Skip to main content
SpringerLink
Log in

Stereotactic body radiotherapy versus intensity-modulated radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Background

It is unclear whether robotic stereotactic body radiotherapy (SBRT) is superior to intensity-modulated radiotherapy (IMRT) in advanced hepatocellular carcinoma (HCC). This study aimed to compare the long-term outcomes of SBRT with those of IMRT in HCCs with portal vein tumor thrombosis (PVTT).

Methods

We retrospectively evaluated 287 HCC patients with PVTT who underwent radiotherapy between January 2000 and January 2017. Of them, 154 and 133 patients were treated with IMRT and SBRT, respectively. Overall survival (OS), progression-free survival (PFS), intrahepatic control (IC), and local control (LC) were evaluated in univariable and propensity-score matched analyses.

Results

After matching, 102 well-paired patients were selected. There was no significant difference in the 6-, 12-, 24-, and 60-month cumulative OS (73.5, 42.9, 23.6, 7.6% vs. 72.4, 45.1, 29.8, 13.2%, p = 0.151), PFS (53.9, 29.3, 21.8, 7.5% vs. 54.5, 19.3, 12.0, 9.6%, p = 0.744), IC (61.4, 45.7, 39.0, 26.8% vs. 75.1, 45.8, 35.9, 28.7%, p = 0.144), and LC (85.2, 56.5, 52.1, 47.4% vs. 87.4, 65.2, 62.1, 62.1%, p = 0.191) between the IMRT and SBRT groups. A biologically effective dose assumed at an a/b ratio of 10 (BED10) of ≥ 100 Gy was the optimal cutoff for predicting the OS, PFS, IC, and LC in the patients who received SBRT.

Conclusions

When high-precision tracking technology is available, SBRT appears to be a safe and more time-efficient treatment, achieving comparable OS, PFS, IC and LC to IMRT for local advanced HCC with PVTT. A BED10 ≥ 100 Gy is recommended if tolerated by normal tissue.

Graphic abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Availability of data and codes

The statistical datasets and codes used and/or analyzed in the current study are available from the corresponding author (sutingshi@163.com) on reasonable request.

Abbreviations

95% CI:

95% Confidence interval

c-RILD:

Classic radiation-induced liver diseasenc

RILD:

Non-classic radiation-induced liver disease

ROC:

Receiver operating characteristic

PSM:

Propensity score matching analysis

ALBI:

Bilirubin-albumin

AFP:

Alpha-fetoprotein

AUC:

Area under the curve

BCLC:

Barcelona Clinic Liver Cancer

BED10 :

Biologically effective dose assumed an a/b ratio of 10

CP:

Child–Pugh class

CT:

Computed tomography

CTCAE:

Common Toxicity Criteria for Adverse Events

CTV:

Clinical target volume

Dmax:

Maximum dose

Dmean:

Mean dose

GI:

Gastrointestinal

GTV:

Gross tumor volume

HCC:

Hepatocellular carcinoma

IC:

Intrahepatic control

IMRT:

Intensity modulated radiation therapy

LC:

Local control

MRI:

Magnetic resonance imaging

OARs:

Organs at risk

OS:

Overall survival

PFS:

Progression-free survival

PT:

Prothrombin time

PTV:

Planning target volume

PVTT:

Portal vein tumor thrombosis

RT:

Radiotherapy

SBRT:

Stereotactic body radiation therapy

TACE:

Trans-arterial chemoembolization

References

  1. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 2019;16(10):589–604

    Article  Google Scholar 

  2. Schoniger-Hekele M, Muller C, Kutilek M, Oesterreicher C, Ferenci P, Gangl A. Hepatocellular carcinoma in Central Europe: prognostic features and survival. Gut 2001;48(1):103–109

    Article  CAS  Google Scholar 

  3. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359(4):378–390

    Article  CAS  Google Scholar 

  4. Bruix J, Raoul JL, Sherman M, Mazzaferro V, Bolondi L, Craxi A, Galle PR, Santoro A, Beaugrand M, Sangiovanni A, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol 2012;57(4):821–829

    Article  CAS  Google Scholar 

  5. Cheng AL, Guan Z, Chen Z, Tsao CJ, Qin S, Kim JS, Yang TS, Tak WY, Pan H, Yu S, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: subset analyses of the phase III Sorafenib Asia-Pacific trial. Eur J Cancer 2012;48(10):1452–1465

    Article  CAS  Google Scholar 

  6. Yoon SM, Ryoo BY, Lee SJ, Kim JH, Shin JH, An JH, Lee HC, Lim YS. Efficacy and safety of transarterial chemoembolization plus external beam radiotherapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: a randomized clinical trial. JAMA Oncol 2018;4(5):661–669

    Article  Google Scholar 

  7. Korean Liver Cancer A, National Cancer Center GK. 2018 Korean liver cancer association-National Cancer Center Korea practice guidelines for the management of hepatocellular carcinoma. Korean J Radiol 2019;20(7):1042–1113

