{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:05:10Z","timestamp":1790057110081,"version":"4.0.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Transcatheter arterial chemoembolization (TACE) with lenvatinib and programmed death-1 (PD-1) inhibitors therapy (triple therapy) demonstrated encouraging efficacy for unresectable hepatocellular carcinoma (uHCC). This study developed and validated a novel prognostic model to evaluate prognosis of uHCC patients with triple therapy, and identify patients who may benefit from triple therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>uHCC patients receiving triple therapy were retrospectively enrolled from multiple centers. Overall survival (OS) was the primary endpoint. The prognostic model was developed based on multivariate Cox regression derived predictors of OS. Prognosis was evaluated by Kaplan-Meier survival curves.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      265 uHCC patients were enrolled (training cohort: n = 160; validation cohort: n = 105). The objective response and disease control rate were 52.5 and 77.7%, respectively. The optimal cut-off point for fibrin degradation products (FDP) and serum iron level were determined as 4.7 \u03bcg\/dL and 60.0 \u03bcg\/dL, respectively. Multivariate Cox regression identified FDP, serum iron level and tumor burden score (TBS) as independent predictors of OS, and these clinical parameters established the FIT model. The FIT model demonstrated favorable discriminative capability for predicting OS with AUC of 0.809 (95% CI: 0.740-0.879) and 0.798 (95% CI: 0.710-0.886) in the training and validation cohorts, respectively. Kaplan-Meier analyses revealed significant prognostic stratification for OS and progression-free survival (PFS) among risk groups defined by FIT model (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). Subgroup analyses in alpha-fetoprotein (AFP), tumor number and Barcelona Clinic Liver Cancer (BCLC) stage subsets confirmed the prognostic relevance of FIT model in uHCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The novel clinical FIT model could effectively predict survival of uHCC patients receiving triple therapy, and facilitate prognostic stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1906593","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:39:01Z","timestamp":1790055541000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel clinical FIT model predicts prognosis of unresectable hepatocellular carcinoma treated with TACE combined with lenvatinib and PD-1 inhibitors therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Minjun","family":"Liao","sequence":"first","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People\u2019s Hospital, Beijing Key Laboratory of Innovative Drug and Device Translation in Endocrine and Metabolic Diseases","place":["Beijing, China"]},{"name":"Department of Gastroenterology, Nanfang Hospital, Southern Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Department of Infectious Diseases, Nanfang Hospital, Southern Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilong","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People\u2019s Hospital, Beijing Key Laboratory of Innovative Drug and Device Translation in Endocrine and Metabolic Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People\u2019s Hospital, Beijing Key Laboratory of Innovative Drug and Device Translation in Endocrine and Metabolic Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ai","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People\u2019s Hospital, Beijing Key Laboratory of Innovative Drug and Device Translation in Endocrine and Metabolic Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linnan","family":"Song","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People\u2019s Hospital, Beijing Key Laboratory of Innovative Drug and Device Translation in Endocrine and Metabolic Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyun","family":"Song","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People\u2019s Hospital, Beijing Key Laboratory of Innovative Drug and Device Translation in Endocrine and Metabolic Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Qin","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Hepatobiliopancreatic Surgery, Nanfang Hospital, Southern Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology and Hepatology Unit, Nanfang Hospital, Southern Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Department of General Surgery, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People\u2019s Hospital, Beijing Key Laboratory of Innovative Drug and Device Translation in Endocrine and Metabolic Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Rao","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People\u2019s Hospital, Beijing Key Laboratory of Innovative Drug and Device Translation in Endocrine and Metabolic Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.02.010","article-title":"Transarterial chemoembolization: modalities, indication, and patient selection","volume":"62","author":"Sieghart","year":"2015","journal-title":"J Hepatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1159\/000485471","article-title":"Patient Selection for Transarterial Chemoembolization in Hepatocellular Carcinoma: Importance of Benefit\/Risk