Abstract:
Patient-derived tumor organoids (PDTOs) have the potential to be used to predict the patient response to chemotherapy. However, the cutoff value of the half-maximal inhibition concentration (IC50) for PDTO drug sensitivity has not been validated with clinical cohort data. We established PDTOs and performed a drug test in 277 samples from 242 CRC patients who received FOLFOX or XELOX chemotherapy. After follow-up and comparison of the PDTO drug test and final clinical outcome results, the optimal IC50 cutoff value for PDTO drug sensitivity was 43.26 μmol/L. This PDTO drug test-defined cutoff value could predict patient response with 75.36% sensitivity, 74.68% specificity, and 75% accuracy. Moreover, this value distinguished groups of patients with significant differences in survival benefit. Our study is the first to define the IC50 cutoff value for the PDTO drug test to effectively distinguish CRC patients with chemosensitivity or nonsensitivity and predict survival benefits.
摘要:
患者来源的肿瘤类器官(PDTOs)有可能用于预测患者对化疗的反应。然而,PDTO药物敏感性的半数最大抑制浓度(IC50)的截断值尚未在临床队列数据中得到验证.我们建立了PDTOs,并对242例接受FOLFOX或XELOX化疗的CRC患者的277个样本进行了药物测试。在随访和比较PDTO药物测试和最终临床结果后,PDTO药物敏感性的最佳IC50截断值为43.26μmol/L。这个PDTO药物测试定义的截止值可以以75.36%的灵敏度预测患者的反应,74.68%的特异性,75%的准确度。此外,这个值区分了在生存获益方面存在显著差异的患者组.我们的研究首次定义了PDTO药物测试的IC50截止值,以有效区分具有化学敏感性或非敏感性的CRC患者并预测生存益处。