Comparing Immunotherapy Effectiveness for Unresectable Hepatocellular Carcinoma: Infiltrative Versus Non-Infiltrative Types in Real-World Settings

Chien-Ming Chiang,Kuan-Kai Huang,Chun-Te Lee, Tzu-Chun Hong,Juei-Seng Wu,Hung-Tsung Wu, Ting-Tsung Chang, Yi-Sheng Liu,Wei-Ting Chen,Chung-Teng Wang, Chen Chang,Po-Jun Chen,Ming-Tsung Hsieh,Chiung-Yu Chen,Chiao-Hsiung Chuang,Ching-Chi Lee,Sheng-Hsiang Lin,Yih-Jyh Lin,Hsin-Yu Kuo

THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY（2025）

Natl Cheng Kung Univ

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Abstract

Background: Infiltrative hepatocellular carcinoma (HCC) is often associated with an unfavorable prognosis, posing a challenge in determining the optimal therapeutic approach. Immunotherapy, employing immune checkpoint inhibitors (ICIs), has become a preferred first-line treatment for advanced HCC. However, the overall effectiveness of ICIs in patients with infiltrative HCC remains unclear. This study aims to compare the effect of ICI treatment on clinical outcomes between patients with infiltrative and non-infiltrative HCC. Materials and methods: A retrospective cohort consisting of unresectable HCC patients who underwent immunotherapy with ICIs, categorized into infiltrative and non-infiltrative groups was studied. Primary outcomes comprised treatment response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, progression-free survival (PFS), and overall survival (OS). Results: Of 198 patients, 60 (30.3%) had infiltrative HCC, while 138 (69.7%) had non-infiltrative HCC. In the infiltrative group, the objective response rate (ORR) was 36.7% and the disease control rate (DCR) was 55.0%. For the non-infiltrative group, the ORR was 33.3% and the DCR was 56.5%, showing no significant difference between the two groups. However, patients in the infiltrative group had significantly shorter median of PFS and OS following immunotherapy, with a PFS of 4.1 months (95% CI: 2.5–6.7; p = 0.0409) and an OS of 10.4 months (95% CI: 6.7–14.4; p = 0.0268), compared with the non-infiltrative group, which had a PFS of 5.5 months (95% CI: 3.2–7.6) and an OS of 17.0 months (95% CI: 12.8–21.8). Conclusion: For immunotherapy, infiltrative HCC exhibits treatment responses similar to non-infiltrative HCC. Nonetheless, infiltrative HCC is associated with shorter survival outcomes, compared with non-infiltrative type. Our findings emphasize the essential of considering type discrepancies when developing management strategies for immunotherapy.

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hepatocellular carcinoma,immune checkpoint inhibitors,infiltrative tumor morphology

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