Abstract 5413: Terry Fox PRecision Oncology For Young peopLE (PROFYLE): A Canadian precision medicine program for children, adolescents and young adults with hard-to-treat cancer
Bibliographic record
Abstract
Abstract Introduction: Over 4300 children, adolescents, and young adults (CAYA) are diagnosed with cancer each year in Canada, 1/3 of whom will have refractory or metastatic disease or will relapse with a very poor prognosis. Most CAYA cancer survivors suffer significant late effects that impose an enormous burden to them, their family and the health care system. To address this urgent medical and socioeconomic need, a pan-Canadian collaborative program, PRecision Oncology For Young peopLE (PROFYLE), was created with the objective to develop and implement the first Canadian precision oncology pipeline providing access to tumour molecular profiling with the aim of identifying novel targeted therapeutic options in a clinically relevant timeframe for CAYA with hard-to-treat cancer. Design: Prior to PROFYLE, 3 programs (Personalized Oncogenomics Project (POG), SickKids Cancer Sequencing Program (KiCS), and Personalized Targeted Therapy in Refractory or Relapsed Cancer in Childhood (TRICEPS)) constituted the bulk of childhood precision oncology efforts in Canada. PROFYLE was designed to unite and build upon them, and consists of interconnected nodes including: genomics/bioinformatics, proteomics, cancer modeling, biomarkers, biobanking/data repositories, therapeutics/clinical trial design and biomedical ethics; unified by a shared governance structure. There are 16+ institutions in the PROFYLE consortium. The PROFYLE profiling strategy consists of initial reporting from a >800 cancer gene panel, followed by whole genome (paired germline/cancer samples) and whole transcriptome analyses. Eligibility criteria: ≤29y; treatment at a Canadian oncology center; diagnosis with a hard-to-treat cancer. Profiling results are reviewed by multidisciplinary Molecular Tumour Boards. A patient-specific molecular research report including summary of results and recommendations (actionable finding, potential targeted therapies, any open clinical trials which the patient may be eligible for, change of diagnosis, and/or referral for genetic counselling) is provided to the treating oncologist. Results: To date, 644 patients have taken part in PROFYLE (n=338) and POG, KiCS, TRICEPS. For the first 100 participants, cancer diagnoses include 43 sarcomas, 23 CNS tumors, 10 leukemia and lymphomas, 10 neuroblastoma and 14 other rare cancers. At study entry, 48% had not yet relapsed, 40% 1 relapse, 10% 2 relapses, and 2% 3+ relapses. 13 had a cancer-predisposing germline mutation and 82 had at least one potentially actionable somatic alteration. The most commonly mutated genes/pathways included TP53, CDNK2A/B, FGFR, MYC, and FLT1/3/4. 82% had results/recommendations from the MTB that informed a medical decision to alter diagnosis, prognosis, or treatment of their disease. In 71%, management recommendations were provided. Analyses of the complete dataset will be presented at the meeting. Conclusion: The goal of developing a national precision oncology pipeline has been realized through the establishment of the PROFYLE initiative. PROFYLE continues to grow through increased recruitment, additional institutions, contribution of new knowledge to the field of precision oncology, improving access to clinical trials for CAYA patients, and advocacy and partnerships on local, national and international scales. Citation Format: Stephanie A. Grover, Jason N. Berman, Jennifer A. Chan, Rebecca J. Deyell, David D. Eisenstat, Conrad V. Fernandez, Paul E. Grundy, Cynthia Hawkins, Meredith S. Irwin, Nada Jabado, Steven J. Jones, Michael Moran, Shahrad R. Rassekh, Adam Shlien, Daniel Sinnett, Poul H. Sorensen, Patrick J. Sullivan, Michael D. Taylor, Anita Villani, James A. Whitlock, David Malkin, on behalf of the Terry Fox PROFYLE Consortium. Terry Fox PRecision Oncology For Young peopLE (PROFYLE): A Canadian precision medicine program for children, adolescents and young adults with hard-to-treat cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5413.
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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 | 0.006 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.007 | 0.003 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.005 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.026 | 0.004 |
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".