Introduction:
Next-generation sequencing (NGS) of tumors can identify an emerging number of therapeutic and prognostic molecular targets. Endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/B) is the established modality of choice to diagnose pancreatic cancer. However, reported feasibility outcomes of EUS-FNA/B providing adequate tissue for NGS have been variable. It is also not well established whether clinical features of the tumor and procedural factors of tissue acquisition affect NGS success rates.

Methods:
We describe a retrospective study of all EUS-FNA/B specimens with pancreatic cancer at Memorial Sloan Kettering Cancer Center in New York City between 2014-2022. NGS was performed with a comprehensive paired tumor-normal, large panel, hybridization-capture based, NGS known as Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT). Clinical, endoscopic, and pathologic data were obtained from the electronic medical record, and MSK-IMPACT results were analyzed.

Results:
MSK-IMPACT testing was requested on 388 EUS-FNA/B specimens with pancreatic cancer and was successful on 294 (76%) of them. The success rates of the assay significantly improved over time (83% in the second half of cases vs 66% in the first half, p=0.02) most likely due to optimized sequencing and DNA extraction methods. Most failed specimens were because of a low DNA concentration, indicating low tissue sampling. Although 24% of specimens had failed MSK-IMPACT testing, all specimens were adequate for routine diagnostic cytology. With regards to clinical features, there was no statistically significant difference in MSK-IMPACT success rates based on tumor size, tumor location within the pancreas, disease stage, and history of prior neoadjuvant therapy. The needle gauge used (22G vs 25G) and number of passes did not significantly affect the MSK-IMPACT success rates. Of the successful cases, 95% of cases identified a significant hotspot mutation.

Conclusions:
This is the largest retrospective review to date investigating the feasibility of EUS-FNA/B for NGS. In this series, EUS-FNA/B reliably provided sufficient tissue for NGS with improved success rates over time. Certain clinical features and procedural factors did not have a significant effect on NGS success. EUS-FNA/B is an appropriate option for comprehensive NGS testing in pancreatic cancer patients.

William Jarnagin

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