Abstract A24: Early-stage pancreatic cancer patient derived xenograft (PDX) models established from endoscopic ultrasound (EUS) fine needle aspiration (FNA) biopsies

Background: We developed and characterized PDX models generated from FNA endoscopic biopsies at the time of diagnosis of pancreatic ductal adenocarcinoma (PDAC). Our goal was to determine if an FNA-PDX model could be established within a clinically relevant time frame to inform treatment decisions prior to disease recurrence in patients with early stage, localized disease. Methods: Patients presenting with a localized mass in the pancreas and no metastatic disease were considered for EUS/FNA biopsy. Under sonographic guidance FNA biopsies were obtained. On-site cytopathology confirmed a histologic diagnosis of PDAC. The diagnostic FNA specimen was sent to pathology for formalin fixed paraffin embedded tissue block analysis per standard institutional pathologic protocols. Additional endoscopic FNA passes from the primary tumor were obtained during the index procedure by EUS guidance. The cell specimen was washed in cold DMEM and centrifuged. The cell pellet was rapidly transplanted into a subcutaneous pocket within the flank of a single NOD.Cg- Prkdc scid Il2rg tm1Wjl /SzJ (NOD scid gamma, NSG) mouse. Tumor growth was monitored with calipers and engrafted tumors were passaged to subsequent mice when they reached a diameter of 10mm 2 . Growth kinetics and immunohistochemical staining for human cells with antibody against the human HLA Class 1 ABC antigen were obtained. Treatment groups were established from the F3 passage and randomized for in vivo chemosensitivity testing using FDA-approved chemotherapeutics: gemcitabine, cisplatin, docetaxel, irinotecan and fluorouracil. Results: The warm ischemia time was negligible. The average cold ischemia time, defined as the time from the endoscope to transplantation in the mouse, was 39 minutes. Engraftment was successful in 9 of 24 (37.5%) individual FNA patient specimens. Engraftment however increased with the number of FNA biopsy passes: 3/12 (25%) engraftment from one pass and 6/12 (50%) from two passes. Tumor size and surgical resectability status by CT imaging did not correlate with engraftment success. Procedural variables such as needle gauge and cytopathologic features such as degree of differentiation and percent tumor cellularity also did not correlate with rate of engraftment. PDX tumor morphology was maintained between F0 and F4 mice by HE Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A24.