Evidence map›Paper›PMID 34311346›Full record

ArticleLung cancer (Amsterdam, Netherlands)2021

Clinical utility of next-generation sequencing-based ctDNA testing for common and novel ALK fusions.

Sebastian Mondaca, Emily S Lebow, Azadeh Namakydoust, Pedram Razavi, Jorge S Reis-Filho, Ronglai Shen, Michael Offin, Hai-Yan Tu, Yonina Murciano-Goroff, Chongrui Xu and 24 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Lung cancer (Amsterdam, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

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  9. Circulating Tumor DNA Enables Sensitive Detection of Actionable Gene Fusions and Rearrangements Across Cancer Types.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  10. Review
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  12. New update to the guidelines on testing predictive biomarkers in non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors at 6 institutions in 4 countries.

Sebastian MondacaDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA; Department of Hematology and Oncology, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362 6th Fl, Rm 609, Santiago, Chile. Electronic address: spmondac@uc.cl.
Emily S LebowDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Azadeh NamakydoustDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Pedram RazaviDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Jorge S Reis-FilhoDepartment of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Ronglai ShenDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering, 1275 York Avenue, New York, NY, USA.
Michael OffinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Hai-Yan TuDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA; Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, China.
Yonina Murciano-GoroffDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Chongrui XuDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA; Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, China.
Alex MakhninDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Andres MartinezDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Nick PavlakisGenesisCare (formerly Northern Cancer Institute), University of Sydney, Macquarie University NSW 2109, Australia.
Stephen ClarkeGenesisCare (formerly Northern Cancer Institute), University of Sydney, Macquarie University NSW 2109, Australia.
Malinda ItchinsGenesisCare (formerly Northern Cancer Institute), University of Sydney, Macquarie University NSW 2109, Australia.
Adrian LeeGenesisCare (formerly Northern Cancer Institute), University of Sydney, Macquarie University NSW 2109, Australia.
Andreas RimnerDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Daniel GomezDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Gaetano RoccoDepartment of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Jamie E ChaftDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Gregory J RielyDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Charles M RudinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
David R JonesDepartment of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Mark LiResolution Bioscience, 550 Kirkland Way #200, Kirkland, WA, USA.
Tristan ShafferResolution Bioscience, 550 Kirkland Way #200, Kirkland, WA, USA.
Seyed Ali HosseiniResolution Bioscience, 550 Kirkland Way #200, Kirkland, WA, USA.
Caterina BertucciResolution Bioscience, 550 Kirkland Way #200, Kirkland, WA, USA.
Lee P LimResolution Bioscience, 550 Kirkland Way #200, Kirkland, WA, USA.
Alexander DrilonDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Michael F BergerDepartment of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York NY, USA.
Ryma BenayedDepartment of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Maria E ArcilaDepartment of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
James M IsbellDepartment of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
Bob T LiDepartment of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA. Electronic address: lib1@mskcc.org.
Memorial Sloan Kettering Cancer Center · USMacquarie University · AUGuangdong Academy of Medical Sciences · CNMolecular Oncology (United States) · USNorthern Cancer Institute · AUUniversity of Sydney · AU

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Clinical and Translational Science CenterUL1TR000457 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI IMPERATO-MCGINLEY, JULIANNE L · 2012 to 2016
$46.0M
Investigational Cancer Therapeutics Training Program (ICTTP)T32CA009207 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Omar Abdel-Wahab, Alexander Drilon · 1985 to 2026
$13.7M
NCATS NIH HHS UL1 TR000457NCI NIH HHS P30 CA008748NCI NIH HHS T32 CA009207
6 · The paper itself

Abstract

objectivesLiquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) can detect ALK fusions, though data on clinical utility of this technology in the real world is limited. MATERIALS AND

methodsPatients with lung cancer without known oncogenic drivers or who had acquired resistance to therapy (n = 736) underwent prospective plasma ctDNA NGS. A subset of this cohort (n = 497) also had tissue NGS. We evaluated ALK fusion detection, turnaround time (TAT), plasma and tissue concordance, matching to therapy, and treatment response.

resultsctDNA identified an ALK fusion in 21 patients (3%) with a variety of breakpoints and fusion partners, including EML4, CLTC, and PON1, a novel ALK fusion partner. TAT for ctDNA NGS was shorter than tissue NGS (10 vs. 20 days; p < 0.001). Among ALK fusions identified by ctDNA, 93% (13/14, 95% CI 66%-99%) were concordant with tissue evaluation. Among ALK fusions detected by tissue NGS, 54% (13/24, 95% CI 33%-74%) were concordant with plasma ctDNA. ctDNA matched patients to ALK-directed therapy with subsequent clinical response, including four patients matched on the basis of ctDNA results alone due to inadequate or delayed tissue testing. Serial ctDNA analysis detected MET amplification (n = 2) and ALK G1202R mutation (n = 2) as mechanisms of acquired resistance to ALK-directed therapy.

conclusionOur findings support a complementary role for ctDNA in detection of ALK fusions and other alterations at diagnosis and therapeutic resistance settings.

Indexed as

Carcinoma, Non-Small-Cell LungCirculating Tumor DNALung NeoplasmsAryldialkylphosphataseHigh-Throughput Nucleotide SequencingHumansMutationProspective StudiesReceptor Protein-Tyrosine KinasesAryldialkylphosphataseCirculating Tumor DNAPON1 protein, humanReceptor Protein-Tyrosine KinasesALK fusionCirculating tumor DNALiquid biopsyNext generation sequencing

Identifiers

PMID34311346
PMCPMC8594131
OpenAlexW3184481127

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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.