Evidence map›Paper›PMID 33070443›Full record

ArticleMolecular oncology2021

Comparison of variant allele frequency and number of mutant molecules as units of measurement for circulating tumor DNA.

Manouk K Bos, Kazem Nasserinejad, Maurice P H M Jansen, Lindsay Angus, Peggy N Atmodimedjo, Evert de Jonge, Winand N M Dinjens, Ron H N van Schaik, Marzia Del Re, Hendrikus J Dubbink and 2 more

Erratum issuedAbstract readComparative Study
In one paragraph

Article in Molecular oncology, 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 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

26 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  20. Circulating Tumor DNA in Pediatric Cancer.Frontiers in molecular biosciences · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Manouk K BosDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.ORCID 0000-0002-2984-7542
Kazem NasserinejadDepartment of Hematology, HOVON Data Center, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
Maurice P H M JansenDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.ORCID 0000-0003-1258-9804
Lindsay AngusDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.ORCID 0000-0002-7928-1102
Peggy N AtmodimedjoDepartment of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
Evert de JongeDepartment of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Winand N M DinjensDepartment of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
Ron H N van SchaikDepartment of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Marzia Del ReDepartment of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Hendrikus J DubbinkDepartment of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
Stefan SleijferDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
John W M MartensDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Quantification of tumor-specific variants (TSVs) in cell-free DNA is rapidly evolving as a prognostic and predictive tool in patients with cancer. Currently, both variant allele frequency (VAF) and number of mutant molecules per mL plasma are used as units of measurement to report those TSVs. However, it is unknown to what extent both units of measurement agree and what are the factors underlying an existing disagreement. To study the agreement between VAF and mutant molecules in current clinical studies, we analyzed 1116 TSVs from 338 patients identified with next-generation sequencing (NGS) or digital droplet PCR (ddPCR). On different study cohorts, a Deming regression analysis was performed and its 95% prediction interval was used as surrogate for the limits of agreement between VAF and number of mutant molecules per mL and to identify outliers. VAF and number of mutant molecules per mL plasma yielded greater agreement when using ddPCR than NGS. In case of discordance between VAF and number of mutant molecules per mL, insufficient molecular coverage in NGS and high cell-free DNA concentration were the main responsible factors. We propose several optimization steps needed to bring monitoring of TSVs in cell-free DNA to its full potential.

Indexed as

Circulating Tumor DNACohort StudiesGene FrequencyHigh-Throughput Nucleotide SequencingHumansMutationRegression AnalysisCirculating Tumor DNAcancercirculating tumor DNAdigital droplet PCRliquid biopsynext-generation sequencingunit of measurement

Identifiers

PMID33070443
PMCPMC7782075

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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.