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

Autor:	Mulder FI; Amsterdam 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. Electronic address: f.i.mulder@amsterdamumc.nl., Kraaijpoel N; Amsterdam UMC location University of Amsterdam, Department of Vascular Medicine, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam, the Netherlands., Carrier M; Department of Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., Guman NA; Amsterdam 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., Jara-Palomares L; Medical Surgical Unit of Respiratory Diseases, Virgen del Rocio Hospital, Seville, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain., Di Nisio M; Department of Medicine and Ageing Sciences, Gabriele D'Annunzio University, Chieti, Italy., Ageno W; Department of Medicine and Surgery, University of Insubria, Varese, Italy., Beyer-Westendorf J; Thrombosis Research Unit, Department of Medicine I, Division Hematology, University Hospital 'Carl Gustav Carus,' Dresden, Germany., Klok FA; Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands., Vanassche T; Department of Cardiovascular Sciences, University Hospitals Leuven, Leuven, Belgium., Otten HB; Department of Internal Medicine, Meander Medisch Centrum, Amersfoort, the Netherlands., Cosmi B; Department of Angiology and Blood Coagulation, S. Orsola-Malpighi University Hospital, IRCSS -University of Bologna, Bologna, Italy., Wolde MT; Department of Internal Medicine, Flevo Hospital, Almere, the Netherlands., In 't Veld SGJG; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, Amsterdam, the Netherlands; Cancer Center Amsterdam and Liquid Biopsy Center, Amsterdam, the Netherlands; Brain Tumor Center Amsterdam, Amsterdam, the Netherlands., Post E; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, Amsterdam, the Netherlands; Cancer Center Amsterdam and Liquid Biopsy Center, Amsterdam, the Netherlands; Brain Tumor Center Amsterdam, Amsterdam, the Netherlands., Ramaker J; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, Amsterdam, the Netherlands; Cancer Center Amsterdam and Liquid Biopsy Center, Amsterdam, the Netherlands; Brain Tumor Center Amsterdam, Amsterdam, the Netherlands., Zwaan K; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, Amsterdam, the Netherlands; Cancer Center Amsterdam and Liquid Biopsy Center, Amsterdam, the Netherlands; Brain Tumor Center Amsterdam, Amsterdam, the Netherlands., Peters M; Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands., Delluc A; Department of Medicine, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., Kamphuisen PW; Amsterdam UMC location University of Amsterdam, Department of Vascular Medicine, Amsterdam, the Netherlands; Department of Internal Medicine, Tergooi Hospital, Hilversum, the Netherlands., Sanchez-Lopez V; Medical Surgical Unit of Respiratory Diseases, Virgen del Rocio Hospital, Seville, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain., Porreca E; Department of Innovative Technologies in Medicine and Dentistry, University 'G. d'Annunzio' of Chieti-Pescara, Chieti, Italy., Bossuyt PMM; Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Büller HR; Amsterdam UMC location University of Amsterdam, Department of Vascular Medicine, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam, the Netherlands., Wurdinger T; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, Amsterdam, the Netherlands; Cancer Center Amsterdam and Liquid Biopsy Center, Amsterdam, the Netherlands; Brain Tumor Center Amsterdam, Amsterdam, the Netherlands., Best MG; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, Amsterdam, the Netherlands; Cancer Center Amsterdam and Liquid Biopsy Center, Amsterdam, the Netherlands; Brain Tumor Center Amsterdam, Amsterdam, the Netherlands., van Es N; Amsterdam UMC location University of Amsterdam, Department of Vascular Medicine, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2023 Apr; Vol. 21 (4), pp. 905-916. Date of Electronic Publication: 2023 Jan 11.
DOI:	10.1016/j.jtha.2023.01.003
Abstrakt:	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. Competing Interests: Declaration of competing interests N.K., F.I.M., N.A.G., M.t.W., H.-M.B.O., S.G.J.G.I.t.V., E.P., V.S.-L., K.Z., J.R., P.M.M.B., and E.P. report no conflicts of interest. M.C. has received research funding from BMS, Pfizer, and LEO Pharma. He has also received Honoria from Bayer, BMS, Pfizer, Servier, and LEO Pharma. A.D. has received research funding from BMS-Pfizer and Honoria from Bayer, BMS-Pfizer, Servier, and LEO Pharma. T.W. is an inventor on relevant patent applications, received funding from Illumina Inc, and is a shareholder of GRAIL, Inc. L.J.-P. has received research funding from LEO Pharma and MSD. He has also received honoraria from Bayer Hispania, Actelion, Pfizer, Rovi, LEO Pharma, Menarini, and MSD. P.W.K. has received research grants from Daiichi Sankyo and Roche Diagnostics M.D.N. has received research funding from LEO Pharma and honoraria and consultancy fees from Daiichi Sankyo, Bayer, BMS-Pfizer, Sanofi, and LEO Pharma outside the submitted work. M.G.B. is an inventor on relevant patent applications. W.A. has received research funding from Bayer and honoraria from Bayer, BMS-Pfizer, Aspen, Sanofi, Janssen, Werfen, LEO Pharma, and Portola. J.B.-W. has received research funding from Bayer, Daiichi Sankyo, Pfizer, and Portola/Alexion. He has also received Honoria from Bayer, Daiichi Sankyo, Pfizer, and Portola/Alexion. T.V. has served as a speaker and/or advisor for Boehringer Ingelheim, Daiichi Sankyo, BMS/Pfizer, Bayer, Sanofi, and LEO Pharma. F.A.K. has received research grants from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Daiichi Sankyo, Actelion, the Dutch thrombosis association, and the Dutch Heart foundation. B.C. has received speakers’ fees from Daiichi Sankyo and Sanofi. H.B. reports personal fees from Daiichi Sankyo, Bayer Healthcare, BMS/Pfizer, Boehringer Ingelheim, Portola, Medscape, Eli Lilly, Sanofi Aventis, and Ionis. N.v.E. has received advisory board honoraria from Daiichi Sankyo, Bayer, and LEO Pharma which were transferred to his institute. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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