Role of stereotactic body radiation therapy for hepatocellular carcinoma

Table 1 Eligibility criteria for different treatment modalities

	Surgery	Percutaneous ablative therapy	TACE	SBRT
Tumor size	< 5 cm (or more)	< 3 cm	> 3-5 cm	4 (or 5) cm
Number of tumors	< 3	Depends on location	1-multiple (> 4)	< 1-3
Location or characteristics	Depends on liver function	Away from large vessels or biliary system	Hypervascular lesions	Away from bowels
Local control (2 yr)	> 90%	> 90%	< 65%	> 90%
Level of evidence	High	Intermediate-high	Intermediate-high	Low
Invasiveness	High	Less	Less	None
Damage to the liver	High	Low	Low-moderate	Low-moderate

SBRT: Stereotactic body radiation therapy; TACE: Transarterial chemoembolization.

Table 2 Prospective studies of stereotactic body radiation therapy for hepatocellular carcinoma and other liver tumors

Ref.	Country	Patient number	Median volume, mL	Median size, cm	Median dose (range)/fraction, Gy	Median follow-up (range), mo	Local control	Overall survival
Cárdenes et al[29]	United States (Indiana)	17	34(8-95)	-	VariableCP-A: 36-48 Gy/3 frCP-B: 40 Gy/5 fr	24(10-42)	100%	75% (1 yr)60% (2 yr)
Andolino et al[37]	United States (Indiana)	60	29(2-112)	3.2(1-6.5)	FixedCP-A: 44 Gy/3 frCP-B: 40 Gy/5 fr	27(2-52)	90% (2 yr)	67% (2 yr)
Bujold et al[30]	Canada	102	117(1-1913)	7.2(1.4-23.1)	Variable36 (24-54) Gy/6 fr	31(2-36)	87% (1 yr)	Median 17 mo
Kang et al[31]	South Korea	47	15(2-213)	2.9(1.3-7.8)	57 (42-60) Gy/3 fr	17(6-38)	95% (2 yr)	69% (2 yr)
	(Korea Inst. of Radiological and Medical Sciences)

CP: Child-Pugh.

Table 3 Retrospective studies of stereotactic body radiation therapy for hepatocellular carcinoma and other liver tumors

Ref.	Country	Patient number	Median volume (mL)	Median size, cm	Median dose (range)/fraction, Gy	Median follow-up (range) (mo)	Local control	Overall survival
Choi et al[32], 2006	South Korea(The Catholic Univ. of Korea)	20	-	3.8 (2-6.5)	Fixed50 Gy/5 or 10 fr	23(3-55)	100%	70%(1 yr)43%(2 yr)
Zhang et al[72], 2007	China(Hebei)	27	-	< 5 cm: 18%3-5 cm: 41%> 5 cm: 41%	Median40 (32-42) Gy/5 fr	10(3-21)	22%(1 yr)	-
Choi et al[33], 2008	South Korea(The Catholic Univ. Korea)	31	25(4-57)	-	Variable33 (30-39) Gy/3 fr	11(2-19)	100%	81%(1 yr)
Louis et al[34], 2010	Belgium	25	48(7-363)	-	Fixed45 Gy/3 fr	13(1-24)	95%(1 yr)	79%(1 yr)52%(2 yr)
Kwon et al[35], 2010	South Korea(The Catholic Univ. of Korea)	42	15(3-82)	-	Variable30-39 Gy/3fr	29(8-4)	72%(1 yr)68%(3 yr)	93%(1 yr)59%(3 yr)
Seo et al[36], 2010	South Korea(Korea Inst. of Radiological and Medical Sciences)	38	41(11-464)	-	Variable33-57 Gy/3-4 fr	15(3-27)	66%(2 yr)	61%(2 yr)
Huang et al[38], 2012	Taiwan	36	-	4.4(1.1-12)	Variable37 (25-48 Gy)/4-5 fr	14(2-35)	88%(1 yr)75%(2 yr)	64%(2 yr)
Honda et al[39], 2012	Japan(Hiroshima)	30	-	1.6(1-3)	Fixed 48 Gy/4 fr or 60 Gy/8 fr	12(6-38)	100%	100%(1 yr)100%(3 yr)
Bae et al[40], 2013	South Korea(Korea Inst. of Radiological and Medical Sciences)	35	131(21-2189)	-	Variable45 (30-60) Gy/3-5 fr	14(1-44)	69%(1 yr)51%(3 yr)	52%(1 yr)21%(2 yr)
Xi et al[41], 2013	China(Sun Yat-sen Univ.)	41	65 (± 48)	-	Variable36 (30-48) Gy/6 fr	10(4-25)	95%	50%(1 yr)
Sanuki et al[43], 2013	Japan(Ofuna)	185	8(1.5-65)	-	FixedCP-A: 40 Gy/5 fr/CP-B: 35 Gy/5 fr/	24(3-80)	91%(3 yr)	70%(3 yr)

