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Record W4403486661 · doi:10.1158/1078-0432.ccr-24-2105

Genomic Landscape of ctDNA and Real-World Outcomes in Advanced Endometrial Cancer

2024· article· en· W4403486661 on OpenAlexaff
Pamela Soberanis Pina, Keelia Clemens, Adrian Bubie, Brooke Grant, G. Clark Haynes, Nicole Zhang, Leylah Drusbosky, Stéphanie Lheureux

Bibliographic record

VenueClinical Cancer Research · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsPrincess Margaret Cancer CentreUniversity Health Network
Fundersnot available
KeywordsKRASPTENMedicineOncologyInternal medicineMutationCancerARID1AEndometrial cancerCohortGermline mutationRetrospective cohort studyCancer researchGeneColorectal cancerGeneticsBiology

Abstract

fetched live from OpenAlex

PURPOSE: ctDNA is a novel technique extensively studied in solid tumors, although not currently well defined in endometrial cancer. EXPERIMENTAL DESIGN: A de-identified retrospective analysis of 1,988 patients with advanced/recurrent endometrial cancer was performed. In addition, an analysis of a real-world evidence cohort was completed (n = 1,266). Patients underwent ctDNA testing using Guardant360 during routine clinical care. The objective was to describe and assess molecular landscape using ctDNA. RESULTS: Among 1,988 ctDNA samples, at least one somatic alteration was detected in 91.6% (n = 1,821). Most frequently altered genes were TP53 (64%), PIK3CA (29%), PTEN (25%), ARID1A (20%), and KRAS (14%). Overall, 18.5% had amplifications, with the majority identified in CCNE1 (40.9%), PIK3CA (22%), and EGFR (19.3%). From the real-world evidence cohort, those with TP53 mutations had a worse overall survival (OS) versus those without TP53 mutations (P = 0.02) and those with TP53 comutations had an inferior OS in comparison with TP53-mutated only (P = 0.016). Amongst these, patients with a PIK3CA comutation (P = 0.012) and CCNE1 amplification (P = 0.01) had an inferior OS compared with those with only TP53 mutations. Fifty-seven patients with newly diagnosed endometrial cancer had at least two serial ctDNA samples showing evolution in detected variants compared with baseline samples, with TP53 being the most frequent change. CONCLUSIONS: This study is one of the largest cohorts of ctDNA currently reported in endometrial cancer. The presence of TP53 mutation and other comutations detected by ctDNA have a negative effect on outcomes. This report suggests that ctDNA analysis is feasible and could become a useful biomarker for endometrial cancer.

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)0.001
metaresearch head score (Gemma)0.001
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 score0.195
Threshold uncertainty score0.629

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
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 head0.106
GPT teacher head0.501
Teacher spread0.396 · 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

Citations13
Published2024
Admission routes1
Has abstractyes

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