ASO Visual Abstract: An Organoid Model for the Therapeutic Effect of Hyperthermic Intraperitoneal Chemotherapy for Colorectal Cancer

BackgroundConsensus regarding the hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer (CRC) regimen remains elusive. In this study, patient-derived tumor organoids from CRC were utilized as a preclinical model for in vitro drug testing of HIPEC regimens commonly used in clinical practice. This approach was used to facilitate the clinical formulation of HIPEC.MethodTumor tissues and corresponding clinical data were obtained from patients diagnosed with CRC at the Sixth Affiliated Hospital of Sun Yat-Sen University. Qualified samples were cultured and passaged. We aimed to assess the sensitivity of in vitro hyperthermic perfusion using five different regimens, i.e. mitomycin C, mitomycin C combined with cisplatin, mitomycin C combined with 5-fluorouracil, oxaliplatin, and oxaliplatin combined with 5-fluorouracil.ResultsTumor organoids obtained from 46 patients with CRC were cultured, and in vitro hyperthermic perfusion experiments were conducted on 42 organoids using five different regimens. The average inhibition rate of mitomycin C was 85.2% (95% confidence interval [CI] 80.4-89.9%), mitomycin C combined with cisplatin was 85.5% (95% CI 80.2-90.7%), mitomycin C combined with 5-fluorouracil was 65.6% (95% CI 59.6-71.6%), oxaliplatin was 37.9% (95% CI 31.5-44.3%), and oxaliplatin combined with 5-fluorouracil was 40.7% (95% CI 33.9-47.5%).ConclusionIn vitro hyperthermic perfusion demonstrates that the inhibition rate of mitomycin C, both alone and in combination with cisplatin, surpasses that of the combination of mitomycin C with 5-fluorouracil and oxaliplatin. In clinical practice, the combination of mitomycin C and cisplatin can be regarded as the optimal choice for HIPEC in CRC.