Abstract B035: Stratified Medicine Paediatrics2 – advancing precision medicine in paediatric cancer
Notice bibliographique
Résumé
Abstract Stratified Medicine Paediatrics (SMPaeds) was the UK’s first national profiling platform and successfully provided an infrastructure to triage patients for targeted treatments and clinical trials by identifying molecular abnormalities in relapsed childhood cancer. The molecular panels provided as part of SMPaeds have now been implemented into the National Health Service (NHS) Test directory as routine Standard of Care (SoC). Paired whole genome sequencing (PWGS) has also been available for children with cancer in the UK since 2021, although the uptake of this molecular assay at diagnosis and relapse has varied nationally. In centres that have routinely implemented WGS, a clinical benefit has been demonstrated. However, due to the costs and prolonged turnaround time, its utility is limited to 1-2 timepoints for any patient. SMPaeds recruited >800 patients, with a turnaround time of 21-28 days for reporting results to clinicians via the NMTB. A germline cancer predisposition was identified in 8% of patients, leading to a change or refinement in diagnosis in 13%. A pathogenic event was found in 72% of patients, the NMTB provided a treatment recommendation in 37% and 16% entered a clinical trial. These results are comparable with other international precision medicine programmes for paediatric cancer (NCI-COG Ped MATCH, INFORM, MAPPYACTS and ZERO). There is still significant unmet need in paediatric cancer, with a proportion of patients not having actionable variants identified in tumour tissue, and their response/resistance to recommended treatment being unmonitored molecularly. SMPaeds2 will build on the success of SMPaeds. The main objective of this programme is to identify novel and potentially actionable drivers of aggressive disease, treatment resistance factors and developing less invasive “liquid biopsies” for improved patient selection and monitoring in future clinical trials. SMPaeds2 will also develop assays amenable to serial sampling to monitor patients through their treatment journey. Patients aged 0-21 years and older patients with paediatric cancers at relapse will be eligible. Tumour tissue, paired blood samples (and CSF if applicable) will be collected to study genetic, epigenetic, proteomic, metabolomic and immunologic events to make informed recommendations for relapse treatment. The utility of liquid biopsies will be established within cancer subtypes as less invasive diagnostic assays. Serial liquid biopsies to extract circulating tumour DNA (ctDNA) will then be used to monitor response to therapy and emergence of treatment resistance to allow early, molecularly guided alterations to treatment. Expanding beyond single assay genomic testing, SMPaeds2 will provide a comprehensive genetic, epigenetic and immunologic understanding of each childhood cancer patient to improve precision diagnostics and therapies. The programme will also extend to research-based platforms including spatial transcriptomics, and detection of minimal residual disease in blood and CSF. Citation Format: Aditi Vedi, Sally George, Thomas Jacques, Isidro Cortes-Ciriano, Michael Hubank, Andrew Beggs, Maggie Cheang, Nuria Porta, Ciaran Hutchinson, Louise Hopkins, Amina Bukhari, Regan Barfoot, Steve Clifford, David O'Connor, Timothy Ritzmann, Amos Burke, John Anderson, Darren Hargrave, Louis Chesler. Stratified Medicine Paediatrics2 – advancing precision medicine in paediatric cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B035.
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 | 0,020 | 0,041 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,002 | 0,002 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,004 | 0,002 |
| Science ouverte | 0,002 | 0,006 |
| Intégrité de la recherche | 0,003 | 0,005 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,036 | 0,010 |
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 ».