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Record W3181684306 · doi:10.1016/j.jtocrr.2021.100212

A Pan-Canadian Validation Study for the Detection of EGFR T790M Mutation Using Circulating Tumor DNA From Peripheral Blood

2021· article· en· W3181684306 on OpenAlexafffundabout
Shamini Selvarajah, Sophie Plante, Marsha Speevak, Andrea K. Vaags, Darren Hamelinck, Martin Butcher, M. Elizabeth McCready, Daria Grafodatskaya, Normand Blais, Danh Tran‐Thanh, Xiaoduan Weng, Rami Nassabein, Wenda Greer, Ryan N. Walton, Bernard Lo, Doug Demetrick, Stephanie Santos, Bekim Sadiković, Xiao Zhang, Tong Zhang, Tara Spence, Tracy Stockley, Harriet Feilotter, Philippe Joubert

Bibliographic record

VenueJTO Clinical and Research Reports · 2021
Typearticle
Languageen
FieldMedicine
TopicLung Cancer Treatments and Mutations
Canadian institutionsQueen's UniversityKingston Health Sciences CentreLondon Health Sciences CentreUniversity of CalgaryUniversity Health NetworkOttawa HospitalUniversité LavalCentre Hospitalier de l’Université de MontréalHamilton Regional Laboratory Medicine ProgramQueen Elizabeth II Health Sciences CentreInstitut universitaire de cardiologie et de pneumologie de QuébecTrillium Health CentreAstraZeneca (Canada)McMaster UniversityDalhousie UniversityHamilton Health SciencesWestern UniversityUniversity of Toronto
FundersRocheAstraZeneca CanadaAstraZenecaPfizer
KeywordsT790MConcordanceDigital polymerase chain reactionMutationMedicineResistance mutationPolymerase chain reactionOncologyInternal medicineBiologyGeneticsGeneKRASReverse transcriptase

Abstract

fetched live from OpenAlex

INTRODUCTION: T790M resistance mutation in patients with advanced NSCLC with resistance to EGFR inhibitors. To facilitate standardization and clinical adoption of ctDNA testing across Canada, we developed a 2-phase multicenter study to standardize T790M mutation detection using plasma ctDNA testing. METHODS: variants and concordance with a clinically validated test at the reference laboratory. RESULTS: All laboratories in phase 1 detected the variants at 0.5 % and 5.0 % allele frequencies, with no false positives. In phase 2, the concordance with the reference laboratory for detection of both the primary and resistance mutation was high, with next-generation sequencing and droplet digital polymerase chain reaction exhibiting the best overall concordance. Data also suggested that the ability to detect mutations at clinically relevant limits of detection is generally not platform-specific, but rather impacted by laboratory-specific practices. CONCLUSIONS: Discrepancies among sending laboratories using the same assay suggest that laboratory-specific practices may impact performance. In addition, a negative or inconclusive ctDNA test should be followed by tumor testing when possible.

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 distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation 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 score0.120
Threshold uncertainty score0.977

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.171
GPT teacher head0.501
Teacher spread0.330 · 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 teacher head, 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

Citations3
Published2021
Admission routes3
Has abstractyes

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