Four types of tumor progression after microwave ablation of single hepatocellular carcinoma of ≤5 cm: incidence, risk factors and clinical significance

Figures & data

Figure 1. Flow diagram of patients identified, included, and excluded. MWA: microwave ablation; HCC: hepatocellular carcinoma.

Figure 2. The graphical representations of four types of tumor recurrence after MWA. (A) LTP was defined according to imaging results of abnormal nodular, disseminated, and/or unusual patterns of peripheral enhancement around the ablation site in patients treated with MWA; (B) IDR was described as the appearance of an abnormal nodular, disseminated, or unusual patterns of peripheral enhancement of intrahepatic lesions, which were further away from the ablation zone after MWA treatment; (C) AIR was described as the generation of multiple nodular (≥3) distant from the edge of the ablation zone and the infiltrative recurrence in the treated liver segment that showed enhancement in hepatic arterial phase images and washout on portal or delayed venous phase images at follow-up. The AIR was confined to the initial manifestation of tumor recurrence in patients who were previously considered to have a disease-free status at least 6 months after initial MWA to avoid confusion with IDR [18]; (D) EDR was defined as distant metastasis in the extrahepatic, which has the appearance of an abnormal nodular, disseminated, or unusual patterns of peripheral enhancement of intrahepatic lesions.

Table 1. Baseline patient characteristics.

Characteristic	BCLC 0 group (n = 134)	BCLC A group (n = 206)	p-Value
Demographic and history
Age (years)			0.764^a
Mean ± SD	57.4 ± 10.3	57.7 ± 10.8
Range	24–83	25–81
Sex			0.519^b
Male	108 (87.9)	160 (77.3)
Female	26 (12.1)	46 (22.7)
Comorbid disease			0.085^b
Absence	30 (30.3)	31 (36.1)
Presence	104 (69.7)	175 (63.9)
Etiology			0.024^b*
No	2 (6.1)	5 (13.4)
HBV	124 (90.9)	182 (67.0)
HCV	8 (3.0)	19 (19.6)
Cirrhosis			0.360^b
Absence	3 (87.9)	8 (91.8)
Presence	131 (12.1)	188 (8.2)
CTP grade			0.394^c
A	133 (100)	206 (97.6)
B	1 (0)	0 (2.4)
α-fetoprotein level (ng/ml)			0.254^a
Median	21.7	22.9
Range	3.2–381.2	4.8–762.8
Tumor data
Maximal tumor diameter (cm)
Mean ± SD	1.5 ± 0.2	3.7 ± 0.4	<0.001^a
Range	0.5–1.9	2.0–5.0
Tumor capsule			0.008^b
Absence	26 (78.8)	67 (58.8)
Presence	108 (21.2)	139 (41.2)
Defined tumor margin			0.742^b
Poor	28 (78.8)	43 (78.8)
Well	106 (21.2)	163 (21.2)
Tumor shape			0.189^b
Regular	65 (78.8)	85 (78.8)
Irregular	69 (21.2)	121 (21.2)
Abutting portal vein			0.726^b
Absence	53 (39.6)	83 (40.3)
Presence	81 (60.4)	123 (59.7)
Ablation data (mean/median, range)
Insertion points	1.2 (1–3)	2.5 (1–6)	<0.001^a
Ablation time (s)	472.8 ± 24.2 (120–1920)	661.5 ± 36.4 (220–3920)	<0.001^a
Ablation power (W)	51.8 ± 0.4 (40–70)	51.6 ± 0.3 (40–60)	0.600^a
Ablation energy (J)	24,560 (12,970–31,330)	26,300 (17,890–42,860)	0.002^a
Ablation sessions			0.035^b
1	125 (93.3)	177 (85.9)
2	9 (6.7)	29 (14.1)
Postoperative data
LTP^§#	10 (16.1)	11 (11.6)	0.492^b
IDR^§#	39 (62.9)	59 (62.1)	0.971^b
AIR^§#	5 (8.1)	6 (6.3)	0.681^b
EDR^§#	8 (12.9)	19 (20.0)	0.219^b
Technique effectiveness^§#	134/134 (100)	206/206 (100)	1.000^b
Complications^§#	1/134 (0.7)	3/206 (1.5)	0.485^c
Follow-up (years)			0.787^a
Median	27.3	24.0
Range	3.1–69.4	4.4–68.5

Note. Except where indicated, data are numbers of patients. Data in parentheses are percentages and were calculated by using the total number of patients in each group as the denominator.

