Can Current Preoperative Imaging Be Used to Detect Microvascular Invasion of Hepatocellular Carcinoma?

Renzulli, Matteo; Brocchi, Stefano; Cucchetti, Alessandro; Mazzotti, Federico; Mosconi, Cristina; Sportoletti, Camilla; Brandi, Giovanni; Pinna, Antonio Daniele; Golfieri, Rita

doi:10.1148/radiol.2015150998

Cited by 302 publications

(287 citation statements)

References 33 publications

(40 reference statements)

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“…Sinusoid-like microvascular pattern was also described as "vessels that encapsulate tumor cluster (VETC)" and it has been reported that this particular microvascular pattern could facilitate the microvascular invasion [29]. In line with the recently suggested biological mechanism of microvascular invasion, IRE and microvascular invasion are closely related in the present study and several previous studies [30,31]. Taken together, less enhancement of the central portion of the tumor in IRE-HCCs appears to be associated with low microvascular density and a sinusoid-like pattern, which are linked to poor differentiation, frequent microvascular invasion, and poor outcomes in HCC patients [21,25].…”

Section: Discussionsupporting

confidence: 89%

Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features

Rhee

An²,

Kim

et al. 2018

Liver Cancer

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Background and Aims: The purpose of our study was to examine the histopathologic characteristics of hepatocellular carcinoma (HCC) with irregular rim-like arterial phase enhancement (IRE), which has been reported to be associated with more aggressive tumor behavior. Methods: We investigated 84 pathologically confirmed HCCs in 84 patients who underwent curative hepatic resection after gadoxetate-enhanced magnetic resonance imaging between January 2008 and February 2013. Two abdominal radiologists independently reviewed these images and classified HCCs into two categories: HCC showing IRE (IRE-HCC) and HCC showing hypoenhancement or diffuse arterial enhancement (non-IRE-HCC). Twenty-two HCCs were classified as IRE-HCCs, and 51 were classified as non-IRE-HCCs concordantly by both reviewers. The remaining 11 HCCs, on whose radiologic classifications the reviewers disagreed, were classified as HCCs with intermediate enhancement patterns. The HCC clinicopathologic characteristics and patient outcomes were then compared. Results: IRE-HCCs showed more frequent microvascular invasion (91 vs. 35%), lower microvascular density (246.5 vs. 426.5/mm²), higher proportions of sinusoid-like microvascular pattern (55 vs. 0%) and macrotrabecular pattern (45 vs. 0%), and larger areas of tumor necrosis (15 vs. 0%) and fibrous stroma (8.3 vs. 2.1%) than non-IRE-HCCs. IRE-HCCs also expressed higher levels of immunomarkers of hypoxia (carbonic anhydrase IX, 64 vs. 8%) and stemness (EpCAM, 50 vs. 20%). p values were < 0.001 for all comparisons except for EpCAM (p = 0.026). HCCs with intermediate enhancement patterns showed mixed/intermediate pathologic features from both IRE- and non-IRE-HCCs. IRE-HCC patients showed poorer 5-year disease-free survival after curative resection than non-IRE-HCC patients (p = 0.005). Conclusions: IRE-HCCs demonstrate aggressive histopathologic features, including more hypoxic and fibrotic tumor microenvironments and increased stemness, compared to non-IRE-HCCs. IRE might therefore serve as a noninvasive imaging biomarker for aggressive HCC.

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Section: Discussionsupporting

confidence: 89%

Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features

Rhee

An²,

Kim

et al. 2018

Liver Cancer

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“…In the present study, abnormal AFP level, an independent risk factor for MVI, was also significantly associated with MVI. However, tumor size and neoplasm grade were not associated with MVI status in either cohort in our study; this finding is in agreement with that of Chandarana et al (36) and inconsistent with that of Renzulli et al (15). There are conflicting data regarding the efficiency of tumor size in predicting MVI in HCC.…”

Section: Discussionsupporting

confidence: 70%

“…A previous study reported radiogenomic venous invasion (RVI), which included internal arteries, hypodense halo, and tumor-liver difference, as a contrast-enhanced CT biomarker for prediction of MVI (13). Another study reported "two-trait predictor of venous invasion" (TTPVI), which included internal arteries and hypodense halo, to exhibit a high predictive accuracy (15). However, these previous studies were limited by the irrelatively small sample sizes and lack of internal or external validation.…”

Section: Discussionmentioning

confidence: 99%

“…Each image was validated by a senior radiologist. Imaging features were determined for each HCC, in accordance with previous studies (13,15).…”

Section: Analysis Of Radiologic Featuresmentioning

confidence: 99%

“…to be predictors of MVI status, there is still debate about the best predictive feature of MVI in HCC (13)(14)(15). Therefore, establishing these radiologic features require further validation studies.…”

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confidence: 99%

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A radiomics nomogram for preoperative prediction of microvascular invasion risk in hepatitis B virus-related hepatocellular carcinoma

