Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

Table 1 Patient characteristics n (%)

Characteristics	Parameter	Patients
No. of patients		65 (100)
Sex
	Male	51 (78)
	Female	14 (22)
Age, yr
	Median	71
	Minimum-Maximum	26-93
Viral hepatitis
	HCV	35 (54)
	HBV	9 (14)
	None	21 (32)
Child-Pugh classification
	A	38 (58)
	B	24 (37)
	C	2 (3)
	NA	1 (2)
ECOG perfomance status
	0	16 (25)
	1-2	43 (66)
	3	6 (9)
Previous treatments
	Surgery	24 (37)
	RFA	28 (43)
	TACE	49 (75)
	Sorafenib	13 (20)
	Radiation	7 (11)
BCLC stage
	C	59 (91)
	D	6 (9)
AFP (ng/mL)
	Median	256
	Minimum-Maximum	1-240700
PIVKA II (mAU/mL)
	Median	1431
	Minimum-Maximum	8-316400

ECOG: Eastern Cooperative Oncology Group; BCLC: Barcelona Clinic Liver Cancer staging system; AFP: Alpha fetoprotein; PIVKA II: Proteins induced by vitamin K absence; HCV: Hepatitis C virus; HBV: Hepatitis B virus; RFA: Radiofrequency ablation; TACE: Transarterial chemoembolization; NA: Not available.

Table 2 Lesions and treatment outcomes

Variables	Total lesions (n = 95)	Size (mm)		Radiation (Gy)			Response
	n	Median	Range	Dose	Range	Fraction	CR	PR	SD	PD	NA
Liver
Portal vein	9	34.5	(15-54)	36	(28-50)	(3-6)	2		2	1	4
Hepatic vein	4	38	(20-54)	32.1	(28-36)	(4-10)	1	1		1	1
Bile duct	4	19.5	(12-29)	38.5	(28-45)	(5-7)		1	1		2
Bone	52	24.5	(10-52)	21.5	(8-33)	(1-6)	1	13	16	11	11
Lung	9	19	(18-48)	40	(27-48)	(3-4)		4		1	4
Brain	7	23.5	(12-38)	22	(14-30)	(1-3)	2			2	3
Others	10	31	(15-53)	30	(16-48	(1-6)	1	6			3

CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease. NA: Not available.

Table 3 Prognostic factors for tumor response n (%)

Prognostic factors	Response (+)	Response (-)	P value
	CR, PR, SD	PD
Gender			0.716
Female	8 (73)	3 (27)
Male	43 (77)	13 (23)
Age (yr)			1.000
< 70	23 (77)	7 (23)
≥ 70	28 (76)	9 (24)
AFP (ng/mL)			0.123
< 400	25 (69)	11 (31)
≥ 400	23 (88)	3 (12)
BCLC			1.000
Advanced	46 (75)	15 (25)
Terminal	5 (83)	1 (17)
Child-Pugh			0.363
< 7	36 (80)	9 (20)
≥ 7	15 (68)	7 (32)
Diameter (mm)			0.401
< 30	29 (81)	7 (19)
≥ 30	22 (71)	9 (29)
Dose (Gy)			0.119
< 30	33 (70)	14 (30)
≥ 30	18 (90)	2 (10)
Dose/fraction (Gy)			0.137
< 8	22 (88)	3 (12)
≥ 8	29 (69)	13 (31)
Lesion			0.274
Intrahepatic	10 (91)	1 (9)
Extrahepatic	41 (73)	15 (27)
Fiducial			0.126
(-)	34 (71)	14 (29)
(+)	17 (89)	2 (11)
Sorafenib			0.460
(-)	43 (78)	12 (22)
(+)	8 (67)	4 (33)

Fisher's exact test was used to evaluate prognostic factors for tumor response. Complete response (CR), Partial response (PR) and stable disease (SD) were categorized into response (+), progressive disease (PD) was categorized into response (-).

