Abstract
BACKGROUND AND STUDY AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a poor prognostic malignancy. Comprehensive genomic profiling (CGP) has improved outcomes in many cancers, but widespread uptake in PDAC remains elusive. This study investigated the feasibility of using endoscopic ultrasound with fine-needle biopsy (EUS-FNB) for CGP in advanced PDAC. PATIENTS AND METHODS EXPERIMENTAL DESIGN: A multicenter prospective cohort study was conducted to assess the feasibility of using DNA and RNA extracted from fresh frozen or archival formalin-fixed paraffin-embedded (FFPE) EUS-FNB for CGP on advanced PDAC using the TSO-500 gene panel testing. Results of the CGP were reviewed at a molecular tumor board (MTB) and subsequent treatment recommendations were forwarded to the referring clinicians. RESULTS: CGP was successful in 129 of 143 patients (90%) enrolled between May 2020 to September 2023. Fresh frozen EUS-FNB provided suitable genetic material for CGP in 123 of 133 patients (92%). Conversely, CGP was successful on FFPE biopsy blocks from only six of 16 patients (38%). Fifty-two of 143 patients (36%) had a potentially targetable mutation detected, and eight of these patients (6%) were treated with targeted therapy based on their EUS-FNB-derived molecular profile. Patients who received personalized therapy had a significant ( P < 0.0001) increase in survival versus standard or no therapy at 12 and 36 months. Median patient survival on standard therapy was 9.47 months versus > 18 months for personalized therapy. CONCLUSIONS: This real-world study confirms the feasibility and utility of CGP using EUS-FNB in advanced PDAC. It illustrates the importance of timely access to personalized therapy informed by CGP, which can impact the treatment pathway and improve survival outcomes.