Comparison of endoscopic ultrasound-guided fine-needle biopsy versus fine-needle aspiration for genomic profiling and DNA yield in pancreatic cancer: a randomized crossover trial

Abstract

Background National guidelines recommend genomic profiling of tumor tissue to guide precision therapy. We compared the specimen adequacy for genomic profiling and yield of DNA between endoscopic ultrasound (EUS)-guided fine-needle biopsy (FNB) and EUS-guided fine-needle aspiration (FNA).

Methods In our tandem, randomized controlled trial, consecutive patients undergoing EUS for evaluation of pancreatic masses underwent both conventional EUS-FNA with a 25-gauge needle and paired EUS-FNB (19 or 22-gauge needle), with the order randomized (EUS-FNA first followed by EUS-FNB, or vice versa). A minimum of one pass with each needle was obtained for histology. Second and third passes were performed to collect DNA. Specimens were evaluated by a cytopathologist blinded to the needle type. Specimen adequacy for genomic profiling was calculated based on FoundationOne clinical diagnostic (CDx) adequacy requirements. We compared the adequacy for genomic profiling DNA (quantity) and histology yields with both needles.

Results Analysis included 50 patients (25 men; mean age 68 [standard deviation (SD) 13] years), with a mean lesion size of 38 (SD 17) mm; 37 lesions (74 %) were pancreatic ductal adenocarcinoma (PDAC). The mean DNA concentrations in PDAC by FNB and FNA needles were 5.930 (SD 0.881) µg/mL vs. 3.365 (SD 0.788) µg/mL, respectively (P = 0.01). The median standardized histology score per pass with EUS-FNB was 5 (sufficient for histology) and for EUS-FNA was 2 (enough for cytology). Specimen adequacy for genomic profiling and yield of DNA was significantly higher with FNB than with FNA needles.

Conclusions In this study, adequacy for genomic profiling, DNA, and histology yield were considerably superior using an EUS-FNB needle compared with an EUS-FNA needle.

