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Clinicopathologic features and prognostic implications of epidermal growth factor receptor (EGFR) gene mutations detected by denaturing high-performance liquid chromatography (dHPLC) in non-small cell lung cancer (NSCLC)

2007· article· en· W2525323356 on OpenAlexaff
V. Cohen, Jason Agulnik, C. Ang, Goulnar Kasymjanova, George Chong, N. A. Tejada, Carmela Pepe, Gerald Batist, David Small, W. H. Miller

Bibliographic record

VenueJournal of Clinical Oncology · 2007
Typearticle
Languageen
FieldMedicine
TopicLung Cancer Treatments and Mutations
Canadian institutionsJewish General Hospital
Fundersnot available
KeywordsGefitinibDenaturing high performance liquid chromatographyMedicineExonLung cancerEpidermal growth factor receptorErlotinibPoint mutationROS1MutationInternal medicineOncologyGene mutationCancer researchAdenocarcinomaCancerGeneBiologyGenetics

Abstract

fetched live from OpenAlex

7594 Background: Somatic mutations of the EGFR gene predict sensitivity to erlotinib and gefitinib and confer a favorable prognosis in patients (pts) with NSCLC. We have recently shown that dHPLC is an efficient and more sensitive method for mutation screening compared with DNA sequencing. The goal of this study was to describe the relationship between EGFR status (mutation status and type) and clinicopathologic factors. Methods: Tumor samples were analysed for EGFR exon 19 deletions and exon 21 L858R point mutations. DNA was extracted from paraffin-embedded tumor specimens and genotyped using dHPLC. The results were correlated with gender, smoking status, pathologic subtype, disease stage, and overall survival. Results: 215 NSCLC pts were genotyped. Mutations were present in 25% of cases (54 of 215). Among pts with mutations, 70% (38 of 54) had an exon 19 mutation whereas 30% had EGFR L858R. EGFR mutations were more common in women (31% vs 14%; p=0.008), in nonsmokers than ever-smokers (54% vs 17%; p<0.001), in adenocarcinomas/BAC than with other NSCLC histologies (31% vs 11%; p=0.004) and more frequently detected in advanced-stage than in early-stage disease (36% vs 15%; p=0.001). Median survival times of pts with stage IIIB-IV disease with and without EGFR mutations were 20 and 14 months, respectively. Those with exon 19 deletion mutations had a longer median survival than pts with L858R point mutations. Data describing the impact of tyrosine kinase inhibitor therapy on survival outcomes are pending and will be presented. Conclusion: dHPLC is a reliable tool for EGFR mutation detection. Mutations were preferentially observed in women, nonsmokers, adenocarcinomas/BAC and in patients with advanced disease. Pts with mutations experienced improved survival and those harboring deletions fared better than those with point mutations. These observations warrant confirmation in large prospective trials and exploration of the biological mechanisms of the differences between mutation types. No significant financial relationships to disclose.

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 imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.029
GPT teacher head0.402
Teacher spread0.374 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2007
Admission routes1
Has abstractyes

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