Feasibility of comprehensive genotyping specimens from radial endobronchial ultrasonography and electromagnetic navigation bronchoscopy

Abstract

IntroductionMini-invasive bronchoscopic techniques (such as radial endobronchial ultrasonography (rEBUS) and electromagnetic navigation (EMN)) have been developed to reach the peripheral lung but result in small samples. The feasibility of an adequate molecular testing from these specimens has been very little studied.MethodsWe retrospectively reviewed EMN and rEBUS procedures performed in patients diagnosed with lung cancer in our institution in 2017 and 2018. We analysed the sensitivity for rEBUS and EMN and each sampling method, and the feasibility of a comprehensive molecular testing.Results317 rEBUS and 14 EMN were performed. Median sizes of tumors were 16 and 32 mm for EMN and rEBUS, respectively. Overall sensitivity for rEBUS and EMN was 84.3%. Cytology was found to be complementary with biopsies, with 13.3% of cancer diagnosed on cytology while biopsies were negative. Complication rate was 2.4% (pneumothorax 1.5%, mild hemoptysis 0.9%). Genotyping (immunohistochemistry (IHC) for ROS1 and ALK followed by FISH if positive and hybrid capture next-generation sequencing (NGS) covering 48-genes), when ordered (n=188), was feasible in 69.1% (EGFR 17.7%, KRAS 31.7%, BRAF 4.8%, ALK 1.2%, MET 3.1%, HER2 0.8%). PD-L1 expression, when ordered (n=232), could be analysed in 94% of cases. 56.9% (33/58) of patients for whom genotyping was not feasible underwent a second sampling (12 pretreatment, 21 at progression), allowing for the detection of 6 actionable genotypes (5 EGFR, 1 MET).ConclusionrEBUS and EMN are sensitive and safe procedures that result in limited samples, often not suitable for genotyping, highlighting the importance to integrate liquid biopsy in routine.

Suitability of transbronchial needle aspiration for genotyping peripheral pulmonary tumors

“…Fielding et al ( 20 ) achieved high concordance rates in detecting mutations between smeared cytology and cell block and showed that DNA extracted from smears has higher rates of mutations than DNA obtained by cell block. Robin M et al ( 21 ), using both cytology and histology samples, were able to genotyping the tumor in 69.1% and to evaluate PD-L1 expression in 94% of 331 patients who underwent transbronchial approach to lung tumor with the guidance of rEBUS or electromagnetic navigation. However, in that study the cytological material was obtained only by brushing and catheter rinse.…”

NSCLC in the Era of Targeted and Immunotherapy: What Every Pulmonologist Must Know

“…One report evaluated feasibility of NGS and PD-L1 testing from samples obtained via rEBUS and ENB procedures. PD-L1 testing was successfully performed on 94% (n = 232) of cases [ 66 ]. A smaller cohort underwent subsequent surgical resection with perfect concordance among the 50% threshold (n = 15), whereas the >1% threshold identified three false negative cases (n = 8) from bronchoscopy specimens [ 66 ].…”

“…PD-L1 testing was successfully performed on 94% (n = 232) of cases [ 66 ]. A smaller cohort underwent subsequent surgical resection with perfect concordance among the 50% threshold (n = 15), whereas the >1% threshold identified three false negative cases (n = 8) from bronchoscopy specimens [ 66 ]. Unfortunately, exhausted tissue, leading to unacceptable NGS analysis, affected 30.9% (n = 188) of cases, disproportionately impacting early-stage disease [ 66 ].…”

“…A smaller cohort underwent subsequent surgical resection with perfect concordance among the 50% threshold (n = 15), whereas the >1% threshold identified three false negative cases (n = 8) from bronchoscopy specimens [ 66 ]. Unfortunately, exhausted tissue, leading to unacceptable NGS analysis, affected 30.9% (n = 188) of cases, disproportionately impacting early-stage disease [ 66 ]. These results suggest the importance of procuring larger tissue samples while maintaining a minimally invasive approach.…”

Detection of Tumor DNA in Bronchoscopic Fluids in Peripheral NSCLC: A Proof-of-Concept Study

“…Unfortunately, in approximately 30% of cases, these samples are noncontributory for genomic analysis owing to a lack of available tumor tissue. 5 , 6 , 7 In this context, ctDNA analysis could represent an alternative for genomic characterization.…”