Peng

Zhang

et al. 2018

Diagn Interv Radiol

153

124

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H epatocellular carcinoma (HCC) is the sixth most common type of cancer and ranks third as a cause of cancer-related death globally. Worldwide, approximately 630 000 new cases of HCC occur annually, with more than half of these cases occurring in China (1). This disease is related to hepatitis B virus (HBV) infection in almost 70%-90% of cases in the highly endemic Asia-Pacific regions, especially in China (2, 3). Partial hepatectomy and liver transplantation are the most effective curative treatments, albeit in a limited number of cases (4). Indeed, the 5-year recurrence rates after surgical treatment and liver transplantation are as high as 70% and 35%, respectively (5-7). It is, therefore, necessary to find effective biomarkers that can identify aggressive behavior and predict tumor recurrence after liver resection and transplantation.In HCC, the presence of microvascular invasion (MVI) is a histopathologic feature indicative of aggressive behavior (8). Previous studies have identified MVI as a major risk factor for early recurrence in the first two years after liver resection and transplantation (9). Precise identification of MVI involvement in patients with HCC is critical to develop treatment strategies and arrive at prognoses. Over the past decade, researchers have made persistent endeavors towards the preoperative prediction of MVI (10-12). Although several radiologic features on contrast-enhanced magnetic resonance imaging (MRI) and computed tomography (CT) images (such as tumor margin, internal arteries, and hypodense halos) are known PURPOSE We aimed to develop and validate a radiomics nomogram for preoperative prediction of microvascular invasion (MVI) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODSA total of 304 eligible patients with HCC were randomly divided into training (n=184) and independent validation (n=120) cohorts. Portal venous and arterial phase computed tomography data of the HCCs were collected to extract radiomic features. Using the least absolute shrinkage and selection operator algorithm, the training set was processed to reduce data dimensions, feature selection, and construction of a radiomics signature. Then, a prediction model including the radiomics signature, radiologic features, and alpha-fetoprotein (AFP) level, as presented in a radiomics nomogram, was developed using multivariable logistic regression analysis. The radiomics nomogram was analyzed based on its discrimination ability, calibration, and clinical usefulness. Internal cohort data were validated using the radiomics nomogram. RESULTSThe radiomics signature was significantly associated with MVI status (P < 0.001, both cohorts). Predictors, including the radiomics signature, nonsmooth tumor margin, hypoattenuating halos, internal arteries, and alpha-fetoprotein level were reserved in the individualized prediction no- CONCLUSIONThe radiomics nomogram, as a noninvasive preoperative prediction method, shows a favorable predictive accuracy for MVI status in patients with HBV-related HCC.

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Contrast‐enhanced CT radiomics for preoperative evaluation of microvascular invasion in hepatocellular carcinoma: A two‐center study

Zhang

Ruan

Xiao

et al. 2020

Clinical & Translational Med

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Background The present study constructed and validated the use of contrast‐enhanced computed tomography (CT)‐based radiomics to preoperatively predict microvascular invasion (MVI) status (positive vs negative) and risk (low vs high) in patients with hepatocellular carcinoma (HCC). Methods We enrolled 637 patients from two independent institutions. Patients from Institution I were randomly divided into a training cohort of 451 patients and a test cohort of 111 patients. Patients from Institution II served as an independent validation set. The LASSO algorithm was used for the selection of 798 radiomics features. Two classifiers for predicting MVI status and MVI risk were developed using multivariable logistic regression. We also performed a survival analysis to investigate the potentially prognostic value of the proposed MVI classifiers. Results The developed radiomics signature predicted MVI status with an area under the receiver operating characteristic curve (AUC) of .780, .776, and .743 in the training, test, and independent validation cohorts, respectively. The final MVI status classifier that integrated two clinical factors (age and α‐fetoprotein level) achieved AUC of .806, .803, and .796 in the training, test, and independent validation cohorts, respectively. For MVI risk stratification, the AUCs of the radiomics signature were .746, .664, and .700 in the training, test, and independent validation cohorts, respectively, and the AUCs of the final MVI risk classifier‐integrated clinical stage were .783, .778, and .740, respectively. Survival analysis showed that our MVI status classifier significantly stratified patients for short overall survival or early tumor recurrence. Conclusions Our CT radiomics‐based models were able to predict MVI status and MVI risk of HCC and might serve as a reliable preoperative evaluation tool.

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Can Current Preoperative Imaging Be Used to Detect Microvascular Invasion of Hepatocellular Carcinoma?

Abstract: "Worrisome" imaging features, such as tumor dimension, nonsmooth tumor margins, peritumoral enhancement, and TTPVI, have high accuracy in the prediction of MVI in HCC.

Cited by 302 publications

References 33 publications

Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features

Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features

A radiomics nomogram for preoperative prediction of microvascular invasion risk in hepatitis B virus-related hepatocellular carcinoma

Contrast‐enhanced CT radiomics for preoperative evaluation of microvascular invasion in hepatocellular carcinoma: A two‐center study

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