Background: Pleural cytology is currently used to assess targetable mutations in patients with advanced lung adenocarcinoma. However, it is fraught with low diagnostic yield.
Research Question: Can pleural cell-free DNA (cfDNA) be used to assess targetable mutations in lung adenocarcinoma patients with malignant pleural effusions (MPE)?
Study Design And Methods: Patients with lung adenocarcinoma MPE were recruited prospectively between January 2017 and September 2021. Oncogenic mutations were assessed by treating providers using pleural fluid cytology or lung cancer biopsies. Pleural and plasma cfDNA were used to assess the mutations using next-generation sequencing (NGS).
Results: Fifty-four pleural fluid samples were collected from 42 patients. The diagnostic yield to detect oncogenic mutations for pleural cfDNA, pleural cytology, biopsy, and plasma cfDNA was 49/54 (90.7%), 16/33 (48.5%), 22/25 (88%), and 24/32 (75%), respectively, P < .001. The agreement of mutations in positive samples between pleural cfDNA and pleural cytology was 100%, whereas the agreement of pleural cfDNA with biopsies was 89.4%. The median concentration (interquartile range) of pleural cfDNA was higher than plasma: 28,444 (4,957-67,051) vs 2,966.5 (2,167-5,025) copies of amplifiable DNA per mL, P < .01. Median of 5 mL (interquartile range, 4.5-5) of pleural fluid supernatant was adequate for cfDNA testing.
Interpretation: The diagnostic yield of pleural cfDNA NGS for oncogenic mutations in lung adenocarcinoma patients is comparable to tumor biopsies and higher than pleural cytology and plasma cfDNA. The pleural cfDNA can be longitudinally collected, can be readily incorporated in clinical workflow, and may decrease the need for additional biopsies.
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http://dx.doi.org/10.1016/j.chest.2023.01.019 | DOI Listing |
JTO Clin Res Rep
December 2024
Mayo Clinic, Rochester, Minnesota.
Introduction: The spatially complex nature of mesothelioma and interventions like pleurodesis, surgery, and radiation often complicate imaging-based assessment. Further, cell-free DNA (cfDNA) based monitoring strategies are inadequate for mesothelioma, given the presence of a few recurring nonsynonymous somatic variants. However, patient-specific chromosomal rearrangements are commonly found in mesothelioma.
View Article and Find Full Text PDFHealth Sci Rep
November 2024
Centre for Global Health Research Saveetha Institute of Medical and Technical Sciences, Saveetha Medical College and Hospital Chennai India.
Background And Aims: Cancer therapy is one of the most researched upon medical field in the world. Non invasive technologies such as liquid biopsy are gaining more importance in cancer therapy because of their manifold advantages over traditional invasive biopsy methods. Liquid biopsy is used to analyze nucleic acids such as ctDNA, cfDNA and RNA, cellular and subcellular components such as proteins, extracellular vesicles and circulating tumor cells in various biological fluids such as blood, urine, cerebrospinal fluid, pleural fluid and ascites fluid for diagnosis of cancer.
View Article and Find Full Text PDFPLoS One
September 2024
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Objectives: This study was performed to investigate the detection rate of EGFR T790M mutation by repeated rebiopsy, to identify the clinical factors related to repeated rebiopsy, and to assess survival outcomes according to the methods and numbers of repeated rebiopsies in patients with lung adenocarcinoma who received sequential osimertinib after failure of previous 1st or 2nd generation EGFR-tyrosine kinase inhibitors.
Methods: This retrospective study included patients with advanced-stage lung adenocarcinoma who were confirmed to have EGFR T790M mutation and to have received osimertinib from January 2020 to February 2021 at Samsung Medical Center. The presence of T790M mutation was assessed based on either plasma circulating tumor DNA (ctDNA) or tissue specimens.
Mil Med Res
August 2024
Department of Pathology, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China.
Mol Diagn Ther
November 2024
Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
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.
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