Transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) is the mainstay treatment for unresectable hepatocellular carcinoma (uHCC). However, studies investigating different combinations of agents have shown inconsistent results. Here, we used network meta-analysis (NMA) to compare different agents across 41 studies (36 cohort studies and five RCTs) in 11,540 patients. Multiple RCTs and cohort studies were searched to evaluate TACE combined with different TKIs. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and tumor response. NMA used a random-effects consistency model to pool evidence from direct and indirect comparisons. Hazard ratio (HR) and relative risks (RR) with 95% confidence intervals (CI) were analyzed. Further, heterogeneity and publication bias analyses were performed and agents were ranked. TACE plus lenvatinib provided the maximal OS (Rank probability: 0.7559), PFS (Rank probability: 0.8595), CR (Rank probability: 0.4179), and DCR (Rank probability: 0.3857). TACE plus anlotinib demonstrated the highest PR (p = 0.62649) and ORR (p = 0.51158). SD was more often associated with TACE plus sorafenib (Rank probability: 0.601685). TACE plus lenvatinib provides optimal treatment for uHCC based on the highest ranking of OS, PFS, and DCR rates. However, given the lack of statistically significant OS benefit, shared decision making should include other TKIs as acceptable alternatives.

Tumor growth rate (TGR) is a dynamic biomarker for evaluating therapeutic response and prognosis in unresectable hepatocellular carcinoma (uHCC) with tripl

Purpose: To investigate the prognostic value of post-treatment prognostic nutritional index (PNI) in advanced hepatocellular carcinoma (HCC) patients treated with immune‑based therapy, and explore its correlation with nutritional-inflammatory markers and treatment response. Methods: This retrospective study enrolled 133 patients with unresectable or metastatic HCC who received first- or second-line immune-based regimens (February 2019–September 2022). Patients were stratified by median post-treatment PNI (46.3). Survival was analyzed using Kaplan-Meier and Cox regression methods; subgroup interaction, Spearman correlation, and ROC analyses were also performed. Results: Significant baseline differences in Child-Pugh grade, vascular invasion, tumor size, baseline PNI, and median follow-up were observed between groups (all P < 0.05) and adjusted for in multivariate models. Elevated post-treatment PNI independently predicted longer overall survival (median 24.80 vs. 12.27 months, HR = 0.597, 95% CI 0.362– 0.983, P = 0.043) and progression-free survival (median 17.07 vs. 7.47 months, HR = 0.558, 95% CI 0.317– 0.981, P = 0.043). No significant subgroup interaction was observed for PFS (all interaction P > 0.05); for OS, effect modification was suggested for tumor number (interaction P = 0.036) and AFP level (interaction P = 0.035). Post-treatment PNI positively correlated with albumin (r = 0.862) and lymphocyte count (r = 0.632), and negatively with NLR (r = − 0.429) and CRP (r = − 0.354). It showed moderate discriminatory ability for objective response (AUC = 0.663). Dynamic change in PNI (ΔPNI) lacked prognostic significance. Median follow-up was 17.2 months. Conclusion: Post‑treatment PNI is an independent prognostic biomarker in advanced HCC treated with immune‑based therapy, closely reflecting nutritional-inflammatory status and showing moderate discriminatory ability for treatment response. Dynamic PNI changes provided no incremental prognostic value in this cohort.

The baseline CRAFITY score, derived from AFP and C-reactive protein, is a validated prognostic biomarker for hepatocellular carcinoma (HCC) patients receiving immunotherapy. However, whether its prognostic value can be improved by on-treatment reassessment remains unclear. We evaluated the two-cycle on-treatment CRAFITY score in 108 advanced-HCC patients who received immune-based combination therapy as first- or second-line treatment. The score was calculated at baseline and after two cycles. Kaplan–Meier, Cox regression, time-dependent ROC, landmark, and sensitivity analyses were performed. The two-cycle score significantly stratified overall survival (median OS from landmark: 34.6, 12.9, and 6.7 months for scores 0, 1, and 2; p < 0.0001) and remained independently associated with OS after adjustment for vascular invasion, treatment line, and concomitant transarterial chemoembolization (TACE) (HR 2.36, 95% CI 1.70–3.29, p < 0.001). The baseline score showed only borderline associations (OS p = 0.07; PFS p = 0.09). The two-cycle score had an apparent AUC of 0.709 (95% CI 0.586–0.832) at 6 months and 0.745 (95% CI 0.658–0.832) at 12 months. The corresponding values for the baseline score were 0.645 and 0.638. Adding the two-cycle score to a clinical reference model increased the 12-month AUC from 0.699 to 0.811 (ΔAUC = 0.112). Bootstrap internal validation yielded an optimism-corrected C-index of 0.698 (95% CI 0.650–0.776). In conclusion, the two-cycle CRAFITY score provides complementary posttreatment prognostic information for early risk stratification, but prospective external validation is required before clinical application.