{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:20:26Z","timestamp":1787242826516,"version":"build-2736575974"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"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>Tumor lysis syndrome (TLS) is extraordinarily rare in solid tumors. However, the combination of atezolizumab and bevacizumab (AB) in advanced hepatocellular carcinoma (HCC) has raised concerns for abrupt metabolic derangements. We describe a fatal episode of TLS precipitated by AB in HCC with main portal vein (Vp4) invasion, highlighting the need for vigilant risk stratification and early biochemical surveillance for high-tumor-burden disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 65-year-old man with chronic hepatitis B and massive HCC (Vp4 invasion) had relatively preserved organ function at baseline. Two days after initiating atezolizumab (1,200 mg) and bevacizumab (15 mg\/kg), he developed fever (38.5\u00b0C) and tachycardia (heart rate 112 beats\/min [bpm]), rapidly progressing to circulatory shock on day 3. Laboratory workup revealed hyperuricemia (12.4 mg\/dL), hyperphosphatemia (12.9 mg\/dL), hyperkalemia (6.8 mmol\/L), hypocalcemia (7.7 mg\/dL), and acute kidney injury, meeting the Cairo\u2013Bishop criteria for TLS. Imaging demonstrated abrupt cystic changes of the hepatic mass, suggesting rapid tumor necrosis. Despite aggressive fluid resuscitation and the initiation of hemodialysis, the patient succumbed to multiorgan failure within eight days after initiating AB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case underscores that advanced HCC with extensive vascular invasion is at risk of severe TLS shortly after potent immuno-antiangiogenic therapy. Clinicians should incorporate thorough baseline risk assessments, prompt laboratory monitoring, and timely intervention into standard care algorithms for high-risk HCC. The rapid metabolic collapse observed here serves as a reminder that while combination therapy holds promise for improving survival in advanced HCC, it can also lead to life-threatening complications in specific subgroups. Careful selection of therapeutic options and shared decision-making with patients are critical to balancing potential benefits against severe adverse events, such as TLS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2025.1624908","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T06:27:15Z","timestamp":1756967235000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case Report: Tumor lysis syndrome in advanced, massive hepatocellular carcinoma with main portal vein invasion following atezolizumab plus bevacizumab therapy"],"prefix":"10.3389","volume":"15","author":[{"given":"Tien-Shin","family":"Chou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Feng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Lang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Wei","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01200-4","article-title":"Hepatocellular carcinoma","volume":"400","author":"Vogel","year":"2022","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745","article-title":"Atezolizumab plus\u00a0bevacizumab in unresectable hepatocellular carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e8355","DOI":"10.7759\/cureus.8355","article-title":"Tumor lysis syndrome in solid tumors: A comprehensive literature review, new insights, and novel strategies to improve outcomes","volume":"12","author":"Findakly","year":"2020","journal-title":"Cureus"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/ca.22350","article-title":"Clinical and surgical anatomy of the liver: a review for clinicians","volume":"27","author":"Juza","year":"2014","journal-title":"Clin Anat"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2018181494","article-title":"Liver imaging reporting and data system (LI-RADS) version 2018: imaging of hepatocellular carcinoma in at-risk patients","volume":"289","author":"Chernyak","year":"2018","journal-title":"Radiology"},{"key":"B6","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":"B7","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21388","article-title":"The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more \u201cpersonalized\u201d approach to cancer staging","volume":"67","author":"Amin","year":"2017","journal-title":"CA\u00a0Cancer J Clin"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/00000421-198212000-00014","article-title":"Toxicity and response criteria of the Eastern Cooperative Oncology Group","volume":"5","author":"Oken","year":"1982","journal-title":"Am J Clin Oncol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1365-2141.2004.05094.x","article-title":"Tumour lysis syndrome: new therapeutic strategies and\u00a0classification","volume":"127","author":"Cairo","year":"2004","journal-title":"Br J Haematol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-related adverse events associated with immune checkpoint blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0904569","article-title":"The tumor lysis syndrome","volume":"364","author":"Howard","year":"2011","journal-title":"N Engl J Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e19128","DOI":"10.7759\/cureus.19128","article-title":"Tumor lysis syndrome in patients