Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
권호 표지
DOI QR코드

DOI QR Code

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma

  • Yu, Jeong Il (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Yoo, Gyu Sang (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, Youngyih (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Seyjoon (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Boram (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kang, Wonseok (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Sinn, Dong Hyun (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Paik, Yong-Han (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Gwak, Geum-Youn (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Choi, Moon Seok (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Joon Hyeok (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Koh, Kwang Cheol (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Paik, Seung Woon (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Hee Chul (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2017.08.16
  • Accepted : 2017.11.15
  • Published : 2018.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. Materials and Methods: HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of $62-92GyE_{10}$. Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. Conclusion: PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

Keywords

References

  1. Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol 2017;3:524-48. https://doi.org/10.1001/jamaoncol.2016.5688
  2. Kim BH, Lim YS, Kim EY, et al. Temporal improvement in survival of patients with hepatocellular carcinoma in a hepatitis B virus-endemic population. J Gastroenterol Hepatol 2018;33:475-83. https://doi.org/10.1111/jgh.13848
  3. Kudo M, Izumi N, Ichida T, et al. Report of the 19th followup survey of primary liver cancer in Japan. Hepatol Res 2016;46:372-90. https://doi.org/10.1111/hepr.12697
  4. Lencioni R, Petruzzi P, Crocetti L. Chemoembolization of hepatocellular carcinoma. Semin Intervent Radiol 2013;30:3-11. https://doi.org/10.1055/s-0033-1333648
  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. Cha H, Park HC, Yu JI, et al. Clinical practice patterns of radiotherapy in patients with hepatocellular carcinoma: a Korean Radiation Oncology Group study (KROG 14-07). Cancer Res Treat 2017;49:61-9. https://doi.org/10.4143/crt.2016.097
  7. Kim TH, Kim DY, Park JW, et al. Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with threedimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys 2007;67:225-31. https://doi.org/10.1016/j.ijrobp.2006.08.015
  8. Yu JI, Cho JY, Park HC, Lim DH, Gwak GY, Paik SW. Child-Pugh score maintenance in cirrhotic hepatocellular carcinoma patients after radiotherapy: aspects of gastroduodenal complications. Tumori 2014;100:645-51. https://doi.org/10.1177/1778.19270
  9. Yu JI, Park HC, Lim DH, Park WY. Predictive factors for Child-Pugh score elevation in hepatocellular carcinoma patients treated with conformal radiation therapy: dose-volume histogram analysis. Tumori 2013;99:164-71.
  10. Pan CC, Kavanagh BD, Dawson LA, et al. Radiationassociated liver injury. Int J Radiat Oncol Biol Phys 2010;76(3 Suppl):S94-100. https://doi.org/10.1016/j.ijrobp.2009.06.092
  11. Sakurai H, Ishikawa H, Okumura T. Proton beam therapy in Japan: current and future status. Jpn J Clin Oncol 2016;46:885-92. https://doi.org/10.1093/jjco/hyw102
  12. Bowen SR, Saini J, Chapman TR, et al. Differential hepatic avoidance radiation therapy: Proof of concept in hepatocellular carcinoma patients. Radiother Oncol 2015;115:203-10. https://doi.org/10.1016/j.radonc.2015.04.011
  13. Chung K, Han Y, Kim J, et al. The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center. Radiat Oncol J 2015;33:337-43. https://doi.org/10.3857/roj.2015.33.4.337
  14. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020-2. https://doi.org/10.1002/hep.24199
  15. Takamatsu S, Yamamoto K, Maeda Y, et al. Evaluation of focal liver reaction after proton beam therapy for hepatocellular carcinoma examined using Gd-EOB-DTPA enhanced hepatic magnetic resonance imaging. PLoS One 2016;11:e0167155. https://doi.org/10.1371/journal.pone.0167155
  16. 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
  17. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010;30:52-60. https://doi.org/10.1055/s-0030-1247132
