{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:40:35Z","timestamp":1789656035593,"version":"4.0.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011828","name":"Guangxi Zhuang Autonomous Region Health and Family Planning Commission","doi-asserted-by":"publisher","award":["Z-A20230555"],"award-info":[{"award-number":["Z-A20230555"]}],"id":[{"id":"10.13039\/501100011828","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) exhibit a dismal prognosis, occurring in 44%\u201362.2% of cases at initial diagnosis. The optimal treatment for this population remains undefined.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this prospective, multicenter, single-arm phase II trial across three Chinese centers, eligible HCC patients with Vp3\/4 PVTT received combined stereotactic body radiotherapy (SBRT), cadonilimab, and lenvatinib. Primary endpoint was objective response rate (ORR) in primary liver lesions (RECIST v1.1\/mRECIST); secondary endpoints included ORR in PVTT, progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Of 24 enrolled patients, 21 were evaluable for efficacy. ORR for primary lesions was 38.1% (RECIST v1.1) and 47.6% (mRECIST), with a disease control rate (DCR) of 100% by both criteria. For PVTT, ORR and DCR were 76.2% and 100%, respectively. At a median follow-up of 19.7 months, median PFS was 6.8 months (95% CI: 4.6\u201312.9), DOR was 10.4 months (95% CI: 2.9\u2013NE), and OS was 13.4 months (95% CI: 6.8\u2013NE). Early biomarker declines (\u226575% AFP reduction or \u226550% PIVKA-II decline at 6 weeks) correlated with superior outcomes: AFP reduction predicted longer PFS (HR=0.22, p=0.006) and OS (HR=0.25, p=0.024); PIVKA-II reduction similarly predicted PFS (HR=0.28, p=0.007) and OS (HR=0.18, p=0.002). Common treatment-related adverse events (TRAEs) included hypertension (50%), thrombocytopenia (42%), and fatigue (38%).<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The combination of SBRT, cadonilimab, and lenvatinib showed promising efficacy and manageable toxicity in HCC patients with Vp3\/4 PVTT. Early AFP or PIVKA-II response at 6 weeks may serve as a prognostic biomarker.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n ClinicalTrials.gov<\/jats:ext-link>\n , identifier NCT06040177.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1687344","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T05:18:01Z","timestamp":1762751881000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Stereotactic body radiation therapy combined with cadonilimab and lenvatinib in the treatment of hepatocellular carcinoma with Vp3 or Vp4 portal vein tumor thrombus: a prospective, multicenter, single-arm, phase II clinical trial"],"prefix":"10.3389","volume":"16","author":[{"given":"Ning","family":"Mo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeying","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuchao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuizhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiping","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiwen","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyuan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixue","family":"Lao Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rensheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112152-20240119-00035","article-title":"Cancer incidence and mortality in China, 2022","volume":"46","author":"Zheng","year":"2024","journal-title":"Zhonghua Zhong Liu Za Zhi"},{"key":"B3","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ijsu.2015.05.009","article-title":"The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus","volume":"20","author":"Zhang","year":"2015","journal-title":"Int J Surg"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1089\/acm.2019.0334","article-title":"Fufang banmao capsule, a traditional Chinese medicinal formulation, enhances the survival of patients with hepatocellular carcinoma and vp3\u20134 portal vein tumor thrombosis undergoing supportive treatment","volume":"26","author":"Liu","year":"2020","journal-title":"J Altern Complementary Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.06.014","article-title":"Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase iii trial","volume":"57","author":"Bruix","year":"2012","journal-title":"J Hepatol"},{"key":"B6","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":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745","article-title":"Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00252-7","article-title":"Sintilimab plus a bevacizumab biosimilar (Ibi305) versus sorafenib in unresectable hepatocellular carcinoma (Orient-32): A randomised, open-label, phase 2\u20133 study","volume":"22","author":"Ren","year":"2021","journal-title":"Lancet Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00961-3","article-title":"Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (Cares-310): A randomised, open-label, international phase 3 study","volume":"402","author":"Qin","year":"2023","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00469-2","article-title":"Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (Leap-002): A randomised, double-blind, phase 3 