Prognosis of Primary Liver Cancer Based on LI-RADS Classification with Extracellular Agent-Enhanced MRI

Figures & data

Figure 1 Flowchart of the study cohort.

Abbreviations: HCC, hepatocellular carcinoma; iCCA, intrahepatic cholangiocarcinoma; cHCC-CCA, combined hepatocellular carcinoma-cholangiocarcinoma.

Table 1 Clinical and Pathologic Characteristics of Study Patients

Variable	HCC	cHCC-CCA	iCCA	P value
Number	239	100	93
Mean age (y) *	57.22±10.78	54.80±11.02	59.98±10.92	0.006
All patients
Men	195 (81.6%)	74 (74%)	68 (73.1%)	0.134
Women	44 (18.4%)	26 (26%)	25 (26.9%)
M:F ratio	195/44	37/13	68/25
Mean nodule size (cm) *	4.04±2.95	3.82±2.82	4.35±2.23	0.416
Cause of cirrhosis
Hepatitis B	207 (86.6%)	90 (90%)	80 (86%)	0.134
Hepatitis C	26 (10.9%)	6 (6%)	6 (6.5%)
Alcoholism	6 (2.5%)	4 (4%)	7 (7.5%)
Tumor location
Left lobe	70 (29.3%)	28 (28%)	33 (35.5%)
Right lobe	163 (68.2%)	70 (70%)	60 (64.5%)
Caudate lobe	6 (2.5%)	2 (2%)	0
Tumor maker value
AFP (≥20ng/mL)	109 (45.6%)	54 (54%)	13 (14%)	< 0.001
CEA (≥5ng/mL)	19 (7.9%)	16 (16%)	13 (14%)	0.064
CA 19–9 (≥37ng/mL)	30 (12.6%)	24 (24%)	39 (41.9%)	< 0.001
Microvascular invasion	77 (30.8%)	34 (34%)	29 (31.2%)	0.001

Notes: Except where indicated, data are numbers of patients, with percentages in parentheses. *Data are means ± standard deviations.

Abbreviations: AFP, alpha fetoprotein; CEA, carcinoembryonic antigen; CA 19–9, carbohydrate antigen 19–9; cHCC-CCA, combined hepatocellular-cholangiocarcinoma; HCC, hepatocellular carcinoma; iCCA, intrahepatic cholangiocarcinoma.

Table 2 Imaging Characteristics of Hepatic Tumors in Cirrhotic Liver at Gadolinium Diethylenetriamine Pentaacetic Acid–Enhanced MRI

Variable	HCC (n=239)	cHCC-CCA (n=100)	iCCA (n=93)	P value	Kappa Value
Major imaging features
Nodule size				0.096
<10mm	7 (2.9%)	5 (5%)	0
10–19mm	32 (13.4%)	18 (18%)	9 (9.7%)
≥20mm	200 (83.7%)	77 (77%)	84 (90.3%)
Non-rim arterial phase hyperenhancement	221 (92.5%)	59 (59%)	21 (22.6%)	< 0.001	0.89
Non-peripheral washout	203 (84.9%)	56 (56%)	11 (11.8%)	< 0.001	0.88
Enhancing capsule	193 (80.7%)	53 (53%)	22 (23.7%)	< 0.001	0.88
Targetoid mass imaging features
Rim arterial phase hyperenhancement	22 (9.2%)	49 (49%)	72 (77.4%)	< 0.001	0.90
Peripheral washout	5 (2.1%)	4 (4%)	25 (26.9%)	< 0.001	0.86
Delayed central enhancement	18 (7.5%)	29 (29%)	69 (74.2%)	< 0.001	0.87
Targetoid restriction	10 (4.2%)	24 (24%)	24 (25.8%)	< 0.001	0.87
Tumor in the vein	10 (4.2%)	11 (11%)	12 (12.9%)	0.022	0.89
Ancillary imaging features
Mild-moderate T2 hyperintensity	226 (94.6%)	94 (94%)	87 (93%)	0.42	0.84
Restricted diffusion	234 (97.9%)	98 (98%)	88 (95%)	0.053	1.0
Nodule-in-nodule	9 (3.8%)	8 (8%)	2 (2.2%)	0.127	0.76
Mosaic	42 (17.6%)	25 (25%)	6 (6.5%)	0.002	0.90
Fat in mass, more than adjacent liver	33 (21.2%)	7 (7%)	1 (1.1%)	< 0.001	0.83
Blood products in mass	40 (16.7%)	15 (15%)	7 (7.5%)	0.196	0.86
Peritumoral biliary dilatation	17 (7.1%)	30 (30%)	27 (29%)	< 0.001	0.92
Liver surface retraction	35 (14.6%)	17 (17%)	37 (39.8%)	< 0.001	0.95
Corona enhancement	33 (13.8%)	23 (23%)	41 (44.1%)	< 0.001	0.84

Note: Data are numbers of lesions, with percentages in parentheses.

