Prognostic Significance of Pan-Immune-inflammation Value in Hepatocellular Carcinoma Treated by Curative Radiofrequency Ablation: Potential Role for Individualized Adjuvant Systemic Treatment

Background: This study aimed to explore the prognostic role of pan-immune-inflammation value (PIV) and develop a new risk model to guide individualized adjuvant systemic treatment following radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC). Materials and methods: Patients with early-stage HCC treated by RFA were randomly divided into training cohort A (n = 65) and testing cohort B (n = 68). Another 265 counterparts were enrolled into external validating cohort C. Various immune-inflammatory biomarkers (IIBs) were screened in cohort A. Prognostic role of PIV was evaluated and validated in cohort B and C, respectively. A nomogram risk model was built in cohort C and validated in pooled cohort D. Clinical benefits of adjuvant anti-angiogenesis therapy plus immune checkpoint inhibitor (AA-ICI) following RFA was assessed in low- and high-risk groups. Results: The cutoff point of PIV was 120. High PIV was an independent predictor of unfavorable recurrence-free survival (RFS) and overall survival (OS). RFS and OS rates of patients with high PIV were significantly lower than those with low PIV both in cohort B (P-RFS=0.016, P-OS=0.011) and C (P-RFS<0.001, P-OS<0.001). The nomogram model based on PIV, tumor number and BCLC staging performed well in risk stratification in external validating cohort C. Adjuvant AA-ICI treatment showed an added benefit in OS (p = 0.011) for high-risk patients. Conclusions: PIV is a feasible independent prognostic factor for RFS and OS in early-stage HCC patients who received curative RFA. The proposed PIV-based nomogram risk model could help clinicians identify high-risk patients and tailor adjuvant systemic treatment and disease follow-up scheme.