Abstract 368P
Background
Plasma ctDNA enables targeted therapy prescription in metastatic lung cancer by identifying oncogenic drivers and is now applied to fluids like pleural fluid or CSF. This study assessed ctDNA and ctRNA accuracy in bronchoscopic fluid for detecting oncogenic mutations.
Methods
We conducted a bicenter prospective study involving patients undergoing bronchoscopy for lung cancer diagnosis or follow-up. Next-generation sequencing (ThermoFisher®) targeted 59 genes for DNA and 23 for RNA in proven NSCLC. Molecular diagnostic accuracy of bronchoscopic fluid was evaluated with histological samples as reference standard.
Results
Between February and May 2024, 78 patients were screened in two French University hospitals, and 54 with confirmed NSCLC were included. Bronchoscopy was performed for NSCLC diagnostic in 94.5% of cases. Median age was 67 years; 72.2%were smokers, 77.8% had non-squamous lung cancer, and 50% were stage IV. Molecular abnormalities were detected in 96% of cases, including KRAS (n=13), EGFR (n=10), BRAF (n=4), and ALK rearrangements (n=3). A bronchus sign on CT was present in 75.9% of cases, and 46.3% of bronchoscopies revealed endobronchial abnormalities. Bronchial histological diagnosis was achieved in 72% of bronchoscopies with abnormalities and in 3.4% in macroscopically normal bronchoscopies. All but one ctDNA analyses on bronchoscopic fluid succeeded, but 44.4% of ctRNA analyses failed due to technical issues. Compared with tissue molecular analysis, ctDNA sensitivity in bronchoscopic fluid was 81.3%, with a specificity of 100%. In bronchoscopies with negative histology results, sensitivity was 70%. In case of macroscopically abnormal and normal bronchoscopies, sensitivity was 91.7% and 70.8%, respectively. Plasma ctDNA sensitivity was 30% across all stages. Subgroup analyses showed higher ctDNA sensitivity in bronchoscopic fluid in tumors >4 cm (92.8% vs 65%; p=0.024), bronchus sign presence (89% vs. 54%; p=0.020), and stage IV disease (96% vs 62.2%; p=0.006).
Conclusions
Liquid biopsy via bronchoscopy is a promising, minimally invasive tool for molecular diagnostics in NSCLC, offering high sensitivity and specificity, particularly in advanced disease and with a bronchus sign.
Clinical trial identification
BiLiBro; NCT06228508
Legal entity responsible for the study
Assistance Publique Hôpitaux de Paris
Funding
ACTT - Amis du Centre des Tumeurs de Tenon
Disclosure
C. Mahiat: Financial Interests, Personal, Invited Speaker: MSD. A. Canellas: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, Amgen. J. Cadranel: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Boehringer Ingelheim, Daiichi Sankyo Inc, F. Hoffman La Roche, Janssen, Lilly, MSD, Novartis, Pfizer, Sanofi, Takeda. V. Fallet: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Takeda, Roche, Pfizer, Sanofi, Sandoz, Jansen, Regeneron, MSD, Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Takeda, Pfizer, MSD, Sanofi, ISIS Medical; Financial Interests, Personal, Expert Testimony: GSK, Boehringer Ingelheim. All other authors have declared no conflicts of interest.