Gustave Roussy Immune Score Predicts Outcomes in Hepatocellular Carcinoma Treated with TACE and Immunotherapy.

[OBJECTIVE] To evaluate the prognostic value of the Gustave Roussy Immune (GRIm) score and the hepatocellular carcinoma-specific GRIm (HCC-GRIm) score in unresectable hepatocellular carcinoma (uHCC) treated with transarterial chemoembolization (TACE) plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/tyrosine kinase inhibitors (TKIs), and to examine their association with hepatitis B virus (HBV) activation and immune markers.

[METHODS] This retrospective study enrolled uHCC patients receiving TACE plus ICIs and anti-VEGF antibodies/TKIs. Baseline blood tests were used to calculate GRIm and HCC-GRIm scores and determine HBV activation (HBV DNA > 60 IU/mL). Patients were stratified by GRIm, HCC-GRIm, and HBV activation. Objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and peripheral immune markers were compared across groups. Cox regression identified independent prognostic factors, and the prognostic value of key predictors was compared with Barcelona Clinic Liver Cancer (BCLC) and China Liver Cancer (CNLC) staging systems.

[RESULTS] Sixty-seven patients were included. ORR and DCR were 53.7% and 86.6%; median OS was 30.4 months. High GRIm and HCC-GRIm scores were associated with shorter OS than low scores (GRIm: 15.4 vs 34.0 months, = 0.019; HCC-GRIm: 15.4 vs 36.7 months, = 0.002). OS and response did not differ significantly by HBV activation within score strata. Igλ, Igκ, and IgG levels were higher in patients with elevated GRIm/HCC-GRIm scores (all < 0.01). ECOG performance status, GRIm, HCC-GRIm, and CD3⁺CD8⁺ proportion were independent prognostic factors, and CD3⁺CD8⁺ stratification showed better OS discrimination than GRIm, HCC-GRIm, BCLC, and CNLC.

[CONCLUSION] GRIm and HCC-GRIm are effective prognostic indicators in uHCC patients treated with TACE plus ICIs and anti-VEGF antibodies/TKIs, reflecting systemic immune and inflammatory status. Both scores retain prognostic value regardless of pre-treatment HBV activation but do not predict tumor response. In this single-center cohort, GRIm provided prognostic discrimination comparable to HCC-GRIm, and CD3⁺CD8⁺ T-cell stratification also showed prognostic value, offering an additional approach for risk assessment. Future larger, multicenter studies are needed to validate these findings and to define the optimal roles of GRIm, HCC-GRIm, and CD3⁺CD8⁺-based stratification in routine clinical practice.