Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?

Table 1 Criteria for transarterial chemoembolization resistance

The evaluation was performed on the day of TACE and 1 mo after the TACE; the following were observed at least two times

Staining with the injected agent (lipiodol-anticancer agent emulsion) was considered insufficient with evaluation CT [the occupation rate was less than 50% of lesion(s)]

Appearance of multiple new recurrent lesions on the evaluation CT

Appearance of vessel invasion after TACE

Appearance of distal metastasis after TACE

Persistent elevation of tumor marker(s) regardless of TACE

TACE: Transarterial chemoembolization; CT: Computed tomography.

Table 2 Comparison of the patient characteristics in the two groups prior to hepatic arterial infusion chemotherapy n (%)

	Group A	Group B	Pvalue
Patients	23	19
Age (yr)	66.6 ± 6.9	65.5 ± 7.3	NS (P = 0.635)
Gender
Male/female	20 (87)/3 (13)	15 (79)/4 (21)	NS (P = 0.488)
Etiology of LC
HCV	13 (57)	11 (58)	NS (P = 0.070)
HBV	2 (9)	6 (32)
HCV + HBV	0 (0)	1 (5)
Alcohol	4 (17)	0 (0)
NonB-nonC	4 (17)	1 (5)
Albumin (g/dL)	3.6 ± 0.6	3.5 ± 0.6	NS (P = 0.503)
Total bilirubin (mg/dL)	1.1 ± 0.7	1.3 ± 0.5	NS (P = 0.397)
PT (INR)	1.19 ± 0.13	1.17 ± 0.10	NS (P = 0.607)
AST (U/L)	64 ± 33	79 ± 51	NS (P = 0.256)
ALT (U/L)	47 ± 30	53 ± 38	NS (P = 0.569)
GGT (U/L)	155 ± 169	76 ± 76	NS (P = 0.067)
WBC (/μL)	4600 ± 1400	4400 ± 900	NS (P = 0.431)
Hb (g/dL)	13.1 ± 2.0	12.8 ± 1.0	NS (P = 0.521)
Plt (× 104/μL)	14.3 ± 6.5	12.1 ± 5.8	NS (P = 0.262)
AFP (median, ng/mL)	7550	3116	NS (P = 0.434)
DCP (median, mAU/mL)	12314	3363	NS (P = 0.159)
Child-Pugh
A/B	12 (52)/11 (48)	6 (32)/13 (68)	NS (P = 0.219)
Child-Pugh score	6.8 ± 1.7	7.1 ± 1.4	NS (P = 0.582)
Number of tumor (s)
≤ 5/6-10/> 10	5 (22)/7 (30) /11 (48)	5 (26)/8 (42) /6 (32)	NS (P = 0.515)
Size of the largest tumor (cm)	7.3 ± 5.2	3.8 ± 1.3	P = 0.008
Vessel invasion
presence/absence	12 (52)/11 (48)	7 (37)/12 (63)	NS (P = 0.320)
Clinical stage
I/II/III/IVA	0 (0)/0 (0)/ 11 (48)/12 (52)	0 (0)/0 (0)/ 13 (68)/6 (32)	NS (P = 0.180)
Duration of treatment received prior to HAIC (mo)	16.3 ± 20.7	36.2 ± 21.5	P = 0.004
Previous number of TACE session (s)	0.9 ± 0.6	4.5 ± 1.8	P < 0.0001
HAIC regimens
5-FU, cisplatin	8 (35)	7 (37)	NS (P = 0.923)
5-FU, natural IFN-α	4 (17)	4 (21)
5-FU, PEG-IFN-α2b	11 (48)	8 (42)

HCV: Hepatitis C virus; HBV: Hepatitis B virus; LC: Liver cirrhosis; PT: Prothrombin time; INR: International ratio; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: γ glutamyl transferase; AFP: α-fetoprotein; WBC: White blood cell; DCP: Des-γ-carboxyprothrombin; HAIC: Hepatic arterial infusion chemotherapy; TACE: Transarterial chemoembolization; 5-FU: 5-fluorouracil; IFN: Interferon; PEG-IFN-α2b: Pegylated interferon-α2b.

Table 3 Multivariate analysis (Cox proportional hazards regression model) to identify factors influencing the survival

	Odds ratio	95% CI	Pvalue
Age > 66 (yr)	0.284	0.077-1.044	NS (P = 0.058)
Gender: female	3.995	0.704-22.662	NS (P = 0.118)
Resistance to TACE	8.264	1.770-38.461	P = 0.007
AFP > 200 (ng/mL)	0.385	0.121-1.230	NS (P = 0.107)
DCP > 200 (mAU/mL)	1.181	0.218-6.390	NS (P = 0.847)
Albumin > 3.5 (g/dL)	0.012	0.001-0.181	P = 0.001
Total bilirubin > 1.0 (mg/dL)	4.000	1.004-15.933	P = 0.049
PT (INR) > 1.20	0.490	0.155-1.551	NS (P = 0.225)
ALT > 50 (U/L)	1.229	0.378-3.999	NS (P = 0.732)
Plt > 15.0 (× 104/μL)	1.251	0.330-4.736	NS (P = 0.742)
Number of tumors > 6	0.403	0.090-1.794	NS (P = 0.233)
Size of the largest tumor > 5.0 cm	0.913	0.215-3.884	NS (P = 0.902)
Clinical stage: IVA	13.800	1.638-116.257	P = 0.016
Response to HAIC: CR, PR	0.024	0.004-0.160	P = 0.0001
Child-Pugh: B	0.251	0.019-3.307	NS (P = 0.293)
Hepatic encephalopathy: presence	0.643	0.123-3.347	NS (P = 0.599)
Ascites: presence	3.471	0.835-14.419	NS (P = 0.087)

TACE: Transarterial chemoembolization; AFP: α-fetoprotein; DCP: Des-γ-carboxyprothrombin; PT: Prothrombin time; INR: International ratio; ALT: Alanine aminotransferase; HAIC: Hepatic arterial infusion chemotherapy; CR: Complete response; PR: Partial response; CI: Confidence interval.