Efficacy and safety of transcatheter arterial chemoembolization combined with microwave ablation for hepatic hemangiomas (> 5 cm)

Table 1 Baseline characteristics, n (%)

Characteristics1	All (n = 82)	Control group (n = 32)	Observation group (n = 50)	P value2
Age (years)	46 (40-54)	47 (41-55)	44 (39-52)	0.122
Longest tumor diameter (cm)	8.4 (5-20)	8.5 (5-20)	8.3 (5-19.2)	0.860
Disease duration (years)	6 (1-13)	7 (2-12)	5 (1-14)	0.668
Sex				0.527
Female	65 (79.27)	27 (84.38)	38 (76.00)
Male	17 (20.73)	5 (15.62)	12 (24.00)
Measurable lesions3				0.993
Single	73 (89.02)	29 (90.62)	44 (88.00)
Multiple	9 (10.98)	3 (9.38)	6 (12.00)
Lesion distribution				0.909
Right lobe	59 (71.95)	24 (75.00)	35 (70.00)
Left lobe	10 (12.20)	3 (9.38)	7 (14.00)
Junction of the right and left lobes	11 (13.41)	4 (12.50)	7 (14.00)
Caudate lobe	2 (2.44)	1 (3.12)	1 (2.00)
Lesion classification4				0.624
Huge	63 (76.83)	26 (81.25)	37 (74.00)
Giant	19 (23.17)	6 (18.75)	13 (26.00)
Symptoms				0.099
Asymptomatic	52 (63.41)	16 (50.00)	36 (72.00)
Abdominal discomfort	27 (32.93)	15 (46.88)	12 (24.00)
Gastrointestinal symptoms	3 (3.66)	1 (3.12)	2 (4.00)
Comorbidities				0.473
No comorbidities	67 (81.71)	25 (78.12)	42 (84.00)
Hypertension	10 (12.20)	5 (15.62)	5 (10.00)
Hyperlipidemia	2 (2.44)	0 (0.00)	2 (4.00)
Diabetes mellitus	2 (2.44)	1 (3.12)	1 (2.00)
SLE	1 (1.22)	1 (3.12)	0 (0.00)
Anxiety status				1.0
No anxiety	75 (91.46)	29 (90.62)	46 (92.00)
Mild anxiety	7 (8.54)	3 (9.38)	4 (8.00)
Reason for treatment				0.128
Enlargement of hemangioma	52 (63.41)	19 (59.38)	33 (66.00)
Symptomatic hemangioma	18 (21.95)	6 (18.75)	12 (24.00)
Anxiety	2 (2.44)	0 (0.00)	2 (4.00)
≥ 2 reasons	10 (12.20)	7 (21.88)	3 (6.00)

¹Continuous variables are expressed as mean ± SD for normally distributed data or median (interquartile range) for non-normally distributed data based on the Shapiro-Wilk test for normality. Categorical variables, including sex and lesion classification, are presented as frequencies (percentages).

²P value was calculated using the independent samples t-test for normally distributed data and the Mann-Whitney U test for non-normally distributed data. The χ² test or Fisher’s exact test was used for categorical variables, and Fisher’s exact test was applied when the expected frequencies were < 5.

³In this study, measurable lesions were defined as lesions with a longest diameter > 5 cm, reflecting a clinically significant disease burden. For patients with multiple hepatic hemangioma lesions (n = 9), we predefined the longest diameter lesion as the “index lesion” for this patient. Each of these 9 patients contained 2 to 3 hemangiomas larger than 5 cm in diameter. Patients with multiple lesions were represented by the index lesion in statistical analyses.

⁴Huge was defined as hemangiomas whose longest tumor diameter ranges from 5 to 10 cm. Giant was defined as hepatic hemangiomas whose longest tumor diameter is > 10 cm.

SLE: Systemic lupus erythematosus.

Table 2 Ablation parameters of the observation group, n (%)

Ablation parameters1	Observation group (n = 50)
Number of ablation procedures
1	47 (94.00)
2	3 (6.00)
Number of ablation probes
1	33 (66.00)
2	17 (34.00)
Average ablation sites	5.78 ± 3.00
Ablation power (W)2
40	1 (2.00)
50	34 (68.00)
60	15 (30.00)
Ablation duration (minute), mean ± SD	27.88 ± 14.11
Embolization to ablation interval3
< 1 week	16 (32.00)
1-3 weeks	10 (20.00)
> 3 weeks	24 (48.00)

¹Continuous variables are expressed as mean ± SD if they are normally distributed or expressed as median ± interquartile range if they are non-normally distributed; categorical variables are expressed as frequency (percentage).

²Ablation power (W) represents the average power output of the ablation device during the procedure. The power settings were adjusted according to the lesion volume and tissue properties.

³The embolization to ablation interval refers to the time interval between embolization and ablation procedures, categorized as < 1 week, 1-3 weeks, and > 3 weeks. Categorization was based on postoperative patient responses and clinical observations.

