Abstract A033 Early relapse detection: The power and potential of adrenergic and mesenchymal neuroblastoma specific mRNA-based minimal residual disease detection in liquid biopsies
Notice bibliographique
Résumé
Abstract Outcome in high-risk neuroblastoma is still poor, about 50% of patients, assumed to be in complete remission, will suffer from a relapse. More sensitive biomarkers are needed to identify the patients at risk for an event, or to detect this event early. Neuroblastoma specific mRNA panels, including adrenergic (ADR) and mesenchymal (MES) markers, detected in liquid biopsies, are promising biomarkers. We performed a prospective neuroblastoma mRNA qPCR validation study in 345 high-risk neuroblastoma patients, treated in NB2004 (GPOH) or NBL2009 (DCOG) trials. Method: Serial paired bone marrow (BM) and peripheral blood (PB) samples were collected at designated time points and tested with the ADR marker panel (PHOX2B, TH, DDC, CHRNA3, and GAP43) and MES panel (PRRX1, POSTN and FMO3) by RT-qPCR. Association with event-free survival (EFS) and overall survival (OS) was estimated using Kaplan-Meier’s methodology, and hazard ratios were estimated with multivariable Cox regression models. Results: High ADR mRNA levels in BM and PB at diagnosis correlated with 5-year EFS of 17.1% and OS of 26.8% (p < .001). Post-induction BM response correlated with 5-years EFS of 26.6% vs 60.4% (p <.0001) and OS of 43.8% vs 65.7% (p = .001) for RT-qPCRpos patients vs RT-qPCRneg patients respectively. Post-induction BM immunocytology (IC) did not correlate with outcome, however qPCR stratified ICneg BM samples, with 5-year EFS of 20.8 (6.8) vs. 55.8 (7.6) and 5-year OS of 37.6 (8.0) vs. 62.8 (7.4) for ICneg/qPCRpos samples and ICneg/qPCRneg, respectively. For Dutch patients, combining post-induction MIBG (SIOPEN) scores with qPCR stratified patients with SIOPEN score ≤3, with 5-year relapse free survival of 32% vs. 57%, for qPCRpos vs qPCRneg, respectively. MES mRNA detection at diagnosis was prognostic for EFS, because these were detected in samples with high ADR mRNA levels, which correlated with poor outcome. Most GD2-ICneg BM samples were MES qPCR only positive, suggesting that the MES-phenotype is GD2 negative. After 2 chemotherapy courses MES-mRNA identified plasticity in paired analysis with BM GD2-IC, demonstrating 5Y EFS for GD2-ICneg/MESpos of 15.0% vs 57% for GD2ICneg/MESneg, respectively. In all samples, MES-mRNA was detected in more patients with relapse than those who remained disease free (48% vs. 33%, respectively; p=0.002). In patients with relapse, MES mRNA-levels increased during therapy but were not detectable at relapse, potentially reverting back to an ADR-phenotype. Finally, the ADR panel detected relapses up to 140 days prior to standard of care imaging. Conclusion: mRNA detection by qPCR is efficient, inexpensive, standardized, and very sensitive to detect BM disease in high-risk neuroblastoma. This prospective validation study shows the power and potential for sensitive MRD detection of ADR mRNA markers, its superiority to BM IC and MIBG-based response evaluation. Finally, the detection of plasticity by the MES markers identifies the patients at risk of an event when the tumor cells are undetectable by the current techniques. Citation Format: Godelieve tytgat, Lieke van Zogchel, Nina Gelineau, C. Ellen van der Schoot, Marta Fiocco, Aleksandra Letunovska, Zeinab Van Gestel-Fadaie. Early relapse detection: The power and potential of adrenergic and mesenchymal neuroblastoma specific mRNA-based minimal residual disease detection in liquid biopsies [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 A033.
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 | 0,002 | 0,001 |
| 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 | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 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 ».