Abbreviations: cHCC-CCA, combined hepatocellular-cholangiocarcinoma; HCC, hepatocellular carcinoma; iCCA, intrahepatic cholangiocarcinoma.

Table 3 Results of LI-RADS Categorization of 432 Hepatic Tumors

Variable	LR-3	LR-4	LR-5	LR-M	LR-TIV	P value
All Tumors (n=432)						0
HCC	4 (1.7%)	5 (2.1%)	194 (81.2%)	26 (10.8%)	10 (4.2%)
cHCC-CCA	4 (4%)	3 (3%)	29 (29%)	53 (53%)	11 (11%)
iCCA	1 (1.1%)	4 (4.3%)	5 (5.4%)	71 (76.3%)	12 (12.9%)

Notes: Data are numbers of lesions, with percentages in parentheses. P value was obtained from the comparison among HCC, cHCC-CCA, and iCCA. Liver Imaging Reporting and Data System (LI-RADS) categories are defined as LR-3 (intermediate probability of HCC), LR-4 (probably hepatocellular carcinoma [HCC]), LR-5 (definitely HCC), LR-M (probably malignant, not specific for HCC), and LR-TIV (nodule with definite tumor in the vein).

Abbreviations: HCC, hepatocellular carcinoma; cHCC-CCA, combined hepatocellular-cholangiocarcinoma; iCCA, intrahepatic cholangiocarcinoma.

Table 4 Univariable and Multivariable Analyses of Clinical Factors Affecting Overall Survival and Recurrence-Free Survival

Variable	Overall Survival		Recurrence-Free Survival
	Univariable Analysis	Multivariable Analysis	Univariable Analysis	Multivariable Analysis
Age	1.020(0.999, 1.042)[0.068]		0.999(0.985, 1.013)[0.895]
Sex	1.021(0.595, 1.750)[0.941]		0.933(0.655, 1.330)[0.703]
HBV	0.731(0.309, 1.731)[0.476]		1.254(0.675, 2.329)[0.474]
AFP (≥20ng/mL)	1.156(0.737, 1.813)[0.528]		1.024(0.755, 1.388)[0.879]
CEA (≥5ng/mL)	1.546(0.834, 2.869)[0.167]		1.293(0.839, 1.991)[0.244]
CA 19–9 (≥37ng/mL)	2.212(1.349, 3.629)[0.002]		1.658(1.171, 2.347)[0.004]
Tumor size (>3cm)	1.988(1.210, 3.264)[0.007]	2.131(1.241, 3.659)[0.006]	1.392(1.022, 1.895)[0.036]	1.429(1.034, 1.975)[0.031]
Pathologic diagnosis
cHCC-CCA	2.551(1.504, 4.326)[0.001]		2.094(1.476, 2.973) [<0.01]	1.580(1.029, 2.427)[0.037]
iCCA	2.649(1.451, 4.835)[0.002]		1.702(1.151, 2.518)[0.008]	1.119(0.665, 1.884)[0.671]
HCC	1		1
* LI-RADS category
LR-4 or LR-5	1
LR-M	2.595(1.580, 4.264)[<0.01]	1.869(1.002, 3.486)[0.049]	1.962(1.431, 2.691)[<0.01]	1.698(1.143, 2.522)[0.009]

Notes: Data are hazard ratios. Numbers in parentheses are 95% confidence intervals, and numbers in brackets are P values. *LI-RADS categories were defined as LR-4 (probably HCC), LR-5 (definitely HCC), and LR-M (probably malignant, not specific for HCC).

Abbreviations: cHCC-CCA, combined hepatocellular-cholangiocarcinoma; HCC, hepatocellular carcinoma; iCCA, intrahepatic cholangiocarcinoma; AFP, alpha fetoprotein; CEA, carcinoembryonic antigen; CA 19–9, carbohydrate antigen 19–9.

Figure 2 Recurrence-free survival and overall survival of 432 patients after surgical resection of primary liver cancer according to the Liver Imaging Reporting and Data System (LI-RADS) category and pathologic diagnosis. (a and b) Kaplan–Meier curves for overall survival (a) and recurrence-free survival (b) for patients with HCC, iCCA and HCC-CC. (c and d) Kaplan–Meier curves for overall survival (c) and recurrence-free survival (d) in the LR-M and LR-4/5 categories.

Abbreviations: cHCC-CCA, combined hepatocellular carcinoma-cholangiocarcinoma; HCC, hepatocellular carcinoma; iCCA, intrahepatic cholangiocarcinoma.

Figure 3 Recurrence-free survival and overall survival in patients with single primary liver cancer categorized as LR-M with tumor size >30 mm. Kaplan–Meier curves for overall survival (a) and recurrence-free survival (b) in LR-M with tumor size >30 mm according to pathologic diagnosis.

