Subject Ph. D.

Surgery, especially if followed by adjuvant chemotherapy, offers the only chance of cure for pancreatic cancer. At first diagnosis, after careful evaluation, only 10 to 15% of patients are considered candidates for surgical resection and approximately 7% have potentially resectable disease. These potentially resectable tumors termed "borderline resectable pancreatic cancer" (BRPC) are conceptualized as those that involve the mesenteric vasculature to a limited extent and those for which resection, although possible, would likely be compromised by positive surgical margins (R1 ) in the absence of neoadjuvant treatment. R0 resection is in fact considered an independent prognostic factor for survival when surgical procedures, histological examination and definition of microscopic invasion are standardized. The goals of neoadjuvant treatments for BRPC are to reduce the tumor volume before surgery in order to improve the chances of radical resection (R0) and to reduce the rate of lymph node positivity and recurrence. The primary endpoint of published studies is generally the R0 resection rate, but these results also depend on the number of margins examined and the definition of microscopic margin involvement. Prospective studies with consistent selection criteria and standardized endpoints are needed. Different neoadjuvant therapeutic strategies have been tested in pilot studies: preoperative chemoradiotherapy or neoadjuvant chemotherapy, followed or not by preoperative (chemo)radiotherapy. Due to the lack of randomized studies, the best sequence of treatment administration has not been established. The aim of this prospective, randomized, multicenter trial is to evaluate the rate of R0 resection with neoadjuvant Folfirinox, followed or not by chemoradiotherapy for patients with borderline resectable pancreatic cancers. Patient inclusions and follow- up are now complete and the final results will be presented in September 2024. The proposed thesis work is a translational study to the PANDAS study: TranPANDAS. The aim of the TransPANDAS study is to determine whether the use of liquid biopsy allows better management of patients with pancreatic adenocarcinoma treated with neoadjuvant chemotherapy with mFOLFIRINOX associated or not with chemoradiotherapy. To do this, we propose to analyze circulating tumor DNA and circulating miRs from plasma collected from the 130 patients included in the PANDAS study. Each patient underwent repeated blood sampling.