Evidence map›Paper›PMID 25842160›Full record

Trial reportThe Lancet. Oncology2015

Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study.

Mark Roschewski, Kieron Dunleavy, Stefania Pittaluga, Martin Moorhead, Francois Pepin, Katherine Kong, Margaret Shovlin, Elaine S Jaffe, Louis M Staudt, Catherine Lai and 6 more

Erratum issued 3 registry-linked trialsOpen access · greenAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 3 registered trials, which are not on this map. Cited by 245 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
245citing papers in PubMed, 3 pooled it
27.5field-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.

NCT03079947 unknown statusnot on this mapstarted 2017, after this paper: background citation

Effectiveness of Circulating DNA for Predicting the Relapse and Overall Survival in Non-hodgkin Lymphoma Patients

TypeobservationalSponsorPeking Union Medical College HospitalRan2017 to 2020Enrolled300ConditionsDiffuse Large B Cell Lymphoma, Peripheral T Cell Lymphoma
NCT03421132 active not recruitingnot on this mapstarted 2018, after this paper: background citation

The Terry Fox Pan-Canadian Multiple Myeloma Molecular Monitoring Study

TypeobservationalSponsorHorizon Health NetworkRan2018 to 2026Enrolled96ConditionsMultiple Myeloma
NCT04237168 unknown statusnot on this mapstarted 2020, after this paper: background citation

Non-invasive Tumor Immunoglobulin Gene Next Generation Sequencing (IgNGS) in Diffuse Large B Cell Lymphoma (DLBCL): Prognostic Implications and Assessment of Tumor Response

TypeobservationalSponsorFundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauRan2020 to 2022Enrolled30ConditionsLymphoma, Large B-Cell, DiffuseArmsIgNGS from circulating tumor DNA
3 · Its place in the literature

Who cites it

245 citing papers in PubMed, 3 syntheses or guidelines pooled it, 451 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
  2. Circulating tumour cells in patients with lung cancer universally indicate poor prognosis.European respiratory review : an official journal of the European Respiratory Society · 2022
    Pooled it
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  13. Detection of the MYD88Annals of hematology · 2020
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185 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 1 country.

Mark RoschewskiLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Kieron DunleavyLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Stefania PittalugaLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Martin MoorheadAdaptive Biotechnologies, South San Francisco, CA, USA.
Francois PepinAdaptive Biotechnologies, South San Francisco, CA, USA.
Katherine KongAdaptive Biotechnologies, South San Francisco, CA, USA.
Margaret ShovlinLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Elaine S JaffeLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Louis M StaudtLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Catherine LaiLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Seth M SteinbergOffice of the Clinical Director, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Clara C ChenNuclear Medicine Division, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Jianbiao ZhengAdaptive Biotechnologies, South San Francisco, CA, USA.
Thomas D WillisAdaptive Biotechnologies, South San Francisco, CA, USA.
Malek FahamAdaptive Biotechnologies, South San Francisco, CA, USA.
Wyndham H WilsonLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. Electronic address: wilsonw@mail.nih.gov.
Adaptive Biotechnologies (United States) · USCenter for Cancer Research · USNational Cancer Institute · USNational Institutes of Health Clinical Center · US

Funding

Lymphoma Disease Discovery and DefintionZIASC000550 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI JAFFE, ELAINE · 2009 to 2025
$16.9M
Hematopathology DiagnosisZIABC011070 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI JAFFE, ELAINE · 2009 to 2025
$14.5M
Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

backgroundDiffuse large-B-cell lymphoma is curable, but when treatment fails, outcome is poor. Although imaging can help to identify patients at risk of treatment failure, they are often imprecise, and radiation exposure is a potential health risk. We aimed to assess whether circulating tumour DNA encoding the clonal immunoglobulin gene sequence could be detected in the serum of patients with diffuse large-B-cell lymphoma and used to predict clinical disease recurrence after frontline treatment.

methodsWe used next-generation DNA sequencing to retrospectively analyse cell-free circulating tumour DNA in patients assigned to one of three treatment protocols between May 8, 1993, and June 6, 2013. Eligible patients had diffuse large-B-cell lymphoma, no evidence of indolent lymphoma, and were previously untreated. We obtained serial serum samples and concurrent CT scans at specified times during most treatment cycles and up to 5 years of follow-up. VDJ gene segments of the rearranged immunoglobulin receptor genes were amplified and sequenced from pretreatment specimens and serum circulating tumour DNA encoding the VDJ rearrangements was quantitated.

findingsTumour clonotypes were identified in pretreatment specimens from 126 patients who were followed up for a median of 11 years (IQR 6·8-14·2). Interim monitoring of circulating tumour DNA at the end of two treatment cycles in 108 patients showed a 5-year time to progression of 41·7% (95% CI 22·2-60·1) in patients with detectable circulating tumour DNA and 80·2% (69·6-87·3) in those without detectable circulating tumour DNA (p<0·0001). Detectable interim circulating tumour DNA had a positive predictive value of 62·5% (95% CI 40·6-81·2) and a negative predictive value of 79·8% (69·6-87·8). Surveillance monitoring of circulating tumour DNA was done in 107 patients who achieved complete remission. A Cox proportional hazards model showed that the hazard ratio for clinical disease progression was 228 (95% CI 51-1022) for patients who developed detectable circulating tumour DNA during surveillance compared with patients with undetectable circulating tumour DNA (p<0·0001). Surveillance circulating tumour DNA had a positive predictive value of 88·2% (95% CI 63·6-98·5) and a negative predictive value of 97·8% (92·2-99·7) and identified risk of recurrence at a median of 3·5 months (range 0-200) before evidence of clinical disease.

interpretationSurveillance circulating tumour DNA identifies patients at risk of recurrence before clinical evidence of disease in most patients and results in a reduced disease burden at relapse. Interim circulating tumour DNA is a promising biomarker to identify patients at high risk of treatment failure.

fundingNational Cancer Institute and Adaptive Biotechnologies.

Indexed as

High-Throughput Nucleotide SequencingAdolescentAdultAgedAged, 80 and overBiomarkers, TumorChildDNA, NeoplasmFemaleHumansLymphoma, Large B-Cell, DiffuseMaleMiddle AgedNeoplastic Cells, CirculatingTomography, X-Ray ComputedBiomarkers, TumorDNA, Neoplasm

Identifiers

PMID25842160
PMCPMC4460610
OpenAlexW2137816642

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.