I n Spring 2020, New York City (NYC) rapidly became an epicenter of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) global pandemic, with a reported 200,547 cases between March 8 and May 31, 2020. 1 Over one fifth of hospitalized patients in NYC were critically ill, many on mechanical ventilation with multi-organ failure requiring prolonged sedation. 2 The neurology consultation service quickly became an integral part of the care for the many critically ill patients with COVID-19 with impaired consciousness. The mechanism of these disorders of consciousness in patients infected by COVID-19 is poorly understood and may be due to multi-organ failure, hypoxia, systemic inflammation, hypercoagulability, and possible neuro-invasion. 3 Uncertainty about the trajectory of this novel disease as well as concerns for health care worker safety created challenges in relying on standard behavioral, electrophysiological, imaging, and laboratory data that guides diagnostic workup and prognostication in patients with disorders of consciousness. To provide a comprehensive weighing of the rapidly evolving body of evidence in an area of great uncertainty, we instituted a multidisciplinary COVID-19 Coma Board modeled after the tumor board concept. 4 This biweekly, secure web-based multidisciplinary conference first met on May 13, 2020, with participants representing neurocritical care, epilepsy, stroke, neuroradiology, neurovascular, neurohospitalist, neuroinfectious disease, rehabilitation medicine, and pharmacology. Data was presented by the consult team using a standardized data collection format (Table). This study was approved by the institutional review board at Columbia University Irving Medical Center. The requirement for written informed consent was waived because the observational study design involves no more than minimal risk. In our first 8 case discussions, 5 patients were above 60 years old (53%), 3 were women (38%), 4 had episodes of hypoxia (defined as at least one documented arterial blood gas with a PO2 below 55 mmHg), 1 suffered cardiopulmonary arrest, and

ed to support enhanced digital visualizations for training and surgical planning using mixed reality (MR), virtual reality (VR), and augmented reality (AR). These extended reality technologies have been safely used to explore the operative field from different viewpoints, visualizing the neurovascular anatomy hidden from the surgical field, thereby offering an enhanced comprehensive sensory experience, especially in keyhole approaches to deep-lying targets. 1,2 Together with the fusion of additional imaging data such as indocyanine green (ICG), 5-aminolevulinic acid (5-ALA), or fluorescein angiography, MR has increased the precision in neurosurgical procedures. With work hour limitations and erstwhile COVID-19 restrictions, these technological advances also offer exemplary training and practicing tools for both novices and experts alike, resulting in their recent exponential growth. In addition, MR can be utilized for telecasting, patient education, and long-distance telecollaboration, and it can help bridge the global educational gap in the field of neurosurgery, including the scope of credentialing and recertifications. [3][4][5][6] Virtual RealityBased on the level of immersion, VR can be classified into non-immersive, semi-immersive, and fully immersive VR. With non-immersive VR, the virtual environment is viewed through a window on a standard monitor. Keyboard, mouse, or enhanced 3D interaction devices are used to interact with non-immersive VR. Semi-immersive VR combines high-performing graphics with a large screen projector, or multiple display projections, to widen the field of view and provide the user with an enhanced

TPS9603 Background: While anti-PD-1 and anti-CTLA4 immunotherapies are widely used in the treatment of metastatic melanoma, including melanoma brain metastases (MBM), their efficacy in patients with symptomatic MBM is very limited. In the Checkmate-204 trial of ipilimumab with nivolumab in MBM, the 6-month progression free survival (PFS) rate was 19% with a median PFS of only 1.2 months in symptomatic participants (those with neurological symptoms including steroids up to 4 mg/day of dexamethasone, n=18). (Tawbi, Lancet et al., 2021) In the COMBI-MB study of BRAF/MEK-inhibitors in BRAF-V600 mutant MBM, median PFS was 5.5 months in those with symptomatic metastases (n=17). (Davies et al., Lancet Oncol, 2017) The combination of anti-PD-1/PD-L1 therapy with BRAF/MEK inhibitors has been tested in various trials. The single-arm phase 2 TRICOTEL study explored the triplet regimen of vemurafenib + cobimetinib + atezolizumab in MBM; in the symptomatic brain met cohort, 6-month PFS was 57% (n=24). (Dummer et al., Lancet Oncol 2022). Methods: SWOG S2000 is a randomized phase 2 trial exploring the efficacy of a triplet regimen of BRAF/MEK inhibitors with PD-1 therapy (encorafenib 450 mg qday + binimetinib 30 mg BID + nivolumab 480 mg IV q4 weeks) versus ipilimumab 3 mg/kg + nivolumab 1 mg/kg q3 weeks in patients with symptomatic BRAF-mutant MBM. (The study was amended to exclude patients with asymptomatic MBM.) Eligible patients are ≥18 years old, ECOG 0-2, and prior neoadjuvant or adjuvant anti-PD-1, CTLA-4, or BRAF/MEK-inhibitors is permitted. Steroids up to 8 mg of dexamethasone/day (or equivalent), leptomeningeal spread, and prior local therapy (radiation or surgery) for brain mets are permitted, if a patient has at least one measurable, progressing brain met ≥0.5 cm in size. Primary objective is to compare PFS per (RECIST 1.1) between the two study arms. Secondary objectives include overall survival, toxicity profile, objective tumor response, intracranial response and duration per modified RECIST 1.1, modified RANO-BM, and iRANO criteria, and evaluation of radiographic response criteria by centralized review of banked images. This study is powered to detect an increase in estimated 6-month PFS from 20% to 52% with 80% power and type I error rate of 10%, with 24 eligible patients required. Total sample size is 28 to account for ineligible patients. Available blood, tissue, CSF and stool samples are banked for future correlative studies. The study is currently enrolling patients through SWOG, ECOG and NRG centers. Funding: NIH/NCI grants U10CA180888, U10CA180819, U10CA180820 U10CA180868; and in part by Pfizer, Inc. Clinical trial information: NCT04511013 .