TY - JOUR
T1 - Impact of complications after resection of pancreatic cancer on disease recurrence and survival, and mediation effect of adjuvant chemotherapy
T2 - nationwide, observational cohort study
AU - Henry, Anne Claire
AU - Van Dongen, Jelle C.
AU - Van Goor, Iris W.J.M.
AU - Smits, F. Jasmijn
AU - Nagelhout, Anne
AU - Besselink, Marc G.
AU - Busch, Olivier R.
AU - Bonsing, Bert A.
AU - Bosscha, Koop
AU - Van Dam, Ronald M.
AU - Festen, Sebastiaan
AU - Groot Koerkamp, Bas
AU - Van Der Harst, Erwin
AU - De Hingh, Ignace H.
AU - Van Der Kolk, Marion
AU - Liem, Mike S.L.
AU - De Meijer, Vincent E.
AU - Patijn, Gijs A.
AU - Roos, Daphne
AU - Schreinemakers, Jennifer M.
AU - Wit, Fennie
AU - Daamen, Lois A.
AU - Van Santvoort, Hjalmar C.
AU - Molenaar, I. Quintus
AU - Van Eijck, Casper H.J.
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of BJS Society Ltd.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - Background: The causal pathway between complications after pancreatic cancer resection and impaired long-term survival remains unknown. The aim of this study was to investigate the impact of complications after pancreatic cancer resection on disease-free interval and overall survival, with adjuvant chemotherapy as a mediator. Methods: This observational study included all patients undergoing pancreatic cancer resection in the Netherlands (2014-2017). Clinical data were extracted from the prospective Dutch Pancreatic Cancer Audit. Recurrence and survival data were collected additionally. In causal mediation analysis, direct and indirect effect estimates via adjuvant chemotherapy were calculated. Results: In total, 1071 patients were included. Major complications (hazards ratio 1.22 (95 per cent c.i. 1.04 to 1.43); P = 0.015 and hazards ratio 1.25 (95 per cent c.i. 1.08 to 1.46); P = 0.003) and organ failure (hazards ratio 1.86 (95 per cent c.i. 1.32 to 2.62); P < 0.001 and hazards ratio 1.89 (95 per cent c.i. 1.36 to 2.63); P < 0.001) were associated with shorter disease-free interval and overall survival respectively. The effects of major complications and organ failure on disease-free interval (-1.71 (95 per cent c.i. -2.27 to -1.05) and -3.05 (95 per cent c.i. -4.03 to -1.80) respectively) and overall survival (-1.92 (95 per cent c.i. -2.60 to -1.16) and -3.49 (95 per cent c.i. -4.84 to -2.03) respectively) were mediated by adjuvant chemotherapy. Additionally, organ failure directly affected disease-free interval (-5.38 (95 per cent c.i. -9.27 to -1.94)) and overall survival (-6.32 (95 per cent c.i. -10.43 to -1.99)). In subgroup analyses, the association was found in patients undergoing pancreaticoduodenectomy, but not in patients undergoing distal pancreatectomy. Conclusion: Major complications, including organ failure, negatively impact survival in patients after pancreatic cancer resection, largely mediated by adjuvant chemotherapy. Prevention or adequate treatment of complications and use of neoadjuvant treatment may improve oncological outcomes.
AB - Background: The causal pathway between complications after pancreatic cancer resection and impaired long-term survival remains unknown. The aim of this study was to investigate the impact of complications after pancreatic cancer resection on disease-free interval and overall survival, with adjuvant chemotherapy as a mediator. Methods: This observational study included all patients undergoing pancreatic cancer resection in the Netherlands (2014-2017). Clinical data were extracted from the prospective Dutch Pancreatic Cancer Audit. Recurrence and survival data were collected additionally. In causal mediation analysis, direct and indirect effect estimates via adjuvant chemotherapy were calculated. Results: In total, 1071 patients were included. Major complications (hazards ratio 1.22 (95 per cent c.i. 1.04 to 1.43); P = 0.015 and hazards ratio 1.25 (95 per cent c.i. 1.08 to 1.46); P = 0.003) and organ failure (hazards ratio 1.86 (95 per cent c.i. 1.32 to 2.62); P < 0.001 and hazards ratio 1.89 (95 per cent c.i. 1.36 to 2.63); P < 0.001) were associated with shorter disease-free interval and overall survival respectively. The effects of major complications and organ failure on disease-free interval (-1.71 (95 per cent c.i. -2.27 to -1.05) and -3.05 (95 per cent c.i. -4.03 to -1.80) respectively) and overall survival (-1.92 (95 per cent c.i. -2.60 to -1.16) and -3.49 (95 per cent c.i. -4.84 to -2.03) respectively) were mediated by adjuvant chemotherapy. Additionally, organ failure directly affected disease-free interval (-5.38 (95 per cent c.i. -9.27 to -1.94)) and overall survival (-6.32 (95 per cent c.i. -10.43 to -1.99)). In subgroup analyses, the association was found in patients undergoing pancreaticoduodenectomy, but not in patients undergoing distal pancreatectomy. Conclusion: Major complications, including organ failure, negatively impact survival in patients after pancreatic cancer resection, largely mediated by adjuvant chemotherapy. Prevention or adequate treatment of complications and use of neoadjuvant treatment may improve oncological outcomes.
UR - http://www.scopus.com/inward/record.url?scp=85164392846&partnerID=8YFLogxK
U2 - 10.1093/bjsopen/zrac174
DO - 10.1093/bjsopen/zrac174
M3 - Article
AN - SCOPUS:85164392846
SN - 2474-9842
VL - 7
JO - BJS open
JF - BJS open
IS - 2
M1 - zrac174
ER -