{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T06:00:19Z","timestamp":1785218419809,"version":"3.55.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"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>Previous studies have shown that locoregional therapy combined with systemic treatment provides survival benefits with manageable safety in patients with intermediate-to-advanced large hepatocellular carcinoma (HCC). However, the optimal treatment strategy for HCC beyond the up-to-7 criteria remains unclear because of the high tumor burden and recurrence risk. This study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) plus microwave ablation (MWA) followed by targeted immunotherapy in patients with HCC beyond the up-to-7 criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center retrospective study included patients with HCC beyond the up-to-7 criteria treated at our institution between October 2018 and December 2023. The study group received TACE plus MWA followed by ICIs combined with anti-VEGF\/TKI therapy, while the control group received TACE followed by ICIs combined with anti-VEGF\/TKI therapy. The primary endpoint was progression-free survival (PFS) assessed by mRECIST, and the secondary endpoints were overall survival (OS) and treatment-related adverse events (TRAEs).Baseline data were balanced using a one-to-one propensity score matching (PSM) and inverse probability of treatment weighting (IPTW).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      Among the 80 included patients, the median follow-up time was 68.4 months. Thirty patients had hepatitis B and 40 had hepatitis C. Patients were classified as BCLC stage A\u2013C, with a median tumor size of 7.1\u00a0cm. The control and study groups included 41 and 39 patients, respectively. The median PFS was 5.7 months(95%CI:3.617-7.716) versus 11.4 months(95%CI:8.741-14.125), and the median OS was 16.5 months(95%CI:10.863-22.071) versus 40.2 months (95%CI:34.302-46.165), respectively (both\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05). After PSM analysis, the survival outcomes remained consistent with those observed in the primary cohort(both\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05). Following sIPTW adjustment, the OS benefit remained statistically significant, whereas PFS showed a similar trend toward improvement(\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.051). Multivariate Cox analysis identified combination therapy as an independent protective factor for PFS and OS, while AFP \u2265200 ng\/mL was an independent risk factor for PFS. Most TRAEs were grade 1\u20132, with few grade 3\u20134.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TACE combined with MWA followed by immune checkpoint inhibitors and anti-VEGF\/TKI therapy prolonged progression-free and overall survival in patients with HCC beyond the up-to-7 criteria, with manageable safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1885307","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:37:14Z","timestamp":1785217034000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of TACE combined with MWA followed by immune checkpoint inhibitors and anti-VEGF\/tyrosine kinase inhibitors in hepatocellular carcinoma beyond the up-to-7"],"prefix":"10.3389","volume":"17","author":[{"given":"Yang","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Oncology, the Affiliated Hospital of Yanbian University (Yanbian Hospital)","place":["Yanji, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyu","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Oncology, the Affiliated Hospital of Yanbian University (Yanbian Hospital)","place":["Yanji, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Oncology, the Affiliated Hospital of Yanbian University (Yanbian Hospital)","place":["Yanji, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology Center, the Affiliated Hospital of Yanbian University (Yanbian Hospital)","place":["Yanji, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianchun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Oncology, the Affiliated Hospital of Yanbian University (Yanbian Hospital)","place":["Yanji, China"]},{"name":"Central Laboratory, the Affiliated Hospital of Yanbian University (Yanbian Hospital)","place":["Yanji, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songnan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, the Affiliated Hospital of Yanbian University (Yanbian Hospital)","place":["Yanji, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"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 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