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

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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 forEGFR,KRAS,ALK,HER2, PI3KandBRAFthroughout the study, andc-METandROS1alterations 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 forEGFRandALK, 87 forKRAS,86 forHER2,PI3KandBRAFand 14 for c-MET. Forty-one mutations were identified (23KRAS, 10EGFR, 2BRAF, 1HER2and 5ALKrearrangements). Fourc-METoverexpressions 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.SUMMARY AT A GLANCEThe 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.

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