Comparison of adequacy between transbronchial lung cryobiopsy samples and endobronchial ultrasound‐guided transbronchial needle aspiration samples for next‐generation sequencing analysis

Abstract

Background: Most lung cancer patients present with lesions in both lung fields and lymphadenopathy. Thus, transbronchial lung cryobiopsy (TBLC) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are commonly performed for diagnosing lung cancer. However, the adequacy of these samples for next-generation sequencing (NGS) analysis remains unclear. This study aimed to compare the adequacy between TBLC and EBUS-TBNA samples for NGS analysis. Methods: This retrospective cohort study included patients whose lung samples were collected via TBLC or EBUS-TBNA and analyzed using NGS. Out of 46 genes, the number of genes in TBNA and TBLC samples that could not be assessed via NGS analysis was mainly evaluated. Results: A total of 37 patients were included and classified into two groups (TBLC group, n = 18 and TBNA group, n = 19). The mean number of genes that could not be evaluated via NGS analysis was significantly lower in the TBLC group than in the TBNA group (0.9 vs. 10.3, P = 0.024). The median total area of tumor cells in TBLC samples was significantly greater than that in TBNA samples (6.3 [1.6-4.2] vs. 2.6 [0.2-17.3] mm 2 , P < 0.01). In the TBNA group, there were two fully inadequate samples for NGS analysis with a high degree of cell crush or low tumor content, while there was no fully inadequate sample in the TBLC group. Conclusions: TBLC is more effective in obtaining adequate samples for NGS analysis than EBUS-TBNA. TBLC should be performed to obtain adequate samples for NGS analysis in lung cancer patients with target lesions in lung fields, even if they have lymphadenopathy.

Suitability of Bronchoscopic Biopsy Tissue Samples for Next-Generation Sequencing

“…Blood contamination was detected in the EBUS-TBNA samples, which could have affected the tumor content ratio [23,24]. The low tumor content ratio in the EUBS-TBNA samples and the high concentration of crushed tumor cells could reduce the success rate of NGS analyses [22]. The success rate of the ODxTT on the EBUS-TBNA samples was high (100%) in the present study.…”

“…Therefore, NGS analyses that can detect large numbers of genes require large tumor samples, and the success rate of NGS using small samples can be low [20]. In a previous study using ODxTT, all 18 samples collected with TBB and cryobiopsy were considered successful [22]. The mean total area of the samples was 8.5 mm 2 (3.6-32.0 mm 2 ).…”

The Impact of Core Tissues on Successful Next-Generation Sequencing Analysis of Specimens Obtained through Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

“…NGS panels vary according to institution and country. We used ODxTT, which is a relatively small-panel NGS testing method that can analyze 46 cancer-related genes [5,[9][10][11][12][13].…”

“…In 2017, the US Food and Drug Administration approved the Oncomine TM Dx Target Test (ODxTT; Thermo Fisher Scientific, San Jose, CA, USA) as an NGS-based companion diagnosis for NSCLC. Using as little as 10 ng of DNA or RNA, it can simultaneously evaluate 46 cancer-related genes [ 5 , 9 , 10 , 11 , 12 , 13 , 14 ]; further, it facilitates companion diagnosis of the following driver oncogenes: EGFR , EML4/ALK , ROS1 , and BRAF . The ODxTT multi-companion diagnostics (CDx) system is a common NGS test covered by insurance in Japan.…”

Safety Profile and Risk Factors for Bleeding in Transbronchial Cryobiopsy Using a Two-Scope Technique for Peripheral Pulmonary Lesions

“…On the other hand, unlike ILD, cryobiopsy can be avoided in places with large blood vessels such as bronchial arteries by referring to R-EBUS images routinely checked in PPLs [31]. Furthermore, several (3-6) cryobiopsies from multiple areas and lobes are required to reduce sampling error in ILDs, whereas 1-2 specimens from one area are clinically su cient for diagnosis of lung cancer and nextgeneration sequencing [32,33]. In addition to effective hemostasis with the technique, the above differences in clinical backgrounds may have led to differences in the degree of bleeding between PPLs and ILDs with cryobiopsy.…”