Abstract B012: Clinical utility of real-time comprehensive molecular profiling in childhood brain tumors
Notice bibliographique
Résumé
Abstract Introduction: The ZERO Childhood Cancer Program offers precision medicine for all children with cancer in Australia through the ZERO2 Study. The study has been open at all 9 Australian pediatric oncology centres since October 2023, with the goal to evaluate the clinical utility of real-time comprehensive molecular profiling in different cancer types and risk groups. Methods: The ZERO precision medicine platform includes paired tumor-germline whole genome sequencing, whole transcriptomic sequencing and DNA methylation. Samples are sent for sequencing in parallel with diagnostic work-up and oncologists receive somatic and germline results in real-time. Here we report the clinical utility in the first 181 consecutive CNS tumors. Results: Of the 181 patients with CNS tumor, 80% were enrolled at diagnosis and 20% had relapse/refractory disease. Low-grade glioma was the most frequent (39%), followed by medulloblastoma (15%), ependymoma (11%), high-grade glioma (9%), other CNS embryonal tumors (9%), diffuse midline glioma H3 K27M-altered (DMG) (8%) and other tumor types (9%). Comprehensive molecular profiling provided clinical utility for 161/181 (89%) of CNS tumor patients in 4 categories: diagnosis, molecular classification, therapy, and germline. In 16/181 (9%) patients, results were non-informative due to very low tumor content, none of which were DMG samples. 64 (35%) patients derived clinical benefit from 1 category, 74 (41%) from 2 categories and 23 (13%) from 3 categories. Diagnostic utility in 77 (43%) included confirming histologic diagnosis in 64, solving diagnostic dilemma in 7 (e.g., high-grade glioneuronal tumor to CNS neuroblastoma with FOXR2 activation; embryonal tumor to ETMR without C19MC alteration) and changing diagnosis in 6 (e.g., rhabdomyosarcoma to intracranial DICER1-mutant sarcoma; low-grade to high-grade glioma in Li Fraumeni syndrome). Molecular classification was refined in 82 (45%) including 40 with prognostic significance (e.g., Group 3/4 medulloblastoma subtypes; IDH mutant glioma subtypes). Therapeutic molecular targets were identified in 92 (51%). Of the 62 low-grade gliomas with adequate tumor content, only 30 (48%) had a KIAA1549-BRAF fusion or BRAF V600E mutation. The remaining 32 (52%) included other BRAF fusions, RAF1 fusion, ALK fusion, FGFR1 alterations, IDH1/2 mutation, PDGFRA mutation, and MYB/MYBL1 alterations). 31/181 (17%) patients had reportable germline variants:18 were related to a cancer predisposition syndrome, of which 12 were not previously known. The remaining 13 were secondary findings. Molecular reports were returned at a median of 3.7 weeks from receiving samples, including 13 expedited reports at 3.0 weeks and 25 Group 3/4 medulloblastoma methylation subtype reports at 2.5 weeks. Conclusion: Real-time comprehensive molecular profiling has high clinical utility in childhood brain tumors. Citation Format: Loretta M.S. Lau, Dong-Anh Khuong-Quang, Jordan Staunton, Nicholas Sanders, Shampavi Sriharan, Sarah Trinder, Neevika Manoharan, Paulette Barahona, Ann-Kristin Altekoester, Kimberley Dias, Megan Rumford, Dianne Sylvester, Jasmine Parhar, Marion K. Mateos, Marie Wong, Chelsea Mayoh, Mark J. Cowley, Paul G. Ekert, Michelle Haber, Vanessa Tyrrell, David S Ziegler. Clinical utility of real-time comprehensive molecular profiling in childhood brain tumors [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 B012.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
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 tête enseignante, 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 ».