PO11 | THROMBOEMBOLIC EVENTS DURING PERIOPERATIVE THERAPY FOR RESECTABLE AND BORDERLINE RESECTABLE PANCREATIC CANCER IN THE PREOPANC-2 TRIAL

R.A.L. Willems^1|5, A.E. Van Diepen^1|2|6, EN. Dekker⁷, Q.P. Janssen⁷, J.L. Van Dam⁷, N. Michiels⁸, C.W.F. Van Eijck⁹, K.E.P.E. Hermans^1|2, B.A. Bonsing⁸, K.P. Bosscha¹⁰, S.A.W. Bouwense^11|12, O. R. Busch^13|14, H. Ten Cate^4|5|15|16, P.P.L.O. Coene¹⁷, C.H.J. Van Eijck⁷, N. Van Es^18|19, E. Van Der Harst¹⁷, I.H.J.T. De Hingh²⁰, T.M. Karsten²¹, G. Kazemier^13|14, M.B. Van Der Kolk²², B. De Laat^3|5, M.S.L. Liem²², J.S.D. Mieog⁸, V.B. Nieuwenhuijs²⁴, G.A. Patijn²⁴, M. Roest³, H.C. Van Santvoort²⁵, L. Valkenburg-Van Iersel^1|2, R. F. De Wilde⁷, F. Wit²⁶, B.M. Zonderhuis^13|14, M.G. Besselink^13|14, M.Y.V. Homs⁶, G. Van Tienhoven^14|27, J. W. Wilmink^14|28, B. Groot Koerkamp⁷, J. De Vos-Geelen^1|2 | ¹Maastricht University Medical Center, Department of Internal Medicine, Division of Medical Oncology; ²GROW – Research Institute for Oncology & Reproduction, Maastricht University, Maastricht; ³Synapse Research Institute, Department of Functional Coagulation, Maastricht; ⁴Maastricht University Medical Center, Thrombosis Expert Center Maastricht, Maastricht; ⁵Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), School for Cardiovascular Diseases, Maastricht; ⁶Erasmus MC Cancer Institute, Department of Medical Oncology, Rotterdam; ⁷Erasmus MC Cancer Institute Rotterdam, University Medical Center Rotterdam, Department of Surgery; ⁸Leiden University Medical Center, Department of Surgery, Leiden; ⁹Solid Tumour Immunology Research Rotterdam (STIRR), Department of Pulmonary Medicine, Erasmus University Medical Centre, Rotterdam; ¹⁰Jeroen Bosch Hospital, Department of Surgery, Den Bosch; ¹¹Maastricht University Medical Center, Department of Surgery, Maastricht; ¹²Maastricht University Medical Center, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht; ¹³Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam; ¹⁴Cancer Center Amsterdam; ¹⁵Maastricht University Medical Center, Department of Internal Medicine, Division Vascular Medicine, Maastricht; ¹⁶Maastricht University, Department of Biochemistry, Laboratory for Clinical Thrombosis and Hemostasis, Maastricht; ¹⁷Maasstad Hospital, Department of Surgery, Rotterdam; ¹⁸Amsterdam UMC, location University of Amsterdam, Department of Vascular Medicine, Amsterdam; ¹⁹Amsterdam UMC, location University of Amsterdam, Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam; ²⁰Catharina Hospital, Department of Surgery, Eindhoven; ²¹OLVG, Department of Surgery, Amsterdam; ²²Radboud University Medical Center, Department of Surgery, Nijmegen; ²³Medisch Spectrum Twente, Department of Surgery, Enschede; ²⁴Isala Oncology Center, Department of Surgery, Zwolle; ²⁵Regional Academic Cancer Center Utrecht, St. Antonius Hospital and University Medical Center Utrecht, Department of Surgery, Utrecht; ²⁶Frisius MC, location Leeuwarden, Department of Surgery, Leeuwarden; ²⁷Amsterdam UMC, location University of Amsterdam, Department of Radiation Oncology, Amsterdam; ²⁸Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands

Introduction. Pancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of venous thromboembolism (VTE), which is burdensome and associated with decreased survival. While neoadjuvant treatment is increasingly used in patients with PDAC, data on VTE in this setting remain scarce.

Aim. This study evaluated VTE incidence during (neo)adjuvant therapy for resectable and borderline resectable PDAC and its relation to survival.

Methods. This study included patients from the investigator-initiated, multicenter, randomized controlled phase 3 PREOPANC-2 trial. Patients were randomized to neoadjuvant FOLFIRINOX followed by surgery (FFX arm) or neoadjuvant gemcitabine-based chemoradiotherapy, followed by surgery and adjuvant gemcitabine (CRT arm). VTE was defined as both incidental and symptomatic lower or upper extremity deep-vein thrombosis, pulmonary embolism (PE), splanchnic vein thrombosis, and catheter-related thrombosis. VTE occurrence was retrospectively evaluated from randomization to 12 months post-randomization. The association with overall survival (OS) was analyzed using Cox regression analysis.

Results. VTE was diagnosed in 28 of 325 patients (9%): 9 (3%) preoperatively and 19 (8%) postoperatively. Most VTEs were symptomatic (54%). Although a higher proportion of patients developed postoperative VTE in the CRT arm (FFX 3% vs CRT 12%, p=0.02), the 12-month cumulative incidence did not differ between arms (6% vs. 11%, p=0.06). Two patients died from PE-related causes in the CRT arm. VTE was independently associated with reduced OS (adjusted time-varying HR 2.13, p=0.002).

Conclusions. VTE occurred in 9% of patients with (borderline) resectable PDAC undergoing (neo)adjuvant treatment in the year post-randomization and was associated with decreased OS. These results underscore the need for standardized reporting of thromboembolic events in clinical trials and future studies assessing the potential benefits of thromboprophylaxis during neoadjuvant therapy.