DOI QR코드

DOI QR Code

Is higher dose always the right answer in stereotactic body radiation therapy for small hepatocellular carcinoma?

  • Lee, Kyung Hwa (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Yu, Jeong Il (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Hee Chul (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Su Yeon (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Shin, Jung Suk (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Shin, Eun Hyuk (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Cho, Sungkoo (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jung, Sang Hoon (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Han, Young Yih (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lim, Do Hoon (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2018.01.03
  • Accepted : 2018.03.19
  • Published : 2018.06.30

Abstract

Purpose: This study was conducted to compare clinical outcomes and treatment-related toxicities after stereotactic body radiation therapy (SBRT) with two different dose regimens for small hepatocellular carcinomas (HCC) ${\leq}3cm$ in size. Materials and Methods: We retrospectively reviewed 44 patients with liver-confined HCC treated between 2009 and 2014 with SBRT. Total doses of 45 Gy (n = 10) or 60 Gy (n = 34) in 3 fractions were prescribed to the 95% isodose line covering 95% of the planning target volume. Rates of local control (LC), intrahepatic failure-free survival (IHFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Median follow-up was 29 months (range, 8 to 64 months). Rates at 1 and 3 years were 97.7% and 95.0% for LC, 97.7% and 80.7% for OS, 76% and 40.5% for IHFFS, and 87.3% and 79.5% for DMFS. Five patients (11.4%) experienced degradation of albumin-bilirubin grade, 2 (4.5%) degradation of Child-Pugh score, and 4 (9.1%) grade 3 or greater laboratory abnormalities within 3 months after SBRT. No significant difference was seen in any oncological outcomes or treatment-related toxicities between the two dose regimens. Conclusions: SBRT was highly effective for local control without severe toxicities in patients with HCC smaller than 3 cm. The regimen of a total dose of 45 Gy in 3 fractions was comparable to 60 Gy in efficacy and safety of SBRT for small HCC.

