Prognostic model for unresectable hepatocellular carcinoma treated with dual PD-1 and angiogenesis blockade therapy.

BACKGROUND AND AIMS:Dual programmed death 1 (PD-1) and angiogenesis blockade therapy is a frontline treatment for hepatocellular carcinoma (HCC). An accepted model for survival prediction and risk stratification in individual patients receiving this treatment is lacking. Aimed to develop a simple prognostic model specific to these patients. APPROACH AND RESULTS:Patients with unresectable HCC undergoing dual PD-1 and angiogenesis blockade therapy were included in training cohort (n=168) and validation cohort (n=72). We investigated the prognostic value of clinical variables on overall survival using a Cox model in the training set. A prognostic score model was then developed and validated. Predictive performance and discrimination were also evaluated. Largest tumor size and Alpha-fetoprotein concentration at baseline and Neutrophil count and Spleen volume change after 6 weeks of treatment were identified as independent predictors of overall survival in multivariable analysis and used to develop LANS score. Time-dependent receiver operating characteristic analysis, calibration curves, and C-index showed LANS score had favorable performance in survival prediction. Patients were divided into three risk categories based on LANS score. Median survival for patients with low, intermediate, and high LANS scores was 31.7, 23.5, and 11.5 months, respectively (p<0.0001). The disease control rates were 96.4%, 64.3%, and 32.1%, respectively (p<0.0001). The predictive performance and risk stratification ability of the LANS score were confirmed in validation and entire cohorts. CONCLUSION:The LANS score model can provide individualized survival prediction and risk stratification in patients with unresectable HCC undergoing dual PD-1 and angiogenesis blockade therapy.