• Lyudmyla Demyan, Amber N Habowski, Dennis Plenker, Daniel A King, Oliver J Standring, Caitlin Tsang, Luce St Surin, Arvind Rishi, James M Crawford, Jeff Boyd, Shamsher A Pasha, Hardik Patel, Zachary Galluzzo, Christine Metz, Peter K Gregersen, Sharon Fox, Cristina Valente, Sonya Abadali, Steffi Matadial-Ragoo, Danielle K DePeralta, Gary B Deutsch, Joseph M Herman, Mark A Talamini, David A Tuveson, and Matthew J Weiss.
• Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY.
• Ann. Surg. 2022 Sep 1; 276 (3): 450462450-462.

ObjectiveTo evaluate if patient-derived organoids (PDOs) may predict response to neoadjuvant (NAT) chemotherapy in patients with pancreatic adenocarcinoma.BackgroundPDOs have been explored as a biomarker of therapy response and for personalized therapeutics in patients with pancreatic cancer.MethodsDuring 2017-2021, patients were enrolled into an IRB-approved protocol and PDO cultures were established. PDOs of interest were analyzed through a translational pipeline incorporating molecular profiling and drug sensitivity testing.ResultsOne hundred thirty-six samples, including both surgical resections and fine needle aspiration/biopsy from 117 patients with pancreatic cancer were collected. This biobank included diversity in stage, sex, age, and race, with minority populations representing 1/3 of collected cases (16% Black, 9% Asian, 7% Hispanic/Latino). Among surgical specimens, PDO generation was successful in 71% (15 of 21) of patients who had received NAT prior to sample collection and in 76% (39 of 51) of patients who were untreated with chemotherapy or radiation at the time of collection. Pathological response to NAT correlated with PDO chemotherapy response, particularly oxaliplatin. We demonstrated the feasibility of a rapid PDO drug screen and generated data within 7 days of tissue resection.ConclusionHerein we report a large single-institution organoid biobank, including ethnic minority samples. The ability to establish PDOs from chemotherapy-naive and post-NAT tissue enables longitudinal PDO generation to assess dynamic chemotherapy sensitivity profiling. PDOs can be rapidly screened and further development of rapid screening may aid in the initial stratification of patients to the most active NAT regimen.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

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