Thromboembolic Events During Perioperative Therapy for Resectable and Borderline Resectable Pancreatic Cancer in the PREOPANC-2 Trial
Abstract
PURPOSE Pancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of venous thromboembolism (VTE), which is burdensome and associated with decreased survival. Although neoadjuvant treatment is increasingly used in patients with PDAC, data on VTE in this setting remain scarce. 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 III PREOPANC-2 trial. Patients were randomly assigned to neoadjuvant 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin followed by surgery (FFX arm) or neoadjuvant gemcitabine-based chemoradiotherapy (CRT), 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 random assignment to 12 months after random assignment. The association with overall survival (OS) was analyzed using Cox regression analysis. RESULTS VTE was diagnosed in 28 of 325 patients (9%): nine (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% v CRT 12%, P = .02), the 12-month cumulative incidence did not differ between arms (6% v 11%, P = .06). Two patients died from PE-related causes in the CRT arm. VTE was independently associated with reduced OS (adjusted time-varying hazard ratio, 2.13, P = .002). CONCLUSION VTE occurred in 9% of patients with (borderline) resectable PDAC undergoing (neo)adjuvant treatment in the year after random assignment 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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (65)
Ruth A.L. Willems
Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
Aniek E. van Diepen
Esther N. Dekker
Department of Surgery, Erasmus MC Cancer Institute Rotterdam, University Medical Center Rotterdam, Rotterdam, the Netherlands
Quisette P. Janssen
Department of Surgery, Erasmus MC Cancer Institute Rotterdam, University Medical Center Rotterdam, Rotterdam, the Netherlands
Jacob L. van Dam
Department of Surgery, Erasmus MC Cancer Institute Rotterdam, University Medical Center Rotterdam, Rotterdam, the Netherlands
Nynke Michiels
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
Casper W.F. van Eijck
Department of Pulmonary Medicine, Erasmus University Medical Centre, Solid Tumour Immunology Research Rotterdam (STIRR), Rotterdam, the Netherlands
Karlijn E.P.E. Hermans
Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
Bert A. Bonsing
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
Koop P. Bosscha
Department of Surgery, Jeroen Bosch Hospital, Den Bosch, the Netherlands
Stefan A.W. Bouwense
Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
Olivier R. Busch
Department of Surgery, Location University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
Hugo ten Cate
Department of Internal Medicine and Thrombosis Expertise Center, Maastricht University Medical Center, Maastricht, the Netherlands
Peter-Paul L.O. Coene
Department of Surgery, Maasstad Hospital, Rotterdam, the Netherlands
Casper H.J. van Eijck
Department of Surgery, Erasmus MC Cancer Institute Rotterdam, University Medical Center Rotterdam, Rotterdam, the Netherlands
Nick van Es
Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam
Erwin van der Harst
Department of Surgery, Maasstad Hospital, Rotterdam, the Netherlands
Ignace H.J.T. de Hingh
Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
Tom M. Karsten
Department of Surgery, OLVG, Amsterdam, the Netherlands
Geert Kazemier
Department of Surgery, Location University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
Marion B. van der Kolk
Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
Bas De Laat
4Department of Functional Coagulation, Synapse Research Institute, Maastricht, Netherlands
Mike S.L. Liem
Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
J. Sven D. Mieog
Vincent B. Nieuwenhuijs
Department of Surgery, Medisch Spectrum Twente, Enschede, the Netherlands
Gijsbert A. Patijn
Department of Surgery, Isala Oncology Center, Zwolle, the Netherlands
Mark Roest
Hjalmar C. van Santvoort
Department of Surgery, St Antonius Hospital and University Medical Center Utrecht, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
Liselot Valkenburg-van Iersel
Roeland F. de Wilde
Department of Surgery, Erasmus MC Cancer Institute Rotterdam, University Medical Center Rotterdam, Rotterdam, the Netherlands
Fennie Wit
Department of Surgery, Frisius MC, Location Leeuwarden, Leeuwarden, the Netherlands
Barbara M. Zonderhuis
Department of Surgery, Location University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
Marc G. Besselink
Department of Surgery, Location University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
Marjolein Y.V. Homs
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands
Geertjan van Tienhoven
Radiation Oncology, Amsterdam University Medical Center, Amsterdam
Johanna W. Wilmink
Cancer Center Amsterdam, Amsterdam, the Netherlands
Bas Groot Koerkamp
Erasmus MC Cancer Institute, Rotterdam, Netherlands
Judith de Vos-Geelen
Laurens V. Beerepoot
Marlies L. van Bekkum
Hendrik Bos
Lieke Brouwer-Hol
Anna M.E. Bruynzeel
Geert A. Cirkel
Jan Willem B. de Groot
Brigitte C.M. Haberkorn
Olaf J.L. Loosveld
Misha D.P. Luyer
Saskia A.C. Luelmo
Leonie J.M. Mekenkamp
Joost J.M.E. Nuyttens
D. ten Oever
Martijn W.J. Stommel
Mirte M. Streppel
Albert J. ten Tije
Eva Versteijne
Suzan Vrijaldenhoven
Daphne H.M. Droogh
T.F. Stoop
Bo T.M. Strijbos
Ingmar F. Rompen
R.T. Theijse
Maaike K. Veenstra
Eva M.M. Verkolf
Anouk J. de Wilde