Risk factors for the recurrence of early hepatocellular carcinoma treated by percutaneous radiofrequency ablation with a multiple-electrode switching system: a multicenter prospective study

Figures & data

Figure 1. Representative case showing the usefulness of the multiple-electrode switching system radiofrequency ablation (MESS-RFA) in ablating a large volume at one time. (A) Image before MESS-RFA showing. A 3.5-cm nodule (arrowheads) with enhancement in the arterial phase. (B) Intra-procedural contrast-enhanced ultrasound guiding tumor (arrowheads) targeting and monitoring. (C) Axial CT image immediately after MESS-RFA showing that the ablation zone (arrowheads) covers the index tumor (5.5 cm in size). (D) Coronal CT image reconstructed from the immediate post-procedural CT scan shows that the ablation zone (arrowheads) measures 5.4 cm in its coronal long axis.

Figure 2. The flow chart shows the first-line treatment results for 139 HCC patients who met the Milan criteria and were treated with a multiple-electrode switching system radiofrequency ablation (MESS-RFA).

Table 1. Baseline characteristics of the 139 patients with HCC treated by percutaneous MESS-RFA.

Characteristic	The first affiliated hospital N = 66	The second affiliated hospital N = 42	The third affiliated hospital N = 31
Age (years)
Mean ± SD^a	52.26 ± 12.16	57.57 ± 10.70	54.23 ± 13.96
Range	25–79	34–77	19–79
Gender: male/female	62/4	36/6	21/10
AFP (ng/ml)
Mean ± SD	119.83 ± 247.79	117.82 ± 172.13	167.31 ± 285.98
Range	1.20–1416.68	1.86–864.00	1.05–1169.00
Abnormal prothrombin (mAU/m)
Mean ± SD	25.65 ± 14.73	26.33 ± 12.22	29.55 ± 17.33
Range	4.50–73.00	6.10–55.00	8.20–108.00
Platelet count (×10^9/L)
Mean ± SD	117.33 ± 37.95	115.60 ± 32.44	103.74 ± 33.68
Range	63–273	71–189	48–182
Serum albumin (g/L)
Mean ± SD	41.85 ± 3.79	41.70 ± 3.85	41.15 ± 3.75
Range	32.70–49.90	36.40–49.30	35.90–49.50
Prothrombin time (s)
Mean ± SD	12.77 ± 1.50	12.66 ± 1.40	12.52 ± 1.42
Range	10.10–15.40	10.20–16.40	10.10–14.90
Child–Pugh class
A	32	21	17
B	34	21	14
Number of tumors
Mean ± SD	1.45 ± 0.64	1.50 ± 0.67	1.55 ± 0.57
Range	1–3	1–3	1–3
<2/≥2	41/25	25/17	15/17
Tumor size (cm)
Mean ± SD	2.89 ± 0.51	3.03 ± 0.66	2.98 ± 0.78
Range	1.8–4.3	1.5–4.4	1.5–4.5
≤4 cm/>4 cm	61/5	36/6	26/5
Follow-up time (months)
Mean ± SD	61.14 ± 13.27	57.60 ± 16.88	57.87 ± 17.05
Range	11–72	13–72	11–72

Data are the number of patients unless otherwise indicated.

^aData are the mean ± standard deviation (SD).

AFP: α-fetoprotein; MESS-RFA: multiple-electrode switching system radiofrequency ablation

Figure 3. The overall recurrence-free survival curve. Sixty-nine patients (49.7%) out of the 139 patients were found to have intrahepatic recurrence (LTP and/or IDR) during follow-up. These recurrences occurred 60 months after ablation (ranging from 3 to 72 months).

Table 2. Risk factors for LTP in univariate and multivariate analysis.

	Univariate analysis		Multivariate analysis
Factor	Hazard ratio (HR) (95% CI)	p	HR (95% CI)	p
Age	1.028 (0.985, 1.072)	.2059	–	–
Male	0.605 (0.171, 2.145)	.4366	–	–
Alkaline phosphatase (ALP)	1.007 (1.000, 1.014)	.0597	–	–
Abnormal prothrombin	0.998 (0.965, 1.032)	.9173	–	–
Prothrombin time	0.951 (0.672, 1.345)	.7763	–	–
Platelet count	0.991 (0.975, 1.007)	.2787	–	–
Child–Pugh class B	1.628 (0.580, 4.576)	.3549	–	–
AFP level > 400 ug/L	2.533 (0.713, 8.992)	.1505	–	–
Albumin level	1.084 (0.952, 1.235)	.2234	–	–
Tumor diameter > 4 cm	6.804 (2.466, 18.770)	.015	4.349 (3.241, 5.836)	.015
Subcapsular (yes)	1.113 (0.146, 8.479)	.9176	–	–
Number of tumors ≥ 2	0.578 (0.160, 2.089)	.4030	–	–

