Jon Emery^1
1University of Melbourne

Polygenic risk scores (PRS) have been validated for several common cancers including melanoma, breast, colorectal and prostate. The challenge now is how to apply these to clinical care, specifically to tailor cancer prevention and screening. In this presentation I will summarise evidence on risk-stratified cancer screening and the potential application of PRS for this purpose. I will present findings from our research on applying a PRS to tailor colorectal cancer screening and more recent data on using a multi-cancer PRS to provide tailored advice on screening for melanoma, breast, colorectal and prostate. This will include evidence on the psychosocial consequences of receiving a PRS and impacts on risk-appropriate cancer screening. 

Omico/PrOSPeCT

Vanessa Tyrrell^1;2, Chelsea Mayoh^2;3, Paul Ekert^2;3;4, Mark Cowley^2;3, David Ziegler^2;3;5, Marie Wong^2;3, Paulette Barahona², Mark Pinese^2;3, Michelle Haber^2;3, Rob Salomon², Eliza Courtney^2;5, Richard Lock^2;3, Noemi Fuentes-Bolanos^2;3;5, Glenn Marshall^2;3;5, Meera Warby⁵, Toby Trahair^2;3;5, Dong Anh Khuong Quang^6;7, Claire Wakefield³, Katherine Tucker^3;5;8, Kristine Barlow-Stewart^2;9, Bhavna Padhye¹⁰, Loretta Lau^2;3;5

¹UNSW Sydney, School of Clinical Medicine, UNSW Medicine and Health, Sydney, Australia; ²Children’s Cancer Institute, Randwick, Australia; ³UNSW Sydney, School of Clinical Medicine, UNSW Medicine & Health, Sydney, Australia; ⁴Peter MacCallum Cancer Centre, Melbourne, Australia; ⁵Sydney Children’s Hospital, Randwick, Kids Cancer Centre, Randwick, Australia; ⁶The Royal Children’s Hospital Melbourne, Children’s Cancer Centre, Parkville, Australia; ⁷Murdoch Children’s Research Institute, Parkville, Australia; ⁸Prince Of Wales Hospital, Hereditary Cancer Clinic, Randwick, Australia; ⁹University of Sydney School of Medicine, Camperdown, Australia; ¹⁰The Children’s Hospital at Westmead, Cancer Centre for Children, Westmead, Australia

Precision medicine is revolutionising the way cancers are detected, characterised, and treated, by identifying targetable vulnerabilities by matching genomic profiling with molecularly targeted agents. The Zero Childhood Cancer (ZERO) national precision medicine program was launched, initially for children with the most aggressive cancers with a less than 30% chance of survival. ZERO utilises comprehensive molecular profiling, integrating germline and tumour whole genome sequencing, RNA sequencing and methylation profiling, and where possible, in vitro and in vivo testing of patient tumour cells for response to chemotherapeutic and novel targeted agents. 

Between September  2017 and October 2023, 1000 children with high risk, rare, and undiagnosable cancers were enrolled on ZERO’s first national trial. Recent analyses of 384 consecutively enrolled high-risk child cancer patients, with >18 months of follow up, demonstrated that those receiving a precision-guided treatment (PGT), informed by comprehensive multiomic profiling, led to doubling (27% vs 11%) 2 year progression free survival when compared to standard-of-care cytotoxic therapies and a substantive 5 times higher when comparing PGT to that of an unguided novel therapy (a novel agent not chosen on the basis of molecular findings).

These findings demonstrate the power of multiomic profiling to improve outcomes for children with high-risk cancer. In November 2023, ZERO became available to all Australian children and young people diagnosed with cancer, irrespective of cancer type, stage, or risk, with over 1000 children enrolled in the first 12 months. ZERO is changing the model of care for Australian children with cancer, with the goal of guiding more effective treatment options and improving long-term outcomes for all children with cancer.