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Publications

Journal Article Epublish

PubMed: 42835688 DOI: 10.1016/j.jlb.2026.100492

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.

J Liq Biopsy 14:100492

Authors: Luca Arecco, Françoise Rothé, David Venet, Andrea Gombos, Anthony Gonçalves, Eleonora De Maio D'Esposito, Philippe Barthélémy, Vincent Vanhaudenarde, Florian Clatot, Stephane Holbrechts, Francois P Duhoux, Edith Borcoman, Claire Cheymol, Joseph Gligorov, Hannelore Denys, Paul M Clement, Kevin Punie, Caroline Duhem, Lore Decoster, Jean-Luc Canon, Florence Lefranc, Marika Rasschaert, Nadège Kindt, Katarina Čular, Gabriella Gentile, Kristanto Paulus, Elisabeth Pop, Diane Delaroche, Evandro de Azambuja, Ahmad Awada, Nuria Kotecki

Affiliations

  • Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Institut Jules Bordet, Bruxelles, Belgium.
  • Breast Cancer Translational Research Laboratory J.-C. Heuson, Université Libre de Bruxelles, Institut Jules Bordet, Bruxelles, Belgium.
  • Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.
  • IUCT Oncopole - Institut Claudius Regaud, Toulouse, France.
  • Medical Oncology Department, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
  • CHU UCL Namur, site Sainte-Elisabeth Hospital, Namur, Belgium.
  • Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
  • Medical Oncology Department, CHU Helora Site Kennedy, Mons, Belgium.
  • Department of Medical Oncology, Institut Roi Albert II, Cliniques universitaires Saint-Luc and Institut de Recherche Expérimentale et Clinique (pôle MIRO), U.C. Louvain, Brussels, Belgium.
  • Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France.
  • Centre Oscar Lambret, Lille, France.
  • Institut Universitaire de Cancérologie, AP-HP Sorbonne Université, Paris, France.
  • Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium.
  • Department of Medical Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
  • Clinique Du Sein, Centre Hospitalier Du Luxembourg, Luxembourg.
  • Universitair Ziekenhuis Brussels, Bruxelles, Belgium.
  • Department of Medical Oncology, Grand Hôpital de Charleroi, Charleroi, Belgium.
  • Department of Neurosurgery, Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Erasme University Hospital, Brussels, 1070, Belgium.
  • Department of Medical Oncology, University Hospital Antwerp, Edegem, Belgium.
  • Department of Experimental Medicine, Sapienza University, Rome, Italy.
  • Oncology Department, Chirec Cancer Institute, Bruxelles, Belgium.

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 TP53, PIK3CA, and ERBB2.

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.

MeSH

Genes, Dna Fingerprinting, Circulating Tumor Dna, Neoplasms, Central Nervous System, Neoplasm Metastasis, Nervous System, Tissues, Plasma