{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:02:13Z","timestamp":1789552933007,"version":"build-2803163510"},"reference-count":18,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Changes in alpha-fetoprotein (AFP) after initiating lenvatinib may reflect response in patients with hepatocellular carcinoma (HCC), but the optimal assessment time point and AFP decline threshold remain unstandardized. This study evaluated the association between AFP change at the first post-treatment measurement and imaging response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Materials and Methods: This retrospective study included 191 patients with HCC treated with lenvatinib. The primary analysis population comprised patients with pretreatment AFP \u2265 20 ng\/mL and \u22651 post-treatment AFP measurement. AFP response was defined as a \u226540% decrease from pretreatment levels. The primary endpoints were the objective response rate (ORR) and disease control rate (DCR) according to mRECIST; progression-free survival (PFS) and overall survival (OS) were exploratory. Associations were assessed using multivariable logistic regression adjusted for AFP timing, albumin\u2013bilirubin (ALBI) score, macrovascular invasion, and tumor number \u2265 5. Sensitivity and 2-month landmark analyses were also performed. Results: Of 124 patients, 47 (37.9%) achieved an AFP response. ORR was 44.7% versus 6.5% in the non-response group (OR 11.36; 95% confidence interval [CI] 3.68\u201342.67; p &lt; 0.001); DCR was 83.0% versus 57.1% (OR 3.62; 95% CI 1.42\u201310.19; p = 0.003). After adjustment, AFP response remained independently associated with ORR (aOR 12.96; 95% CI 3.85\u201343.66; p &lt; 0.001) and DCR (aOR 5.76; 95% CI 1.95\u201317.00; p = 0.002); findings were unchanged when restricted to cycle-1 measurements (aOR 12.27). In exploratory analyses, median PFS was 8.51 versus 4.30 months and median OS 18.53 versus 10.15 months; landmark analysis gave concordant estimates (PFS HR 0.38; OS HR 0.45). Conclusions: A \u226540% AFP decline at the first post-treatment measurement was independently associated with ORR and DCR according to mRECIST in patients with HCC and pretreatment AFP \u2265 20 ng\/mL. These findings are hypothesis-generating and require confirmation in prospective, multicenter studies with independent validation before AFP kinetics can be considered in routine practice.<\/jats:p>","DOI":"10.3390\/medicina62091774","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:58:59Z","timestamp":1789545539000},"page":"1774","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Predictive Value of On-Treatment Alpha-Fetoprotein Change for Lenvatinib Response in Patients with Hepatocellular Carcinoma: A Real-World Retrospective Study in Vietnam"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9745-0329","authenticated-orcid":false,"given":"Ngoc-Tan","family":"Hoang","sequence":"first","affiliation":[{"name":"Department of Oncology, Hanoi Medical University, No. 1 Ton That Tung Street, Hanoi 100000, Vietnam"},{"name":"Vietnam National Cancer Hospital, No. 30 Cau Buou Street, Thanh Liet Ward, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van-Quang","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hanoi Medical University, No. 1 Ton That Tung Street, Hanoi 100000, Vietnam"},{"name":"Vietnam National Cancer Hospital, No. 30 Cau Buou Street, Thanh Liet Ward, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thang","family":"Tran","sequence":"additional","affiliation":[{"name":"Vietnam National Cancer Hospital, No. 30 Cau Buou Street, Thanh Liet Ward, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Thi-Que","family":"Pham","sequence":"additional","affiliation":[{"name":"Vietnam National Cancer Hospital, No. 30 Cau Buou Street, Thanh Liet Ward, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Thi-Dung","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Hanoi Oncology Hospital, No. 42A Thanh Nhan Street, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi-Cuc","family":"Hoang","sequence":"additional","affiliation":[{"name":"Vietnam National Cancer Hospital, No. 30 Cau Buou Street, Thanh Liet Ward, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh-Phuong","family":"Pham","sequence":"additional","affiliation":[{"name":"Vietnam National Cancer Hospital, No. 30 Cau Buou Street, Thanh Liet Ward, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Thi-Hoa","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Vietnam National Cancer Hospital, No. 30 Cau Buou Street, Thanh Liet Ward, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","first-page":"e70090","article-title":"Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries","volume":"76","author":"Sung","year":"2026","journal-title":"CA Cancer J. 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