ArticleThe journal of liquid biopsy2026
Cerebrospinal fluid circulating tumor DNA profiling in central nervous system metastases from solid tumors: A prospective multicentre translational analysis of the BrainStorm (OncoDistinct-006) study.
Article in The journal of liquid biopsy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04109131 (A Brain Metastases Research Platform to Tackle the Challenge of CNS Metastases in Solid Tumours - BrainStorm Program), which is not on this map. Not yet cited in PubMed.
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A Brain Metastases Research Platform to Tackle the Challenge of CNS Metastases in Solid Tumours - BrainStorm Program
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31 authors.
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Abstract
Background: Central nervous system (CNS) metastases represent a complication in solid tumors and often harbour unique genomic alterations diverging from those in primary tumor tissue or plasma; however, direct sampling of CNS lesions carries procedural risks, limiting its molecular profiling. The main aim of the present analysis was to assess the feasibility of Cerebrospinal Fluid (CSF) ctDNA profiling and to descriptively compare genomic alterations detected in matched tumor tissue, plasma, and CSF samples, including in patients with leptomeningeal metastases (LM). Patients and methods: BrainStorm (NCT04109131) is a prospective, international, multicenter study enrolling patients at high risk of developing CNS metastases from different solid tumors. In the present analysis, we evaluated matched samples of tumor tissue, plasma, and CSF ctDNA from patients who developed CNS metastases. Tumor tissue was profiled using the OncoDEEP® 638-gene NGS panel, while matched plasma and CSF ctDNA were sequenced with OncoFOLLOW® tumor-informed panel (plus 50 hotspot genes). Descriptive statistics and Jaccard index-based concordance analyses were performed to compare mutational profiles across compartments. Results: CSF ctDNA was detectable in 21 out of the 25 evaluable CSF samples (84%) and in 10 out of 11 patients with LM (91%). Overall concordance among genomic alterations in samples was 52% between tissue and plasma, 45% between tissue and CSF, and 75% between plasma and CSF. In the subset of 11 patients with LM, concordance was 39% (tissue-plasma), 42% (tissue-CSF) and 91% (plasma-CSF). Overall, seven alterations were identified exclusively in CSF or CSF and tissue but not in plasma, including variants in Conclusions: These preliminary findings indicate that CSF ctDNA can provide a sensitive, compartment-specific molecular portrait of CNS disease, complementing plasma-based analyses, and supporting its integration as a minimally invasive tool to capture the evolving genomic landscape of CNS metastases. Clinical trial registration number: NCT04109131.
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