I-CLIP: Improved Stratification of Advanced Hepatocellular Carcinoma Patients by Integrating Plasma IGF-1 into CLIP Score

Abstract

Objective: Improving the prognostic stratification of unresectable hepatocellular carcinoma (HCC) patients is critically needed. Since patients’ survival is closely linked to the severity of the underlying liver disease, and insulin-like growth factor-1 (IGF-1) is produced predominantly in the liver, we hypothesized that IGF-1 may correlate with patients’ survival and hence improve the prognostic ability of the Cancer of the Liver Italian Program (CLIP) score. Methods: Baseline plasma IGF-1 and clinicopathologic parameters were available from 288 patients. Multivariate Cox regression models, Kaplan-Meier curves, and the log-rank test were applied. Recursive partitioning was used to determine the optimal cut point for IGF-1 using training/validation samples. Prognostic ability of the I-CLIP (I = IGF) was compared to CLIP using C-index. Results: IGF-1 significantly correlated with the clinicopathologic features. With an optimal IGF-1 cut point of 26 ng/ml, the overall survival of patients with IGF-1 >26 was 17.7 months (95% CI 13.6–22.8), and with IGF-1 ≤26 was 5.8 months (95% CI 4.0–12.5), p < 0.0001. The concordance probabilities for CLIP and I-CLIP were 0.7037 and 0.7096, respectively (p < 0.0001). Conclusions: Our preliminary results indicate that I-CLIP significantly improved prognostic stratification of patients with advanced HCC. However, independent validation of our study is warranted.

Serum Insulin-Like Growth Factor-1 Levels Predict Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy

“…The associations were independent of other clinicopathologic variables such as hepatitis etiologies, performance status, a-fetoprotein levels, and CLIP scores. Although previous studies have shown that blood IGF-1 levels are a prognostic marker for HCC (13,14,22), this is the first study showing the potential association between serum IGF-1 levels and the efficacy of systemic therapy for advanced HCC. The study was a retrospective analysis and did not include a control group of patients who did not receive therapy.…”

“…However, patients with HCC had lower circulating IGF-1 levels than healthy controls (10). On the basis of an HCC patient cohort with heterogeneous disease status and treatment, Kaseb and colleagues found that low plasma IGF-1 levels were associated with extensive liver involvement, vascular invasion, and poorer OS (13,14). Most circulating IGF-1 is produced in the liver (3,4).…”

“…In addition, low serum IGF-1 levels were associated with extensive liver involvement and vascular invasion in patients with HCC (12,13). The inclusion of serum IGF-1 level into the common HCC staging systems improves their prognostic stratification (13,14).…”

Serum Insulin-like Growth Factor-I Level Is an Independent Predictor of Recurrence and Survival in Early Hepatocellular Carcinoma: A Prospective Cohort Study

“…Nonetheless, our results are consistent with recent studies of the levels of circulating IGF-I and prognosis in patients with hepatocellular carcinoma. Kaseb and colleagues showed that lowplasma IGF-I levels were associated with advanced clinicopathologic factors and shorter OS in patients with heterogeneous stages of hepatocellular carcinoma (11,21). Similarly, low-baseline serum IGF-I levels correlated with poor treatment response, progression-free survival, and OS in patients who received antiangiogenic therapy for advanced hepatocellular carcinoma (12).…”

Diagnosis and treatment of hepatocellular carcinoma: An update

“…In this group of patients, the BCLC classification correlates best with survival than other staging systems and their survival rates are better due to the possibility of providing curative treatment of larger lesions in turn, leading to decreased recurrences (27% vs 73%) and greater survival (81% vs 23%) [116,117] . Upon recent inclusion of molecular markers such as wtER, IGF and VEGF-1 in prognostic scoring systems such as CLIP, their precision has been favorable although they are not currently routinely used [118][119][120] .…”