TY - JOUR
T1 - Pathological validation and prognostic potential of quantitative MRI in the characterization of pancreas cancer: preliminary experience
AU - Klaassen, Remy
AU - Steins, Anne
AU - Gurney-Champion, Oliver J.
AU - Bijlsma, Maarten F.
AU - van Tienhoven, Geertjan
AU - Engelbrecht, Marc R. W.
AU - van Eijck, Casper H. J.
AU - Suker, Mustafa
AU - Wilmink, Johanna W.
AU - Besselink, Marc G.
AU - Busch, Olivier R.
AU - de Boer, Onno J.
AU - van de Vijver, Marc J.
AU - Verheij, Joanne
AU - Stoker, Jaap
AU - Nederveen, Aart J.
AU - van Laarhoven, Hanneke W. M.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Patient stratification based on biological variation in pancreatic ductal adenocarcinoma (PDAC) subtypes could help to improve clinical outcome. However, noninvasive assessment of the entire tumor microenvironment remains challenging. In this study, we investigate the biological basis of dynamic contrast-enhanced (DCE), intravoxel incoherent motion (IVIM), and R2*-derived magnetic resonance imaging (MRI) parameters for the noninvasive characterization of the PDAC tumor microenvironment and evaluate their prognostic potential in PDAC patients. Patients diagnosed with treatment-naïve resectable PDAC underwent MRI. After resection, a whole-mount tumor slice was analyzed for collagen fraction, vessel density, and hypoxia and matched to the MRI parameter maps. MRI parameters were correlated to immunohistochemistry-derived tissue characteristics and evaluated for prognostic potential. Thirty patients were included of whom 21 underwent resection with whole-mount histology available in 15 patients. DCE K trans and v e, ADC, and IVIM D correlated with collagen fraction. DCE k ep and IVIM f correlated with vessel density and R2* with tissue hypoxia. Based on MRI, two main PDAC phenotypes could be distinguished; a stroma-high phenotype demonstrating high vessel density and high collagen fraction and a stroma-low phenotype demonstrating low vessel density and low collagen fraction. Patients with the stroma-high phenotype (high k ep and high IVIM D, n = 8) showed longer overall survival (not reached vs. 14 months, P = 0.001, HR = 9.1, P = 0.004) and disease-free survival (not reached vs. 2 months, P < 0.001, HR 9.3, P = 0.003) compared to the other patients (n = 22). Median follow-up was 41 (95% CI: 36–46) months. MRI was able to accurately characterize tumor collagen fraction, vessel density, and hypoxia in PDAC. Based on imaging parameters, a subgroup of patients with significantly better prognosis could be identified. These first results indicate that stratification-based MRI-derived biomarkers could help to tailor treatment and improve clinical outcome and warrant further research.
AB - Patient stratification based on biological variation in pancreatic ductal adenocarcinoma (PDAC) subtypes could help to improve clinical outcome. However, noninvasive assessment of the entire tumor microenvironment remains challenging. In this study, we investigate the biological basis of dynamic contrast-enhanced (DCE), intravoxel incoherent motion (IVIM), and R2*-derived magnetic resonance imaging (MRI) parameters for the noninvasive characterization of the PDAC tumor microenvironment and evaluate their prognostic potential in PDAC patients. Patients diagnosed with treatment-naïve resectable PDAC underwent MRI. After resection, a whole-mount tumor slice was analyzed for collagen fraction, vessel density, and hypoxia and matched to the MRI parameter maps. MRI parameters were correlated to immunohistochemistry-derived tissue characteristics and evaluated for prognostic potential. Thirty patients were included of whom 21 underwent resection with whole-mount histology available in 15 patients. DCE K trans and v e, ADC, and IVIM D correlated with collagen fraction. DCE k ep and IVIM f correlated with vessel density and R2* with tissue hypoxia. Based on MRI, two main PDAC phenotypes could be distinguished; a stroma-high phenotype demonstrating high vessel density and high collagen fraction and a stroma-low phenotype demonstrating low vessel density and low collagen fraction. Patients with the stroma-high phenotype (high k ep and high IVIM D, n = 8) showed longer overall survival (not reached vs. 14 months, P = 0.001, HR = 9.1, P = 0.004) and disease-free survival (not reached vs. 2 months, P < 0.001, HR 9.3, P = 0.003) compared to the other patients (n = 22). Median follow-up was 41 (95% CI: 36–46) months. MRI was able to accurately characterize tumor collagen fraction, vessel density, and hypoxia in PDAC. Based on imaging parameters, a subgroup of patients with significantly better prognosis could be identified. These first results indicate that stratification-based MRI-derived biomarkers could help to tailor treatment and improve clinical outcome and warrant further research.
KW - carcinoma
KW - diffusion magnetic resonance imaging
KW - histological techniques
KW - magnetic resonance imaging
KW - pancreatic ductal
KW - prognosis
UR - http://www.scopus.com/inward/record.url?scp=85087318176&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/1878-0261.12688
DO - https://doi.org/10.1002/1878-0261.12688
M3 - Article
C2 - 32285559
SN - 1574-7891
VL - 14
SP - 2176
EP - 2189
JO - Molecular Oncology
JF - Molecular Oncology
IS - 9
ER -