AR7 - Colon and Appendiceal Cancer Organoids for Comparison of Ex-Vivo Efficacy of Mitomycin C and Oxaliplatin Perfusion Regimens

Introduction: The optimal concentration, temperature and duration of chemotherapy in HIPEC procedures is unknown. We propose an ex-vivo tumor organoid system to model treatment with personalized response data.

Methods: Biospecimens from 6 appendiceal and 4 colon cancer HIPEC patients were applied for personalized organoid development. Organoids were perfused in parallel at 37 and 42 Celsius with low and high dose oxaliplatin (360 mg/3 L over 2 hours vs 874 mg/3L over 30 minutes) and MMC (40 mg/3L over 2 hours). Live/dead staining and viability assays were standardized to controls and pooled for statistical analysis.

Results: Adequate organoid number for testing was generated for 100% (4/4) of colon and 67% of appendiceal cancer patients. MMC and low dose oxaliplatin had equal effect on viability of both appendiceal and colon organoids (34% vs 41% (p=0.47) and 36% vs 39% (p=0.71) respectively), whereas heated MMC was more effective than high dose oxaliplatin in both primaries. (34% vs 74% (p=0.005) and 36% vs 67% (p=0.002)). In both appendiceal and colon tumor organoids, heated low dose oxaliplatin displayed increased killing efficacy as compared to high dose oxaliplatin (post treatment viability 41% vs 74% (p=0.02) and 39% vs 67% (p=0.003)). Despite all heated conditions displaying lower viability than normal temperature, in colon cancer tumor organoids, only MMC displayed an at least 50% tumor killing (p=0.03).

Conclusion: Colon and appendiceal cancer organoids, treated with low dose heated oxaliplatin for 2 hours displayed increased susceptibility in comparison to a 30-minute high dose oxaliplatin. Organoid technology may offer an opportunity, tailoring HIPEC conditions to the individual patient.