Imaging response predictors following drug eluting beads chemoembolization in the neoadjuvant liver transplant treatment of hepatocellular carcinoma

Table 1 Clinical characteristics according to objective response - target lesion response

Variable	NR (n = 44)	RE (n = 141)	Total (n = 185)	P value
Gender (male), n (%)	39 (88.6)	118 (83.7)	157 (84.9)	0.424
Age (yr), mean ± SD	58.7 ± 9.2	57.4 ± 8.1	57.7 ± 8.4	0.3631
BMI, mean ± SD	27.2 ± 4.2	27 ± 4.8	27.1 ± 4.7	0.7171
Systemic hypertension, n (%)	19 (43.2)	60 (42.6)	79 (42.7)	0.941
DM, n (%)	17 (38.6)	46 (32.6)	63 (34.1)	0.463
DLP, n (%)	1 (2.3)	9 (6.4)	10 (5.4)	0.4562
Smoker (%)	12 (27.3)	28 (19.9)	40 (21.6)	0.297
Coagulopathy3, 4, n (%)	21 (47.7)	63 (44.7)	84 (45.4)	0.723
Thrombocitopenia5, n (%)	28 (63.6)	93 (66)	121 (65.4)	0.778
CHILD, n (%)				0.7056
A	19 (45.2)	72 (52.6)	91 (50.8)
B	20 (47.6)	56 (40.9)	76 (42.5)
C	3 (7.1)	9 (6.6)	12 (6.7)
MELD, mean ± SD	12.1 ± 3.5	11.9 ± 3.5	12 ± 3.5	0.6051
Downstaging7 - Milan Criteria, n (%)	9 (20.5)	45 (31.9)	54 (29.2)	0.144
Multinodular HCC, n (%)	19 (43.2)	68 (48.2)	87 (47)	0.558

χ²-test.

¹Student’s t-test;

²Fisher’s exact test;

³Can’t calculate;

⁴Patients with INR > 1.2[19];

⁵Patients with serum platelet counts < 150.000/mm³[20];

⁶Probability ratio test;

⁷Patients undergoing neoadjuvant liver transplant treatment excluded from the Milan Criteria. NR: Non-responder; RE: Responder; BMI: Body mass index; DM: Diabetes mellitus; DLP: Dyslipidemia; CHILD: Child-Turcotte-Pugh classification; MELD: Model for end-stage liver disease; DEB-TACE: Drug-eluting beads transarterial chemoembolization; INR: International normalized ratio; HCC: Hepatocellular carcinoma.

Table 2 Pre procedure laboratory characteristics according to objective response - target lesion response (mRECIST)

Variable	NR (n = 44)	RE (n = 141)	Total (n = 185)	P value
Hb (g/dL)	12.9 ± 2.5	12.9 ± 2	12.9 ± 2.1	0.6671
Ht (%)	37.1 ± 6.7	37.4 ± 5.6	37.3 ± 5.9	0.8621
Creatinine (mg/dL)	0.95 ± 0.81	0.92 ± 0.86	0.93 ± 0.84	0.4591
Albumin (g/dL)	3.43 ± 0.53	3.34 ± 0.55	3.37 ± 0.54	0.5751
Alphafetoprotein (UI/mL)	200.3 ± 463	435.1 ± 2307.2	379.3 ± 2027.7	0.3201
Direct bilirubin (mg/dL)	0.73 ± 0.49	0.65 ± 0.41	0.67 ± 0.43	0.6481
Indirec bilirubina (mg/dL)	1.43 ± 0.87	1.14 ± 0.71	1.21 ± 0.76	0.0501
Total bilirubin (mg/dL)	1.9 ± 1.11	1.78 ± 0.89	1.81 ± 0.94	0.8421
INR	1.31 ± 0.19	1.31 ± 0.21	1.31 ± 0.2	0.7781
Platelets (x 103/mm3)	85 ± 42.9	91.7 ± 54.8	90.1 ± 52.1	0.8101
AST (U/L)	87 ± 68.1	84.4 ± 59	85.1 ± 61.3	0.8421
ALT (U/L)	71.4 ± 52.4	71.5 ± 49.7	71.5 ± 50.2	0.8251

¹Student's t-test. NR: Non-responder; RE: Respondent; Hb: Hemoglobin; Ht: Hematocrit; INR: International normalized ratio; AST: Glutamic-oxalacetic transamisnase; ALT: Glutamic-pyruvic transaminase.

Table 3 Intraoperative information according to objective response - target lesion response (mRECIST)

Variable	NR (n = 44)	RE (n = 141)	Total (n = 185)	P value
Duration (min)	60.9 ± 24.9	64.5 ± 24.8	63.6 ± 24.8	0.3721
Radioscopy time (min)	25.2 ± 11.7	25.2 ± 12	25.2 ± 11.9	0.9271
Contrast volume (mL)	251.8 ± 70.1	249.6 ± 63.1	250.1 ± 64.6	0.8881

¹Student's t-test. NR: Non-responder; RE: Responder; Duration: Total time of chemoembolization procedure; Radioscopy time: Radioscopy time of the chemoembolization procedure.

