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Abstract 5224: The PRecision Oncology For Young peopLE (PROFYLE) Program: A national precision oncology program for children, adolescents and young adults with hard-to-cure cancer in Canada


 Background: Over 4,300 children, adolescents, and young adults (CAYA) are diagnosed with cancer each year in Canada, 1/3 of whom have refractory/metastatic disease or will relapse. A national collaborative program, PRecision Oncology For Young peopLE (PROFYLE), was created with the goal to develop and implement a pipeline providing access to tumor molecular profiling to identify novel targeted treatment options in a clinically relevant timeframe for CAYA with hard-to-cure cancers.
 Design: PROFYLE includes more than 20 institutions, building upon 3 pre-existing regional precision oncology programs (Personalized Oncogenomics (POG), SickKids Cancer Sequencing (KiCS), and Personalized Targeted Therapy in Refractory or Relapsed Cancer in Childhood (TRICEPS)). PROFYLE has united an interdisciplinary team of experts, leaders, research team, end-users and advocates from across Canada to form 14 domain specific nodes unified by a shared governance structure. PROFYLE includes genomic and transcriptomic sequencing of paired germline/cancer fresh/frozen samples. Inclusion criteria: ≤29y; treatment at a Canadian center; diagnosis of a hard-to-cure cancer. Profiling results are reviewed by multidisciplinary Molecular Tumor Boards. A report including a results/recommendations summary of actionable findings (therapeutic, diagnostic, prognostic, cancer predisposition), potential targeted therapy options including available clinical trials, clarification of diagnosis, and genetic counseling recommendations is provided to the treating oncologist.
 Results: To date, >900 CAYA are enrolled. Cancer diagnoses: 36% sarcoma, 16% leukemia/lymphoma, 16% CNS tumor, 13% neuroblastoma, 19% other. At study entry, 44% of participants had not relapsed, 40% had 1 relapse, 9% 2 relapses, 4% 3+ relapses. 17% had a cancer-predisposing pathogenic/likely pathogenic germline variant, 40% had ≥1 potentially actionable somatic alteration, 9.7% had a therapeutically targetable somatic alteration. The most frequent classes of therapeutic alterations were cell cycle (15%), RAS/MAPK (14%), epigenetic (13%), RTK (12%), PI3K/AKT/mTOR (10%), DNA repair (9%), immune checkpoint (8%). Of clinicians who reported the utility of results, 56% indicated the findings were useful for clinical management.
 Future Directions: With a comprehensive molecular view of cancer, PROFYLE will transform our understanding of underlying disease mechanisms, facilitate and improve diagnostic and prognostic indicators, and identify new therapeutic strategies and targets. Data from this interdisciplinary, multi-institutional research program will inform the development of a framework to innovatively link research, clinical and system considerations with Canadian values relevant to genomic profiling and drug access for CAYA in Canada.
 Citation Format: Stephanie A. Grover, Lesleigh Abbott, Jason N. Berman, Jennifer A. Chan, Avram E. Denburg, Rebecca J. Deyell, Conrad V. Fernandez, Cynthia Hawkins, Jan-Willem Henning, Meredith S. Irwin, Nada Jabado, Steven J. Jones, Philipp F. Lange, Michael F. Moran, Daniel A. Morgenstern, Antonia Palmer, Shahrad R. Rassekh, Donna L. Senger, Adam Shlien, Daniel Sinnett, Caron Strahlendorf, Patrick J. Sullivan, Michael D. Taylor, Suzanne Vercauteren, Anita Villani, James A. Whitlock, David Malkin, on behalf of the Terry Fox PROFYLE Consortium. The PRecision Oncology For Young peopLE (PROFYLE) Program: A national precision oncology program for children, adolescents and young adults with hard-to-cure cancer in Canada [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5224.