Abstract A039 Circulating tumor DNA in pleuropulmonary blastoma (PPB)
Notice bibliographique
Résumé
Abstract Background: Pleuropulmonary blastoma (PPB) is a rare but often aggressive tumor seen primarily in infants and young children. Type I PPB is a purely cystic lesion, Type II PPB is cystic and solid and Type III PPB is a purely solid sarcoma. Types II and III PPB are aggressive sarcomas, treated with surgery and intensive, multiagent chemotherapy with or without radiation. Novel therapies to diagnose PPB and progression/recurrence are urgently needed. Nearly all PPBs have one of a specific set of somatic missense variants in the DICER1 gene in the RNase IIIb domain termed the “hotspot” region; most of these variants occur in a specific set of codons (E1705, D1709, G1809, D1810, E1813). One of eleven specific base substitutions are detected in 92% of PPBs. We hypothesized that a limited panel could be designed to detect these “hotspot” variants to facilitate noninvasive detection of PPB and monitor disease status. Methods: Children enrolled in the International PPB/DICER1 Registry (www.ppbregistry.org). Informed consent (and assent when applicable) was obtained. Pathology was centrally reviewed. Treatment remained at the discretion of the treating institutions; clinical course including imaging, surgery and disease status were abstracted. Tumor size was analyzed using largest solid tumor dimension. Tumors were sequenced to determine the tumor-specific RNase IIIb missense variant. Blood samples were collected in Streck tubes at specified timepoints including pre-chemotherapy and between cycles 4 and 5 of chemotherapy and analyzed using digital droplet PCR to determine the presence of the RNase IIIb variant in the extracted circulating tumor DNA (ctDNA). Results: Overall, 35 individuals with Type II or III PPB provided blood samples and had clinical and laboratory data available for analysis. In Type II or III PPB, pre-chemotherapy, 9/16 children had detectable ctDNA, 2/16 indeterminate and 5/16 undetectable ctDNA. Nine of 11 children with unresected tumors had detectable ctDNA versus 0/5 patients with resected tumors (p=0.005). The two patients with unresected tumors and indeterminate/undetectable ctDNA had smaller tumors (1 and 2.5 cm in largest dimension compared with 7.1 to 19.4 cm for the remaining cases). Among the 11 patients with unresected tumors, Spearman’s rank correlation between tumor size and number of variant droplets per PCR reaction was 0.59 (p=0.061). Seventeen individuals had samples drawn after cycle 4 and prior to cycle 5 of chemotherapy. Of these, 1/17 had detectable ctDNA, 5/17 indeterminate and 11/17 undetectable ctDNA. The single unresected patient at this timepoint had detectable ctDNA vs. 0/16 who had undergone resection by this timepoint. (p=0.059). Conclusion: In children with Types II and III PPB, detection of ctDNA is associated with resection status and tumor size. Ascertainment of ctDNA in children with Type II and III PPB represents a potential noninvasive detection method. Further research is needed to clarify the ability of current technologies to detect minimal residual disease in DICER1-related cancers. Citation Format: Kris Ann P. Schultz, Amanda L. Field, Dave Watson, Paige HR Mallinger, Alexander T. Nelson, Anna Dybvik, Nicole Frederickson, Melissa Abraham, Paige Reimche, Yoav H. Messinger, Louis P. Dehner, Chenyu Xu, Anne K. Harris, D. Ashley Hill. Circulating tumor DNA in pleuropulmonary blastoma (PPB) [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 A039.
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».