Nick van Es, MD; Grégoire Le Gal, MD, PhD; Hans-Martin Otten, MD, PhD; Philippe Robin, MD, PhD; Andrea Piccioli, MD, PhD; Ramón Lecumberri, MD, PhD; Luis Jara-Palomares, MD; Piotr Religa, MD, PhD; Virginie Rieu, MD; Matthew Rondina, MD; Mariëlle M. Beckers, MD, PhD; Paolo Prandoni, MD, PhD; Pierre-Yves Salaun, MD, PhD; Marcello Di Nisio, MD, PhD; Patrick M. Bossuyt, PhD; Harry R. Büller, MD, PhD; Marc Carrier, MD
Acknowledgment: The authors thank Dr. Noémie Kraaijpoel (Academic Medical Center, Amsterdam, the Netherlands) for her help in performing the risk-of-bias assessment.
Disclosures: Dr. Le Gal reports grants from Portola Pharmaceuticals; was a co-investigator for trials conducted by Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, Leo Pharma, Daiichi Sankyo, and Bayer; and received honoraria from Bayer, Pfizer, GlaxoSmithKline, Leo Pharma, Sanofi, and bioMérieux, outside the submitted work. Dr. Jara-Palomares reports personal fees from Bayer Hispania, Actelion, Rovi, Pfizer, Menarini, and Leo Pharma outside the submitted work. Dr. Salaun reports a PHRC-K grant from the French Health Ministry during the conduct of the study. Dr. Di Nisio reports consulting fees from Bayer and Daiichi Sankyo outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0868.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Available at BMJ Open (http://bmjopen.bmj.com/content/7/6/e015562.long). Statistical code: Available from Dr. van Es (e-mail, firstname.lastname@example.org). Data set: The authors are open to sharing data. Requests may be sent to Dr. Carrier (e-mail, email@example.com) and will be discussed with all authors.
Requests for Single Reprints: Marc Carrier, MD, Ottawa Hospital Research Institute, University of Ottawa, Ottawa Hospital General Campus, 501 Smyth Road, Box 201a, Ottawa, Ontario K1H 8L6, Canada; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. van Es and Büller: Academisch Medisch Centrum, Afdeling Vasculaire Geneeskunde, Room F4-136, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
Drs. Le Gal and Carrier: Ottawa Hospital Research Institute, University of Ottawa, Ottawa Hospital General Campus, 501 Smyth Road, Box 201a, Ottawa, Ontario K1H 8L6, Canada.
Dr. Otten: MC Slotervaart, Afdeling Interne Geneeskunde, Louwesweg 6, 1066 EC, Amsterdam, the Netherlands.
Drs. Robin and Salaun: Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, 2 Avenue Foch, 29609, Brest, France.
Drs. Piccioli and Prandoni: Department of Medicine, University Hospital of Padua, Via Giustiniani 2, 35128 Padova, Italy.
Dr. Lecumberri: Hematology Service, Clinica Universidad de Navarra, Avenida de Pío XII, 36, 31008 Pamplona, Navarra, Spain.
Dr. Jara-Palomares: Medical Surgical Unit of Respiratory Diseases, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, 41013 Sevilla, Spain.
Dr. Religa: Department of Medicine, Karolinska Institutet, Solnavägen 1, 171 77 Solna, Sweden.
Dr. Rieu: Department of Internal Medicine, Centre Hospitalo-Universitaire Estaing, 1 Rue Lucie Aubrac, 63100 Clermont-Ferrand, France.
Dr. Rondina: Division of General Internal Medicine, University of Utah Hospital, 50 North Medical Drive, Salt Lake City, UT 84132.
Dr. Beckers: Afdeling Hematologie, UZ Leuven, Herestraat 49, 3000 Leuven, Belgium.
Dr. Di Nisio: Department of Medicine and Ageing Sciences, University G. D'Annunzio, Via dei Vestini, 31, 66100 Chieti CH, Italy.