AFP: α-fetoprotein; HR: hazard ratio; 95% CI: 95% confidence interval; LTP: local tumor progression

Figure 4. IDR-free survival curve. Fifty-five (39.56%) patients out of the 139 patients had IDR, and the estimated 1-year, 3-year and 5-year IDR-free survival rates were 78.75, 61.79 and 60.17%, respectively. The average follow-up time was 64 months (ranging from 11 to 72 months).

Table 3. Risk factors for IDR in univariate and multivariate analysis.

	Univariate analysis		Multivariate analysis
Factor	HR (95% CI)	p	HR (95% CI)	p
Age	0.996 (0.975, 1.018)	.7452	–	–
Male	1.023 (0.463, 2.262)	.9550	–	–
ALP	1.011 (1.008, 1.014)	.0001	1.007 (1.004, 1.011)	<.0001
Abnormal prothrombin	1.012 (0.999, 1.026)	.0761	–	–
Prothrombin time	0.975 (0.813, 1.169)	.7836	–	–
Platelet count	0.998 (0.991, 1.006)	.6499	–	–
Child-Pugh class B	1.134 (0.668, 1.924)	.6410	–	–
AFP level > 400 ug/L	0.641 (0.200, 2.053)	.4536	–	–
Albumin level	0.972 (0.904, 1.046)	.4482	–	–
Tumor diameter > 4 cm	0.151 (0.021, 1.094)	.0613	–	–
Subcapsular (yes)	1.351 (0.537, 3.400)	.5225	–	–
Number of tumors ≥ 2	8.633 (4.424, 16.846)	<.001	4.827 (2.479, 10.819)	<.001

ALP: Alkaline phosphatase; AFP: α-fetoprotein; HR: hazard ratio; 95% CI: 95% confidence interval; IDR: intrahepatic distant recurrence

Figure 5. Overall survival curve. The average follow-up time was 59.33 ± 15.34 months, the median follow-up time was 64 months, and 1 patient was lost to follow-up after 24 months. During the follow-up, 27 (19.42%) people died. Among the 27 dead patients, the deaths of 26 patients (18.70%) were associated with HCC progression and one patient (0.71%) had gastric fundus hemorrhage.

Table 4. Risk factors for overall survival in univariate and multivariate analysis.

	Univariate analysis		Multivariate analysis
Factor	HR (95% CI)	p	HR (95% CI)	p
Age	1.018 (0.987, 1.049)	.2582	–	–
Male	0.618 (0.251, 1.527)	.2973	–	–
ALP	1.005 (1.000, 1.010)	.0760	–	–
Abnormal prothrombin	1.014 (0.995, 1.034)	.1465	–	–
Prothrombin time	1.165 (0.902, 1.503)	.2416	–	–
Platelet count	0.996 (0.985, 1.007)	.4358	–	–
Child-Pugh class B	0.923 (0.439, 1.941)	.8326	–	–
AFP level > 400 ug/L	3.105 (1.255, 7.684)	.0142	3.105 (1.255, 7.684)	.0142
Albumin level	1.026 (0.931, 1.130)	.6061	–	–
Tumor diameter > 4 cm	1.666 (0.633, 4.384)	.3012	–	–
Subcapsular (yes)	1.603 (0.483, 5.314)	.4406	–	–
Number of tumors ≥ 2	1.782 (0.847, 3.747)	.1277	–	–

ALP: Alkaline phosphatase; AFP: α-fetoprotein; HR: hazard ratio; 95% CI: 95% confidence interval

Table 5. Comparison of the recurrence time and different survival states.

	Interval of recurrence (months)
	Mean	Standard deviation	Median	Minimal value	Maximal value	T	p
Survival	49.13	23.51	62.00	7.00	72.00	6.61	<.0001
Death	12.64	14.11	8.00	3.00	67.00	–	–

An independent sample t-test showed that the interval of recurrence of surviving patients was longer than that of the dead patients, and the difference was statistically significant.