Highlights
- •The performance of extensive DNA and RNA NGS panels using EBUS-TBNA samples is highly successful.
- •Sampling more advanced nodal stations and samples with higher tumor cellularity are associated with a higher likelihood of DNA NGS success.
- •More than 3 EBUS-TBNA passes from the same nodal station did not result in better NGS performance.
Abstract
Introduction/Background
Samples from endobronchial ultrasound-guided fine needle aspiration (EBUS-TBNA) are
frequently used for next generation sequencing (NGS) in patients with non-small cell
lung cancer (NSCLC) to look for genetic driver mutations. The objective of the current
study was to evaluate the performance of extended NGS panels using EBUS-TBNA samples
in a real-world setting and identify factors associated with the success of NGS.
Materials and Methods
This study included all patients who underwent EBUS and were diagnosed with non-squamous
NSCLC with mediastinal metastasis from 2016 to 2019 at the University of Pennsylvania.
We reviewed demographic information, imaging studies, procedure reports, pathology
and NGS reports. Logistic regression was used to analyze factors associated with the
success of NGS panels.
Results
The success rates of NGS using EBUS-TBNA samples were 92.5%, and 91.5% for DNA and
RNA NGS panels respectively. Samples from higher N stage (N2 and N3 lymph nodes) and
with higher tumor cellularity (>25%) resulted in higher success rate for DNA NGS.
The effect of tumor cellularity remained borderline significant after entering multivariable
logistic regression. The short-axis diameter of the sampled lymph node on CT scan,
FDG-avidity on PET CT and >3 EBUS passes per lymph node during the procedure were
not associated with NGS success.
Conclusion
Both DNA and RNA extended-panel NGS had high performance using EBUS-TBNA samples.
Sampling more advanced nodal stations and obtaining samples with higher tumor cellularity
were associated with higher success rate of DNA NGS. Other imaging or procedural factors
did not affect NGS performance.
Keywords
Abbreviations:
NGS (next generation sequencing), NSCLC (non-small cell lung cancer), EBUS-TBNA (endobronchial ultrasound-guided transbronchial needle aspiration), FNA (fine needle aspiration), ROSE (rapid on-site evaluation), FB (flexible Bronchoscopy), EBBx (endobronchial biopsy), TBBx (transbronchial biopsy), IHC (immunohistochemistry stains), STP (solid tumor panel), FTP (fusion transcription panel), PD-L1 (programmed death-ligand 1), EML4-ALK (Echinoderm microtubule-associated protein-like 4 - anaplastic lymphoma kinase), RET (rearranged during transfection), ROS1 (proto-oncogene tyrosine-protein kinase 1), FISH (fluorescence in situ hybridization), CT (computed tomography), PET (positron emission tomography), FDG (Fluorodeoxyglucose), SUVmax (maximum standardized uptake value), IQR (interquartile range), OR (Odds Ratio), CI (confidence interval), ctDNA (circulating tumor DNA), FFPE (formalin-fixed paraffin-embedded)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Lung CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
REFERENCES
- Cancer statistics, 2021.Ca Cancer J Clin. 2021; 71: 7-33https://doi.org/10.3322/caac.21708
- Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409https://doi.org/10.1056/NEJMoa1102873
- Combined Inhibition of EGFR and VEGF pathways in patients with EGFR-mutated non-small cell lung cancer: a systematic review and meta-analysis.Curr Oncol Rep. 2020; 22: 119https://doi.org/10.1007/s11912-020-00981-0
- Perspective on treatment for unresectable locally advanced non-small cell lung cancer with oncogene-driven mutation: a narrative review.Transl Lung Cancer Res. 2020; 9: 2137-2144https://doi.org/10.21037/tlcr-20-722
- Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the college of american pathologists, the international association for the study of lung cancer, and the association for molecular pathology.J Mol Diagn. 2018; 20: 129-159https://doi.org/10.1016/j.jmoldx.2017.11.004