Figure 4 Recurrence-free survival and overall survival in patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) according to the Liver Imaging Reporting and Data System (LI-RADS) category in comparison with patients categorized as LR-4/5 with hepatocellular carcinoma (HCC) and patients categorized as LR-M with intrahepatic cholangiocarcinoma (iCCA). Kaplan–Meier curves show (a) overall survival and (b) recurrence-free survival after surgical resection of primary liver cancer.

Figure 5 A 64-year-old male patient with hepatitis B–related liver cirrhosis and cHCC-CCA is categorized as Liver Imaging Reporting and Data System category LR-M. A 3.5 cm tumor in the right lobe of the liver shows heterogeneous hyperintensity on T2-weighted imaging (a) and diffusion weighted imaging (b). (c) The arterial phase shows peripheral enhancement on contrast-enhanced T1-weighted imaging with the contrast agent Gd-DTPA, and the nodule exhibits peripheral washout (red arrow) and an enhancing capsule (white arrow) in the delayed phase (d). Small recurrent lesions were found 5 months after surgery in this patient.

Figure 6 A 54-year-old male patient with hepatitis B–related liver cirrhosis and HCC is categorized as LR-M category. A 40-mm nodule shows heterogeneous hyperintensity on (a) diffusion weighted imaging. (b) T1-weighted imaging shows heterogeneous hypointensity in hepatic segment VIII. It presents rim arterial phase hyperenhancement (arrow) on contrast enhanced T1-weighted imaging (c) with contrast agent Gd-DTPA, resulting in delayed central enhancement (arrow) in (d) the delayed phase.

Table 5 Univariable and Multivariable Analyses of Imaging Features Affecting Overall Survival and Recurrence-Free Survival

Variable	Overall Survival	Multivariable Analysis	Recurrence-Free Survival	Multivariable Analysis
	Univariable Analysis		Univariable Analysis
Tumor size (>3cm)	1.988(1.210, 3.264)[0.007]	1.816(1.023, 3.224)[0.042]	1.392(1.022, 1.895)[0.036]
Pathologic diagnosis
cHCC-CCA	2.551(1.504, 4.326)[0.001]		2.094(1.476, 2.973) [<0.01]	1.802(1.182, 2.746)[0.006]
iCCA	2.649(1.451, 4.835)[0.002]		1.702(1.151, 2.518)[0.008]	1.382(0.809, 2.361)[0.236]
HCC	1		1
Non rim arterial phase hyperenhancement	0.441(0.278, 0.699)[0.001]		0.586(0.429, 0.801)[0.001]
Nonperipheral washout	0.483(0.306, 0.761)[0.002]		0.701(0.516, 0.951)[0.022]
Enhancing capsule	0.490(0.311, 0.773)[0.002]		0.981(0.719, 1.340)[0.906]
Rim arterial phase hyperenhancement	2.928(1.853, 4.627)[<0.01]	2.929(1.053, 8.149)[0.040]	1.947(1.435, 2.642)[<0.01]	2.322(1.148, 4.697)[0.019]
Peripheral washout	1.925(0.876, 4.229)[0.103]		1.286(0.729, 2.271)[0.385]
Delayed central enhancement	1.962(1.206, 3.192)[0.007]		1.323(0.949, 1.846)[0.099]
Targetoid restriction	1.358(0.746, 2.471)[0.317]		1.798(1.235, 2.617)[0.002]
Tumor in the vein	2.600(1.398, 4.834)[0.003]		1.091(0.620, 1.921)[0.763]
Nodule-in-nodule	0.712(0.221, 2.292)[0.569]		1.780(0.904, 3.504)[0.095]
Mosaic	2.020(1.199, 3.403)[0.008]		1.322(0.896, 1.952)[0.159]
Fat in mass, more than adjacent liver	0.498(0.227, 1.1.091)[0.082]		0.900(0.575, 1.410)[0.646]
Blood products in mass	1.779(1.046, 3.028)[0.034]		1.520(1.040, 2.224)[0.031]
Peritumoral biliary dilatation	1.758(1.034, 2.990)[0.037]		1.466(1.015, 2.117)[0.041]
Liver surface retraction	1.034(0.596, 1.793)[0.905]		1.488(1.053, 2.103)[0.024]
Corona enhancement	2.850(1.799, 4.513)[<0.01]	1.784(1.052, 3.027)[0.032]	1.264(0.895, 1.786)[0.183]
Mild-moderate T2 hyperintensity	1.070(0.336, 3.402)[0.909]		2.230(0.827, 6.014)[0.113]
Restricted diffusion	0.048(0.00, 24.363)[0.339]		1.607(0.512, 5.041)[0.416]

Notes: Data are hazard ratios. Numbers in parentheses are 95% confidence intervals, and numbers in brackets are P values.

Abbreviations: cHCC-CCA, combined hepatocellular-cholangiocarcinoma; HCC, hepatocellular carcinoma; iCCA, intrahepatic cholangiocarcinoma; LI-RADS, Liver Imaging Reporting and Data System.