Evidence map›Paper›PMID 36534496›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2023

Metastatic Colorectal Cancer Treatment Response Evaluation by Ultra-Deep Sequencing of Cell-Free DNA and Matched White Blood Cells.

Iris van 't Erve, Jamie E Medina, Alessandro Leal, Eniko Papp, Jillian Phallen, Vilmos Adleff, Elaine Jiayuee Chiao, Adith S Arun, Karen Bolhuis, John K Simmons and 9 more

Abstract readClinical Trial, Phase III
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–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. Trial
  2. plasmaCHORD: A Machine Learning Approach to Distinguish Clonal Hematopoiesis-Derived Variants in Liquid Biopsies from Patients with Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  3. Review
  4. Novel Liquid Biopsy in Gastrointestinal Cancers.Journal of gastroenterology and hepatology · 2026
    Review
  5. Review
  6. Review
  7. Review
  8. Characterization of Plasma Cell-Free DNA Variants as of Tumor or Clonal Hematopoiesis Origin in 16,812 Advanced Cancer Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
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  20. Article
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

19 authors.

Iris van 't Erve *Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.ORCID 0000-0003-3667-9185
Jamie E Medina *Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0002-6124-0548
Alessandro LealSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0001-7967-3213
Eniko PappPersonal Genome Diagnostics, Baltimore, Maryland.ORCID 0000-0002-9022-7238
Jillian PhallenSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0002-5492-9013
Vilmos AdleffSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0002-5001-1766
Elaine Jiayuee ChiaoSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0002-2275-9080
Adith S ArunSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0003-3675-9521
Karen BolhuisDepartment of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0001-5196-1790
John K SimmonsPersonal Genome Diagnostics, Baltimore, Maryland.ORCID 0000-0003-4691-6770
Aanavi KarandikarPersonal Genome Diagnostics, Baltimore, Maryland.ORCID 0000-0001-9995-0150
Kenneth C ValkenburgPersonal Genome Diagnostics, Baltimore, Maryland.ORCID 0000-0003-3858-1923
Mark SausenPersonal Genome Diagnostics, Baltimore, Maryland.ORCID 0000-0002-2916-5269
Samuel V AngiuoliPersonal Genome Diagnostics, Baltimore, Maryland.ORCID 0000-0001-9525-4350
Robert B ScharpfSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0003-4702-2656
Cornelis J A PuntDepartment of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0003-4196-4896
Gerrit A MeijerDepartment of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.ORCID 0000-0003-0330-3130
Victor E VelculescuSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0003-1195-438X
Remond J A FijnemanDepartment of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.ORCID 0000-0003-2076-5521

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
ECOG-ACRIN Thoracic Malignancies Integrated Translational Science CenterUG1CA233259 · NCI · EMORY UNIVERSITY · PI CARBONE, DAVID P., LEAL, TICIANA · 2019 to 2025
$5.1M
Large-Scale Genetic Analyses of Human CancerR01CA121113 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANAGNOSTOU, VALSAMO, VELCULESCU, VICTOR E. · 2006 to 2022
$4.3M
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA121113NCI NIH HHS UG1 CA233259
6 · The paper itself

Abstract

purposeCirculating tumor DNA (ctDNA) has the potential to guide therapy selection and monitor treatment response in patients with metastatic cancer. However, germline and clonal hematopoiesis-associated alterations can confound identification of tumor-specific mutations in cell-free DNA (cfDNA), often requiring additional sequencing of tumor tissue. The current study assessed whether ctDNA-based treatment response monitoring could be performed in a tumor tissue-independent manner by combining ultra-deep targeted sequencing analyses of cfDNA with patient-matched white blood cell (WBC)-derived DNA. EXPERIMENTAL

designIn total, 183 cfDNA and 49 WBC samples, along with 28 tissue samples, from 52 patients with metastatic colorectal cancer participating in the prospective phase III CAIRO5 clinical trial were analyzed using an ultra-deep targeted sequencing liquid biopsy assay.

resultsThe combined cfDNA and WBC analysis prevented false-positives due to germline or hematopoietic variants in 40% of patients. Patient-matched tumor tissue sequencing did not provide additional information. Longitudinal analyses of ctDNA were more predictive of overall survival than standard-of-care radiological response evaluation. ctDNA mutations related to primary or acquired resistance to panitumumab were identified in 42% of patients.

conclusionsAccurate calling of ctDNA mutations for treatment response monitoring is feasible in a tumor tissue-independent manner by combined cfDNA and patient-matched WBC genomic DNA analysis. This tissue biopsy-independent approach simplifies sample logistics and facilitates the application of liquid biopsy ctDNA testing for evaluation of emerging therapy resistance, opening new avenues for early adaptation of treatment regimens.

Indexed as

Cell-Free Nucleic AcidsCirculating Tumor DNAColonic NeoplasmsRectal NeoplasmsBiomarkers, TumorDNA, NeoplasmHigh-Throughput Nucleotide SequencingHumansMutationProspective StudiesBiomarkers, TumorCell-Free Nucleic AcidsCirculating Tumor DNADNA, Neoplasm

Identifiers

PMID36534496
PMCPMC9975664

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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.