Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Table 1 Association between baseline circulating markers and outcome in patients treated with various treatments for hepatocellular carcinoma

Ref.	Markers	Patients (n)	Study design	Treatment	Level values	Clinical impact	Conclusion/comments
Schoenleber et al[85]	VEGF-A	1018	Systemic review and meta-analysis including only serum-based studies	Various (surgery, LRT and systemic therapies)	High serum VEGF level	Poorer OS	Serum VEGF method detection varied among studies
						Poorer DFS	Serum VEGF levels seem more reliable than tissue VEGF for HCC prognosis
Poon et al[115]	bFGF	88	Prospective	Surgery	High serum level > 10.8 pg/mL	Larger tumor > 5 cm	High bFGF serum level before surgery was shown to be an independent factor of early recurrence. No further studies confirmed these findings
						Venous invasion
Vejchapipat et al[105]	HGF	55	Retrospective	BSC	High level (≥ 1.0 ng/mL	Advanced pTNM stage Poorer prognosis Poorer OS	Although a control group was included, results of this small cohort study need confirmation in larger prospective analysis
Chau et al[104]		40	Retrospective	Resection	High portal and serum HGF level (> 699 pg/mL)	Multiple tumor	One limit of this study were the feasibility in routine of intraoperative puncture of the portal vein was difficult
						Poorer prognosis
Mizuguchi et al[106]		100	Retrospective	Resection	High serum level (≥ 0.35 ng/mL)	Postoperative complications	No correlation was observed between HGF level and RFS
						Poorer OS
Kaseb et al[87]	IGF-1	288	Prospective	Various	Low plasma level (26 ng/mL)	High Child-Pugh score	The authors proposed that IGF-1 plasma level to be integrated into the BCLC staging system to predict OS for personal management in patients with HCC. This proposal was not yet adopted in clinical practice
						High AST level
						High tumor size
						Multiple tumor
						Vascular invasion
						Poorer OS

BCLC: Barcelona clinic liver cancer; bFGF: Basic fibroblast growth factor; BSC: Best supportive care; DFS: Disease-free survival; HGF: Hepatocyte growth factor; IGF-1: Insulin growth factors 1; LRT: Loco-regional treatment; OS: Overall survival; RFS: Recurrence-free survival; VEGF: Vascular endothelial growth factors.