{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:51:56Z","timestamp":1791348716479,"version":"4.3.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Stereotactic body radiotherapy (SBRT) combined with lenvatinib and tislelizumab has shown potential activity in advanced hepatocellular carcinoma (HCC), but early treatment failure (ETF) remains common. We developed an exploratory model to estimate ETF, defined as radiologically confirmed progressive disease (PD) or all-cause death within 6 months after treatment initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center retrospective study included advanced HCC patients treated with the triple regimen from June 2021 to June 2024. Baseline clinical, imaging, and hematological variables were analyzed. LASSO regression with 10-fold cross-validation was used for feature selection. Restricted cubic splines assessed linearity, and \u03bb.1se was examined as a sensitivity analysis. A multivariable logistic regression model was presented as a nomogram. Discrimination, calibration, and decision curve analysis (DCA) were evaluated, with 1000-resample bootstrap internal validation repeating the modeling pipeline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 118 patients, 33 (27.9%) experienced ETF; 28 had radiologically confirmed PD and 5 died without prior documented PD. At \u03bb.min, LASSO selected maximum tumor diameter, Vp4 portal vein tumor thrombosis (PVTT), baseline systemic immune-inflammation index (SII), ALBI score, and log10-transformed alpha-fetoprotein (AFP). Under \u03bb.1se, four predictors were retained, with SII excluded. The final model had an apparent ROC-AUC of 0.903 and an optimism-corrected ROC-AUC of 0.866. Calibration showed acceptable agreement between predicted and observed risks. DCA suggested net benefit over an exploratory threshold range of approximately 0.10-0.50, which should not be interpreted as a validated treatment-switching threshold.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The nomogram showed promising internal discrimination for estimating 6-month ETF risk in advanced HCC patients receiving SBRT, lenvatinib, and tislelizumab. Given the modest sample size and single-center design, the model remains exploratory and hypothesis-generating. External multicenter validation is required before clinical implementation or use for treatment selection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1905052","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:47:41Z","timestamp":1791348461000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["LASSO-based nomogram to predict early treatment failure in advanced hepatocellular carcinoma treated with SBRT, lenvatinib, and tislelizumab"],"prefix":"10.3389","volume":"16","author":[{"given":"Yingchun","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Oncology, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"He","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","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 Clin"},{"key":"B2","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":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.018","article-title":"BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update","volume":"76","author":"Reig","year":"2022","journal-title":"J Hepatol"},{"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":"10.3389\/fimmu.2022.1070961","article-title":"PD-1\/PD-L1 checkpoint inhibitors in advanced hepatocellular carcinoma immunotherapy","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-023-01135-7","article-title":"Sequencing systemic therapy in hepatocellular carcinoma","volume":"24","author":"Ponvilawan","year":"2023","journal-title":"Curr Treat Options Oncol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1186\/s12916-024-03356-5","article-title":"Efficacy and safety of tislelizumab plus lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma: a multicenter, single-arm, phase 2 trial","volume":"22","author":"Xu","year":"2024","journal-title":"BMC Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.00808","article-title":"Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma","volume":"38","author":"Finn","year":"2020","journal-title":"J Clin Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.29271\/jcpsp.2021.05.532","article-title":"CyberKnife radiosurgery in hepatocellular carcinoma","volume":"31","author":"Memon","year":"2021","journal-title":"J Coll Phys Surg Pak"},{"key":"B10","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s13045-022-01307-2","article-title":"Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors","volume":"15","author":"Xu","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.17998\/jlc.20.2.128","article-title":"Infiltration of T cells and programmed cell death ligand 1-expressing macrophages as a potential predictor of lenvatinib response in hepatocellular carcinoma","volume":"20","author":"Sung","year":"2020","journal-title":"J Liver Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1665348","article-title":"Clinical efficacy of hepatic arterial infusion chemotherapy combined with transhepatic arterial embolization plus lenvatinib and tislelizumab or transarterial chemoembolization combined with lenvatinib plus tislelizumab in the treatment of advanced hepatocellular carcinoma","volume":"15","author":"Peng","year":"2025","journal-title":"Front Oncol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.1016\/j.cgh.2022.11.015","article-title":"Healthcare costs for Medicare patients with hepatocellular carcinoma in the United