    Article  Google Scholar 

  8. Zhou J, Sun HC, Wang Z, Cong WM, Wang JH, Zeng MS, Yang JM, Bie P, Liu LX, Wen TF, et al. Guidelines for diagnosis and treatment of primary liver cancer in China (2017 edition). Liver Cancer 2018;7(3):235–260

    Article  Google Scholar 

  9. Su TS, Liang P, Liang J, Lu HZ, Jiang HY, Cheng T, Huang Y, Tang Y, Deng X. Long-term survival analysis of stereotactic ablative radiotherapy versus liver resection for small hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2017;98(3):639–646

    Article  Google Scholar 

  10. Su T-S, Liang P, Zhou Y, Huang Y, Cheng T, Qu S, Chen L, Xiang B-D, Zhao C, Huang D-J, et al. Stereotactic body radiation therapy vs. transarterial chemoembolization in inoperable barcelona clinic liver cancer stage a hepatocellular carcinoma: a retrospective, propensity-matched analysis. Front Oncol 2020;10:347

    Article  CAS  Google Scholar 

  11. Wahl DR, Stenmark MH, Tao Y, Pollom EL, Caoili EM, Lawrence TS, Schipper MJ, Feng M. Outcomes after stereotactic body radiotherapy or radiofrequency ablation for hepatocellular carcinoma. J Clin Oncol 2016;34(5):452–459

    Article  CAS  Google Scholar 

  12. Bettinger D, Pinato DJ, Schultheiss M, Sharma R, Rimassa L, Pressiani T, Burlone ME, Pirisi M, Kudo M, Park JW, et al. Stereotactic body radiation therapy as an alternative treatment for patients with hepatocellular carcinoma compared to sorafenib: a propensity score analysis. Liver Cancer 2019;8(4):281–294

    Article  CAS  Google Scholar 

  13. Kim JY, Yoo EJ, Jang JW, Kwon JH, Kim KJ, Kay CS. Hypofractionated radiotheapy using helical tomotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis. Radiat Oncol 2013;8:15

    Article  CAS  Google Scholar 

  14. Chen SW, Lin LC, Kuo YC, Liang JA, Kuo CC, Chiou JF. Phase 2 study of combined sorafenib and radiation therapy in patients with advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2014;88(5):1041–1047

    Article  CAS  Google Scholar 

  15. Hou JZ, Zeng ZC, Wang BL, Yang P, Zhang JY, Mo HF. High dose radiotherapy with image-guided hypo-IMRT for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombi is more feasible and efficacious than conventional 3D-CRT. Jpn J Clin Oncol 2016;46(4):357–362

    Article  Google Scholar 

  16. Im JH, Yoon SM, Park HC, Kim JH, Yu JI, Kim TH, Kim JW, Nam TK, Kim K, Jang HS, et al. Response to Is radiotherapy the best option for treating hepatocellular carcinoma with PVTT? Liver Int 2017;37(2):308–309

    Article  Google Scholar 

  17. Xi M, Zhang L, Zhao L, Li QQ, Guo SP, Feng ZZ, Deng XW, Huang XY, Liu MZ. Effectiveness of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombosis. PLoS One 2013;8(5):e63864

    Article  CAS  Google Scholar 

  18. Yang JF, Lo CH, Lee MS, Lin CS, Dai YH, Shen PC, Chao HL, Huang WY. Stereotactic ablative radiotherapy versus conventionally fractionated radiotherapy in the treatment of hepatocellular carcinoma with portal vein invasion: a retrospective analysis. Radiat Oncol 2019;14(1):180

    Article  Google Scholar 

  19. Chopra S, George K, Engineer R, Rajamanickam K, Nojin S, Joshi K, Swamidas J, Shetty N, Patkar S, Patil P, et al. Stereotactic body radiotherapy for inoperable large hepatocellular cancers: results from a clinical audit. Br J Radiol 2019;92(1101):20181053

    Article  Google Scholar 

  20. Liu HY, Lee Y, McLean K, Leggett D, Hodgkinson P, Fawcett J, Mott R, Stuart K, Pryor D. Efficacy and toxicity of stereotactic body radiotherapy for early to advanced stage hepatocellular carcinoma—initial experience from an Australian Liver Cancer Service. Clin Oncol (R Coll Radiol) 2020;32(10):e194–e202

    Article  CAS  Google Scholar 

  21. Yadav HP, Kumar R, Gupta A, Thaper D, Kamal R, Kirti S. Efficacy and toxicity of SBRT in advanced hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective study. Int J Radiat Oncol 2020;108:E622–E622

    Article  Google Scholar 

  22. Rim CH, Kim CY, Yang DS, Yoon WS. Comparison of radiation therapy modalities for hepatocellular carcinoma with portal vein thrombosis: a meta-analysis and systematic review. Radiother Oncol 2018;129(1):112–122

