Evidence map›Paper›PMID 34103179›Full record

Trial reportEuropean urology2021

Elucidating Prostate Cancer Behaviour During Treatment via Low-pass Whole-genome Sequencing of Circulating Tumour DNA.

Semini Sumanasuriya, George Seed, Harry Parr, Rossitza Christova, Lorna Pope, Claudia Bertan, Diletta Bianchini, Pasquale Rescigno, Ines Figueiredo, Jane Goodall and 21 more

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European urology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

  1. Pooled it
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  4. RNASEH2B loss and PARP inhibition in advanced prostate cancer.The Journal of clinical investigation · 2024
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  20. Comparison of discovery rates and prognostic utility of [European journal of nuclear medicine and molecular imaging · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors at 7 institutions in 4 countries.

Semini SumanasuriyaThe Institute of Cancer Research, University of London, London, UK; The Royal Marsden Hospital, London, UK.
George SeedThe Institute of Cancer Research, University of London, London, UK.
Harry ParrThe Institute of Cancer Research, University of London, London, UK.
Rossitza ChristovaThe Institute of Cancer Research, University of London, London, UK.
Lorna PopeThe Institute of Cancer Research, University of London, London, UK.
Claudia BertanThe Institute of Cancer Research, University of London, London, UK.
Diletta BianchiniThe Institute of Cancer Research, University of London, London, UK; The Royal Marsden Hospital, London, UK.
Pasquale RescignoThe Institute of Cancer Research, University of London, London, UK; The Royal Marsden Hospital, London, UK.
Ines FigueiredoThe Institute of Cancer Research, University of London, London, UK.
Jane GoodallThe Institute of Cancer Research, University of London, London, UK.
Gemma FowlerThe Institute of Cancer Research, University of London, London, UK.
Penelope FlohrThe Institute of Cancer Research, University of London, London, UK.
Niven MehraThe Institute of Cancer Research, University of London, London, UK; The Royal Marsden Hospital, London, UK.
Antje NeebThe Institute of Cancer Research, University of London, London, UK.
Jan RekowskiThe Institute of Cancer Research, University of London, London, UK.
Mario EisenbergerJohns Hopkins University, Baltimore, MD, USA.
Oliver SartorTulane Medical School, New Orleans, LA, USA.
Stéphane OudardHôpital Européen Georges Pompidou and Université de Paris, Paris, France.
Christine Geffriaud-RicouardSanofi-Genzyme, Paris, France.
Ayse OzatilganSanofi-Genzyme, Paris, France.
Mustapha ChadjaaSanofi-Genzyme, Paris, France.
Sandrine MacéSanofi-Genzyme, Paris, France.
Chris LordThe CRUK Gene Function Laboratory and Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK.
Joe BaxterThe CRUK Gene Function Laboratory and Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK.
Stephen PettittThe CRUK Gene Function Laboratory and Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK.
Maryou LambrosThe Institute of Cancer Research, University of London, London, UK; The Royal Marsden Hospital, London, UK.
Adam SharpThe Institute of Cancer Research, University of London, London, UK; The Royal Marsden Hospital, London, UK.
Joaquin MateoVall d'Hebron Institute of Oncology, Barcelona, Spain.
Suzanne CarreiraThe Institute of Cancer Research, University of London, London, UK; The Royal Marsden Hospital, London, UK.
Wei YuanThe Institute of Cancer Research, University of London, London, UK; The Royal Marsden Hospital, London, UK.
Johann S de BonoThe Institute of Cancer Research, University of London, London, UK; The Royal Marsden Hospital, London, UK. Electronic address: johann.de-bono@icr.ac.uk.
University of London · GBSanofi (France) · FRInstitute of Cancer Research · GBJohns Hopkins University · USTulane Medical Center · USUniversité Paris Cité · FRVall d'Hebron Institute of Oncology · ES

Funding

Cancer Research UK 24439Department of Health
6 · The paper itself

Abstract

backgroundBetter blood tests to elucidate the behaviour of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed to drive therapeutic decisions. Plasma cell-free DNA (cfDNA) comprises normal and circulating tumour DNA (ctDNA). Low-pass whole-genome sequencing (lpWGS) of ctDNA can provide information on mCRPC behaviour.

objectiveTo validate and clinically qualify plasma lpWGS for mCRPC. DESIGN, SETTING, AND

participantsPlasma lpWGS data were obtained for mCRPC patients consenting to optional substudies of two prospective phase 3 trials (FIRSTANA and PROSELICA). In FIRSTANA, chemotherapy-naïve patients were randomised to treatment with docetaxel (75 mg/m RESULTS AND LIMITATIONS: Plasma tumour fraction was prognostic for overall survival in univariable and stratified multivariable analyses (hazard ratio 1.75, 95% confidence interval 1.08-2.85; p = 0.024) and offered added value compared to existing biomarkers (C index 0.722 vs 0.709; p = 0.021). Longitudinal changes were associated with drug response. PROSELICA samples were enriched for LSTs (p = 0.029) indicating genomic instability, and this enrichment was associated with prior abiraterone and enzalutamide treatment but not taxane or radiation therapy. Higher LSTs were correlated with losses of RB1/RNASEH2B, independent of BRCA2 loss.

conclusionsPlasma lpWGS of ctDNA describes CRPC behaviour, providing prognostic and response data of clinical relevance. The added prognostic value of the ctDNA fraction over established biomarkers should be studied further. PATIENT SUMMARY: We studied tumour DNA in blood samples from patients with prostate cancer. We found that levels of tumour DNA in blood were indicative of disease prognosis, and that changes after treatment could be detected. We also observed a "genetic scar" in the results that was associated with certain previous treatments. This test allows an assessment of tumour activity that can complement existing tests, offer insights into drug response, and detect clinically relevant genetic changes.

Indexed as

Circulating Tumor DNAPharmaceutical PreparationsProstatic Neoplasms, Castration-ResistantDNA, NeoplasmDocetaxelHumansMaleProspective StudiesCirculating Tumor DNADNA, NeoplasmDocetaxelPharmaceutical PreparationsCabazitaxelCell-free DNAcfDNActDNALow-pass whole-genome sequencinglpWGSmCRPCMetastatic castration-resistant prostate cancerTaxanesTumour fraction

Identifiers

PMID34103179
PMCPMC8329366
OpenAlexW3170276561

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.