Relationship of fusion protein status and outcome for children with intermediate-risk rhabdomyosarcoma: A Children's Oncology Group report.
Bibliographic record
Abstract
9535 Background: Rhabdomyosarcoma (RMS) includes both alveolar (ARMS) and embryonal (ERMS) subtypes, with ARMS generally having a worse prognosis. Most ARMS express one of two fusion genes generated by balanced translocations fusing DNA binding domains of PAX3 or PAX7 with FOXO1 (P3F and P7F, respectively). The prognostic value of fusion gene versus histological subtype is not clear. We carried out a multi-institutional clinical trial through the Children’s Oncology Group (COG) to evaluate this molecular feature. Methods: All participants were enrolled on COG D9803 from 1999-2005 for children and young adults with intermediate risk ARMS or ERMS, and were treated with vincristine, dactinomycin, and cyclophosphamide (+/- topotecan), radiotherapy, and surgery. Diagnostic specimens were reviewed centrally and fusion gene was assessed by fluorescence in situ hybridization (FISH), RT-PCR, or both. Event-free (EFS) and overall survival (OAS) at 5 years (yr) was correlated with histology and fusion gene status. Results: Of 327 cases included in a re-review of the pathology, 295 could be classified biologically. Cases with ARMS but unknown trans status (N=23) and those with mixed or RMS-NOS histology without trans (N=17) and 12 with inadequate clinical data were excluded. ARMS cases with detectable fusion gene were defined as ARMS P3F+, ARMS P7F+, while ARMSn was reserved for those without detectable fusion. P3F and P7F were not observed in ERMS. An additional 189 pts with ERMS tumors not re-reviewed were also included in the survival analysis. There was a trend toward better EFS for those with ARMSn than for ERMS (p=0.15); EFS for ARMS P3F+ and P7F+ were worse than that for ERMS (p<0.001). Only ALV P3F+ cases had poorer OAS (p=0.004). Conclusions: ARMSn has an outcome similar to ERMS and a superior EFS compared to ARMS with P3F or P7F, when given therapy designed for intermediate risk RMS. This analysis, from a single, prospective trial restricted to those with non-metastatic disease and with near universal molecular evaluation, supports incorporating fusion status into treatment allocation. [Table: see text]
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".