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
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,006 | 0,006 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,007 | 0,003 |
| Communication savante | 0,003 | 0,001 |
| Science ouverte | 0,002 | 0,005 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,026 | 0,004 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».