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Study Description

Colorectal cancer (CRC) patients with peritoneal metastases (CRPM) have limited treatment options and the lowest CRC survival rates. We trialed the possibility of organoid directed precision treatment for CRPM patients. CRPM organoids (peritonoids) isolated from patients underwent next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing. Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for 2 patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications. In conclusion, our approach is feasible, reproducible and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.

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Study Attribution
  • Principal Investigator
    • Susan L Woods. School of Medicine, University of Adelaide, Adelaide, SA, Australia.
    • Robert G Ramsay. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia and Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia.
    • Vignesh Narasimhan. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia and Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia.
    • Daniel L Worthley. Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA Australia.
  • Co-Investigator
    • Alexander Heriot. 1Peter MacCallum Cancer Centre, Melbourne, VIC, Australia and Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia.
    • Carla Grandori. SEngine Precision Medicine, Seattle, WA, USA.
    • Siddhartha Mukherjee. Department of Medicine, Columbia University Medical Center, New York, NY, USA.
    • Jeanne Tie. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia and Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia.