Pathological validation and prognostic potential of quantitative MRI in the characterization of pancreas cancer: preliminary experience

Molecular Oncology

Hanneke W. M. vanLaarhoven¹  Johanna W. Wilmink¹  Remy Klaassen¹  Anne Steins¹  Gerrit K. J. Hooijer²  Joanne Verheij²  Onno J. deBoer²  Marc J. van deVijver²  Geertjan vanTienhoven³  Aart J. Nederveen⁴  Jaap Stoker⁴  Marc R. W. Engelbrecht⁴  Oliver J. Gurney‐Champion⁴  Olivier R. Busch⁵  Marc G. Besselink⁵  Mustafa Suker⁶  Casper H. J. vanEijck⁶  Maarten F. Bijlsma⁷ 

[1] Department of Medical Oncology Cancer Center Amsterdam Amsterdam UMC University of Amsterdam The Netherlands;Department of Pathology Cancer Center Amsterdam Amsterdam UMC University of Amsterdam The Netherlands;Department of Radiation Oncology Cancer Center Amsterdam Amsterdam UMC University of Amsterdam The Netherlands;Department of Radiology & Nuclear Medicine Cancer Center Amsterdam Amsterdam UMC University of Amsterdam The Netherlands;Department of Surgery Cancer Center Amsterdam Amsterdam UMC University of Amsterdam The Netherlands;Department of Surgery Erasmus Medical Center Rotterdam The Netherlands;Laboratory for Experimental Oncology and Radiobiology Center for Experimental and Molecular Medicine Cancer Center Amsterdam Amsterdam UMC University of Amsterdam The Netherlands;

关键词: carcinoma;    pancreatic ductal;    magnetic resonance imaging;    diffusion magnetic resonance imaging;    histological techniques;    prognosis;   

DOI  :  10.1002/1878-0261.12688

来源: DOAJ

【 摘 要 】

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 Ktrans and ve, ADC, and IVIM D correlated with collagen fraction. DCE kep 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 kep 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.

【 授权许可】

Unknown