Evidence map›Paper›PMID 27601595›Full record

Observational studyClinical cancer research : an official journal of the American Association for Cancer Research2016

Detection of Therapeutically Targetable Driver and Resistance Mutations in Lung Cancer Patients by Next-Generation Sequencing of Cell-Free Circulating Tumor DNA.

Jeffrey C Thompson, Stephanie S Yee, Andrea B Troxel, Samantha L Savitch, Ryan Fan, David Balli, David B Lieberman, Jennifer D Morrissette, Tracey L Evans, Joshua Bauml and 12 more

Registry-linked trialAbstract readObservational Study
In one paragraph

Observational study in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05853887 (iNUDGE), which is not on this map. Cited by 201 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
201citing papers in PubMed, 4 pooled it
18.5field-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.

NCT05853887 naactive not recruitingnot on this mapstarted 2023, after this paper: background citation

iNUDGE: INtegration of liqUiD Biopsy Based Next Generation Gene sEquencing in Newly Diagnosed NSCLC - A Stepped Wedge Cluster Randomized Clinical Trial

TypeinterventionalSponsorCharu AggarwalRan2023 to 2026Enrolled260ConditionsNon Small Cell Lung Cancer Metastatic, Newly Diagnosed NSCLC, Non-Squamous Non-Small Cell Neoplasm of LungArmsiNUDGE
3 · Its place in the literature

Who cites it

201 citing papers in PubMed, 4 syntheses or guidelines pooled it, 326 citations in OpenAlex.

  1. Pooled it
  2. Detection ofFrontiers in oncology · 2023
    Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
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  7. RELAY Subgroup Analyses by EGFR Ex19del and Ex21L858R Mutations for Ramucirumab Plus Erlotinib in Metastatic Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Trial
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  10. Monitoring Therapeutic Response and Resistance: Analysis of Circulating Tumor DNA in Patients With ALK+ Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2019
    Trial
  11. Trial
  12. Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma.Annals of oncology : official journal of the European Society for Medical Oncology · 2018
    Trial
  13. Trial
  14. Interpretable deep learning model of circulating genomics for quantitative survival prediction in advanced 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 · 2026
    Article
  15. Article
  16. Article
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141 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

22 authors at 1 institution in 1 country.

Jeffrey C ThompsonDivision of Pulmonary, Allergy and Critical Care Medicine, Thoracic Oncology Group, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Stephanie S YeeDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Andrea B TroxelCenter for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania.
Samantha L SavitchDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Ryan FanDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
David BalliAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
David B LiebermanDepartment of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Jennifer D MorrissetteDepartment of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Tracey L EvansDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Joshua BaumlDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Charu AggarwalDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
John A KostevaDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Evan AlleyDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Christine CiunciDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Roger B CohenDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Stephen BagleyDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Susan Stonehouse-LeeDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Victoria E SherryDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Elizabeth GilbertDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Corey LangerDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Anil VachaniDivision of Pulmonary, Allergy and Critical Care Medicine, Thoracic Oncology Group, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Erica L CarpenterDivision of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. erical@upenn.edu.
University of Pennsylvania · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Susan M Domchek · 1985 to 2026
$222.3M
CANCER CLINICAL EPIDEMIOLOGY TRAINING GRANTT32CA009679 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Richard Aplenc, Karen Glanz · 1992 to 2026
$11.1M
TRAINING IN PULMONARY IMMUNOLOGYT32HL007586 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MEYER, NUALA JENNINGS · 1985 to 2025
$8.8M
NCI NIH HHS P30 CA016520NCI NIH HHS T32 CA009679NHLBI NIH HHS T32 HL007586
6 · The paper itself

Abstract

purposeThe expanding number of targeted therapeutics for non-small cell lung cancer (NSCLC) necessitates real-time tumor genotyping, yet tissue biopsies are difficult to perform serially and often yield inadequate DNA for next-generation sequencing (NGS). We evaluated the feasibility of using cell-free circulating tumor DNA (ctDNA) NGS as a complement or alternative to tissue NGS. EXPERIMENTAL

designA total of 112 plasma samples obtained from a consecutive study of 102 prospectively enrolled patients with advanced NSCLC were subjected to ultra-deep sequencing of up to 70 genes and matched with tissue samples, when possible.

resultsWe detected 275 alterations in 45 genes, and at least one alteration in the ctDNA for 86 of 102 patients (84%), with EGFR variants being most common. ctDNA NGS detected 50 driver and 12 resistance mutations, and mutations in 22 additional genes for which experimental therapies, including clinical trials, are available. Although ctDNA NGS was completed for 102 consecutive patients, tissue sequencing was only successful for 50 patients (49%). Actionable EGFR mutations were detected in 24 tissue and 19 ctDNA samples, yielding concordance of 79%, with a shorter time interval between tissue and blood collection associated with increased concordance (P = 0.038). ctDNA sequencing identified eight patients harboring a resistance mutation who developed progressive disease while on targeted therapy, and for whom tissue sequencing was not possible.

conclusionsTherapeutically targetable driver and resistance mutations can be detected by ctDNA NGS, even when tissue is unavailable, thus allowing more accurate diagnosis, improved patient management, and serial sampling to monitor disease progression and clonal evolution. Clin Cancer Res; 22(23); 5772-82. ©2016 AACR.

Indexed as

AdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Non-Small-Cell LungCirculating Tumor DNADNA, NeoplasmDrug Resistance, NeoplasmFemaleGenotypeHigh-Throughput Nucleotide SequencingHumansLung NeoplasmsMaleMiddle AgedMutationBiomarkers, TumorCirculating Tumor DNADNA, Neoplasm

Identifiers

PMID27601595
PMCPMC5448134
OpenAlexW2508716485

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.