driven burr and Kerrison rongeurs. Laminectomy can be accomplished more rapidly and with less bone destruction, an advantage when planning laminoplasty. There is, however, scant literature describing complications of dural laceration using this technique. A 48-year-old male underwent T7-10 laminectomy for resection of an intramedullary spinal cord tumor. During the upward cut of the hemi-lamina at T7-9, a dural laceration occurred that proved not amenable to direct suture closure. The dural was closed with a dural patch placed along the inner surface of the dura and a fat graft on the outer surface with adjunctive use of a lumbar drain. While the footplate laminectomy technique has merits touted in prior publications, including the ability to open the spinal canal quickly at numerous levels and an enhanced ability to achieve an osteoplastic laminoplasty, surgeons should be cognizant of the risk of associated dural laceration. We believe that it is important to emphasize that the initial placement of the lip of the footplate must be well-seated under the inferior aspect of the lowest lamina and over the ligamentum flavum and that the footplate should not be directed beyond the border of the laminae and facet, as this can result in dura and root injury.