The Role of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma Patients: A Literature Review

Angela Giselvania, Sri Mutya Sekarutami, Arie Munandar, Devina Adella Halim, Felix Wijovi

Abstract


Background: Globally, hepatocellular carcinoma (HCC) is the most prevalent kind of primary liver cancer. Treatment options for HCC include radiotherapy, immunotherapy, surgery, targeted therapy, transarterial chemoembolization, and hepatic arterial infusion chemotherapy. Limited efficacy was observed since 70-80% of cases are diagnosed late and unresectable. Growing evidence reported that SBRT is a viable option for locoregional treatments like radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) for patients who did not respond to those treatments.

 

Methods: A thorough search of electronic databases including PubMed, Cochrane Library, and Embase was conducted for studies on Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma published in English over the past 10 years. The review process followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to ensure a systematic approach. Inclusion criteria encompassed studies focusing on SBRT use in HCC treatment, with extracted data synthesized to provide a comprehensive overview of current evidence. Any discrepancies during the review were resolved through consultation with a third reviewer when necessary.

 

Results: In comparison to conventional radiation therapy, Stereotactic Body Radiation Therapy (SBRT) offers precise administration of the high dose of radiotherapy, given in fewer fractions, and may be used in conjunction with other therapy modalities. Global guidelines, including in Indonesia, have proposed the implementation of SBRT. Local control was reportedly achieved in around 90–95% of HCC patients. Multimodal therapies, combined with TACE, showed superior results regarding the local control and overall survival. SBRT may eventually become the definitive treatment for early-stage HCC patients and has a critical role as a transitional therapy for patients awaiting liver transplantation. Improved outcomes and quality of life were also observed in patients with portal vein thrombosis (PVT) and extrahepatic metastases who underwent SBRT.

 

Conclusions: SBRT results in promising local control, raises overall survival, and improves the quality of life in HCC patients with various stages.


Keywords


advanced HCC, EBRT, hepatocellular carcinoma, portal vein thrombosis, radiotherapy, SBRT

Full Text: View | Download

DOI: 10.33371/ijoc.v18i3.1190

Article Metrics

Abstract View: 130,
PDF Download: 71
             

References


Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021; 7: 6.

Gerum S, Jensen AD, Roeder F. Stereotactic body radiation therapy in patients with hepatocellular carcinoma: A mini-review. World J Gastrointest Oncol 2019; 11: 367–376.

Moore A, Cohen-Naftaly M, Tobar A, et al. Stereotactic body radiation therapy (SBRT) for definitive treatment and as a bridge to liver transplantation in early stage inoperable Hepatocellular carcinoma. Radiation Oncology 2017; 12: 163.

Matsuo Y. Stereotactic Body Radiotherapy for Hepatocellular Carcinoma: A Brief Overview. Current Oncology 2023; 30: 2493–2500.

Dawson LA, Hashem S, Bujold A. Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma. American Society of Clinical Oncology Educational Book 2012; 261–264.

Thomas HR, Feng M. Stereotactic Body Radiation Therapy (SBRT) in Hepatocellular Carcinoma. Curr Hepatol Rep 2021; 20: 12–22.

Cárdenes HR, Price TR, Perkins SM, et al. Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma. Clinical and Translational Oncology 2010; 12: 218–225.

Sebastian NT, Xu-Welliver M, Williams TM. Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC): contemporary insights and advances. J Thorac Dis 2018; 10: S2451–S2464.

Robbins JR, Schmid RK, Hammad AY, et al. Stereotactic body radiation therapy for hepatocellular carcinoma: Practice patterns, dose selection and factors impacting survival. Cancer Med 2019; 8: 928–938.

Alongi F, Arcangeli S, Filippi AR, et al. Review and Uses of Stereotactic Body Radiation Therapy for Oligometastases. Oncologist 2012; 17: 1100–1107.

Li LQ, Su TS, Wu QY, et al. Therapeutic Outcome of Stereotactic Body Radiotherapy for Small Hepatocellular Carcinoma Lesions – A Systematic Review and Network Meta-analysis. Clin Oncol. Epub ahead of print July 2023.

Paoletti L, Ceccarelli C, Menichelli C, et al. Special stereotactic radiotherapy techniques: procedures and equipment for treatment simulation and dose delivery. Reports of Practical Oncology and Radiotherapy 2022; 27: 1–9.

Benedict SH, Yenice KM, Followill D, et al. Stereotactic body radiation therapy: The report of AAPM Task Group 101. Med Phys 2010; 37: 4078–4101.

Solberg TD, Balter JM, Benedict SH, et al. Quality and safety considerations in stereotactic radiosurgery and stereotactic body radiation therapy: Executive summary. Pract Radiat Oncol 2012; 2: 2–9.

Fuks Z, Kolesnick R. Engaging the vascular component of the tumor response. Cancer Cell 2005; 8: 89–91.

Hall EJ, Brenner DJ. The radiobiology of radiosurgery: Rationale for different treatment regimes for AVMs and malignancies. International Journal of Radiation Oncology*Biology*Physics 1993; 25: 381–385.

