MBCL-34. EFFICACY OF METHOTREXATE (MTX) ACCORDING TO MOLECULAR SUB-TYPE IN YOUNG CHILDREN WITH MEDULLOBLASTOMA (MB): A REPORT FROM CHILDREN’S ONCOLOGY GROUP PHASE III TRIAL ACNS0334
Bibliographic record
Abstract
Abstract ACNS0334, a Phase 3 trial, compared outcomes of children <36 months treated with intensive chemotherapy +/-high-dose methotrexate. Nodular-desmoplastic M0-stage MB were excluded. Treatment included 3 induction cycles (cyclophosphamide/etoposide/vincristine/cisplatin+/-mtx) and 3 consolidation cycles (carboplatin/thiotepa with stem cell rescue). Radiation (RT) was at physician discretion. Molecular sub-typing was by DNA-methylation. Log-rank testing was used to compare survival differences. Molecular sub-typing of 38 MB identified 11 Sonic Hedgehog (SHH), 25 Group 3 (GP3), 2 Group 4 (GP4). Five-year survival (OS) was 100% for 5 SHH with MTX and 4 SHH without MTX; 80% for 10 GP3 with MTX, 40% for 15 GP3 without MTX (p=0.025). Only 6/14 survivors received RT: 4 for residual following therapy (1 SHH and 3 GP3) and 2 GP3 salvaged after progression. Two GP3 deaths were associated with toxicity; all others were due to disease. Histology among SHH was nodular-desmoplastic (8) or classic (3); GP3 histology was classic (17) or anaplastic (7). Whole-exome sequencing identified 6 somatic PTCH1 and 1 germline SUFU alteration(s) among 9 SHH. Among GP3, no p53 mutations were found; copy-number analysis identified 5/25 with myc-amplification, 5/25 iso17q, 11/25 with 8 loss, 14/25 with loss of 11. Among GP3, 14/19 had no significant germline mutation. ACNS0334 achieved 100% survival for metastatic SHH. Benefit of methotrexate was observed in GP3 MB supporting incorporation of methotrexate into standard therapy for GP3. Upfront central pathology review and molecular sub-typing are critical for future clinical trial risk stratification of young children with embryonal tumors.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".