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
Bibliographic record
Abstract
Abstract 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.006 | 0.002 |
| Scholarly communication | 0.002 | 0.000 |
| Open science | 0.002 | 0.004 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.013 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".