ArticleJournal of hepatocellular carcinoma2026
Association of week-2 Contrast-Enhanced Ultrasound Perfusion Changes with Response to Lenvatinib Plus PD-1 Inhibitors in Unresectable Hepatocellular Carcinoma: A Retrospective Exploratory Study.
Article in Journal of hepatocellular carcinoma, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: To explore whether early contrast-enhanced ultrasound (CEUS)-derived tumor perfusion changes were associated with subsequent response to Lenvatinib plus PD-1 inhibitors in unresectable hepatocellular carcinoma (HCC). Methods: This study included 74 patients with unresectable HCC treated with Lenvatinib plus PD-1 inhibitors in routine clinical practice retrospectively. Baseline and early on-treatment CEUS examinations at approximately 2 weeks after treatment initiation were analyzed to quantify tumor perfusion parameters. Objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were study endpoints. Associations between CEUS findings and treatment outcomes were analyzed. Results: ORR of Lenvatinib plus PD-1 inhibitors among 74 patients with HCC was 33.8% (95% CI: 23.2-45.7%) and DCR was 73.0% (95% CI: 61.4-82.6%). Median DoR among the 25 responders was 8.7 months (95% CI: 7.39-10.01 months). After a median follow-up duration of 21.1 months, median PFS was 6.9 months (95% CI: 4.33-9.47 months) and median OS was 21.3 months (95% CI: 14.70-27.90 months). CEUS perfusion analysis showed that baseline tumor enhancement did not significantly differ between eventual responders and non-responders. In contrast, week-2 CEUS-derived perfusion changes, particularly percentage reduction in AUC, were associated with subsequent radiologic response. Using an exploratory cutoff of ≥35% AUC reduction, patients above this threshold showed longer PFS and OS than those below the threshold. These associations remained exploratory because the threshold was derived within a limited retrospective cohort. Treatment was generally well tolerated, no unexpected adverse events occurred, and there were no treatment-related deaths in this cohort. Conclusion: In this single-center retrospective exploratory cohort, week-2 CEUS-derived AUC reduction was associated with subsequent radiological response and survival outcomes in patients with unresectable HCC receiving Lenvatinib plus PD-1 inhibitors. These findings should be interpreted as hypothesis-generating and require prospective validation before CEUS-based perfusion changes can be used for clinical decision-making.
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