Disease control and failure patterns of unresectable hepatocellular carcinoma following transarterial radioembolization with yttrium-90 microspheres and with/without sorafenib

doi:10.3748/wjg.v27.i47.8166

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World Journal of Gastroenterology

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World J Gastroenterol. Dec 21, 2021; 27(47): 8166-8181
Published online Dec 21, 2021. doi: 10.3748/wjg.v27.i47.8166

Table 1 Patient and tumor characteristics at time of transarterial radioembolization procedures

Parameters	All procedures (n = 169)	*TARE_alone* (n = 63)	*TARE_sorafenib* (n = 81)	*TARE_no_sorafenib* (n = 25)
ECOG
0	82 (48.5)	32 (50.8)	40 (49.4)	10 (40)
1	82 (48.5)	28 (44.4)	40 (49.4)	14 (56)
2	4 (2.4)	2 (3.2)	1 (1.2)	1 (4)
3	1 (0.6)	1 (1.6)	0	0
BCLC
A	5 (3)	5 (7.9)	0	0
B	45 (26.6)	26 (41.3)	16 (19.8)	3 (12)
C	118 (69.8)	31 (49.2)	65 (80.2)	22 (88)
D	1 (0.6)	1 (1.6)	0	0
Child-pugh class
A	157 (92.9)	57 (90.5)	78 (96.3)	22 (88.0)
B	12 (7.1)	6 (9.5)	3 (3.7)	3 (12.0)
AFP¹
< 400 ng/mL	118 (70.2)	54 (85.7)	52 (64.2)	12 (50)
≥ 400 ng/mL	50 (29.8)	9 (14.3)	29 (35.8)	12 (50)
Cirrhosis
Absence	52 (30.8)	15 (23.8)	29 (35.8)	8 (32)
Presence	117 (69.2)	48 (76.2)	52 (64.2)	17 (68)
Infiltrative tumor
Absence	133 (78.7)	63 (100)	58 (71.6)	12 (48)
Presence	36 (21.3)	0	23 (28.4)	13 (52)
Vascular invasion²
Absence	131 (78)	63 (100)	56 (70)	12 (48)
Presence	37 (22)	0	24 (30)	13 (52)
Extrahepatic disease
Absence	137 (81.1)	63 (100)	60 (74.1)	14 (56)
Presence	32 (18.9)	0	21 (25.9)	11 (44)
Number of tumors
Single	28 (16.6)	12 (19)	9 (11.1)	7 (28)
Multiple	141 (83.4)	51 (81)	72 (88.9)	18 (72)
Lobar involvement
Unilobar	63 (37.3)	33 (52.4)	22 (27.2)	8 (32)
Bilobar	106 (62.7)	30 (47.6)	59 (72.8)	17 (68)
Intrahepatic tumor
≤ 50%	116 (68.6)	63 (100)	37 (45.7)	16 (64)
> 50%	53 (31.4)	0	44 (54.3)	9 (36)
TARE procedures
1	151 (89.3)	56 (88.9)	71 (87.7)	24 (96)
2	16 (9.5)	7 (11.1)	8 (9.9)	1 (4)
3	2 (1.2)	0	2 (2.5)	0

¹Unavailable AFP in one TARE_no_sorafenib patient.

²Unavailable vascular invasion in one TARE_sorafenib patient.

Values represent number of procedures (%). TARE: Transarterial radioembolization; ECOG: Eastern cooperative oncology group; BCLC: Barcelona clinic liver cancer; AFP: Alpha-fetoprotein.

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Table 2 Characteristics of transarterial radioembolization procedures

	All procedures (n = 169)	*TARE_alone* (n = 63)	*TARE_sorafenib* (n = 81)	*TARE_no_sorafenib* (n = 25)
LSF, %	6.0 (0.8-30.4)	4.6 (1.0-26.4)	6.1 (0.8-30.4)	6.3 (2.0-13.6)
Lung mean dose, Gy¹	8.2 (0.3-29.7)	4.7 (0.3-29.2)	10.1 (0.5-29.7)	11.2 (2.0-29.2)
Mean dose to treated liver volume, Gy¹	110 (80-135)	110 (80-135)	110 (80-135)	110 (80-135)
Interval between Tc-99m MAA and TARE, d¹	20 (0-125)	21 (0-125²)	17 (0-44)	21 (10-34)
Administered activity, GBq	2.5 (0.3-8.1)	1.7 (0.3-6.3)	2.9 (0.6-8.1)	2.7 (0.8-5.9)
TARE approach, n (%)
Whole liver³	47 (27.8)	16 (25)	25 (31)	6 (24)
Lobar + segment	22 (13)	4 (6)	15 (18)	3 (12)
Lobar	66 (39.1)	23 (37)	30 (37)	13 (52)
Multiple segments	23 (13.6)	13 (21)	7 (9)	3 (12)
Single segment	11 (6.5)	7 (11)	4 (5)	0

¹Mean absorbed doses values for each treatment session.

²The outliner interval of 125 d was from a single patient whose initial treatment plan was a whole liver treatment with sequential lobar infusion three weeks apart. His subsequent left lobar treatment was delayed for months because of his medical conditions. Administered activity of left lobar approach was calculated using the original Tc-99m MAA plan and re-evaluation CT scan performed prior to left lobar treatment.