trial","volume":"24","author":"Llovet","year":"2023","journal-title":"Lancet Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2100070","article-title":"Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma","volume":"1","author":"Abou-Alfa","year":"2022","journal-title":"NEJM Evid"},{"key":"B12","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":"B13","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/s1470-2045(21)00604-5","article-title":"Nivolumab versus sorafenib in advanced hepatocellular carcinoma (Checkmate 459): A randomised, multicentre, open-label, phase 3 trial","volume":"23","author":"Yau","year":"2022","journal-title":"Lancet Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(23)00411-4","article-title":"Safety and antitumour activity of cadonilimab, an anti-pd-1\/ctla-4 bispecific antibody, for patients with advanced solid tumours (Compassion-03): A multicentre, open-label, phase 1b\/2 trial","volume":"24","author":"Gao","year":"2023","journal-title":"Lancet Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1238667","article-title":"The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (Compassion-08): A phase ib\/ii single-arm clinical trial","volume":"14","author":"Qiao","year":"2023","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1159\/000523997","article-title":"Guidelines for diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus in China (2021 edition)","volume":"11","author":"Sun","year":"2022","journal-title":"Liver Cancer"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13411","article-title":"Clinical practice guidelines for hepatocellular carcinoma: the Japan society of hepatology 2017 (4th jsh-hcc guidelines) 2019 update","volume":"49","author":"Kokudo","year":"2019","journal-title":"Hepatol Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s13014-022-02075-6","article-title":"Efficacy and safety of radiotherapy plus anti-pd1 versus transcatheter arterial chemoembolization plus sorafenib for advanced hepatocellular carcinoma: A real-world study","volume":"17","author":"Li","year":"2022","journal-title":"Radiat Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.211545","article-title":"Sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib for hepatocellular carcinoma with major portal vein tumor thrombosis: A randomized trial","volume":"303","author":"Zheng","year":"2022","journal-title":"Radiology"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-2592","article-title":"Efficacy and safety of stereotactic body radiotherapy combined with camrelizumab and apatinib in patients with hepatocellular carcinoma with portal vein tumor thrombus","volume":"29","author":"Hu","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S318070","article-title":"Portal vein tumor thrombosis and hepatocellular carcinoma - the changing tides","volume":"8","author":"Khan","year":"2021","journal-title":"J Hepatocell Carcinoma"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27533","article-title":"Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization","volume":"118","author":"Kang","year":"2012","journal-title":"Cancer"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2017.11.013","article-title":"Comparison of radiation therapy modalities for hepatocellular carcinoma with portal vein thrombosis: A meta-analysis and systematic review","volume":"129","author":"Rim","year":"2018","journal-title":"Radiother Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.568759","article-title":"Combinational immunotherapy for hepatocellular carcinoma: radiotherapy, immune checkpoint blockade and beyond","volume":"11","author":"Lee","year":"2020","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2024.03.035","article-title":"Stereotactic body radiotherapy combined with lenvatinib with or without pd-1 inhibitors as initial treatment for unresectable hepatocellular carcinoma","volume":"120","author":"Wang","year":"2024","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B26","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1159\/000503685","article-title":"Chinese expert consensus on multidisciplinary diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus (2018 edition)","volume":"9","author":"Cheng","year":"2020","journal-title":"Liver Cancer"},{"key":"B27","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.jhep.2018.03.019","article-title":"Easl clinical practice guidelines: management of hepatocellular carcinoma","volume":"69","year":"2018","journal-title":"J Hepatol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1007\/s00534-010-0314-0","article-title":"A new classification for hepatocellular carcinoma with portal vein tumor thrombus","volume":"18","author":"Shi","year":"2011","journal-title":"J Hepatobiliary Pancreat Sci"},{"key":"B29","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/s1055-3207(02)00082-0","article-title":"Results of hepatic resection for hepatocellular carcinoma invading major portal and\/or hepatic veins","volume":"12","author":"Ikai","year":"2003","journal-title":"Surg Oncol Clin N Am"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1608986","article-title":"Recent developments in radiotherapy","volume":"377","author":"Citrin","year":"2017","journal-title":"N Engl J Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.02184","article-title":"Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: A randomized, open-label, multicenter controlled study","volume":"37","author":"Wei","year":"2019","journal-title":"J Clin Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-21-3275","article-title":"Alpha-fetoprotein as a potential surrogate biomarker for atezolizumab + Bevacizumab treatment of hepatocellular carcinoma","volume":"28","author":"Zhu","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1186\/s12885-021-08428-w","article-title":"Reductions in afp and pivka-ii can predict the efficiency of anti-pd-1 immunotherapy in hcc patients","volume":"21","author":"Sun","year":"2021","journal-title":"BMC Cancer"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.21037\/atm-20-4164","article-title":"Combined locoregional and systemic therapy for advanced hepatocellular carcinoma: finally, the future is obscure","volume":"8","author":"Farsad","year":"2020","journal-title":"Ann Transl Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i32.7289","article-title":"Management of hepatocellular carcinoma with portal vein tumor thrombosis: review and update at 2016","volume":"22","author":"Chan","year":"2016","journal-title":"World J Gastroenterol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1177\/1533033821995286","article-title":"Evaluation of the efficacy and toxicity of radiotherapy for type iii-iv portal vein tumor thrombi","volume":"20","author":"Bai","year":"2021","journal-title":"Technol Cancer Res Treat"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.addr.2017.01.004","article-title":"Radiotherapy for cancer: present and future","volume":"109","author":"Allen","year":"2017","journal-title":"Adv Drug Delivery Rev"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3212","DOI":"10.3390\/ijms20133212","article-title":"Tumor microenvironment as a \u201cGame changer\u201d in cancer radiotherapy","volume":"20","author":"Jarosz-Biej","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41575-020-00395-0","article-title":"Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma","volume":"18","author":"Llovet","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S172042","article-title":"Targeting vegf pathway to normalize the vasculature: an emerging insight in cancer therapy","volume":"11","author":"Wu","year":"2018","journal-title":"Onco Targets Ther"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.2147\/jhc.S79353","article-title":"Early Α-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib","volume":"2","author":"Lee","year":"2015","journal-title":"J Hepatocellular Carcinoma"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)31046-2","article-title":"Nivolumab in patients with advanced hepatocellular carcinoma (Checkmate 040): an open-label, non-comparative, phase 1\/2 dose escalation and expansion trial","volume":"389","author":"El-Khoueiry","year":"2017","journal-title":"Lancet"},{"key":"B43","doi-asserted-by":"publisher","first-page":"779","DOI":"10.3390\/cancers12040779","article-title":"Early predictors of objective response in patients with hepatocellular carcinoma undergoing lenvatinib treatment","volume":"12","author":"Saeki","year":"2020","journal-title":"Cancers"},{"key":"B44","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/s12885-025-13568-4","article-title":"Pivka-ii as a surrogate biomarker for therapeutic response in non-afp-secreting hepatocellular carcinoma","volume":"25","author":"Chen","year":"2025","journal-title":"BMC Cancer"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2023.2180794","article-title":"Cadonilimab, a tetravalent pd-1\/ctla-4 bispecific antibody with trans-binding and enhanced target binding avidity","volume":"15","author":"Pang","year":"2023","journal-title":"MAbs"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1107542","article-title":"Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study","volume":"14","author":"Wang","year":"2023","journal-title":"Front Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15102","article-title":"Efficacy and safety of atezolizumab plus bevacizumab in korean patients with advanced hepatocellular carcinoma","volume":"42","author":"Cheon","year":"2022","journal-title":"Liver Int"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2421","DOI":"10.1016\/j.cgh.2022.07.035","article-title":"Risk of variceal bleeding in patients with advanced hepatocellular carcinoma receiving atezolizumab\/bevacizumab","volume":"21","author":"Ha","year":"2023","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s13014-024-02527-1","article-title":"Stereotactic body radiotherapy versus lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis: A propensity matching score analysis","volume":"19","author":"Ji","year":"2024","journal-title":"Radiat Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1687344\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T05:18:03Z","timestamp":1762751883000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1687344\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":49,"alternative-id":["10.3389\/fimmu.2025.1687344"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1687344","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]},"article-number":"1687344"}}