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Quantification of cerebrospinal fluid tumor DNA in lung cancer patients with suspected leptomeningeal carcinomatosis.
Azad, Tej D; Nanjo, Shigeki; Jin, Michael C; Chabon, Jacob J; Kurtz, David M; Chaudhuri, Aadel A; Connolly, Ian D; Hui, Angela Bik-Yu; Liu, Chih Long; Merriott, David; Ko, Ryan; Yoo, Christopher; Carter, Justin; Chen, Emily; Bonilla, Rene; Hata, Akito; Katakami, Nobuyuki; Irie, Kei; Yano, Seiji; Okimoto, Ross; Bivona, Trever G; Newman, Aaron M; Iv, Michael; Nagpal, Seema; Gephart, Melanie Hayden; Alizadeh, Ash A; Diehn, Maximilian.
Afiliação
  • Azad TD; Department of Neurosurgery, Johns Hopkins University, Baltimore, MD, USA.
  • Nanjo S; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Jin MC; Department of Medicine, University of California, San Francisco, CA, USA.
  • Chabon JJ; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
  • Kurtz DM; Department of Respiratory Medicine, Kanazawa University Hospital, Kanazawa, Japan.
  • Chaudhuri AA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Connolly ID; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
  • Hui AB; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Liu CL; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Merriott D; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
  • Ko R; Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
  • Yoo C; Mayo Clinic Comprehensive Cancer Center, Rochester, MN, USA.
  • Carter J; Department of Neurosurgery, Stanford University, Stanford, CA, USA.
  • Chen E; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Bonilla R; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
  • Hata A; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Katakami N; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
  • Irie K; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Yano S; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
  • Okimoto R; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Bivona TG; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
  • Newman AM; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Iv M; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
  • Nagpal S; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Gephart MH; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
  • Alizadeh AA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Diehn M; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
NPJ Precis Oncol ; 8(1): 121, 2024 May 28.
Article em En | MEDLINE | ID: mdl-38806586
ABSTRACT
Cerebrospinal fluid tumor-derived DNA (CSF-tDNA) analysis is a promising approach for monitoring the neoplastic processes of the central nervous system. We applied a lung cancer-specific sequencing panel (CAPP-Seq) to 81 CSF, blood, and tissue samples from 24 lung cancer patients who underwent lumbar puncture (LP) for suspected leptomeningeal disease (LMD). A subset of the cohort (N = 12) participated in a prospective trial of osimertinib for refractory LMD in which serial LPs were performed before and during treatment. CSF-tDNA variant allele fractions (VAFs) were significantly higher than plasma circulating tumor DNA (ctDNA) VAFs (median CSF-tDNA, 32.7%; median plasma ctDNA, 1.8%; P < 0.0001). Concentrations of tumor DNA in CSF and plasma were positively correlated (Spearman's ρ, 0.45; P = 0.03). For LMD diagnosis, cytology was 81.8% sensitive and CSF-tDNA was 91.7% sensitive. CSF-tDNA was also strongly prognostic for overall survival (HR = 7.1; P = 0.02). Among patients with progression on targeted therapy, resistance mutations, such as EGFR T790M and MET amplification, were common in peripheral blood but were rare in time-matched CSF, indicating differences in resistance mechanisms based on the anatomic compartment. In the osimertinib cohort, patients with CNS progression had increased CSF-tDNA VAFs at follow-up LP. Post-osimertinib CSF-tDNA VAF was strongly prognostic for CNS progression (HR = 6.2, P = 0.009). Detection of CSF-tDNA in lung cancer patients with suspected LMD is feasible and may have clinical utility. CSF-tDNA improves the sensitivity of LMD diagnosis, enables improved prognostication, and drives therapeutic strategies that account for spatial heterogeneity in resistance mechanisms.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article