³Consisted of single infusion (n = 19), separate infusion (n =24) and sequential infusion (n = 4).

Values represent median (range) unless otherwise stated. TARE: Transarterial radioembolization; Tc-99m MAA: The technetium-99m macro aggregated albumin.

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Table 3 Summary of the best radiologic response (modified response evaluation criteria in solid tumors) following transarterial radioembolization

	All procedures (n = 169)	*TARE_alone* (n = 63)	*TARE_sorafenib* (n = 81)	*TARE_no_sorafenib* (n = 25)
Treated area
CR	12 (7.1)	2 (3.2)	9 (11.1)	1 (4)
PR	61 (36.1)	24 (38.1)	34 (42)	3 (12)
SD	66 (39.1)	28 (44.4)	28 (34.6)	10 (40)
PD	30 (17.8)	9 (14.3)	10 (12.3)	11 (44)
OR	73 (43.2)	26 (41.3)	43 (53.1)	4 (16)
DC	139 (82.2)	54 (85.7)	71 (87.7)	14 (56)
Intrahepatic area
CR	12 (7.1)	2 (3.2)	9 (11.1)	1 (4)
PR	58 (34.3)	22 (34.9)	33 (40.7)	3 (12)
SD	59 (34.9)	26 (41.3)	26 (32.1)	7 (28)
PD	40 (23.7)	13 (20.6)	13 (16)	14 (56)
OR	70 (41.4)	24 (38.1)	42 (51.9)	4 (16)
DC	129 (76.3)	50 (79.4)	68 (84)	11 (44)
Overall
CR	10 (5.9)	2 (3.2)	7 (8.6)	1 (4)
PR	52 (30.8)	22 (34.9)	28 (34.6)	2 (8)
SD	56 (33.1)	26 (41.3)	23 (28.4)	7 (28)
PD	51 (30.2)	13 (20.6)	23 (28.4)	15 (60)
OR	62 (36.7)	24 (38.1)	35 (43.2)	3 (12)
DC	107 (69.8)	50 (79.4)	58 (71.6)	10 (40)

Values represent number of procedures (%). Objective response consisted of complete response (CR) and partial response (PR). Disease control consisted of CR, PR and stable disease. CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; OR: Objective response; DC: Disease control; TARE: Transarterial radioembolization.

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Table 4 Site of first progression in all cases of progression

	All procedures (n = 169)	*TARE_alone* (n = 63)	*TARE_sorafenib* (n = 81)	*TARE_no_sorafenib* (n = 25)
No progression	58 (34.3)	27 (42.9)	24 (29.6)	7 (28)
Progression	111 (65.7)	36 (57.1)	57 (70.4)	18 (72)
Intrahepatic only	67 (39.6)	28 (44.5)	31 (38.4)	8 (32)
Treated area only	36 (21.3)	16 (25.4)	17 (21)	3 (12)
Untreated area only	20 (11.8)	10 (15.9)	6 (7.4)	4 (16)
Both treated and untreated areas	11 (6.5)	2 (3.2)	8 (9.9)	1 (4)
Extrahepatic only	17 (10.1)	3 (4.8)	13 (16)	1 (4)
Intra- and extrahepatic	27 (16)	5 (7.9)	13 (16)	9 (36)

Values represent number of procedures (%). TARE: Transarterial radioembolization.

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Table 5 First pattern of intrahepatic progression in cases with intrahepatic progression

	All procedures (n = 100)	*TARE_alone* (n = 34)	*TARE_sorafenib* (n = 49)	*TARE_no_sorafenib* (n = 17)
Progression in treated area	75 (75)	23 (67.6)	40 (81.6)	12 (70.6)
New HCC	34 (34)	12 (35.3)	19 (38.8)	3 (17.6)
Recurrence/increased enhancement of previously treated HCC	20 (20)	5 (14.7)	9 (26.5)	6 (35.3)
With new MVI	8 (8)	2 (5.9)	6 (12.2)	0
With progressive MVI	3 (3)	0	3 (6.1)	0
With mixed patterns¹	10 (10)	4 (11.8)	3 (6.1)	3 (17.6)
Progression in untreated area	25 (25)	11 (32.4)	9 (18.4)	5 (29.4)

¹New HCC with one or more other patterns (n = 11) and new MVI with increased enhancement of previously treated HCC (n = 1). Values represent number of procedures (%). TARE: Transarterial radioembolization; HCC: Hepatocellular carcinoma; MVI: Macrovascular invasion.

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Table 6 Time to progression

	All procedures (n = 169)	*TARE_alone* (n = 63)	*TARE_sorafenib* (n = 81)	*TARE_no_sorafenib* (n = 25)
Treated area
Censored patients	87	39	37	11
TTP, mo	7.8 (6.4-9.3)	12.3 (10.4-14.1)	7.5 (6.2-8.8)	3.6 (0.8-6.4)
Untreated area
Censored patients	119	47	59	13
TTP, mo	12.8 (4.3-21.3)	22.9 (10.2-35.7)	11.9 (8.0-15.8)	3.6 (2.1-5.1)
Overall
Censored patients	58	27	24	7
TTP, mo	4.9 (3.9-5.9)	8.6 (3.4-13.8)	5.1 (4.0-6.2)	2.7 (2.2-3.1)

TTP values represent median (95%CI) in months. TTP: Time to progression; TARE: Transarterial radioembolization.