• References

• 1 Rahib L, Smith BD, Aizenberg R. et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014; 74: 2913-2921
• 2 Shaib Y, Davila J, Naumann C. et al. The impact of curative intent surgery on the survival of pancreatic cancer patients: a US Population-based study. Am J Gastroenterol 2007; 102: 1377
• 3 Schmidt KT, Chau CH, Price DK. et al. Precision oncology medicine: the clinical relevance of patient‐specific biomarkers used to optimize cancer treatment. J Clin Pharmacol 2016; 56: 1484-1499
• 4 Golan T, Hammel P, Reni M. et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. NEJM 2019; 381: 317-327
• 5 Bang JY, Hawes R, Varadarajulu S. A meta-analysis comparing ProCore and standard fine-needle aspiration needles for endoscopic ultrasound-guided tissue acquisition. Endoscopy 2016; 48: 339-349
• 6 Wani S, Muthusamy VR, Komanduri S. EUS-guided tissue acquisition: an evidence-based approach (with videos). Gastrointest Endosc 2014; 80: 939-959. e937
• 7 Kandel P, Tranesh G, Nassar A. et al. EUS-guided fine needle biopsy sampling using a novel fork-tip needle: a case-control study. Gastrointest Endosc 2016; 84: 1034-1039
• 8 DiMaio CJ, Kolb JM, Benias PC. et al. Initial experience with a novel EUS-guided core biopsy needle (SharkCore): results of a large North American multicenter study. Endosc Int Open 2016; 4: E974-E979
• 9 Brais RJ, Davies SE, O’Donovan M. et al. Direct histological processing of EUS biopsies enables rapid molecular biomarker analysis for interventional pancreatic cancer trials. Pancreatology 2012; 12: 8-15
• 10 Cheng B, Zhang Y, Chen Q. et al. Analysis of fine-needle biopsy vs fine-needle aspiration in diagnosis of pancreatic and abdominal masses: a prospective, multicenter, randomized controlled trial. Clin Gastroenterol Hepatol 2018; 16: 1314-1321
• 11 Bang JY, Hebert-Magee S, Navaneethan U. et al. EUS-guided fine needle biopsy of pancreatic masses can yield true histology. Gut 2018; 67: 2081-2084
• 12 Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMC Med 2010; 8: 18
• 13 Paik WH, Park Y, Park DH. et al. Prospective evaluation of new 22 gauge endoscopic ultrasound core needle using capillary sampling with stylet slow-pull technique for intra-abdominal solid masses. J Clin Gastroenterol 2015; 49: 199-205
• 14 Foundation Medicine Inc. FoundationOne CDx: Specimen Instructions. 2019 Accessed 12 February 2020 https://assets.ctfassets.net/vhribv12lmne/6ms7OiT5PaQgGiMWue2MAM/53f9bdd91bfa22549087a28b53225fa5/F1_CDx_SpecimenInstructions_14.pdf
• 15 Foundation Medicine Inc. FoundationOne CDx. Accessed 12 February 2020 https://www.foundationmedicine.com/genomic-testing/foundation-one-cdx
• 16 Gerke H, Rizk M, Vanderheyden A. et al. Randomized study comparing endoscopic ultrasound‐guided Trucut biopsy and fine needle aspiration with high suction. Cytopathology 2010; 21: 44-51
• 17 Jones S, Zhang X, Parsons DW. et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008; 321: 1801-1806
• 18 Wei S, Lieberman D, Morrissette JJ. et al. Using “residual” FNA rinse and body fluid specimens for next‐generation sequencing: An institutional experience. Cancer Cytopathol 2016; 124: 324-329
• 19 Gleeson FC, Kerr SE, Kipp BR. et al. Targeted next generation sequencing of endoscopic ultrasound acquired cytology from ampullary and pancreatic adenocarcinoma has the potential to aid patient stratification for optimal therapy selection. Oncotarget 2016; 7: 54526-54536
• 20 Bournet B, Pointreau A, Souque A. et al. Gene expression signature of advanced pancreatic ductal adenocarcinoma using low density array on endoscopic ultrasound-guided fine needle aspiration samples. Pancreatology 2012; 12: 27-34
• 21 Berry W, Lundy J, Croagh D. et al. Reviewing the utility of EUS FNA to advance precision medicine in pancreatic cancer. Cancers 2018; 10: 35
• 22 Lowery MA, Jordan EJ, Basturk O. et al. Real-time genomic profiling of pancreatic ductal adenocarcinoma: Potential actionability and correlation with clinical phenotype. Clin Cancer Res 2017; 23: 6094-6100
• 23 Hayashi H, Kohno T, Ueno H. et al. Utility of assessing the number of mutated KRAS, CDKN2A, TP53, and SMAD4 genes using a targeted deep sequencing assay as a prognostic biomarker for pancreatic cancer. Pancreas 2017; 46: 335-340
• 24 Waddell N, Pajic M, Patch A-M. et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015; 518: 495
• 25 Bang JY, Hebert-Magee S, Navaneethan U. et al. Randomized trial comparing the Franseen and Fork-tip needles for EUS-guided fine-needle biopsy sampling of solid pancreatic mass lesions. Gastrointest Endosc 2018; 87: 1432-1438
• 26 van Riet PA, Larghi A, Attili F. et al. A multicenter randomized trial comparing a 25-gauge EUS fine-needle aspiration device with a 20-gauge EUS fine-needle biopsy device. Gastrointest Endosc 2019; 89: 329-339
• 27 Elhanafi S, Mahmud N, Vergara N. et al. Comparison of endoscopic ultrasound tissue acquisition methods for genomic analysis of pancreatic cancer. J Gastroenterol Hepatol 2019; 34: 907-913
• 28 Park JK, Lee JH, Noh DH. et al. Factors of endoscopic ultrasound-guided tissue acquisition for successful next-generation sequencing in pancreatic ductal adenocarcinoma. Gut Liver 2020; 14: 387-394
• 29 Kandel P, Wallace MB. Recent advancement in EUS-guided fine needle sampling. J Gastroenterol 2019; 54: 377-387
• 30 Tiriac H, Bucobo JC, Tzimas D. et al. Successful creation of pancreatic cancer organoids by means of EUS-guided fine-needle biopsy sampling for personalized cancer treatment. Gastrointest Endosc 2018; 87: 1474-1480