Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation

Table 1 Baseline characteristics of the study population n (%)

Variable	All treated patients (n= 38)	Type of TACE		P value
		DEB-TACE (n= 22)	c-TACE (n= 16)
Age at LT (yr)	56.5 ± 6.5	57.2 ± 6.5	55.6 ± 6.5	0.4545
Male gender	34 (89.5)	19 (86.4)	15 (93.7)	0.6245
MELD score	10 (6-27)	9 (6-27)	10 (7-16)	0.4688
Etiology of cirrhosis				0.1834
HCV-related	22 (57.9)	10 (45.5)	12 (75.0)
HBV-related	11 (28.9)	8 (36.3)	3 (18.7)
Non-viral	5 (13.2)	4 (18.2)	1 (6.3)
Waiting list time (mo)	3.1 (0.1-26.7)	2.9 (0.1-24.3)	3.3 (0.6-26.7)	0.5844
Interval between last TACE and LT (mo)	3.6 (0.1-15.9)	2.3 (0.2-13.8)	5.5 (0.9-15.9)	0.0625
Repeated TACE	20 (52.6)	12 (54.5)	8 (50.0)	0.7817
Adherence to MC at imaging before TACE				0.3243
Within MC	21 (55.3)	14 (63.6)	7 (43.7)
Beyond MC	17 (44.7)	8 (36.4)	9 (56.3)
BCLC stage before TACE				0.3243
A	21 (55.3)	14 (63.6)	7 (43.7)
B	17 (44.7)	8 (36.4)	9 (56.3)
Number of nodules before TACE	2 (1-5)	2 (1-5)	2 (1-5)	0.8708
Nodule number class before TACE				0.2222
1 nodule	16 (42.1)	8 (36.4)	8 (50.0)
1 < nodules < 4	13 (34.2)	10 (45.4)	3 (18.8)
Nodules ≥ 4	9 (23.7)	4 (18.2)	5 (31.2)
1Serum α-fetoprotein > 70 ng/mL	8/33 (24.2)	3/18 (16.7)	5/15 (33.3)	0.4811
Post-LT follow-up (mo)	39.9 ± 22.5	34.9 ± 19.0	46.8 ± 25.6	0.1065

Continuous variables are reported as the mean and standard deviation or median and range and compared using Student’s t test or the Mann-Whitney U test as appropriate. Categorical variables are reported as numbers and percentages.

¹Value of serum α-fetoprotein was not available for 5 patients. TACE: Transcatheter arterial chemoembolization; DEB: Doxorubicin-eluting bead; MC: Milan Criteria; LT: Liver transplantation; HCV: Hepatitis C virus; HBV: Hepatitis B virus; MELD: Model for End Stage Liver Disease; c-TACE: Conventional TACE; BCLC: Barcelona Clinic Liver Cancer.

Table 2 Analysis of the treated nodules according to the type of transcatheter arterial chemoembolization (per nodule analysis) n (%)

Variable	All treated nodules 63 in 38 patients	Type of TACE		P value
		DEB-TACE 38 in 22 patients	c-TACE 25 in 16 patients
Degree of necrosis	54.3% ± 41.2%	55.7% ± 41.9%	52.2% ± 40.9%	0.7420
Complete necrosis (100%)	21 (33.3)	14 (36.8)	7 (28.0)	0.5877
Histological response				0.2834
Appropriate (necrosis ≥ 90%)	25 (39.7)	17 (44.7)	8 (32.0)
Partial (50% < necrosis < 90%)	9 (14.3)	3 (7.9)	6 (24.0)
Inadequate (necrosis ≤ 50%)	29 (46.0)	18 (47.4)	11 (44.0)
Diameters of nodules (cm)	2 (0.7-10)	1.8 (0.7-4.5)	2.2 (1-10)	0.1752
Number of nodules				0.2492
Single	17 (27.0)	8 (21.1)	9 (36.0)
Degree of necrosis	63.1% ± 37.8%	69.7% ± 34.8%	57.2% ± 41.5%	0.5144
Multiple	46 (73.0)	30 (78.9)	16 (64.0)
Degree of necrosis	51.1% ± 42.3%	52.0% ± 43.4%	49.4% ± 41.7%	0.8454
Modality of TACE				0.3015
Superselective	34 (54.0)	23 (60.5)	11 (44.0)
Degree of necrosis	73.9% ± 34.3%	76.2% ± 33.8%	69.1% ± 36.5%	0.5803
Non-superselective	29 (46.0)	15 (39.5%)	14 (56.0)
Degree of necrosis	31.3% ± 37.0%	24.3% ± 33.3%	38.9% ± 40.5%	0.2970

Analysis performed considering nodules reached by transarterial treatment (targeted lesions). Continuous variables are reported as median and range or mean and standard deviation and compared using the Student’s t test or Mann-Whitney U test as appropriate. TACE: Transcatheter arterial chemoembolization; DEB: Doxorubicin-eluting bead; c-TACE: Conventional TACE.

