TY - JOUR
T1 - Preoperative serum ADAM12 levels as a stromal marker for overall survival and benefit of adjuvant therapy in patients with resected pancreatic and periampullary cancer
AU - Strijker, Marin
AU - van der Sijde, Fleur
AU - Suker, Mustafa
AU - Boermeester, Marja A
AU - Bonsing, Bert A
AU - Bruno, Marco J
AU - Busch, Olivier R
AU - Doukas, Michail
AU - van Eijck, Casper H
AU - Gerritsen, Arja
AU - Groot Koerkamp, Bas
AU - Haj Mohammad, Nadia
AU - van Hilst, Jony
AU - de Hingh, Ignace H
AU - van Hooft, Jeanin E
AU - Luyer, Misha D
AU - Quintus Molenaar, I
AU - Verheij, Joanne
AU - Waasdorp, Cynthia
AU - Wilmink, Johanna W
AU - Besselink, Marc G
AU - van Laarhoven, Hanneke W
AU - Bijlsma, Maarten F
N1 - Funding Information:
MDL has received grants from Medtronic, Galvani and Nutricia.
Funding Information:
IdH has received grants from Roche Pharmaceutical, QPS/RanD and Medtronic.
Funding Information:
MFB has received research funding from Celgene and acted as a consultant for Servier. MFB is inventor on a patent application describing the use of serum ADAM12 levels in gastrointestinal cancers.
Funding Information:
JEH has acted as a consultant for Boston Scientific, Cook Medical, Medtronics and has received research grants from Cook Medical and Abbott.
Funding Information:
This work was supported by the Dutch Cancer Society [grant number UVA2013-5842] and the AMC foundation.
Funding Information:
MJB has received research funding from Boston Scientific, Cook Medical, Pentax Medical, Mylan and 3 M, and acted as a consultant Boston Scientific, Cook Medical, Pentax Medical, Mylan and 3 M.
Publisher Copyright:
© 2021 The Authors
PY - 2021/12
Y1 - 2021/12
N2 - BACKGROUND: We evaluated the stroma marker A Disintegrin And Metalloprotease 12 (ADAM12) as a preoperative prognostic and treatment-predictive marker for overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) and periampullary cancers.METHODS: Materials were derived from the prospective nationwide Dutch Pancreas Biobank (2015-2017). We included patients who underwent resection because of PDAC/periampullary cancer or non-invasive IPMN (control group) and had a preoperative serum sample available. ADAM12 levels were dichotomized using a pre-defined cut-off (316 pg/mL). Univariable and multivariable Cox regression analyses (backward selection) were performed.RESULTS: Median ADAM12 levels were 161 (IQR 79-352) pg/mL in 215 PDAC and periampullary adenocarcinomas. High ADAM12 levels (>316 pg/mL) predicted poor OS in the total group of pancreatic and periampullary adenocarcinomas (P = 0.04), but not after adjustment. In distal cholangiocarcinoma (n = 33), high ADAM12 levels predicted poor OS in univariable analysis (P = 0.02), but not in PDAC (P = 0.63). PDAC patients (n = 135) with high ADAM12 levels benefited from adjuvant treatment (median OS 27 vs 14 months, P = 0.02), whereas those with low levels did not (21 vs 21 months, P = 0.87).CONCLUSION: High circulating ADAM12 levels, as a proxy for activated stroma, predict survival benefit from adjuvant chemotherapy in PDAC, requiring validation in future studies.
AB - BACKGROUND: We evaluated the stroma marker A Disintegrin And Metalloprotease 12 (ADAM12) as a preoperative prognostic and treatment-predictive marker for overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) and periampullary cancers.METHODS: Materials were derived from the prospective nationwide Dutch Pancreas Biobank (2015-2017). We included patients who underwent resection because of PDAC/periampullary cancer or non-invasive IPMN (control group) and had a preoperative serum sample available. ADAM12 levels were dichotomized using a pre-defined cut-off (316 pg/mL). Univariable and multivariable Cox regression analyses (backward selection) were performed.RESULTS: Median ADAM12 levels were 161 (IQR 79-352) pg/mL in 215 PDAC and periampullary adenocarcinomas. High ADAM12 levels (>316 pg/mL) predicted poor OS in the total group of pancreatic and periampullary adenocarcinomas (P = 0.04), but not after adjustment. In distal cholangiocarcinoma (n = 33), high ADAM12 levels predicted poor OS in univariable analysis (P = 0.02), but not in PDAC (P = 0.63). PDAC patients (n = 135) with high ADAM12 levels benefited from adjuvant treatment (median OS 27 vs 14 months, P = 0.02), whereas those with low levels did not (21 vs 21 months, P = 0.87).CONCLUSION: High circulating ADAM12 levels, as a proxy for activated stroma, predict survival benefit from adjuvant chemotherapy in PDAC, requiring validation in future studies.
UR - http://www.scopus.com/inward/record.url?scp=85107400989&partnerID=8YFLogxK
U2 - 10.1016/j.hpb.2021.05.001
DO - 10.1016/j.hpb.2021.05.001
M3 - Article
C2 - 34103247
SN - 1365-182X
VL - 23
SP - 1886
EP - 1896
JO - International Hepato-Pancreato Biliary Association.
JF - International Hepato-Pancreato Biliary Association.
IS - 12
ER -