94P - Harnessing circulating tumor DNA in bronchoalveolar lavage fluid for precise molecular diagnosis of NSCLC

Background

Thirty percent of patients with early-stage NSCLC are treated without a pathological diagnosis. With upcoming neoadjuvant immuno- and targeted therapies it is important to complete a molecular diagnosis before treatment. Bronchoalveolar lavage fluid (BALF) is easily collected and minimal invasive but has poor diagnostical yield in standard cytological work-up. A potential new diagnostic tool could be detection of circulating tumor DNA (ctDNA), in which genetic and epigenetic alterations of the tumor can be detected. The aim of this study is to determine if cell free (cfDNA) analysis in BALF is representative for the molecular diagnosis in NSCLC.

Methods

49 BALF samples of patients with suspected NSCLC have been analyzed. During the routine bronchoscopy or EBUS, bronchoalveolar lavage was performed in the affected lobe and usual material for routine diagnostics was obtained. Samples were analyzed using the Oncomine PAN-Cancer Cell-free NGS panel and the molecular results were compared.

Results

Analysis has been done on 53 patients. In 42 patients a molecular alteration was found. In 79% of the cases the cfDNA analysis of the BALF was completely or partly representative. In 12 patients a molecular alteration was found in BALF while this was not found with a regular endoscopy (bronchoscopy and or EBUS). After more diagnostics (eg CT guided biopsy) 18 patients did not have a cyto-or histopathological molecular result pretreatment, 6 of those had a positive BALF cfDNA result. BALF analysis reduced the number of patients in this cohort without a pretreatment molecular diagnosis by a third.

Conclusions

In conclusion, cfDNA from BALF as a source for molecular diagnostics is highly comparable with routine diagnostic material and could reduce the number of patients treated without a molecular diagnosis. Furthermore, BALF is easily obtained, and the procedure is relatively minimal invasive. In 10 cases the only pathogenic variant found in BALF is a TP53 mutation. When only a TP53 mutation is found, no hard conclusions can be drawn regarding the origin of the tumor and thus the diagnosis NSCLC, since TP53 is also often found in other malignancies. As long as this is considered, BALF could be an additional diagnostic tool for patients with NSCLC.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The author.

Funding

Team Westland.

Disclosure

The author has declared no conflicts of interest.