Evidence map›Paper›PMID 26085511›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015

Serial Next-Generation Sequencing of Circulating Cell-Free DNA Evaluating Tumor Clone Response To Molecularly Targeted Drug Administration.

Jean Sebastien Frenel, Suzanne Carreira, Jane Goodall, Desam Roda, Raquel Perez-Lopez, Nina Tunariu, Ruth Riisnaes, Susana Miranda, Ines Figueiredo, Daniel Nava-Rodrigues and 13 more

Registry-linked trialAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02730923 (A Multicentric, Randomized, Non Comparative, Open-label Phase I/II Evaluating AZD2014), which is not on this map. Cited by 101 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed, 3 pooled it
11.6field-weighted citation impact, top 1% 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.

NCT02730923 phase1 / phase2unknown statusnot on this mapstarted 2016, after this paper: background citation

A Multicentric, Randomized, Non Comparative, Open-label Phase I/II Evaluating AZD2014 (Dual Mammalian Target of Rapamycin Complex 1/2 (mTORC1/mTORC2) Inhibitor) in Combination With Anastrozole Versus Anastrozole Alone in the Treatment of Metastatic Hormone Receptor-positive Endometrial Adenocarcinoma

TypeinterventionalSponsorCentre Leon BerardRan2016 to 2024Enrolled72ConditionsEndometrial Carcinoma, Metastatic Carcinoma, Hormone Receptor Positive TumorArmsAZD2014, Anastrozole
3 · Its place in the literature

Who cites it

101 citing papers in PubMed, 3 syntheses or guidelines pooled it, 184 citations in OpenAlex.

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  10. Liquid Biopsy in Solid Tumours: An Overview.Cytopathology : official journal of the British Society for Clinical Cytology · 2025
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41 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

23 authors at 4 institutions in 3 countries.

Jean Sebastien FrenelThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom. Institut de Cancerologie de l'Ouest, Nantes-Saint Herblain, France.
Suzanne CarreiraThe Institute of Cancer Research, Sutton, Surrey, London, United Kingdom.
Jane GoodallThe Institute of Cancer Research, Sutton, Surrey, London, United Kingdom.
Desam RodaThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom.
Raquel Perez-LopezThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom.
Nina TunariuThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom.
Ruth RiisnaesThe Institute of Cancer Research, Sutton, Surrey, London, United Kingdom.
Susana MirandaThe Institute of Cancer Research, Sutton, Surrey, London, United Kingdom.
Ines FigueiredoThe Institute of Cancer Research, Sutton, Surrey, London, United Kingdom.
Daniel Nava-RodriguesThe Institute of Cancer Research, Sutton, Surrey, London, United Kingdom.
Alan SmithThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom.
Christophe LeuxDépartement de Santé Publique, CHU de Nantes, Nantes Cedex 1, France.
Isaac Garcia-MurillasThe Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom.
Roberta FerraldeschiThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom.
David LorenteThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom.
Joaquin MateoThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom.
Michael OngThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom.
Timothy A YapThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom.
Udai BanerjiThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom.
Delila Gasi TandefeltThe Institute of Cancer Research, Sutton, Surrey, London, United Kingdom.
Nick TurnerThe Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom.
Gerhardt AttardThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom.
Johann S de BonoThe Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, London, United Kingdom. Johann.de-Bono@icr.ac.uk.
Royal Marsden NHS Foundation Trust · GBInstitute of Cancer Research · GBBreast Cancer Research Foundation · USCentre Hospitalier Universitaire de Nantes · FR

Funding

Cancer Research UK 11566Cancer Research UK 13239Cancer Research UK 16642Cancer Research UK A15573Department of Health C51/A7401Medical Research Council G0502133Medical Research Council MR/M003272/1Prostate Cancer UK PG12-49Wellcome Trust
6 · The paper itself

Abstract

purposeWe evaluated whether next-generation sequencing (NGS) of circulating cell-free DNA (cfDNA) could be used for patient selection and as a tumor clone response biomarker in patients with advanced cancers participating in early-phase clinical trials of targeted drugs. EXPERIMENTAL

designPlasma samples from patients with known tumor mutations who completed at least two courses of investigational targeted therapy were collected monthly, until disease progression. NGS was performed sequentially on the Ion Torrent PGM platform.

resultscfDNA was extracted from 39 patients with various tumor types. Treatments administered targeted mainly the PI3K-AKT-mTOR pathway (n = 28) or MEK (n = 7). Overall, 159 plasma samples were sequenced with a mean sequencing coverage achieved of 1,685X across experiments. At trial initiation (C1D1), 23 of 39 (59%) patients had at least one mutation identified in cfDNA (mean 2, range 1-5). Out of the 44 mutations identified at C1D1, TP53, PIK3CA and KRAS were the top 3 mutated genes identified, with 18 (41%), 9 (20%), 8 (18%) different mutations, respectively. Out of these 23 patients, 13 received a targeted drug matching their tumor profile. For the 23 patients with cfDNA mutation at C1D1, the monitoring of mutation allele frequency (AF) in consecutive plasma samples during treatment with targeted drugs demonstrated potential treatment associated clonal responses. Longitudinal monitoring of cfDNA samples with multiple mutations indicated the presence of separate clones behaving discordantly. Molecular changes at cfDNA mutation level were associated with time to disease progression by RECIST criteria.

conclusionsTargeted NGS of cfDNA has potential clinical utility to monitor the delivery of targeted therapies.

Indexed as

AdultAgedBiomarkers, TumorDisease ProgressionDNA, ComplementaryDNA, NeoplasmFemaleHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedMutationNeoplastic Cells, CirculatingPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktras ProteinsBiomarkers, TumorDNA, ComplementaryDNA, NeoplasmMTOR protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktras ProteinsTOR Serine-Threonine Kinases

Identifiers

PMID26085511
PMCPMC4580992
OpenAlexW1893269340

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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.