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Table 7 Univariate analysis of time to progression using Kaplan-Meier method

Prognostic factors	*TARE_alone* (n = 63)				*TARE_sorafenib* (n = 81)
Prognostic factors	n¹	c¹	HR (95%CI)	P value	n¹	c¹	HR (95%CI)	P value
ECOG²
0	32	13	0.57 (0.27-1.19)	0.131	40	8	1.96 (1.11-3.45)	0.018
1	28	13		0.131	40	16		0.018
BCLC stage³
B	26	9	0.62 (0.30-1.28)	0.193	16	5	1.02 (0.53-1.99)	0.947
C	31	14		0.193	65	19		0.947
Child-pugh class
A	57	24	0.35 (0.10-1.22)	0.083	78	23	0.75 (0.18-3.13)	0.694
B	6	3		0.083	3	1		0.694
AFP
< 400 ng/mL	54	22	0.73 (0.25-2.10)	0.556	52	15	0.78 (0.45-1.35)	0.378
≥ 400 ng/mL	9	5		0.556	29	9		0.378
Cirrhosis
Absence	15	6	1.08 (0.51-2.32)	0.835	29	7	1.39 (0.82-2.38)	0.222
Presence	48	21		0.835	52	17		0.222
Number of tumors
Single	12	6	0.71 (0.29-1.73)	0.449	9	5	0.59 (0.21-1.65)	0.308
Multiple	51	21			72	19
Lobar involvement
Unilobar	33	16	0.52 (0.27-1.04)	0.058	22	7	0.95 (0.52-1.74)	0.870
Bilobar	30	11			59	17
Infiltrative tumor⁴
Absence					58	15	1.14 (0.62-2.09)	0.673
Presence					23	9		0.673
MVI⁴
Absence					56	12	1.76 (0.92-3.35)	0.081
Presence					24	11		0.081
EHD⁴
Absence					60	23	0.37 (0.21-0.65)	< 0.001
Presence					21	1		< 0.001
IHT⁴
≤ 50%					37	15	0.54 (0.32-0.93)	0.024
> 50%					44	9		0.024

¹Total patients (n) and censored patients (c).

²ECOG 2 (n = 2 TARE_alone, n = 1 TARE_sorafenib) and ECOG 3 (n = 1 TARE_alone, n = 0 TARE_sorafenib) excluded.

³BCLC A (n = 5 TARE_alone, n = 0 TARE_sorafenib) and BCLC D (n = 1 TARE_alone, n = 0 TARE_sorafenib) excluded.

⁴Absent in all TARE_alone procedures according to institutional treatment algorithm.

Hazard ratios (HR) with Cox proportional hazard regression and P value with log-rank test. TARE: Transarterial radioembolization; ECOG: Eastern cooperative oncology group; BCLC: Barcelona clinic liver cancer; AFP: Alpha-fetoprotein; MVI: Macrovascular invasion; EHD: Extrahepatic disease; IHT: Intrahepatic tumor.

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Table 8 Multivariate analysis of time to progression using Cox proportional hazard model

Population	Prognostic factors	n¹	c¹	HR (95%CI)	P value
TARE_alone (n = 63)	Child-pugh class
	A	57	24	0.32 (0.09-1.10)	0.073
	B	6	3
	Lobar involvement
	Unilobar	33	16	0.51 (0.26-1.00)	0.051
	Bilobar	30	11
TARE_sorafenib (n = 81)	ECOG²
	0	40	8	0.85 (0.59-1.22)	0.370
	1	40	16
	MVI
	Absence	56	12	1.15 (0.74-1.80)	0.532
	Presence	24	11
	EHD
	Absence	60	23	0.37 (0.24-0.56)	< 0.001
	Presence	21	1
	IHT
	≤ 50%	37	15	0.72 (0.49-1.06)	0.096
	> 50%	44	9

¹Total patients (n) and censored patients (c).

²ECOG 2 (n = 1) and ECOG 3 (n = 0) excluded.

TARE: Transarterial radioembolization; ECOG: Eastern cooperative oncology group; MVI: Macrovascular invasion; EHD: Extrahepatic disease; IHT: Intrahepatic tumor.

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Citation: Teyateeti A, Mahvash A, Long J, Abdelsalam M, Avritscher R, Kaseb A, Odisio B, Ravizzini G, Surasi D, Teyateeti A, Macapinlac H, Kappadath SC. Disease control and failure patterns of unresectable hepatocellular carcinoma following transarterial radioembolization with yttrium-90 microspheres and with/without sorafenib. World J Gastroenterol 2021; 27(47): 8166-8181
URL: https://www.wjgnet.com/1007-9327/full/v27/i47/8166.htm
DOI: https://dx.doi.org/10.3748/wjg.v27.i47.8166