Assessment","volume":"7","author":"Piscaglia","year":"2018","journal-title":"Liver Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(18)30207-1","article-title":"Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial","volume":"391","author":"Kudo","year":"2018","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/s2468-1253(21)00110-2","article-title":"Lenvatinib versus sorafenib for first-line treatment of unresectable hepatocellular carcinoma: patient-reported outcomes from a randomised, open-label, non-inferiority, phase 3 trial","volume":"6","author":"Vogel","year":"2021","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(25)00403-9","article-title":"Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial","volume":"405","author":"Yau","year":"2025","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.003","article-title":"Combination immunotherapy for hepatocellular carcinoma","volume":"79","author":"Rimassa","year":"2023","journal-title":"J Hepatol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"102367","DOI":"10.1016\/j.eclinm.2023.102367","article-title":"Transcatheter arterial chemoembolisation combined with lenvatinib plus camrelizumab as conversion therapy for unresectable hepatocellular carcinoma: a single-arm, multicentre, prospective study","volume":"67","author":"Wu","year":"2024","journal-title":"EClinicalMedicine"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyaf058","article-title":"Long-term survival in advanced unresectable HCC treated with transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors","volume":"30","author":"Zeng","year":"2025","journal-title":"Oncologist"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1586914","article-title":"Efficacy and safety of lenvatinib plus transarterial chemoembolization with or without programmed death-1 inhibitors in the treatment of intermediate or advanced hepatocellular carcinoma: a systematic review and meta-analysis","volume":"16","author":"Lei","year":"2025","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12957-025-03788-0","article-title":"Comparative efficacy and safety of transarterial chemoembolization combined with tyrosine kinase inhibitors and immune checkpoint inhibitors versus tyrosine kinase inhibitors and immune checkpoint inhibitors alone in advanced hepatocellular carcinoma: a systematic review and meta-analysis","volume":"23","author":"Tian","year":"2025","journal-title":"World J Surg Oncol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41392-025-02498-z","article-title":"Lenvatinib plus transarterial chemoembolization and PD-1 inhibitors as conversion therapies for unresectable intermediate-advanced hepatocellular carcinoma: a phase 2 trial and exploratory biomolecular study","volume":"11","author":"Zhang","year":"2026","journal-title":"Signal Transduct Target Ther"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-023-10613-x","article-title":"The TAE score predicts prognosis of unresectable HCC patients treated with TACE plus lenvatinib with PD-1 inhibitors","volume":"18","author":"Zeng","year":"2024","journal-title":"Hepatol Int"},{"key":"B14","doi-asserted-by":"publisher","first-page":"112401","DOI":"10.1016\/j.ejrad.2025.112401","article-title":"Predicting tumor response to TACE plus lenvatinib and PD-1 inhibitors for unresectable HCC: A multicenter observational study","volume":"192","author":"Deng","year":"2025","journal-title":"Eur J Radiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29086","article-title":"AASLD guidelines for the treatment of hepatocellular carcinoma","volume":"67","author":"Heimbach","year":"2018","journal-title":"Hepatology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1247132","article-title":"Modified RECIST (mRECIST) assessment for hepatocellular carcinoma","volume":"30","author":"Lencioni","year":"2010","journal-title":"Semin Liver Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.09.026","article-title":"mRECIST for HCC: Performance and novel refinements","volume":"72","author":"Llovet","year":"2020","journal-title":"J Hepatol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-022-10480-y","article-title":"Real-world efficacy and prognostic factors of lenvatinib plus PD-1 inhibitors in 378 unresectable hepatocellular carcinoma patients","volume":"17","author":"Yang","year":"2023","journal-title":"Hepatol Int"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(24)02575-3","article-title":"Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study","volume":"405","author":"Kudo","year":"2025","journal-title":"Lancet"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2022.07.005","article-title":"Lenvatinib, toripalimab plus hepatic arterial infusion chemotherapy in patients with high-risk advanced hepatocellular carcinoma: A biomolecular exploratory, phase II trial","volume":"174","author":"Lai","year":"2022","journal-title":"Eur J Cancer"},{"key":"B21","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/s41420-024-02116-x","article-title":"Programmed cell death in hepatocellular carcinoma: mechanisms and therapeutic prospects","volume":"10","author":"Wu","year":"2024","journal-title":"Cell Death Discov"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1560750","article-title":"Efficacy and safety of TACE combined with lenvatinib and PD-1 Inhibitor in intermediate-stage HCC exceeding the up-7 criteria: a retrospective cohort study","volume":"16","author":"Xue","year":"2025","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/js9.0000000000004131","article-title":"Efficacy and safety of TACE plus lenvatinib