Herve Tiriac1, Juan Carlos Bucobo2, Demetrios Tzimas2, Suman Grewel2, Joseph F Lacomb2, Leahana M Rowehl2, Satish Nagula2, Maoxin Wu3, Joseph Kim4, Aaron Sasson4, Shivakumar Vignesh5, Laura Martello5, Maria Munoz-Sagastibelza5, Jonathan Somma6, David A Tuveson1, Ellen Li2, Jonathan M Buscaglia2. 1. Cold Spring Harbor Laboratory, Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, New York, USA. 2. Division of Gastroenterology and Hepatology, Department of Medicine, Stony Brook University School of Medicine, Stony Brook, New York, USA. 3. Division of Cytopathology, Department of Pathology, Stony Brook University School of Medicine, Stony Brook, New York, USA. 4. Division of Surgical Oncology, Department of Surgery, Stony Brook University School of Medicine, Stony Brook, New York, USA. 5. Division of Gastroenterology and Hepatology, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA. 6. Division of Cytopathology, Department of Pathology, SUNY Downstate Medical Center, Brooklyn, New York, USA.
Abstract
BACKGROUND AND AIMS: Pancreatic cancer organoids are tumor models of individualized human pancreatic ductal adenocarcinoma (PDA), created from surgical specimens and used for personalized treatment strategies. Unfortunately, most patients with PDA are not operative candidates. Creation of human PDA organoids at the time of initial tumor diagnosis is therefore critical. Our aim was to assess the feasibility of creating human PDA organoids by EUS fine-needle biopsy (EUS-FNB) sampling in patients with PDA. METHODS: In this prospective clinical trial in patients referred to evaluate a pancreatic mass, EUS-FNA was performed for initial onsite diagnosis. Two additional needle passes were performed with a 22-gauge FNB needle for organoid creation. Primary outcome was successful isolation of organoids within 2 weeks of EUS-FNB sampling (P0, no passages), confirmed by organoid morphology and positive genotyping. RESULTS: Thirty-seven patients with 38 PDA tumors were enrolled. Successful isolation of organoids (P0) was achieved in 33 of 38 tumors (87%). Establishment of PDA organoid lines for ≥5 passages of growth (P5, five passages) was reached in 25 of 38 tumors (66%). In the single patient with successful P5 FNB sampling-derived and P5 surgically derived organoids, there was identical matching of specimens. There were no serious adverse events. Two patients developed bleeding at the EUS-FNB puncture site requiring hemostasis clips. CONCLUSIONS: Pancreatic cancer organoids can be successfully and rapidly created by means of EUS-FNB sampling using a 22-gauge needle at the time of initial diagnosis. Successful organoid generation is essential for precision medicine in patients with pancreatic cancer in whom most are not surgically resectable. (Clinical trial registration number: NCT03140592.).
BACKGROUND AND AIMS: Pancreatic cancer organoids are tumor models of individualized humanpancreatic ductal adenocarcinoma (PDA), created from surgical specimens and used for personalized treatment strategies. Unfortunately, most patients with PDA are not operative candidates. Creation of humanPDA organoids at the time of initial tumor diagnosis is therefore critical. Our aim was to assess the feasibility of creating humanPDA organoids by EUS fine-needle biopsy (EUS-FNB) sampling in patients with PDA. METHODS: In this prospective clinical trial in patients referred to evaluate a pancreatic mass, EUS-FNA was performed for initial onsite diagnosis. Two additional needle passes were performed with a 22-gauge FNB needle for organoid creation. Primary outcome was successful isolation of organoids within 2 weeks of EUS-FNB sampling (P0, no passages), confirmed by organoid morphology and positive genotyping. RESULTS: Thirty-seven patients with 38 PDAtumors were enrolled. Successful isolation of organoids (P0) was achieved in 33 of 38 tumors (87%). Establishment of PDA organoid lines for ≥5 passages of growth (P5, five passages) was reached in 25 of 38 tumors (66%). In the single patient with successful P5 FNB sampling-derived and P5 surgically derived organoids, there was identical matching of specimens. There were no serious adverse events. Two patients developed bleeding at the EUS-FNB puncture site requiring hemostasis clips. CONCLUSIONS:Pancreatic cancer organoids can be successfully and rapidly created by means of EUS-FNB sampling using a 22-gauge needle at the time of initial diagnosis. Successful organoid generation is essential for precision medicine in patients with pancreatic cancer in whom most are not surgically resectable. (Clinical trial registration number: NCT03140592.).
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