Real time ex vivo chemosensitivity assay for pancreatic adenocarcinoma

Abstract

Background: Patient-derived organoids (PDOs) and xenografts (PDXs) have been extensively studied for drug-screening. However, their usage is limited due to lengthy establishment time, high engraftment failure rates and different tumor microenvironment from original tumors. To overcome the limitations, we developed real time-live tissue sensitivity assay (RT-LTSA) using fresh tumor samples.

Methods: Tissue slices from resected pancreatic cancer samples were placed in 96-well plates, and the slices were treated with chemotherapeutic agents. The correlation between the chemo-sensitivity of tissue slices and each patient’s clinical outcome was analyzed.

Results: The viability and tumor microenvironment of the tissue slices are well-preserved over 5 days. The drug sensitivity assay results are available within 5 days after tissue collection. While all 4 patients who received RT-LTSA sensitive adjuvant regimens did not develop recurrence, 7 of 8 patients who received resistant adjuvant regimens developed recurrence. We observed significantly improved disease-free survival in the patients who received RT-LTSA sensitive adjuvant regimens (median: not reached versus 10.6 months, P = 0.02) compared with the patient who received resistant regimens. A significant negative correlation between RT-LTSA value and relapse-free survival was observed (Somer’s D: −0.58; P = 0.016).

Conclusions: RT-LTSA which maintains the tumor microenvironment and architecture as found in patients may reflect clinical outcome and could be used as a personalized strategy for pancreatic adenocarcinoma. Further, studies are warranted to verify the findings.