    Article  Google Scholar 

  23. Sun J, Zhang T, Wang J, Li W, Zhang A, He W, Zhang D, Li D, Ding J, Duan X. Biologically effective dose (BED) of stereotactic body radiation therapy (SBRT) was an important factor of therapeutic efficacy in patients with hepatocellular carcinoma (≤ 5 cm). BMC Cancer 2019;19(1):846

    Article  Google Scholar 

  24. Su TS, Lu HZ, Cheng T, Zhou Y, Huang Y, Gao YC, Tang MY, Jiang HY, Lian ZP, Hou EC, et al. Long-term survival analysis in combined transarterial embolization and stereotactic body radiation therapy versus stereotactic body radiation monotherapy for unresectable hepatocellular carcinoma >5 cm. BMC Cancer 2016;16(1):834

    Article  Google Scholar 

  25. Scorsetti M, Comito T, Cozzi L, Clerici E, Tozzi A, Franzese C, Navarria P, Fogliata A, Tomatis S, D’Agostino G, et al. The challenge of inoperable hepatocellular carcinoma (HCC): results of a single-institutional experience on stereotactic body radiation therapy (SBRT). J Cancer Res Clin Oncol 2015;141(7):1301–1309

    Article  CAS  Google Scholar 

  26. Robbins JR, Schmid RK, Hammad AY, Gamblin TC, Erickson BA. Stereotactic body radiation therapy for hepatocellular carcinoma: practice patterns, dose selection and factors impacting survival. Cancer Med 2019;8(3):928–938

    Article  Google Scholar 

  27. Su TS, Luo R, Liang P, Cheng T, Zhou Y, Huang Y. A prospective cohort study of hepatic toxicity after stereotactic body radiation therapy for hepatocellular carcinoma. Radiother Oncol 2018;129(1):136–142

    Article  Google Scholar 

  28. Liang SX, Zhu XD, Xu ZY, Zhu J, Zhao JD, Lu HJ, Yang YL, Chen L, Wang AY, Fu XL, et al. Radiation-induced liver disease in three-dimensional conformal radiation therapy for primary liver carcinoma: the risk factors and hepatic radiation tolerance. Int J Radiat Oncol Biol Phys 2006;65(2):426–434

    Article  Google Scholar 

  29. Liang SX, Huang XB, Zhu XD, Zhang WD, Cai L, Huang HZ, Li YF, Chen L, Liu MZ. Dosimetric predictor identification for radiation-induced liver disease after hypofractionated conformal radiotherapy for primary liver carcinoma patients with Child–Pugh Grade A cirrhosis. Radiother Oncol 2011;98(2):265–269

    Article  Google Scholar 

  30. Xu ZY, Liang SX, Zhu J, Zhu XD, Zhao JD, Lu HJ, Yang YL, Chen L, Wang AY, Fu XL, et al. Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma. Int J Radiat Oncol Biol Phys 2006;65(1):189–195

    Article  Google Scholar 

Download references

Acknowledgements

This abstract was submitted in part as a conference presentation at the Chinese Conference on Oncology (CCO 2020) and the 23rd Annual Meeting of Chinese Society of Clinical Oncology (CSCO 2020) in China.

Funding

This research was supported by the National Natural Science Foundation of China (81903257), Guangxi Natural Science Foundation (2020GXNSFAA297171), China International Medical Foundation-Tumor Precise Radiotherapy Spark Program (2019-N-11-01), Guangxi Medical University Training Program for Distinguished Young Scholars, and Guangxi BaGui Scholars’ Special Fund.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, No.71, River Road, Nanning, 530001, Guangxi Zhuang Autonomous Region, China

    Li-Qing Li, Shi-Xiong Liang & Ting-Shi Su

  2. Department of Radiation Oncology, Rui Kang Hospital, Guangxi Traditional Chinese Medical University, Nanning, 530001, Guangxi Zhuang Autonomous Region, China

    Ying Zhou, Yong Huang & Ping Liang

Authors
  1. Li-Qing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yong Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ping Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shi-Xiong Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ting-Shi Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Data curation, YZ, YH, PL, L-QL, and T-SSu; formal analysis, L-QL, S-XL, and T-SS; funding acquisition, T-SS; writing—original draft, L-QL and T-SS; writing—review & editing, S-XL and T-SS.

Corresponding authors

Correspondence to Shi-Xiong Liang or Ting-Shi Su.

Ethics declarations

Conflict of interest

Li-Qing Li, Ying Zhou, Yong Huang, Ping Liang, Shi-Xiong Liang and Ting-Shi Su declare no conflict of interest.

Ethics approval and consent to participate

The study design was approved by the ethics review board of Guangxi Medical University Cancer Hospital (LW2020045). The requirement of written informed consent for participation was waived owing to the retrospective nature of the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 110 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, LQ., Zhou, Y., Huang, Y. et al. Stereotactic body radiotherapy versus intensity-modulated radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis. Hepatol Int 15, 630–641 (2021). https://doi.org/10.1007/s12072-021-10173-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-021-10173-y

Keywords

Search

Navigation