Accuracy of Using a Patient-Derived Tumor Organoid Culture Model to Predict the Response to Chemotherapy Regimens In Stage IV Colorectal Cancer: A Blinded Study.

BACKGROUND Patient-derived tumor organoid culture has emerged as a preclinical model that has the potential to predict individual drug response. However, the predictive accuracy of patient-derived tumor organoid culture models for responses to chemotherapy regimens in stage IV colorectal cancer remains unknown. OBJECTIVE To evaluate the predictive accuracy of the patient-derived tumor organoid culture model for responses to chemotherapy regimens in stage IV colorectal cancer. DESIGN A pilot study was performed to define the half-maximal inhibitory concentration of the response to chemotherapy regimens in the patient-derived tumor organoid culture model. Then, a blinded study was performed to evaluate the predictive accuracy of the patient-derived tumor organoid culture model for responses to chemotherapy regimens. SETTING Cancer samples were collected from stage IV colorectal cancer patients at Nanfang Hospital of Southern Medical University in China. PATIENTS In the pilot study, 30 patients were enrolled, and 43 samples were collected. In the blinded study, 71 patients were enrolled, and 96 samples were collected. INTERVENTION Patient-derived tumor organoid culture and chemotherapy regimens were tested. MAIN OUTCOME MEASURES The predictive accuracy of the patient-derived tumor organoid model for responses to chemotherapy regimens. RESULTS The median (range) time of organoid culture and drug testing was 9 (7-14) days. In the pilot study, 30 (69.77% [30/43]) samples were successfully cultured. The half-maximal inhibitory concentration of the chemotherapy response was 10 µmol/L according to clinical chemotherapy outcomes. In the blinded study, 77 samples (80.21% [77/96]) from 57 patients were successfully cultured. The sensitivity, specificity, and accuracy of the patient-derived tumor organoid model for predicting responses to chemotherapy regimens were 63.33%, 94.12%, 79.69%, respectively. LIMITATIONS This was a blinded study rather than a prospective, randomized and controlled study. CONCLUSIONS The patient-derived tumor organoid culture model effectively predicts responses to existing chemotherapy regimens for individual patients. Video Abstract at http://links.lww.com/DCR/B511.