Comparison of tissue acquisition techniques for Next-Generation Sequencing of non-small cell lung cancer (NSCLC).

[BACKGROUND] Next-Generation Sequencing (NGS) allows the use of more efficacious targeted treatments for lung cancer; however, sample inadequacy can cause delays in patient pathways. Here, we compare various methods of tissue acquisition used in clinical practice and identify factors associated with inadequate sampling.

[MATERIALS AND METHODS] Specimens submitted for NGS from a large single-centre UK academic institution following confirmation of lung cancer were reviewed. The primary objectives were to assess the proportion in which such analysis was successfully completed and identify factors, including the method of tissue acquisition, associated with sample inadequacy for, or failure of, the analysis. Secondary analyses included an assessment of genomic alterations identified by NGS-based analysis and specimen processing times.

[RESULTS] DNA-based NGS analysis was successfully completed in 87.1% (n=511/587) of all specimens, with known oncogenic driver variants being identified in 60.6% (n=310/511). Success rates for specific specimen acquisition techniques included 90.0% (n=126/140) for endobronchial ultrasound-guided transbronchial needle aspiration, 79.3% (n=88/111) for percutaneous image-guided lung biopsies, 66.7% (n=14/21) for pleural fluid cell blocks and 60% (n=9/15) for percutaneous image-guided pleural biopsies.Sequential RNA-based NGS analysis was successfully completed in 81.4% (n=92/113) cases, yielding a further 20 fusion gene events. Overall, actionable genomic alterations were identified in a total of 28.0% (n=143/511) of specimens across DNA-based and RNA-based analyses.

[CONCLUSION] Pleural fluid cell blocks and percutaneous image-guided pleural biopsies were least likely to be associated with successful NGS-based processing. Where possible, other sites for tissue acquisition should be considered in individuals with pleural disease to prevent delays in their pathway.