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Record W4416003940 · doi:10.1016/j.cell.2025.10.020

Longitudinal ultrasensitive ctDNA monitoring for high-resolution lung cancer risk prediction

2025· article· en· W4416003940 on OpenAlexfundno aff
James R. Black, Takahiro Karasaki, Charles W. Abbott, Bailiang Li, Selvaraju Veeriah, Maise Al Bakir, Wing Kin Liu, Ariana Huebner, Carlos Martínez‐Ruiz, Piotr Pawlik, David A. Moore, Daniele Marinelli, Oliver Shutkever, Cian Murphy, Lydia Liu, Charlotte Grieco, Karen Grimes, Fábio C. P. Navarro, Rachel Marty Pyke, Gábor Bartha, Kathleen C. Keough, Steven Dea, Neeraja Ravi, John Lyle, Jason Harris, Katherine D. Brown, Fiona Blackhall, Dean A. Fennell, Nicholas McGranahan, Jacqui Shaw, Christopher Abbosh, Allan Hackshaw, Mariam Jamal‐Hanjani, Alexander M. Frankell, Sean M. Boyle, Charles Swanton

Bibliographic record

VenueCell · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsnot available
FundersStoneygate TrustEuropean Research CouncilMedical Research CouncilImperial Experimental Cancer Medicine CentreUniversity College London Hospitals NHS Foundation TrustBreast Cancer Research FoundationBroad InstituteEuropean CommissionRosetrees TrustUniversity College LondonCanadian Institutes of Health ResearchRoyal SocietyUCLH Biomedical Research CentreJapan Society for the Promotion of ScienceHorizon 2020 Framework ProgrammeCancer Research UKNovo Nordisk Foundation Center for Basic Metabolic ResearchNational Institute for Health and Care ResearchMark Foundation For Cancer ResearchWellcome TrustFrancis Crick Institute
KeywordsCirculating tumor DNALung cancerRisk stratificationAdjuvantStage (stratigraphy)Adjuvant therapyDisease

Abstract

fetched live from OpenAlex

Biomarkers accurately informing prognostic assessment and therapeutic strategy are critical for improving patient outcome in oncology. Here, we apply a whole-genome, tumor-informed circulating tumor DNA (ctDNA) detection approach to address this challenge, leveraging 1,800 variants across 2,994 plasma samples from 431 patients with non-small cell lung cancer (NSCLC) from the TRACERx study. We show that ultrasensitive ctDNA detection below 80 parts per million both pre- and postoperatively is highly prognostic, and combinatorial analysis of the pre- and postoperative ctDNA status identifies an intermediate risk group, improving disease stratification. ctDNA kinetics demonstrate clinical utility during adjuvant therapy, where patients that "clear" ctDNA during adjuvant therapy experience improved outcomes. Moreover, characterization of patterns in postoperative ctDNA kinetics reveals insights into the timing, risk, and anatomical pattern of relapses. By incorporating longitudinal ultrasensitive ctDNA detection, we propose a refined schema for guiding the stratification and treatment recommendations in early stage NSCLC.

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)0.002
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 score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
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 head0.006
GPT teacher head0.252
Teacher spread0.245 · 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

Citations13
Published2025
Admission routes1
Has abstractyes

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