Development and validation of insulin-like growth factor-1 score to assess hepatic reserve in hepatocellular carcinoma

Ahmed O. Kaseb*, Lianchun Xiao, Manal M. Hassan, Young Kwang Chae, Ju Seog Lee, Jean Nicolas Vauthey, Sunil Krishnan, Sheree Cheung, Hesham M. Hassabo, Thomas Aloia, Claudius Conrad, Steven A. Curley, John M. Vierling, Prasun Jalal, Kanwal Raghav, Michael Wallace, Asif Rashid, James L. Abbruzzese, Robert A. Wolff, Jeffrey S. Morris

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background Child-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. Methods We 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. Results Patients' 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). Conclusions The 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.

Original languageEnglish (US)
Article numberdju088
JournalJournal of the National Cancer Institute
Volume106
Issue number5
DOIs
StatePublished - May 14 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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