Song CW, Glatstein E, Marks LB, et al. Biological Principles of Stereotactic Body Radiation Therapy (SBRT) and Stereotactic Radiation Surgery (SRS): Indirect Cell Death. International Journal of Radiation Oncology*Biology*Physics 2021; 110: 21–34.

Tsang MWK. Stereotactic body radiotherapy: current strategies and future development. J Thorac Dis 2016; 8: S517–S527.

Kimura T, Takeda A, Sanuki N, et al. Multicenter prospective study of stereotactic body radiotherapy for previously untreated solitary primary hepatocellular carcinoma: The STRSPH study. Hepatology Research 2021; 51: 461–471.

Yoon SM, Kim SY, Lim Y-S, et al. Stereotactic body radiation therapy for small (≤5 cm) hepatocellular carcinoma not amenable to curative treatment: Results of a single-arm, phase II clinical trial. Clin Mol Hepatol 2020; 26: 506–515.

Durand-Labrunie J, Baumann A-S, Ayav A, et al. Curative Irradiation Treatment of Hepatocellular Carcinoma: A Multicenter Phase 2 Trial. International Journal of Radiation Oncology*Biology*Physics 2020; 107: 116–125.

Kim JW, Kim DY, Han K-H, et al. Phase I/II trial of helical IMRT-based stereotactic body radiotherapy for hepatocellular carcinoma. Digestive and Liver Disease 2019; 51: 445–451.

Takeda A, Sanuki N, Tsurugai Y, et al. Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation. Cancer 2016; 122: 2041–2049.

Lasley FD, Mannina EM, Johnson CS, et al. Treatment variables related to liver toxicity in patients with hepatocellular carcinoma, Child-Pugh class A and B enrolled in a phase 1-2 trial of stereotactic body radiation therapy. Pract Radiat Oncol 2015; 5: e443–e449.

Bujold A, Massey CA, Kim JJ, et al. Sequential Phase I and II Trials of Stereotactic Body Radiotherapy for Locally Advanced Hepatocellular Carcinoma. Journal of Clinical Oncology 2013; 31: 1631–1639.

Kang J-K, Kim M-S, Cho CK, et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer 2012; 118: 5424–5431.

Hu Y, Zhao C, Ji R, et al. The role of stereotactic body radiotherapy in hepatocellular carcinoma: guidelines and evidences. Journal of the National Cancer Center 2022; 2: 171–182.

Lewis S, Dawson L, Barry A, et al. Stereotactic body radiation therapy for hepatocellular carcinoma: From infancy to ongoing maturity. JHEP Reports 2022; 4: 100498.

Lin TA, Lin JS, Wagner T, et al. Stereotactic body radiation therapy in primary hepatocellular carcinoma: current status and future directions. J Gastrointest Oncol 2018; 9: 858–870.

Bang A, Dawson LA. Radiotherapy for HCC: Ready for prime time? JHEP Reports 2019; 1: 131–137.

Jang W Il, Kim MS, Bae SH, et al. High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma. Radiation Oncology 2013; 8: 250.

Jang W Il, Kim MS, Bae SH, et al. High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma. Radiation Oncology 2013; 8: 250.

Gerum S, Jensen AD, Roeder F. Stereotactic body radiation therapy in patients with hepatocellular carcinoma: A mini-review. World J Gastrointest Oncol 2019; 11: 367–376.

Sapisochin G, Barry A, Doherty M, et al. Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis. J Hepatol 2017; 67: 92–99.

Mathew AS, Dawson LA. Current Understanding of Ablative Radiation Therapy in Hepatocellular Carcinoma. J Hepatocell Carcinoma 2021; Volume 8: 575–586.

Garg R, Foley K, Movahedi B, et al. Outcomes After Stereotactic Body Radiation Therapy as a Bridging Modality to Liver Transplantation for Hepatocellular Carcinoma. Adv Radiat Oncol 2021; 6: 100559.

Angeli-Pahim I, Chambers A, Duarte S, et al. Current Trends in Surgical Management of Hepatocellular Carcinoma. Cancers (Basel) 2023; 15: 5378.

Huo YR, Eslick GD. Transcatheter Arterial Chemoembolization Plus Radiotherapy Compared With Chemoembolization Alone for Hepatocellular Carcinoma. JAMA Oncol 2015; 1: 756.

Su TS, Luo R, Liang P, et al. A prospective cohort study of hepatic toxicity after stereotactic body radiation therapy for hepatocellular carcinoma. Radiotherapy and Oncology 2018; 129: 136–142.

Jiazhi Li, Zhiyong Dong, Xinjing Zhang, Chenyu Huang, Jing Xu. Transcatheter arterial chemoembolization in combination with stereotactic body radiation therapy in primary liver carcinoma: a systematic review and meta-analysis. International Journal of Clinical and Experimental Medicine. 2017;10(2):1816-1827 .

Zhao J, Zeng L, Wu Q, et al. Stereotactic Body Radiotherapy Combined with Transcatheter Arterial Chemoembolization versus Stereotactic Body Radiotherapy Alone as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis and Systematic Review. Chemotherapy 2019; 64: 248–258.

