Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis.

Autor:	Liang SK; Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan., Liao WY; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: wyliao33@ntu.edu.tw., Shih JY; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan., Hsu CL; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan., Yang CY; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan., Wu SG; Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan., Lin YT; Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan., Wen YF; Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan., Chen LC; Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan., Chen YF; Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan., Chen YF; Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan., Lin YH; Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan., Yu CJ; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan.
Jazyk:	angličtina
Zdroj:	Neoplasia (New York, N.Y.) [Neoplasia] 2024 Dec 21; Vol. 60, pp. 101113. Date of Electronic Publication: 2024 Dec 21.
DOI:	10.1016/j.neo.2024.101113
Abstrakt:	Leptomeningeal metastasis (LM) is a challenging complication of non-small cell lung cancer (NSCLC). Cerebrospinal fluid (CSF) cell-free DNA (cfDNA) analysis using next-generation sequencing (NGS) offers insights into resistance mechanisms and potential treatment strategies. We conducted a study from February 2022 to April 2023 involving patients from five hospitals in Taiwan who had recurrent or advanced NSCLC with LM. These patients underwent CSF cfDNA analysis using a 118-gene targeted panel for NGS, with comprehensive clinical data collected. Among 25 enrolled patients, 22 (88.0 %) had EGFR mutations, while three (12.0 %) had EML4-ALK fusion, KIF5B-RET fusion, and ERBB2 A775_G776insSVMA. CSF cfDNA sequencing of 27 samples (from 25 patients) all confirmed their original driver mutations. Of total cohort, 18 patients (72.0 %) underwent intrathecal pemetrexed (ITP), with a median survival time of 7.4 months (95.0 % confidence interval, 3.3-11.6) from the initiation of ITP to death. Among them, ten individuals (55.6 %) survived beyond 6 months. Notably, MET copy number gain (CNG) correlated significantly with survival time exceeding 6 months after ITP (p = 0.007). The coexistence of EGFR T790M and EGFR-independent resistance alterations was associated with shorter survival times after ITP, with a median survival time of 1.9 months compared to 9.9 months for those without EGFR T790M (p = 0.010). Our results highlight CSF cfDNA NGS's potential in LM resistance understanding and ITP efficacy prediction. MET CNG positively impacts survival for ITP recipients, whereas the coexistence of EGFR T790M and EGFR-independent resistance mechanisms leads to poor outcomes. Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SKL received speaking honoraria from ACTgenomics, Boehringer Ingelheim, AstraZeneca, Pfizer, Novartis, Bristol-Myers Squibb, and Chugai Pharma Taiwan. WYL reported receiving speaking honorariums from AstraZeneca, Roche, Boehringer Ingelheim, Eli Lilly, Pfizer, MSD Oncology, Novartis, TSH Biopharm, Bristol-Myers Squibb, Johnson & Johnson, Bayer, and Chugai Pharma Taiwan outside of the submitted work. JYS received speaking honoraria from ACTgenomics, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharma, CStone Pharmaceuticals, Daiichi Sankyo, Eli Lilly, Genconn Biotech, GSK, Janssen, Lotus Pharmaceutical Co., Merck Sharp & Dohme, MundiPharma, Novartis, Ono Pharmaceutical, Orient EuroPharma, Pfizer, Roche, Takeda, TSH Biopharm, TTY Biopharm; received support for attending meetings from AstraZeneca, Roche, and Chugai Pharma; as well as grant from Roche. The other authors have no relevant conflicts of interest to declare. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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