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

Keigo Uchimura,Hideaki Furuse,Takaaki Tsuchida,Shinji Sasada,Yuki Takeyasu,Midori Tanaka,Tatsuya Imabayashi,Yuji Matsumoto,Komei Yanase

doi:10.3390/cancers13235879

Abstract

Simple SummaryNext-generation sequencing (NGS) with specimens obtained through endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been used to identify cancer-related genes among patients with lung cancer. However, the reported success rates vary, and the clinical factors associated with successful NGS remain unclear. We retrospectively reviewed consecutive patients with non-small-cell lung cancer who underwent EBUS-TBNA for NGS (OncomineTM Dx Target Test). The numbers of punctures and core tissues, as well as computed tomography (CT) and EBUS findings, were evaluated. The success rate of NGS was 83.3% (130/156). The cut-off value for the number of core tissues was 4, and the sensitivity and specificity for successful NGS were 73.8% and 61.5%, respectively. CT and EBUS findings were not associated with successful NGS. In logistic regression analysis, the number of core tissues (≥4) was the sole predictor of successful NGS. Bronchoscopists should obtain sufficient core tissues for successful NGS using EBUS-TBNA specimens.The success rate of next-generation sequencing (NGS) with specimens obtained through endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) among patients with lung cancer as well as the related clinical factors remain unclear. We aimed to determine the optimal number of punctures and core tissues during EBUS-TBNA for NGS in patients with non-small-cell lung cancer (NSCLC) as well as the association of chest computed tomography (CT) and EBUS findings with successful NGS. We retrospectively reviewed 156 consecutive patients with NSCLC who underwent EBUS-TBNA for NGS (OncomineTM Dx Target Test). Using the receiver operating characteristic curve, we calculated the optimal numbers of punctures and core tissues for NGS and evaluated CT and EBUS findings suggestive of necrosis and vascular pattern within the lesion. The success rate of NGS was 83.3%. The cut-off value for the number of core tissues was 4, and the sensitivity and specificity of successful NGS were 73.8% and 61.5%, respectively. Logistic regression analysis revealed that the number of core tissues (≥4) was the sole predictor of successful NGS. CT and EBUS findings were not associated with successful NGS. Bronchoscopists should obtain sufficient core tissues for successful NGS using EBUS-TBNA specimens.

Highlights

Various molecular-targeted drugs for treating patients with advanced-stage non-smallcell lung cancer (NSCLC) that are tailored for specific driver gene mutations, including epidermal growth factor receptor gene (EGFR), fusions of echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4/ALK), c-ros oncogene 1 (ROS1), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF), improve prognosis better than conventional cytotoxic chemotherapy [1–5]
Logistic regression analysis revealed that the number of core tissues (≥4) was the only independent predictor of successful next-generation sequencing (NGS) with EBUS-TBNA specimens
Our results demonstrated that NGS could be performed even for EBUS-TBNA specimens obtained from target lesions with necrosis or/and abundant blood flow if such basic puncture site selection is performed

Summary

Introduction

Various molecular-targeted drugs for treating patients with advanced-stage non-smallcell lung cancer (NSCLC) that are tailored for specific driver gene mutations, including epidermal growth factor receptor gene (EGFR), fusions of echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4/ALK), c-ros oncogene 1 (ROS1), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF), improve prognosis better than conventional cytotoxic chemotherapy [1–5]. Companion diagnostic tests for each gene mutation were used; next-generation sequencing (NGS) has recently allowed simultaneous searching of various gene mutation types [7,8]. In 2017, the US Food and Drug Administration approved the OncomineTM Dx Target Test (ODxTT; Thermo Fisher Scientific, San Jose, CA, USA) as an NGS-based companion diagnosis for NSCLC. Compared with previous companion diagnostic tests, NGS requires tumor tissues with sufficient quantity and quality, including tumor content ratio and the number of tumor cells in the specimens. Recent studies have reported on the success rate of NGS using bronchoscopic specimens [8,10–19]

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