Mammalian target of rapamycin inhibitors after post-transplant hepatocellular carcinoma recurrence: Is it too late?

Table 1 Baseline characteristics at the time of liver transplantation

	mTOR inhibitor (n = 79)	No mTOR inhibitor (n = 64)	P value
Age at transplant (years)	57 (50-62)	53 (46-59)	0.07
Gender (%M)	75 (95%)	57 (89%)	0.19
Etiology			0.28
Cryptogenic	1 (1%)	4 (6%)
HBV	72 (91%)	59 (92%)
HCV	4 (5%)	1 (2%)
Alcoholic liver disease	3 (4%)	2 (3%)
Primary/salvage transplant	49/30	43/21	0.52
Cadaveric/living related	53/26	47/17	0.41
Whole graft/partial graft	53/26	47/17	0.41
No. of tumours	2 (1-5)	2 (1-6)	0.85
Size of largest tumour (cm)	4.3 (2.9-6.6)	4.0 (2.5-6.5)	0.68
AFP (ng/mL)	144 (14-1388)	111 (19-817)	0.51
Within Milan criteria	21 (27%)	14 (22%)	0.54
Within UCSF criteria	26 (33%)	15 (23%)	0.22

AFP: Alpha-fetoprotein; HBV: Hepatitis B virus; HCV: Hepatitis C virus; mTOR: Mammalian target of rapamycin.

Table 2 Recurrence characteristics

	mTOR inhibitor (n = 79)	No mTOR inhibitor (n = 64)	P value
Date of recurrence	7/2013	3/2008	< 0.001
Age at recurrence (years)	58 (52-64)	55 (46-61)	0.06
Time from transplant (mo)	12 (6-24)	12 (5-25)	0.73
Number of tumours	2 (1-5)	5 (1-9)	0.02
Size of largest tumour (cm)	2.0 (1.1-3.2)	2.1 (1.1-3.9)	0.74
Number of organs involved	1 (1-1)	1 (1-2)	0.50
Site of recurrence
Liver	34 (43%)	28 (44%)	0.93
Lung	36 (46%)	35 (55%)	0.33
Bone	17 (22%)	6 (9%)	0.049
Peritoneum	4 (5%)	8 (13%)	0.11
Adrenal	5 (6%)	6 (9%)	0.50
Lymph node	6 (8%)	4 (6%)	0.75
AFP upon recurrence (ng/mL)	14 (4-139)	32 (6-855)	0.19
Immunosuppression
Calcineurin Inhibitor	49 (62%)	62 (97%)	< 0.001
Tacrolimus level	3.0 (0-4.9)	5.2 (3.7-6.1)	0.03
Treatment
Surgery	22 (28%)	11 (17%)	0.13
RFA	7 (9%)	6 (9%)	0.89
TACE	19 (24%)	10 (16%)	0.23
Radiotherapy	31 (39%)	14 (22%)	0.03
Targeted therapy	47 (59%)	15 (23%)	< 0.001
Immunotherapy	2 (3%)	0 (0%)	0.18
Supportive	3 (4%)	23 (36%)	< 0.001

AFP: Alpha-fetoprotein; RFA: Radiofrequency ablation; TACE: Trans-arterial chemoembolization; mTOR: Mammalian target of rapamycin.

Table 3 Survival analysis

	Univariate		Multivariate
	P value	OR (95%CI)	P value	OR (95%CI)
Date of recurrence	0.006	1.00 (1.00-1.00)	0.79
Age at recurrence (years)	0.93
Time from transplant	< 0.001	0.977 (0.966-0.988)	0.001	0.977 (0.963-0.991)
Number of tumours	< 0.001	1.01 (1.01-1.02)	0.33
Size of largest tumour	0.02	1.11 (1.02-1.20)	0.02	1.13 (1.02-1.24)
Number of organs involved	0.01	1.14 (1.11-1.89)	0.27
Site of recurrence
Liver	0.01	1.62 (1.13-2.31)	0.01	1.92 (1.14-3.25)
Lung	0.43
Bone	0.17
Peritoneal	0.46
Adrenal	0.52
Lymph node	0.49
AFP upon recurrence	0.02	1.00 (1.00-1.00)	0.02	1.00 (1.00-1.00)
Immunosuppression after recurrence
mTOR inhibitor	< 0.001	0.485 (0.339-0.695)	0.04	0.482 (0.241-0.966)
Calcineurin Inhibitor	0.07
Tacrolimus trough (μg/L)	0.002	1.13 (1.04-1.22)	0.16
Treatment
Surgery	< 0.001	0.380 (0.240-0.601)	0.22
RFA	0.16
TACE	0.32
Radiotherapy	0.90
Targeted therapy	0.97
Immunotherapy	0.80
Supportive	< 0.001	2.34 (1.49-3.67)	0.73

AFP: Alpha-fetoprotein; RFA: Radiofrequency ablation; TACE: Trans-arterial chemoembolization; mTOR: Mammalian target of rapamycin.