^aStudent’s t-test; ^bPearson’s χ² test; ^cFisher’s exact test.

^#Data are the number of treatments; ^§Data in parentheses are percentages.

AFP: α-fetoprotein; LTP = local tumor progression; IDR: intrahepatic distant recurrence; AIR: aggressive intrasegmental recurrence; EDR: extrahepatic distant recurrence; CTP: Child–Turcotte–Pugh; BCLC: Barcelona clinic liver cancer; SD: standard deviation.

Table 2. Univariate analysis for prognostic factors of four types of tumor progressions.

Factors	LTP		IDR		AIR		EDR
	HR	p-Value	HR	p-Value	HR	p-Value	HR	p-Value
Age (years)	1.546 (0.753, 3.108)	0.672	0.753 (0.413, 1.326)	0.182	2.365 (0.977, 5.328)	0.056	1.515 (0.463, 2.828)	0.762
<65
≥65
Gender	0.664 (0.176, 2.507)	0.546	0.864 (0.553, 1.403)	0.555	1.386 (0.402, 4.660)	0.616	1.780 (0.534, 5.930)	0.348
Male
Female
Comorbidities	1.231 (0.261, 5.808)	0.793	0.694 (0.445, 1.084)	0.108	2.216 (0.635, 7.706)	0.211	2.216 (0.635, 7.706)	0.411
Yes
No
Cirrhosis	0.805 (0.102, 6.330)	0.836	0.515 (0.274, 0.968)	0.039*	0.549 (0.151, 1.865)	0.545	0.582 (0.582, 3.745)	0.321
Yes
No
HBV	0.785 (0.131, 4.698)	0.790	1.212 (0.764, 1.925)	0.416	1.738 (0.788, 3.830)	0.171	0.352 (0.200, 1.693)	0.276
Yes
No
Tumor size	2.285 (1.529, 4.112)	0.735	0.953 (0.594, 1.532)	0.841	0.562 (0.165, 1.936)	0.355	1.415 (0.615, 3.255)	0.415
＜3 cm
3–5 cm
Tumor margin	1.345 (0.824, 2.052)	0.531	0.672 (0.346, 1.672)	0.368	1.112 (0.814, 2.655)	0.234	1.228 (0.816, 2.361)	0.739
Poor
Well
Tumor capsule	0.768 (0.254, 2.338)	0.225	0.982 (0.448, 2.782)	0.113	1.045 (0.814, 2.353)	0.576	1.345 (0.814, 2.152)	0.2281
Yes
No
Tumor shape	1.134 (0.567, 2.225)	0.412	0.728 (0.344, 1.982)	0.256	0.278 (0.009, 1.119)	0.582	0.273 (0.104, 1.182)	0.111
Regular
Irregular
CTP grade	0.049 (0.000, 2.572)	0.891	20.43 (12.27, 189.25)	0.003*	11.52 (1.52, 89.25)	0.018*	0.050 (0.000, 3.472)	0.872
A
B
AFP	0.820 (0.217, 3.090)	0.769	1.220 (0.805, 1.849)	0.350	0.904 (0.351, 2.330)	0.834	0.769 (0.325, 1.822)	0.551
>400 ng/ml
≤400 ng/ml
Abutting major vessel	2.278 (0.655, 7.919)	0.195	0.607 (0.331, 1.188)	0.145	2.903 (1.261, 9.932)	0.012*	1.067 (0.377, 3.021)	0.903
Yes
No
BCLC grade	0.780 (0.238, 2.557)	0.682	1.007 (0.672, 1.510)	0.971	0.741 (0.315, 1.746)	0.493	1.672 (0.730, 3.829)	0.224
0
A
Sessions	0.785 (0.105, 5.502)	0.814	1.129 (0.641, 1.991)	0.674	1.348 (0.445, 1.578)	0.359	1.405 (0.493, 4.006)	0.524
1
>1

Note. Numbers in parentheses are the 95% CI.

*Significant statistical difference.

LTP: local tumor progression; IDR: regional recurrence-free survival; AIR: aggressive intrasegmental recurrence; EDR: distant recurrence-free survival; HR: hazard ratio; AFP: α-fetoprotein; CTP: Child–Turcotte–Pugh; BCLC: Barcelona clinic liver cancer.

Table 3. Multivariate analysis for prognostic factors of tumor progression.

