Development and Validation of Insulin-like Growth Factor-1 Score to Assess Hepatic Reserve in Hepatocellular Carcinoma

Abstract

BackgroundChild-Turcotte-Pugh (CTP) score is the standard tool to assess hepatic reserve in hepatocellular carcinoma (HCC), and CTP-A is the classic group for active therapy. However, CTP stratification accuracy has been questioned. We hypothesized that plasma insulin-like growth factor 1 (IGF-1) is a valid surrogate for hepatic reserve to replace the subjective parameters in CTP score to improve its prognostic accuracy.MethodsWe retrospectively tested plasma IGF-1 levels in the training set (n = 310) from MD Anderson Cancer Center. Recursive partitioning identified three optimal IGF-1 ranges that correlated with overall survival (OS): greater than 50ng/mL = 1 point; 26 to 50ng/mL = 2 points; and less than 26ng/mL = 3 points. We modified the CTP score by replacing ascites and encephalopathy grading with plasma IGF-1 value (IGF-CTP) and subjected both scores to log-rank analysis. Harrell’s C-index and U-statistics were used to compare the prognostic performance of both scores in both the training and validation cohorts (n = 155). All statistical tests were two-sided.ResultsPatients’ stratification was statistically significantly stronger for IGF-CTP than CTP score for the training (P = .003) and the validation cohort (P = .005). Patients reclassified by IGF-CTP relative to their original CTP score were better stratified by their new risk groups. Most important, patients classified as A by CTP but B by IGF-CTP had statistically significantly worse OS than those who remained under class A by IGF-CTP in both cohorts (P = .03 and P < .001, respectively, from Cox regression models). AB patients had a worse OS than AA patients in both the training and validation set (hazard ratio [HR] = 1.45, 95% confidence interval [CI] = 1.03 to 2.04, P = .03; HR = 2.83, 95% CI = 1.65 to 4.85, P < .001, respectively).ConclusionsThe IGF-CTP score is simple, blood-based, and cost-effective, stratified HCC better than CTP score, and validated well on two independent cohorts. International validation studies are warranted.

Validation of a Modified Child-Turcotte-Pugh Classification System Utilizing Insulin-Like Growth Factor-1 for Patients with Hepatocellular Carcinoma in an HBV Endemic Area

“…[10] Cut-off points for total bilirubin, albumin, and PT are identical with those in the original CTP classification. Cut-off points for IGF-1, which were previously derived from recursive partitioning methods and survival analyses, are 26 and 50 ng/mL.…”

“…[7–9] Therefore, Kaseb et al constructed a modified CTP classification system (IGF-CTP) to predict survival in patients with HCC by replacing the two subjective parameters in the traditional CTP system with IGF-1 level (S1 Table). [10] They observed that the IGF-CTP classification provided better risk stratification than the original CTP classification in both American and international validation cohorts. [10, 11] However, the value of the IGF-CTP classification for prognostic stratification has not been evaluated in chronic hepatitis B (CHB) endemic areas, such the Asia-Pacific region.…”

“…[10] They observed that the IGF-CTP classification provided better risk stratification than the original CTP classification in both American and international validation cohorts. [10, 11] However, the value of the IGF-CTP classification for prognostic stratification has not been evaluated in chronic hepatitis B (CHB) endemic areas, such the Asia-Pacific region.…”

Obesity Early in Adulthood Increases Risk but Does Not Affect Outcomes of Hepatocellular Carcinoma

“…11–13 Overall survival (OS) was defined as the time between HCC diagnosis and death (as a result of all causes) or end of follow-up (censored observations). Underlying cirrhosis was determined by pathological findings (diagnostic biopsies) and by computed tomography scans.…”

Systematic tracking of disrupted modules identifies significant genes and pathways in hepatocellular carcinoma

“…Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer-associated mortality (1), which explains the importance of identifying novel early diagnostic markers and therapeutic targets (2). HCC primarily develops from cirrhosis caused by chronic infection with hepatitis B virus or hepatitis C virus (HCV), alcoholic injury, and, to a lesser extent, from genetically determined disorders (3).…”