Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children’s Oncology Group
Bibliographic record
Abstract
BACKGROUND: Embryonal brain tumors are the leading cause of cancer death in young children. METHODS: ACNS0334 was a phase 3 randomized study evaluating high-dose methotrexate in young children < 36 months old with newly diagnosed high-risk embryonal brain tumors. Treatment included 3 cycles of induction chemotherapy with or without methotrexate followed by 3 cycles of high-dose consolidation chemotherapy with hematopoietic stem-cell infusion. Primary endpoint was complete response (CR) at the end of therapy. Secondary endpoints included a comparison of event-free survival (EFS) between arms and to historical controls. Molecular characterization was conducted retrospectively. Tests of significance were one-sided. RESULTS: Of 77 eligible patients, 59 with detectable disease were evaluated for response and 28 (47.5%) achieved CR, 15/30 (50%) treated with methotrexate compared to 13/29 (45%) without methotrexate (P = 0.35). For MB, CR was 12/19 (63%) with methotrexate compared to 6/20 (30%) without methotrexate (P = 0.039). Considering molecular diagnosis, all SHH MB (n = 11) were survivors. Five-year EFS was 70% (90% CI: 39.6-87.2) for 10 Group 3 MB with methotrexate versus 33.3% (90% CI: 15.0-52.9) for 15 without (P = 0.037). In other embryonal tumors, CR was 3/11 (27%) with methotrexate compared to 7/9 (78%) without (P = 0.99). No benefit with methotrexate was observed for Embryonal Tumor with Multilayered Rosettes (n = 14, EFS 20.0% [90% CI: 1.8-52.5] with methotrexate versus 33.3% [90% CI: 10.8-58.1] without, P = 0.58), or pineoblastoma (n = 9, EFS 16.7% [90% CI: 1.6-46.1] with methotrexate versus 0% without, P = 0.52). CONCLUSIONS: The addition of methotrexate to intensive chemotherapy improved CR and EFS for young children with high-risk Group 3 MB, but not other diagnoses.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".