Profiling Cell-Free DNA from Malignant Pleural Effusion for Oncogenic Driver Mutations in Patients with Treatment-Naive Stage IV Adenocarcinoma: A Multicenter Prospective Study.

Autor: Chang SC; Division of Chest Medicine, Department of Internal Medicine, National Yang Ming Chiao Tung University Hospital, Yi-Lan, Taiwan., Wei YF; School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan.; Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan., Chen CY; Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan., Lai YC; Division of Chest Medicine, Department of Internal Medicine, National Yang Ming Chiao Tung University Hospital, Yi-Lan, Taiwan., Hu PW; Division of Chest Medicine, Department of Internal Medicine, National Yang Ming Chiao Tung University Hospital, Yi-Lan, Taiwan., Hung JC; Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan., Chang CY; Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan. koala2716@gmail.com.; College of Electrical and Communication Engineering, Taoyuan City, Taiwan. koala2716@gmail.com.
Jazyk: angličtina
Zdroj: Molecular diagnosis & therapy [Mol Diagn Ther] 2024 Nov; Vol. 28 (6), pp. 803-810. Date of Electronic Publication: 2024 Aug 15.
DOI: 10.1007/s40291-024-00736-8
Abstrakt: Introduction: Comprehensive next-generation sequencing (NGS) of non-small-cell lung cancer specimens can identify oncogenic driver mutations and their corresponding targeted therapies. Plasma cell-free DNA (cfDNA) genotyping is easy to perform; however, false negatives cannot be overlooked. We explored malignant pleural effusion (MPE), a rich source of cfDNA, as a non-inferior alternative to tumor tissues for genotyping.
Methods: We conducted a prospective trial including 39 patients with newly diagnosed stage IV lung adenocarcinoma who presented with MPE. Tissue tests matching hotspot variants, including EGFR, ALK, and ROS1, were compared with the AlphaLiquid100 of PE-cfDNA.
Results: Among the 39 PE-cfDNA samples successfully sequenced, 32 (82.1%) had a PE cell-block tumor content of < 10%. Standard tissue or cell-block testing for EGFR, ALK, and ROS1 identified 20 mutations (51.3%), whereas PE cfDNA identified 25 mutations (64.1%). Five EGFR mutations were observed in PE cfDNA but not in Cobas EGFR owing to coverage or insufficient tumor content issues. The overall rate of oncogenic mutations identified in the PE cfDNA was 92.3%, and the mutation distribution was as follows: even with a very low cfDNA input, high detection rates could be achieved. Otherwise, most patients harbored co-mutations. Comparison of pleural fluid NGS with traditional testing revealed differences in accuracy. We also followed up with patients with EGFR-sensitizing mutations who had a treatment response rate of 97.2% after 3 months.
Conclusions: Genotyping of MPE supernatant cfDNA is feasible in clinical practice, in addition to plasma and tumor testing, to improve diagnostic yield and extend patients' benefit from targeted therapies.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: