Efficacy of stereotactic body radiotherapy combined with sintilimab and bevacizumab in treatment of unresectable hepatocellular carcinoma

Teng ZHANG; Quan WANG; Wengang LI; Xuezhang DUAN

doi:10.12449/JCH250111

Volume 41 Issue 1

Jan. 2025

Turn off MathJax

Article Contents

Abstract

References

Article Navigation > Journal of Clinical Hepatology > 2025 > 41(1): 69-74

PDF( 1358 KB)

Efficacy of stereotactic body radiotherapy combined with sintilimab and bevacizumab in treatment of unresectable hepatocellular carcinoma

DOI: 10.12449/JCH250111

Department of Radiation Oncology，Senior Department of Oncology，The Fifth Medical Center of PLA General Hospital，Beijing 100039，China

More Information

Corresponding author: DUAN Xuezhang， duanxuezhang2006@163.com （ORCID： 0000-0002-1941-9317）
Received Date: 2024-06-11
Accepted Date: 2024-09-04
Published Date: 2025-01-25

Abstract

Abstract

Objective To investigate the efficacy and safety of stereotactic body radiotherapy （SBRT） combined with sintilimab and bevacizumab in the treatment of patients with unresectable hepatocellular carcinoma （uHCC） and related prognostic factors. Methods A total of 42 patients with uHCC who underwent SBRT combined with sintilimab and bevacizumab in Department of Radiation Oncology， The Fifth Medical Centre of PLA General Hospital， from March to December 2022 were enrolled. The prescribed dose of planning target volume was 36‍ ‍—‍ ‍50 Gy in 5‍ ‍—‍ ‍6 fractions for continuous irradiation， followed by the regimen of sintilimab and bevacizumab. Each course of treatment was 3 weeks until the presence of tumor progression or serious adverse events. The Kaplan-Meier method was used to calculate overall survival （OS） rate and progression-free survival （PFS） rate， and the log-rank test was used for comparison between groups； the Cox proportional hazards model was used to investigate the influencing factors for prognosis. Results The median follow-up time was 21.6 months， with an objective response rate of 69%， a disease control rate of 85.7%， a median PFS of 10.0 months （95% confidence interval ［CI］： 6.7‍ ‍—‍ ‍13.0）， and a median OS of 23.3 months （95%CI： 14.7‍ ‍—‍ ‍31.8）. Most adverse events were grade 1‍ ‍—‍ ‍2 events， and there were no fatal adverse events. At 6‍ ‍—‍ ‍8 weeks after treatment， the AFP response group had a significantly better OS than the non-AFP response group （not reached vs 11.8 months， P=0.007）. The multivariate analysis showed that AFP response was associated with the good prognosis of patients （hazard ratio=0.31， 95%CI： 0.13‍ ‍—‍ ‍0.75， P=0.009）. Conclusion For patients with uHCC， SBRT combined with sintilimab and bevacizumab can improve survival with a manageable safety profile， and a >50% reduction in AFP at 6‍ ‍—‍ ‍8 weeks after treatment can be used as a potential prognostic indicator.
- Liver Neoplasms,
- Radiotherapy,
- alpha-Fetoproteins,
- Treatment Outcome

FullText(HTML)

References(25)

References

[1]	REIG M, FORNER A, RIMOLA J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update[J]. J Hepatol, 2022, 76( 3): 681- 693. DOI: 10.1016/j.jhep.2021.11.018.
[2]	FINN RS, QIN SK, IKEDA M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med, 2020, 382( 20): 1894- 1905. DOI: 10.1056/NEJMoa1915745.
[3]	REN ZG, XU JM, BAI YX, et al. Sintilimab plus a bevacizumab biosimilar(IBI₃05) versus sorafenib in unresectable hepatocellular carcinoma(ORIENT-32): A randomised, open-label, phase 2-3 study[J]. Lancet Oncol, 2021, 22( 7): 977- 990. DOI: 10.1016/S1470-2045(21)00252-7.
[4]	PINTER M, JAIN RK, DUDA DG. The current landscape of immune checkpoint blockade in hepatocellular carcinoma: A review[J]. JAMA Oncol, 2021, 7( 1): 113- 123. DOI: 10.1001/jamaoncol.2020.3381.
[5]	CHENG AL, QIN SK, IKEDA M, et al. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma[J]. J Hepatol, 2022, 76( 4): 862- 873. DOI: 10.1016/j.jhep.2021.11.030.
[6]	WANG Q, JI XQ, SUN J, et al. Stereotactic body radiotherapy combined with lenvatinib with or without PD-1 inhibitors as initial treatment for unresectable hepatocellular carcinoma[J]. Int J Radiat Oncol Biol Phys, 2024. DOI: 10.1016/j.ijrobp.2024.03.035.[ Online ahead of print]
[7]	LIU LX, ZHANG WZ. Minimally invasive treatment strategies for hepatocellular carcinoma[J]. Chin J Dig Surg, 2024, 23( 4): 548- 553. DOI: 10.3760/cma.j.cn115610-20240202-00061. 刘连新, 张维志. 肝细胞癌的微创治疗策略[J]. 中华消化外科杂志, 2024, 23( 4): 548- 553. DOI: 10.3760/cma.j.cn115610-20240202-00061.
[8]	ZHU SM, ZHANG T, ZHENG L, et al. Combination strategies to maximize the benefits of cancer immunotherapy[J]. J Hematol Oncol, 2021, 14( 1): 156. DOI: 10.1186/s13045-021-01164-5.
[9]	HACK SP, ZHU AX, WANG YL. Augmenting anticancer immunity through combined targeting of angiogenic and PD-1/PD-L1 pathways: Challenges and opportunities[J]. Front Immunol, 2020, 11: 598877. DOI: 10.3389/fimmu.2020.598877.
[10]	BENEDICT SH, YENICE KM, FOLLOWILL D, et al. Stereotactic body radiation therapy: The report of AAPM Task Group 101[J]. Med Phys, 2010, 37( 8): 4078- 4101. DOI: 10.1118/1.3438081.
[11]	WEN W, ZHANG Y, ZHANG H, et al. Clinical outcomes of PD-1/PD-L1 inhibitors in patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis[J]. J Cancer Res Clin Oncol, 2023, 149( 3): 969- 978. DOI: 10.1007/s00432-022-04057-3.
[12]	ZHANG B, TAO BR, LI YT, et al. Dual immune checkpoint inhibitors or combined with anti-VEGF agents in advanced, unresectable hepatocellular carcinoma[J]. Eur J Intern Med, 2023, 111: 37- 46. DOI: 10.1016/j.ejim.2022.12.025.
[13]	LEE YH, TAI D, YIP C, et al. Combinational immunotherapy for hepatocellular carcinoma: Radiotherapy, immune checkpoint blockade and beyond[J]. Front Immunol, 2020, 11: 568759. DOI: 10.3389/fimmu.2020.568759.
[14]	PIERINI S, MISHRA A, PERALES-LINARES R, et al. Combination of vasculature targeting, hypofractionated radiotherapy, and immune checkpoint inhibitor elicits potent antitumor immune response and blocks tumor progression[J]. J Immunother Cancer, 2021, 9( 2): e001636. DOI: 10.1136/jitc-2020-001636.
[15]	SU K, GUO L, MA WQ, et al. PD-1 inhibitors plus anti-angiogenic therapy with or without intensity-modulated radiotherapy for advanced hepatocellular carcinoma: A propensity score matching study[J]. Front Immunol, 2022, 13: 972503. DOI: 10.3389/fimmu.2022.972503.
[16]	ZHU M, LIU Z, CHEN S, et al. Sintilimab plus bevacizumab combined with radiotherapy as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A multicenter, single-arm, phase 2 study[J]. Hepatology, 2024, 80( 4): 807- 815. DOI: 10.1097/HEP.0000000000000776.
[17]	SHAO GL, BAI YX, YUAN XL, et al. Ramucirumab as second-line treatment in Chinese patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib(REACH-2 China): A randomised, multicentre, double-blind study[J]. EClinicalMedicine, 2022, 54: 101679. DOI: 10.1016/j.eclinm.2022.101679.
[18]	JI XQ, XU Z, SUN J, et al. Lenvatinib with or without stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: A retrospective study[J]. Radiat Oncol, 2023, 18( 1): 101. DOI: 10.1186/s13014-023-02270-z.
[19]	YOON SM, RYOO BY, LEE SJ, et al. Efficacy and safety of transarterial chemoembolization plus external beam radiotherapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: A randomized clinical trial[J]. JAMA Oncol, 2018, 4( 5): 661- 669. DOI: 10.1001/jamaoncol.2017.5847.
[20]	HU X, CHEN RG, WEI Q, et al. The landscape of alpha fetoprotein in hepatocellular carcinoma: Where are we?[J]. Int J Biol Sci, 2022, 18( 2): 536- 551. DOI: 10.7150/ijbs.64537.
[21]	SUDDLE A, REEVES H, HUBNER R, et al. British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults[J]. Gut, 2024, 73( 8): 1235- 1268. DOI: 10.1136/gutjnl-2023-331695.
[22]	KIM DY, TOAN BN, TAN CK, et al. Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region[J]. Clin Mol Hepatol, 2023, 29( 2): 277- 292. DOI: 10.3350/cmh.2022.0212.
[23]	TIAN BW, YAN LJ, DING ZN, et al. Early alpha-fetoprotein response predicts prognosis of immune checkpoint inhibitor and targeted therapy for hepatocellular carcinoma: A systematic review with meta-analysis[J]. Expert Rev Gastroenterol Hepatol, 2023, 17( 1): 73- 83. DOI: 10.1080/17474124.2022.2156859.
[24]	SHAO YY, LIU TH, HSU C, et al. Early alpha-foetoprotein response associated with treatment efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma[J]. Liver Int, 2019, 39( 11): 2184- 2189. DOI: 10.1111/liv.14210.
[25]	ZHU AX, DAYYANI F, YEN CJ, et al. Alpha-fetoprotein as a potential surrogate biomarker for atezolizumab+bevacizumab treatment of hepatocellular carcinoma[J]. Clin Cancer Res, 2022, 28( 16): 3537- 3545. DOI: 10.1158/1078-0432.CCR-21-3275.

Relative Articles

[1]	Chinese Association for Therapeutic Radiation Oncologists, Chinese Society for Therapeutic Radiology and Oncology, Chinese Medical Association, Committee of Radiation Oncology, Chinese Anti-Cancer Association. Chinese radiotherapy guidelines for primary hepatocellular carcinoma (2020 edition)[J]. Journal of Clinical Hepatology, 2021, 37(5): 1029-1033. doi: 10.3760/cma.j.cn371439-20201208-00001
[2]	Gang REN, Yingjie WANG. Advances in radiotherapy for pancreatic cancer from 2019 to 2020[J]. Journal of Clinical Hepatology, 2021, 37(3): 733-736. doi: 10.3969/j.issn.1001-5256.2021.03.048
[3]	Wenjun LIU, Dan DU, Baojie CHEN, Ting YAO, Xianfu LI. Application of stereotactic body radiotherapy in small hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2021, 37(5): 1212-1215. doi: 10.3969/j.issn.1001-5256.2021.05.050
[4]	Precise Radiotherapy Study Group, Chinese Society of Liver Cancer, Chinese Medical Doctor Association, Liver Cancer Study Group, Committee of Radiation Oncology, Chinese Research Hospital Association, Committee of Tumor Radiobiology and Multimodal Imaging and Therapy, Chinese Research Hospital Association, Liver Cancer Study Group, Precise Radiotherapy Branch, Chinese Society of Biomedical Engineering. Consensus on radiation therapy for primary liver cancer (2020)[J]. Journal of Clinical Hepatology, 2021, 37(2): 296-301. doi: 10.3969/j.issn.1001-5256.2021.02.010
[5]	Liu YueChen, Gu MengYu, Cheng Yu, Yang GuiYuan. An excerpt of radiation therapy for pancreatic cancer: Executive summary of an ASTRO clinical practice guideline (2019)[J]. Journal of Clinical Hepatology, 2020, 36(1): 50-52. doi: 10.3969/j.issn.1001-5256.2020.01.010
[6]	Yang Zhao, Xie Hui, Wang Quan, Zhang Tao, Wang HuaMing, He WeiPing, Duan XueZhang. Short-term clinical effect of cyberknife versus radiofrequency ablation in treatment of small hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2019, 35(9): 1965-1969. doi: 10.3969/j.issn.1001-5256.2019.09.016
[7]	Tian Zhou, Zhang JianHuai. A threshold analysis of alpha-fetoprotein in diagnosis and screening of hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2018, 34(11): 2352-2355. doi: 10.3969/j.issn.1001-5256.2018.11.016
[8]	Li TianTian, Sun Jing, Wang Quan, Ding JunQiang, Wang Jia, Xue Hui, Zhang Tao, Duan XueZhang. Clinical effect of stereotactic body radiotherapy in treatment of patients with small hepatocellular carcinoma and related prognostic factors[J]. Journal of Clinical Hepatology, 2018, 34(8): 1702-1706. doi: 10.3969/j.issn.1001-5256.2018.08.022
[9]	Lu NingNing, Sun Bin, Cui XiongWei, Long Jiang, Gao WenFeng, Zheng JiaSheng. Diagnosis and treatment of subcapsular hemorrhage after liver tumor ablation[J]. Journal of Clinical Hepatology, 2017, 33(12): 2326-2330. doi: 10.3969/j.issn.1001-5256.2017.12.014
[10]	Zhang Tao, Sun Jing, He WeiPing, Li Huan, Wang Hui, Sun YingZhe, Po JunJie, Zhang JunHua, Xu HuiJun, Duan XueZhang. Clinical effect of Cyber Knife stereotactic radiosurgery in treatment of patients with small hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2017, 33(4): 694-698. doi: 10.3969/j.issn.1001-5256.2017.04.019
[11]	Zhang Qin, Dan HongLi, Xu Wei. Value of serum GP73,AFP,and AFP-L3 in diagnosis of liver cancer and recurrence monitoring after radiofrequency ablation[J]. Journal of Clinical Hepatology, 2015, 31(2): 232-235. doi: 10.3969/j.issn.1001-5256.2015.02.021
[12]	Zhu Chen, Sun YuanYuan, Jin Yan. Values of serum AFP, GGTⅡ and GP73 in diagnosis of primary hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2014, 30(10): 1064-1066. doi: 10.3969/j.issn.1001-5256.2014.10.022
[13]	Fang ZiYan, Huang Long, Li Gong. Research progress in radiotherapy for liver tumors reported in 2013 ASTRO Annual Meeting[J]. Journal of Clinical Hepatology, 2014, 30(4): 383-385. doi: 10.3969/j.issn.1001-5256.2014.04.025
[14]	Jia Jia, Qi XingShun, Han GuoHong. Prognostic value of α-fetoprotein response in treatment of hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2013, 29(8): 576-580. doi: 10.3969/j.issn.1001-5256.2013.08.006
[15]	Zhao ChunHua, Zhou WenFeng, Chen WeiHua, Xi Zhen, Zhang ChunMei. Clinical significance of α- fetoprotein in initial diagnosis of primary hepatic cancer[J]. Journal of Clinical Hepatology, 2013, 29(9): 698-701. doi: 10.3969/j.issn.1001-5256.2013.09.017
[16]	Chen MinHua. Standardization of thermal ablation in treatment of liver tumor[J]. Journal of Clinical Hepatology, 2013, 29(8): 561-563. doi: 10.3969/j.issn.1001-5256.2013.08.001
[17]	Yao Min, Yang Yan, Yao DengFu, Bian YinZhu, Yu DanDan, Yan XiaoDi, Chen Jie. Clinical value of circulating peripheral blood mononuclear cell glypican-3 mRNA and alpha fetoprotein for diagnosing and monitoring metastasis of hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2012, 28(10): 777-781.
[18]	Song MengQi, Yang YongFei, Wang DongDong, You FaPing, Chen LiBo. The diagnostic role of combination of glypican-3 and AFP in primary hepatic carcinoma[J]. Journal of Clinical Hepatology, 2011, 27(4): 391-393+399.
[19]	Yang BiWei, Gan YuHong, Ye ShengLong, Zhang BoHeng, Ren ZhengGang, Xia JingLin, Wang YanHong, Ge NingLing, Chen Yi, Li LiXin, Le Fan, Zhang Lan. Necrosis range and safety of radiofrequency combined with systemic chemotherapy and radiofrequency alone.[J]. Journal of Clinical Hepatology, 2004, 20(6): 364-365.
[20]	Guo ZhanWen, Li Yu, Yan Ying, Tian QiHe, Xu Rui. Clinical study of 3-dimensional conformal radiotherapy on primary liver cancer.[J]. Journal of Clinical Hepatology, 2002, 18(3): 164-165.

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(3) / Tables(3)

Get Citation

PDF

XML

Article Metrics

Article views (231) PDF downloads(34)

Efficacy of stereotactic body radiotherapy combined with sintilimab and bevacizumab in treatment of unresectable hepatocellular carcinoma

DOI: 10.12449/JCH250111

Abstract

References

Relative Articles

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Efficacy of stereotactic body radiotherapy combined with sintilimab and bevacizumab in treatment of unresectable hepatocellular carcinoma

DOI: 10.12449/JCH250111

Abstract

References

Relative Articles

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content