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Comparing health utility scores, treatments, and outcomes in lung cancer patients with rare EGFR mutations with those with exon 19 deletion (del) and L858R mutations.

2019· article· en· W2980696228 on OpenAlexaff
Lorin Dodbiba, Katrina Hueniken, Shirley Jiang, Sze Wah Samuel Chan, Elliot Smith, Lawson Eng, Devalben Patel, Maryam Razooqi, M. Catherine Brown, Frances A. Shepherd, Natasha B. Leighl, Penelope Ann Bradbury, Wei Xu, Adrian G. Sacher, Geoffrey Liu

Bibliographic record

VenueJournal of Clinical Oncology · 2019
Typearticle
Languageen
FieldMedicine
TopicLung Cancer Treatments and Mutations
Canadian institutionsUniversity Health NetworkPrincess Margaret Cancer CentreUniversity of TorontoMcMaster University
Fundersnot available
KeywordsMedicineInternal medicineHazard ratioExonLung cancerOncologyMutationProportional hazards modelRetrospective cohort studyConfidence intervalGeneticsGeneBiology

Abstract

fetched live from OpenAlex

102 Background: Precision oncology divides patients into smaller cohorts each with unique characteristics, treatment and outcomes. Cost-effectiveness assessments that rely on quality-adjusted life years will require mutation-specific health utility scores (HUS). We assessed the impact of having exon 19 del, L858R and rare EGFR mutations on outcomes and HUS. Methods: From a retrospective database of 719 patients with EGFR mutations, specific baseline EGFR mutations, clinicodemographic and treatment characteristics, and outcomes (overall survival, OS; progression-free survival, PFS) were analyzed using Cox models (adjusted hazard ratios, HR). In a subset of 289 patients with metastatic disease, serial HUS data collected through EQ-5D-5L at clinic visits were compared by mutation using t-tests. Results: Of 380 (53%) patients with exon 19 del, 288 (40%) with L858R, and 51 (7%) with rare mutations (mostly G719A/C, Exon 18 or 20 insertion, L861Q, compound mutations): 68% were female; median age was 74 years; 51% were Asian; and 74% were never smokers. In 334 Stage I-III pts, recurrence-free survival was not associated with specific mutations. In contrast, among 365 stage IV pts on TKIs, when compared to a reference of patients with exon 19 del, outcomes were worse in patients with L858R mutations (PFS: 1.35, 95% CI 1.1-1.7; OS: HR 1.39, 95% CI 1.0-1.9) and for rare mutations (PFS: 1.16 95% CI 0.7-1.9; OS: 1.45 95% CI 0.7-2.9). From an analysis of 1064 clinic encounters, different TKIs were used in similar proportions by mutation. In stable disease, mean HUS [SEM] were 0.80 [0.008] (exon 19), 0.81 [0.009] (L858R), and 0.82 [0.02] (rare mutation). Progressive disease led to significant drops in mean HUS for exon 19 (0.76 [0.01]; p = 0.01 compared to stable disease) and L858R, mean HUS = 0.74 [0.02] p < 0.001, but less so for rare mutations, mean HUS = 0.79 [0.05] p = 0.65. Conclusions: Patients in this EGFR mutated cohort had similar exposures of different TKI therapy regardless of specific EGFR mutation. L858R and rare mutations had inferior survival outcomes but similar HUS as patients with exon 19 del mutations.

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)0.001
metaresearch head score (Gemma)0.004
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 score0.003
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
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 head0.067
GPT teacher head0.474
Teacher spread0.407 · 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".

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Citations1
Published2019
Admission routes1
Has abstractyes

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