Table 3 Summary of postprocedural adverse events

Adverse events1	Clavien-Dindo grade	All (n = 82)	Control group (n = 32)	Observation group (n = 50)	P value2
Postprocedural pain	I	20 (24.39)	8 (25.00)	12 (24.00)	1.0
Fever	I	5 (6.10)	1 (3.12)	4 (8.00)	0.669
Nausea and vomiting	I	17 (20.73)	6 (18.75)	11 (22.00)	0.94
Mild perihepatic hemorrhage	I	10 (12.20)	0 (0.00)	10 (20.00)	0.019a
Anemia3	I	0 (0.00)	0 (0.00)	0 (0.00)	1.0
Neutropenia3	I	0 (0.00)	0 (0.00)	0 (0.00)	1.0
Thrombocytopenia3	I	0 (0.00)	0 (0.00)	0 (0.00)	1.0
Hemoglobinuria	I	0 (0.00)	0 (0.00)	0 (0.00)	1.0
Hepatic injury	II	20 (24.39)	2 (6.25)	18 (36.00)	0.005a
Jaundice	II	7 (8.54)	0 (0.00)	7 (14.00)	0.071
Biliary fistula	II	0 (0.00)	0 (0.00)	0 (0.00)	1.0
Liver abscess	II	0 (0.00)	0 (0.00)	0 (0.00)	1.0
Acute kidney injury	IV	0 (0.00)	0 (0.00)	0 (0.00)	1.0

^aP < 0.05; P values < 0.05 were considered statistically significant. Risk ratio for hepatic injury in the observation group compared to the control group was 5.76 (95% confidence interval: 1.43-23.17).

¹Adverse events are listed in ascending order according to the Clavien-Dindo classification, from minor (grade I) to more severe complications (grade IV).

²P value was calculated using the χ² test to compare the distribution of adverse events between the groups.

³Hematologic parameters were monitored considering potential bleomycin-induced bone marrow suppression. Anemia: Hemoglobin < 10.0 g/dL. Neutropenia: Absolute neutrophil count < 1.5 × 10⁹/L. Thrombocytopenia: Platelet count < 75 × 10⁹/L.

Table 4 Comparison of pre- and post-treatment laboratory parameters, mean ± SD

Characteristics	All (n = 82)	Control group (n = 32)	Observation group (n = 50)	P value1
ALT (U/L)
Pre-treatment	25.34 ± 22.85	16.25 ± 11.10	31.16 ± 26.39	< 0.001
Postoperative within 1 week	74.55 ± 122.15	30.62 ± 38.36	102.66 ± 147.19	< 0.001
Postoperative at 1 month	23.39 ± 26.06	18.84 ± 7.13	26.30 ± 32.68	0.227
TBIL (μmol/L)
Pre-treatment	12.81 ± 5.43	11.20 ± 4.53	13.85 ± 5.74	0.034
Postoperative within 1 week	18.83 ± 10.52	14.71 ± 7.53	21.46 ± 11.35	< 0.001
Postoperative at 1 month	11.86 ± 4.05	11.20 ± 3.78	12.28 ± 4.20	0.248
DBIL (μmol/L)
Pre-treatment	3.88 ± 1.68	3.44 ± 1.65	4.16 ± 1.66	0.038
Postoperative within 1 week	4.66 ± 2.36	3.59 ± 1.21	5.35 ± 2.65	< 0.001
Postoperative at 1 month	3.65 ± 1.48	3.38 ± 1.46	3.83 ± 1.47	0.166
Albumin (g/L)
Pre-treatment	43.85 ± 3.94	44.06 ± 5.10	43.72 ± 3.02	0.33
Postoperative within 1 week	40.95 ± 3.08	41.72 ± 3.31	40.46 ± 2.84	0.09
Postoperative at 1 month	43.98 ± 2.57	43.81 ± 3.34	44.08 ± 1.96	0.759
WBC (× 109/L)
Pre-treatment	5.81 ± 1.52	5.77 ± 1.48	5.83 ± 1.56	0.844
Postoperative within 1 week	8.47 ± 3.08	8.86 ± 3.77	8.21 ± 2.56	0.794
Postoperative at 1 month	5.69 ± 1.11	5.69 ± 0.95	5.69 ± 1.21	0.555
Neutrophils (× 109/L)
Pre-treatment	3.78 ± 1.38	3.53 ± 1.07	3.94 ± 1.53	0.274
Postoperative within 1 week	7.02 ± 2.98	7.34 ± 3.67	6.81 ± 2.46	0.761
Postoperative at 1 month	3.59 ± 1.04	3.54 ± 0.83	3.63 ± 1.16	0.775
Platelets (× 109/L)
Pre-treatment	218.45 ± 56.88	220.47 ± 65.79	217.16 ± 51.05	0.799
Postoperative within 1 week	198.87 ± 60.03	201.38 ± 80.27	197.26 ± 43.29	0.868
Postoperative at 1 month	225.18 ± 53.08	228.53 ± 63.39	223.04 ± 45.87	0.816
Hemoglobin (g/L)
Pre-treatment	134.45 ± 17.30	134.97 ± 16.50	134.12 ± 17.96	0.83
Postoperative within 1 week	128.63 ± 20.91	130.38 ± 15.33	127.51 ± 23.90	0.936
Postoperative at 1 month	132.59 ± 13.43	132.88 ± 14.73	132.40 ± 12.67	0.659
Creatinine (μmol/L)
Pre-treatment	63.68 ± 13.16	62.09 ± 13.94	64.70 ± 12.67	0.232
Postoperative within 1 week	59.72 ± 12.02	59.36 ± 11.12	59.95 ± 12.68	0.985
Postoperative at 1 month	63.57 ± 9.05	62.25 ± 9.02	64.42 ± 9.06	0.175

