Evidence map›Paper›PMID 34432811›Full record

Observational studyPloS one2021

Clinical correlates of circulating cell-free DNA tumor fraction.

Joerg Bredno, Jafi Lipson, Oliver Venn, Alexander M Aravanis, Arash Jamshidi

Registry-linked trialOpen access · goldAbstract readMulticenter StudyObservational Study
In one paragraph

Observational study in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02889978 (The Circulating Cell-free Genome Atlas Study), which is not on this map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
4.1field-weighted citation impact, top 4% 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.

NCT02889978 unknown statusnot on this map

The Circulating Cell-free Genome Atlas Study

TypeobservationalSponsorGRAIL, Inc.Ran2016 to 2024Enrolled15,254ConditionsNeoplasms, Cancer
3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 64 citations in OpenAlex.

  1. Liquid and Tissue Biopsies for Identifying MET Exon 14 Skipping NSCLC: Analyses from the Phase II VISION Study of Tepotinib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Trial
  2. Modeled Sojourn Time and Sensitivity for Detecting Preclinical Cancers Retrospectively by a Multicancer Early Detection Test.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026
    Article
  3. Clinical and Molecular Correlates of Circulating Tumor Fraction in Patients with Metastatic Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  4. Review
  5. Assessment of methylated BCAT1 and IKZF1 circulating tumor DNA as a prognostic biomarker in esophagogastric adenocarcinomas.Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus · 2026
    Article
  6. Article
  7. Article
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  9. Article
  10. Impact of Population Cancer Risk on the Cost-effectiveness of Multicancer Early Detection Testing in the United States.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025
    Article
  11. Article
  12. ctDNA in Pancreatic Adenocarcinoma: A Critical Appraisal.Current oncology (Toronto, Ont.) · 2025
    Review
  13. Article
  14. Review
  15. Review
  16. Article
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  19. Review
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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

5 authors at 1 institution in 1 country.

Joerg BrednoGRAIL, Inc., Menlo Park, California, United States of America.ORCID 0000-0002-2302-2339
Jafi LipsonGRAIL, Inc., Menlo Park, California, United States of America.
Oliver VennGRAIL, Inc., Menlo Park, California, United States of America.
Alexander M AravanisGRAIL, Inc., Menlo Park, California, United States of America.
Arash JamshidiGRAIL, Inc., Menlo Park, California, United States of America.
Grail (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOncology applications of cell-free DNA analysis are often limited by the amount of circulating tumor DNA and the fraction of cell-free DNA derived from tumor cells in a blood sample. This circulating tumor fraction varies widely between individuals and cancer types. Clinical factors that influence tumor fraction have not been completely elucidated. METHODS AND

findingsCirculating tumor fraction was determined for breast, lung, and colorectal cancer participant samples in the first substudy of the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978; multi-cancer early detection test development) and was related to tumor and patient characteristics. Linear models were created to determine the influence of tumor size combined with mitotic or metabolic activity (as tumor mitotic volume or excessive lesion glycolysis, respectively), histologic type, histologic grade, and lymph node status on tumor fraction. For breast and lung cancer, tumor mitotic volume and excessive lesion glycolysis (primary lesion volume scaled by percentage positive for Ki-67 or PET standardized uptake value minus 1.0, respectively) were the only statistically significant covariates. For colorectal cancer, the surface area of tumors invading beyond the subserosa was the only significant covariate. The models were validated with cases from the second CCGA substudy and show that these clinical correlates of circulating tumor fraction can predict and explain the performance of a multi-cancer early detection test.

conclusionsPrognostic clinical variables, including mitotic or metabolic activity and depth of invasion, were identified as correlates of circulating tumor DNA by linear models that relate clinical covariates to tumor fraction. The identified correlates indicate that faster growing tumors have higher tumor fractions. Early cancer detection from assays that analyze cell-free DNA is determined by circulating tumor fraction. Results support that early detection is particularly sensitive for faster growing, aggressive tumors with high mortality, many of which have no available screening today.

Indexed as

Breast NeoplasmsCirculating Tumor DNAColorectal NeoplasmsFemaleGlycolysisHumansLung NeoplasmsMitosisModels, BiologicalNeoplasmsNeoplasm StagingReproducibility of ResultsCirculating Tumor DNA

Identifiers

PMID34432811
PMCPMC8386888
OpenAlexW3194596778

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.