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

Abstract

Background: Small lung lesions can represent early-stage lung cancer but are difficult to diagnose. The bronchoscopic approach has the lowest risk of complications; however, the diagnostic yield is generally lower compared to trans-thoracic biopsies. Cell-free tumor DNA (cftDNA) is fragmented DNA stemming from a tumor. CftDNA in the form of methylated HOXA9 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 methylated HOXA in BL could be utilized as an add-on diagnostic modality for bronchoscopic tissue sampling.

Method: 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 methylated HOXA using a predefined cutoff and compared to histopathology or the result of CT surveillance.

Results: One hundred seventy-two patients were included, with samples collected from 155 patients. A definite diagnosis was obtained from bronchoscopic biopsies in 47.1%. The sensitivity and specificity of methylated HOXA9 in BL were 68.0 (58.0-76.8) and 76.3 (59.8-88.6), respectively. The positive likelihood ratio of methylated HOXA9 in patients with a non-diagnostic biopsy was 2.11.

Conclusion: The diagnostic accuracy of methylated HOXA9 in BL was too low to confirm or refute malignancy following an inconclusive biopsy; however, BL was superior to blood samples.