RACS Mark Killingback Prize Winner - PREDICTORG: A Multicentre Personalised Medicine Approach in the Management of Colorectal Peritoneal Metastases

Colorectal Peritoneal Metastases(CPM) develop in 13% of CRC patients, however, a subset of patients can be offered Cytoreductive Surgery(CRS) with Hyperthermic intraperitoneal chemotherapy(HIPEC), with favourable median survival of 40months, compared to 16months on systemic-therapy alone. PRODIGE-7 has questioned the efficacy of HIPEC, demonstrating no survival benefit of CRS+OX-HIPEC when compared to CRS alone, creating clinical equipoise in the management of CPM.

PredictORG is a novel translational study that identifies the best HIPEC drug for individual patients based on in-vitro sensitivity demonstrated by patient-derived organoids. Intra-operative CPM-biopsies were collected from three interstate peritonectomy centres (RPAH, TQEH and PMCC) and transported to PMCC for tissue processing, organoid cultivation, and drug screening. Patients’ organoids were incubated for 4 days and exposed to Mitomycin-C/OX/IRI as monotherapy. A machine learning algorithm was developed to identify organoid viability unique to each patient’s organoid phenotype.

Across the three sites, 27 patients were recruited and an overall organoid success rate was 77%(14/18). The mean time to successful organoid cultivation was 17.8(8-34) days and time drug assay result 24.8(15-41)days. Success rates did not differ between local and interstate samples (PMCC (6/8)75%; RPAH(6/8)75%; TQEH(2/2)100%).

Overall, multicentre tissue retrieval, organoid cultivation and drug screening is feasible within the 4-week period that patients are optimised for their definitive CRS and HIPEC. There is consensus from all Australian peritonectomy centres to proceed to a funded nationwide translational clinical trial investigating the improvement in oncological outcomes utilising this translational, personalised medicine approach.