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

Jakob M. Riedl; Esther Schwarzenbacher; Florian Moik; Lena Horvath; Antonia Gantschnigg; Felix Renneberg; Florian Posch; Dominik A. Barth; Michael Stotz; Martin Pichler; Stefan Hatzl; Simon Fandler-Höfler; Paul Gressenberger; Thomas Gary; Philipp J. Jost; Richard Greil; Cihan Ay; Angela Djanani; Armin Gerger; Konstantin Schlick

doi:10.1055/a-1548-4847

Thrombosis and Haemostasis, Table of Contents

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‡^*

¹Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

,

Esther Schwarzenbacher‡^*

¹Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

,

Florian Moik

²Division of Hematology and Hemostaseology, Department of Medicine I and Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria

,

Lena Horvath

³Department of Internal Medicine V: Hematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria

,

Antonia Gantschnigg

⁴Department of Surgery, Paracelsus Medical University, Salzburg, Austria

,

Felix Renneberg

⁵IIIrd Medical Department of Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectious Disease, Salzburg Cancer Research Institute, Paracelsus Medical University, Salzburg, Austria

,

Florian Posch

¹Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

,

Dominik A. Barth

¹Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

,

Michael Stotz

¹Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

,

Martin Pichler

¹Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

,

Stefan Hatzl

⁶Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

,

Simon Fandler-Höfler

⁷Department of Neurology, Medical University of Graz, Austria

,

Paul Gressenberger

⁸Division of Angiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

,

Thomas Gary

⁸Division of Angiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

,

Philipp J. Jost

¹Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

,

Richard Greil

⁵IIIrd Medical Department of Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectious Disease, Salzburg Cancer Research Institute, Paracelsus Medical University, Salzburg, Austria

,

Cihan Ay

²Division of Hematology and Hemostaseology, Department of Medicine I and Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria

⁹I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

,

Angela Djanani

¹⁰Department of Internal Medicine I, Gastroenterology, Hepatology, Metabolism and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria

,

Armin Gerger

¹Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

,

Konstantin Schlick

⁵IIIrd Medical Department of Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectious Disease, Salzburg Cancer Research Institute, Paracelsus Medical University, Salzburg, Austria

› Author Affiliations

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

Full Text

References

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Supplementary Material