{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:55:52Z","timestamp":1770818152422,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["NSTC-111-2314-B-016-049"],"award-info":[{"award-number":["NSTC-111-2314-B-016-049"]}]},{"name":"National Science and Technology Council","award":["TSGH-C04-110030"],"award-info":[{"award-number":["TSGH-C04-110030"]}]},{"name":"Tri-Service General Hospital Research Foundation","award":["NSTC-111-2314-B-016-049"],"award-info":[{"award-number":["NSTC-111-2314-B-016-049"]}]},{"name":"Tri-Service General Hospital Research Foundation","award":["TSGH-C04-110030"],"award-info":[{"award-number":["TSGH-C04-110030"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Approximately 10\u201340% of hepatocellular carcinoma (HCC) patients have definite vascular invasion at the time of diagnosis. Without curative treatment options, these patients have an abysmal prognosis with a median survival of only a few months following systemic therapy. However, supportive evidence of combining multiple locoregional treatments with systemic therapy is limited. This study compared the outcomes of sorafenib alone versus multimodality therapy with sorafenib, radiotherapy (RT), and transarterial chemoembolization (TACE) in advanced HCC patients with macrovascular invasion (MaVI). Methods: The process took place over a nine-year period between March 2009 and October 2017, wherein 78 HCC patients with MaVI who underwent either sorafenib therapy alone (n = 49) or combined sorafenib\/RT\/TACE (n = 29) therapy were chosen for the retrospective study. We compared the overall survival (OS) between the two groups using the Cox regression hazard model and adjusted imbalances using propensity score matching (PSM). Results: At the last follow-up, 76 patients had died, with a median follow-up time of 4.8 months for all patients and 31 months for those who were alive. Patients treated with sorafenib\/RT\/TACE had superior OS compared to those treated with sorafenib alone, showing a median survival of 9.3 vs. 2.7 months and a one-year survival of 37.1% vs. 6.1% (p &lt; 0.001). In the multivariable analysis, new diagnosis or recurrence of HCC and treatment modalities (sorafenib alone vs. sorafenib\/RT\/TACE) were independent prognostic factors for OS. Compared to patients treated with sorafenib alone, significantly better OS was further verified using PSM (p &lt; 0.001) in patients who received multiple therapeutic modalities. Conclusion: Multimodality therapy with sorafenib\/RT\/TACE increased OS threefold versus sorafenib therapy alone in HCC patients with MaVI. This study offers promising benefits of combined locoregional and systemic therapy for advanced HCC in current patient management and prospective clinical trials.<\/jats:p>","DOI":"10.3390\/cancers15102687","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T03:32:27Z","timestamp":1683689547000},"page":"2687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Beneficial Effect of Combining Radiotherapy and Transarterial Chemoembolization on Patient Survival in Hepatocellular Carcinomas and Macrovascular Invasion Treated with Sorafenib"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-741X","authenticated-orcid":false,"given":"Meng-Chuan","family":"Lu","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Yen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu-Lung","family":"Fan","sequence":"additional","affiliation":[{"name":"Division of Organ Transplantation Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teng-Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Organ Transplantation Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Chou","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsuan-Hwai","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4629-4393","authenticated-orcid":false,"given":"Yu-Lueng","family":"Shih","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsai-Yuan","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9736-9933","authenticated-orcid":false,"given":"Wei-Chen","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"},{"name":"Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Warren 1019A, 55 Fruit Street, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1056\/NEJMra1713263","article-title":"Hepatocellular Carcinoma","volume":"380","author":"Villanueva","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1200\/JCO.2015.61.4925","article-title":"Outcomes after stereotactic body radiotherapy or radiofrequency ablation for hepatocellular carcinoma","volume":"34","author":"Wahl","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s00423-021-02370-y","article-title":"The characteristics of patients with macrovascular invasion in hepatocellular carcinoma: When East meets West","volume":"407","author":"Yen","year":"2021","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_4","first-page":"447","article-title":"Efficacy of combined modality therapy with sorafenib following hepatic arterial injection chemotherapy and three-dimensional conformal radiotherapy for advanced hepatocellular carcinoma with major vascular invasion","volume":"11","author":"Nomura","year":"2019","journal-title":"Mol. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1001\/jamaoncol.2017.5847","article-title":"Efficacy and safety of transarterial chemoembolization plus external beam radiotherapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: A randomized clinical trial","volume":"4","author":"Yoon","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.3389\/fonc.2019.01065","article-title":"Safety and efficacy of transcatheter arterial chemoembolization plus radiotherapy combined with sorafenib in hepatocellular carcinoma showing macrovascular invasion","volume":"9","author":"Zhao","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/hep.510290145","article-title":"Natural history of untreated nonsurgical hepatocellular carcinoma: Rationale for the design and evaluation of therapeutic trials","volume":"29","author":"Llovet","year":"1999","journal-title":"Hepatology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7561","DOI":"10.3748\/wjg.v12.i47.7561","article-title":"Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus","volume":"12","author":"Minagawa","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"681","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":"ref_10","doi-asserted-by":"crossref","first-page":"1894","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":"ref_11","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S1470-2045(08)70285-7","article-title":"Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial","volume":"10","author":"Cheng","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1016\/j.ejca.2011.12.006","article-title":"Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: Subset analyses of the phase III Sorafenib Asia\u2013Pacific trial","volume":"48","author":"Cheng","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1163","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":"ref_15","doi-asserted-by":"crossref","unstructured":"Chiang, C.