Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors
The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors.
Authors
- Carl Campos (ORCID: https://orcid.org/0000-0002-7616-8518)
- Matthias A. Karajannis (ORCID: https://orcid.org/0000-0002-7151-6528)
- Richard A. Hickman (ORCID: https://orcid.org/0000-0002-8329-6083)
- Elena Pentsova (ORCID: https://orcid.org/0000-0001-5854-0251)
- Helena A. Yu (ORCID: https://orcid.org/0000-0002-0377-9510)
- Kiana Chabot (ORCID: https://orcid.org/0000-0003-2897-0845)
- Tejus Bale (ORCID: https://orcid.org/0000-0003-3641-9287)
- Neerav Narendra Shukla (ORCID: https://orcid.org/0000-0003-2516-2965)
- Ingo K. Mellinghoff (ORCID: https://orcid.org/0000-0002-4347-8149)
- Satshil Rana (ORCID: https://orcid.org/0000-0001-9670-1810)
- Maya Srikanth Graham (ORCID: https://orcid.org/0000-0003-4748-974X)
- Khédoudja Nafa (ORCID: https://orcid.org/0000-0002-7467-6682)
- Michael F. Berger (ORCID: https://orcid.org/0000-0003-3882-5000)
- Adam Price (ORCID: https://orcid.org/0000-0001-6114-6298)
- Anne S. Reiner (ORCID: https://orcid.org/0000-0002-1258-6112)
- Bob T. Li (ORCID: https://orcid.org/0000-0001-6661-8733)
- Thomas Kaley (ORCID: https://orcid.org/0000-0002-2540-8518)
- Marc Ladanyi (ORCID: https://orcid.org/0000-0001-9055-7213)
- Adrienne Ann Boire (ORCID: https://orcid.org/0000-0002-9029-1248)
- Maria E. Arcila (ORCID: https://orcid.org/0000-0001-5824-6554)
- Justin Jee (ORCID: https://orcid.org/0000-0001-9783-0139)
- Gregory J. Riely (ORCID: https://orcid.org/0000-0001-5357-4313)
- Alexandra Miller (ORCID: https://orcid.org/0000-0003-2048-579X)
- Katherine Hill (ORCID: https://orcid.org/0000-0002-1439-8174)
- Christina Ombres
- Alexandra N. Gewirtz (ORCID: https://orcid.org/0000-0002-1807-9226)
- Subhiksha Nandakumar (ORCID: https://orcid.org/0000-0003-0258-3484)
- A. Rose Brannon (ORCID: https://orcid.org/0000-0003-4610-0149)
- Bridget M Holle
- Siyang Liu
- Dara S. Ross (ORCID: https://orcid.org/0009-0003-4677-9398)
- Chad Vanderbilt
Institutions
- Memorial Sloan Kettering Cancer Center (US)
- Kettering University (US)
- NYU Langone Health (US)
- Foundation Medicine (United States)
- New York University (US)
Publication Details
- Journal
- Acta Neuropathologica Communications
- Published
- 2024-09-17
- DOI
- https://doi.org/10.1186/s40478-024-01846-4
- Citations
- 17
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 4.85
Funders
- Cycle for Survival
- National Institutes of Health
- Marie-Josée and Henry R. Kravis Center for Molecular Oncology
- National Cancer Institute
- National Institute of Neurological Disorders and Stroke