The NOB has made substantial progress towards building an infrastructure necessary for fulfilling its mission of developing new and improved therapies for children and adults with brain and spinal cord tumors. Since Dr. Gilbert's arrival at the NIH in November 2014, he has rebuilt the Brain Tumor Clinical and Clinical Research Program: a highly collaborative, robust translational research program centered on finding treatments for brain and other central nervous system tumors. In addition to conducting basic and translational research, the NOB has become a nationally recognized resource for patient information and referrals for second opinions. In addition to seeing and treating brain tumor patients, Dr. Gilbert currently runs a significant number of national clinical trials and helps organize and administrate over several large national Neuro Oncology translational science initiatives. Importantly, Dr. Gilbert led RTOG 0825 which evaluated the role of the antiangiogenic agent, bevacizumab, in patients with newly diagnosed glioblastoma in a double blind placebo controlled randomized phase III trial. This study accrued 973 patients and successfully incorporated upfront stratification by two molecular parameters, as there was 100% compliance with tumor tissue submission. This study, which did not demonstrate a survival benefit for bevacizumab, demonstrated neurocognitive decline and worsened symptom burden and quality of life in the patients treated with bevacizumab. This study was presented at the Plenary Session at ASCO and published in the New England Journal of Medicine. These efforts have led to his leadership of NRGBN002, a clinical trial that is testing the safety of adding the immune checkpoint inhibitors, ipilimumab (anti CTLA 4) and nivolumab (anti PD 1) in patients with newly diagnosed glioblastoma. This is the prelude to an NOB study that will help determine whether these immune checkpoint inhibitors have efficacy in glioblastoma by determining if patients who demonstrate a peripheral immune response have improved survival outcomes. A critical component of the trial will be the immunologic monitoring which will comprise testing of tumor tissue for mediators of immune reactivity and serial monitoring of peripheral blood mononuclear cells as an indicator of the impact of treatment on "immune competence". Dr. Gilbert has also transitioned the Brain Tumor Trials Collaborative (BTTC) from M. D. Anderson Cancer Center. This is a national consortium that was founded on philanthropic support. The mission of the BTTC is to rapidly develop and complete innovative clinical trials for patients with primary brain tumors. To date, the BTTC has completed a study that used a factorial design (8 treatment arms were evaluated simultaneously) and a trial that used an adaptive randomized design (patient allocation based on treatment efficacy using patient by patient rebalancing). This effort is currently being transferred from the M. D. Anderson Cancer Center to the NCI. There are currently 3 active studies and once relaunched, and addition study concepts are anticipated. The list of participating sites is provided below: Aurora Advanced Healthcare, National Institutes of Health, Baylor University, Northwestern University, Feinberg School of Medicine, Case Western Reserve SOM, Ohio State University, Cedar Sinai Medical Center, Rush University Cancer Center, Cleveland Clinic, Texas Oncology, Columbia University, The Methodist Hospital, Dana Farber Cancer Institute, University of North Carolina, Henry Ford Health System, University of Kansas, Medical University of South Carolina, University of Utah, Orlando Health, University of Washington, Mayo Clinic, UT M. D. Anderson Cancer Center, Northshore University Health System, UT Southwestern Medical Center at Dallas. The NOB has created a vibrant, robust and clinically busy center for neuro oncology excellence that serves as a national resource for patients with CNS malignancies (regardless of their ability to pay), for information, consultation, clinical trials or referrals to their local centers of excellence for clinical care and NCI sponsored trials. This was an important accomplishment because: Part of the mission of the NCI is to provide expertise to patients and physicians for a lethal tumor type not frequently seen in the community and for whom standard treatment options are limited. A busy and robust clinical program ensures a steady flow of patients with primary CNS tumors imperative for stimulating clinical and translational research by ensuring rapid patient accrual to clinical trials, efficient acquisition of tissue for basic and translational research, and for enticing pharmaceutical biotechnology companies to co develop novel CNS tumor agents with the NOB and the NCI at large. A multi disciplinary tumor board convenes weekly and is attended by neuro oncologists, radiation oncologists, neurosurgeons, neuropathologists and laboratory investigators. Three of four weeks, this meeting is virtual and open to colleagues from the BTTC network. Complex and challenging patients are presented and discussed, optimizing individual patientcare and leading to many collaborative interactions and research projects. This Tumor Board is complemented by a biweekly pathology review where NIH neuropathologists prepare specimens from active clinical patients that are examined microscopically and morphologic and genetic features are discussed in conjunction with members of the Brain Tumor Clinical Team. Additionally, a Molecular Tumor Board has been incorporated into the Pathology Review that reviews all of the available molecular information from individual patient's tumors so that therapies can be considered in the context of this information. Below are partial lists of accomplishments in the building of an NIH wide multidisciplinary Brain Tumor Clinic with active participation from three different NCI Branches (ROB, MOCRU, CCRLP), five different NIH Institutions (NCI, NINDS, NEI, NHLBI, NIMH), and six different Clinical Center Programs (Neuroradiology, Psychiatry, Pain and Palliation, Rehabilitation Medicine, Social Work). Expertise represented in the clinic includes Medical Oncology, Radiation Oncology, Neurosurgery, Neurology, Ophthalmology, Cardiology, Psychiatry, Endocrinology, Social Work, and Rehabilitation Medicine; Assembled a primary neuro oncology clinical care research team. Additionally, the NOB provides neuro oncology services for Walter Reed Medical Center, in Bethesda; established close collaborative clinical programs with Johns Hopkins Medical Center, George Washington Medical Center, Fairfax Inova and Washington Hospital Center and a wide array of private neurosurgical, radiation, and oncology practice groups locally and nationally; created a neuro oncology fellowship training program between the NIH and the Johns Hopkins Medical Center. Since the Brain Tumor Clinical and Clinical Research Program reinitiated in 2015, the NOB has launched 20 clinical trials, including 2 new established (IRB001534: PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications and 000860: Study of Zotiraciclib for Recurrent High Grade Gliomas With Isocitrate Dehydrogenase 1 or 2 (IDH1 or IDH2) Mutations)