UCSF Neurological Surgery 2019 Annual Report Contents 3 Brain Tumor Center Department of Neurological Surgery 20 California Center for University of California, Pituitary Disorders San Francisco 505 Parnassus Ave 22 Brain and Spinal Injury Center Room M779 Dear Colleague: San Francisco, CA 25 Neurospinal Disorders 94143-0112 Phone: (415) 353-7500 I am thrilled to be sharing some of the clinical and research highlights from 28 Vascular Neurosurgery Fax: (415) 353-2889 our Department in 2019. From a new blood test for concussion to the first neurosurgery.ucsf.edu demonstration of synthetic speech, there are fascinating stories from every 31 Pain and Peripheral Nerve subspecialty of neurosurgery. Disorders UCSF has also again been ranked in the top three neurosurgery and © The Regents of the University neurology programs in the nation – and best on the West Coast – by U.S. 32 Movement Disorders of California News & World Report’s 2019-20 survey of Best Hospitals, reflecting the Executive Editor: Ilona Garner outstanding dedication of our faculty and staff. 36 Pediatric Neurosurgery Writer: Andrew Schwartz UCSF adult and pediatric neurosurgery clinics are available in Marin, Napa and Oakland to provide easy coordination with local physicians and convenient Illustration: Kenneth Xavier Probst 40 Epilepsy access for patients in those areas. Our spine specialists are also available to Design: Victoria Maier Magbilang, see patients at the new Berkeley Outpatient Center – a collaboration between Aqua Design Studio UCSF and John Muir Health. 44 Center for Neural Engineering and Prostheses As always, thank you for allowing us to partner with you in the care of your patients. 46 Community Extension Mitchel S. Berger, MD Professor and Chair Department of Neurological Surgery Berthold and Belle N. Guggenhime Endowed Chair Director, Brain Tumor Center Brain Tumor Center Steady Success in Identifying Genetic Drivers of Brain Tumors Neuropathologist and molecular says Solomon, whose research ensuring the most accurate diagnosis fundamental mechanisms by which neuro-oncologist David Solomon, laboratory investigates the molecular while also identifying potentially cancer develops and escapes MD, PhD, is UCSF Health’s director pathogenesis of human brain tumors. targetable mutations in the tumor standard treatment regimens, which of Molecular Neuropathology, Solomon points out that the and uncovering any type of germ-line will allow us to come up with new responsible for all genomic testing UCSF500 next-generation mutation associated with increased and better therapies,” says Solomon. performed on brain and spinal cord cancer risk. sequencing panel, which he oversees Solomon’s dedication to classifying tumors at UCSF Medical Center. His and which is one of the world’s At the same time, the research and deciphering the molecular basis efforts have been instrumental in leading targeted panels for brain continues on multiple fronts. of the many distinct brain tumor facilitating a molecularly integrated tumor diagnosis and therapy, has led Solomon’s lab recently published an entities – including in the last year diagnostic scheme and enabling a to multiple precision medicine trials. article in Nature Communications chordoid glioma, ganglioglioma, spinal precision medicine approach for the that explains how the STAG2 gene cord diffuse gliomas and radiation- treatment of neuro-oncology patients. In one of these trials, clinicians analyze resected tumors using the – which is commonly mutated in induced gliomas – has led to his being “We hope that if we can determine UCSF500 panel, and a molecular several human cancer types – plays part of the scientific team working to the genetic alterations that are tumor board will decide upon an essential role in DNA replication, update the World Health Organization responsible for driving the different the best personalized targeted thus revealing new potential (WHO)’s Classification of Tumors of brain tumor types – as well as the therapies, with a particular focus on mechanisms for therapeutically the Central Nervous System. cellular pathways that these genetic combination therapies. targeting those glioblastomas alterations deregulate to fuel tumor harboring STAG2 mutations. In fact, today the UCSF500 panel is development – we can intervene with “This work not only helps individual highly specific targeted therapies,” now used to study the vast majority of brain tumors resected at UCSF, patients, but it also builds our knowledge base about the STAG2 is one of the most commonly mutated genes in (left to right) glioblastoma, bladder cancer, and Ewing sarcoma. Mondal G, Stevers M, Goode B, creates a targetable synthetic lethality in Ashworth A, Solomon DA. A requirement cohesin-mutant cancers. Nat Commun. for STAG2 in replication fork progression 2019;10(1):1686. 