The following is a summary of “High Yield of Pleural Cell-Free DNA for Diagnosis of Oncogenic Mutations in Lung Adenocarcinoma,” published in the July 2023 issue of the Chest by Mahmood et al.

Currently, pleural cytology is used to evaluate patients with advanced lung adenocarcinoma for targetable mutations. Nonetheless, it has a minimal diagnostic yield. Can pleural cell-free DNA (cfDNA) be used to evaluate targetable mutations in patients with malignant pleural effusions (MPE) and lung adenocarcinoma? Patients with MPE lung adenocarcinoma were prospectively enrolled from January 2017 to September 2021. Using cytology of pleural fluid or biopsies of lung cancer, treating physicians assessed oncogenic mutations. 

Next-generation sequencing (NGS) evaluated mutations in pleural and plasma cfDNA. From 42 patients, 54 pleural fluid samples were collected. The diagnostic yield to detect oncogenic mutations was 49/54 (90.7%), 16/33 (48.5%), 22/25 (88%), and 24/32 (75%) for pleural cfDNA, pleural cytology, and plasma cfDNA, respectively, P< .001. The agreement between pleural cfDNA and pleural cytology for mutations in positive samples was 100%, whereas the agreement between pleural cfDNA and biopsies was 89.4%. 

The median concentration (interquartile range) of pleural cfDNA was higher than plasma: 28,444 (4,957-67,051) copies of amplifiable DNA per mL versus 2,966.5 (2,167-5,025) copies per mL (P <.01). About 5 mL of pleural fluid supernatant (interquartile range, 4.5-5) was sufficient for cfDNA testing. In lung adenocarcinoma patients, the diagnostic yield of pleural cfDNA NGS for oncogenic mutations is comparable to tumor biopsies and greater than pleural cytology and plasma cfDNA. The pleural cfDNA can be collected longitudinally, easily integrated into clinical workflow, and may reduce the need for additional biopsies.

Source: sciencedirect.com/science/article/abs/pii/S0012369223001265