-L., Chan, S.-K., Lee, S.-F., and Choi, H.C.-W. (2021). First-line atezolizumab plus bevacizumab versus sorafenib in hepatocellular carcinoma: A cost-effectiveness analysis. Cancers, 13.","DOI":"10.3390\/cancers13050931"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/cac2.12110","article-title":"Atezolizumab plus bevacizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma: A cost-effectiveness analysis","volume":"40","author":"Hou","year":"2020","journal-title":"Cancer Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.31557\/APJCP.2020.21.6.1797","article-title":"The prognosis of hepatocellular carcinoma treated with sorafenib in combination with TACE","volume":"21","author":"Kimura","year":"2020","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.jvir.2014.10.019","article-title":"Comparison of chemoembolization with and without radiation therapy and sorafenib for advanced hepatocellular carcinoma with portal vein tumor thrombosis: A propensity score analysis","volume":"26","author":"Kim","year":"2015","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/liv.12445","article-title":"The feasibility of combined transcatheter arterial chemoembolization and radiotherapy for advanced hepatocellular carcinoma","volume":"34","author":"Cho","year":"2014","journal-title":"Liver Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/jgh.12087","article-title":"Stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma","volume":"28","author":"Honda","year":"2013","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jhep.2018.03.019","article-title":"EASL clinical practice guidelines: Management of hepatocellular carcinoma","volume":"69","author":"Galle","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.ijrobp.2019.05.066","article-title":"Comparison of stereotactic body radiation therapy and transarterial chemoembolization for unresectable medium-sized hepatocellular carcinoma","volume":"105","author":"Shen","year":"2019","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1148\/radiology.148.2.6306721","article-title":"Hepatic artery embolization in 120 patients with unresectable hepatoma","volume":"148","author":"Yamada","year":"1983","journal-title":"Radiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1111\/ans.12803","article-title":"Efficacy of transarterial chemoembolization for hepatocellular carcinoma with portal vein thrombosis: A meta-analysis","volume":"86","author":"Leng","year":"2016","journal-title":"ANZ J. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Xue, T.-C., Xie, X.-Y., Zhang, L., Yin, X., Zhang, B.-H., and Ren, Z.-G. (2013). Transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: A meta-analysis. BMC Gastroenterol., 13.","DOI":"10.1186\/1471-230X-13-60"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1148\/radiol.10101058","article-title":"Transarterial chemoembolization can be safely performed in patients with hepatocellular carcinoma invading the main portal vein and may improve the overall survival","volume":"258","author":"Chung","year":"2011","journal-title":"Radiology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1186\/1748-717X-8-250","article-title":"High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma","volume":"8","author":"Jang","year":"2013","journal-title":"Radiat. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yoon, S.M., Lim, Y.-S., Park, M.J., Kim, S.Y., Cho, B., Shim, J.H., Kim, K.M., Lee, H.C., Chung, Y.-H., and Lee, Y.S. (2013). Stereotactic body radiation therapy as an alternative treatment for small hepatocellular carcinoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079854"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5424","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":"ref_30","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.ijrobp.2011.11.058","article-title":"Stereotactic body radiation therapy in recurrent hepatocellular carcinoma","volume":"84","author":"Huang","year":"2012","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ijrobp.2017.09.001","article-title":"Stereotactic body radiation therapy as an alternative to transarterial chemoembolization for hepatocellular carcinoma","volume":"100","author":"Sapir","year":"2018","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Xi, M., Zhang, L., Zhao, L., Li, Q.-Q., Guo, S.-P., Feng, Z.-Z., Deng, X.-W., Huang, X.-Y., and Liu, M.-Z. (2013). Effectiveness of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein and\/or inferior vena cava tumor thrombosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063864"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s13014-018-1136-5","article-title":"Stereotactic body radiotherapy based treatment for hepatocellular carcinoma with extensive portal vein tumor thrombosis","volume":"13","author":"Shui","year":"2018","journal-title":"Radiat. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.2169\/internalmedicine.9826-17","article-title":"The safety and efficacy of combination therapy of sorafenib and radiotherapy for advanced hepatocellular carcinoma: A retrospective study","volume":"57","author":"Wada","year":"2018","journal-title":"Intern. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/imr.12573","article-title":"Abscopal, immunological effects of radiotherapy: Narrowing the gap between clinical and preclinical experiences","volume":"280","author":"Brix","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.pharmthera.2018.12.002","article-title":"Immune mechanisms mediating abscopal effects in radioimmunotherapy","volume":"196","author":"Rodriguez","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.it.2018.06.001","article-title":"Immunological mechanisms responsible for radiation-induced abscopal effect","volume":"39","author":"Melero","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.2174\/092986712800099811","article-title":"Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by ionizing irradiation-implications for cancer therapies","volume":"19","author":"Frey","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/MCG.0b013e31822b36cc","article-title":"Younger hepatocellular carcinoma patients have better prognosis after percutaneous radiofrequency ablation therapy","volume":"46","author":"Kao","year":"2012","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0140-6736(16)32453-9","article-title":"Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"389","author":"Bruix","year":"2017","journal-title":"Lancet"},{"key":"ref_41","doi-asserted-by":"crossref","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."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/10\/2687\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:31:48Z","timestamp":1760124708000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/10\/2687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["cancers15102687"],"URL":"https:\/\/doi.org\/10.3390\/cancers15102687","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,10]]}}}