Patient-derived organoids from pancreatic cancer after pancreatectomy: Feasibility and organoid take rate in treatment-naïve periampullary tumors.

Abstract

Background/objective: Patient-derived organoids (PDOs) have emerged as essential for ex vivo modelling for pancreatic cancer (PDAC) but reports on efficacy and organoid take rate are scarce. This study aimed to assess the feasibility of establishing PDOs from resected specimens in periampullary tumors.

Methods: Patients undergoing surgery for suspected periampullary cancer were included. PDO protocol amendments were tested, with organoid take rate as outcome measure. Samples from resected specimens were processed and expanded per protocol. Pooled estimate of take rates of PDOs in PDAC was derived from literature search.

Results: 23 specimens were available for PDO, of which 10 were PDAC. In 15 patients other histopathology was found: neuroendocrine tumors (NET; n = 2), neuroendocrine carcinoma (NEC; n = 1), intraductal papillary mucinous neoplasm (IPMN; n = 4), distal cholangiocarcinoma (dCCA; n = 1), ampullary carcinoma (n = 1), duodenal carcinoma (n = 1), intra-ampullary papillary tubular neoplasm (IAPN; n = 1), indeterminate PDAC/ampullary carcinoma(n = 1), and one patient with chronic inflammation/fibrosis. Organoid cultures were grown from 7 of 10 (70 %) PDAC, 1 dCCA, 1 NEC, 1 duodenal carcinoma, 1 indeterminate tumor type and 1 ampullary carcinoma (i.e. 12/18; 66.7 % across periampullary cancers). Overall take rate of PDOs was 12 of 23 (52.2 %) for all tumors. A pooled mean estimate PDO take rate of 62.3 % (95 % CI:54.8-69.3 %) was reported across available studies in the literature.

Conclusion: In the current study, we found that PDOs could be established from resected pancreatic tumors in over half of resected periampullary tumors, and highest in PDACs. As such, generating a pancreatic cancer PDO biobank for translational research was feasible after cryopreservation.