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Identifying Factors of Organoid Establishment in Pancreatic Cancer: A Prospective Observational Study

Year: 2025

Type: article

Abstract: BACKGROUND: Patient-derived organoid (PDO) models have emerged as critical tools in pancreatic ductal adenocarcinoma (PDAC) research and are used as surrogates for studying the individual's tumor biology. Still, PDO-based concepts for direct clinical application remain challenging. In this prospective observational trial (OrgaPanCCC-01), we aim to address clinical feasibility, identify predictive factors for PDO establishment, and assess the prognostic potential of PDO establishment for patient's survival. METHODS: Samples for PDO generation were prospectively collected via endoscopy, surgery, and transcutaneous punch biopsy, or from ascites. Patients were followed up for a median time of 14.6 months. We evaluated the clinical feasibility by determining the PDO establishment rate and the time required for establishment. Uni- and multivariate analyses were performed to examine the effect of clinical and sample characteristics on PDO establishment. For the predictive and prognostic potential, PDO establishment was correlated to the patients' disease-free (DFS), progression-free (PFS) and overall survival (OS). RESULTS: Between 2021 and 2023, 75 patients were enrolled with radiologically suspected PDAC at the Charité Universitätsmedizin Berlin and at the Waldfriede Krankenhaus Berlin. PDAC was confirmed in 62 patients (83%). PDO establishment was achieved in 58% (n = 36/62) of patients within a median of 28 days, supporting the feasibility of clinical implementation. In the uni- and multivariate analysis, samples from metastatic sites (p = 0.04) and higher CA19-9 levels (p = 0.03) were found to be positively correlated with PDO growth. Patients without PDO growth tended to have longer PFS (p = 0.32), whereas no statistically significant correlation was observed between PDO growth and OS. CONCLUSION: In this prospective observational trial, we show that PDO generation is feasible at a success rate of 58% within a clinically reasonable time frame of 6 weeks. The efficacy of PDO establishment depended on sample site, with metastatic samples showing higher establishment rates. Higher CA 19-9 levels were positively correlated with PDO growth. Successful PDO establishment did not have a prognostic value for OS. Overall, our findings underline the great potential of PDO-based precision medicine approaches, which should further be evaluated in prospective interventional translational trials.

Source: Cancer Medicine

DOI: 10.1002/cam4.71490