with PD-1 inhibitor for unresectable huge hepatocellular carcinoma: a multicenter retrospective cohort study","volume":"112","author":"Liang","year":"2025","journal-title":"Int J Surg"},{"key":"B24","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.5114\/wo.2013.34611","article-title":"The role of fibrinogen, fibrin and fibrin(ogen) degradation products (FDPs) in tumor progression","volume":"17","author":"Ko\u0142odziejczyk","year":"2013","journal-title":"Contemp Oncol (Pozn)"},{"key":"B26","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V67.5.1468.1468","article-title":"Analysis of elevated fibrin(ogen) degradation product levels in patients with liver disease","volume":"67","author":"vanDeWater","year":"1986","journal-title":"Blood"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.11387","article-title":"High lymphocyte\u2011to\u2011monocyte ratio is associated with low \u03b1\u2011fetoprotein expression in patients with hepatitis B virus\u2011associated hepatocellular carcinoma","volume":"22","author":"Wang","year":"2020","journal-title":"Mol Med Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.2147\/cmar.S227418","article-title":"Correlation Analysis Between Preoperative Serum Iron Level and Prognosis as Well as Recurrence of HCC After Radical Resection","volume":"12","author":"Li","year":"2020","journal-title":"Cancer Manag Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00066","article-title":"Serum Iron Levels Decreased in Patients with HBV-Related Hepatocellular Carcinoma, as a Risk Factor for the Prognosis of HBV-Related HCC","volume":"9","author":"Wei","year":"2018","journal-title":"Front Physiol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.Epi-21-0754","article-title":"Serum Biomarkers of Iron Status and Risk of Hepatocellular Carcinoma Development in Patients with Nonalcoholic Fatty Liver Disease","volume":"31","author":"Yu","year":"2022","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-022-01753-2","article-title":"Hepcidin in hepatocellular carcinoma","volume":"127","author":"Joachim","year":"2022","journal-title":"Br J Cancer"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.15593","article-title":"Tumor burden score as a new prognostic marker for patients with hepatocellular carcinoma undergoing transarterial chemoembolization","volume":"36","author":"Ho","year":"2021","journal-title":"J Gastroenterol Hepatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1159\/000517393","article-title":"Redefining Tumor Burden in Patients with Intermediate-Stage Hepatocellular Carcinoma: The Seven-Eleven Criteria","volume":"10","author":"Hung","year":"2021","journal-title":"Liver Cancer"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1159\/000502905","article-title":"A New Treatment Option for Intermediate-Stage Hepatocellular Carcinoma with High Tumor Burden: Initial Lenvatinib Therapy with Subsequent Selective TACE","volume":"8","author":"Kudo","year":"2019","journal-title":"Liver Cancer"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2024.101216","article-title":"Tumor burden with AFP improves survival prediction for TACE-treated patients with HCC: An international observational study(\u2606)","volume":"7","author":"Xia","year":"2025","journal-title":"JHEP Rep"},{"key":"B36","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s40364-023-00535-z","article-title":"Biomarkers and prognostic factors of PD-1\/PD-L1 inhibitor-based therapy in patients with advanced hepatocellular carcinoma","volume":"12","author":"Zhang","year":"2024","journal-title":"Biomark Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1614392","article-title":"Nomogram for predicting postoperative recurrence in patients with microvascular invasion-negative hepatocellular carcinoma: development and validation","volume":"16","author":"Ye","year":"2025","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1186\/s12885-025-14516-y","article-title":"Trajectories of \u03b1-fetoprotein and unresectable hepatocellular carcinoma outcomes receiving lenvatinib: a retrospective, multicenter cohort study","volume":"25","author":"Zheng","year":"2025","journal-title":"BMC Cancer"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-024-10762-7","article-title":"HAIC plus lenvatinib and tislelizumab for advanced hepatocellular carcinoma with Vp4 portal vein invasion","volume":"19","author":"Tang","year":"2025","journal-title":"Hepatol Int"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.62347\/sxmj5155","article-title":"Key prognostic factors in transarterial chemoembolization combined with sorafenib treatment for hepatocellular carcinoma with portal vein tumor thrombosis","volume":"15","author":"Lei","year":"2025","journal-title":"Am J Cancer Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/hep.0000000000001182","article-title":"Distinct immune microenvironment of venous tumor thrombus in hepatocellular carcinoma at single-cell resolution","volume":"82","author":"Zhou","year":"2025","journal-title":"Hepatology"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1906593\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:39:02Z","timestamp":1790055542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1906593\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":41,"alternative-id":["10.3389\/fimmu.2026.1906593"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1906593","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"article-number":"1906593"}}