Abstract CT202: CSFctDNA as a surrogate for tumor tissue DNA in BC pts with CNS metastases: First results from the Brainstorm program (Oncodistinct 006)
(2024) AACR Annual Meeting 2024
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- Background: Central nervous system (CNS) metastases display molecular alterations that differ from primary tumors and metastatic sites, which might confer special CNS sensitivity for targeted treatments. Brain biopsies are an invasive approach and liquid biopsies (LB) are therefore being investigated as a potential tool for detecting these molecular alterations in cerebrospinal fluid (CSF) ctDNA. Methods: The BrainStorm program (NCT04109131) is an international, prospective, interventional study aiming to build a large clinico-pathological database to investigate the development of CNS metastases: (A) before the diagnosis; (B) at diagnosis; and (C) after the diagnosis of CNS metastases. Molecular landscape of CSFctDNA was analyzed and explored as a surrogate for CNS tumor tissue DNA using large next-generation sequencing panels in tumor tissue and tumor-informed targeted gene panels in LB (OncoDEEP®/OncoFOLLOW®) for patients (pts) included in Part (B). Results: As of October 2023, CSF was available for 30 out of 67 pts included in Part (B) of the study and analyses were performed for 12 matched extra-CNS tumor, plasma and CSF samples. The 12 cases were derived from pts with breast cancer (BC) (luminal n=6; triple negative (TN) n=2; HER2-positive n=4) and among them 4 pts were diagnosed with leptomeningeal metastases (LM). CSFctDNA was detectable in 7 out of the 12 CSF samples (58%) and in 3 out of 4 pts with LM (75%). In pts with detectable CSFctDNA, detection rate for known pathogenic molecular alterations was 80% (Table 1). No safety concerns from lumbar puncture were identified. Conclusion: The use of CSFctDNA as a surrogate for tumor tissue DNA in CNS metastases appears to be a feasible and safe approach. Clinically actionable alterations have been identified in CSFctDNA of pts with BC. Further results will be presented at a later stage.
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Kotecki, N., Martins-Branco, D., Nader-Marta, G., Gombos, A., Barthelemy, P., Gonçalves, A., Borcoman, E., Clatot, F., Holbrechts, S., D’Esposito, E. S. d. M., Cheymol, C., Vanhaudenarde, V., Duhoux, F., Duhem, C., Clement, P., Decoster, L., Denys, H., Lefranc, F., Canon, J.-L., et al. (2024). Abstract CT202: CSFctDNA as a surrogate for tumor tissue DNA in BC pts with CNS metastases: First results from the Brainstorm program (Oncodistinct 006). Cancer Research, 84(7_Supplement), CT202-CT202. https://doi.org/10.1158/1538-7445.am2024-ct202 (Original work published 2024)