{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T10:57:44Z","timestamp":1785581864870,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,29]]},"group-title":"Oncology","reference-count":31,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>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 (&gt;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.<\/jats:p>","DOI":"10.64898\/2026.07.25.26358936","type":"posted-content","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T16:10:12Z","timestamp":1785341412000},"source":"Crossref","is-referenced-by-count":0,"title":["High clinical utility of comprehensive multi-omic molecular profiling of rare and hard-to-diagnose pediatric tumors"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3818-0614","authenticated-orcid":false,"given":"Ashleigh J.","family":"Sullivan","sequence":"first","affiliation":[{"name":"Oncology Service, Children\u2019s Health Queensland Hospital and Health Service, Brisbane, QLD, Australia"},{"name":"Children\u2019s Cancer Institute at Minderoo Children\u2019s Comprehensive Cancer Centre, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6305-7790","authenticated-orcid":false,"given":"Dong-Anh","family":"Khuong-Quang","sequence":"additional","affiliation":[{"name":"Children\u2019s Cancer Institute at Minderoo Children\u2019s Comprehensive Cancer Centre, Sydney, NSW, Australia"},{"name":"Children\u2019s Cancer Centre, Royal Children\u2019s Hospital, Melbourne, Victoria, Australia"},{"name":"Department of Paediatrics, Murdoch Children\u2019s Research Institute, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3283-2197","authenticated-orcid":false,"given":"Anita","family":"Villani","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, The Hospital for Sick Children, Toronto, ON, Canada"},{"name":"Department of Pediatrics, University of Toronto, Toronto, ON, 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