Table 4 Prognostic factors for alpha fetoprotein response n (%)

Prognostic factors	Univariate analysis			Multivariate analysis
	AFP		P value	Odds ratio	95%CI	P value
	Decrease	Increase
Gender			0.478
Female	4 (44)	5 (56)
Male	26 (59)	18 (41)
Age (yr)			< 0.001
< 70	11 (37)	19 (63)
≥ 70	19 (83)	4 (17)		0.116	0.029-0.460	0.002
AFP (ng/mL)			0.570
< 400	20 (61)	13 (39)
≥ 400	10 (50)	10 (50)
BCLC			1.000
Advanced	27 (57)	20 (43)
Terminal	3 (50)	3 (50)
Child-Pugh			0.151
< 7	22 (65)	12 (35)
≥ 7	8 (42)	11 (58)
Diameter (mm)			0.054
< 30	11 (42)	15 (58)
≥ 30	19 (70)	8 (30)		0.286	0.073-1.120	0.072
Dose (Gy)			0.013
< 30	18 (46)	21 (54)
≥ 30	12 (86)	2 (14)		0.992	0.093-10.50	0.995
Dose/fraction (Gy)			0.555
< 8	11 (65)	6 (35)
≥ 8	19 (53)	17 (47)
Lesion			0.270
Intrahepatic	7 (78)	2 (22)
Extrahepatic	23 (52)	21 (48)
Fiducial			0.025
(-)	19 (48)	21 (52)
(+)	11 (85)	2 (15)		0.152	0.026-0.887	0.036
Sorafenib			0.738
(-)	23 (55)	19 (45)
(+)	7 (64)	4 (36)

Fisher's exact test and a logistic regression model were used to evaluate prognostic factors for AFP response. AFP: Alpha fetoprotein.

Table 5 Prognostic factors for PIVKA II response n (%)

Prognostic factors	Univariate analysis			Multivariate analysis
	PIVKA II		P value	Odds ratio	95%CI	P value
	Decrease	Increase
Gender			0.278
Female	3 (33)	6 (67)
Male	25 (57)	19 (43)
Age (yr)			0.052
< 70	12 (40)	18 (60)
≥ 70	16 (70)	7 (30)		0.359	0.093-1.390	0.139
AFP (ng/mL)			0.738
< 400	18 (55)	15 (45)
≥ 400	10 (50)	10 (50)
BCLC			0.404
Advanced	26 (55)	21 (45)
Terminal	2 (33)	4 (67)
Child-Pugh			0.267
< 7	20 (59)	14 (41)
≥ 7	8 (42)	11 (58)
Diameter (mm)			0.056
< 30	10 (38)	16 (62)
≥ 30	18 (67)	9 (33)		0.185	0.047-0.730	0.016
Dose (Gy)			< 0.001
< 30	15 (38)	24 (62)
≥ 30	13 (93)	1 (7)		0.270	0.021-3.40	0.312
Dose/Fraction (Gy)			0.769
< 8	8 (47)	9 (53)
≥ 8	20 (56)	16 (44)
Lesion			0.026
Intrahepatic	8 (89)	1 (11)
Extrahepatic	20 (45)	24 (55)		0.000	0.00-∞	0.994
Fiducial			0.001
(-)	16 (40)	24 (60)
(+)	12 (92)	1 (8)		0.035	0.003-0.342	0.004
Sorafenib			1.000
(-)	22 (52)	20 (48)
(+)	6 (55)	5 (45)

Fisher's exact test and a logistic regression model were used to evaluate prognostic factors for PIVKA II response.

Table 6 Univariate and multivariate analysis for overall survival

Prognostic factors	Univariate analysis			Multivariate analysis
	Hazard ratio	95%CI	P value	Hazard ratio	95%CI	P value
Gender (male)	0.968	0.387-2.419	0.945
Age (≥ 70 yr)	0.770	0.355-1.670	0.508
AFP (≥ 400 ng/mL)	2.662	1.181-6.001	0.018	2.548	1.070-6.068	0.035
BCLC (terminal)	7.022	2.442-20.19	< 0.001	9.809	2.589-37.17	< 0.001
Child-Pugh (≥ 7)	3.031	1.258-7.301	0.013	1.364	0.510-3.645	0.536
Diameter (≥ 30 mm)	0.654	0.285-1.500	0.316
Dose (≥ 30 Gy)	0.302	0.114-0.804	0.017	0.274	0.093-0.7541	0.012
Dose/fraction (≥ 8 Gy)	1.889	0.790-4.516	0.153
Lesion (extrahepatic)	1.789	0.665-4.817	0.250
Fiducial (+)	0.491	0.195-1.238	0.132	0.783	0.264-2.321	0.659
Sorafenib (+)	1.068	0.247-4.618	0.930

Cox proportional hazards model was used to evaluate the prognostic factors for overall survival. AFP: Alpha fetoprotein; BCLC: Barcelona Clinic Liver Cancer.