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IV-HCC: Clinical and prognostic implications of plasma IGF-1 and VEGF in patients with hepatocellular carcinoma.

155 Background: Hepatocellular carcinoma (HCC) is a vascular tumor, derived mainly by vascular endothelial growth factor (VEGF)-mediated angiogenesis. It is always associated with chronic liver disease (CLD) and cirrhosis, which directly affect survival of HCC patients. Insulin-like growth factor-1 (IGF-1) is produced predominantly in the liver, and therefore, CLD is associated with low levels of IGF-1.


METHODS
288 new consecutive patients with HCC were eligible for the study between 2001 and 2008 at M. D. Anderson Cancer Center. Baseline clinicopathologic features, CLIP and BCLC staging, plasma IGF-1 and VEGF levels were available and multivariate Cox regression models and median survival were calculated. Kaplan-Meier curves were used to estimate overall survival and the log-rank test was used to compare survival probabilities in patients with different IGF-1 and VEGF levels. Recursive partitioning was used to determine the optimal cut point for IGF-1 and VEGF, using repeated training/validation samples, each using 2/3 of the data to determine the best cut point and the remaining 1/3 to validate it. Prognostic ability of different molecular staging systems was compared using C-index.


RESULTS
Lower plasma IGF-1 and higher plasma VEGF levels significantly correlated with advanced clinicopathologic parameters and poor overall survival, with an optimal cut point of 26 pg/mL and 450 pg/mL respectively. The combination of low IGF-1 and high VEGF predicts median OS of 2.7 months compared with 19 month for patients with high IGF-1 and low VEGF (p-value=<0.0001), and further refines the prognostic ability of BCLC and CLIP HCC staging systems (p<0.0001).


CONCLUSIONS
Molecular classification of HCC using baseline plasma IGF-1 and VEGF significantly correlated with clinical features and survival of HCC patients. Furthermore, integrating IGF-1 and VEGF into HCC staging systems, CLIP and BCLC, significantly enhanced their ability to predict prognosis. It may prove to be useful in designing strategies to personalize treatment approaches to these patients. No significant financial relationships to disclose.