Plasma Transforming Growth Factor α and Amphiregulin Protein Levels in NCIC Clinical Trials Group BR.21
Bibliographic record
Abstract
PURPOSE: To evaluate the prognostic and predictive significance of plasma levels of the epidermal growth factor receptor (EGFR) ligands, transforming growth factor α (TGF-α) and amphiregulin, in patients with non-small-cell lung cancer (NSCLC) enrolled in NCIC Clinical Trials Group BR.21 comparing erlotinib with placebo. PATIENTS AND METHODS: TGF-α and amphiregulin were assessed retrospectively by enzyme-linked immunosorbent assay from available prospectively collected baseline plasma samples in 565 of 731 BR.21 patients. Cutoff points were determined for both amphiregulin (low, <10 pg/mL; high, ≥10 pg/mL) and TGF-α (low, ≤12 pg/mL; high, >12 pg/mL) using a graphical method. Cox regression models were used to correlate biomarker data and baseline characteristics with outcomes including overall (OS) and progression-free survival (PFS). RESULTS: High TGF-α and amphiregulin were associated with poorer performance status (P=.06 and P<.0001, respectively) and no prior platinum therapy (P=.06 and P=.02, respectively). High amphiregulin was also associated with anemia (P=.001), increased lactate dehydrogenase (P=.03), ever-smokers (P=.04), and non-Asian ethnicity (P=.001). Patients on the placebo arm with high amphiregulin had poorer OS than patients with low amphiregulin (hazard ratio [HR]=1.88; 95% CI, 1.34 to 2.64; P=.0002), which remained significant in multivariate analysis. Amphiregulin levels did not predict for benefit from erlotinib (interaction P=.87). Conversely, TGF-α levels did not have prognostic significance, but high TGF-α predicted lack of benefit from erlotinib compared with low TGF-α (TGF-α low, OS HR=0.66; 95% CI, 0.54 to 0.81; P<.0001; high, OS HR=1.32; 95% CI, 0.73 to 2.39; P=.36; interaction P=.04). CONCLUSION: High baseline amphiregulin is a poor prognostic factor, whereas high baseline TGF-α predicts for lack of benefit from erlotinib in advanced NSCLC.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.015 | 0.031 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".