Comparison of Taqman low density array (TLDA) five-gene assay for tumor cells in bone marrow and blood with histologic bone marrow examination and imaging for disease assessment and outcome in patients with recurrent/refractory neuroblastoma (NBL): A new approaches to neuroblastoma therapy (NANT) study.
Bibliographic record
Abstract
10039 Background: Accurate quantification of tumor burden in NBL patients is needed to define homogenous populations for therapy and establish response criteria that predict outcome. The 5-gene TLDA assay was developed for quantification of NBL cells in bone marrow (BM) and blood (BLD). Methods: Expression of CHGA, DCX, DDC, PHOX2B, and TH (NBL genes) was quantified with TLDA and reported as the geometric mean cycle threshold for the 5 genes (DGS=detection gene score; inversely related to tumor content, 40=negative). Sixty-three patients with recurrent/refractory NBL had TLDA performed on 107 BM and 99 BLD samples (66 paired) at 140 time points. Based on central review of reports, tumor longest diameter (LD) on CT/MRI (n=118), and number of 123I-MIBG avid sites (n=120) were recorded. Percentage of tumor cells in BM was from institutional reports of bilateral BM aspirates/biopsies (n=109). Overall response was assessed per NANT Response Criteria. Spearman rank correlation was performed. Results:TLDA detected tumor cells in 62/99(63%) BLD (average DGS=37.45) and 91/107(85%) BM samples (average DGS=33.42). 39/91(42%) with positive BM TLDA were negative by morphology. BLD and BM TLDA were correlated r = 0.6540, p< 0.0001 with stronger correlation with lower BM DGS scores. The BM and BLD DGS correlated with % BM involvement (BM r= -0.63, p<0.0001; BLD r= -0.35, p=0.0023) and number of MIBG sites (BM r=-0.34, p=0.001, BLD r=-0.51 p<0.0001) but not LD. Number of MIBG sites was also correlated with % BM involvement (r= 0.45, p<0.001) and LD (r= 0.28, p=0.0039). Analysis of 43 BM pairs demonstrated decreasing DGS correlated with overall progressive disease (r= 0.39, p=0.01). Conclusions: This TLDA assay detects NBL cells in both BM and BLD at high rates, and frequently detects tumor cells when BM morphology is negative. Quantification of tumor with DGS correlates with % BM involvement and number MIBG sites. TLDA may provide an additional parameter to delineate response in NBL. Clinical trial information: NCT01587300.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".