Presentation and outcomes of KRASG12C mutant non-small cell lung cancer patients with stage IV disease at diagnosis (de novo) versus at recurrence
Bibliographic record
Abstract
• Patients with metastatic KRAS G12C -mutated NSCLC have few therapy options. • Patients who develop metastasis at recurrence may have better performance than patients with initial metastatic disease ( de novo ). • We found that de novo patients had more disease and were less fit for therapy compared to recurrent patients. • There is an urgent need for targeted therapy for patients with de novo KRAS G12C –mutated NSCLCs. Close monitoring after diagnosis of patients with stage I-III non-small cell lung cancer (NSCLC) may result in fitter patients with lower disease burden at the time of metastatic recurrence or progression compared to patients diagnosed initially as stage IV ( de novo ). We compared the presentation, treatments, and outcomes of patients with KRAS G12C -mutated NSCLC with de novo versus recurrent stage IV disease. Of 109 patients, 94% had a smoking history. When compared to patients with KRAS G12C -mutated NSCLC who developed stage IV disease at recurrence ( n = 38), de novo s tage IV patients ( n = 71) had worse ECOG performance status ( p = 0.007), greater numbers of extra-thoracic metastatic sites ( p = 0.001), and were less likely to receive 2nd/3rd line systemic therapy ( p = 0.05, p = 0.002) or targeted therapy ( p = 0.001). De novo metastatic patients had shorter overall survival than metastatic patients at recurrence (9.1 versus 24.2 months; adjusted-hazard-ratio=1.94 (95% CI: 1.14–3.28; p = 0.01)). There is a critical need for well-tolerated targeted therapies in the first-line setting for metastatic patients with de novo , high-burden, stage IV KRAS G12C -mutated NSCLCs.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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) | 0.000 | 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".