  18. 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
  19. Cheng S, Chen M, Cai J; National Research Cooperative Group for Diagnosis and Treatment of Hepatocellular Carcinoma with Tumor Thrombus. Chinese expert consensus on multidisciplinary diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus: 2016 edition. Oncotarget 2017;8:8867-76.
  20. Park HC, Yu JI, Cheng JC, et al. Consensus for radiotherapy in hepatocellular carcinoma from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014): current practice and future clinical trials. Liver Cancer 2016;5:162-74. https://doi.org/10.1159/000367766
  21. Yu JI, Park JW, Park HC, et al. Clinical impact of combined transarterial chemoembolization and radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: an external validation study. Radiother Oncol 2016;118:408-15. https://doi.org/10.1016/j.radonc.2015.11.019
  22. Cho JY, Paik YH, Park HC, et al. The feasibility of combined transcatheter arterial chemoembolization and radiotherapy for advanced hepatocellular carcinoma. Liver Int 2014;34:795-801. https://doi.org/10.1111/liv.12445
  23. Kokudo T, Hasegawa K, Matsuyama Y, et al. Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. J Hepatol 2016;65:938-43. https://doi.org/10.1016/j.jhep.2016.05.044
  24. Lee JM, Jang BK, Lee YJ, et al. Survival outcomes of hepatic resection compared with transarterial chemoembolization or sorafenib for hepatocellular carcinoma with portal vein tumor thrombosis. Clin Mol Hepatol 2016;22:160-7. https://doi.org/10.3350/cmh.2016.22.1.160
  25. Keane FK, Wo JY, Zhu AX, Hong TS. Liver-directed radiotherapy for hepatocellular carcinoma. Liver Cancer 2016;5:198-209. https://doi.org/10.1159/000367764
  26. Wilson RR. Radiological use of fast protons. Radiology 1946;47:487-91. https://doi.org/10.1148/47.5.487
  27. Kim DY, Park JW, Kim TH, et al. Risk-adapted simultaneous integrated boost-proton beam therapy (SIB-PBT) for advanced hepatocellular carcinoma with tumour vascular thrombosis. Radiother Oncol 2017;122:122-9. https://doi.org/10.1016/j.radonc.2016.12.014
  28. Yoon H, Oh D, Park HC, et al. Predictive factors for gastroduodenal toxicity based on endoscopy following radiotherapy in patients with hepatocellular carcinoma. Strahlenther Onkol 2013;189:541-6. https://doi.org/10.1007/s00066-013-0343-0
  29. Kim H, Lim DH, Paik SW, et al. Predictive factors of gastroduodenal toxicity in cirrhotic patients after threedimensional conformal radiotherapy for hepatocellular carcinoma. Radiother Oncol 2009;93:302-6. https://doi.org/10.1016/j.radonc.2009.05.017
  30. Hong TS, Wo JY, Yeap BY, et al. Multi-institutional phase II study of high-dose hypofractionated proton beam therapy in patients with localized, unresectable hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol 2016;34:460-8.
  31. Kim TH, Park JW, Kim YJ, et al. Phase I dose-escalation study of proton beam therapy for inoperable hepatocellular carcinoma. Cancer Res Treat 2015;47:34-45.
  32. Oldrini G, Huertas A, Renard-Oldrini S, et al. Tumor response assessment by MRI following stereotactic body radiation therapy for hepatocellular carcinoma. PLoS One 2017;12:e0176118. https://doi.org/10.1371/journal.pone.0176118
  33. Weiner AA, Olsen J, Ma D, et al. Stereotactic body radiotherapy for primary hepatic malignancies: report of a phase I/II institutional study. Radiother Oncol 2016;121:79-85. https://doi.org/10.1016/j.radonc.2016.07.020
  34. Kim JW, Seong J, Lee IJ, Woo JY, Han KH. Phase I dose escalation study of helical intensity-modulated radiotherapybased stereotactic body radiotherapy for hepatocellular carcinoma. Oncotarget 2016;7:40756-66.

Cited by

  1. Proton therapy for hepatocellular carcinoma: Current knowledges and future perspectives vol.24, pp.28, 2018, https://doi.org/10.3748/wjg.v24.i28.3090
  2. Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma vol.25, pp.20, 2019, https://doi.org/10.3748/wjg.v25.i20.2416
  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. Development of a Daily-Treatment Beam-Monitoring System Based Gafchromic EBT3 Film for Pencil-Beam Scanning Proton Therapy vol.76, pp.8, 2018, https://doi.org/10.3938/jkps.76.769
  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. 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
  9. Current role of proton beam therapy in patients with hepatocellular carcinoma vol.10, pp.4, 2018, https://doi.org/10.18528/ijgii210043