Notice bibliographique
Résumé
To the outside world, it may seem that neuro-oncologists involved in the development of novel treatment approaches to gliomas are narrow-minded and very preoccupied with one drug, temozolomide (TMZ), and one enzyme, O6-methylguanylmethyltransferase (MGMT). TMZ was approved for recurrent anaplastic glioma and glioblastoma in 1997 and soon became a standard of care in this setting.1,2 In 2005, the European Organization for Research and Treatment of Cancer-National Cancer Institute of Canada trial set a new standard of care for newly diagnosed glioblastoma3 and the role of TMZ in recurrent glioblastoma became questionable because fewer and fewer patients were TMZ-naive at recurrence. In the absence of promising competitor agents, however, it soon became clinical practice to re-expose TMZ-pretreated patients to the same drug (rechallenge) when relapse occurred after a treatment-free interval. Moreover, for patients failing the standard TMZ, various competing alternative TMZ dosing regimens of temozolomide were explored based on various theoretical assumptions, including MGMT depletion in tumor cells and anti-angiogenic, metronomic chemotherapy-like effects of TMZ; such regimens included continuous daily temozolomide (see also: clinicaltrials.gov NCT00392171),4 3 weeks on/1 week off,5 and 1 week on/1 week off.6 In the present issue of Neuro-Oncology, Kong and colleagues7 report another small phase II study of continuous daily TMZ (40–50 mg/m2) in patients with recurrent glioblastoma. Their progression-free survival rate at 6 months of 32.5% confirms to the point what has been reported in this setting.4,8 Because of the small patient numbers and different patterns of prior treatment, it is impossible to select the best of these schedules to carry forward, for example, for combination trials, but it can be assumed that the rate of progression-free survival at 6 months with these regimens will be in the range of 30% even in TMZ-pretreated patients. Two of these regimens are currently being studied in a non-comparative randomized phase II design (DIRECTOR, clinicaltrials.gov NCT00941460). Uniformly all studies report that the MGMT promoter methylation status determined at diagnosis does not correlate with the benefit derived from alternative TMZ regimens given at recurrence.5–7 Although many of the rationales for using alternative TMZ dosing regimens at recurrence center on overcoming MGMT-mediated resistance, surprisingly little is known regarding the MGMT status at recurrence and its prognostic or predictive significance. Also in this issue of Neuro-Oncology, Brandes and colleagues9 assessed the MGMT status in 38 paired samples of primary and recurrent glioblastomas. The MGMT status changed in 14 patients (37%), more often from methylated to unmethylated (8 of 13 patients) than from unmethylated to methylated (6 of 25 patients). Again, only the MGMT status determined at diagnosis was prognostic. While both new reports7,9 advance our understanding of the role of TMZ and MGMT status at recurrence, several questions remain. How can we be sure that pseudoprogression did not contribute to the 30% rate of stable disease at 6 months, particularly patients switched to alternative TMZ regimens during the 6 standard maintenance cycles? Which mechanisms drive changes in the MGMT status from first to recurrent tumor and how reliable are such assessments, and is MGMT status within the recurrent tumor as homogeneous as it presumably is in primary tumors? Answers to these questions are clinically relevant and will shape the standards of care in the diagnosis and treatment of glioblastoma for years, justifying our current apparent preoccupation with temozolomide and MGMT.10
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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 | 0,002 | 0,002 |
| 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 ».