Optimal postoperative adjuvant treatment strategy for HBV-related hepatocellular carcinoma with microvascular invasion: a propensity score analysis

Figures & data

Table 1 Comparisons of Baseline demographics and clinicopathological characteristics in patients undergoing TACE or RT before and after propensity score matching analysis

Characteristic	RT (N=46)	Before matching		After matching
		TACE (N=71)	P-value	TACE (N=46)	P-value
Age (years)	50.98±10.53	51.59±10.84	0.763	51.52±11.40	0.813
Sex			0.144		0.119
Male	43 (93%)	60 (85%)		37 (80%)
Female	3 (7%)	11 (15%)		9 (20%)
Operative time	233.65±77.82	233.73±83.00	0.996	233.26±87.45	0.982
Operative procedure			0.582		0.529
Major	19 (41%)	33 (46%)		22 (48%)
Minor	27 (5%)	38 (54%)		24 (52%)
Operative method			0.717		0.676
Anatomical	21 (46%)	30 (42%)		23 (50%)
Nonanatomical	25 (54%)	41 (58%)		23 (50%)
Blood loss (mL)	568.48±487.10	483.52±424.43	0.321	464.78±482.34	0.308
Surgical margin			0.082		0.116
≤1 cm	35 (76%)	43 (60%)		28 (61%)
>1 cm	11 (24%)	28 (40%)		18 (39%)
Tumor size (cm)	5.39±2.74	6.57±3.65	0.048	5.50±3.07	0.851
Number of tumor			0.654		0.726
Single	42 (91%)	63 (61%)		41 (89%)
Multiple	4 (9%)	8 (39%)		5 (11%)
Differentiation			0.582		0.529
Well-moderate	27 (59%)	38 (54%)		24 (52%)
Poorly	19 (41%)	33 (56%)		22 (58%)
MVI classification			0.005		0.492
M1	34 (74%)	34 (48%)		31 (67%)
M2	12 (26%)	37 (52%)		15 (33%)
Envelope invasion			0.185		0.634
Present	32 (70%)	57 (80%)		34 (74%)
Absent	14 (30%)	14 (20%)		12 (26%)
Cirrhosis			0.477		0.536
Present	41 (89%)	60 (85%)		39 (85%)
Absent	5 (9%)	11 (15%)		7 (15%)
HBV-Ag			0.899		0.599
Negative	8 (17%)	13 (18%)		10 (22%)
Positive	38 (83%)	58 (82%)		36 (78%)
Preoperative AFP level			0.071		0.436
Negative	18 (39%)	15 (21%)		15 (32%)
≦400 ng/L	18 (39%)	30 (42%)		24 (53%)
>400 ng/L	10 (22%)	26 (37%)		7 (15%)
Preoperative ALT level (U/L)	35.33±17.52	32.48±16.87	0.382	31.21±16.30	0.247
Preoperative TBIL level (µmol/L)	12.05±4.79	12.41±4.72	0.690	11.84±4.37	0.826
Preoperative ALB level (g/L)	42.54±4.06	43.11±5.24	0.519	43.35±4.67	0.379
Preoperative PTa level (%)	82.67±10.74	85.36±10.12	0.172	86.28±10.21	0.102

Note: Variables are expressed as the mean ± SD (median with range) or N (%) (number with percentages), unless otherwise indicated.

Abbreviations: TACE, transcatheter arterial chemoembolization; RT, radiotherapy; AFP, alpha-fetoprotein; ALT, alanine aminotransferase; TBIL, total bilirubin; ALB, albumin; PTa, prothrombin time.

Table 2 Univariate and multivariate survival analysis of RFS and OS in HCC patients with MVI undergoing RT or TACE before propensity score matching analysis

Variable	Cox
	Univariate analysis		Multivariate analysis
	HR (95% CI)	P-value	HR (95% CI)	P-value
RFS
Age (years)	0.984 (0.965–1.004)	0.123
Gender	1.145 (0.551–2.377)	0.717
Operative procedure	0.981 (0.631–1.523)	0.931
Operative method	1.063 (0.685–1.650)	0.784
Surgical margin	0.972 (0.608–1.554)	0.907
Tumor size	1.146 (1.037–1.224)	0.000	1.083 (1.013–1.158)	0.019
Number of tumors	0.961 (0.480–1.924)	0.910
Differentiation	1.085 (0.697–1.691)	0.717
MVI classification	4.388 (2.758–6.982)	<0.001	3.525 (2.161–5.749)	<0.001
Envelope invasion	2.091 (1.172–3.730)	0.013
Cirrhosis	1.012 (0.520–1.968)	0.972
AFP level	1.569 (1.166–2.111)	0.003
Postoperative treatment strategies	0.385 (0.238–0.623)	<0.001	0.509 (0.309–0.840)	0.008
OS
Age (years)	0.980 (0.955–1.006)	0.130
Gender	0.844 (0.357–1.995)	0.699
Operative procedure	1.238 (0.694–2.209)	0.470
Operative method	1.010 (0.565–1.808)	0.972
Surgical margin	0.970 (0.516–1.827)	0.926
Tumor size	1.228 (1.132–1.331)	<0.001	1.169 (1.076–1.269)	<0.001
Number of tumors	0.651 (0.202–2.098)	0.472
Differentiation	0.801 (0.439–1.460)	0.468
MVI classification	4.238 (2.264–7.935)	0.000	3.151 (1.629–6.097)	0.001
Envelope invasion	3.014 (1.190–7.634)	0.020
Cirrhosis	0.904 (0.354–2.306)	0.833
AFP level	1.576 (1.069–2.323)	0.022
Postoperative treatment strategies	0.522 (0.281–0.969)	0.040

