title: Development and validation of insulin-like growth factor-1 score to assess hepatic reserve in hepatocellular carcinoma.
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 50 ng/mL = 1 point; 26 to 50 ng/mL = 2 points; and less than 26 ng/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.
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ). akaseb@mdanderson.org.
authors.forename: Ahmed O
authors.initials: AO
authors.lastname: Kaseb
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Lianchun
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Manal M
authors.initials: MM
authors.lastname: Hassan
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Young Kwang
authors.initials: YK
authors.lastname: Chae
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Vauthey
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Sheree
authors.initials: S
authors.lastname: Cheung
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Hassabo
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Thomas
authors.initials: T
authors.lastname: Aloia
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Claudius
authors.initials: C
authors.lastname: Conrad
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Steven A
authors.initials: SA
authors.lastname: Curley
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: John M
authors.initials: JM
authors.lastname: Vierling
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Prasun
authors.initials: P
authors.lastname: Jalal
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Kanwal
authors.initials: K
authors.lastname: Raghav
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Michael
authors.initials: M
authors.lastname: Wallace
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.affiliation: Affiliations of authors: Department of Gastrointestinal Medical Oncology (AOK, MMH, YKC, SC, HM H, KR, JLA, RW), Department of Biostatistics (LX, JSM), Department of Systems Biology (JSL), Department of Surgical Oncology (JNV, TA, CC, SAC), Department of Radiation Oncology (SK), Department of Interventional Radiology (MW), and Department of Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hepatology, Baylor College of Medicine, Houston, TX (JMV, PJ).
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Morris
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000378:metabolism*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000097:blood / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D007334:Insulin-Like Growth Factor I