Primitive Desmoplastic Neuroepithelial Tumor of the Skull Base
Notice bibliographique
Résumé
The WHO categorizes desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) as one diagnosis. Little genetic/ molecular characterization of DIG/DIA has been published, with scattered results. We aim to better understand genetic underpinnings of DIG and DIA, natural histories, and their relationships to other glial-neuronal CNS tumors. Methods: Targeted, massively-parallel gene sequencing assays that detect mutations of cancer-related genes using next-generation “deep” sequencing was performed on specimens obtained from 30 patients diagnosed with DIG/DIA by histology. An individual patient data meta-analysis (IPDMA) was performed after an exhaustive search of the existing literature on DIG/DIA. Outcome measures were mortality and tumor recurrence. We performed univariate Cox regression analyses to determine the effect of age, pathology, extent of resection (EOR), radiation, chemotherapy, malignant transformation, leptomeningeal metastasis at presentation, BRAF mutation, and deep tumor location on outcome. A multi-variable Cox regression analysis was performed on variables with a p-value <0.2 on univariate analysis to identify independent predictors of outcome. Results: Among the 30 native tumor samples, we found no genetic aberrations in 22 (73.3%). Within the other eight native tumors, we discovered four (13.3%) BRAFV600E mutations, three (10%) BRAFV600D mutations, and one ALK-EML4 fusion. BRAF mutation defines a subset of DIG/DIA. Seven of 30 (23.3%) patients harbored non-synonymous single nucleotide substitutions on the BRAF gene. Four were of the canonical V600E valine-to-glutamic acid variety; interestingly, 3 of these 4 were found in histologically-diagnosed DIAs. The other 3 were exceptionally rare V600D valine-to-aspartic acid point mutations, which account for <1% of all V600 BRAF mutations. BRAF mutations were discovered in 4 of 26 (15.4%) of DIGs, but in 3 of 4 (75%) of DIAs. Deep-seated DIGs and DIAs have a more malignant natural history. We obtained individual patient data in 100 articles with a total of 239 relevant patients. Of this cohort, 75 articles with a total of 137 patients contained outcome variables of interest eligible for this IPDMA. The first endpoint was mortality. Univariate Cox regression analyses demonstrate that skull base tumor location, EOR, and leptomeningeal metastasis at presentation were predictors of mortality. Specifically, gross total resection (GTR) was associated with a mortality HR of 0.048 ( p = 0.003). Tumor recurrence was a second variable analyzed with time-to-analysis. Tumor pathology, leptomeningeal disease at presentation, skull base tumor location, EOR, and malignant transformation all contribute to statistically significant differences in outcome in Cox regression analysis. Multivariate analysis was performed for co-variates for both outcomes (death and tumor recurrence). The multivariate analysis of predictors of tumor recurrence includes skull base tumor location ( p = 0.015) and malignant transformation ( p = 0.015). Though tumor biology is typically benign, patients experienced poorer outcomes after subtotal resection of DIG/DIAs in comparison to complete resection. Thirteen (56.5%) DIAs presented in deep-seated locations. In comparison, of the 208 cases of DIG, only 10 (4.8%) were deep-seated. DIG and DIA had not been previously differentiated in terms of natural history or expected outcomes. However, a skull base location portends worse prognosis, which could potentially be affected by better EOR.
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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| 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) | 0,001 | 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 ».