3 Precision Medicine Trial Offers Individualized Therapy Based on Tumor Genetics In 2019, UCSF neuro-oncologist Repurposing existing drugs is one While the team is using the Jennifer Clarke, MD, initiated a pilot way to more quickly offer alternative Clinical Laboratory Improvement precision medicine trial for adult therapies to patients with life-limiting Amendments (CLIA)-approved patients with recurrent glioblastoma. illness who may not be eligible for UCSF500 next-generation In the trial, 15 eligible participants other clinical trials. A previous pilot sequencing panel to create the undergo surgery as part of their study in 2014, run through the Ivy profile and determine treatment, standard of care, with tumor tissue Foundation Early Phase Clinical when adequate tissue is collected for sequencing aimed Trials Consortium, demonstrated available, patients’ tumors will at determining each tumor’s gene the feasibility of making the also undergo whole-genome expression profile. A multidisciplinary recommendation in a timely fashion and RNA sequencing to assess genomic tumor board reviews the but did not provide the actual drugs whether this would change profile and looks for FDA-approved for treatment. treatment recommendations. In drugs to determine any that may “With this new trial, we are addition, patients’ tumor cells will target the abnormalities found in the excited to actually implement be cultured and inoculated into patient’s tumors, such as overactive the individualized treatments, to organoids to generate patient- tyrosine kinases or growth factors. start to assess the efficacy of this specific models for further testing. The tumor board then recommends approach,” says Clarke. an individualized regimen of up to four FDA-approved drugs. 4 Robust Clinical Trials Program Continues Its Growth The world-renowned clinical trials program at the UCSF Brain Tumor Center more accurate characterization of tumor burden and response to treatment. continues to grow, offering an increasing array of promising treatment options Such projects keep UCSF at the forefront of advancing understanding of how for nearly any brain tumor patient, at any point in their cancer journey. to effectively treat and eventually cure brain cancers. “Our trials cover the spectrum,” says Susan Chang, MD, director of the “The synergy and collaborations among our basic scientists and clinicians Division of Neuro-Oncology. “We have options for newly diagnosed or help us accelerate the development of exciting new treatments for our recurrent tumors, low-grade or high-grade tumors, as well as window-of- patients,” says Chang. opportunity studies when a promising treatment modality becomes available.” Among the most exciting: The center’s innovative approaches to forging connections between its • UCSF is one of only a few institutions offering a clinical trial of personalized clinical trials and basic research has helped it secure game-changing grants, treatment vaccines for low-grade glioma in adults, as well as pediatric gliomas including a P01 Program Project grant from the NIH that was renewed like diffuse instrinsic pontine glioma (DIPG), as noted below. in 2019. “Noninvasive Metabolic Signatures to Improve Management of Molecular Subtypes of Glioma” consists of four integrated and synergistic • The clinical trials program offers a number of immunotherapies that involve projects and two cores, with the overall goal of identifying metabolic engineered viruses or DNA plasmids, including oncolytic virus therapies. One signatures associated with subgroups of glioma defined by various molecular of these oncolytic virus trials is testing a modified poliovirus directed against characteristics. The plan is to integrate these signatures with multiparameter recurrent glioblastoma. Other trials are assessing treatments for glioma, DIPG, imaging strategies that assess spatial and temporal changes in individual medulloblastoma and atypical teratoid/rhabdoid tumor (AT/RT) in children. patients during the course of their disease. The hope is that this will provide a • There are several ongoing clinical trials investigating the use of immune checkpoint inhibitors, either alone or in combination with other therapies like radiation. “The synergy and collaborations among our basic scientists and clinicians help us accelerate the development of exciting new treatments for our patients.” - Susan Chang, MD 5 6 UCSF Researchers Awarded Competitive Grant to Fund Immunotherapy Studies This year, Brain Tumor Center researchers Joseph Costello, PhD; Hideho found using single-sample analysis and, the researchers hope, will facilitate Okada, MD, PhD; and Aaron Diaz, PhD, were awarded Brain Tumor Funders’