Evidence map›Paper›PMID 36208697›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2023

Prognostic value of plasma circulating tumor DNA fraction across four common cancer types: a real-world outcomes study.

Z R Reichert, T M Morgan, G Li, E Castellanos, T Snow, F G Dall'Olio, R W Madison, A D Fine, G R Oxnard, R P Graf and 1 more

Abstract read
In one paragraph

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed, 3 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

125 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Tissue-Free Circulating Tumor DNA Assay and Patient Outcome in a Phase III Trial of FOLFOX-Based Adjuvant Chemotherapy (Alliance N0147).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
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  8. 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
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  12. Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Trial
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  14. Article
  15. Applications of circulating tumor DNA in unresectable and advanced non-small cell lung cancer immunotherapy: from stratification to therapeutic guidance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  16. Role of ctDNA Tumor Fraction in Selecting Immunotherapy-Based Regimens in Advanced Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  17. Article
  18. Article
  19. Review
  20. Article

65 more citing papers are in PubMed but not listed here.

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

11 authors.

Z R ReichertUniversity of Michigan, Ann Arbor, USA.
T M MorganUniversity of Michigan, Ann Arbor, USA.
G LiFoundation Medicine, Cambridge, USA.
E CastellanosFlatiron Health, New York, USA.
T SnowFlatiron Health, New York, USA.
F G Dall'OlioGustave Roussy, Villejuif, France; University of Bologna, Bologna, Italy.
R W MadisonFoundation Medicine, Cambridge, USA.
A D FineFoundation Medicine, Cambridge, USA.
G R OxnardFoundation Medicine, Cambridge, USA.
R P GrafFoundation Medicine, Cambridge, USA.
D G StoverThe Ohio State University, Columbus, USA. Electronic address: Daniel.stover@osumc.edu.

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
Assay Validation of Cell-Free DNA Shallow Whole Genome Sequencing To Determine 'Tumor Fraction' in Advanced CancersUH3CA239105 · NCI · BROAD INSTITUTE, INC. · PI ADALSTEINSSON, VIKTOR, LENNON, NIALL JOHN · 2022 to 2024
$762k
Assay Validation of Cell-Free DNA Shallow Whole Genome Sequencing To Determine 'Tumor Fraction' in Advanced CancersUH2CA239105 · NCI · BROAD INSTITUTE, INC. · PI ADALSTEINSSON, VIKTOR, LENNON, NIALL JOHN · 2020 to 2021
$321k
NCI NIH HHS P30 CA016058NCI NIH HHS UH2 CA239105NCI NIH HHS UH3 CA239105
6 · The paper itself

Abstract

backgroundGenomic analysis of circulating tumor DNA (ctDNA) is increasingly incorporated into the clinical management of patients with advanced cancer. Beyond tumor profiling, ctDNA analysis also can enable calculation of circulating tumor fraction (TF), which has previously been found to be prognostic. While most prognostic models in metastatic cancer are tumor type specific and require significant patient-level data, quantification of TF in ctDNA has the potential to serve as a pragmatic, tumor-agnostic prognostic tool. PATIENTS AND

methodsThis study utilized a cohort of patients in a nationwide de-identified clinico-genomic database with metastatic castration-resistant prostate cancer (mCRPC), metastatic breast cancer (mBC), advanced non-small-cell lung cancer (aNSCLC), or metastatic colorectal cancer (mCRC) undergoing liquid biopsy testing as part of routine care. TF was calculated based on single-nucleotide polymorphism aneuploidy across the genome. Clinical, disease, laboratory, and treatment data were captured from the electronic health record. Overall survival (OS) was evaluated by TF level while controlling for relevant covariables.

resultsA total of 1725 patients were included: 198 mCRPC, 402 mBC, 902 aNSCLC, and 223 mCRC. TF ≥10% was highly correlated with OS in univariable analyses for all cancer types: mCRPC [hazard ratio (HR) 3.3, 95% confidence interval (CI) 2.04-5.34, P < 0.001], mBC (HR 2.4, 95% CI 1.71-3.37, P < 0.001), aNSCLC (HR 1.68, 95% CI 1.34-2.1, P < 0.001), and mCRC (HR 2.11, 95% CI 1.39-3.2, P < 0.001). Multivariable assessments of TF had similar point estimates and CIs, suggesting a consistent and independent association with survival. Exploratory analysis showed that TF remained consistently prognostic across a wide range of cutpoints.

conclusionsPlasma ctDNA TF is a pragmatic, independent prognostic biomarker across four advanced cancers with potential to guide clinical conversations around expected treatment outcomes. With further prospective validation, ctDNA TF could be incorporated into care paradigms to enable precision escalation and de-escalation of cancer therapy based on patient-level tumor biology.

Indexed as

Breast NeoplasmsCarcinoma, Non-Small-Cell LungCirculating Tumor DNALung NeoplasmsProstatic Neoplasms, Castration-ResistantBiomarkers, TumorFemaleHumansMalePrognosisBiomarkers, TumorCirculating Tumor DNAbreast cancercolorectal cancernon-small-cell lung cancerprognosisprostate cancertumor fraction

Identifiers

PMID36208697
PMCPMC9805517

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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.