Model to estimate survival in ambulatory patients with hepatocellular carcinoma

Abstract

Survival of patients with hepatocellular carcinoma (HCC) is determined by the extent of the tumor and the underlying liver function. We aimed to develop a survival model for HCC based on objective parameters including the Model for Endstage Liver Disease (MELD) as a gauge of liver dysfunction. This analysis is based on 477 patients with HCC seen at Mayo Clinic Rochester between 1994 and 2008 (derivation cohort) and 904 patients at the Korean National Cancer Center between 2000 and 2003 (validation cohort). Multivariate proportional hazards models and corresponding risk score were created based on baseline demographic, clinical, and tumor characteristics. Internal and external validation of the model was performed. Discrimination and calibration of this new model were compared against existing models including Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging (JIS) scores. The majority of the patients had viral hepatitis as the underlying liver disease (100% in the derivation cohort and 85% in the validation cohort). The survival model incorporated MELD, age, number of tumor nodules, size of the largest nodule, vascular invasion, metastasis, serum albumin, and alpha-fetoprotein. In cross-validation, the coefficients remained largely unchanged between iterations. Observed survival in the validation cohort matched closely with what was predicted by the model. The concordance (c)-statistic for this model (0.77) was superior to that for BCLC (0.71), CLIP (0.70), or JIS (0.70). The score was able to further classify patient survival within each stage of the BCLC classification.

Conclusion: A new model to predict survival of HCC patients based on objective parameters provides refined prognostication and supplements the BCLC classification.

Figure 1. Impact of MELD on the 3 year mortality prediction after adjusting for other risk score variables

MELD=10*(0.957*log(creatinine) + 1.12*log(INR) + 0.378*log(total bilirubin) + 0.643)

Figure 2. Expected survival of three hypothetical patients

Figure 3

Expected versus observed survival in the validation cohort Patients were divided into three tiers at the 25th and 75th percentiles of the risk score (Tier 1 includes the best 25%, Tier 2 the middle 50%, and Tier 3 the worst 25%).

Figure 4. Observed survival in MESIAH score tiers within BCLC groups Patients were divided into three tiers at the 25th and 75th percentiles of the risk score within each stratum of the BCLC staging system