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Patterns of Thromboembolism in Patients with Advanced Pancreatic Cancer Undergoing First-Line Chemotherapy with FOLFIRINOX or Gemcitabine/nab-Paclitaxel
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.
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.
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.
Received: 14 March 2021
Accepted: 10 July 2021
12 July 2021 (online)
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
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