P26.10.B OPTIMIZING DELIVERY OF CHEMOTHERAPEUTIC AGENTS BY INTRA-ARTERIAL INFUSION IN GLIOBLASTOMA
Notice bibliographique
Résumé
Abstract BACKGROUND Being the most aggressive malignant primary brain tumor, glioblastoma (GBM) is a difficult disease to treat. The first line treatment consists in maximal resection followed by concomitant radiotherapy and temozolomide. However, most patients will relapse during the after treatment. The overall survival is only 14,6 months while the progression-free survival is 6,9 months. Even if the first-line treatment is well established, there is no consensus for the second line. At our institution, Dr. Fortin prioritize the intra-arterial (IA) administration of chemotherapeutic agents (CTA), which conveys a higher drug concentration to the tumor site. Carboplatin is the most used chemotherapeutic, but certain patients will not respond or will even develop chemoresistance to this treatment. Therefore, there is a strong need for bringing different CTAs into clinical care to offer more options. Topotecan, cytarabine and paclitaxel are molecules evaluated in this study since they are all already used intravenously (IV) in the treatment of GBMs. MATERIAL AND METHODS Since these agents have never been used for IA, we need to determine their maximal tolerable dose (MTD) to avoid any adverse effects. As such, healthy rats were given the CTA by retrograde infusion in the external carotid. They were euthanized five days following that surgery. After determining the right dosages, the survival study was initiated. Indeed, every CTAs were administered IA but also IV to compare both administrations. We used the Fischer-F98 glioma rat model. For the efficacy study, we implanted 10 000 F98 cells into the brain of the Fischer rats. At day 10, they received the treatment associated to their group. The animals were followed every day following the surgeries and were euthanized when their condition was too deteriorated. The IV doses used (found in the literature) were topotecan: 4 mg/kg, cytarabine: 40 mg/kg and paclitaxel: 10 mg/kg. RESULTS The doses found in the MTD study for topotecan and cytarabine were 4 mg/kg and 8,75 mg/kg respectively. However, paclitaxel was toxic when administered via IA, probably because of its lipidic vehicle. As for the efficacy study, the IA group of topotecan showed a promising outcome with a higher survival rate (29 days) compared to IV (23,5 days). As for cytarabine groups, IA was detrimental, with a 22 days median survival, compared to 26,5 days for the IV group. CONCLUSION While topotecan and cytarabine could be given intra-arterially, only topotecan showed conclusive results with a higher survival rate. More animals will be added to this group to validate this outcome. Cytarabine does not appear to be a good option since the MTD IA dose yielded a worse survival rate than the dose administered via IV. As for paclitaxel, considering it cannot be used intra-arterially, intra-tumoral infusion will be tested to see if we can get positive results.
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 | 0,000 | 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 | 0,000 |
| 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 ».