1187P - Molecular diagnosis of lung cancer via ctDNA and ctRNA detection on bronchoscopic fluid specimens from 31 patients: A retrospective analysis

Background

While cytological or tissue analysis is standard for lung cancer diagnosis, plasma ctDNA is increasingly recognized as sufficient for initiating targeted therapy upon identification of an oncogenic driver. ctDNA application has expanded to other fluids like pleural fluid or CSF. This study assesses the diagnostic accuracy of ctDNA and ctRNA in detecting oncogenic mutations in bronchoscopic fluid specimens.

Methods

We conducted a single-center retrospective study at Tenon Hospital APHP, including patients who underwent bronchoscopy with ctDNA and ctRNA assessments in bronchial aspiration or bronchoalveolar lavage from April 2022 to January 2024. Next generation sequencing (Ampliseq Focus Illumina®) targeted mutations in 40 genes for DNA and 23 for RNA. Molecular results from bronchoscopic fluid were compared with molecular diagnostics obtained from histological samples.

Results

31 patients were included. Median age was 71 years; 52% were male; 77% were smokers; 68% were diagnosed at stage IV. Peripheral lesions were identified in 58% of cases and 61% of bronchoscopies revealed endobronchial abnormalities. Molecular analyses of ctDNA and ctRNA in bronchoscopic fluid samples identified mutations in KRAS (n=10), EGFR (n=3), MET ex14 (n=1), BRAF (n=1) and PIK3CA (n=2) and one fusion CD74-ROS1, with an overall detection rate of 58%. The median turnaround time for results was 12 days. All ctDNA analyses were completed, although 23% of ctRNA analyses were unsuccessful due to technical difficulties. Compared to tissue molecular analysis, overall sensitivity and specificity were 73.7% and 71.4% respectively, 91.6% and 66.6% in cases of abnormal bronchoscopy, and 42.8% and 75% in cases of normal bronchoscopy. For comparison, histological diagnosis was achieved in only 8.3% of cases with normal bronchoscopy and 57.9% with abnormal bronchoscopy.

Conclusions

Our retrospective study suggests that liquid biopsy via bronchoscopy is a promising tool for the molecular diagnosis and management of lung cancer. A prospective study is ongoing (NCT06228508) to further validate these findings and assess the clinical implications of detecting bronchial ctDNA and ctRNA.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

V. Fallet: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Takeda, Roche, Pfizer, Sanofi, Sandoz, Janssen, GSK, Boehringer, Regeneron, MSD, Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Takeda, Pfizer, MSD, Sanofi, ISIS Medical. All other authors have declared no conflicts of interest.