TY - JOUR
T1 - Platelet RNA sequencing for cancer screening in patients with unprovoked venous thromboembolism
T2 - a prospective cohort study
AU - Mulder, Frits I
AU - Kraaijpoel, Noémie
AU - Carrier, Marc
AU - Guman, Noori A
AU - Jara-Palomares, Luis
AU - Di Nisio, Marcello
AU - Ageno, Walter
AU - Beyer-Westendorf, Jan
AU - Klok, Frederikus A
AU - Vanassche, Thomas
AU - Otten, Hans-Martin B
AU - Cosmi, Benilde
AU - Wolde, Marije Ten
AU - In 't Veld, Sjors G J G
AU - Post, Edward
AU - Ramaker, Jip
AU - Zwaan, Kenn
AU - Peters, Mike
AU - Delluc, Aurélien
AU - Kamphuisen, Pieter W
AU - Sanchez-Lopez, Veronica
AU - Porreca, Ettore
AU - Bossuyt, Patrick M M
AU - Büller, Harry R
AU - Wurdinger, Thomas
AU - Best, Myron G
AU - van Es, Nick
N1 - Funding Information: Funding information This investigator-initiated study received a research grant from the Dutch Thrombosis Foundation (nr: 2017-02), Tergooi Academy (Tergooi Hospital), and CanVECTOR (pilot trial grant, nr: 2017-01). These funders had no role in the design of the study, nor in the data collection, analyses, writing of the manuscript, or in the decision to submit the article for publication. Funding Information: This investigator-initiated study received a research grant from the Dutch Thrombosis Foundation (nr: 2017-02) and CanVECTOR (pilot trial grant, nr: 2017-01). The funders had no role in the design of the study, nor in the data collection, analyses, writing of the manuscript, or in the decision to submit the article for publication. Publisher Copyright: © 2023 The Authors
PY - 2023/4/1
Y1 - 2023/4/1
N2 - 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.
AB - 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.
KW - blood platelets
KW - early detection of cancer
KW - neoplasms
KW - thrombosis
KW - tumor biomarkers
KW - venous thromboembolism
UR - http://www.scopus.com/inward/record.url?scp=85150953168&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85150953168&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36841648
U2 - https://doi.org/10.1016/j.jtha.2023.01.003
DO - https://doi.org/10.1016/j.jtha.2023.01.003
M3 - Article
C2 - 36841648
SN - 1538-7933
VL - 21
SP - 905
EP - 916
JO - Journal of thrombosis and haemostasis : JTH
JF - Journal of thrombosis and haemostasis : JTH
IS - 4
ER -