A window of opportunity study of potential tumor and soluble biomarkers of response to preoperative erlotinib in early stage non-small cell lung cancer
Bibliographic record
Abstract
// Adrian G. Sacher 1, 5 , Lisa W. Le 2 , Humberto Lara-Guerra 3 , Thomas K. Waddell 3 , Shingo Sakashita 4 , Zhuo Chen 1 , Lucia Kim 4 , Tong Zhang 4 , Suzanne Kamel-Reid 4 , Alexandra Salvarrey 1, 3 , Gail Darling 3 , Kazuhiro Yasufuku 3 , Shaf Keshavjee 3 , Marc de Perrot 3 , Frances A. Shepherd 1 , Geoffrey Liu 1 , Ming Sound Tsao 3 , Natasha B. Leighl 1 1 Division of Medical Oncology/Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada 2 Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada 3 Division of Thoracic Surgery, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada 4 Department of Pathology and Laboratory Medicine, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada 5 Division of Hematology and Oncology, Columbia University/New York-Presbyterian Hospital, New York, New York, USA Correspondence to: Natasha B. Leighl, e-mail: Natasha.Leighl@uhn.ca Keywords: erlotinib, NSCLC, preoperative window study Received: May 04, 2015 Accepted: March 10, 2016 Published: March 25, 2016 ABSTRACT Background: Erlotinib is highly active in EGFR mutant NSCLC, but may benefit some with wild-type tumors. We examined pre-operative erlotinib in early stage NSCLC to assess response and correlation with potential biomarkers. Results: Twenty-five patients were enrolled; 22 received erlotinib treatment and were evaluable (median follow-up 4.4 years). Histology was predominantly adenocarcinoma although 31% had squamous carcinoma. PET response was observed in 2 patients (9%), both with squamous carcinoma. Most (20/22) had stable disease (RECIST), with frequent minor radiographic regression and histologic findings of fibrosis/necrosis including in squamous histology. Only two had EGFR mutations identified, one with minor radiographic response and the other stable disease after 4 weeks of EGFR TKI. High pre-treatment serum levels of TGF-α correlated with primary resistance to erlotinib ( p = 0.02), whereas high post-treatment soluble EGFR levels correlated with response ( p = 0.03). EGFR, PTEN, cMET and AXL expression did not correlate with tumor response. Methods: Clinical stage IA–IIB NSCLC patients received erlotinib 150 mg daily for 4 weeks followed by resection. Tumor response was assessed using CT, PET and pathological response. Tumor genotype was established using Sequenom Mass ARRAY; EGFR, PTEN, cMET and AXL expression was assessed by immunohistochemistry, circulating markers of EGFR activation (TGF-α, amphiregulin, epiregulin, EGFR ECD) by ELISA and EGFR, MET copy number by FISH. Conclusions: Erlotinib appears to demonstrate activity in EGFR wild-type tumors including squamous carcinoma. Further research is needed to characterize those wild-type patients that may benefit from EGFR TKI and predictive biomarkers including TGF-α, EGFR copy and others.
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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 | 0.000 | 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) | 0.000 | 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".