TGF-α and amphiregulin levels in non-small cell lung cancer (NSCLC) patients (pts) treated with erlotinib/placebo in the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) BR.21
Bibliographic record
Abstract
11023 Background: In BR.21, erlotinib prolonged survival of previously treated NSCLC pts. We examined the predictive/ prognostic effects of the EGFR ligands, TGFa and amphiregulin(Am). Methods: Plasma was collected prior to treatment in consenting pts. TGFa and Am were analyzed by ELISA (R&D Systems). Samples were blinded, measured in duplicate and ligand concentrations determined following interpolation of a standard curve generated from known quantities of recombinant proteins. Sensitivity was ∼3pg/ml. Cutoff points for TGFa were <10 (low) and ≥10 (high); for Am <1.5 (low) vs 1.5–10 (intermediate) vs >10 (high). Standard statistical methods were used to correlate biomarker data with baseline characteristics and outcomes. Results: In 731 randomized pts, 539 were evaluable for both markers; there was a significant interaction (p=0.03) between the evaluable and inevaluable cohorts (erlotinib benefit favoring the evaluable cohort); evaluable pts were more likely to be male, > 60 and to have EGFR amplification. Baseline high TGFa was associated with poorer ECOG PS (p=0.03) while high Am was associated with worse PS (p<0.0001), anemia (p<0.0001), non response to prior therapies (p=0.01) and no-prior platinum therapy (p=0.02). Although TGFa was not prognostic for OS (HR=1.0, p=0.99), high Am was (HR: Middle vs low: 0.94, 95% C.I 0.49 -1.81; high vs.low: 2.04, 95% C.I 1.43 - 2.91; p=0.0002). High TGFa was a poor prognostic factor for PFS (HR 1.4, p=0.07) as was elevated Am (HR: Middle vs low: 1.02, 95% C.I 0.56 -1.85; high vs. low: 1.67, 95% C.I 1.19 - 2.35, p=0.01). In multivariate analyses including both ligands, high Am remained prognostic, but neither ligand was predictive. Conclusions: High levels of baseline Am appears to be a poor prognostic factor, while low levels of TGFa showed a trend to predict benefit from erlotinib in univariate analyses. [Table: see text] [Table: see text]
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 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 | 0.001 |
| 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".