TY - JOUR
T1 - Thromboembolic Events During Perioperative Therapy for Resectable and Borderline Resectable Pancreatic Cancer in the PREOPANC-2 Trial
AU - Willems, Ruth A L
AU - van Diepen, Aniek E
AU - Dekker, Esther N
AU - Janssen, Quisette P
AU - van Dam, Jacob L
AU - Michiels, Nynke
AU - van Eijck, Casper W F
AU - Hermans, Karlijn E P E
AU - Bonsing, Bert A
AU - Bosscha, Koop P
AU - Bouwense, Stefan A W
AU - Busch, Olivier R
AU - Ten Cate, Hugo
AU - Coene, Peter-Paul L O
AU - van Eijck, Casper H J
AU - van Es, Nick
AU - van der Harst, Erwin
AU - de Hingh, Ignace H J T
AU - Karsten, Tom M
AU - Kazemier, Geert
AU - van der Kolk, Marion B
AU - de Laat, Bas
AU - Liem, Mike S L
AU - Mieog, J Sven D
AU - Nieuwenhuijs, Vincent B
AU - Patijn, Gijsbert A
AU - Roest, Mark
AU - van Santvoort, Hjalmar C
AU - Valkenburg-van Iersel, Liselot
AU - de Wilde, Roeland F
AU - Wit, Fennie
AU - Zonderhuis, Barbara M
AU - Besselink, Marc G
AU - Homs, Marjolein Y V
AU - van Tienhoven, Geertjan
AU - Wilmink, Johanna W
AU - Groot Koerkamp, Bas
AU - de Vos-Geelen, Judith
N1 - Publisher Copyright:
© 2026 American Society of Clinical Oncology
PY - 2026/3/10
Y1 - 2026/3/10
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105030517901
U2 - 10.1200/JCO-25-01935
DO - 10.1200/JCO-25-01935
M3 - Article
C2 - 41610374
SN - 0732-183X
VL - 44
SP - 662
EP - 675
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 8
ER -