Clinical outcome and biological predictors of relapse following nephrectomy only for very low risk Wilms tumor (VLR WT): A report from Children’s Oncology Group AREN0532.
Bibliographic record
Abstract
10023 Background: An earlier study of observation only following nephrectomy for VLR WT defined as stage I, age < 2 years, favorable histology with a weight<550 grams was suspended for excess relapse. Follow up revealed a higher salvage rate than originally predicted and suggested novel prognostic biomarkers. In this study, we sought to determine if 1) an observation alone strategy in centrally reviewed VLR WT demonstrates an Event Free Survival (EFS) of > 85% and Overall Survival (OS) of > 95%, and 2) to validate prognostic biomarkers. Methods: From 10/30/2006-8/12/2013, 116 eligible patients were enrolled with VLR WT; negative lymph node sampling was required and predisposition syndromes were excluded. All cases had central review of pathology, diagnostic imaging and surgical reports on the AREN03B2 biology and classification study. Evaluable tumors were analyzed for mutation of WT1, 1p and 16q loss of heterozygosity (LOH) using microsatellite analysis, 1q gain, 1p and 16q loss by MLPA, and 11p15 loss or retention of imprinting (LOI, ROI) using methylation restriction sites analysis. Results: Median follow up was 80 months (5-97). Median age was 11.5 months (0.1-23). 12 patients relapsed with no deaths. Estimated 4-year EFS was 89.7% (95% CI 84.1-95.2%) and OS was 100%. 1 patient is alive with disease after 4 relapses. First site of relapse was lung (n=5), tumor bed (n=4), abdomen (n=2), contralateral kidney (n=1). Median time to first relapse was 4.2 months (2.2-43). The presence of intralobar (p=0.46) or perilobar rests (p=1.0) was not associated with relapse, nor was histological subtype (p=0.16). 1q gain, 1p loss and/or 16q loss did not predict relapse, nor did WT1 mutation (but 13/14 with WT1 mutations also had 11p15 LOH). 11p15 methylation status predicted relapse. Conclusions: Most patients meeting VLR criteria can be safely managed by nephrectomy alone. 11p15 LOH/LOI predicts relapse. Future trials considering expansion of an observation alone strategy for low risk WT should incorporate these biomarkers. Clinical trial information: NCT00352534. Relapse No Relapse Yes Total P value 11p15 LOH 32 (80%) 8 (20%) 40 0.0106 11p15 ROI 58 (97%) 2 (3%) 60 11p15 LOI 6 (75%) 2 (25%) 8 Total 96 (89%) 12 (11%) 108
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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) | 0.000 | 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".