- Molecular diagnostic profiling of lung cancer specimens with a semiconductor-based massive parallel sequencing approach: feasibility, costs, and performance compared with conventional sequencing.J Mol Diagn. 2013; 15: 765-775https://doi.org/10.1016/j.jmoldx.2013.06.002
- Library construction for next-generation sequencing: overviews and challenges.Biotechniques. 2014; 56: 61-64https://doi.org/10.2144/000114133
- Next generation sequencing for gene fusion analysis in lung cancer: a literature review.Diagnostics (Basel). 2020; 10: 521https://doi.org/10.3390/diagnostics10080521
- Guideline for the acquisition and preparation of conventional and endobronchial ultrasound-guided transbronchial needle aspiration specimens for the diagnosis and molecular testing of patients with known or suspected lung cancer.Respiration. 2014; 88: 500-517https://doi.org/10.1159/000368857
- Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group.Thorax. 2016; 71: 177-184https://doi.org/10.1136/thoraxjnl-2014-206677
- Biomarker testing in lung carcinoma cytology specimens: a perspective from members of the pulmonary pathology society.Arch Pathol Lab Med. 2016; 140: 1267-1272https://doi.org/10.5858/arpa.2016-0091-SA
- Clinical next-generation sequencing in patients with non-small cell lung cancer.Cancer. 2015; 121: 631-639https://doi.org/10.1002/cncr.29089
- Feasibility of endobronchial ultrasound transbronchial needle aspiration for massively parallel next-generation sequencing in thoracic cancer patients.Lung Cancer. 2018; 119: 85-90https://doi.org/10.1016/j.lungcan.2018.03.003
- RNA-based assay for next-generation sequencing of clinically relevant gene fusions in non-small cell lung cancer.Cancers (Basel). 2021; : 13https://doi.org/10.3390/cancers13010139
- The eighth edition lung cancer stage classification.Chest. 2017; 151: 193-203
- Using “residual” FNA rinse and body fluid specimens for next-generation sequencing: an institutional experience.Cancer Cytopathology. 2016; 124: 324-329https://doi.org/10.1002/cncy.21666
- How we read oncologic FDG PET/CT.Cancer Imaging. 2016; 16: 1-4
- A systematic review and meta-analysis of the adequacy of endobronchial ultrasound transbronchial needle aspiration for next-generation sequencing in patients with non-small cell lung cancer.Lung Cancer. 2022; 166: 17-26https://doi.org/10.1016/j.lungcan.2022.01.018
- Feasibility of endobronchial ultrasound-guided transbronchial needle aspiration cytology specimens for next generation sequencing in non-small-cell lung cancer.Clin Lung Cancer. 2018; 19: e232https://doi.org/10.1016/j.cllc.2017.11.010
- The impact of core tissues on successful next-generation sequencing analysis of specimens obtained through endobronchial ultrasound-guided transbronchial needle aspiration.Cancers (Basel). 2021; : 13https://doi.org/10.3390/cancers13235879
- Suitability of bronchoscopic biopsy tissue samples for next-generation sequencing.Diagnostics (Basel). 2021; : 11https://doi.org/10.3390/diagnostics11030391
- Next generation sequencing for liquid biopsy based testing in non-small cell lung cancer in 2021.Crit Rev Oncol Hematol. 2021; 161103311https://doi.org/10.1016/j.critrevonc.2021.103311
- RAS testing of colorectal carcinoma—a guidance document from the association of clinical pathologists molecular pathology and diagnostics group.Practice Guideline. 2014; 67: 751-757https://doi.org/10.1136/jclinpath-2014-202467
- Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists.J Mol Diag. 2017; 19: 4-23https://doi.org/10.1016/j.jmoldx.2016.10.002
- The role of EBUS-TBNA in lung cancer restaging and mutation analysis.Mediastinum. 2020; 4: 23https://doi.org/10.21037/med-20-24
Article info
Publication history
Published online: December 04, 2022
Accepted:
November 23,
2022
Received in revised form:
November 23,
2022
Received:
September 21,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
