Convection-Enhanced Delivery in Malignant Gliomas: A Review of Toxicity and Efficacy
Bibliographic record
Abstract
Malignant gliomas are undifferentiated or anaplastic gliomas. They remain incurable with a multitude of modalities, including surgery, radiation, chemotherapy, and alternating electric field therapy. Convection-enhanced delivery (CED) is a local treatment that can bypass the blood-brain barrier and increase the tumor uptake of therapeutic agents, while decreasing exposure to healthy tissues. Considering the multiple choices of drugs with different antitumor mechanisms, the supra-additive effect of concomitant radiation and chemotherapy, CED appears as a promising modality for the treatment of brain tumors. In this review, the CED-related toxicities are summarized and classified into immediate, early, and late side effects based on the time of onset, and local and systemic toxicities based on the location of toxicity. The efficacies of CED of various therapeutic agents including targeted antitumor agents, chemotherapeutic agents, radioisotopes, and immunomodulators are covered. The phase III trial PRECISE compares CED of IL13-PE38QQR, an interleukin-13 conjugated to Pseudomonas aeruginosa exotoxin A, to Gliadel® Wafer, a polymer loaded with carmustine. However, in this case, CED had no significant median survival improvement (11.3 months vs. 10 months) in patients with recurrent glioblastomas. In phase II studies, CED of recombinant poliovirus (PVSRIPO) had an overall survival of 21% vs. 14% for the control group at 24 months, and 21% vs. 4% at 36 months. CED of Tf-diphtheria toxin had a response rate of 35% in recurrent malignant gliomas patients. On the other hand, the TGF-β2 inhibitor Trabedersen, HSV-1-tk ganciclovir, and radioisotope 131I-chTNT-1/B mAb had a limited response rate. With this treatment, patients who received CED of the chemotherapeutic agent paclitaxel and immunomodulator, oligodeoxynucleotides containing CpG motifs (CpG-ODN), experienced intolerable toxicity. Toward the end of this article, an ideal CED treatment procedure is proposed and the methods for quality assurance of the CED procedure are discussed.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".