Table 3 Patient analysis according to the type of transcatheter arterial chemoembolization (per patient analysis) n (%)

Variable	All treated patients (n= 38)	Type of TACE		P value
		DEB-TACE (n= 22)	c-TACE (n= 16)
Number of nodules per patients	2.2 ± 1.3	2.2 ± 1.2	2.1 ± 1.4	0.7019
Untreated nodules	21/84 (25.0)	13/51 (25.4)	8/33 (24.2)	0.8934
Nodule number class at pathology				0.1473
1 nodule	17 (44.7)	8 (36.4)	9 (56.3)
1 < nodules < 4	14 (36.8)	11 (50.0)	3 (18.7)
≥ 4 nodules	7 (18.4)	3 (13.6)	4 (25.0)
Sum of tumor diameters (cm)	4.2 ± 2.8	4.1 ± 2.4	4.5 ± 3.3	0.5813
CTA (cm2)	5.5 (0.8-78.5)	4.6 (1.5-19.1)	7.2 (0.8-78.5)	0.8592
Necrosis on CTA	55.2% ± 37.0%	58.8% ± 36.6%	50.2% ± 38.1%	0.4856
Adherence to MC at pathology				0.4250
Within MC	31 (81.6)	19 (86.4)	12 (75.0)
Beyond MC	7 (18.4)	3 (13.6)	4 (25.0)
Histological response				0.2896
Appropriate (necrosis on CTA ≥ 90%)	11 (28.9)	8 (36.4)	3 (18.7)
Partial (50% < necrosis on CTA < 90%)	8 (21.1)	3 (13.6)	5 (31.3)
Inadequate (necrosis on CTA ≤ 50%)	19 (50.0)	11 (50.0)	8 (50.0)
Risk factors for recurrence
Microvascular invasion	7 (18.4)	5 (22.7)	2 (12.5)	0.4271
1Grading > 2	7 (18.4)	2/18 (11.1)	5/14 (35.7)	0.1948

Analysis includes the 21 nodules not reached by transarterial treatment (non-targeted lesions). Continuous variables are reported as medians and ranges or means and standard deviations.

¹Assessment of tumor grading was not available for 6 patients who had complete necrosis at explant examination. TACE: Transcatheter arterial chemoembolization; DEB: Doxorubicin-eluting bead; CTA: Cumulative tumor area; MC: Milan Criteria; c-TACE: Conventional TACE.

Table 4 Univariate and multivariate analysis of risk factors related to tumor recurrence

Risk factors	Univariate analysis			Multivariate analysis
	3-yr recurrence-free survival rate	HR (95%CI)	Log rank P value	Exp(b) (95%CI)	P value
Tumor grading G3-G4 (vs G1-G2)	66.7% vs 74.2%	1.76 (0.289-13.149)	0.4934
Presence of microvascular invasion (vs absence)	60.0% vs 80.7%	2.74 (0.451-39.277)	0.2071
Multiple nodules at pathology (vs single)	69.1% vs 85.7%	2.15 (0.460-9.070)	0.3478
Repeated TACE (vs single)	74.1% vs 80.0%	1.08 (0.244-4.821)	0.9148
Necrosis on CTA ≤ 50% (vs > 50%)	59.3% vs 100.0%	NA1	0.0098	NA1	NA1
MC unfulfilled at pathology (vs fulfilled)	21.4% vs 92.0%	13.84 (10.121-636.416)	< 0.0001	11.6 (1.932-69.646)	0.0077
Absence of DEB-TACE (vs presence)	61.5% vs 87.4%	4.47 (1.005-22.188)	0.0493	15.45 (1.457-163.766)	0.0237
α-fetoprotein > 70 ng/mL (vs ≤ 70 ng/mL)	33.3% vs 90.9%	10.31 (4.749-370.242)	0.0008	15.31 (1.766-132.614)	0.0137

¹Heart rate calculation and the inclusion of the covariate in the multivariate analysis was not applicable due to the lack of hepatocellular carcinoma recurrence events in necrosis on the cumulative tumor area (CTA) > 50% group. TACE: Transcatheter arterial chemoembolization; DEB: Doxorubicin-eluting bead; MC: Milan Criteria; NA: Not available.