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Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.

ABSTRACT: The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here we report that Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in combination with serum alpha-fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd-EOB-DTPA uptake in the hepatobiliary phase was observed in ?15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd-EOB-DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd-EOB-DTPA uptake in vivo. HCC classification based on EOB-MRI and serum AFP levels predicted overall survival in a single-institution cohort (n=70), and its prognostic utility was validated independently in a multi-institution cohort of early-stage HCCs (n=109).This noninvasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease.

SUBMITTER: Yamashita T

PROVIDER: S-EPMC4142120 | biostudies-other | 2014 Nov

REPOSITORIES: biostudies-other

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Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.

Yamashita Taro T Kitao Azusa A Matsui Osamu O Hayashi Takehiro T Nio Kouki K Kondo Mitsumasa M Ohno Naoki N Miyati Tosiaki T Okada Hikari H Yamashita Tatsuya T Mizukoshi Eishiro E Honda Masao M Nakanuma Yasuni Y Takamura Hiroyuki H Ohta Tetsuo T Nakamoto Yasunari Y Yamamoto Masakazu M Takayama Tadatoshi T Arii Shigeki S Wang XinWei X Kaneko Shuichi S

Hepatology (Baltimore, Md.) 20140929 5

<h4>Unlabelled</h4>The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here we report that Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in combination with serum alpha ...[more]

PMID: 24700365

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Project description:BackgroundThe precise differentiation of intrahepatic cholangiocarcinoma (ICC) from atypical hepatocellular carcinoma (HCC) is vital for treatment strategy and prognostic prediction. In clinical practice, nearly 40% of HCCs demonstrate atypical manifestations, particularly HCCs with rim arterial phase hyperenhancement (APHE), which is challenging to differentiate from mass-forming ICC. Thus, we aimed to develop a diagnostic regimen of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) contrast-enhanced magnetic resonance imaging (MRI) combined with serum tumor markers in differentiating mass-forming ICC from atypical HCC in at-risk patients with the hepatitis B virus (HBV).MethodsThis study enrolled 129 patients with pathologically proven mass-forming ICCs (n=53) and atypical HCCs (n=76) who had undergone preoperative Gd-EOB-DTPA contrast-enhanced MRI. The clinical data and imaging findings were analyzed. Univariate and multivariate logistic analyses were performed to identify the independent predictors for differentiating mass-forming ICCs from atypical HCCs. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curves, and DeLong test was used to compare the areas under curves of all independent predictors.ResultsUnivariate logistic regression analysis revealed normal alpha fetoprotein (AFP), elevated carbohydrate antigen 19-9 (CA19-9) level, elevated carcinoma embryonic antigen (CEA) level, central hyperintensity on T2-weighted imaging (T2WI), central hypointensity on T2WI, and targetoid sign on hepatobiliary phase (HBP) and targetoid restriction on diffusion-weighted imaging (DWI) were more likely to be significant predictors favoring mass-forming ICCs (all P values <0.05). In contrast, multifocal hyperintensity on T2WI and capsule sign were more frequently seen in patients with atypical HCC (all P values <0.05). Multivariate analysis revealed normal AFP, elevated CA19-9 level, targetoid sign on HBP, and targetoid restriction on DWI (all P=0.001) were independent predictors for differentiating mass-forming ICCs from atypical HCCs; DeLong test showed that the area under curve (AUC) increased to 0.949 when the above predictors were combined (all P values <0.05), and the sensitivity, specificity, and accuracy of the combined independent predictors were 88.7%, 93.4%, and 91.5%, respectively.ConclusionsA diagnostic regimen integrating tumor markers (AFP, CA19-9) and imaging biomarkers (targetoid restriction on DWI and/or targetoid sign on HBP) using Gd-EOB-DTPA-enhanced MRI could help to differentiate mass-forming ICCs from atypical HCCs and achieve high diagnostic performance of mass-forming ICCs in at-risk patients with the HBV.KeywordsMass-forming intrahepatic cholangiocarcinoma (mass-forming ICC); atypical hepatocellular carcinoma (atypical HCC); magnetic resonance imaging (MRI); gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA); hepatobiliary phase (HBP).

Project description:BackgroundNuclear protein Ki-67 indicates the status of cell proliferation and has been regarded as an attractive biomarker for the prognosis of HCC. The aim of this study is to investigate which radiomics model derived from different sequences and phases of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI was superior to predict Ki-67 expression in hepatocellular carcinoma (HCC), then further to validate the optimal model for preoperative prediction of Ki-67 expression in HCC.MethodsThis retrospective study included 151 (training cohort: n = 103; validation cohort: n = 48) pathologically confirmed HCC patients. Radiomics features were extracted from the artery phase (AP), portal venous phase (PVP), hepatobiliary phase (HBP), and T2-weighted (T2W) images. A logistic regression with the least absolute shrinkage and selection operator (LASSO) regularization was used to select features to build a radiomics score (Rad-score). A final combined model including the optimal Rad-score and clinical risk factors was established. Receiver operating characteristic (ROC) curve analysis, Delong test and calibration curve were used to assess the predictive performance of the combined model. Decision cure analysis (DCA) was used to evaluate the clinical utility.ResultsThe AP radiomics model with higher decision curve indicating added more net benefit, gave a better predictive performance than the HBP and T2W radiomic models. The combined model (AUC = 0.922 vs. 0.863) including AP Rad-score and serum AFP levels improved the predictive performance more than the AP radiomics model (AUC = 0.873 vs. 0.813) in the training and validation cohort. Calibration curve of the combined model showed a good agreement between the predicted and the actual probability. DCA of the validation cohort revealed that at a range threshold probability of 30-60%, the combined model added more net benefit compared with the AP radiomics model.ConclusionsA combined model including AP Rad-score and serum AFP levels based on enhanced MRI can preoperatively predict Ki-67 expression in HCC.

Dataset Information

Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.

Publications

Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.

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