Suitability of Bronchoscopic Biopsy Tissue Samples for Next-Generation Sequencing

Area of Science:

• Oncology
• Molecular Diagnostics
• Pulmonary Medicine

Background:

• Advanced non-small-cell lung cancer (NSCLC) diagnosis often relies on small biopsy specimens.
• Performing next-generation sequencing (NGS) typically requires a substantial tissue sample for a high success rate.
• Limited tissue availability poses a challenge for comprehensive molecular profiling in NSCLC patients.

Purpose of the Study:

• To evaluate the impact of biopsy sample size and tumor content on the success rate of NGS.
• To determine the minimum tissue surface area required for successful Oncomine Dx Target Test (ODxTT).
• To compare the efficacy of different bronchoscopic biopsy techniques in obtaining adequate samples for NGS.

Main Methods:

• Collected biopsy samples from 184 NSCLC patients.
• Assessed tissue surface area, tumor cell count, and tumor content rate.
• Evaluated the success rate of ODxTT based on tissue surface area (≥1 mm²) and tumor content rate (≥30%).
• Compared tissue acquisition using small endobronchial ultrasonography with a guide sheath (EBUS-GS), large EBUS-GS, and endobronchial biopsy (EBB).

Main Results:

• The mean tissue surface area varied by method: 1.23 mm² (small EBUS-GS), 2.16 mm² (large EBUS-GS), and 1.81 mm² (EBB).
• Proportion of samples ≥1 mm²: 48.8% (small EBUS-GS), 79.2% (large EBUS-GS), 78.6% (EBB).
• Overall DNA and RNA sequencing success rates were 84.1% and 92.7%, respectively.
• Large EBUS-GS and EBUS-TBNA yielded higher sequencing success rates (93.4-100%) compared to small EBUS-GS (57.1-71.4%) and EBB (62.5-100%).

Conclusions:

• A tissue surface area of ≥1 mm² is adequate for successful NGS testing, irrespective of the biopsy device used.
• Larger tissue samples obtained with techniques like large EBUS-GS and EBUS-TBNA improve NGS success rates.
• Optimizing biopsy techniques is crucial for maximizing molecular profiling success in NSCLC patients with limited tissue samples.