Feasibility of endobronchial ultrasound transbronchial needle aspiration for massively parallel next-generation sequencing in thoracic cancer patients.

INTRODUCTION: Next-generation sequencing (NGS) allows for the identification of a growing number of therapeutic and prognostic molecular targets. However, NGS typically requires greater quantities of DNA than traditional molecular testing does. Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure used to sample central thoracic lesions, but it is not well established whether this technique provides sufficient material for NGS.

METHODS: We performed a retrospective review of EBUS-TBNA at our institution (3/1/14-9/28/16). NGS was performed using a comprehensive hybrid-capture based assay (MSK-IMPACT) that detects >340 gene mutations. Samples found to be diagnostic for malignancy and for which MSK-IMPACT had been attempted were identified. Pathologic and clinical data were obtained from the medical record, and the results of MSK-IMPACT were examined.

RESULTS: In total, 784 EBUS-TBNA procedures were performed during the study period. MSK-IMPACT was requested for 115 malignant samples and was successful for 99 (86.1%), identifying an average of 12.7 mutations at a mean coverage depth of 806X. NGS was performed on paraffin-embedded cell blocks in 93 cases (93.9%) and on cell-free DNA in needle rinse fluid in 6 cases. The success rate of the assay improved significantly from the first third of cases (76.3%), to 92.3% for the final one-third of cases (p < 0.05).

CONCLUSIONS: EBUS-TBNA reliably provided adequate tissue for hybrid capture NGS, and is a suitable option for comprehensive NGS testing in patients with thoracic malignancies.