States","volume":"21","author":"Karim","year":"2023","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1172\/jci131194","article-title":"Time to dissect the autoimmune etiology of cancer antibody immunotherapy","volume":"130","author":"Dougan","year":"2020","journal-title":"J Clin Invest"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1113389","article-title":"Toripalimab in combination with anlotinib for unresectable hepatocellular carcinoma after SBRT: A prospective, single-arm, single-center clinical study","volume":"13","author":"Chen","year":"2023","journal-title":"Front Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2012-0279","article-title":"The financial toxicity of cancer treatment: a pilot study assessing out-of-pocket expenses and the insured cancer patient's experience","volume":"18","author":"Zafar","year":"2013","journal-title":"Oncologist"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13767","article-title":"Patient-reported out-of-pocket costs and financial toxicity during early-phase oncology clinical trials","volume":"26","author":"Huey","year":"2021","journal-title":"Oncologist"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-024-00722-6","article-title":"The prognostic value of systemic immune-inflammation index in patients with unresectable hepatocellular carcinoma treated with immune-based therapy","volume":"13","author":"He","year":"2025","journal-title":"biomark Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100347","article-title":"ALBI score: Evidence for an improved model for liver functional estimation in patients with hepatocellular carcinoma","volume":"3","author":"Demirtas","year":"2021","journal-title":"JHEP Rep"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071862","article-title":"Immunotherapy in hepatocellular cancer patients with mild to severe liver dysfunction: Adjunctive role of the ALBI grade","volume":"12","author":"Pinato","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14194873","article-title":"The clinical impact of hepatic arterial infusion chemotherapy New-FP for hepatocellular carcinoma with preserved liver function","volume":"14","author":"Iwamoto","year":"2022","journal-title":"Cancers"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2147\/jhc.s442487","article-title":"Pretreatment non-invasive biomarkers as predictors to estimate portal vein tumor thrombosis (PVTT) risk and long-term survival in HBV-related hepatocellular carcinoma patients without PVTT","volume":"10","author":"Liu","year":"2023","journal-title":"J Hepatocell Carcinoma"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.14701\/ahbps.24-048","article-title":"Surgical outcome and risk scoring to predict survival after hepatic resection for hepatocellular carcinoma with portal vein tumor thrombosis","volume":"28","author":"Kim","year":"2024","journal-title":"Ann Hepatobiliary Pancreat Surg"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1086095","article-title":"Combined iodine-125 seed strand, portal vein stent, transarterial chemoembolization, lenvatinib and anti-PD-1 antibodies therapy for hepatocellular carcinoma and Vp4 portal vein tumor thrombus: A propensity-score analysis","volume":"12","author":"Zhang","year":"2022","journal-title":"Front Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2147\/jhc.s432542","article-title":"Effectiveness and safety of the PD-1 inhibitor lenvatinib plus radiotherapy in patients with HCC with main PVTT: Real-world data from a tertiary centre","volume":"10","author":"Li","year":"2023","journal-title":"J Hepatocell Carcinoma"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/js9.0000000000001208","article-title":"Using stepwise regression to address multicollinearity is not appropriate","volume":"110","author":"Xi","year":"2024","journal-title":"Int J Surg"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1038\/s41598-023-49770-2","article-title":"A CIC-related-epigenetic factors-based model associated with prediction, the tumor microenvironment and drug sensitivity in osteosarcoma","volume":"14","author":"Yu","year":"2024","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/s41598-024-84342-y","article-title":"Application of the Lasso regularisation technique in mitigating overfitting in air quality prediction models","volume":"15","author":"Pak","year":"2025","journal-title":"Sci Rep"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/evlett\/qrad064","article-title":"Regularized regression can improve estimates of multivariate selection in the face of multicollinearity and limited data","volume":"8","author":"Sztepanacz","year":"2024","journal-title":"Evol Lett"},{"key":"B30","doi-asserted-by":"publisher","first-page":"g7594","DOI":"10.1136\/bmj.g7594","article-title":"Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement","volume":"350","author":"Collins","year":"2015","journal-title":"BMJ"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","year":"2013","journal-title":"JAMA"},{"key":"B32","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":"B33","doi-asserted-by":"publisher","first-page":"52","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":"B34","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-14-0442","article-title":"Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma","volume":"20","author":"Hu","year":"2014","journal-title":"Clin Cancer Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.57.9151","article-title":"Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI score","volume":"33","author":"Johnson","year":"2015","journal-title":"J Clin Oncol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.10.021","article-title":"Diagnosis