Network meta-analysis of treatment regimens for inoperable advanced hepatocellular carcinoma with portal vein invasion

Figures & data

Table 1 Baseline characteristics of studies included in the network meta-analysis

Study and treatment	Study quality	Study design	Propensity score matching	Child–Pugh score	ECOG PS	Vascular invasion	Serum AFP ≥400 ng/mL (n)	End point outcome used	Toxicity ≥ grade 3	I^2
TACE + sorafenib vs TACE or sorafenib alone										18%
1. Choi et al,^Citation27 Korea; TACE + sorafenib (=164); sorafenib alone (n=191)	High	Retrospective	Yes	A/B: 119/45; A/B: 136/55	NA	PVTT + extrahepatic meta	83; 104	OS, DCR	Leucopenia: 6 vs 3; hand–foot: 29 vs 23
2. Bai et al,^Citation28 China; TACE + sorafenib (=82); TACE alone (n=146)	High	Prospective non-RCT	Yes	A/B: 63/19; A/B: 163/59	0/1/2/3: 30/38/12/1/1; 0/1/2/3: 85/119/18/0/0	MVI + extrahepatic metastasis	NA	OS, DCR	Hand–foot: 2 vs 0; diarrhea: 4 vs 0
TACE vs sorafenib alone
3. Pinter et al,^Citation29 Austria; TACE alone (n=34); sorafenib alone (n=63)	High	Retrospective	No	A/B: 20/14; A/B: 28/35	0/≥1: 9/25; 0/≥1: 21/42	MVI + extrahepatic metastasis	8; 19	OS, DCR	Leucopenia: 2 vs 1; hand–foot: 0 vs 2
TACE + 3D-RT vs TACE										0%
4. Li et al,^Citation30 China; TACE + RT (n=108); TACE alone (n=108)	High	Retrospective	Yes	A/B: 102/6; A/B: 105/3	NA	PVTT + extrahepatic metastasis	66; 61	OS, DCR	NA
5. Lu et al,^Citation31 China; TACE + RT (n=30); TACE alone (n=33)	High	Retrospective	No	A/B: 20/10; A/B: 21/12	NA	PVTT + extrahepatic meta	12; 11	OS, DCR	NA
6. Koo et al,^Citation32 Korea; TACE + RT (n=42); TACE alone (n=29)	High	Prospective	No	A/B: 26/16; A/B: 17/12	0–2	IVCTT	≤1,000 ng/mL; 22; 14	OS, DCR	NA
HAIC + 3D-RT vs HAIC alone										17%
7. Chuma et al,^Citation21 Japan; HAIC + RT (n=20); HAIC alone (n=20)	Moderate	Retrospective	No	A/B: 15/5; A/B: 13/7	NA	PVTT	NA	OS, DCR	Leucopenia: 3 vs 2
8. Fujino et al,^Citation19 Japan; HAIC + RT (n=41); HAIC alone (n=42)	High	Retrospective	No	A/B/C: 19/14/8; A/B/C: 14/18/10	0/1: 37/4; 0/1: 35/7	PVTT	464; 1,742	OS, DCR	Leucopenia: 5 vs 6; thrombocytopenia: 5 vs 6
9. Katamura et al,^Citation22 Japan; HAIC + RT (n=16); HAIC alone (n=16)	Moderate	Prospective	No	A/B: 12/4; A/B: 13/3	NA	PVTT	184.8; 586.7	OS, DCR	Leucopenia: 9 vs 3; thrombocytopenia: 6 vs 5
10. Onishi et al,^Citation20 Japan; HAIC + RT (n=33); HAIC alone (n=34)	High	Retrospective	No	B: 16; B: 16	NA	PVTT	575; 399	OS, DCR	Blood bile increase: 3 vs 2; leucopenia: 15 vs 2
Sorafenib alone vs HAIC alone										0%
11. Jeong et al,^Citation33 Korea; HAIC alone (n=21); sorafenib alone (n=20)	High	Retrospective	No	A/B: 10/11; A/B: 14/6	1/2: 19/2; 1/2: 16/4	PVTT + extrahepatic meta	12; 13	OS, DCR	Neutropenia: 5 vs 0; thrombocytopenia: 6 vs 0; hand–foot: 0 vs 2
12. Kawaoka et al,^Citation34 Japan; HAIC alone (n=136); sorafenib alone (n=41)	Moderate	Retrospective	No	A: 136; A: 41	NA	MVI	Median: 415.3; 136	OS, DCR	Liver failure: 3 vs 0; hand–foot: 0 vs 2
13. Song et al,^Citation35 Japan; HAIC alone (n=136); sorafenib alone (n=41)	High	Retrospective	No	A/B: 45/4; A/B: 47/13	NA	PVTT + extrahepatic meta	Serum AFP ≥200 ng/mL; 32 vs 51	OS, DCR	Hematologya: 106 vs 0; diarrhea: 0 vs 13
SBRT + TACE vs SBRT										0%
14. Kang et al,^Citation36 China; SBRT + TACE (n=71); SBRT (n=30)	Moderate	Retrospective	No	A/B: 48/19; A/B: 24/11	NA	PVTT	27; 9	OS, DCR	NA
15. Sapir et al,^Citation37 USA TACE (n=84); SBRT (n=125)	Moderate	Retrospective	Yes	A: 84; 125	<2: 142/95; ≤2: 24; 25	PVTT	NA	OS, DCR	Hypervolemia: 3 vs 1; GI and biliary: 2 vs 7
Pooled data										19%

