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. 2011 Oct 10;29(29):3892-9.
doi: 10.1200/JCO.2011.36.0636. Epub 2011 Sep 12.

Clinical and prognostic implications of plasma insulin-like growth factor-1 and vascular endothelial growth factor in patients with hepatocellular carcinoma

Ahmed O Kaseb  1 , Jeffrey S Morris, Manal M Hassan, Adnan M Siddiqui, E Lin, Lianchun Xiao, Eddie K Abdalla, Jean-Nicolas Vauthey, Thomas A Aloia, Sunil Krishnan, James L Abbruzzese
Affiliations

Clinical and prognostic implications of plasma insulin-like growth factor-1 and vascular endothelial growth factor in patients with hepatocellular carcinoma

Ahmed O Kaseb et al. J Clin Oncol. .

Abstract

Purpose: Cirrhosis and hepatocellular carcinoma (HCC) together form a two-disease state that affects survival of patients with HCC and dictates treatment decisions and prognostic stratification of patients in clinical trials. The study objective was to improve prognostic stratification of patients with HCC.

Patients and methods: We prospectively collected plasma samples and baseline clinicopathologic features from 288 new patients with HCC, and plasma insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) levels were tested. We applied Cox regression and log-rank tests to assess association of IGF-1 and VEGF with overall survival (OS), Kaplan-Meier curves to estimate OS, and recursive partitioning to determine optimal cutoff points for IGF-1 and VEGF. Prognostic ability of conventional and molecular Barcelona Clinic Liver Cancer classifications was compared using the c-index.

Results: Lower plasma IGF-1 and higher plasma VEGF levels significantly correlated with advanced clinicopathologic parameters and poor OS, with optimal cut points of 26 ng/mL and 450 pg/mL, respectively. The combination of low IGF-1 and high VEGF predicted median OS of 2.7 months compared with 19 months for patients with high IGF-1 and low VEGF (P < .001), further refining the prognostic ability of conventional HCC staging (P < .001).

Conclusion: Baseline levels of plasma IGF-1 and VEGF correlated significantly with survival in patients with HCC. Integrating IGF-1 and VEGF into HCC staging significantly enhanced prognostic stratification of patients. If validated, these results may prove to be useful in designing strategies to personalize management approaches among these patients.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Barcelona Clinic Liver Cancer staging. CLT, cadaveric liver transplantation; HCC, hepatocellular carcinoma; LDLT, living-donor liver transplantation; PEI, percutaneous ethanol injection; PST, performance status; RF, radio-frequency ablation; TACE, trans-arterial chemoembolization; ttc, treatment.
Fig 2.
Fig 2.
Kaplan-Meier estimates of overall survival in (A) all patients (n = 288; reprinted with permission) and (B) patients split by combination of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) levels. HH, high VEGF, high IGF-1; HL, high VEGF, low IGF-1; LH, low VEGF, high IGF-1; LL, low VEGF, low IGF-1.
See this image and copyright information in PMC

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