Neoadjuvant Therapy and Venous Thromboembolism after Surgery in Pancreatic Cancer

Abstract

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the most thrombogenic cancers and PDAC-patients are at 12-19% risk of venous thromboembolism (VTE). Chemotherapy is one of the risk factors for VTE. The purpose of this study was to investigate the relation between neoadjuvant therapy (NAT) and VTE after surgery in PDAC and the overall survival in NAT patients with VTE. Method: PDAC-patients surgically treated in Helsinki University Hospital 2006-2017 were identified (n=493). Following data was collected: venous thromboembolic events, body mass index (BMI), age at surgery, neoadjuvant and adjuvant therapy, medication, resection marginal, tumor size, positive lymph node ratio, perivascular- and perineural invasion, surgical method, vascular reconstruction, and other cancers. The follow-up was at least 2 years or until death. Patients with another cancer (n=36), immediate death after surgery (n=5), stage IV and inoperable disease (n=54), lack of monitoring data (n=11), or coagulation disorders (Activated Protein C-resistance n=2) were excluded. One patient was operated twice and was included from the first operation. All diagnoses were histologically determined. Results: 384 patients were analyzed. Overall incidence of VTE after surgery was higher in NAT patients compared to upfront surgery (US) patients (n = 28 (30.1%) vs. n = 59 (20.3% p = 0.049)). NAT was a statistically significant risk factor for VTE after surgery: HR 1.61 (95% CI 1.03-2.53 p = 0.037) (Aalen-Johansen analysis in Figure 1). In multivariate analysis of VTE, NAT was a significant risk factor (HR 1.74 95% CI 1.07-2.81 p = 0.025). In overall survival (OS) analysis VTE was a statistically significant risk factor in both NAT (HR 3.25 95% CI 2.36-4.44 p < 0.001) and US groups (HR 2.91 95% CI 1.74-4.85 p < 0.001). Characteristics associated with VTE in the NAT group were BMI ≥ 30 and disease recurrence. Conclusion: Neoadjuvant therapy is an independent risk factor for venous thromboembolism after surgery in PDAC. VTE is associated with increased mortality in both the US and the NAT group. Obesity and disease recurrence are associated with VTE in NAT patients.