Factors	LTP		IDR		AIR		EDR
	HR	p-Value	HR	p-Value	HR	p-Value	HR	p-Value
Age (years)	…	…	…	…	2.619 (1.067, 6.429)	0.036	…	…
<65
≥65
Cirrhosis	…	…	0.510 (0.271, 0.958)	0.036	…	…	…	…
Yes
No
HBV	…	…	…	…	…	…	…	…
Yes
No
Tumor size	…	…	…	…	…	…	…	…
<3 cm
3–5 cm
CTP grade	…	…	21.599 (2.861, 163.056)	0.003	19.863 (2.489, 158.454)	0.005	…	…
A
B
α-fetoprotein	…	…	…	…	…	…	…	…
>400 ng/ml
≤400 ng/ml
Abutting major vessel	…	…	…	…	3.193 (1.356, 7.517)	0.008	…	…
Yes
No

Note. Numbers in parentheses are the 95% CI.

LTP: local tumor progression; IDR: regional recurrence-free survival; AIR: aggressive intrasegmental recurrence; EDR: distant recurrence-free survival; HR: hazard ratio; AFP: α-fetoprotein; CTP: Child–Turcotte–Pugh; BCLC: Barcelona clinic liver cancer.

Figure 3. Kaplan–Meier curves comparing OS, RFS and four types of tumor progression outcomes after MWA between BCLC stage 0 and A group. (A) comparing OS between BCLC stage 0 and A group; (B) comparing RFS between BCLC stage 0 and A group; (C) comparing LTP between BCLC stage 0 and A group; (D) comparing IDR between BCLC stage 0 and A group; (E) comparing AIR between BCLC stage 0 and A group; (F) comparing EDR between BCLC stage 0 and A group. OS: overall survival; RFS: recurrence-free survival; MWA: microwave ablation; BCLC: Barcelona clinic liver cancer; LTP: local tumor progression; IDR: intrahepatic distant recurrence; AIR: aggressive intrasegmental recurrence; EDR: extrahepatic distant recurrence.

Figure 4. Overall survival curves for patients with and patients without TP of HCC after MWA. Curves were obtained with Kaplan–Meier method. (A) Overall survival curves for patients with and patients without LTP of HCC after MWA; (B) Overall survival curves for patients with and patients without IDR of HCC after MWA; (C) Overall survival curves for patients with and patients without AIR of HCC after MWA; (D) Overall survival curves for patients with and patients without EDR of HCC after MWA. HCC: hepatocellular carcinoma; MWA: microwave ablation; LTP: local tumor progression; IDR: intrahepatic distant recurrence; AIR: aggressive intrasegmental recurrence; EDR: extrahepatic distant recurrence.

Table 4. Univariate and multivariable analysis of prognostic factors for overall survival after MWA.

Factors	Univariate analysis		Multivariate analysis
	HR	p-Value	HR	p-Value
Age (year)	2.783 (1.703, 4.547)	<0.001	2.478 (1.503, 4.084)	<0.001
<65
≥65
Comorbid disease	1.864 (1.023, 3.397)	0.042	…	…
No
Yes
Cirrhosis	1.483 (0.594, 3.700)	0.398	…	…
No
Yes
Tumor size (cm)	1.181 (0.689, 2.027)	0.545	…	…
<3
3–5
CTP grade	2.564 (0.354, 18.569)	0.351	…	…
A
B
Occurrence of LTP	1.181 (0.689, 2.027)	0.273	…	…
Yes
No
Occurrence of IDR	1.719 (1.065, 2.774)	0.027
Yes
No			…	…
Occurrence of AIR	3.628 (2.041, 6.449)	0.001	2.648 (1.457, 4.815)	<0.001
Yes
No
Occurrence of EDR	2.638 (1.462, 4.763)	0.009	2.222 (1.218, 4.054)	0.002
Yes
No

Note. Time-dependent Cox proportional hazards model was used for multivariate analysis. Numbers in parentheses are the 95% CI.

MWA: microwave ablation; AFP: α-fetoprotein; HBV: hepatitis B virus; LTP: local tumor progression; IDR: regional recurrence-free survival; AIR: aggressive intrasegmental recurrence; EDR: distant recurrence-free survival; HR: hazard ratio; CTP: Child–Turcotte–Pugh.

Ahmed M. Image-guided tumor ablation: standardization of terminology and reporting criteria-a 10-year update: supplement to the consensus document. J Vasc Interv Radiol. 2014;25(11):1706–1708.

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