A multi-institutional, multi-tumor analysis of fine needle aspiration (FNA) cytology smear (FNAC) performance in clinical comprehensive genomic profiling

Background . FNAC are generated during the FNA procedure - for example, commonly used in conjunction with endobronchial ultrasound (EBUS-FNA) as a minimally invasive tool for the diagnosis and management of non small-cell lung cancer (NSCLC) - as a histologic QC for the presence of malignant cells. Formalin-fixed core biopsies and aspirate cell blocks (FNACB) are then created for comprehensive genomic profiling (CGP). However, the routine pathology workup may render the FNACB unable to generate a CGP result, while the FNAC remain in reserve. In the current study we performed a retrospective multi-cancer, multi-institutional analysis of FNAC performance, including computed tumor purity analysis, using a regulated commercial grade CGP assay. Experimental procedures . 119 FNAC met minimum specimen cellularity (10K total cellularity) and DNA extraction (50ng) criteria for CGP. Extracted DNA from FNACS underwent hybrid-capture-based CGP for all classes of genomic alterations in 315 genes. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. A comparison set of 182 FNACB specimens underwent the same CGP assay. Individual specimen CGPs were annotated as Pass, Fail, or Qualified per computational biology standard procedures that factor in sequencing quality metrics such as mean target coverage and computational tumor purity modeling. Results . The 119 FNAC, collected at 14 different medical facilities, encompassed 44 distinct tumor disease ontologies (DO) from 17 unique anatomic biopsy sites. 105 of 119 FNACS (88%) received a passing report, 10 (8%) were qualified, and 4 (3%) failed. In the FNACB comparison group, 155 of 182 reports were pass (85%), 22 qualified (12%), and 5 failed (3%). The number of passing reports in FNACS versus FNACB was equivalent (P=0.5). The FNAC had a significantly higher mean target coverage than FNACB (703 vs 665; P= 0.04995). The average computational tumor purity metric was significantly higher in FNACS than in FNACB (57.9% vs. 45.3%; P=0.00001). Conclusions . This study provides new data from FNAC that further support their utility for clinical testing. FNAC derived from multiple medical facilities, biopsy sites, and tumor types were found to be equivalent or superior to FNACB for CGP. Finally, the relative cellular homogeneity and high tumor cell content of both FNAC and FNACB likely confirms the discohesiveness of malignant cells and enables CGP without required enrichment given that macrodissection would be challenging for these samples in a daily practice setting. Citation Format: Jonathan K. Killian, Dean Pavlick, Lindsay Croshier, John Truesdell, Chris Wright, Tim Brennan, Vera Banning, Lazaro Garcia, Laurie Gay, Gene Stirchak, Jo-Anne Vergilio, Christine Malboeuf, Nhu Ngo, Julia Elvin, Siraj Ali, Vince Miller, Jeffrey S. Ross. A multi-institutional, multi-tumor analysis of fine needle aspiration (FNA) cytology smear (FNAC) performance in clinical comprehensive genomic profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1694.