Abbreviations: RFS, relapse-free survival; OS, overall survival; HCC, hepatocellular carcinoma; MVI, microvascular invasion; RT, radiotherapy; TACE, transcatheter arterial chemoembolization; AFP, alpha-fetoprotein.

Table 3 Univariate and multivariate survival analyses of RFS and OS in HCC patients with MVI undergoing RT or TACE after propensity score matching analysis

Variable	Cox
	Univariate analysis		Multivariate analysis
	HR (95% CI)	P-value	HR (95% CI)	P-value
RFS
Age (years)	0.982 (0.960–1.005)	0.121
Gender	1.238 (0.532–2.882)	0.621
Operative procedure	0.823 (0.489–1.385)	0.464
Operative method	1.155 (0.691–1.930)	0.583
Surgical margin	1.179 (0.680–2.044)	0.558
Tumor size	1.127 (1.030–1.233)	0.009	1.104 (1.011–1.205)	0.027
Number of tumors	0.883 (0.379–2.056)	0.772
Differentiation	0.980 (0.582–1.651)	0.940
MVI classification	4.500 (2.620–7.729)	<0.001	4.533 (2.612–7.869)	<0.001
Envelope invasion	2.072 (1.096–3.916)	0.025
Cirrhosis	1.239 (0.531–2.894)	0.620
AFP level	1.258 (0.880–1.798)	0.208
Postoperative treatment strategies	0.461 (0.273–0.779)	0.004	0.447 (0.264–0.757)	0.003
OS
Age (years)	0.978 (0.950–1.008)	0.144
Gender	1.015 (0.355–2.898)	0.978
Operative procedure	1.137 (0.574–2.252)	0.713
Operative method	1.276 (0.637–1.276)	0.492
Surgical margin	0.792 (0.356–1.763)	0.568
Tumor size	1.223 (1.094–1.367)	0.000	1.175 (1.048–1.317)	0.006
Number of tumors	0.261 (0.036–1.909)	0.186
Differentiation	0.749 (0.368–1.524)	0.425
MVI classification	5.127 (2.458–10.69)	<0.001	5.083 (2.249–11.485)	<0.001
Envelope invasion	3.119 (1.096–8.878)	0.033
Cirrhosis	1.061 (0.321–3.510)	0.923
AFP level	1.447 (0.898–2.333)	0.127	1.704 (1.015–2.861)	0.044
Postoperative treatment strategies	0.672 (0.334–1.351)	0.264

Abbreviations: RFS, relapse-free survival; OS, overall survival; HCC, hepatocellular carcinoma; MVI, microvascular invasion; RT, radiotherapy; TACE, transcatheter arterial chemoembolization; AFP, alpha-fetoprotein.

Figure 1 Before PSM: (A) RFS rates of the RT and TACE groups (B) OS rates of the RT and TACE groups.

Abbreviations: RT, radiotherapy; TACE, transcatheter arterial chemoembolization; PSM, propensity score matching; RFS, relapse-free survival; OS, overall survival.

Figure 2 After PSM: (A) RFS rates of the RT and TACE groups (B) OS rates of the RT and TACE groups.

Abbreviations: RT, radiotherapy; TACE, transcatheter arterial chemoembolization; PSM, propensity score matching; RFS, relapse-free survival; OS, overall survival.

Table 4 Pattern of recurrence and treatment in the RT and TACE groups

Recurrence pattern	RT (N=25)	Before matching		After matching
		TACE (N=56)	P-value	TACE (N=34)	P-value
Growth pattern
Nodular	16 (64%)	18 (32%)	0.007	15 (44%)	0.131
Diffuse	9 (36%)	38 (68%)	0.285	19 (56%)	0.297
Location
Intrahepatic	19 (76%)	48 (86%)		30 (88%)
Extrahepatic	6 (24%)	8 (14%)		4 (12%)
Resection
Margin	4 (16%)	9 (16%)	1.000	7 (21%)	0.745
Nonmargin	21 (84%)	47 (84%)		27 (79%)
Treatment for the first recurrence
Resection/ablation	10 (40%)	7 (13%)	0.017	7 (21%)	0.253
TACE	11 (44%)	39 (70%)		21 (62%)
Chemotherapy/sorafenib	4 (16%)	10 (17%)		6 (17%)

Abbreviations: RT, radiotherapy; TACE, transcatheter arterial chemoembolization.