
==== Front
Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.031
vdae090.031
Final Category: Biomarkers
AcademicSubjects/MED00300
AcademicSubjects/MED00310
BMRK-11 REAL-WORLD EXPERIENCE WITH CIRCULATING TUMOR DNA IN CEREBROSPINAL FLUID IN PATIENTS WITH CENTRAL NERVOUS SYSTEM TUMORS
Hickman Richard Human Oncology & Pathogenesis Program, Sloan Kettering Institute, New York, NY, USA
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Miller Alexandra M Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Holle Bridget M Human Oncology & Pathogenesis Program, Sloan Kettering Institute, New York, NY, USA

Jee Justin Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Liu Si-Yang Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Ross Dara Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Yu Helena Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Riley Gregory J Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Ombres Christina Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Gewirtz Alexandra Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Reiner Anne S Department of Epidemiology and Biostatistics; Memorial Sloan Kettering Cancer Center, New York, NY, USA

Nandakumar Subhiksha Human Oncology & Pathogenesis Program, Sloan Kettering Institute, New York, NY, USA

Price Adam Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Kaley Thomas J Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Graham Maya S Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Vanderbilt Chad Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Rana Satshil Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Hill Katherine Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Chabot Kiana Human Oncology & Pathogenesis Program, Sloan Kettering Institute, New York, NY, USA

Campos Carl Human Oncology & Pathogenesis Program, Sloan Kettering Institute, New York, NY, USA

Nafa Khedoudja Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Shukla Neerav Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Karajannis Matthias Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Li Bob Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Berger Michael Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Ladanyi Marc Human Oncology & Pathogenesis Program, Sloan Kettering Institute, New York, NY, USA
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Pentsova Elena Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Boire Adrienne Human Oncology & Pathogenesis Program, Sloan Kettering Institute, New York, NY, USA
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Brannon A Rose Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Bale Tejus Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Mellinghoff Ingo K Human Oncology & Pathogenesis Program, Sloan Kettering Institute, New York, NY, USA
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Arcila Maria E Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i10i10
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

Next generation sequencing (NGS) of circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) offers a minimally invasive approach to identify somatic alterations for individuals with central nervous system (CNS) cancers. Here, we review our ‘real world’ experience using a clinically validated, FDA-authorized platform, MSK-IMPACTTM, to comprehensively profile ctDNA from CSF samples with and without clinically documented CNS involvement by cancer (1007 samples, 711 patients). The patient cohort included patients with over 90 distinct tumor types of primary CNS and metastatic origin, with lung cancer (n = 188), breast cancer (n = 150), and glioma (n = 148) representing the most common broad categories. We identified genetic alterations (ctDNA-positive) in 489/922 (53.0%) CSF samples from patients with clinically documented CNS cancer. Over half of these ctDNA-positive samples (248, 50.7%) possessed a biomarker that was predictive of response to an FDA-approved drug (OncoKB level 1). Furthermore, the distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Of patients without clinical documentation of CNS cancer, none of these 85 CSF samples were ctDNA-positive (specificity = 100%). Successive CSF sequencing over time identified clonal evolution and the emergence of resistance mechanisms to therapies. ctDNA positivity corresponded with shortened overall survival after CSF collection (HR: 3.23, 95% CI: 2.58-4.05, P < 0.001). NGS of CSF cfDNA can detect clinically actionable somatic alterations in a large subset of CNS cancer patients and allows tracking of tumor evolution. Detection of somatic alterations in CSF may be a useful prognostic biomarker for survival in cancer patients.
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