Evidence map›Paper›PMID 26968843›Full record

ArticleBMC cancer2016

Mutational status of synchronous and metachronous tumor samples in patients with metastatic non-small-cell lung cancer.

Gilles Quéré, Renaud Descourt, Gilles Robinet, Sandrine Autret, Odile Raguenes, Brigitte Fercot, Pierre Alemany, Arnaud Uguen, Claude Férec, Isabelle Quintin-Roué and 1 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 5% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
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  5. Review
  6. Article
  7. Strategies to overcome acquired resistance to EGFR TKI in the treatment of non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019
    Review
  8. Differential molecular markers of primary lung tumors and metastatic sites indicate different possible treatment selections in patients with metastatic lung adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019
    Article
  9. Review
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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 2 institutions in 1 country.

Gilles QuéréCHRU de Brest, Institut de Cancérologie et d'Hématologie, Brest, France.
Renaud DescourtCHRU de Brest, Institut de Cancérologie et d'Hématologie, Brest, France.
Gilles RobinetCHRU de Brest, Institut de Cancérologie et d'Hématologie, Brest, France.
Sandrine AutretCHRU de Brest, Hôpital Morvan, Bat 5 bis, Laboratoire de Génétique Moléculaire et d'Histocompatibilité, 2 Avenue Foch, 29200, Brest, France.
Odile RaguenesCHRU de Brest, Hôpital Morvan, Bat 5 bis, Laboratoire de Génétique Moléculaire et d'Histocompatibilité, 2 Avenue Foch, 29200, Brest, France.
Brigitte FercotCHRU de Brest, Hôpital Morvan, Bat 5 bis, Laboratoire de Génétique Moléculaire et d'Histocompatibilité, 2 Avenue Foch, 29200, Brest, France.
Pierre AlemanyPlateforme de Génétique Moléculaire des Cancers (INCa), Brest, France.
Arnaud UguenPlateforme de Génétique Moléculaire des Cancers (INCa), Brest, France.
Claude FérecCHRU de Brest, Hôpital Morvan, Bat 5 bis, Laboratoire de Génétique Moléculaire et d'Histocompatibilité, 2 Avenue Foch, 29200, Brest, France.
Isabelle Quintin-RouéPlateforme de Génétique Moléculaire des Cancers (INCa), Brest, France.
Gérald Le GacCHRU de Brest, Hôpital Morvan, Bat 5 bis, Laboratoire de Génétique Moléculaire et d'Histocompatibilité, 2 Avenue Foch, 29200, Brest, France. gerald.legac@univ-brest.fr.
Centre Hospitalier Régional Universitaire de Brest · FRUniversité de Bretagne Occidentale · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundsDespite reported discordance between the mutational status of primary lung cancers and their metastases, metastatic sites are rarely biopsied and targeted therapy is guided by genetic biomarkers detected in the primary tumor. This situation is mostly explained by the apparent stability of EGFR-activating mutations. Given the dramatic increase in the range of candidate drugs and high rates of drug resistance, rebiopsy or liquid biopsy may become widespread. The purpose of this study was to test genetic biomarkers used in clinical practice (EGFR, ALK) and candidate biomarkers identified by the French National Cancer Institute (KRAS, BRAF, PIK3CA, HER2) in patients with metastatic non-small-cell lung cancer for whom two tumor samples were available.

methodsA retrospective study identified 88 tumor samples collected synchronously or metachronously, from the same or two different sites, in 44 patients. Mutation analysis used SNaPshot (EGFR, KRAS, BRAF missense mutations), pyrosequencing (EGFR and PIK3CA missense mutations), sizing assays (EGFR and HER2 indels) and IHC and/or FISH (ALK rearrangements).

resultsAbout half the patients (52%) harbored at least one mutation. Five patients had an activating mutation of EGFR in both the primary tumor and the metastasis. The T790M resistance mutation was detected in metastases in 3 patients with acquired resistance to EGFR tyrosine kinase inhibitors. FISH showed discordance in ALK status between a small biopsy sample and the surgical specimen. KRAS mutations were observed in 36% of samples, six patients (14%) having discordant genotypes; all discordances concerned sampling from different sites. Two patients (5%) showed PI3KCA mutations. One metastasis harbored both PI3KCA and KRAS mutations, while the synchronously sampled primary tumor was mutation free. No mutations were detected in BRAF and HER2.

conclusionsThis study highlighted noteworthy intra-individual discordance in KRAS mutational status, whereas EGFR status was stable. Intratumoral heterogeneity for ALK rearrangement suggests a limitation of single-biopsy analysis for therapeutic strategy with crizotinib.

Indexed as

Molecular Targeted TherapyAdultAgedAnaplastic Lymphoma KinaseBiomarkers, TumorBiopsyCarcinoma, Non-Small-Cell LungClass I Phosphatidylinositol 3-KinasesErb-b2 Receptor Tyrosine KinasesErbB ReceptorsFemaleHumansMaleMiddle AgedMutationNeoplasm MetastasisALK protein, humanAnaplastic Lymphoma KinaseBiomarkers, TumorBRAF protein, humanClass I Phosphatidylinositol 3-KinasesEGFR protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesErbB ReceptorsKRAS protein, humanPhosphatidylinositol 3-KinasesPIK3CA protein, humanProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)Receptor Protein-Tyrosine KinasesGenetic biomarkersMetastatic lesionNon-small-cell lung cancerRebiopsyTargeted therapy

Identifiers

PMID26968843
PMCPMC4788951
OpenAlexW2295993661

What OpenQuestion holds

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LicenceCC BY
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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.