Abstract A41: TRICEPS: A feasibility study of personalized targeted therapy in relapsed/refractory childhood cancers
Notice bibliographique
Résumé
Abstract In Canada, about 1500 pediatric cancers are diagnosed each year. Despite improvements in risk-stratified treatments, around 20% of childhood cancer patients do not respond to current therapies and ultimately succumb to their disease, urging the need for new and more effective therapeutic approaches. Personalized targeted therapy (PTT) based on next generation sequencing (NGS) may be a key component to increase cure rates and decrease treatment-related morbidity and mortality. To assess the feasibility of performing PTT clinical trials in the context of childhood cancers, a pilot study is currently underway at the Sainte-Justine UHC, Montreal, where 30 relapsed or refractory cancer patients (aged 0-21 years) are being recruited over a 2 year period and offered in-depth genomic and transcriptomic investigation to identify patient-specific alterations. This pilot study will allow us to determine the number of children with cancer who are suitable candidates for targeted therapy, to determine the number and type of driver mutation(s) found in the recurrent or refractory childhood cancers, to determine the number of cancer patients who harbor actionable driver mutation(s) that can be targeted with a Health Canada/FDA approved targeted drug and to assess the feasibility of going from biopsy to a detailed tumour analysis report within a clinically-relevant timeframe. Thus far, sixteen patients have been recruited in this study between April 2014 and July 2015. Study subject accrual has been successful with 100% compliance. Eight patients have undergone extensive genomic investigation in a real-time manner. We identified clinically relevant genomic alterations (singe nucleotide variants or structural variations) that can be used to inform clinical management for 8/8 of these patients. Patient screen failures occurred due to benign tumor biopsies, necrotic tumor tissue or low tumor purity, resulting in suboptimal DNA/RNA quantity or quality for NGS. Identified relapse-specific mutations allowed follow up of minimal residual disease, particularly post-transplant for relapsed leukemia cases, influenced patient management and revealed alternative therapeutic options for future personalized targeted therapy. This feasibility study shows that PTT based on NGS technology is a useful approach that could be implemented in the clinic within a foreseeable future to guide treatment of relapsed or refractory childhood cancer patients. The following step toward translating our results into novel personalized therapeutic approaches will be the development of phase II clinical trials to evaluate the efficacy of these targeted therapies in terms of therapeutic response, survival, and overall quality of life. Our overreaching goal is to be able to offer personalized targeted therapy options to all patients upon primary diagnosis of their cancer. Citation Format: Sylvie Langlois, Jasmine Healy, Mathieu Lajoie, Sophie Dumoucel, Fida Khater, Thomas Sontag, Pascal St-Onge, Patrick Beaulieu, Henrique Bittencourt, Dorothée Dal Soglio, Anne-Sophie Carret, Sonia Cellot, Josette Champagne, Michel Duval, Maja Krajinovic, Jean-Marie Leclerc, Natalie Patey, Nelson Piché, Yvan Samson, Pierre Teira, Monia Marzouki, Daniel Sinnett. TRICEPS: A feasibility study of personalized targeted therapy in relapsed/refractory childhood cancers. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A41.
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 | 0,004 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
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 ».