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Thromb Haemost 2022; 122(04): 633-645
DOI: 10.1055/a-1548-4847
Stroke, Systemic or Venous Thromboembolism

Patterns of Thromboembolism in Patients with Advanced Pancreatic Cancer Undergoing First-Line Chemotherapy with FOLFIRINOX or Gemcitabine/nab-Paclitaxel

Jakob M. Riedl‡   *
1   Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Esther Schwarzenbacher‡   *
1   Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Florian Moik
2   Division of Hematology and Hemostaseology, Department of Medicine I and Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
,
Lena Horvath
3   Department of Internal Medicine V: Hematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria
,
Antonia Gantschnigg
4   Department of Surgery, Paracelsus Medical University, Salzburg, Austria
,
Felix Renneberg
5   IIIrd Medical Department of Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectious Disease, Salzburg Cancer Research Institute, Paracelsus Medical University, Salzburg, Austria
,
Florian Posch
1   Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Dominik A. Barth
1   Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Michael Stotz
1   Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Martin Pichler
1   Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Stefan Hatzl
6   Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Simon Fandler-Höfler 
7   Department of Neurology, Medical University of Graz, Austria
,
Paul Gressenberger 
8   Division of Angiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Thomas Gary
8   Division of Angiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Philipp J. Jost
1   Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Richard Greil
5   IIIrd Medical Department of Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectious Disease, Salzburg Cancer Research Institute, Paracelsus Medical University, Salzburg, Austria
,
Cihan Ay
2   Division of Hematology and Hemostaseology, Department of Medicine I and Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
9   I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
,
Angela Djanani
10   Department of Internal Medicine I, Gastroenterology, Hepatology, Metabolism and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
,
Armin Gerger
1   Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Konstantin Schlick
5   IIIrd Medical Department of Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectious Disease, Salzburg Cancer Research Institute, Paracelsus Medical University, Salzburg, Austria
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Abstract

Introduction Recent advances in prophylactic anticoagulation and antineoplastic treatment for advanced pancreatic cancer (aPC) warrant an updated reassessment of thromboembolic risk in this population. This multicenter retrospective cohort study aims to comprehensively characterize incidence, risk factors, and outcomes of venous (VTE) and arterial thromboembolism (ATE) in homogenously treated patients with aPC.

Methods Four hundred and fifty-five patients with aPC undergoing palliative first-line chemotherapy (Gemcitabine/nab-Paclitaxel (GN) or FOLIRINOX) were included. Primary outcomes were objectively confirmed VTE and/or ATE.

Results Over a median follow-up of 26 months, 86 VTE (cumulative incidence: 20.0%; 95% confidence interval [CI]: 16.3–24.0) and 11 ATE events (cumulative incidence: 2.8%; 95% CI: 1.5–4.9) were observed. VTE diagnosis was associated with increased mortality (transition hazard ratio [THR]: 1.59 [95% CI: 1.21–2.09]) and increased risk of cancer progression (THR: 1.47 [95% CI: 1.08–2.01]), while the impact of ATE on mortality was numerically but not statistically significant (THR: 1.85 [95% CI: 0.87–3.94]). The strongest predictor of increased VTE risk was history of cancer-associated VTE (subdistribution hazard ratio [SHR]: 3.29 [95% CI: 2.09–5.18]), while the Khorana score (SHR: 0.78 [0.57–1.06]) failed to predict VTE risk. A history of cerebrovascular disease was associated with markedly increased ATE risk (SHR: 22.05 [95% CI: 6.83–71.22], p < 0.001), especially ischemic stroke. Risk of VTE/ATE did not significantly differ according to type of first-line chemotherapy.

Conclusion Patients with aPC undergoing palliative first-line chemotherapy with FOLFIRINOX or GN face a high risk for VTE/ATE and its diagnosis is linked to worse clinical outcomes. VTE-risk prediction models have limited ability to sub-stratify thrombotic events in this high-risk scenario.

Keywords

arterial thromboembolism - venous thromboembolism - pancreatic cancer

Ethics Approval and Consent to Participate

The study was approved by the Institutional Review Board of the Medical University of Graz, Austria; document number 31–035 ex 18/19. Written informed consent was not obtained from individual patients, because this is not mandated in Austria for retrospective database studies given approval by an ethics committee. Patients were neither involved in the design or conduct of this study, nor in the writing of this manuscript.


Availability of Data and Materials

All data generated or analyzed during this study are included in this published article (and its Supplementary Information files). Statistical analysis code is available on request from F.M. The dataset analyzed during the current study cannot be shared under the current protocol and ethics committee approval.


Author Contributions

The lead author (J.M.R.) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported and that no important aspects of the study have been omitted.Conceived and designed the study: J.M.R., E.S., F.M., A.D., A.G., and K.S. Collected data and contributed patients: J.M.R., E.S., L.H., A.G., F.R., F.P., D.A.B., M.S., M.P., P.G., T.G., P.J.J., R.G., A.D., A.G., and K.S. Performed all statistical analyses: F.M. and F.P. Interpreted the results: all authors. Wrote the first draft of the manuscript: J.M.R., E.S., and F.M. Contributed to the writing of the manuscript: all authors. Agree with the manuscript's results and conclusions: all authors. ICMJE criteria for authorship read and met: all authors.


* These authors contributed equally to this work.


Supplementary Material



Publication History

Received: 14 March 2021

Accepted: 10 July 2021

Accepted Manuscript online:
12 July 2021

Article published online:
24 August 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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