with hepatocellular carcinoma: A systematic review of published case reports","volume":"13","author":"Chou","year":"2021","journal-title":"Cureus"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e30652","DOI":"10.7759\/cureus.30652","article-title":"Tumor lysis syndrome in patients with solid tumors: A systematic review of reported cases","volume":"14","author":"Alqurashi","year":"2022","journal-title":"Cureus"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.21037\/tcr-20-1158","article-title":"Successful treatment of acute tumor lysis syndrome associated with transcatheter chemoembolization with large hepatocellular carcinomas: two case reports","volume":"9","author":"Wang","year":"2020","journal-title":"Transl Cancer Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1159\/000508583","article-title":"Tumor lysis syndrome after combination therapy of nivolumab and sorafenib in a woman with advanced hepatocellular carcinoma","volume":"14","author":"Yen","year":"2020","journal-title":"Case\u00a0Rep Gastroenterol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16142534","article-title":"The treatment of hepatocellular carcinoma with major vascular invasion","volume":"16","author":"Tadokoro","year":"2024","journal-title":"Cancers (Basel)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2022.07.003","article-title":"Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. Sorafenib for unresectable hepatocellular carcinoma","volume":"12","author":"Roy","year":"2022","journal-title":"J Clin Exp Hepatol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.08.028","article-title":"EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma","volume":"82","year":"2025","journal-title":"J Hepatol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.4073","article-title":"IMbrave150: Exploratory efficacy and safety results of hepatocellular carcinoma (HCC) patients\u00a0(pts)\u00a0with main trunk and\/or contralateral portal vein invasion (Vp4) treated with atezolizumab (atezo)+ bevacizumab (bev) versus sorafenib (sor) in a global Ph III study","volume":"39","author":"Breder","year":"2021","journal-title":"J Clin Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1159\/000539897","article-title":"Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma with Main Trunk and\/or Contralateral Portal Vein Invasion in IMbrave150","volume":"13","author":"Finn","year":"2024","journal-title":"Liver Cancer"},{"key":"B21","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":"B22","doi-asserted-by":"publisher","first-page":"EVIDoa2100070","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":"B23","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.14193","article-title":"Sorafenib vs. Lenvatinib as first-line therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis","volume":"40","author":"Kuzuya","year":"2020","journal-title":"Anticancer Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"81","DOI":"10.17998\/jlc.2023.12.25","article-title":"Comparison of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis","volume":"24","author":"Park","year":"2024","journal-title":"J Liver Cancer"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00469-2","article-title":"Lenvatinib plus\u00a0pembrolizumab 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":"B26","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01963","article-title":"Arterial chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced hepatocellular carcinoma: A biomolecular exploratory, randomized, phase III trial (FOHAIC-1)","volume":"40","author":"Lyu","year":"2022","journal-title":"J Clin Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15174233","article-title":"Comparative analysis of atezolizumab plus bevacizumab and hepatic artery infusion chemotherapy in unresectable hepatocellular carcinoma: A multicenter, propensity score study","volume":"15","author":"Kim","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1159\/000513706","article-title":"Hepatic arterial infusion chemotherapy combined with radiation therapy for advanced hepatocellular carcinoma with tumor thrombosis of the main trunk or bilobar of the portal vein","volume":"10","author":"Kosaka","year":"2021","journal-title":"Liver Cancer"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S418387","article-title":"Hepatic arterial infusion chemotherapy combined with lenvatinib plus humanized programmed death receptor-1 in patients with high-risk advanced hepatocellular carcinoma: A real-world study","volume":"10","author":"Chang","year":"2023","journal-title":"J\u00a0Hepatocell Carcinoma"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.0177","article-title":"Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review","volume":"26","author":"Coiffier","year":"2008","journal-title":"J Clin Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1624908\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T06:27:18Z","timestamp":1756967238000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1624908\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":30,"alternative-id":["10.3389\/fonc.2025.1624908"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1624908","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,3]]},"article-number":"1624908"}}