V-CLIP: Integrating plasma vascular endothelial growth factor into a new scoring system to stratify patients with advanced hepatocellular carcinoma for clinical trials.
BACKGROUND
Several staging systems have been proposed for hepatocellular carcinoma (HCC); however, none has incorporated circulating angiogenic biomarkers. The purpose of this study was to determine whether vascular endothelial growth factor (VEGF) could independently predict overall survival in patients with HCC, and whether adding VEGF level into the Cancer of the Liver Italian Program (CLIP) score could improve patient stratification and prediction of overall survival.


METHODS
Between 2001 and 2008, baseline plasma VEGF levels were available from 288 patients, and multivariate Cox regression models and median survival (95% confidence intervals) were calculated. Recursive partitioning was used to determine the optimal cutpoint for VEGF, using 10 repeated training/validation samples, each using two-thirds of the data to determine the best cutpoint and the remaining one-third to validate it. Prognostic ability of CLIP and V-CLIP was compared using the concordence index.


RESULTS
Plasma VEGF was a significant independent predictor of overall survival, with an optimal VEGF cutpoint of 450 pg/mL. After CLIP validation in our patients, we added VEGF to the CLIP score and found that the new V-CLIP score better separates patients into homogenous prognostic groups (P = .005).


CONCLUSIONS
The assessment of baseline plasma VEGF levels increases the precision of the CLIP scoring system for predicting HCC prognosis, which may assist in equally randomizing patients with HCC in clinical trials. Prospective validation of the V-CLIP scoring system is warranted.
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. akaseb@mdanderson.org.
Ahmed O
AO
Kaseb
Manal M
MM
Hassan
E
E
Lin
Lianchun
L
Xiao
Vikas
V
Kumar
Priyanka
P
Pathak
Richard
R
Lozano
Asif
A
Rashid
James L
JL
Abbruzzese
Jeffrey S
JS
Morris
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015203:Reproducibility of Results; D012306:Risk; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A
CLIP; VEGF; hepatocellular carcinoma; prognosis; staging