title: Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients.
abstract: ESSENTIALS: We performed a pooled analysis of 926 patients with cancer-associated incidental pulmonary embolism (IPE). Vitamin K antagonists (VKA) are associated with a higher risk of major hemorrhage. Recurrence risk is comparable after subsegmental and more proximally localized IPE. Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE.
  
  
  BACKGROUND
  Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management.
  
  
  METHODS
  Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed.
  
  
  RESULTS
  In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval [CI] 3.7-8.3%), 4.7% (95% CI 3.0-6.8%), and 37% (95% CI 28-47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio [HR] 0.9; 95% CI 0.3-3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91-7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6-10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50-2.4).
  
  
  CONCLUSIONS
  These results support the current recommendation to anticoagulate cancer-associated IPE with LMWH and argue against different management of subsegmental IPE.
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van der Hulle
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: P L
authors.initials: PL
authors.lastname: den Exter
authors.affiliation: Department of Respiratory and Intensive Care Medicine, Hôpital Européen Georges-Pompidou, Université Paris Descartes, INSERM U 965, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Planquette
authors.affiliation: Department of Respiratory and Intensive Care Medicine, Hôpital Européen Georges-Pompidou, Université Paris Descartes, INSERM U 965, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Meyer
authors.affiliation: Department of Internal Medicine, Hospital Sant Jaume, Olot, Gerona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Soler
authors.affiliation: Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Monreal
authors.affiliation: Respiratory Department, Ramon y Cajal Hospital, IRYCIS and Alcala de Henares University, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Jiménez
authors.affiliation: Respiratory Department, Ramon y Cajal Hospital, IRYCIS and Alcala de Henares University, Madrid, Spain.
authors.forename: A K
authors.initials: AK
authors.lastname: Portillo
authors.affiliation: Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: O'Connell
authors.affiliation: Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Liebman
authors.affiliation: Pulmonology Institute, Faculty of Medicine, Carmel Medical Center, Technion, Israel Institute of Technology, Haifa, Israel.|CF Center, Faculty of Medicine, Carmel Medical Center, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Shteinberg
authors.affiliation: Pulmonology Institute, Faculty of Medicine, Carmel Medical Center, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Adir
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Tiseo
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bersanelli
authors.affiliation: Department of Internal Medicine and Department of Radiology, King Hussein Cancer Center, Amman, Jordan.
authors.forename: H N
authors.initials: HN
authors.lastname: Abdel-Razeq
authors.affiliation: Department of Internal Medicine and Department of Radiology, King Hussein Cancer Center, Amman, Jordan.
authors.forename: A H
authors.initials: AH
authors.lastname: Mansour
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds and St James' Institute of Oncology, Leeds, UK.
authors.forename: O G
authors.initials: OG
authors.lastname: Donnelly
authors.affiliation: St James' Institute of Oncology, Leeds, UK.
authors.forename: G
authors.initials: G
authors.lastname: Radhakrishna
authors.affiliation: St James' Institute of Oncology, Leeds, UK.
authors.forename: S
authors.initials: S
authors.lastname: Ramasamy
authors.affiliation: Queen's Centre for Oncology and Haematology, Castle Hill Hospital, Hull and East Yorkshire Hospitals NHS Trust, Cottingham, UK.
authors.forename: G
authors.initials: G
authors.lastname: Bozas
authors.affiliation: Queen's Centre for Oncology and Haematology, Castle Hill Hospital, Hull and East Yorkshire Hospitals NHS Trust and Hull York Medical School, Cottingham, UK.
authors.forename: A
authors.initials: A
authors.lastname: Maraveyas
authors.affiliation: Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Shinagare
authors.affiliation: Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hatabu
authors.affiliation: Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nishino
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: M V
authors.initials: MV
authors.lastname: Huisman
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: F A
authors.initials: FA
authors.lastname: Klok
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000150:complications* / Q000175:diagnosis / Q000517:prevention & control; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D011655:Pulmonary Embolism / Q000150:complications* / Q000175:diagnosis; D012008:Recurrence; D012042:Registries; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000150:complications* / Q000175:diagnosis; D014812:Vitamin K / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014812:Vitamin K
keywords: hemorrhage; incidental finding; prognosis; pulmonary embolism; venous thromboembolism