¹P value was calculated using the χ² test to compare the distribution of adverse events between the groups.

Continuous variables are expressed as mean ± SD if they are normally distributed or expressed as median ± interquartile range if they are non-normally distributed; categorical variables are expressed as frequency (percentage). ALT: Alanine transaminase; DBIL: Direct bilirubin; TBIL: Total bilirubin; WBC: White blood cell.

Table 5 Post-treatment tumor response and follow-up outcomes

Variable	All (n = 82)	Control group (n = 32)	Observation group (n = 50)	P value1
Longest tumor diameter at 1 month	7.0 (5.2-8.2)	6.2 (5.9-9.0)	7.0 (4.95-7.95)	0.70
Longest tumor diameter at 6 months	4.4 (3.2-7.0)	7.5 (4.6-8.9)	4.1 (3.1-6.0)	< 0.05a
Longest tumor diameter at 12 months	4.05 (2.8-6.6)	6.6 (3.5-7.1)	3.7 (2.6-5.2)	< 0.05a
Tumor reduction ratio (%)	46.16 (26.48-58.73)	23.28 (17.5-47.27)	50.98 (37.5-61.8)	< 0.001c
RECIST				< 0.001c
CR	4/51 (7.84%)	1/18 (5.56%)	3/33 (9.09%)
PR	33/51 (64.71%)	5/18 (27.78%)	28/33 (84.85%)
SD	14/51 (27.45%)	12/18 (66.67%)	2/33 (6.06%)
PD	0	0	0
ORR2	37/51 (72.55%)	6/18 (33.33%)	31/33 (93.94%)
Longest tumor diameter at 1-3 years (n = 38)3	3.2 (0.5-5.8)	4.5 (3.5-7.9)	2.8 (0-4)	< 0.05a
RECIST				< 0.01b
CR	7/38 (18.42%)	1/12 (8.33%)	6/26 (23.08%)
PR	24/38 (63.16%)	5/12 (41.67%)	19/26 (73.08%)
SD	6/38 (15.79%)	5/12 (41.67%)	1/26 (3.85%)
PD	1/38 (2.63%)	1/12 (8.33%)	0
ORR2	31/38 (81.58%)	6/12 (50%)	25/26 (96.15%)
Longest tumor diameter at > 3 years (n = 29)3	3.6 (2-5.5)	4.6 (2.05-7.95)	3 (0-4)	0.29
RECIST				0.059
CR	5/29 (17.24%)	1/9 (11.11%)	4/20 (20.00%)
PR	21/29 (72.41%)	5/9 (55.56%)	16/20 (80.00%)
SD	2/29 (6.90%)	2/9 (22.22%)	0
PD	1/29 (3.45%)	1/9 (11.11%)	0
ORR2	26/29 (89.66%)	6/9 (66.67%)	20/20 (100.00%)

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

¹P values were calculated using the χ² test or independent samples t-test, as appropriate. P values < 0.05 were considered statistically significant.

²The objective response rate is defined as the sum of the complete response and partial response.

³At 1-3 years: n = 38 (control group: n = 12; observation group: n = 26); at > 3 years: n = 29 (control group: n = 9; observation group: n = 20). Postoperative follow-up data were primarily collected through enhanced magnetic resonance imaging, while other data were obtained through telephone follow-ups or outpatient visits.

CR: Complete response; ORR: Objective response rate; PD: Progressive disease; PR: Partial response; RECIST: Response Evaluation Criteria in Solid Tumors; SD: Stable disease.

Table 6 Comparison of hospitalization evaluation indicators

Variable1	All (n = 82)	Control group (n = 32)	Observation group (n = 50)	P value
Admission	81.65 ± 21.36	82.50 ± 20.52	81.10 ± 22.07	0.849
Discharge	96.71 ± 6.99	96.41 ± 7.32	96.90 ± 6.84	0.975

¹Activities of daily living scores are expressed as mean ± SD.