Exploring the potential of cell free tumor DNA in bronchoscopic diagnosis of peripheral lung lesions- The DRILL study

<bold>Background:</bold> Small lung lesions can represent low stages of lung cancer but are difficult to diagnose. The bronchoscopic approach has the lowest risk of complications, however the diagnostic yield is generally lower than with other modalities. Cell free tumor DNA (cftDNA) is fragmented DNA stemming from a tumor. CftDNA has previously been detected in bronchial lavage (BL) and has been proposed as an adjunct to conventional biopsies to improve diagnostic yield. The aim of this study was to assess whether cftDNA in BL could serve as an add-on diagnostic modality to bronchoscopic tissue sampling. <bold>Methods:</bold> The study was conducted as a prospective diagnostic accuracy study in accordance with STARD guidelines. Patients undergoing bronchoscopy for diagnosing peripheral lung lesions were included. During bronchoscopy BL samples were collected before and after biopsy. The samples were analyzed for cftDNA using a predefined cut-off and compared to histopathology or six months of CT surveillance. <bold>Results:</bold> One-hundred and seventy-two patients were included with samples collected from 155 patients. 47.1 % of the patients had a definite diagnosis from the biopsies. The sensitivity and specificity of cftDNA in BL was 67.7% (57.5% - 76.7%) and 74.4 (57.9 -87.0), respectively. The Positive likelihood ratio of cftDNA in patients with a non-diagnostic biopsy was nearly 2. <bold>Conclusions:</bold> The diagnostic accuracy of cftDNA in BL were too low to confirm or refute malignancy following an inconclusive biopsy, however BL was superior to blood samples.