The role of neoadjuvant conventional transarterial chemoembolization with radiofrequency ablation in the treatment of recurrent hepatocellular carcinoma after initial hepatectomy with microvascular invasion

Figures & data

Figure 1. Flow chart of the patient selection. HCC: hepatocellular carcinoma; HR: hepatic resection; ECOG: Eastern Cooperative Oncology Group; MVI: microvascular invasion; RFA: radiofrequency ablation; TACE: transarterial chemoembolization.

Table 1. Baseline characteristics of recurrent HCC patients with MVI-positive primary tumor who had undergone neoadjuvant TACE with RFA or RFA alone.

Variable	Neoadjuvant TACE with RFA (n = 146)	RFA alone (n = 322)	P value
Gender (M/F)	131/15	286/36	0.771
Age (yr) (range)	54.8 ± 8.9 (22–75)	54.9 ± 8.5 (22–75)	0.281
HBsAg (±)	116/30	261/61	0.685
Diabetes mellitus (±)	20/126	41/281	0.774.
Hypertension (±)	41/105	98/224	0.606
ALT (U/L) (range)	26.7 ± 11.9 (12.5–74.2)	26.9 ± 12.0 (13.2–72.0)	0.124
ALB (g/L) (range)	35.5 ± 2.1 (32.3–45.0)	35.3 ± 3.2 (32.3–45.0)	0.234
Total bilirubin (umol/L) (range)	12.2 ± 2.8 (4.0–22.5)	12.2 ± 3.0 (4.0–22.5)	0.572
ALBI (≤ −2.60/> −2.60)	113/33	257/65	0.552
Platelet count (×10^9/L)	133.2 ± 34.3 (90–450)	134.2 ± 36.0 (85–450)	0.102
Splenomegaly (yes/no)	43/103	74/248	0.134
AFP (ng/ml) (≤ 400/>400)	95/51	186/136	0.135
Tumor stage of primary HCC (BCLC 0-A/B)	87/59	180/142	0.455
Interval of recurrence from initial treatment (year)			0.636
≤1	91	208
>1	55	114
Tumor size (cm)	2.2 (1.2–3.0)	2.1 (1.0–3.0)	0.654
Initial hepatic resection type			0.147
1 segment	96	189
>1 segment	50	133
Antiviral treatment for hepatitis B (yes/no)	79/37	199/62	0.097

HCC: hepatocellular carcinoma; TACE-RFA: transarterial chemoembolization plus radiofrequency ablation; RFA: radiofrequency ablation; HBsAg: hepatitis B surface antigen; HCV: hepatitis C virus; ALT: alanine aminotransferase; ALB: albumin; GGT: γ-glutamyl transpeptidase; AFP: alpha fetoprotein; BCLC: Barcelona Clinic Liver Cancer; MVI: microvascular invasion.

Figure 2. Kaplan-Meier curves of the survival outcomes of patients with solitary small recurrent HCC with MVI-positive primary tumor who were treated with neoadjuvant TACE and RFA or RFA alone. Kaplan-Meier curves of overall survival (A) and recurrence-free survival (B) for patients who underwent neoadjuvant TACE and RFA or RFA alone. HCC: hepatocellular carcinoma; MVI: microvascular invasion; TACE: transarterial chemoembolization; RFA: radiofrequency ablation.

Figure 3. The hazard ratio of overall survival and recurrence-free survival for patients with solitary small recurrent HCC with MVI-positive primary tumor who were treated with neoadjuvant TACE and RFA or RFA alone in different subgroups stratified by clinical parameters. (A) for overall survival; (B) for recurrence-free survival. HBsAg: hepatitis B surface antigen; ALT: alanine aminotransferase; ALB: albumin; ALBI: albumin bilirubin; AFP: alpha fetoprotein; BCLC: Barcelona Clinic Liver Cancer; TACE: transarterial chemoembolization; RFA: radiofrequency ablation.

Table 2. Univariable and multivariable analyses of predictors of overall survival and recurrence-free survival for recurrent HCC patients with MVI-positive primary tumor.

Factors	Overall survival				Recurrence free survival
	Univariable	Multivariable			Univariable	Multivariable
	P value	HR	95% CI	P value	P value	HR	95% CI	P value
Gender (M/F)	0.219				0.094
Age (≤60/>60)	0.924				0.572
HBsAg (±)	0.737				0.478
Diabetes mellitus (±)	0.213				0.955
Hypertension (±)	0.126				0.699
Platelet count (<100/≥100)	0.039				0.017
Splenomegaly (yes/no)	0.671				0.805
Interval of recurrence from initial treatment (year) ( >1/≤1)	0.015				0.002	0.298	0.095–0.932	0.037
Tumor stage of primary HCC (BCLC 0-A/B)	0.770				<0.001
Total bilirubin level (mg/dL) (≤20.5/>20.5)	0.170				0.665
ALB level (g/L) (<35/≥35)	0.075				0.042
ALT (IU/L) (≤40/>40)	0.413				0.437
ALBI (≤ −2.60/> −2.60)	0.143				0.797
AFP (ng/mL) (>400 /≤400)	0.467				0.205
Maximum diameter of intrahepatic tumors (cm) (≤2/>2)	0.045				<0.001	1.522	1.072–2.159	0.019
Initial hepatic resection type (segment) (1/>1)	0.189				0.653
Treatment allocation (RFA vs. neoadjuvant TACE with RFA)	<0.001	0.516	0.381–0.700	<0.001	<0.001	0.526	0.408–0.678	<0.001
Antiviral treatment for hepatitis B (yes/no)	0.749				0.541

HR: hazard ratio; CI: confidence interval; HBsAg: hepatitis B surface antigen; HCV: hepatitis C virus; HCC: hepatocellular carcinoma; BCLC: Barcelona Clinic Liver Cancer group; ALB: albumin; ALT: alanine aminotransferase; AFP: alpha fetoprotein; RFA: radiofrequency ablation; TACE: transarterial chemoembolization.

Figure 4. Recurrences after the treatments for recurrent HCC patients with MVI-positive primary tumor, and treatment modalities for subsequent recurrences in patients with solitary small recurrent hepatocellular carcinoma. (A) for patients who underwent adjuvant TACE and RFA; (B) for patients who underwent RFA alone. HCC: hepatocellular carcinoma; TACE: transarterial chemoembolization; RFA: radiofrequency ablation; ER: extrahepatic recurrence, IR: intrahepatic recurrence.

Table 3. Complications after treatment.

Variable	Neoadjuvant TACE with RFA (n = 146)	RFA alone (n = 322)	P value
Major complication	18	31	0.428
Pain	3	6	0.891
Liver failure	9	14	0.424
Postoperative hemorrhage	6	11	0.721
Minor complication	133	253	0.312
Fever (temperature> 38.5 °C)	31	54	0.338
Ascites	27	37	0.078
Vomiting	49	106	0.923
Skin burn	1	1	0.567
Lung infection	3	7	0.936
Pleural effusion	22	48	0.969

TACE-RFA: transarterial chemoembolization plus radiofrequency ablation; RFA: radiofrequency ablation.