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Published on: February 13, 2013
Platelet RNA sequencing for cancer screening in patients with unprovoked venous thromboembolism: a prospective cohort
Frits I Mulder1, Noémie Kraaijpoel2, Marc Carrier3
1Amsterdam UMC location University of Amsterdam, Department of Vascular Medicine, Amsterdam, the Netherlands; Department of Internal Medicine, Tergooi Hospital, Hilversum, the Netherlands; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam, the Netherlands.
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.

