A novel clinical FIT model predicts prognosis of unresectable hepatocellular carcinoma treated with TACE combined with lenvatinib and PD-1 inhibitors therapy

Background Transcatheter arterial chemoembolization (TACE) with lenvatinib and programmed death-1 (PD-1) inhibitors therapy (triple therapy) demonstrated encouraging efficacy for unresectable hepatocellular carcinoma (uHCC). This study developed and validated a novel prognostic model to evaluate prognosis of uHCC patients with triple therapy, and identify patients who may benefit from triple therapy. Methods uHCC patients receiving triple therapy were retrospectively enrolled from multiple centers. Overall survival (OS) was the primary endpoint. The prognostic model was developed based on multivariate Cox regression derived predictors of OS. Prognosis was evaluated by Kaplan-Meier survival curves. Results 265 uHCC patients were enrolled (training cohort: n = 160; validation cohort: n = 105). The objective response and disease control rate were 52.5 and 77.7%, respectively. The optimal cut-off point for fibrin degradation products (FDP) and serum iron level were determined as 4.7 μg/dL and 60.0 μg/dL, respectively. Multivariate Cox regression identified FDP, serum iron level and tumor burden score (TBS) as independent predictors of OS, and these clinical parameters established the FIT model. The FIT model demonstrated favorable discriminative capability for predicting OS with AUC of 0.809 (95% CI: 0.740-0.879) and 0.798 (95% CI: 0.710-0.886) in the training and validation cohorts, respectively. Kaplan-Meier analyses revealed significant prognostic stratification for OS and progression-free survival (PFS) among risk groups defined by FIT model ( p < 0.001). Subgroup analyses in alpha-fetoprotein (AFP), tumor number and Barcelona Clinic Liver Cancer (BCLC) stage subsets confirmed the prognostic relevance of FIT model in uHCC. Conclusion The novel clinical FIT model could effectively predict survival of uHCC patients receiving triple therapy, and facilitate prognostic stratification.