MEDU-34. PILOT STUDY OF A SURGERY AND CHEMOTHERAPY-ONLY APPROACH IN THE UPFRONT THERAPY OF CHILDREN WITH WNT-POSITIVE STANDARD RISK MEDULLOBLASTOMA
Bibliographic record
Abstract
BACKGROUND: Molecular subclassification of medulloblastoma identifies Wnt-positive medulloblastoma (WPM) as a highly favorable subtype with event-free survival (EFS) exceeding 90% when treating patients following near total or complete resection with standard dose craniospinal irradiation and boost radiation to the posterior fossa (XRT) followed by adjuvant chemotherapy. This pilot study explored the safety of omitting XRT in children with standard-risk WPM. METHODS: Subjects had to meet usual standard-risk criteria (< 1.5 cm2 residual tumor, no metastatic spread, no anaplasia) and have a WPM. Initial criteria for determination of WPM included nuclear beta-catenin immunopositivity, monosomy 6 and absence of myc-amplification by FISH. Following the first two subject enrollments, criteria for WPM was revised to no longer require nuclear beta-catenin immunopositivity, and substituted gene-expression profiling by Nanostring. Upon consent, eligible subjects received adjuvant chemotherapy following the Children’s Oncology Group ACNS0331 AAB-AAB-AAB (A=cisplatin/CCNU/VCR; B=cyclophosphamide/vincristine) backbone and followed for EFS. RESULTS: Fourteen children underwent prescreening of which six children who met molecular criteria for WPM elected to enroll on study treatment. Subject #1 completed planned protocol therapy, requiring a 50% reduction in cisplatin for most of therapy for ototoxicity, but relapsed 3 months following the completion of therapy. Subject #2 completed planned protocol therapy without dose reductions or delays, but relapsed 6 months following the completion of therapy. In both cases, relapse was local and disseminated. Following the second relapse, further accrual was halted. Of the remaining 4 subjects, two have recently completed protocol therapy and remain free of disease. The final two subjects are in the midst of protocol therapy. Additional therapy in the form of XRT and/or chemotherapy dose intensification has been recommended to these remaining 4 subjects. CONCLUSIONS: Chemotherapy following ACNS0331, in the absence of XRT, appears to be insufficient for the treatment of non-metastatic WPM.
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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 | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 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".