Platelet RNA sequencing for cancer screening in patients with unprovoked venous thromboembolism: a prospective cohort study

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Frits I Mulder - , Amsterdam University Medical Centers (UMC) (Author)
  • Noémie Kraaijpoel - , Amsterdam University Medical Centers (UMC) (Author)
  • Marc Carrier - , Ottawa Hospital Research Institute (Author)
  • Noori A Guman - , Amsterdam University Medical Centers (UMC) (Author)
  • Luis Jara-Palomares - , Hospital Universitario Virgen del Rocio (Author)
  • Marcello Di Nisio - , University "G. d'Annunzio" of Chieti-Pescara (Author)
  • Walter Ageno - , University of Insubria (Author)
  • Jan Beyer-Westendorf - , Department of internal Medicine I, Unit of Thrombosis Research, Division of Hematology and Hemostasis, University Hospital Carl Gustav Carus Dresden (Author)
  • Frederikus A Klok - , Leiden University (Author)
  • Thomas Vanassche - , University Hospitals Leuven (Author)
  • Hans-Martin B Otten - , Erasmus University Medical Center (Author)
  • Benilde Cosmi - , Institute of Neurological Sciences of Bologna (Author)
  • Marije Ten Wolde - , Flevo Hospital (Author)
  • Sjors G J G In 't Veld - , Amsterdam University Medical Centers (UMC) (Author)
  • Edward Post - , Amsterdam University Medical Centers (UMC) (Author)
  • Jip Ramaker - , Amsterdam University Medical Centers (UMC) (Author)
  • Kenn Zwaan - , Amsterdam University Medical Centers (UMC) (Author)
  • Mike Peters - , University Medical Center (UMC) Utrecht (Author)
  • Aurélien Delluc - , Ottawa Hospital Research Institute (Author)
  • Pieter W Kamphuisen - , Amsterdam University Medical Centers (UMC) (Author)
  • Veronica Sanchez-Lopez - , Hospital Universitario Virgen del Rocio (Author)
  • Ettore Porreca - , University "G. d'Annunzio" of Chieti-Pescara (Author)
  • Patrick M M Bossuyt - , University of Amsterdam (Author)
  • Harry R Büller - , Amsterdam University Medical Centers (UMC) (Author)
  • Thomas Wurdinger - , Amsterdam University Medical Centers (UMC) (Author)
  • Myron G Best - , Amsterdam University Medical Centers (UMC) (Author)
  • Nick van Es - , Amsterdam University Medical Centers (UMC) (Author)

Abstract

BACKGROUND: Platelet RNA sequencing has been shown to accurately detect cancer in previous studies.

OBJECTIVES: To compare the diagnostic accuracy of platelet RNA sequencing with standard-of-care limited cancer screening in patients with unprovoked venous thromboembolism (VTE).

METHODS: Patients aged ≥40 years with unprovoked VTE were recruited at 13 centers and followed for 12 months for cancer. Participants underwent standard-of-care limited cancer screening, and platelet RNA sequencing analysis was performed centrally at study end for cases and selected controls. Sensitivity and specificity were calculated, using the predefined primary positivity threshold of 0.54 for platelet RNA sequencing aiming at 86% test sensitivity, and an additional predefined threshold of 0.89 aiming at 99% test specificity.

RESULTS: A total of 476 participants were enrolled, of whom 25 (5.3%) were diagnosed with cancer during 12-month follow-up. For each cancer patient, 3 cancer-free patients were randomly selected for the analysis. The sensitivity of limited screening was 72% (95% CI, 52-86) at a specificity of 91% (95% CI, 82-95). The area under the receiver operator characteristic for platelet RNA sequencing was 0.54 (95% CI, 0.41-0.66). At the primary positivity threshold, all patients had a positive test, for a sensitivity estimated at 100% (95% CI, 87-99) and a specificity of 8% (95% CI, 3.7-16.4). At the secondary threshold, sensitivity was 68% (95% CI, 48-83; p value compared with limited screening 0.71) at a specificity of 36% (95% CI, 26-47).

CONCLUSION: Platelet RNA sequencing had poor diagnostic accuracy for detecting occult cancer in patients with unprovoked VTE with the current algorithm.

Details

Original languageEnglish
Pages (from-to)905-916
Number of pages12
JournalJournal of Thrombosis and Haemostasis
Volume21
Issue number4
Publication statusPublished - Apr 2023
Peer-reviewedYes

External IDs

Scopus 85150953168

Keywords

Sustainable Development Goals

Keywords

  • Humans, Venous Thromboembolism/diagnosis, Early Detection of Cancer, Prospective Studies, Neoplasms/complications, Neoplasms, Unknown Primary/complications, Sequence Analysis, RNA, Risk Factors