Abstract Details

Title Detection of Neoplasms by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid

Topic Neuro-oncology

Presentation(s) S27 - Innovations in Neuro-oncology (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Background CSF cytologic testing and flow cytometry are insensitive for detecting malignant neoplasms of the CNS. Can CSF mNGS, a test designed to diagnose neurological infections, also detect genetic signatures of cancer in patients with presentations suggestive of neuroinflammatory disease?

Objective To ascertain whether cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) can identify aneuploidy, a hallmark of malignant neoplasms, even in difficult-to-diagnose cases of central nervous system (CNS) malignant neoplasm where CSF cytologic testing and flow cytometry are unrevealing.

Design/Methods

Two case-control studies were performed at the University of California, San Francisco (UCSF). The first ‘test performance’ study used 125 CSF specimens collected at the UCSF Clinical Laboratories over two years. The specimens were from 47 patients with a CNS malignant neoplasm and 56 patients with other neurological diseases.

The second ‘neuroinflammatory disease’ study enrolled 12 patients from a prospective study over five years, with presentations suggestive of neuroinflammatory disease but ultimately diagnosed with a CNS malignant neoplasm, and 17 matched controls.

Results The sensitivity of the CSF mNGS assay was 75% (95% CI, 63%-85%), and the specificity was 100% (95% CI, 96%-100%). Aneuploidy was detected in 64% (95% CI, 41%-83%) of the patients in the test performance study with nondiagnostic cytologic testing and/or flow cytometry, and in 55% (95% CI, 23%-83%) of patients in the neuroinflammatory disease study who were ultimately diagnosed with a CNS malignant neoplasm. Of the patients positive for aneuploidy, 38 (90.5%) had multiple copy number aberrations with tumor fractions ranging from 31% to 49%.

Conclusions CSF mNGS, which has low specimen volume requirements, does not require the preservation of cell integrity, and was originally developed to diagnose neurologic infections, can also detect genetic evidence of a CNS malignant neoplasm in patients in whom CSF cytologic testing and/or flow cytometry yielded negative results with a low risk of false-positive results.

Authors/Disclosures
Wei Gu, MD, PhD (Stanford University) PRESENTER	The institution of Prof. Gu has received research support from NIH. The institution of Prof. Gu has received research support from Burroughs Wellcome.
	No disclosure on file
	No disclosure on file
Kelsey Zorn	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Hannah Sample	Hannah Sample, 14202 has nothing to disclose.
	No disclosure on file
	No disclosure on file
Bardia Nourbakhsh, MD (Johns Hopkins University)	The institution of Dr. Nourbakhsh has received research support from Genentech. The institution of Dr. Nourbakhsh has received research support from national MS Society . The institution of Dr. Nourbakhsh has received research support from Department of Defense. The institution of Dr. Nourbakhsh has received research support from NIH.
Carl A. Gold, MD (Stanford University)	Dr. Gold has received personal compensation for serving as an employee of Stanford University. An immediate family member of Dr. Gold has received personal compensation for serving as an employee of Stanford University.
Bruce A. Cree, MD, PhD, MCR, FAAN (UCSF, Multiple Sclerosis Center)	The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyverna. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. The institution of Dr. Cree has received research support from Kyverna. Dr. Cree has received publishing royalties from a publication relating to health care.
Vanja C. Douglas, MD, FAAN (Univ of California, San Francisco)	Dr. Douglas has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Various legal firms. Dr. Douglas has received publishing royalties from a publication relating to health care. Dr. Douglas has received publishing royalties from a publication relating to health care.
Megan Richie, MD (University of California, San Francisco)	Dr. Richie has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology.
Maulik Shah, MD (UCSF Neurology)	Dr. Shah has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for National Football League.
S. A. Josephson, MD, FAAN (UCSF)	Dr. Josephson has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Josephson has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for McGraw Hill---Harrison's Online. Dr. Josephson has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for various legal firms. The institution of Dr. Josephson has received research support from NINDS. Dr. Josephson has received publishing royalties from a publication relating to health care. Dr. Josephson has received publishing royalties from a publication relating to health care.
Jeffrey M. Gelfand, MD, MAS, FAAN (University of California, San Francisco)	Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ventyx Bio. An immediate family member of Dr. Gelfand has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Headache: The Journal of Head and Face Pain. The institution of Dr. Gelfand has received research support from Genentech/Roche. The institution of Dr. Gelfand has received research support from Vigil Neurosciences. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant and Expert, Vaccine Injury Compensation Program with United States Health and Human Services and Department of Justice. Dr. Gelfand has a non-compensated relationship as a Trial Steering Committee Chairperson and member with Roche / Genentech that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Michael R. Wilson, MD, FAAN (University of California San Francisco)	Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Delve Bio. Dr. Wilson has stock in Delve Bio. The institution of Dr. Wilson has received research support from Genentech / Roche. The institution of Dr. Wilson has received research support from NIH. The institution of Dr. Wilson has received research support from UCSF Weill Institute for Neurosciences. The institution of Dr. Wilson has received research support from Novartis. The institution of Dr. Wilson has received research support from National Multiple Sclerosis Society. The institution of Dr. Wilson has received research support from Fanconi Anemia Research Foundation. The institution of Dr. Wilson has received research support from Department of Defense. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as a Expert Witness with US Dept of Justice.