Evidence map›Paper›PMID 24658074›Full record

ArticleNature medicine2014

Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA.

Alain R Thierry, Florent Mouliere, Safia El Messaoudi, Caroline Mollevi, Evelyne Lopez-Crapez, Fanny Rolet, Brigitte Gillet, Celine Gongora, Pierre Dechelotte, Bruno Robert and 10 more

3 registry-linked trialsAbstract readValidation Study
PubMed Publisher
In one paragraph

Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 328 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
328citing papers in PubMed, 5 pooled it
–field-weighted citation impact
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.

NCT03828799 phase1 / phase2completednot on this mapstarted 2019, after this paper: background citation

Safety, Tolerability and Efficacy of Regorafenib in Combination With FOLFIRINOX in Patients With RAS-mutated Metastatic Colorectal Cancer: a Dose-escalation, Phase I/II Trial

TypeinterventionalSponsorInstitut du Cancer de Montpellier - Val d'AurelleRan2019 to 2024Enrolled13ConditionsMetastatic Colorectal CancerArmsFolfirinox + regorafenib
NCT03956940 naterminatednot on this mapstarted 2019, after this paper: background citation

A Sorafenib-Regorafenib Sequence Treatment Monitoring Study Using Liquid Biopsy

TypeinterventionalSponsorInstitut du Cancer de Montpellier - Val d'AurelleRan2019 to 2021Enrolled18ConditionsHepatocarcinomaArmsIntplex test
NCT04262687 phase2unknown statusnot on this mapstarted 2021, after this paper: background citation

Pembrolizumab in Combination With Xelox Bevacizumab in Patients With Microsatellite Stable Mestatic Colorectal Cancer and a High Immune Infiltrate : a Proof of Concept Study

TypeinterventionalSponsorFederation Francophone de Cancerologie DigestiveRan2021 to 2024Enrolled55ConditionsColorectal Cancer Metastatic, High Immune Infiltrate, Microsatellite StableArmsCapecitabine, Oxaliplatin, Bevacizumab, Pembrolizumab
3 · Its place in the literature

Who cites it

328 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
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  5. Circulating Cell-Free DNA and Colorectal Cancer: A Systematic Review.International journal of molecular sciences · 2018
    Pooled it
  6. Trial
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  12. The temporal evaluation of RAS mutation by liquid biopsy at progression after bevacizumab-based treatment in patients with metastatic colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Novel Liquid Biopsy in Gastrointestinal Cancers.Journal of gastroenterology and hepatology · 2026
    Review
  19. Article
  20. Article

268 more citing papers are in PubMed but not listed here.

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

20 authors.

Alain R Thierry1] U896 INSERM, Institut Recherche en Cancérologie de Montpellier, Montpellier, France. [2] Sysdiag UMR3145 CNRS, CAP DELTA, Montpellier, France.
Florent Mouliere1] U896 INSERM, Institut Recherche en Cancérologie de Montpellier, Montpellier, France. [2] Sysdiag UMR3145 CNRS, CAP DELTA, Montpellier, France.
Safia El Messaoudi1] U896 INSERM, Institut Recherche en Cancérologie de Montpellier, Montpellier, France. [2] Sysdiag UMR3145 CNRS, CAP DELTA, Montpellier, France.
Caroline MolleviUnité de Biostatistique, Institut du Cancer de Montpellier, Montpellier, France.
Evelyne Lopez-CrapezLaboratoire de Biologie Spécialisée, Institut du Cancer de Montpellier, Montpellier, France.
Fanny RoletSysdiag UMR3145 CNRS, CAP DELTA, Montpellier, France.
Brigitte GilletCentre Hospitalier Universitaire de Clermont-Ferrand, Service de Chirurgie Digestive Unité d'Oncologie Digestive, UMR Unité Inserm/Université d'Auvergne U1071, Clermont-Ferrand, France.
Celine GongoraU896 INSERM, Institut Recherche en Cancérologie de Montpellier, Montpellier, France.
Pierre DechelotteCentre Hospitalier Universitaire de Clermont-Ferrand, Anatomie Pathologique, Unité d'Oncologie moléculaire, Clermont-Ferrand, France.
Bruno RobertU896 INSERM, Institut Recherche en Cancérologie de Montpellier, Montpellier, France.
Maguy Del RioU896 INSERM, Institut Recherche en Cancérologie de Montpellier, Montpellier, France.
Pierre-Jean LamyLaboratoire de Biologie Spécialisée, Institut du Cancer de Montpellier, Montpellier, France.
Frederic BibeauService de Pathologie, Unité de Biopathologie Institut du Cancer de Montpellier, Montpellier, France.
Michelle NouailleCentre Hospitalier Universitaire de Limoges, Service de Chirurgie Digestive, Centre d'Investigation Clinique, INSERM 0801, Limoges, France.
Virginie LoriotService de Chirurgie Digestive, Institut du Cancer de Montpellier, Montpellier, France.
Anne-Sophie JarrousseCentre Hospitalier Universitaire de Clermont-Ferrand, Anatomie Pathologique, Unité d'Oncologie moléculaire, Clermont-Ferrand, France.
Franck MolinaSysdiag UMR3145 CNRS, CAP DELTA, Montpellier, France.
Muriel MathonnetCentre Hospitalier Universitaire de Limoges, Service de Chirurgie Digestive, Centre d'Investigation Clinique, INSERM 0801, Limoges, France.
Denis PezetCentre Hospitalier Universitaire de Clermont-Ferrand, Service de Chirurgie Digestive Unité d'Oncologie Digestive, UMR Unité Inserm/Université d'Auvergne U1071, Clermont-Ferrand, France.
Marc YchouService de Chirurgie Digestive, Institut du Cancer de Montpellier, Montpellier, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Assessment of KRAS status is mandatory in patients with metastatic colorectal cancer (mCRC) before applying targeted therapy. We describe here a blinded prospective study to compare KRAS and BRAF mutation status data obtained from the analysis of tumor tissue by routine gold-standard methods and of plasma DNA using a quantitative PCR-based method specifically designed to analyze circulating cell-free DNA (cfDNA). The mutation status was determined by both methods from 106 patient samples. cfDNA analysis showed 100% specificity and sensitivity for the BRAF V600E mutation. For the seven tested KRAS point mutations, the method exhibited 98% specificity and 92% sensitivity with a concordance value of 96%. Mutation load, expressed as the proportion of mutant alleles in cfDNA, was highly variable (0.5-64.1%, median 10.5%) among mutated samples. CfDNA was detected in 100% of patients with mCRC. This study shows that liquid biopsy through cfDNA analysis could advantageously replace tumor-section analysis and expand the scope of personalized medicine for patients with cancer.

Indexed as

Point MutationAdultAgedAged, 80 and overCase-Control StudiesCohort StudiesColorectal NeoplasmsDNA, NeoplasmFemaleHumansMaleMiddle AgedNeoplasm MetastasisProspective StudiesProto-Oncogene ProteinsProto-Oncogene Proteins B-rafBRAF protein, humanDNA, NeoplasmKRAS protein, humanProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)ras Proteins

Identifiers

PMID24658074

What OpenQuestion holds

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Registered trials

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.