Note:

a Hematology in HAIC group: leucopenia (36), neutropenia (46), anemia (72), and thrombocytopenia (56).

Abbreviations: AFP, alpha-fetoprotein; DCR, disease control rate; ECOG PS, Eastern Cooperative Oncology Group Performance Status; GI, gastrointestinal; HAIC, hepatic arterial infusion chemotherapy; IVCTT, inferior vena cava tumoral thrombosis; MVI, macrovascular invasion; OS, overall survival; PVTT, portal vein tumor thrombus; RCT, randomized controlled trial; SBRT, stereotactic body radiotherapy; TACE, transarterial chemoembolization; 3D-RT, three-dimensional radiotherapy; NA, not available; RT, radiotherapy.

Figure 1 Flow chart diagram of searching strategy.

Figure 2 Risk of bias.

Figure 3 Comparisons of efficacy in terms of disease control rate in advanced HCC scheme.

Note: The numbers in bold indicate OR and 95% CI are significant.
Abbreviations: HAIC, hepatic arterial infusion chemotherapy; OR, odds ratio; SBRT, stereotactic body radiotherapy; TACE, transarterial chemoembolization; RT, radiotherapy.

Figure 4 Comparisons of efficacy in terms of median OS in advanced HCC.

Note: The numbers in bold indicate OR and 95% CI are significant.
Abbreviations: HAIC, hepatic arterial infusion chemotherapy; OR, odds ratio; OS, overall survival; SBRT, stereotactic body radiotherapy; TACE, transarterial chemoembolization; RT, radiotherapy.

Figure 5 Rankogram of interested treatment modality.

Abbreviations: HAIC, hepatic arterial infusion chemotherapy; SBRT, stereotactic body radiotherapy; TACE, transarterial chemoembolization; RT, radiotherapy.

Figure 6 Comparison of adverse events for regimens in advanced HCC OR (95% CI).

Note: The numbers in bold indicate OR and 95% CI are significant.
Abbreviations: CI, confidence interval; HAIC, hepatic arterial infusion chemotherapy; OR, odds ratio; SBRT, stereotactic body radiotherapy; TACE, transarterial chemoembolization; RT, radiotherapy.

Figure 7 Network inconsistency assessment in fix-effect model.

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