Original Article

Protocol to Improve Genotyping of Non-Small-Cell Lung Cancer Diagnosed Using EBUS-TBNA

Authors: Christina R. Bellinger, MD, Deepankar Sharma, MD, Travis Dotson, MD, Jimmy Ruiz, MD, Graham Parks, MD, Edward F. Haponik, MD

Abstract

Objectives: Targeted therapies for non-small-cell lung cancers (NSCLCs) are based on the presence of driver mutations such as epidermal growth factor receptor (EGFR) and the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation. Endobronchial ultrasound-guided-transbronchial needle aspiration (EBUS-TBNA) is a first-line modality for diagnosing and staging NSCLC. A quality improvement protocol maximizing tissue acquisition for molecular analysis has not been previously described.

Methods: We instituted a standardized protocol designed from a multidisciplinary meeting of the pulmonology, oncology, and pathology departments for the acquisition and on-site processing of samples obtained through EBUS-TBNA to improve the yield for genetic analysis of EGFR and ALK testing.

Results: Preprotocol there were 50 NSCLCs (29 adenocarcinomas) and postprotocol there were 109 NSCLCs (52 adenocarcinomas). A statistically significant increase in yield for molecular analysis was seen in both EGFR (36% preprotocol and 80% postprotocol, P < 0.01) and ALK (41% preprotocol and 80% postprotocol, P < 0.01). There was no difference in complications preprotocol and postprotocol.

Conclusions: Implementation of a standardized protocol with EBUS-TBNA was associated with an increase in adequacy for molecular genetic analysis in NSCLC.

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References

1. Kreamer K, Riordan D. Targeted therapies for non-small cell lung cancer: an update on epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors. Clin J Oncol Nurs 2015;19:734-742.
 
2. Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143(suppl 5):e142S-165S.
 
3. Eberhard DA, Giaccone G, Johnson BE, et al. Biomarkers of response to epidermal growth factor receptor inhibitors in Non-Small-Cell Lung Cancer Working Group: standardization for use in the clinical trial setting. J Clin Oncol 2008;26:983-994.
 
4. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010;363:1693-1703.
 
5. Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143(suppl 5):e211S-250S.
 
6. Herth FJ. Nonsurgical staging of the mediastinum: EBUS and EUS. Semin Respir Crit Care Med 2011;32:62-68.
 
7. Nakajima T, Yasufuku K, Suzuki M, et al. Assessment of epidermal growth factor receptor mutation by endobronchial ultrasound-guided transbronchial needle aspiration. Chest 2007;132:597-602.
 
8. Esterbrook G, Anathhanam S, Plant P. Adequacy of endobronchial ultrasound transbronchial needle aspiration samples in the subtyping of non-small cell lung cancer. Lung Cancer 2013;80:30-34.
 
9. Schuurbiers OCJ, Looijen-Salamon MG, Ligtenberg MJL, et al. A brief retrospective report on the feasibility of epidermal growth factor receptor and KRAS mutation analysis in transesophageal ultrasound- and endobronchial ultrasound-guided fine needle cytological aspirates. J Thorac Oncol 2010;5:1664-1667.
 
10. Jurado J, Saqi A, Maxfield R, et al. The efficacy of EBUS-guided transbronchial needle aspiration for molecular testing in lung adenocarcinoma. Ann Thorac Surg 2013;96:1196-1202.
 
11. Trisolini R, Cancellieri A, Tinelli C, et al. Randomized trial of endobronchial ultrasound-guided transbronchial needle aspiration with and without rapid on-site evaluation for lung gancer genotyping. Chest 2015;148:1430-143.
 
12. Yarmus L, Akulian J, Gilbert C, et al. Optimizing endobronchial ultrasound for molecular analysis. How many passes are needed? Ann Am Thorac Soc 2013;10:636-643.
 
13. Akulian J, Yarmus L, Feller-Kopman D. Tissue acquisition and specimen processing in the diagnosis of NSCLC. Semin Respir Crit Care Med 2013;34:787-791.
 
14. Ruggiero JE, Rughani J, Neiman J, et al. Real-world concordance of clinical practice with ASCO and NCCN guidelines for EGFR/ALK testing in aNSCLC. J Clin Oncol 2017;35(suppl):212.
 
15. Bellinger C, Chatterjee AB, Chin R, Jr et al. Conventional and endobronchial ultrasound-guided transbronchial needle aspiration (TBNA): complementary procedures. South Med J 2012;105:625-629.
 
16. Bellinger C, Chatterjee AB, Adair N, et al. Training in and experience with endobronchial ultrasound. Respiration 2014;88:478-483.
 
17. Miller VA, Kris MG, Shah N, et al. Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced nonsmall-cell lung cancer. J Clin Oncol 2004;22:1103-1109.
 
18. Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection f lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol 2013;8:823-859.
 
19. Gasparini P, Cascione L, Landi L, et al. microRNA classifiers are powerful diagnostic/prognostic tools in ALK-, EGFR-, and KRAS-driven lung cancers. Proc Natl Acad Sci USA 2015;112:14924-14929.
 
20. Bellinger CR, Ruiz J, Dotston T. Negative predictive value of endobronchial ultrasound-guided transbronchial needle aspiration. Clin Pulm Med 2016;23:86-90.
 
21. Ost DE, Ernst A, Lei X, et al. Diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration: results of the AQuIRE Bronchoscopy Registry. Chest 2011;140:1557-1566.
 
22. Casal RF, Lazarus DR, Kuhl K, et al. Randomized trial of endobronchial ultrasound-guided transbronchial needle aspiration under general anesthesia versus moderate sedation. Am J Resp Crit Care Med 2015;191:796-803.
 
23. Dhooria S, Sehgal IS, Gupta N, et al. Diagnostic yield and complications of EBUS-TBNA performed under bronchoscopist-directed conscious sedation: single center experience of 1004 subjects. J Bronchology Interven Pulmonol 2017;24:7-14.
 
24. Hopkins E, Moffat D, Parkinson I, et al. Cell block samples from endobronchial ultrasound transbronchial needle aspiration provide sufficient material for ancillary testing in lung cancer-a quarternary referral centre experience. J Thorac Dis 2016;8:2544-2550.
 
25. Jeyabalan A, Bhatt N, Plummeridge MJ, et al. Adequacy of endobronchial ultrasound-guided transbronchial needle aspiration samples processed as histopathological samples for genetic mutation analysis in lung adenocarcinoma. Mol Clin Oncol 2016;4:119-125.