Risk of Venous Thromboembolism for Patients with Pancreatic Ductal Adenocarcinoma Undergoing Preoperative Chemotherapy Followed by Surgical Resection

Abstract

Background

Pancreatic ductal adenocarcinoma (PDA) is associated with a hypercoagulable state, resulting in a high risk of venous thromboembolism (VTE). Risk of VTE is well established for patients receiving chemotherapy for advanced disease and during the perioperative period for patients undergoing surgical resection. However, data are lacking for patients undergoing neoadjuvant treatment followed by resection, who may have a unique risk of VTE because of exposure to both chemotherapy and surgery.

Methods

The study included patients with PDA who underwent neoadjuvant therapy followed by surgery from 2007 to June 2017. Development of VTE was evaluated from the start of treatment through the 90-day postoperative period. Risk factors including demographic, treatment, and laboratory variables were evaluated.

Results

The study investigated 426 patients receiving neoadjuvant therapy before surgical resection. Of these patients, 20% had a VTE within 90 days postoperatively (n = 87), and 70% of the VTE occurred during the postoperative period. The VTE included pulmonary embolism (30%), deep vein thrombosis (33%), and thrombosis of the portal vein (PV)/superior mesenteric vein (SMV) (40%). A pretreatment hemoglobin level lower than 10 g/dL and a platelet count higher than 443 were independently associated with VTE during neoadjuvant treatment. The independent predictors of postoperative VTE were a body mass index higher than 35 kg/m², a preoperative platelet-to-lymphocyte ratio higher than 260, resection with distal pancreatectomy with celiac axis resection/total pancreatectomy, PV/SMV resection, and longer operative times. Development of VTE was associated with worse overall and disease-free survival and an independent predictor of survival and decreased likelihood of receiving adjuvant chemotherapy.

Conclusions

Venous thromboembolism during neoadjuvant therapy and the subsequent perioperative period is common and has a significant impact on outcome. Further study into novel thromboprophylaxis measures or protocols during neoadjuvant treatment and the perioperative period is warranted.

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