Thromboembolic Events During Perioperative Therapy for Resectable and Borderline Resectable Pancreatic Cancer in the PREOPANC-2 Trial

Author(s): Ruth A.L. Willems, MD1,2,3,4,5; Aniek E. van Diepen, MD1,2,6; Esther N. Dekker, MD7; Quisette P. Janssen, MD, PhD7; Jacob L. van Dam, MD7; Nynke Michiels, MD8; Casper W.F. van Eijck, PhD, MSc9; Karlijn E.P.E. Hermans, PhD, MSc1,2; Bert A. Bonsing, MD, PhD8; Koop P. Bosscha, MD, PhD10; Stefan A.W. Bouwense, MD, PhD11,12; Olivier R. Busch, MD, PhD13,14; Hugo ten Cate, MD, PhD4,5,15,16; Peter-Paul L.O. Coene, MD, PhD17; Casper H.J. van Eijck, MD, PhD7; Nick van Es, MD, PhD18,19; Erwin van der Harst, MD, PhD17; Ignace H.J.T. de Hingh, MD, PhD20; Tom M. Karsten, MD, PhD21; Geert Kazemier, MD, PhD13,14; Marion B. van der Kolk, MD, PhD22; Bas de Laat, MD, PhD3,5; Mike S.L. Liem, MD, PhD22; J. Sven D. Mieog, MD, PhD8; Vincent B. Nieuwenhuijs, MD, PhD23; Gijsbert A. Patijn, MD, PhD24; Mark Roest, PhD, MSc3; Hjalmar C. van Santvoort, MD, PhD25; Liselot Valkenburg-van Iersel, MD, PhD1,2; Roeland F. de Wilde, MD, PhD7; Fennie Wit, MD, PhD26; Barbara M. Zonderhuis, MD, PhD13,14; Marc G. Besselink, MD, PhD13,14; Marjolein Y.V. Homs, MD, PhD6; Geertjan van Tienhoven, MD, PhD14,27; Johanna W. Wilmink, MD, PhD14,28; Bas Groot Koerkamp, MD, PhD7; Judith de Vos-Geelen, MD, PhD1,2; for the Dutch Pancreatic Cancer Group;
Source: DOI: 10.1200/JCO-25-01935
Original Article
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Dr. Anjan Patel's Thoughts

Interesting study that quantifies the risk of Venous Thromboembolism (VTE) in patients undergoing neo(adjuvant) treatment. Risk was about 9% overall, underscoring the need to be aware and potentially provide prophylaxis where appropriate.

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.

Author Affiliations

1Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands; 2GROW???Research Institute for Oncology & Reproduction, Maastricht University, Maastricht, the Netherlands; 3Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands; 4Maastricht University Medical Center, Thrombosis Expert Center Maastricht, Maastricht, the Netherlands; 5School for Cardiovascular Diseases, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, the Netherlands; 6Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 7Department of Surgery, Erasmus MC Cancer Institute Rotterdam, University Medical Center Rotterdam, Rotterdam, the Netherlands; 8Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands; 9Department of Pulmonary Medicine, Erasmus University Medical Centre, Solid Tumour Immunology Research Rotterdam (STIRR), Rotterdam, the Netherlands; 10Department of Surgery, Jeroen Bosch Hospital, Den Bosch, the Netherlands; 11Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands; 12Maastricht University Medical Center, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, the Netherlands; 13Department of Surgery, Location University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; 14Cancer Center Amsterdam, Amsterdam, the Netherlands; 15Division Vascular Medicine, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands; 16Laboratory for Clinical Thrombosis and Hemostasis, Department of Biochemistry, Maastricht University, Maastricht, the Netherlands; 17Department of Surgery, Maasstad Hospital, Rotterdam, the Netherlands; 18Department of Vascular Medicine, Location University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; 19Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Location University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; 20Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands; 21Department of Surgery, OLVG, Amsterdam, the Netherlands; 22Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands; 23Department of Surgery, Medisch Spectrum Twente, Enschede, the Netherlands; 24Department of Surgery, Isala Oncology Center, Zwolle, the Netherlands; 25Department of Surgery, St Antonius Hospital and University Medical Center Utrecht, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands; 26Department of Surgery, Frisius MC, Location Leeuwarden, Leeuwarden, the Netherlands; 27Department of Radiation Oncology, Location University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; 28Department of Medical Oncology, Location University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands

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