Evidence map›Paper›PMID 34294911›Full record

ArticleNature biotechnology2021

Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA.

David M Kurtz, Joanne Soo, Lyron Co Ting Keh, Stefan Alig, Jacob J Chabon, Brian J Sworder, Andre Schultz, Michael C Jin, Florian Scherer, Andrea Garofalo and 19 more

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07514715 (Proof of Concept for Real-time Multicentric Monitoring of Minimal Residual Disease), which is not on this map. Cited by 217 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
217citing papers in PubMed, 1 pooled it
20.5field-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.

NCT07514715 not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Proof of Concept for Real-time Multicentric Monitoring of Minimal Residual Disease (MRD) by PET and Circulating Tumor DNA (ctDNA) in Aggressive B-Cell Lymphomas

TypeobservationalSponsorThe Lymphoma Academic Research OrganisationRan2026 to 2028Enrolled129ConditionsAggressive B-cell LymphomasArmsblood test
3 · Its place in the literature

Who cites it

217 citing papers in PubMed, 1 synthesis or guideline pooled it, 343 citations in OpenAlex.

  1. A genetic profiling guideline to support diagnosis and clinical management of lymphomas.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Guideline
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  3. Minimal Residual Disease Enhances Prognostic Stratification beyond Pathologic Response in Resectable Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Trial
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  14. Value and research advances of ctDNA in perioperative therapy for 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
    Review
  15. Article
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157 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 10 institutions in 6 countries.

David M Kurtz *Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-6382-4651
Joanne Soo *Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Lyron Co Ting KehDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Stefan AligDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-6825-702X
Jacob J ChabonStanford Cancer Institute, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1820-9737
Brian J SworderDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Andre SchultzStanford Cancer Institute, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-2909-3154
Michael C JinDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Florian SchererDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-9635-5487
Andrea GarofaloDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Charles W MacaulayDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Emily G HamiltonProgram in Cancer Biology, Stanford University, Stanford, CA, USA.
Binbin ChenDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-2973-2718
Mari OlsenDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Joseph G Schroers-MartinDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-4128-2537
Alexander F M CraigDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Everett J ModingDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-7913-5351
Mohammad S EsfahaniDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Chih Long LiuDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Ulrich DührsenDepartment of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, University Hospital Essen, Essen, Germany.ORCID http://orcid.org/0000-0002-4034-9472
Andreas HüttmannDepartment of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, University Hospital Essen, Essen, Germany.ORCID http://orcid.org/0000-0003-2230-3873
René-Olivier CasasnovasDepartment of Hematology, Hopital F. Mitterrand, CHU Dijon and INSERM, Dijon, France.ORCID http://orcid.org/0000-0002-1156-8983
Jason R WestinDepartment of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-1824-2337
Mark RoschewskiLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0278-2635
Wyndham H WilsonLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Gianluca GaidanoDivision of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.ORCID http://orcid.org/0000-0002-4681-0151
Davide RossiHematology, Oncology Institute of Southern Switzerland and Institute of Oncology Research, Bellinzona, Switzerland.
Maximilian DiehnStanford Cancer Institute, Stanford University, Stanford, CA, USA. diehn@stanford.edu.ORCID http://orcid.org/0000-0003-2032-0581
Ash A AlizadehDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA. arasha@stanford.edu.ORCID http://orcid.org/0000-0002-5153-5625
Stanford University · USCalifornia Institute for Regenerative Medicine · USEssen University Hospital · DENational Institutes of Health · USInserm · FRInstitute for Stem Cell Biology and Regenerative Medicine · INInstitute of Oncology Research · CHThe University of Texas MD Anderson Cancer Center · USUniversità degli Studi del Piemonte Orientale “Amedeo Avogadro” · ITUniversity of Freiburg · DE

Funding

Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
Therapeutic Strategies and Molecular Correlates in Aggressive B-cell LymphomasZIASC006741 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI WILSON, WYNDHAM H · 2009 to 2025
$10.4M
Circulating Genomic Determinants of Treatment Failure in Hodgkin LymphomaR01CA257655 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, DIEHN, MAXIMILIAN · 2021 to 2025
$3.2M
Modeling the Molecular Determinants of Induced Anti-Tumor Immune Responses in Mantle Cell LymphomaU01CA194389 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, DAVIS, MARK MORRIS · 2015 to 2019
$3.1M
Molecularly-based outcome and toxicity prediction after radiotherapy for lung cancerR01CA254179 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, DIEHN, MAXIMILIAN · 2020 to 2024
$3.1M
Analysis of urine tumor nucleic acids for detection and personalized surveillance of bladder cancerR01CA244526 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, DIEHN, MAXIMILIAN · 2020 to 2024
$3.0M
A Noninvasive Integrated Genomic Approach for Early Cancer Detection and Risk Stratification after TransplantationR01CA229766 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, KHUSH, KIRAN KAUR · 2019 to 2023
$3.0M
A Genomic Framework for Molecular Risk Prediction & Individualized Lymphoma TherapyR01CA233975 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, DIEHN, MAXIMILIAN · 2019 to 2023
$2.8M
Noninvasive monitoring of lung cancer patients treated with radiotherapyR01CA188298 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, DIEHN, MAXIMILIAN · 2015 to 2019
$1.8M
Molecular Characterization and Personalized Approaches to Non-Hodgkin Lymphoma from Circulating Tumor DNAK08CA241076 · NCI · STANFORD UNIVERSITY · PI KURTZ, DAVID MATTHEW · 2019 to 2023
$957k
Rescuing Nucleic Acids from Formalin Damage in Cancer SpecimensR43CA199142 · NCI · CELL DATA SCIENCES, INC. · PI ALIZADEH, ASH ARASH, KOOL, ERIC T. · 2015 to 2015
$180k
NCI NIH HHS K08 CA241076NCI NIH HHS R01 CA188298NCI NIH HHS R01 CA229766NCI NIH HHS R01 CA233975NCI NIH HHS R01 CA244526NCI NIH HHS R01 CA254179NCI NIH HHS R01 CA257655NCI NIH HHS R43 CA199142NCI NIH HHS T32 CA009302NCI NIH HHS U01 CA194389
6 · The paper itself

Abstract

Circulating tumor-derived DNA (ctDNA) is an emerging biomarker for many cancers, but the limited sensitivity of current detection methods reduces its utility for diagnosing minimal residual disease. Here we describe phased variant enrichment and detection sequencing (PhasED-seq), a method that uses multiple somatic mutations in individual DNA fragments to improve the sensitivity of ctDNA detection. Leveraging whole-genome sequences from 2,538 tumors, we identify phased variants and their associations with mutational signatures. We show that even without molecular barcodes, the limits of detection of PhasED-seq outperform prior methods, including duplex barcoding, allowing ctDNA detection in the ppm range in participant samples. We profiled 678 specimens from 213 participants with B cell lymphomas, including serial cell-free DNA samples before and during therapy for diffuse large B cell lymphoma. In participants with undetectable ctDNA after two cycles of therapy using a next-generation sequencing-based approach termed cancer personalized profiling by deep sequencing, an additional 25% have ctDNA detectable by PhasED-seq and have worse outcomes. Finally, we demonstrate the application of PhasED-seq to solid tumors.

Indexed as

Circulating Tumor DNABiomarkers, TumorHigh-Throughput Nucleotide SequencingHumansMutationNeoplasm, ResidualBiomarkers, TumorCirculating Tumor DNA

Identifiers

PMID34294911
PMCPMC8678141
OpenAlexW3184558555

What OpenQuestion holds

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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.