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

## TL;DR

This study compares different tissue sampling methods for lung cancer sequencing, finding that some techniques are less reliable and may delay treatment.

## Contribution

The study identifies specific tissue acquisition methods associated with higher success rates for NGS in non-small cell lung cancer.

## Key findings

- DNA-based NGS was successful in 87.1% of specimens, with endobronchial ultrasound-guided techniques showing the highest success rate.
- Pleural fluid cell blocks and percutaneous pleural biopsies had the lowest success rates for NGS processing.
- Actionable genomic alterations were found in 28% of specimens, with RNA-based analysis revealing additional fusion gene events.

## Abstract

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.

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.

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.

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.