Radioembolization with Yttrium-90 microspheres in hepatocellular carcinoma: Role and perspectives

Table 1 Characteristics of commercially available Yttrium-90-microspheres for transarterial radioembolization (modified from Sangro et al[72])

	SIR-Spheres1	TheraSphere2
Isotope 90Y	Attached to the surface	Incorporated into the glass matrix
Half-life (h)	64.1	64.1
Microsphere material	Resin	Glass
Microsphere diameter (μm)	20-60	20-30
Average size (μm)	32.5	25
Approximate activity per microsphere (Bq)	50	2500
Number of microspheres per 3 GBq	40-80 × 106	1.2 × 106
Specific gravity (g/mL)	1.6	3.6
Activity per commercially available vial (GBq)	3 (can be divided)	3, 5, 7, 10, 15, 20
Activity calculation	Compartmental MIRD macrodosimetry or empirical formula based on liver volume and tumor volume	Non-compartmental MIRD macrodosimetry
Estimated dose to the central vein area (Gy) in the montecarlo simulation3	59	58
Embolic effect	Moderate	Mild
Contrast agent injection	During infusion	None
Indication	United States (FDA PMA): colorectal liver metastases	United States (FDA HDE): hepatocellular carcinoma

¹Sirtex Medical, North Sydney, Australia;

²BTG International Canada Inc., Ottawa, Ontario, Canada;

³From Gulec et al[40]. 90Y: Yttrium-90; MIRD: Medical Internal Radiation Dosimetry; FDA: Food and Drug Administration; PMA: Pre-Market Approval; HDE: Humanitarian Device Exemption.

Table 2 Outcomes after transarterial radioembolization from recent studies (modified from Kim et al[89])

Ref.	No. of patients	Response rate	Survival (mo)	Prognostic factors
Carr et al[48]	65	OR = 38%	Okuda et al[90] I: 21 Okuda et al[90] II: 10
Salem et al[50]	43	PR = 47%	Okuda et al[90] I: 24 Okuda et al[90] II: 13	Main PVTT; AFP > 400 ng/mL tumor burden > 25%
Sangro et al[91]	24	PR = 24%; SD: 64%	7
Young et al[80]	41		Okuda et al[90] I: 21.7 Okuda et al[90] II: 14.2
Kulik et al[92]	71	PR = 42%; SD: 35%	15.5
Salem et al[63]	123	RR = 72%	20.5	Sex (female); Child-Pugh class; UNOS
Sangro et al[8]	325		12.8	ECOG; nodules > 5; INR > 1.2; extrahepatic disease
Mazzaferro et al[56]	52	CR = 9.6%; OR = 40.4%	15	Response; Child Pugh class

PVTT: Portal vein tumour thrombosis; AFP: Alpha-fetoprotein; OR: Odds ratio; PR: Partial response; RR: Response rate; CR: Complete response; SD: Stable disease; UNOS: United Network of Organ Sharing; ECOG: European Cooperative Oncology Group; INR: International Normalized Ratio.

Table 3 Comparison of response and median survival after transarterial radioembolization and transarterial chemoembolization from recent studies (modified from Lau et al[93])

Ref.	Treatment	n	OS (mo)	TTP (mo)	Response (CP/PR) %WHO/RECIST criteria	RR (CP/PR) %EASL criteria	Downstaged/LT %	Mean days in hospitalper treatment
Lewandowski et al[69]	TARE (TheraSphere1)	43	35.7	33.3	61	86	58a	0a
	TACE	43	18.7	18.2	37	71	31	3
Kooby et al[88]	TARE (SIR-Spheres2)	27	6	NR	11	NR	NR	1.7a
	TACE	44	6		6			6
Carr et al[68]	TARE (TheraSphere1)	99	11.5	NR	41	NR	NR	NR
	TACE	691	8.5		60
Salem et al[63]	TARE (TheraSphere1)	123	20.5	13.3	49	72	25	0a
	TACE	122	17.4	8.4	46	69	36	1.8

¹BTG International Canada Inc., Ottawa, Ontario, Canada;

²Sirtex Medical, North Sydney, Australia.

^aP < 0.05, response and median survival after transarterial radioembolization vs transarterial chemoembolization. OS: Overall survival; TTP: Time to tumor progression; CP: Complete response; PR: Partial response; RR: Response rate; WHO: World Health Organization; RECIST: Response Evaluation Criteria in solid tumors; TARE: Transarterial radioembolization; TACE: Transarterial chemoembolization; EASL: European Association for the Study of the Liver; LT: Liver transplantation; NR: Not reported.

Table 4 Response and median survival after transarterial radioembolization in hepatocellular carcinoma with or without portal vein tumour thrombosis from recent studies (modified from Okuda et al[90])

Ref.	PVTT	n	Response (CR/PR) %WHO/RECIST criteria	RR (CR/PR) %EASL criteria	OS
Salem et al[71]	Child-Pugh A	116	52	69	17.2
TheraSphere1	No PVTT	81	53	77	22.1
no EHS	PVTT (mixed)	35	50	50	10.4
	First-order	19	58	58	16.6
	Main	16	40	40	7.7
	Child-Pugh B	122	39	52	7.7
	No PVTT	65	47	67	14.8
	PVTT (mixed)	57	28	32	5.6
	First-order	27	28	40	6.5
	Main	30	28	24	4.5
Hilgard et al[55]	All patients	108	15	40	16.4
TheraSphere1	No PVTT	75	NR	NR	16.4
30% EHS	PVTT [mixed: main (12); first/second order (12); unknown (9)]	33			10
Sangro et al[8]	All patients	325	NR	NR	12.8
SIR-Spheres2	No PVTT	249			15.3
9% EHS	PVTT [mixed: main (32); first order (44)]	76			10.7/9.7
Iñarrairaegui et al[94] TheraSphere1 and SIR-Spheres2	PVTT [mixed: main (6); first/second order (19)]	25	NR	NR	10
Tsai et al[95]	PVTT	22	NR	NR	7
TheraSphere1 and SIR-Spheres2	Main	12			4.4
13% EHS	First order	10			7
Woodall et al[96]	No PVTT	20	NR	NR	13.9
TheraSphere1	PVTT [mixed: main (10)]	15			3.2
Kulik et al[92]	All patients	108	42	70	NR
TheraSphere1	No PVTT	71			15.4
12% EHS	PVTT main	12			4.4
	First order	25			9.9

¹BTG International Canada Inc., Ottawa, Ontario, Canada;

²Sirtex Medical, North Sydney, Australia. PVTT: Portal vein tumor thrombosis; CR: Complete response; PR: Partial response; WHO: World Health Organization; RECIST: Response Evaluation Criteria in solid tumors; RR: Response rate; EASL: European Association for the Study of the liver; EHS: Extrahepatic disease; NR: Not reported; OS: Overall survival; Main: Main portal vein trunk; First order: Right and/or left portal vein; Second order: Segmental branches of portal vein.