Evidence map›Paper›PMID 31125418›Full record

ArticleNeuro-oncology2019

Defining EGFR amplification status for clinical trial inclusion.

Pim J French, Marica Eoli, Juan Manuel Sepulveda, Iris de Heer, Johan M Kros, Annemiek Walenkamp, Jean-Sebastien Frenel, Enrico Franceschi, Paul M Clement, Michael Weller and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2019. 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
2.3field-weighted citation impact, top 12% 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, 42 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 8 institutions in 5 countries.

Pim J FrenchDepartment of Neurology, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands.
Marica EoliCarlo Besta Neurological Institute, Milan, Italy.
Juan Manuel SepulvedaUniversity Hospital, Madrid, Spain.
Iris de HeerDepartment of Neurology, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands.
Johan M KrosDepartment of Pathology, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands.
Annemiek WalenkampUniversity Medical Center Groningen, Groningen, Netherlands.
Jean-Sebastien FrenelWestern Cancer Institute, René Gauducheau Center, Saint-Herblain, France.
Enrico FranceschiAzienda USL/IRCCS Institute of Neurological Sciences, Bologna, Italy.
Paul M ClementUZ Leuven, Leuven, Belgium.
Michael WellerDepartment of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
Peter AnsellAbbVie, North Chicago, Illinois, USA.
Jim LoomanAbbVie, North Chicago, Illinois, USA.
Earle BainAbbVie, North Chicago, Illinois, USA.
Marie MorfouaceEuropean Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium.
Thierry GorliaEuropean Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium.
Martin van den BentDepartment of Neurology, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands.
Erasmus MC Cancer Institute · NLAbbVie (United States) · USEuropean Organisation for Research and Treatment of Cancer · BEFondazione IRCCS Istituto Neurologico Carlo Besta · ITInstitute of Neurological Sciences · ITUniversitair Ziekenhuis Leuven · BEUniversity Medical Center Groningen · NLUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPrecision medicine trials targeting the epidermal growth factor receptor (EGFR) in glioblastoma patients require selection for EGFR-amplified tumors. However, there is currently no gold standard in determining the amplification status of EGFR or variant III (EGFRvIII) expression. Here, we aimed to determine which technique and which cutoffs are suitable to determine EGFR amplification status.

methodsWe compared fluorescence in-situ hybridization (FISH) and real-time quantitative (RT-q)PCR data from patients screened for trial inclusion into the Intellance 2 clinical trial, with data from a panel-based next generation sequencing (NGS) platform (both DNA and RNA).

resultsBy using data from >1000 samples, we show that at least 50% of EGFR amplified nuclei should be present to define EGFR gene amplification by FISH. Gene amplification (as determined by FISH) correlates with EGFR expression levels (as determined by RT-qPCR) with receiver operating characteristics analysis showing an area under the curve of up to 0.902. EGFR expression as assessed by RT-qPCR therefore may function as a surrogate marker for EGFR amplification. Our NGS data show that EGFR copy numbers can strongly vary between tumors, with levels ranging from 2 to more than 100 copies per cell. Levels exceeding 5 gene copies can be used to define EGFR-amplification by NGS; below this level, FISH detects very few (if any) EGFR amplified nuclei and none of the samples express EGFRvIII.

conclusionOur data from central laboratories and diagnostic sequencing facilities, using material from patients eligible for clinical trial inclusion, help define the optimal cutoff for various techniques to determine EGFR amplification for diagnostic purposes.

Indexed as

Patient SelectionClinical Trials as TopicErbB ReceptorsGene AmplificationGene DosageGlioblastomaHigh-Throughput Nucleotide SequencingHumansIn Situ Hybridization, FluorescenceNucleic Acid Amplification TechniquesReal-Time Polymerase Chain ReactionReference ValuesEGFR protein, humanErbB ReceptorsamplificationbiomarkerEGFREGFRvIIIFISHglioblastomascreening

Identifiers

PMID31125418
PMCPMC6784284
OpenAlexW2946676363

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

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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.