Recent advances in prophylactic anticoagulation and antineoplastic treatment for 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.
Four-hundred-fifty-five patients with aPC undergoing palliative 1st-line chemotherapy (Gemcitabine/nab-Paclitaxel (GN) or FOLIRINOX) were included. Primary outcomes were objectively confirmed VTE and/or ATE.
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 disease 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 1st line chemotherapy.
Patients with aPC undergoing palliative 1st-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.

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