1947P - Organoid establishment from multiple biological sources in biliopancreatic cancers

Background

Biliopancreatic cancers are a group of aggressive malignancies affecting pancreas and biliary tract, often diagnosed at advanced stages, and characterized by a poor outcome despite recent therapeutic advances. Thus, there is an urgent need to develop new tools and models with the aim to identify novel effective treatment approaches for patients. Recently, patient-derived organoids (PDOs) have gained substantial value as clinically relevant models that recapitulate the behavior of tumors and play a pivotal role in drug screening to guide personalized medicine approaches for cancer treatment.

Methods

96 patients with diagnosis of biliary tract cancer (BTC) or pancreatic adenocarcinoma (PDAC) were prospectively recruited. PDOs were established from 4 different biological sources: tumor biopsy, tissue from resected tumor, tumor cells derived from ascites and from bile. Bile samples were obtained from patients that underwent endoscopic bile drainage as per clinical practice, ascites samples from patients with advanced disease who underwent paracentesis as per clinical practice. For PDO establishment, cells from the different biological sources were isolated, embedded in Matrigel and cultured in vitro with media supplemented with specific growth factors. PDO histological features were investigated by H&E staining.

Results

PDOs have been obtained from all the 4 biological sources tested. Initial growing kinetics of PDOs is highly heterogeneous. PDO establishment was successful for 88.9% of biopsy samples tested and for 61.8% of bile samples. For resected tissues, the successful rate was 81.1%. Finally, PDOs were obtained from 4 of 5 ascites samples tested (3 CCA, 2 PDAC). Morphological similarities in terms of cellular morphology, nuclear atypia and gland formation have been evaluated between PDOs and tumors showing a high level of consistency.

Conclusions

Our approach demonstrate that PDO establishment is feasible from all the different biological sources tested. In addition, PDOs retain the histopathological architecture of native cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.