Huo YR, Eslick GD. Transcatheter Arterial Chemoembolization Plus Radiotherapy Compared With Chemoembolization Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. JAMA Oncol 2015; 1: 756–65.

Apisarnthanarax S, Barry A, Cao M, et al. External Beam Radiation Therapy for Primary Liver Cancers: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol 2022; 12: 28–51.

Zhao J, Zeng L, Wu Q, et al. Stereotactic Body Radiotherapy Combine with Transcathether Arterial Chemoembolization versus Stereotactic Body Radiotherapy Alone as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis and Systematic Review. Chemotherapy 2020; 64 (5-6): 248- 58.

Park S, Yoon WS, Rim CH. Indications of external radiotherapy for hepatocellular carcinoma from updated clinical guidelines: Diverse global viewpoints. World J Gastroenterol 2020; 26: 393–403.

Kudo M, Izumi N, Kokudo N, et al. Report of the 21st Nationwide Follow‐up Survey of Primary Liver Cancer in Japan (2010–2011). Hepatology Research 2021; 51: 355–405.

Sharma D, Thaper D, Kamal R, et al. Role of palliative SBRT in barcelona clinic liver cancer-stage C hepatocellular carcinoma patients. Strahlentherapie und Onkologie 2023; 199: 838–846.

Galle PR, Forner A, Llovet JM, et al. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018; 69: 182–236.

Benson AB, D’Angelica MI, Abbott DE, et al. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network 2021; 19: 541–565.

Zhou J, Sun H, Wang Z, et al. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer 2020; 9: 682–720.

Korean Liver Cancer Association K, National Cancer Center N. 2018 Korean Liver Cancer Association–National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13: 227–299.

Omata M, Cheng AL, Kokudo N, et al. Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 2017; 11: 317–370.

Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2018; 68: 723–750.

Pelizzaro F, Farinati F, Trevisani F. Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Strategies and Biomarkers Predicting Response and/or Resistance. Biomedicines 2023; 11: 1020.

Sara A, Ruff SM, Noonan AM, et al. Real-World Use of Immunotherapy for Hepatocellular Carcinoma. Pragmat Obs Res 2023; Volume 14: 63–74.

Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76: 681–693.

Jiang J, Diaz DA, Nuguru SP, et al. Stereotactic Body Radiation Therapy (SBRT) Plus Immune Checkpoint Inhibitors (ICI) in Hepatocellular Carcinoma and Cholangiocarcinoma. Cancers (Basel) 2022; 15: 50.

Friedman D, Baird JR, Young KH, et al. Programmed cell death‐1 blockade enhances response to stereotactic radiation in an orthotopic murine model of hepatocellular carcinoma. Hepatology Research 2017; 47: 702–714.

Chiang CL, Chan ACY, Chiu KWH, et al. Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy. Front Oncol; 9. Epub ahead of print 12 November 2019.

Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. The Lancet 2018; 391: 1163–1173.

Casak SJ, Donoghue M, Fashoyin-Aje L, et al. FDA Approval Summary: Atezolizumab Plus Bevacizumab for the Treatment of Patients with Advanced Unresectable or Metastatic Hepatocellular Carcinoma. Clinical Cancer Research 2021; 27: 1836–1841.

Vogel A, Rimassa L, Sun H-C, et al. Comparative Efficacy of Atezolizumab plus Bevacizumab and Other Treatment Options for Patients with Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis. Liver Cancer 2021; 10: 240–248.

Ji X, Xu Z, Sun J, et al. Lenvatinib with or without stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective study. Radiation Oncology 2023; 18: 101.

Shannon AH, Manne A, Diaz Pardo DA, et al.

Combined radiotherapy and immune checkpoint inhibition for the treatment of advanced hepatocellular carcinoma. Front Oncol; 13. Epub ahead of print 24 July 2023. DOI: 10.3389/fonc.2023.1193762.

Menteri Kesehatan Republik Indonesia. Pedoman Nasional Pelayanan Kedokteran Tata Laksana Karsinoma Sel Hati pada Dewasa. 2022.

Matsuo Y. Stereotactic Body Radiotherapy for Hepatocellular Carcinoma: A Brief Overview. Current Oncology 2023; 30: 2493–2500.

Koay EJ, Owen D, Das P. Radiation-Induced Liver Disease and Modern Radiotherapy. Semin Radiat Oncol 2018; 28: 321–331.

Culleton S, Jiang H, Haddad CR, et al. Outcomes following definitive stereotactic body radiotherapy for patients with Child-Pugh B or C hepatocellular carcinoma. Radiotherapy and Oncology 2014; 111: 412–417.

Mayo CS, Moran JM, Bosch W, et al. American Association of Physicists in Medicine Task Group 263: Standardizing Nomenclatures in Radiation Oncology. International Journal of Radiation Oncology*Biology*Physics 2018; 100: 1057–1066.

Apisarnthanarax S, Barry A, Cao M, et al. External Beam Radiation Therapy for Primary Liver Cancers: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol 2022; 12: 28–51.


Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.