Pancreatic Cancer Lifestyle Evolution And Resistance

This study aims at identifying and validating transcriptome signatures in patients with Pancreatic Ductal Adenocarcinoma (PDAC) through EUS-guided biopsies. The study hypothesis is that specific molecular profiles (e.g., "basal-like" vs. "classical" subtypes) obtained at the time of diagnosis can predict primary resistance or sensitivity to standard-of-care first-line chemotherapy regimens (mFOL, NG, or PAXG). By correlating these signatures with clinical outcomes, the study seeks to provide a rationale for personalized therapeutic strategies in advanced PDAC. This is a prospective, single-center, interventional study. Patients with a cytological diagnosis of PDAC (confirmed via Rapid On-Site Evaluation - ROSE) during a standard-of-care EUS-TA are enrolled at baseline. A part of the citology sample is employed for research purpose (RNA-seq). Following the procedure, patients receive standard-of-care chemotherapy (mFOL, NG, or PAXG). The intervention consists of an additional biopsy pass performed during EUS at the time of re-staging after chemotherapy, exclusively for research purposes (RNA-seq). All patients undergo standard longitudinal clinical monitoring to assess Progression-Free Survival (PFS) and Overall Survival (OS) for a total period of 30 months or until death. Primary Objective: To identify baseline transcriptomic signatures associated with treatment response to mFOL, NG, and PAXG in advanced PDAC patients. Primary Endpoint: Response to treatment assessed every 3 months by RECIST 1.1 criteria and defined as Disease Control Rate at 6 months (DCR-6); Progression-Free Survival (PFS) and Overall Survival (OS) during the follow-up period. Secondary Objectives: To investigate the longitudinal evolution of PDAC signatures during treatment Secondary Endpoints: Comparison of transcriptome signatures between baseline EUS-biopsy and repeated biopsy after 6 months of treatment. To evaluate the impact of active smoking on transcriptomic subtypes and treatment outcomes via correlation between smoking status and the distribution of classical vs. basal-like subtypes and clinical outcomes. To compare signatures between primary and metastatic sites throughout the comparison of transcriptomic patterns between primary tumor and metastatic biopsy samples.