High clinical utility of comprehensive multi-omic molecular profiling of rare and hard-to-diagnose pediatric tumors
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: The role of comprehensive genomic profiling for therapeutic decision-making is established in high-risk pediatric cancers, but its utility in rare and diagnostically challenging tumors is unclear. Here we report 123 non-high-risk patients enrolled in the Australian ZERO Childhood Cancer Program for diagnostic uncertainty, clinician request to address a specific molecular query, or other rare tumors. Comprehensive multi-omic profiling led to a change in diagnosis in 17.9% (22/123) of patients, with overall diagnostic utility in 35% (43/123). Molecular queries were resolved in 97.6% (40/41). Multi-omic results informed conventional management in 20.3% (25/123). Precision-guided therapy was recommended in 67.5% (83/123), and administered in 36.1% (30/83), with an objective response or prolonged (>6 months) stable disease in 88.9% of evaluable cases (16/18). Findings were confirmed in an independent cohort from the Canadian KiCS program (n=41). In conclusion, in rare and diagnostically challenging pediatric tumors, multi-omic profiling improved diagnostic accuracy and informed clinical management, supporting its integration into routine care.
Source: Research Square
Authors: David Ziegler, Ashleigh Sullivan, Dong-Anh Khuong-Quang, Anita Villani, Marie Wong, Sarah Trinder, Loretta Lau, Paulette Barahona, Ann-Kristin Altekoester, Megan Rumford, Kimberley Dias, Chelsea Mayoh, Noemi Fuentes Bolanos, Eliza Courtney, Sam El-Kamand, Louise Cui, Angela Lin, Scott Davidson, Kyoko Yuki, Nicholas Sanders, Jordan Staunton, Sophie Jessop, Shampavi Sriharan, Frank Alvaro, Antoinette Anazodo, Kanika Bhatia, Martin Campbell, Steve Foresto, Nick Gottardo, Maria Kirby, Seong Lin Khaw, Neevika Manoharan, Geoffrey McCowage, Andrew Moore, Wayne Nicholls, Matthew O'Connor, Bhavna Padhye, Anne Ryan, Leanne Super, Paul Wood, Janene Davies, Colleen D'Arcy, Andrew Gifford, Michael Rodriguez, Katherine Tucker, Mark Pinese, Paul Ekert, Michelle Haber, Vanessa Tyrrell, Toby Trahair, Glenn Marshall, Adam Shlien, Mark Cowley
Institutions: UNSW Sydney, Children's Health Queensland Hospital and Health Service, Murdoch Children's Research Institute, Great Ormond Street Hospital, Hospital for Sick Children, Princess Margaret Hospital for Children, Perth Children's Hospital, Sydney Children's Hospital, Monash Children’s Hospital, Women's and Children's Hospital, John Hunter Children's Hospital, Royal Children's Hospital, Children's Hospital at Westmead, Westmead Hospital, Monash Health, Royal Brisbane and Women's Hospital, Prince of Wales Hospital, Prince of Wales Hospital
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
Funders: Children's Medical Research, Children's Hospital Foundation, Australian Government, Australian Cancer Research Foundation, Cancer Australia, Cancer Institute NSW, University of New South Wales, Hospital for Sick Children, Cure Brain Cancer Foundation, Minderoo Foundation, Kids Cancer Alliance, New South Wales Government, Tour de Cure, National Institutes of Health, Canadian Institutes of Health Research, Medical Research Council, National Health and Medical Research Council, Garron Family Cancer Centre, National Cancer Institute
OpenAlex ID: W7171719358