Evidence map›Paper›PMID 24465542›Full record

Trial reportPloS one2014

Development of a highly sensitive and specific method for detection of circulating tumor cells harboring somatic mutations in non-small-cell lung cancer patients.

Frank Breitenbuecher, Sandra Hoffarth, Karl Worm, Diana Cortes-Incio, Thomas C Gauler, Jens Köhler, Thomas Herold, Kurt Werner Schmid, Lutz Freitag, Stefan Kasper and 1 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

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  8. Clinical and prognostic significance of detectingTranslational lung cancer research · 2023
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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

11 authors at 3 institutions in 1 country.

Frank BreitenbuecherDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Sandra HoffarthDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Karl WormInstitute of Pathology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Diana Cortes-IncioDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Thomas C GaulerDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany ; Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany.
Jens KöhlerDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Thomas HeroldInstitute of Pathology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany ; German Cancer Research Center, Heidelberg, Germany ; German Cancer Consortium (DKTK), Heidelberg, Germany.
Kurt Werner SchmidInstitute of Pathology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Lutz FreitagDivision of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany.
Stefan KasperDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Martin SchulerDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany ; Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany ; German Cancer Consortium (DKTK), Heidelberg, Germany.
Deutschen Konsortium für Translationale Krebsforschung · DERuhrlandklinik · DEUniversity of Duisburg-Essen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOncogenic mutations are powerful predictive biomarkers for molecularly targeted cancer therapies. For mutation detection patients have to undergo invasive tumor biopsies. Alternatively, archival samples are used which may no longer reflect the actual tumor status. Circulating tumor cells (CTC) could serve as an alternative platform to detect somatic mutations in cancer patients. We sought to develop a sensitive and specific assay to detect mutations in the EGFR gene in CTC from lung cancer patients.

methodsWe developed a novel assay based on real-time polymerase chain reaction (PCR) and melting curve analysis to detect activating EGFR mutations in blood cell fractions enriched in CTC. Non-small-cell lung cancer (NSCLC) was chosen as disease model with reportedly very low CTC counts. The assay was prospectively validated in samples from patients with EGFR-mutant and EGFR-wild type NSCLC treated within a randomized clinical trial. Sequential analyses were conducted to monitor CTC signals during therapy and correlate mutation detection in CTC with treatment outcome.

resultsAssay sensitivity was optimized to enable detection of a single EGFR-mutant CTC/mL peripheral blood. CTC were detected in pretreatment blood samples from all 8 EGFR-mutant lung cancer patients studied. Loss of EGFR-mutant CTC signals correlated with treatment response, and its reoccurrence preceded relapse.

conclusionsDespite low abundance of CTC in NSCLC oncogenic mutations can be reproducibly detected by applying an unbiased CTC enrichment strategy and highly sensitive PCR and melting curve analysis. This strategy may enable non-invasive, specific biomarker diagnostics and monitoring in patients undergoing targeted cancer therapies.

Indexed as

AdultAgedAntineoplastic AgentsBiomarkers, TumorCarcinoma, Non-Small-Cell LungErbB ReceptorsFemaleHumansLung NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalNeoplastic Cells, CirculatingNucleic Acid DenaturationReal-Time Polymerase Chain ReactionSensitivity and SpecificityAntineoplastic AgentsBiomarkers, TumorEGFR protein, humanErbB Receptors

Identifiers

PMID24465542
PMCPMC3897440
OpenAlexW1983553203

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.