Efficacy of busulfan-melphalan high dose chemotherapy consolidation (BuMel) compared to conventional chemotherapy combined with lung irradiation in ewing sarcoma (ES) with primary lung metastases: Results of EURO-EWING 99-R2pulm randomized trial (EE99R2pul).
Bibliographic record
Abstract
11001 Background: EE99R2pul (ISRCTN61438620) was conducted in 16 countries, by 5 cooperative groups: COG, SFCE/GSF, GPOH, UK CCLG, EORTC. It evaluated the effect on event-free (EFS, main endpoint) and overall survival (OS) of BuMel without radiation to the lung, compared to standard chemotherapy with lung irradiation in ES presenting with metastases to the lung or pleura. Methods: Eligible pts had histological confirmation of ES, lung or pleural metastases, no other metastatic site, were aged <50, received chemotherapy with 6 VIDE (vincristine, ifosfamide, doxorubicin, etoposide) courses and 1 VAI (vincristine, actinomycin-D, ifosfamide) before randomization to BuMel with stem cell rescue or VAI x 7 courses and lung irradiation (VAI-RT). The analysis was conducted as intention-to-treat. The estimate of the hazard ratio, HR, and the p-value were corrected for the 3 previous interim analyses by the Inverse Normal Method. Results: Between 2000 and 2014, from 576 pts with lung or pleural metastases, 265 pts (median age, 14 yrs) were randomized to VAI-RT (132) or BuMel (133). Some pts requiring radiation therapy to the primary site were excluded from randomization to avoid excess organ toxicity from interaction between RT and Busulfan. Median follow up is 7.6 yrs. Overall, 3yr-EFS is 53.0% and OS, 68.4%. We did not observe any significant difference in survival outcomes between treatment groups: For BuMel pts, 3yr-EFS was 55.7% (95%CI, 47.0-64.0) vs. 50.3% (95CI%, 41.8-58.9) for VAI-RT pts, hazard ratio (HR) of 0.80 (0.57-1.14), p=0.21. OS is 55.9% for BuMel vs. 51.5% for VAI-RT, HR 0.97 (0.66-1.42), p=0.88. Results were consistent across subgroups, and in the sensitivity analyses. Three pts died of BuMel-related toxicity and none after standard chemotherapy. Significantly more pts in BuMel-arm experienced severe acute toxicities than in the VAI-RT arm. Conclusions: In ES with lung metastases, there is no clear benefit associated with BuMel high-dose chemotherapy without lung irradiation compared to conventional chemotherapy combined with lung irradiation. Clinical trial information: 61438620.
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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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".