Clinical Correlates of Portal Venous or Superior Mesenteric Vein Thrombosis Following Neoadjuvant Therapy with Dose Escalated Radiation for Borderline Resectable or Locally Advanced Pancreatic Adenocarcinoma.

PURPOSE/OBJECTIVE(S) Neoadjuvant regimens for borderline resectable and locally advanced pancreatic adenocarcinoma (PDAC) are incorporating radiation dose escalation through conventional external beam radiation (EBRT), intraoperative radiation therapy (IORT), and stereotactic body radiation (SBRT). We conducted a retrospective review of patients treated with and without IORT dose escalation to identify risk factors for portal vein and superior mesenteric vein thrombosis (PVT/SMVT). MATERIALS/METHODS We identified 96 patients with locally advanced or borderline-resectable PDAC treated at our institution with neoadjuvant therapy followed by exploratory laparotomy between 2009 and 2014. Patients considered at risk for close or positive surgical margins based on preoperative imaging were treated with dose escalated RT consisting of EBRT with or without IORT boost to a biological equivalent dose (BED) greater than 100. Prognostic factors for PVT/SMVT were evaluated using the Wilcoxon rank-sum test, Fisher exact test, and Cox proportional hazards model. RESULTS Median follow-up was 23 months. Fifty-six patients received IORT (58%). Twenty-nine patients (30%) developed PVT/SMVT, fifteen of which (52%) occurred in the setting of local recurrence (LR). Median time to PVT/SMVT was 10 months for patients with and without LR. On multivariate analysis, local recurrence and venous resection and repair with vascular interposition grafts were significantly associated with PVT/SMVT. IORT dose escalation and history of diabetes were not associated with PVT/SMVT. Six patients underwent both IORT and vascular repair, one with vascular interposition graft, of whom 50% developed PVT/SMVT. While the fourteen patients who developed PVT/ SMVT in the absence of LR did not experience a decrease in overall survival, there was significant morbidity associated with PVT/SMVT in this setting, with ten patients developing ascites requiring frequent paracenteses and additional interventions. CONCLUSION Approximately 30% of patients who underwent neoadjuvant chemoradiation for PDAC developed PVT/SMVT a median of 10 months following surgery. This was significantly associated with local recurrence and vascular resection with reconstruction with vascular grafts, but not with escalating RT dose. PVT/SMVT in the absence of LR was associated with significant morbidity.