{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:09:09Z","timestamp":1779167349221,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background\/Objectives: Patients with unresectable hepatocellular carcinoma (uHCC) refractory or intolerant to immune checkpoint inhibitor (ICI)-based regimens represent a growing yet therapeutically underserved population with limited treatment options. We investigated the efficacy, safety, and mechanistic underpinnings of lenvatinib combined with New FP hepatic arterial infusion chemotherapy (LEN\u2013New FP) in this challenging clinical setting. Methods: We retrospectively analyzed 14 consecutive patients with uHCC treated with LEN\u2013New FP between April 2022 and March 2025. Tumor response was assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Proper hepatic artery (PHA) diameter was serially measured on angiography as an exploratory assessment of vascular remodeling, and tumor vascularity was semi-quantitatively evaluated using a 4-point angiographic scoring system (Tumor Vascularity Score [TVS]). Results: The cohort comprised BCLC stage B\/C (7\/7), mALBI grade 1\u20132b, and 13 of 14 patients with prior ICI-containing therapy. The objective response rate and disease control rate were 85.7% and 100%, including two complete responses. Median overall survival was 22.8 months from LEN\u2013New FP initiation (median follow-up: 15.1 months) and 36.2 months from first-line initiation; median intrahepatic progression-free survival was 10.4 months. A total of 11 of 14 patients (78.6%) transitioned to subsequent therapies, including four curative-intent conversions. PHA narrowing was observed in 10 of 13 evaluable patients (76.9%), with no clear association with hepatic function deterioration. TVS decreased in 10 of 12 evaluable patients (83.3%), with reduction observed in 90.0% of PR\/CR cases. Conclusions: LEN\u2013New FP achieved sustained intrahepatic tumor control and encouraging survival in aggressive uHCC, including ICI-refractory or -intolerant disease. The concordant reduction in PHA diameter and tumor vascularity score provides angiographic evidence of VEGFR inhibition-mediated vascular remodeling, offering mechanistic insight into the synergistic antitumor effects of this regimen and supporting LEN\u2013New FP as a promising multimodal strategy within the evolving landscape of HCC treatment.<\/jats:p>","DOI":"10.3390\/curroncol33050286","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T16:26:37Z","timestamp":1778689597000},"page":"286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lenvatinib Combined with New FP Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma: Clinical Efficacy, Vascular Remodeling, and Implications for Immuno-Oncology\u2013Systemic Combination Therapy"],"prefix":"10.3390","volume":"33","author":[{"given":"Susumu","family":"Maruta","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Koshima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Debari","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chihei","family":"Sugihara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gou","family":"Takahata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadashi","family":"Ohshima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuho","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoki","family":"Chiba","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideto","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Chinzei","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiko","family":"Ooka","sequence":"additional","affiliation":[{"name":"Chiba Chuo Clinic, 1-1 Honchiba-cho, Chuo-ku, Chiba 260-0014, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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