Combined analysis of PHOX2B at two time points and its value for further risk stratification in high‐risk neuroblastoma
Bibliographic record
Abstract
Abstract Background Risk stratification of high‐risk neuroblastoma (NB) is crucial for exploring treatments. This study aimed to explore the value of minimal residual disease (MRD) based on PHOX2B levels for further risk stratification in high‐risk NB. Methods The expression of PHOX2B was monitored at two time points (after two and six cycles of induction chemotherapy, TP1 and TP2, respectively) by real‐time polymerase chain reaction (RT‐PCR). The clinical characteristics between groups and survival rates were analyzed. Results The study included 151 high‐risk patients. Positive expression of PHOX2B at diagnosis was seen in 129 cases. PHOX2B was mainly expressed in patients with high lactate dehydrogenase (LDH) and neuron‐specific enolase (NSE) levels (p < .001), bone marrow metastasis (p < .001), more than three metastatic organs (p < .001), 11q23 loss of heterozygosity (LOH) (p = .007), and when more events occurred (p = .012). The 4‐year EFS rate was significantly lower in patients with positive PHOX2B expression compared to the negative group at diagnosis (32.9% ± 6.2% vs. 74.5% ± 10.1%, p = .005). We stratified the 151 patients into three MRD risk groups: low high‐risk (low‐HR), with TP1 less than 10−4 and TP2 less than 10−4; ultra‐HR, with TP1 greater than or equal to 10−2 or TP2 greater than or equal to 10−4, and others classified as intermediate‐HR. Patients in ultra‐HR had the worst survival rate compared with other two groups (p = .02). In a multivariate model, MRD risk stratification based on PHOX2B levels at TP1 and TP2 was an independent prognostic factor for high‐risk patients (p = .001). Patients in ultra‐HR were associated with 11q23 LOH (p < .001), more than three organs of metastasis (p = .005), bone marrow metastasis (p < .001), and occurrence of more events (p = .009). Conclusions MRD risk stratification based on PHOX2B levels at two time points (after two and six cycles of induction chemotherapy) provided a stratification system for high‐risk NB, which successfully predicted treatment outcomes. Our results present an effective method for further stratification of high‐risk NB.
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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 | 0.000 | 0.000 |
| 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".