CP: Child-Pugh.

Table 4 Studies of liver tumors including hepatocellular carcinoma, cholangiocarcinoma, and liver metastasis

Ref.	Country	Study design	Tumors(patient number)	Median volume (mL)	Median size (cm)	Median dose (range)/fraction, Gy	Median follow-up (range) (mo)	Local control	Overall survival
Blomgren et al[24], 1995	Sweden	Retrospective	HCC+CCC/metastasis(20/21)	22	-	Fixed30 Gy/2-3 fr	11	HCC + CCC: 100%Metastasis: 95%	-
Tse et al[28], 2008	Canada	Phase I	HCC/CCC(31/10)	173(9-1913)	-	VariableMedian 36 (24-54) Gy/6 fr	18(11-39)	65% (1 yr)	48% (1 yr)
Herfarth et al[47], 2001	Germany	Phase I-II	HCC/CCC(4/54)	10 (1-132)	-	Dose escalation14-26 Gy/1 fr	6(1-26)	81%(18 mo)	-
Wulf et al[48], 2006	Switzerland	Prospective	HCC + CCC/metastasis(5/51)	HCC+CCC: 14-516Metastasis: 9-355	-	VariableLow dose:30 Gy/3 fr or28 Gy/4 frHigh dose: 36-38 Gy/3 fr or26 Gy/1 fr	HCC + CCC:15 (2-48)Metastasis:15 (2-85)	HCC + CCC: 100%Metastasis: 99% (1 yr), 66% (2 yr)	72% (1 yr)32% (2 yr)
Méndez-Romero et al[49], 2006	The Netherland	Retrospective	HCC/metastasis(11/34)	22(10-322)	3.2(0.5-7.2)	VariableNo cirrhosis and ≥ 4 cm: 37.5 Gy/3 frCirrhosis and< 4 cm: 25 Gy/5 fr or30 Gy/3 fr	13(0.5-31)	94% (1 yr)82% (2 yr)	HCC: 75%(1 yr), 40% (2 yr)Metastasis: 82% (1 yr), 54% (2 yr)
Iwata et al[50], 2010	Japan(Nagoya City University)	Retrospective	HCC/metastasis(6/12)	-	2.3(1.2-3.5)	Variable50 or 55 Gy/10 fr	15	86% (1 yr)	94% (1 yr)
Goodman et al[51], 2010	United States (Memorial Sloan Kettering Cancer Center)	Phase I	HCC/metastasis(2/24)	33(0.8-147)		Dose escalation18-30 Gy/1 fr	17(2-55)	77% (1 yr)	50% (2 yr)
Dewas et al[53], 2012	France	Retrospective	HCC + CCC/metastasis(54/99)	32(0.2-500)	3.3(0.5-11)	Variable45 Gy/3 fr	15(12-18)	84% (1 yr)75% (2 yr)	-
Ibarra et al[54], 2012	United States (Cleveland)	Retrospective, multicenter	HCC/CCC(21/11)	HCC: 334 (10-1914)CCC: 80 (31-819)	-	HCC: 22 (18-26) Gy/1 frCCC: 30 (22-30) Gy/1 fr	13(0.5-54)	84% (1 yr)75% (2 yr)	87% (1 yr)55% (2 yr)

CCC: Cholangiocarcinoma; HCC: Hepatocellular carcinoma.