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.
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.
Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, BGI Research, Hangzhou 310000, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen 518083, China.
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; Department of Medical Oncology, Western Health, Footscray, VIC 3011, Australia.
Department of Medical Oncology, Olivia Newton-John Cancer Wellness & Research Centre, Austin Health, Heidelberg, VIC 3084, 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 Cancer Services, Latrobe Regional Hospital, Traralogon, VIC 3844, Australia; Department of Medical Oncology, The Northern Hospital, Epping, VIC 3076, 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.
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; Department of Surgery, The University of Melbourne, Parkville, VIC 3050, Australia.
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; Department of Surgery, The University of Melbourne, Parkville, VIC 3050, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. Electronic address: sieber.o@wehi.edu.au.
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.
