Clinical Utility of the 3D Tumoroid Technology in Aggressive Pancreatic Ductal Adenocarcinoma with Nodal Involvement and Poor Differentiation

Introduction: Resectable Pancreatic Ductal Adenocarcinoma (PDAC) patients with nodal involvement could benefit from neoadjuvant therapy (NAC), e.g. through increased tumor-resectability, regression of lymph node metastases and better oncological outcomes. The three-dimensional (3D) tumor organoid (tumoroid) technology holds potential to individualize PDAC-therapy by recapitulating the tumor and enabling pre-therapeutic drug-response-profiling. However, tumoroids cannot be obtained from all PDAC-tissue samples to similar extends. Methods: PDAC-tissue (all tumor-stages) is collected for tumoroid generation directly after surgery. Following mechanical and enzymatic tissue dissociation, tumor fragments are plated onto an extracellular matrix and cultured in 3D-culture media. After successful formation and growth, tumoroids are propagated and sustained in subsequent passages – allowing for drug-screenings. Clinical data on tumor-classifications are correlated with tumoroid growth success rates. Results: 39 PDAC-tissue samples were processed for tumoroid generation between January 2020 and February 2021. We observed initial tumoroid growth (IG) in 85% (33/39) and sustained growth (SG) in subsequent passages in 64% (25/39) of prepared samples. Successful establishment of in-vitro tumoroid cultures was significantly associated with poorly differentiated tumors (G3) (SG: 89% vs. 44%; p=0.042) and lymph node involvement (N+) (IG: 91% vs. 56%; p=0.043; SG: 73% vs. 14%; p=0.009) – and thus with advanced UICC-stages (≥III) (SG: 85% vs. 45%; p=0.039). Conclusion: PDAC-tumoroids can reliably be established from tumor-tissue samples of patients displaying more aggressive G3 and N+ tumors. Therefore, these patients might particularly benefit from tumoroid-based drug-screenings subsequent to endoscopic puncture and tissue extraction of the primary tumor - and thus improved clinical NAC responses and tumor resectability.