{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:13:36Z","timestamp":1792800816262,"version":"4.5.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"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><jats:title>Background<\/jats:title><jats:p>Hepatocellular carcinoma (HCC) is one of the prevalent tumors worldwide, posing a global healthcare threat. The existing treatment options for large HCC have poor therapeutic effects and are prone to drug resistance. Spatially fractionated radiation therapy (SFRT) is a highly precise radiotherapy technique that delivers a concentrated high dose of radiation to a well-defined tumor target while minimizing radiation exposure to the surrounding normal tissues. SFRT specially delivers a non-uniform radiation dose to the target area instead of a homogeneous dose throughout the tumor volume. This steep dose gradient within the targeted tumor could increase the immune-rich infiltrate within the tumor, thus enhancing the efficacy of immunotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case report<\/jats:title><jats:p>A 22-year-old man was diagnosed with large HCC, classified as Barcelona Clinic Liver Cancer (BCLC) stage C. The patient received first-line systemic treatment with bevacizumab and atezolizumab, followed by locoregional therapy with hepatic arterial infusion chemotherapy (HAIC). The tumor rapidly grew over the next 2 months. Subsequently, the patient underwent SFRT combined with anti-PD1\/CTLA4 (anti-programmed death 1\/anti-cytotoxic T-lymphocyte antigen-4) immunotherapy and anti-angiogenesis treatment. SFRT was administered using volumetric modulated arc therapy, delivering 26.68 Gy in two fractions every other day to the high-dose spheres and 8 Gy in two fractions to the targeted tumor. The tumor regressed nearly 40% over 2 months after the treatment, without significant treatment-related side effects (grade 3 or 4 acute and subacute toxicities) observed during the subsequent follow-up exams.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SFRT combined with immunotherapy is a promising strategy for large HCC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1591424","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T04:14:33Z","timestamp":1758255273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["SFRT combined with immunotherapy for a growing hepatocellular carcinoma after the failure of anti-angiogenesis and anti-PD1 treatment: a case 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