ArticleJournal of neuro-oncology2023
Cerebrospinal fluid circulating tumour DNA genotyping and survival analysis in lung adenocarcinoma with leptomeningeal metastases.
Article in Journal of neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cerebrospinal fluid ctDNA as a prognostic and disease-activity biomarker in leptomeningeal metastases: systematic review, meta-analysis, and implications for CSF-guided care.Journal of neuro-oncology · 2026Pooled it
- Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review).Oncology letters · 2026Review
- Furmonertinib combined with bevacizumab in EGFR-TKI-resistant leptomeningeal metastasis: analysis of the CSF ctDNA molecular response and survival outcomes.British journal of cancer · 2026Article
- [Chinese Expert Consensus on Clinical Management of Oncogene Addicted Non-small Cell Lung Cancer with Leptomeningeal Metastasis (2026 Edition)].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Article
- MRI-based morphological and spatial characteristics of leptomeningeal metastasis: prognostic value in non-small cell lung cancer.Frontiers in oncology · 2026Article
- Serial monitoring of cerebrospinal fluid in patients with leptomeningeal metastases in lung cancer via the Ommaya reservoir as a predictive indicator of therapeutic efficacy and clinical prognosis.NPJ precision oncology · 2025Article
- Integration of Liquid Biopsy for Optimal Management of Non-small Cell Lung Cancer.Tuberculosis and respiratory diseases · 2025Article
- Strategies Beyond 3rd EGFR-TKI Acquired Resistance: Opportunities and Challenges.Cancer medicine · 2025Review
- Cerebral spinal fluid analyses and therapeutic implications for leptomeningeal metastatic disease.Journal of neuro-oncology · 2025Review
- The research progress on meningeal metastasis in solid tumors.Discover oncology · 2025Review
- Clinical characteristics and analysis of cerebrospinal fluid biochemical, tumor markers and cytologic indices in 209 patients with meningeal carcinomatosis: a cross-sectional study.Frontiers in oncology · 2025Article
- Multimodal omics analysis of the EGFR signaling pathway in non-small cell lung cancer and emerging therapeutic strategies.Oncology research · 2025Review
- Review
- Treatment decision-making for leptomeningeal metastasis after TKI resistance in EGFR-mutant lung cancer: a comprehensive review on staging, resistance patterns, and multimodal interventions.Frontiers in neurologyReview
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Authors and funding
13 authors.
Funding
Abstract
purposeThe prognosis of patients with leptomeningeal metastasis (LM) remains poor. Circulating tumour DNA (ctDNA) has been proven to be abundantly present in cerebrospinal fluid (CSF); hence, its clinical implication as a biomarker needs to be further verified.
methodsWe conducted a retrospective study of 35 lung adenocarcinoma (LUAD) patients with LM, and matched CSF and plasma samples were collected from all patients. All paired samples underwent next-generation sequencing (NGS) of 139 lung cancer-associated genes. The clinical characteristics and genetic profiling of LM were analysed in association with survival prognosis.
resultsLM showed genetic heterogeneity, in which CSF had a higher detection rate of ctDNA (P = 0.003), a higher median mutation count (P < 0.0001), a higher frequency of driver mutations (P < 0.01), and more copy number variation (CNV) alterations (P < 0.001) than plasma. The mutation frequencies of the EGFR, TP53, CDKN2A, MYC and CDKN2B genes were easier to detect in CSF than in LUAD tissue (P < 0.05), possibly reflecting the underlying mechanism of LM metastasis. CSF ctDNA is helpful for analysing the mechanism of EGFR-TKI resistance. In cohort 1, which comprised patients who received 1/2 EGFR-TKIs before the diagnosis of LM, TP53 and CDKN2A were the most common EGFR-independent resistant mutations. In cohort 2, comprising those who progressed after osimertinib and developed LM, 7 patients (43.75%) had EGFR CNV detected in CSF but not plasma. Furthermore, patient characteristics and various genes were included for interactive survival analysis. Patients with EGFR-mutated LUAD (P = 0.042) had a higher median OS, and CSF ctDNA mutation with TERT (P = 0.013) indicated a lower median OS. Last, we reported an LM case in which CSF ctDNA dynamic changes were well correlated with clinical treatment.
conclusionsCSF ctDNA could provide a more comprehensive genetic landscape of LM, indicating the potential metastasis-related and EGFR-TKI resistance mechanisms of LM patients. In addition, genotyping of CSF combined with clinical outcomes can predict the prognosis of LUAD patients with LM.
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