Mutational profiling of 103 unresectable pancreatic ductal adenocarcinomas using EUS-guided fine-needle biopsy.

Background and Objective: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, with a 5-year survival rate of around 9%. Only 20% are candidates for surgery. Most unresectable patients undergo EUS-guided fine-needle biopsy (EUS-FNB) for diagnosis. Identification of targetable mutations using next-generation sequencing (NGS) is increasingly requested. Data on feasibility of EUS-FNB for NGS and knowledge regarding mutational profile of unresectable PDAC are scarce. We evaluated the "technical yield" of EUS-FNB for NGS in unresectable PDAC: relative fraction of diagnostic EUS-FNBs meeting technical criteria. We also investigated the "molecular yield": relative fraction of EUS-FNBs included in NGS containing sufficient DNA for detection of at least one mutation. Furthermore, we determined the relative frequency of cancer-associated mutations in unresectable PDAC. Patients and Methods: Formalin-fixed and paraffin-embedded EUS-FNBs diagnostic of unresectable PDAC and fulfilling these criteria were included ( Results: Technical yield was 48% (105/219) and molecular yield was 98% (103/105). Most frequently mutated genes were Conclusion: EUS-FNB for NGS of unresectable PDAC is feasible. Our technical criteria for NGS, using leftovers in formalin-fixed and paraffin-embedded blocks after routine pathology diagnosis, were met by around half of EUS-FNBs. Almost all EUS-FNBs fulfilling the technical criteria yielded a successful NGS analysis.