Intra-arterial chemotherapy and osmotic blood-brain barrier disruption for primitive neuroectodermal tumors
Bibliographic record
Abstract
2046 Background: The blood-brain barrier (BBB) may, in part, contribute to the poor outcome in primitive neuroectodermal tumors (PNETs) treated with chemotherapy. Intra-arterial chemotherapy and osmotic BBB disruption (IA/BBBD) increases drug delivery to the central nervous system while preserving neurocognitive functioning and minimizing systemic toxicity. Methods: The study aims were evaluation of efficacy and toxicity in patients with PNETs other than medulloblastoma treated with IA/BBBD. A chart review of patients from 3 centers treated on various protocols was conducted. Study outcomes included overall survival (OS) and time to progression (TTP, from date of first study treatment). Times to events were estimated using Kaplan-Meier product limit method. Results: Twenty-nine patients (median age 20.5 years, median Karnofsky performance status 90%) were identified. Pathologic diagnoses included pineoblastoma (n = 13 patients), atypical pineocytoma (n = 2), neuroblastoma (n = 3), and other supratentorial or disseminated PNETs (n = 11). Thirteen patients were pretreated before IA/BBBD: 5 with only chemotherapy, 4 with radiotherapy alone, and 4 with both. Intraarterial chemotherapy included carboplatin (n = 24), methotrexate (n = 3), or a combination of both (n = 2). Six patients had a complete and 11 a partial response to IA/BBBD (response rate 58.6%). Ten patients received adjuvant radiotherapy. Twenty (69%) patients relapsed. Median TTP was 1.1 (95% confidence interval 0.8 to 8.4) years, and 9/28 (32.1%) evaluable patients have not yet progressed. Median OS was 2.5 (1.2–11.7) years, 40% survived 4.0 years, and 30% survived 8.7 years. Nine out of 29 (31%) patients are alive, and 6/29 (20.7%) are alive 11+ years after first treatment. Twenty patients have died: 16 due to disease progression, 3 due to toxicity, and 1 due to other reasons. No deaths or permanent neurologic or vascular sequelae related to the IA/BBBD procedure were observed. Conclusions: Survival in PNETs treated with IA/BBBD appears favorable as compared to the literature, especially when considering that 11 patients received IA/BBBD as salvage treatment. A plateau in survival suggests that select patients may be cured. No significant financial relationships to disclose.
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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".