Table 4 Characteristics of hepatocellular carcinoma according to objective response - nodule-based analysis (mRECIST)

Variable	NR (n = 93)	RE (n = 205)	Total (n = 298)	P value
Preoperative
HCC diameter (cm)	2.2 (1; 8.5)	2.7 (1.1; 8)	2.5 (1; 8.5)	< 0.0011
Liver segment2, n (%)				0.9613
1	2 (2.2)	4 (2)	6 (2)
2	8 (8.6)	24 (11.7)	32 (10.7)
3	5 (5.4)	15 (7.3)	20 (6.7)
4	10 (10.8)	18 (8.8)	28 (9.4)
5	9 (9.7)	23 (11.2)	32 (10.7)
6	19 (20.4)	35 (17.1)	54 (18.1)
7	23 (24.7)	46 (22.4)	69 (23.2)
8	17 (18.3)	40 (19.5)	57 (19.1)
Pseudocapsule, n (%)	47 (50.5)	149 (72.7)	196 (65.8)	< 0.001
Intraoperative
Chemoembolic dosis (mg)	11.4 (1.5; 50)	22.5 (2.4; 100)	18.23 (1.5; 100)	< 0.0011
Feeding vessels				0.0411
mean ± SD	1.2 ± 0.4	1.3 ± 0.5	1.2 ± 0.5
median (min; max)	1 (1; 3)	1 (1; 3)	1 (1; 3)
Selective catheterization@, n (%)				0.1973
Proximal	3 (3.4)	9 (5.2)	12 (4.6)
Segmental	33 (37.9)	47 (27.2)	80 (30.8)
Subsegmental	51 (58.6)	117 (67.6)	168 (64.6)
Hypervascular4, n (%)	70 (75.3)	156 (78.8)	226 (77.7)	0.502
End-point5, n (%)	88 (94.6)	187 (91.2)	275 (92.3)	0.308

¹Mann-Whitney test;

²Liver segmentation according to Couinaud;

³Likelihood ratio test;

⁴Hepatocellular carcinoma identified as hypervascular during hepatic angiography;

⁵Hepatocellular carcinoma that obtained vascular stasis during the first chemoembolization session. NR: Non-responder; RE: Responder; HCC: Hepatocellular carcinoma.

Table 5 Objective response – nodule-based analysis (mRECIST) – responder

Variable	OR	95%CI		P value
		Inferior	Superior
Chemoembolic dose (mg)	1.04	1.02	1.06	< 0.001
Pseudocapsule	2.01	1.18	3.42	0.01

Multiple logistic regression.

Table 6 Characteristics of lesion according to percentage of necrosis - hepatocellular carcinoma treated

Variable	Description	P value
HCC diameter (cm)1	0.21	< 0.001
Chemoembolic dose (mg)1	0.31	< 0.001
Feeding vessel1	0.093	0.11
Liver segment2		0.7093
1	41.7 ± 49.2
2	60.9 ± 43.6
3	64 ± 38.9
4	53 ± 42.4
5	47.3 ± 42
6	50 ± 43.6
7	56.2 ± 41.3
8	59.3 ± 43.2
Pseudocapsule		< 0.0014
No	39.2 ± 43.8
Yes	63.4 ± 39.2
Selective catheterization5		0.0383
Proximal	70.4 ± 43.9
Segmental	46.3 ± 41.6
Subsegmental	59.1 ± 41.9
Hypervascular6		0.9883
No	54.4 ± 43.6
Yes	54.3 ± 42.2
End point7		0.1983
No	66.1 ± 37.7
Yes	54.2 ± 42.6

¹Pearson's correlation;

²Liver segmentation according to Couinaud;

³ANOVA;

⁴Student t-test;

⁵Selective catheterization levels for hepatic chemoembolization (Proximal: right/left hepatic artery trunk; Segmental: right/left hepatic artery segmental branch; Subsegmental: right/left hepatic artery subsegmental branch);

⁶Hepatocellular carcinoma identified as hypervascular during hepatic angiography;

⁷Hepatocellular carcinoma that obtained vascular stasis during the first chemoembolization session. Data expressed as mean ± SD. HCC: Hepatocellular carcinoma.

Table 7 Radiological response – % Necrosis – treated hepatocellular carcinoma

Variable	Coefficient	Standard-error	t value	P value
Constant	27.83	4.64	6	< 0.001
Chemoembolic dose (mg)	0.65	0.14	4.58	< 0.001
Pseudocapsule	18.27	5	3.66	< 0.001

Multiple linear regression.