RESUMEN
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is often the only source of tumor tissue from patients with advanced, inoperable lung cancer. EBUS-TBNA aspirates are used for the diagnosis, staging, and genomic testing to inform therapy options. Here we extracted DNA and RNA from 220 EBUS-TBNA aspirates to evaluate their suitability for whole genome (WGS), whole exome (WES), and comprehensive panel sequencing. For a subset of 40 cases, the same nucleic acid extraction was sequenced using WGS, WES, and the TruSight Oncology 500 assay. Genomic features were compared between sequencing platforms and compared with those reported by clinical testing. A total of 204 aspirates (92.7%) had sufficient DNA (100 ng) for comprehensive panel sequencing, and 109 aspirates (49.5%) had sufficient material for WGS. Comprehensive sequencing platforms detected all seven clinically reported tier 1 actionable mutations, an additional three (7%) tier 1 mutations, six (15%) tier 2-3 mutations, and biomarkers of potential immunotherapy benefit (tumor mutation burden and microsatellite instability). As expected, WGS was more suited for the detection and discovery of emerging novel biomarkers of treatment response. WGS could be performed in half of all EBUS-TBNA aspirates, which points to the enormous potential of EBUS-TBNA as source material for large, well-curated discovery-based studies for novel and more effective predictors of treatment response. Comprehensive panel sequencing is possible in the vast majority of fresh EBUS-TBNA aspirates and enhances the detection of actionable mutations over current clinical testing.
RESUMEN
BACKGROUND AND OBJECTIVES: Autofluorescence (AF) techniques improve the diagnostic yield of white light inspection for preneoplastic lesions in the bronchus and head and neck region. Although highly sensitive, AF has poor specificity, particularly in situations where there have been earlier biopsies or treatments such as radiotherapy. Narrow band imaging (NBI) is a newer imaging technique that enhances the early abnormal angiogenesis seen in preneoplastic lesions. NBI has higher specificity when compared with AF. We aimed to combine these imaging modalities, using AF as an effective screening tool and NBI to confirm AF findings. We also used computer-assisted image analysis techniques to give objective confirmation to our visual inspection. METHODS: Three patients were selected for image analysis of their NBI images using the L*a*b* color scale in manually drawn regions of interest of biopsy-confirmed areas. Each case compared pathology with a different benign condition: normal tissue, postbiopsy effect, and postradiation therapy change. Patients had white light followed by AF inspection. Abnormal areas of AF were cross-examined with NBI. RESULTS: NBI clearly showed dysplasia and carcinoma in situ. It also confirmed abnormal fluorescence because of earlier biopsies and radiation therapy. Analysis of the L*a*b* color space scale in each case showed segmentation between pathology and the benign tissue. CONCLUSIONS: There may be additive and discriminatory benefits of NBI after AF inspection. Further study with computer-assisted color segmentation techniques and image analysis is required before optical diagnosis can become a reality in bronchoscopic techniques in the future.
