P26.10.B OPTIMIZING DELIVERY OF CHEMOTHERAPEUTIC AGENTS BY INTRA-ARTERIAL INFUSION IN GLIOBLASTOMA
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".