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Record W2941797036 · doi:10.1016/j.eururo.2019.04.006

Clinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-resistant Prostate Cancer

2019· article· en· W2941797036 on OpenAlexaff
Adam Sharp, Jon Welti, Maryou B. Lambros, David Dolling, Daniel Nava Rodrigues, Lorna Pope, Caterina Aversa, Ines Figueiredo, Jennifer A. Fraser, Zai Ahmad, Changxue Lu, Pasquale Rescigno, Michael Kolinsky, Cláudia Bertan, George Seed, Ruth Riisnaes, Susana Miranda, Mateus Crespo, Rita Pereira, Ana Ferreira, Gemma Fowler, Berni Ebbs, Penny Flohr, Antje Neeb, Diletta Bianchini, Antonella Petremolo, Semini Sumanasuriya, Alec Paschalis, Joaquı́n Mateo, Nina Tunariu, Wei Yuan, Suzanne Carreira, Stephen R. Plymate, Jun Luo, Johann S. de Bono

Bibliographic record

VenueEuropean Urology · 2019
Typearticle
Languageen
FieldMedicine
TopicProstate Cancer Treatment and Research
Canadian institutionsUniversity of Alberta
FundersDOD Prostate Cancer Research ProgramNational Cancer InstituteMedical Research CouncilImperial Experimental Cancer Medicine CentreStand Up To CancerCancer Research UKAcademy of Medical SciencesU.S. Department of Veterans AffairsPatrick C. Walsh Prostate Cancer Research FundInstitute for Prostate Cancer ResearchProstate Cancer FoundationMovember FoundationNational Institutes of HealthProstate Cancer UKNational Institute for Health and Care ResearchU.S. Department of Defense
KeywordsMedicineProstate cancerInterquartile rangeCirculating tumor cellAndrogen receptorBiopsyInternal medicineHazard ratioOncologyLiquid biopsyPathologyCancerConfidence intervalMetastasis

Abstract

fetched live from OpenAlex

BACKGROUND: Detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumour cells (CTCs) is associated with worse outcome in metastatic castration-resistant prostate cancer (mCRPC). However, studies rarely report comparisons with CTC counts and biopsy AR-V7 protein expression. OBJECTIVE: To determine the reproducibility of AdnaTest CTC AR-V7 testing, and associations with clinical characteristics, CellSearch CTC counts, tumour biopsy AR-V7 protein expression and overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: CTC AR-V7 status was determined for 227 peripheral blood samples, from 181 mCRPC patients with CTC counts (202 samples; 136 patients) and matched mCRPC biopsies (65 samples; 58 patients). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: CTC AR-V7 status was associated with clinical characteristics, CTC counts, and tissue biopsy AR-V7 protein expression. The association of CTC AR-V7 status and other baseline variables with OS was determined. RESULTS AND LIMITATIONS: Of the samples, 35% were CTC+/AR-V7+. CTC+/AR-V7+ samples had higher CellSearch CTC counts (median CTC; interquartile range [IQR]: 60, 19-184 vs 9, 2-64; Mann-Whitney test p<0.001) and biopsy AR-V7 protein expression (median H-score, IQR: 100, 63-148 vs 15, 0-113; Mann-Whitney test p=0.004) than CTC+/AR-V7- samples. However, both CTC- (63%) and CTC+/AR-V7- (62%) patients had detectable AR-V7 protein in contemporaneous biopsies. After accounting for baseline characteristics, there was shorter OS in CTC+/AR-V7+ patients than in CTC- patients (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.23-3.71; p=0.02); surprisingly, there was no evidence that CTC+/AR-V7+ patients had worse OS than CTC+/AR-V7- patients (HR 1.26; 95% CI 0.73-2.17; p=0.4). A limitation of this study was the heterogeneity of treatment received. CONCLUSIONS: Studies reporting the prognostic relevance of CTC AR-V7 status must account for CTC counts. Discordant CTC AR-V7 results and AR-V7 protein expression in matched, same-patient biopsies are reported. PATIENT SUMMARY: Liquid biopsies that determine circulating tumour cell androgen receptor splice variant-7 status have the potential to impact treatment decisions in metastatic castration-resistant prostate cancer patients. Robust clinical qualification of these assays is required before their routine use.

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)0.000
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 score0.076
Threshold uncertainty score0.896

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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)0.0010.000

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 head0.049
GPT teacher head0.349
Teacher spread0.300 · 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

Citations83
Published2019
Admission routes1
Has abstractyes

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