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16.12.2023 | Research

Cerebrospinal fluid circulating tumor DNA contributes to the detection and characterization of leptomeningeal metastasis in non-small cell lung cancer

verfasst von: Qian Miao, Xinlong Zheng, Lifeng Li, Xiaobin Zheng, Longfeng Zhang, Kan Jiang, Shiwen Wu, Haibo Wang, Biao Wu, Yiquan Xu, Qiaofeng Zhong, Zihua Zou, Qiuyu Zhang, Shanshan Yang, Yujing Li, Gen Lin

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2023

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Abstract

Purpose

Cerebrospinal fluid (CSF) has revealed the unique genetic characteristics of leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC). However, the research in this area is still very limited.

Methods

Patients with LM from NSCLC (n = 80) were retrospectively analyzed. Circulating tumor DNA (ctDNA) in CSF was tested by next-generation sequencing (NGS), with paired extracranial tissue or plasma samples included for comparison. An independent non-LM cohort (n = 100) was also analyzed for comparative purposes. Clinical outcomes were compared with Kaplan–Meier log-rank test and Cox proportional hazards methodologies.

Results

An overwhelming 93.8% of patients carried druggable mutations in NSCLC LM, with EGFR (78.8%) being the most prevalent. Notably, 4 patients who tested negative for driver genes in extracranial samples surprisingly showed EGFR mutations in their CSF and subsequently benefited from targeted therapy. There was a clear difference in genetic profiles between CSF and extracranial samples, with CSF showing more driver gene detections, increased Copy Number Variations (CNVs), and varied resistance mechanisms among individuals. Abnormalities in cell-cycle regulatory molecules were highly enriched in LM (50.9% vs 31.0%, p = 0.017), and CDKN2A/2B deletions were identified as an independent poor prognostic factor for LM patients, with a significant reduction in median OS (p = 0.013), supported by multivariate analysis (HR 2.63, 95% CI 1.32–5.26, p = 0.006).

Conclusions

CSF-based ctDNA analysis is crucial for detecting and characterizing genetic alterations in NSCLC LM. The distinct genetic profiles in CSF and extracranial tissues emphasize the need for personalized treatment approaches.

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Titel: Cerebrospinal fluid circulating tumor DNA contributes to the detection and characterization of leptomeningeal metastasis in non-small cell lung cancer
verfasst von: Qian Miao
Xinlong Zheng
Lifeng Li
Xiaobin Zheng
Longfeng Zhang
Kan Jiang
Shiwen Wu
Haibo Wang
Biao Wu
Yiquan Xu
Qiaofeng Zhong
Zihua Zou
Qiuyu Zhang
Shanshan Yang
Yujing Li
Gen Lin
Publikationsdatum: 16.12.2023
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2023
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-023-04520-2

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