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Record W4392232003 · doi:10.1038/s41467-024-45475-w

Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

2024· article· en· W4392232003 on OpenAlexafffund
Nicolette M. Fonseca, Corinne Maurice‐Dror, Cameron Herberts, Wilson Tu, William R. S. Fan, Andrew J. Murtha, Catarina Kollmannsberger, Edmond M. Kwan, Karan Parekh, Elena Schönlau, Cecily Q. Bernales, Gráinne Donnellan, Sarah W.S. Ng, Takayuki Sumiyoshi, Joanna Vergidis, Krista Noonan, Daygen L. Finch, Muhammad Zulfiqar, Stacy Miller, Sunil Parimi, Jean‐Michel Lavoie, Edward Hardy, Maryam Soleimani, Lucia Nappi, Bernhard J. Eigl, Christian Kollmannsberger, Sinja Taavitsainen, Matti Nykter, Sofie H. Tolmeijer, Emmy Boerrigter, Niven Mehra, Nielka P. van Erp, Bram De Laere, Johan Lindberg, Henrik Grönberg, Daniel Khalaf, Matti Annala, Kim N., Alexander W. Wyatt

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsCanada's Michael Smith Genome Sciences CentreBC Cancer AgencyVernon Jubilee HospitalUniversity of British Columbia
FundersCanadian Institutes of Health ResearchStand Up To CancerProstate Cancer CanadaKom op tegen KankerBC Cancer FoundationProstate Cancer FoundationJane ja Aatos Erkon SäätiöMovember Foundation
KeywordsMedicineProstate cancerInternal medicineOncologyLiquid biopsyGenotypingBiomarkerCirculating tumor DNAContext (archaeology)Risk stratificationClinical trialBiobankCancerBioinformaticsGenotypeBiologyGene

Abstract

fetched live from OpenAlex

No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org ). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

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)0.003
metaresearch head score (Gemma)0.010
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 score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.010
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.012
GPT teacher head0.297
Teacher spread0.285 · 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

Citations120
Published2024
Admission routes2
Has abstractyes

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