# Stereotactic body radiation therapy for hepatocellular carcinoma: a comprehensive review

**Authors:** Yupeng Di, Gang Ren, Yingjie Wang, Lingling Meng, Jing Li

PMC · DOI: 10.3389/fonc.2026.1747449 · Frontiers in Oncology · 2026-01-29

## TL;DR

This review explores how stereotactic body radiation therapy (SBRT) can be used to treat hepatocellular carcinoma, focusing on its evolution, dosimetric constraints, and integration with other therapies.

## Contribution

The paper provides a comprehensive roadmap for optimizing SBRT in hepatocellular carcinoma by integrating motion management, metabolic imaging, and AI.

## Key findings

- SBRT shows promise as a curative treatment for HCC when combined with systemic agents like TKIs and ICIs.
- Advanced motion management techniques such as kV-PSI and MR-guidance improve SBRT precision.
- AI is emerging as a tool to automate SBRT planning and adaptive radiotherapy.

## Abstract

Hepatocellular carcinoma (HCC) presents significant challenges in modern surgical and radiation oncology, primarily due to biological heterogeneity and the complexities of underlying liver cirrhosis. This review evaluates stereotactic body radiation therapy (SBRT) as a mature, curative-intent modality within the multidisciplinary management of primary hepatic malignancies. Drawing parallels with high-dose-per-fraction successes in early-stage non-small cell lung cancer, pancreatic adenocarcinoma, and spinal metastases, we analyze the physical evolution, radiobiological principles, and functional dosimetric constraints specific to the hepatic microenvironment. Specifically, we examine advanced motion management, distinguishing pre-treatment setup from real-time intrafractional monitoring via kilovoltage projection streaming images (kV-PSI) and MR-guidance. We evaluate the prognostic value of metabolic imaging parameters, specifically SULpeak and radiomic signatures, alongside the therapeutic synergy between SBRT and systemic agents, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Additionally, the review explores the emerging role of artificial intelligence (AI) in automating planning and executing real-time online adaptive radiotherapy (ART). Finally, by synthesizing pathological evidence of complete necrosis in explanted specimens following conversion therapy, this work provides a roadmap for optimizing SBRT across the clinical spectrum of HCC.

## Linked entities

- **Diseases:** hepatocellular carcinoma (MONDO:0007256), non-small cell lung cancer (MONDO:0005233), pancreatic adenocarcinoma (MONDO:0006047)

## Full-text entities

- **Genes:** CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, HULC (hepatocellular carcinoma up-regulated long non-coding RNA) [NCBI Gene 728655] {aka HCCAT1, LINC00078, NCRNA00078}, PNPLA3 (patatin like domain 3, 1-acylglycerol-3-phosphate O-acyltransferase) [NCBI Gene 80339] {aka ADPN, C22orf20, iPLA(2)epsilon}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, SAMSN1 (SAM domain, SH3 domain and nuclear localization signals 1) [NCBI Gene 64092] {aka HACS1, NASH1, SASH2, SH3D6B, SLy2}, COL11A2 (collagen type XI alpha 2 chain) [NCBI Gene 1302] {aka DFNA13, DFNB53, FBCG2, HKE5, OSMEDA, OSMEDB}, ARID4B (AT-rich interaction domain 4B) [NCBI Gene 51742] {aka BCAA, BRCAA1, RBBP1L1, RBP1L1, SAP180}, ST20 (suppressor of tumorigenicity 20) [NCBI Gene 400410] {aka HCCS-1}, CYTOR (cytoskeleton regulator RNA) [NCBI Gene 112597] {aka C2orf59, LINC00152, NCRNA00152}, CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230] {aka CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}, SHH (sonic hedgehog signaling molecule) [NCBI Gene 6469] {aka HHG1, HLP3, HPE3, MCOPCB5, SMMCI, ShhNC}, IL7 (interleukin 7) [NCBI Gene 3574] {aka IL-7, IMD130}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}
- **Diseases:** lung and liver tumors (MESH:D008175), NAFLD (MESH:D065626), Cancer (MESH:D009369), lymphopenia (MESH:D008231), liver cirrhosis (MESH:D008103), inflammatory (MESH:D007249), chronic liver disease (MESH:D008107), sarcopenia (MESH:D055948), metabolic syndrome (MESH:D024821), cirrhosis (MESH:D005355), pancreatic adenocarcinoma (MESH:D010190), cirrhotic (MESH:D000094724), RILD (MESH:D007953), extrahepatic disease (MESH:D001651), biliary strictures (MESH:D003251), non-small cell lung cancer (MESH:D002289), hypoxia (MESH:D000860), NASH (MESH:D005235), obesity (MESH:D009765), intrahepatic cholangiocarcinoma (MESH:D018281), coagulopathy (MESH:D001778), cytotoxic (MESH:D064420), Child-Pugh B (MESH:C562515), NTCP (MESH:D009380), ascites (MESH:D001201), vascular thrombus (MESH:D013927), PVTT (MESH:D012170), metastases (MESH:D009362), nutritional deficiencies (MESH:D044342), deaths (MESH:D003643), viral hepatitis (MESH:D014777), HCC (MESH:D006528), necrosis (MESH:D009336), liver tumors (MESH:D008113), chronic (MESH:D002908), embolic (MESH:D004617), breast cancer (MESH:D001943), chronic hepatitis B (MESH:D019694), pCN (MESH:D005598), hepatic failure (MESH:D017093)
- **Chemicals:** aflatoxin-B1 (MESH:D016604), oxygen (MESH:D010100), sorafenib (MESH:D000077157), 18F-FDG (MESH:D019788), 11C-choline (-), Gadoxetate disodium (MESH:C073590), alcohol (MESH:D000438), ROS (MESH:D017382)
- **Species:** hepatitis C virus [taxon 11103], Hepatitis B virus (no rank) [taxon 10407], Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC12914947/full.md

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Source: https://tomesphere.com/paper/PMC12914947