Analysis of outcomes in resected early-stage NSCLC with rare targetable driver mutations
Bibliographic record
Abstract
Background: Given advancements in adjuvant treatments for non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)-targeted therapies, it is important to consider postoperative targeted therapies for other early-stage oncogene-addicted NSCLC. Exploring baseline outcomes for early-stage NSCLC with these rare mutations is crucial. Objectives: This study aims to assess relapse-free survival (RFS) and overall survival (OS) in patients with resected early-stage NSCLC with rare targetable driver mutations. Methods: This retrospective single-center study identified stage I–III NSCLC patients with rare targetable mutations who underwent curative surgery. Tissue-based molecular profiling identified mutations in KRASG12C, EGFR Exon20, Erb-B2 receptor tyrosine kinase 2 ( ERBB2), ALK, ROS1, B-Raf proto-oncogene ( BRAF) V600E, mesenchymal–epithelial transition factor ( MET) exon14 skipping, and rearranged during transfection ( RET). Baseline patient and tumor characteristics, mutation subtype, and TP53 co-mutation were correlated with RFS and OS using Cox regression. The KRASG12C cohort was used as the reference for survival comparisons. Results: Among 225 patients, mutations included the following: KRASG12C ( n = 101, 45%), MET exon 14 skipping ( n = 26, 12%), EGFR Exon 20 ( n = 25, 11%), ERBB2 ( n = 25, 11%), ALK fusion ( n = 16, 7%), ROS1 fusion ( n = 14, 6%), BRAF V600E mutation ( n = 13, 6%), and RET fusion ( n = 5, 2%). Five-year survival probabilities were 76% for stage I, 60% for stage II, and 58% for stage III. RFS was shorter across most mutation subgroups compared to KRASG12C, with ROS1 mutations showing significantly poorer RFS (HR 2.70, p = 0.019). By contrast, all mutation subgroups were associated with better OS than KRASG12C. The incidence of brain metastasis was highest in ERBB2 (22% at 5 years). TP53 co-mutation was associated with significantly worse OS (HR 2.35, p = 0.008). Conclusion: While RFS was poorer for most mutations compared to KRASG12C, OS generally was better, suggesting a potential role for postoperative targeted therapies. These findings warrant further investigation through prospective studies and clinical trials to optimize adjuvant treatment strategies for patients with early-stage NSCLC harboring rare driver mutations.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| 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 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".