Improvements in Children’s Oncology Group neuroblastoma risk stratification through a change in age cut-off and use of INRGSS
Bibliographic record
Abstract
We thank the authors for their supportive comments on our manuscript about the revision to the Children's Oncology Group (COG) neuroblastoma risk stratification based on a change in age cut-off from 12 to 18 months (1,2).The authors have provided a well-described and helpful overview of the application of biomarkers to risk stratify patients, as well as describing treatment and late effects.They have nicely summarized the comparative evidence of our successful reduction of therapy due to the described COG risk stratification changes.In addition to the change in age cut-off, COG risk stratification is anticipated to improve by using the INRGSS (International Neuroblastoma Risk Group Staging System) (3) instead of INSS (International Neuroblastoma Staging System) (4,5).INSS was utilized in 2006 when the change in age cut-off was made, but has since been replaced by the INRGSS in the COG neuroblastoma risk classifier version 2.INRGSS is a pre-surgical staging system which quantifies the disease extent at diagnosis, compared to INSS, which is post-surgical and dependent on surgical discretion.The authors describe the use of the International Neuroblastoma Pathology Classification (INPC) as a biomarker in COG risk stratification.Age is one of the factors used to classify tumors as INPC favorable or unfavorable.In the context of risk stratification, using both age and INPC leads to a duplication of the prognostic contribution of age, i.e., confounding.Further improvements in risk stratification should utilize the underlying components of INPC [histologic category, mitosis-karyorrhexis index (MKI), and grade of differentiation] as separate risk factors, to eliminate this problematic confounding (6).We thank the authors for describing the LEAHRN (Late Effects After High-Risk Neuroblastoma) study, the first comprehensive study specifically focused on late effects in survivors of high-risk neuroblastoma (7).These survivors were diagnosed on/after January 1, 2000, with a minimum of 5 years follow-up after diagnosis.The authors state that survivors were treated between 2000-2006; however, many LEAHRN patients were treated after 2006 with more contemporary therapy.The authors state that "While this re-classification saved children to be exposed to unnecessary treatments, their outcome should remain unaltered".Certainly, it was our hope that their outcome remains 'unaltered', but we should clarify our intent.We hypothesized that despite receiving less intensive therapy, these groups would maintain the same outstanding survival outcomes as they had when they received high-risk
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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 | 0.003 | 0.029 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.008 | 0.009 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".