High Yield of Pleural Cell-Free DNA for Diagnosis of Oncogenic Mutations in Lung Adenocarcinoma

Kamran Mahmood*, Parvathi Jampani, Jeffrey M. Clarke, Steven Wolf, Xiaofei Wang, Momen M. Wahidi, Coral X. Giovacchini, Michael Dorry, Scott L. Shofer, Jessica Shier, Greg Jones, Scott J. Antonia, Andrew B. Nixon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)252-261
Number of pages10
JournalCHEST
Volume164
Issue number1
DOIs
StatePublished - Jul 2023

Funding

The work was supported by US Department of Defense , Lung Cancer Research Program, award number W81XWH-20-1-0280. Inivata (Research Triangle Park, NC) performed next-generation sequencing on the research specimens.

Keywords

  • Cell-free DNA
  • lung adenocarcinoma
  • malignant pleural effusion
  • mutations

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine

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