Vol 26, No 4 (2021)
Research paper
Published online: 2021-04-09

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Efficacy and toxicity of SBRT in advanced hepatocellular carcinoma with portal vein tumor thrombosis — a retrospective study

Rishabh Kumar1, Hanuman Prasad Yadav2, Deepak Thaper1, Rose Kamal1, Anil Gupta1, Kirti S.1
DOI: 10.5603/RPOR.a2021.0048
Rep Pract Oncol Radiother 2021;26(4):573-581.

Abstract

BACKGROUND: The purpose of this study was to evaluate the outcome of stereotactic body radiation therapy (SBRT) in patients of unresectable hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombosis (PVTT) who are also unsuitable for other locoregional therapies.

MATERIALS AND METHODS: Between May 2018 and January 2020, twenty-nine patients with advanced unresectable HCCs, treated with SBRT, were enrolled in this retrospective audit. Patients of Child status A5-B7 and with healthy liver volume, ≥ 700 ccs were treated. Local control (LC), overall survival (OS), progression-free survival (PFS), PVTT opening rate, and effect of prognostic factors were analyzed.

RESULTS: The median tumor diameter was 8.6 cm (5–14), and the median tumor volume was 275 cc (151–1196). The median SBRT dose prescription was 48 Gy in 6 fractions (32–50 Gy in 5–6 fractions). The median follow up was eight months (1–20), 1-year local control, progression-free survival, and overall survival were 95%, 53.4%, and 60%, respectively. Overall rate of grade III toxicity was less than 5%, and the most common toxicity was lymphocytopenia. Tumors of more than 350cc had worse OS and PFS when compared to tumors < 350 cc (median OS and PFS of tumors > 350 cc was 4 months and two months, p = .01 and .003, respectively). A total of fifteen patients progressed with the disease and the median time to progression was two months [1–4].

CONCLUSION: SBRT is safe and provides excellent local control in advanced HCC complicated with PVTT. The out of field failure pattern and time to failure in these patients highlights the need for adjuvant systemic therapy after completion of local treatment. Our data warrant the need for multimodality trials in this patient cohort.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1): 7–30.
  2. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394–424.
  3. Zhang Zm, Lai ECH, Zhang C, et al. The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus. Int J Surg. 2015; 20: 8–16.
  4. Llovet JM, Ricci S, Mazzaferro V, et al. SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359(4): 378–390.
  5. Bruix J, Raoul JL, Sherman M, 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.
  6. El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017; 389(10088): 2492–2502.
  7. A Study of Nivolumab in Combination With Ipilimumab in Participants With Advanced Hepatocellular Carcinoma — Full Text View — ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04039607 (04/29/2020).
  8. A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma [IMbrave150] — Full Text View — ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03434379 (04/29/2020).
  9. The general rules for the clinical and pathological study of primary liver cancer. Liver Cancer Study Group of Japan. Jpn J Surg. 1989; 19(1): 98–129.
  10. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009; 10(1): 25–34.
  11. Cheng AL, Guan Z, Chen Z, 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.
  12. Bruix J, Raoul JL, Sherman M, 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.
  13. Xue TC, Xie XY, Zhang L, et al. Transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a meta-analysis. BMC Gastroenterol. 2013; 13: 60.
  14. Leng JJ, Xu YZ, Dong JH. Efficacy of transarterial chemoembolization for hepatocellular carcinoma with portal vein thrombosis: a meta-analysis. ANZ J Surg. 2016; 86(10): 816–820.
  15. Kokudo T, Hasegawa K, Matsuyama Y, et al. Liver Cancer Study Group of Japan. Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. J Hepatol. 2016; 65(5): 938–943.
  16. Rim CH, Kim CY, Yang DS, et al. 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.
  17. Gupta A, Kumar R, Yadav HP, et al. Feasibility of 4D CT simulation with synchronized intravenous contrast injection in hepatocellular carcinoma. Rep Pract Oncol Radiother. 2020; 25(2): 293–298.
  18. Thaper D, Kamal R, Singh G, et al. Dosimetric comparison of dynamic conformal arc integrated with segment shape optimization and variable dose rate versus volumetric modulated arc therapy for liver SBRT. Rep Pract Oncol Radiother. 2020; 25(4): 667–677.
  19. Xi M, Zhang Li, Zhao L, et al. Effectiveness of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombosis. PLoS One. 2013; 8(5): e63864.
  20. Jang WI, Kim MS, Seo YS, et al. A Multicenter Phase II Study of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma. Int J Radiat Oncol Biol Phys. 2016; 96(5): 941.
  21. Kang J, Nie Q, DU R, et al. Stereotactic body radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombosis. Mol Clin Oncol. 2014; 2(1): 43–50.
  22. Chopra S, George K, Engineer R, et al. Stereotactic body radio therapy for inoperable large hepatocellular cancers: results from a clinical audit. Br J Radiol. 2019; 92(1101): 20181053.
  23. Huang YJ, Hsu HC, Wang CY, et al. The treatment responses in cases of radiation therapy to portal vein thrombosis in advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2009; 73(4): 1155–1163.
  24. Matsuo Y, Yoshida K, Nishimura H, et al. Efficacy of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis/inferior vena cava tumor thrombosis: evaluation by comparison with conventional three-dimensional conformal radiotherapy. J Radiat Res. 2016; 57(5): 512–523.
  25. Shui Y, Yu W, Ren X, et al. Stereotactic body radiotherapy based treatment for hepatocellular carcinoma with extensive portal vein tumor thrombosis. Radiat Oncol. 2018; 13(1): 188.
  26. Subbotin VM. Privileged portal metastasis of hepatocellular carcinoma in light of the coevolution of a visceral portal system and liver in the chordate lineage: a search for therapeutic targets. Drug Discov Today. 2018; 23(3): 548–564.
  27. Schaub SK, Hartvigson PE, Lock MI, et al. Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Current Trends and Controversies. Technol Cancer Res Treat. 2018; 17: 1533033818790217.
  28. Chadha AS, Liu G, Chen HC, et al. Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy? Int J Radiat Oncol Biol Phys. 2017; 97(2): 323–332.
  29. Basler L, Andratschke N, Ehrbar S, et al. Modelling the immunosuppressive effect of liver SBRT by simulating the dose to circulating lymphocytes: an in-silico planning study. Radiat Oncol. 2018; 13(1): 10.
  30. Zhao Q, Wang R, Liu T, et al. PO-0687: Spleen dosimetry are associated with lymphopenia during radiotherapy for hepatocellular carcinoma. Radiother Oncol. 2017; 123: S359.
  31. Liu HY, Lee Y, McLean K, et al. 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.