Dr. Bossuyt: Academisch Medisch Centrum, Afdeling Klinische Epidemiologie, Biostatistiek en Bioinformatica, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
Author Contributions: Conception and design: N. van Es, G. Le Gal, H.-M. Otten, M. Di Nisio, P.M. Bossuyt, H.R. Büller, M. Carrier.
Analysis and interpretation of the data: N. van Es, G. Le Gal, P. Robin, A. Piccioli, R. Lecumberri, P. Religa, M. Rondina, P.-Y. Salaun, M. Di Nisio, P.M. Bossuyt, H.R. Büller, M. Carrier.
Drafting of the article: N. van Es, G. Le Gal, L. Jara-Palomares, H.R. Büller, M. Carrier.
Critical revision for important intellectual content: H.-M. Otten, P. Robin, A. Piccioli, R. Lecumberri, L. Jara-Palomares, P. Religa, M. Rondina, M.M. Beckers, P. Prandoni, P.-Y. Salaun, M. Di Nisio, P.M. Bossuyt, M. Carrier.
Final approval of the article: N. van Es, G. Le Gal, H.-M. Otten, P. Robin, A. Piccioli, R. Lecumberri, L. Jara-Palomares, P. Religa, V. Rieu, M. Rondina, M.M. Beckers, P. Prandoni, P.-Y. Salaun, M. Di Nisio, P.M. Bossuyt, H.R. Büller, M. Carrier.
Provision of study materials or patients: R. Lecumberri, L. Jara-Palomares, V. Rieu, P. Prandoni.
Statistical expertise: N. van Es, P.M. Bossuyt.
Obtaining of funding: P. Religa, M. Rondina.
Administrative, technical, or logistic support: N. van Es, M. Rondina, M. Carrier.
Collection and assembly of data: N. van Es, G. Le Gal, H.-M. Otten, P. Robin, A. Piccioli, R. Lecumberri, L. Jara-Palomares, P. Religa, M. Rondina, M.M. Beckers, P.-Y. Salaun, M. Carrier.
Screening for cancer in patients with unprovoked venous thromboembolism (VTE) often is considered, but clinicians need precise data on cancer prevalence, risk factors, and the effect of different types of screening strategies.
To estimate the prevalence of occult cancer in patients with unprovoked VTE, including in subgroups of different ages or those that have had different types of screening.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to 19 January 2016.
Prospective studies evaluating cancer screening strategies in adults with unprovoked VTE that began enrolling patients after 1 January 2000 and had at least 12 months of follow-up.
2 investigators independently reviewed abstracts and full-text articles and independently assessed risk of bias.
10 eligible studies were identified. Individual data were obtained for all 2316 patients. Mean age was 60 years; 58% of patients received extensive screening. The 12-month period prevalence of cancer after VTE diagnosis was 5.2% (95% CI, 4.1% to 6.5%). The point prevalence of cancer was higher in patients who had extensive screening than in those who had more limited screening initially (odds ratio [OR], 2.0 [CI, 1.2 to 3.4]) but not at 12 months (OR, 1.4 [CI, 0.89 to 2.1]). Cancer prevalence increased linearly with age and was 7-fold higher in patients aged 50 years or older than in younger patients (OR, 7.1 [CI, 3.1 to 16]).
Variation in patient characteristics and extensive screening strategies; unavailability of long-term mortality data.
Occult cancer is detected in 1 in 20 patients within a year of receiving a diagnosis of unprovoked VTE. Older age is associated with a higher cancer prevalence. Although an extensive screening strategy initially may detect more cancer cases than limited screening, whether this translates into improved patient outcomes remains unclear.
None. (PROSPERO: CRD42016033371)
Nick van Es, Grégoire Le Gal, Hans-Martin Otten, Philippe Robin, Andrea Piccioli, Ramón Lecumberri, et al. Screening for Occult Cancer in Patients With Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis of Individual Patient Data. Ann Intern Med. 2017;167:410–417. doi: 10.7326/M17-0868
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Published: Ann Intern Med. 2017;167(6):410-417.
Published at www.annals.org on 22 August 2017
Hematology/Oncology, Hospital Medicine, Venous Thromboembolism.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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