Open AccessPathological validation and prognostic potential of quantitative MRI in the characterization of pancreas cancer: preliminary experience
Author(s) -
Klaassen Remy,
Steins Anne,
GurneyChampion Oliver J.,
Bijlsma Maarten F.,
Tienhoven Geertjan,
Engelbrecht Marc R. W.,
Eijck Casper H. J.,
Suker Mustafa,
Wilmink Johanna W.,
Besselink Marc G.,
Busch Olivier R.,
Boer Onno J.,
Vijver Marc J.,
Hooijer Gerrit K. J.,
Verheij Joanne,
Stoker Jaap,
Nederveen Aart J.,
Laarhoven Hanneke W. M.
Publication year - 2020
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12688
Subject(s) - intravoxel incoherent motion , medicine , magnetic resonance imaging , stroma , pathological , pancreatic cancer , pathology , immunohistochemistry , hypoxia (environmental) , dynamic contrast enhanced mri , pancreas , cancer , histology , adenocarcinoma , nuclear medicine , radiology , effective diffusion coefficient , chemistry , organic chemistry , oxygen
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.