Molecular analysis of peripheral non-squamous non-small cell lung cancer sampled by radial EBUS

• Published in: Respirology (Carlton, Vic.) Vol. 21; no. 4; pp. 718 - 726
• Main Authors: Guisier, Florian, Salaün, Mathieu, Lachkar, Samy, Lamy, Aude, Piton, Nicolas, Obstoy, Bérengère, Sabourin, Jean-Christophe, Thiberville, Luc
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01-05-2016; Wiley
• Subjects: Aged; Aged, 80 and over; Biopsy; Bronchoscopy - instrumentation; Bronchoscopy - methods; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Female; Gene Rearrangement; Humans; Life Sciences; Lung - pathology; lung adenocarcinoma; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Middle Aged; molecular analysis; Mutation; navigational bronchoscopy; peripheral lung nodule; Phosphatidylinositol 3-Kinases - genetics; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins p21(ras) - genetics; radial endobronchial-ultrasound bronchoscopy; Receptor Protein-Tyrosine Kinases - genetics; Receptor, Epidermal Growth Factor - genetics; Receptor, ErbB-2 - genetics; Ultrasonography, Interventional - methods; radial endobronchial-ultrasound bronchoscopy; peripheral lung nodule; molecular analysis; lung adenocarcinoma; navigational bronchoscopy
• ISSN: 1323-7799; 1440-1843
• DOI: 10.1111/resp.12737

Background and objective
Treatment optimization of non‐squamous non‐small‐cell lung cancers (nonSq‐NSCLC) relies on the molecular analysis of the tumour. We aimed to assess the predictive factors of molecular analysis feasibility (MAF) from samples of peripheral nonSq‐NSCLC obtained by radial endobronchial ultrasound bronchoscopy (r‐EBUS) and 1.5 mm microbiopsy forceps.
Methods
We reviewed data from consecutive peripheral lung nodules sampled with r‐EBUS between January 2012 and July 2014 at a single French University Hospital. nonSq‐NSCLC were systematically analysed for EGFR, KRAS, ALK, HER2, PI3K and BRAF throughout the study, and c‐MET and ROS1 alterations for the last 10 months.
Results
Of 111 nonSq‐NSCLC diagnosed by r‐EBUS (113 procedures, mean nodule diameter 28 ± 15 mm), 88 were analysed for EGFR and ALK, 87 for KRAS, 86 for HER2, PI3K and BRAF and 14 for c‐MET. Forty‐one mutations were identified (23 KRAS, 10 EGFR, 2 BRAF, 1 HER2 and 5 ALK rearrangements). Four c‐MET overexpressions were noted. MAF rose from 67% for the first 57 procedures to 89% for the last 56 procedures (P = 0.02) likely due to a higher number of biopsies performed (2 ± 1 vs 3 ± 2, P = 0.005). Upper or middle lobe location (OR 1.19, 95% CI: 1.02–1.38, P = 0.03), and at least three biopsies (OR 1.20, 95% CI: 1.04–1.40, P = 0.02) were predictive factors of MAF. Percentage of tumour cells, size of lesion and distance to the pleura did not correlate with MAF.
Conclusion
Multi‐gene molecular analysis could be performed in nearly 80% of paraffin‐embedded biopsies or smear specimens sampled by r‐EBUS assisted bronchoscopy of peripheral tumoral lung nodules.
The optimal treatment of non‐squamous non‐small cell lung cancer currently needs the realization of molecular analysis from the initial diagnostic biopsy sampling. This study shows that multi‐gene analysis (EGFR, ALK, HER2, BRAF) is feasible in 80% of routine radial‐EBUS assisted bronchoscopy sampling of peripheral lung nodules.