and management of toxicities of immune checkpoint inhibitors in hepatocellular carcinoma","volume":"72","author":"Sangro","year":"2020","journal-title":"J Hepatol"},{"key":"B37","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-19425-7","volume-title":"Regression Modeling Strategies With Applications to Linear Models, Logistic and Ordinal Regression, and Survival Analysis","author":"Harrell","year":"2015"},{"key":"B38","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-030-16399-0","volume-title":"Clinical Prediction Models: A Practical Approach to Development, Validation, and Updating","author":"Steyerberg","year":"2019"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization paths for generalized linear models via coordinate descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J Stat Softw"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097-0258(19960229)15:4<361::aid-sim168>3.0.co;2-4","article-title":"Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors","volume":"15","author":"Harrell","year":"1996","journal-title":"Stat Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1177\/0272989x06295361","article-title":"Decision curve analysis: a novel method for evaluating prediction models","volume":"26","author":"Vickers","year":"2006","journal-title":"Med Decis Making"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i6","article-title":"Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests","volume":"352","author":"Vickers","year":"2016","journal-title":"BMJ"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1097\/ede.0b013e3181c30fb2","article-title":"Assessing the performance of prediction models: a framework for traditional and novel measures","volume":"21","author":"Steyerberg","year":"2010","journal-title":"Epidemiology"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.70051","article-title":"Efficacy and safety of hypofractionated radiation therapy combined with immunotherapy for hepatocellular carcinoma with Vp4 portal vein tumor thrombosis","volume":"56","author":"Tameda","year":"2026","journal-title":"Hepatol Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.972503","article-title":"PD-1 inhibitors plus anti-angiogenic therapy with or without intensity-modulated radiotherapy for advanced hepatocellular carcinoma: A propensity score matching study","volume":"13","author":"Su","year":"2022","journal-title":"Front Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4143\/crt.2024.255","article-title":"Role of HIF-1\u03b1 in the responses of tumors to radiotherapy and chemotherapy","volume":"57","author":"Song","year":"2025","journal-title":"Cancer Res Treat"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076495","article-title":"Navigating through the PD-1\/PDL-1 landscape: A systematic review and meta-analysis of clinical outcomes in hepatocellular carcinoma and their influence on immunotherapy and tumor microenvironment","volume":"24","author":"Ailia","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000018571","article-title":"Prognostic impact of elevated pre-treatment systemic immune-inflammation index (SII) in hepatocellular carcinoma: A meta-analysis","volume":"99","author":"Wang","year":"2020","journal-title":"Med (Baltimore)"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1459740","article-title":"Prognostic model for predicting recurrence in hepatocellular carcinoma patients with high systemic immune-inflammation index based on machine learning in a multicenter study","volume":"15","author":"Lu","year":"2024","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1186\/s12885-021-08124-9","article-title":"Systemic immune-inflammation index predicts prognosis of sequential therapy with sorafenib and regorafenib in hepatocellular carcinoma","volume":"21","author":"Hong","year":"2021","journal-title":"BMC Cancer"},{"key":"B51","doi-asserted-by":"publisher","first-page":"3794","DOI":"10.3390\/cancers13153794","article-title":"ALBI score is a strong predictor of toxicity following SIRT for hepatocellular carcinoma","volume":"13","author":"Lescure","year":"2021","journal-title":"Cancers"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7993","article-title":"Minimum sample size for developing a multivariable prediction model: Part I\u2014continuous outcomes","volume":"38","author":"Riley","year":"2019","journal-title":"Stat Med"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7992","article-title":"Minimum sample size for developing a multivariable prediction model: Part II\u2014binary and time-to-event outcomes","volume":"38","author":"Riley","year":"2019","journal-title":"Stat Med"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1016\/S0895-4356(96)00236-3","article-title":"A simulation study of the number of events per variable in logistic regression analysis","volume":"49","author":"Peduzzi","year":"1996","journal-title":"J Clin Epidemiol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.7326\/m18-1376","article-title":"PROBAST: A tool to assess the risk of bias and applicability of prediction model studies","volume":"170","author":"Moons","year":"2019","journal-title":"Ann Intern Med"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1905052\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:47:48Z","timestamp":1791348468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1905052\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":55,"alternative-id":["10.3389\/fonc.2026.1905052"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1905052","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"1905052"}}