Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Oncology, Western Health, Footscray, VIC 3011, Australia; Department of Medical Oncology, Eastern Health, Box Hill, VIC 3128, Australia; Eastern Health Clinical School, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Box Hill, VIC 3128, Australia.
Cell Rep Med. 2023 Dec 19;4(12):101335. doi: 10.1016/j.xcrm.2023.101335.
Predictive drug testing of patient-derived tumor organoids (PDTOs) holds promise for personalizing treatment of metastatic colorectal cancer (mCRC), but prospective data are limited to chemotherapy regimens with conflicting results. We describe a unified framework for PDTO-based predictive testing across standard-of-care chemotherapy and biologic and targeted therapy options. In an Australian community cohort, PDTO predictions based on treatment-naive patients (n = 56) and response rates from first-line mCRC clinical trials achieve 83% accuracy for forecasting responses in patients receiving palliative treatments (18 patients, 29 treatments). Similar assay accuracy is achieved in a prospective study of third-line or later mCRC treatment, AGITG FORECAST-1 (n = 30 patients). "Resistant" predictions are associated with inferior progression-free survival; misclassification rates are similar by regimen. Liver metastases are the optimal site for sampling, with testing achievable within 7 weeks for 68.8% cases. Our findings indicate that PDTO drug panel testing can provide predictive information for multifarious standard-of-care therapies for mCRC.
基于患者来源的肿瘤类器官（PDTOs）的预测性药物测试有望实现转移性结直肠癌（mCRC）的个体化治疗，但前瞻性数据仅限于化疗方案，且结果相互矛盾。我们描述了一种统一的框架，用于基于 PDTO 的预测性测试，涵盖了标准护理化疗以及生物和靶向治疗选择。在澳大利亚社区队列中，基于治疗初治患者（n=56）和一线 mCRC 临床试验的反应率的 PDTO 预测，对接受姑息治疗的患者（18 名患者，29 种治疗）的反应预测准确率达到 83%。在前瞻性 mCRC 三线或更后线治疗的 AGITG FORECAST-1 研究中（n=30 名患者），也实现了类似的检测准确性。“耐药”预测与无进展生存期较差相关；按方案分类的错误率相似。肝转移是采样的最佳部位，68.8%的病例可在 7 周内完成检测。我们的研究结果表明，PDTO 药物面板测试可为 mCRC 的多种标准护理治疗提供预测信息。
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