Evidence map›Paper›PMID 25137181›Full record

Trial reportPloS one2014

Assessment of EGFR mutations in circulating tumor cell preparations from NSCLC patients by next generation sequencing: toward a real-time liquid biopsy for treatment.

Antonio Marchetti, Maela Del Grammastro, Lara Felicioni, Sara Malatesta, Giampaolo Filice, Irene Centi, Tommaso De Pas, Armando Santoro, Antonio Chella, Alba Ariela Brandes and 4 more

Open access · goldAbstract readClinical Trial, Phase IIMulticenter Study
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 92 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 2 pooled it
8.1field-weighted citation impact, top 2% 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

92 citing papers in PubMed, 2 syntheses or guidelines pooled it, 148 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Detection of T790M, the Acquired Resistance EGFR Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016
    Trial
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Circulating tumor cellsTranslational breast cancer research : a journal focusing on translational research in breast cancer · 2024
    Review
  10. Review
  11. Article
  12. Review
  13. CirculatingInternational journal of molecular sciences · 2022
    Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review

32 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

14 authors at 8 institutions in 1 country.

Antonio MarchettiCenter of Predictive Molecular Medicine, Center of Excellence on Aging, University-Foundation, Chieti, Italy.
Maela Del GrammastroCenter of Predictive Molecular Medicine, Center of Excellence on Aging, University-Foundation, Chieti, Italy.
Lara FelicioniCenter of Predictive Molecular Medicine, Center of Excellence on Aging, University-Foundation, Chieti, Italy; Oncological and Cardiovascular Molecular Medicine Unit, Center of Excellence on Aging, University-Foundation, Chieti, Italy.
Sara MalatestaCenter of Predictive Molecular Medicine, Center of Excellence on Aging, University-Foundation, Chieti, Italy.
Giampaolo FiliceCenter of Predictive Molecular Medicine, Center of Excellence on Aging, University-Foundation, Chieti, Italy.
Irene CentiHospital "SS Annunziata", Pathology Unit, Chieti, Italy.
Tommaso De PasDepartment of Medicine, European Institute of Oncology, Milan, Italy.
Armando SantoroDepartment of Oncology, Humanitas Cancer Center IRCCS, Rozzano, Italy.
Antonio ChellaCardiothoracic Department, University of Pisa, Pisa, Italy.
Alba Ariela BrandesDepartment of Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL of Bologna, Bologna, Italy.
Paola VenturinoRoche S.p.A., Monza, Italy.
Franco CuccurulloCenter of Predictive Molecular Medicine, Center of Excellence on Aging, University-Foundation, Chieti, Italy.
Lucio CrinòDepartment of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
Fiamma ButtittaCenter of Predictive Molecular Medicine, Center of Excellence on Aging, University-Foundation, Chieti, Italy; Oncological and Cardiovascular Molecular Medicine Unit, Center of Excellence on Aging, University-Foundation, Chieti, Italy.
University of Chieti-Pescara · ITAzienda Ospedaliera di Perugia · ITAzienda USL di Bologna · ITEuropean Institute of Oncology · ITHumanitas University · ITOspedale SS. Annunziata · ITRoche (Italy) · ITUniversity of Pisa · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAssessment of EGFR mutation in non-small cell lung cancer (NSCLC) patients is mandatory for optimization of pharmacologic treatment. In this respect, mutation analysis of circulating tumor cells (CTCs) may be desirable since they may provide real-time information on patient's disease status. EXPERIMENTAL

designBlood samples were collected from 37 patients enrolled in the TRIGGER study, a prospective phase II multi-center trial of erlotinib treatment in advanced NSCLC patients with activating EGFR mutations in tumor tissue. 10 CTC preparations from breast cancer patients without EGFR mutations in their primary tumors and 12 blood samples from healthy subjects were analyzed as negative controls. CTC preparations, obtained by the Veridex CellSearch System, were subjected to ultra-deep next generation sequencing (NGS) on the Roche 454 GS junior platform.

resultsCTCs fulfilling all Veridex criteria were present in 41% of the patients examined, ranging in number between 1 and 29. In addition to validated CTCs, potential neoplastic elements were seen in 33 cases. These included cells not fulfilling all Veridex criteria (also known as "suspicious objects") found in 5 (13%) of 37 cases, and isolated or clustered large naked nuclei with irregular shape observed in 33 (89%) cases. EGFR mutations were identified by NGS in CTC preparations of 31 (84%) patients, corresponding to those present in matching tumor tissue. Twenty-five (96%) of 26 deletions at exon 19 and 6 (55%) of 11 mutations at exon 21 were detectable (P = 0.005). In 4 (13%) cases, multiple EGFR mutations, suggesting CTC heterogeneity, were documented. No mutations were found in control samples.

conclusionsWe report for the first time that the CellSearch System coupled with NGS is a very sensitive and specific diagnostic tool for EGFR mutation analysis in CTC preparations with potential clinical impact.

Indexed as

MutationAntineoplastic AgentsBase SequenceBiomarkers, TumorCarcinoma, Non-Small-Cell LungCase-Control StudiesErbB ReceptorsErlotinib HydrochlorideExonsGene ExpressionHigh-Throughput Nucleotide SequencingHumansLung NeoplasmsMolecular Sequence DataNeoplastic Cells, CirculatingProtein Kinase InhibitorsAntineoplastic AgentsBiomarkers, TumorEGFR protein, humanErbB ReceptorsErlotinib HydrochlorideProtein Kinase InhibitorsQuinazolines

Identifiers

PMID25137181
PMCPMC4138040
OpenAlexW1963552997

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.