Keywords

References

  1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557-76. https://doi.org/10.1053/j.gastro.2007.04.061
  2. Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology 2005;42:1208-36. https://doi.org/10.1002/hep.20933
  3. Camma C, Schepis F, Orlando A, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 2002;224:47-54. https://doi.org/10.1148/radiol.2241011262
  4. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002;35:1164-71. https://doi.org/10.1053/jhep.2002.33156
  5. Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002;359:1734-9. https://doi.org/10.1016/S0140-6736(02)08649-X
  6. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003;37:429-42. https://doi.org/10.1053/jhep.2003.50047
  7. Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo) embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 2011;(3):CD004787.
  8. Kwon JH, Bae SH, Kim JY, et al. Long-term effect of stereotactic body radiation therapy for primary hepatocellular carcinoma ineligible for local ablation therapy or surgical resection: stereotactic radiotherapy for liver cancer. BMC Cancer 2010;10:475. https://doi.org/10.1186/1471-2407-10-475
  9. Andolino DL, Johnson CS, Maluccio M, et al. Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2011;81:e447-53. https://doi.org/10.1016/j.ijrobp.2011.04.011
  10. Kang JK, Kim MS, Cho CK, et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer 2012;118:5424-31. https://doi.org/10.1002/cncr.27533
  11. Bujold A, Massey CA, Kim JJ, et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 2013;31:1631-9. https://doi.org/10.1200/JCO.2012.44.1659
  12. Yoon SM, Lim YS, Park MJ, et al. Stereotactic body radiation therapy as an alternative treatment for small hepatocellular carcinoma. PLoS One 2013;8:e79854. https://doi.org/10.1371/journal.pone.0079854
  13. Scorsetti M, Comito T, Cozzi L, et al. The challenge of inoperable hepatocellular carcinoma (HCC): results of a singleinstitutional experience on stereotactic body radiation therapy (SBRT). J Cancer Res Clin Oncol 2015;141:1301-9. https://doi.org/10.1007/s00432-015-1929-y
  14. Huertas A, Baumann AS, Saunier-Kubs F, et al. Stereotactic body radiation therapy as an ablative treatment for inoperable hepatocellular carcinoma. Radiother Oncol 2015;115:211-6. https://doi.org/10.1016/j.radonc.2015.04.006
  15. Kimura T, Aikata H, Takahashi S, et al. Stereotactic body radiotherapy for patients with small hepatocellular carcinoma ineligible for resection or ablation therapies. Hepatol Res 2015;45:378-86. https://doi.org/10.1111/hepr.12359
  16. 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;122:2041-9. https://doi.org/10.1002/cncr.30008
  17. Korean Liver Cancer Study Group (KLCSG); National Cancer Center, Korea (NCC). 2014 Korean Liver Cancer Study Group- National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma. Korean J Radiol 2015;16:465-522. https://doi.org/10.3348/kjr.2015.16.3.465
  18. Jung SH, Yu JI, Park HC, Lim DH, Han Y. A feasibility study evaluating the relationship between dose and focal liver reaction in stereotactic ablative radiotherapy for liver cancer based on intensity change of Gd-EOB-DTPA-enhanced magnetic resonance images. Radiat Oncol J 2016;34:64-75. https://doi.org/10.3857/roj.2016.34.1.64
  19. Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol 2015;33:550-8. https://doi.org/10.1200/JCO.2014.57.9151
  20. Bae SH, Park HC, Lim DH, et al. Salvage treatment with hypofractionated radiotherapy in patients with recurrent small hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2012;82:e603-7. https://doi.org/10.1016/j.ijrobp.2011.09.053
  21. Yu JI, Park HC, Lim DH, Paik SW. Do biliary complications after hypofractionated radiation therapy in hepatocellular carcinoma matter? Cancer Res Treat 2016;48:574-82. https://doi.org/10.4143/crt.2015.076
  22. 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. https://doi.org/10.1016/j.prro.2015.02.007
  23. Toesca DA, Osmundson EC, von Eyben R, Shaffer JL, Koong AC, Chang DT. Assessment of hepatic function decline after stereotactic body radiation therapy for primary liver cancer. Pract Radiat Oncol 2017;7:173-82. https://doi.org/10.1016/j.prro.2016.10.003
  24. Velec M, Haddad CR, Craig T, et al. Predictors of liver toxicity following stereotactic body radiation therapy for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2017;97:939-46. https://doi.org/10.1016/j.ijrobp.2017.01.221

Cited by

  1. Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma vol.25, pp.20, 2019, https://doi.org/10.3748/wjg.v25.i20.2416
  2. Current status of stereotactic body radiotherapy for the treatment of hepatocellular carcinoma vol.36, pp.3, 2018, https://doi.org/10.12701/yujm.2019.00269
  3. Clinical significance of radiotherapy before and/or during nivolumab treatment in hepatocellular carcinoma vol.8, pp.16, 2018, https://doi.org/10.1002/cam4.2570
  4. A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy vol.126, pp.2, 2018, https://doi.org/10.1002/cncr.32502
  5. Comparison of clinical outcomes between passive scattering versus pencil-beam scanning proton beam therapy for hepatocellular carcinoma vol.146, pp.None, 2018, https://doi.org/10.1016/j.radonc.2020.02.019
  6. Clinical Significance of Systemic Inflammation Markers in Newly Diagnosed, Previously Untreated Hepatocellular Carcinoma vol.12, pp.5, 2018, https://doi.org/10.3390/cancers12051300
  7. Do Biliary Complications after Proton Beam Therapy for Perihilar Hepatocellular Carcinoma Matter? vol.12, pp.9, 2020, https://doi.org/10.3390/cancers12092395
  8. Stereotactic body radiation therapy for small (≤5 cm) hepatocellular carcinoma not amenable to curative treatment: Results of a single-arm, phase II clinical trial vol.26, pp.4, 2020, https://doi.org/10.3350/cmh.2020.0038
  9. Clinical outcomes of stereotactic body radiation therapy for small hepatocellular carcinoma vol.35, pp.11, 2020, https://doi.org/10.1111/jgh.15011
  10. Favorable response to multimodal treatment in hepatocellular carcinoma with inferior vena cava and right atrial tumor thrombus and left adrenal gland metastasis : A case report and literature review vol.100, pp.49, 2021, https://doi.org/10.1097/md.0000000000027987