Factors associated with survival following relapse of high-risk neuroblastoma: A study from the International Neuroblastoma Risk Group (INRG) Data Commons.
Bibliographic record
Abstract
10052 Background: Outcomes for high-risk neuroblastoma (HR-NBL) following relapse are poor, although there is a paucity of data on overall survival post-relapse (OSPR) in the contemporary era. Prognostic factors associated with OSPR across all neuroblastoma risk groups (INSS stage, MYCN status and time to first relapse) have previously been described. Here we present an analysis focussed specifically on HR-NBL. Methods: We conducted a retrospective analysis using INRG Data Commons including HR-NBL patients diagnosed ≥1985 with relapse/progression ≤2022. HR-NBL was defined as age ≥547days at diagnosis with INRGSS M; or INRGSS L2 MYCN-amplified disease. The final cohort excluded patients without relapse/progression and with death as first event. Primary endpoint was OSPR, with Kaplan-Meier estimates of survival and sub-group comparisons using log-rank tests. Results: Of the 25,245 NBL patients in the INRG Data Commons, 4045 were included in the final analysis. The majority had INRGSS M disease (96%) and were < 5 years at diagnosis (74%), with MYCN amplification in 36% of those with available data. OSPR was 22±0.7% at 2 years and 8±0.4% at 5 years, with median OSPR 0.76 years (95% CI: 0.73-0.82). OSPR improved over time; for example, 2-year OSPR was 16+/-2.8% for patients diagnosed 1985-1989 vs 32%±2.8% for 2015-2019 (p < 0.0001). Across the whole cohort, patients with a diagnosis of NBL (vs nodular ganglioneuroblastoma), greater number of involved metastatic compartments (MSI) or elevated LDH at diagnosis, tumors with MYCN amplification, higher MKI, 1p LOH and presence of ALK mutation had statistically significantly worse OSPR than respective counterparts. OSPR for INRGG M was significantly better than for INRGSS L2. Serum ferritin, tumor grade and ploidy were not associated with OSPR, while 11q LOH and age showed non-proportional hazards, with patients aged ≥5 years at diagnosis having a better early OSPR but poorer long-term outcome than those < 5 years. Conclusions: In this, the largest analysis of patients with relapsed HR-NBL, multiple factors at diagnosis were associated with OSPR, emphasising the importance of tumor biology and disease burden. The finding of improved OSPR for INRG M vs L2 is unexpected but may relate to MYCN amplification. Further analyses will focus on changes in prognostic factors over time, non-proportional hazards and the impact of upfront and relapse treatment paradigms on OSPR and prognostic factors.
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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 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".