A Case Report of Recurred Hepatocellular Carcinoma Patient Treated with Radio-Frequency Hyperthermia in Conjunction with Sorafenib

고주파 온열치료와 소라페닙을 병용하여 호전된 재발성 간암환자 1례

  • Kim, Jee-Hye (East West Cancer Center, Dunsan Korean Medicine Hospital of Daejeon University) ;
  • Lee, Jong-Hoon (Integrative Cancer Center, Woosuk Korean Medicine Hospital of Woosuk University) ;
  • Joo, Jong-Cheon (Integrative Cancer Center, Jeonju Korean Medicine Hospital of Wonkwang University) ;
  • Lee, Jeong-Bok (East West Cancer Center, Dunsan Korean Medicine Hospital of Daejeon University) ;
  • Cho, Chong-Kwan (East West Cancer Center, Dunsan Korean Medicine Hospital of Daejeon University) ;
  • Yoo, Hwa-Seung (East West Cancer Center, Dunsan Korean Medicine Hospital of Daejeon University)
  • 김지혜 (대전대학교 둔산한방병원 동서암센터) ;
  • 이종훈 (우석대학교 한방병원 통합암센터) ;
  • 주종천 (원광대학교 전주한방병원 통합암센터) ;
  • 이정복 (대전대학교 둔산한방병원 동서암센터) ;
  • 조종관 (대전대학교 둔산한방병원 동서암센터) ;
  • 유화승 (대전대학교 둔산한방병원 동서암센터)
  • Received : 2016.11.18
  • Accepted : 2016.12.05
  • Published : 2016.12.30


Objective : The purpose of this study is to report the effects of radio-frequency hyperthermia cancer treatment in conjunction with Sorafenib on hepatocellular carcinoma patient. Method : The patient was diagnosed with hepatocellular carcinoma at S6/7 and treated with right posterior sectionectomy. After 4 months, tumor recurrence was found at S4, 5 and 8. After transarterial chemoembolization, the patient was prescribed Sorafenib (proprietary name $Nexavar^{(R)}$ ) as well as proceeding with radio-frequency hyperthermia. The clinical outcomes were measured by computed tomography, laboratory findings including tumor markers (AFP, PIVKA-II), natural killer (NK) cell activity, and numeric rating scales (NRS). Results : After the treatment, tumor size was decreased accompanying by reducing the level of tumor markers (AFP, PIVKA-II). Major clinical symptoms were improved with increasing NK cell activity. There were no adverse events based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Conclusion : This case suggests that radio-frequency hyperthermia has synergistic effect for the treatment of hepatocellular carcinoma patient in conjunction with Sorafenib.


Supported by : 대전대학교


  1. 이효석, 이정훈, 서경석, 임호경. 종양학. 일조각. 2012. p.339.
  2. 보건복지부, 중앙암등록본부, 국립암센터. 국가암등록사업 연례보고서(2013년 암등록통계). 2015.
  3. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64(19):7099-7109.
  4. Chang YS, Adnane J, Trail PA, Levy J, Henderson A, Xue D et al. Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol. 2007;59(5):561-574.
  5. Keating GM, Santoro A. Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs. 2009;69(2):223-240.
  6. Ito Y, Sasaki Y, Horimoto M, Wada S, Tanaka Y, Kasahara A et al. Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma. Hepatology. 1998 Apr;27(4):951-958.
  7. 바이엘코리아. 넥사바(R)정 200mg 제품설명서. 2014. available at
  8. van der Zee J. Heating the patient: a promising approach? Ann Oncol. 2002;13(8):1173-1184.
  9. Falk MH, Issels RD. Hyperthermia in oncology. Int J Hyperthermia. 2001 Jan-Feb;17(1):1-18.
  10. G Baronzio, A Gramaglia, G Fiorentini. Hyperthermia and immunity. A brief overview. In Vivo, 2006;20:689-695.
  11. Vernon CC, Hand JW, Field SB, Machin D, Whaley JB, van der Zee J. Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Collaborative Hyperthermia Group. Int J Radiat Oncol Biol Phys 1996;35:731-744.
  12. Sneed PK, Stauffer PR, McDermott MW, Diederich CJ, Lamborn KR, Prados MD et al. Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost ${\pm}$ hyperthermia for glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 1998;40:287-295.
  13. Berdov BA, Menteshashvili GZ. Thermoradiotherapy of patients with locally advanced carcinoma of the rectum. Int J Hyperthermia. 1990;6(5):881-890.
  14. van der Zee J, Gonzalez Gonzalez D, van Rhoon GC, van Dijk JD, van Putten WL, Hart AA. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Lancet. 2000;355:1119-1125.
  15. Colombo R, Da Pozzo LF, Lev A, Freschi M, Gallus G, Rigatti P. Neoadjuvant combined microwave induced local hyperthermia and topical chemotherapy versus chemotherapy alone for superficial bladder cancer. J Urol. 1996;155:1227-1232.
  16. Overgaard J, Gonzalez Gonzalez D, Hulshof MC, Arcangeli G, Dahl O, Mella O, et al. Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. Lancet. 1995;345:540-543.
  17. Gadaleta-Caldarola G, Infusino S, Galise I, Ranieri G, Vinciarelli G, Fazio V. Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study. Oncol Lett. 2014;8(4):1783-1787.
  18. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours:Revised RECIST guideline (version1.1). Eur J Cancer 2009;45:228-247.
  19. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v.4.0, 2010. Available at
  20. 대한간암학회, 국립암센터. 2014 간세포 암종 진료 가이드라인. available at
  21. Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg. 1999;229(2):216-222.
  22. Poon RT Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer. 2000;89(3):500-507.<500::AID-CNCR4>3.0.CO;2-O
  23. Shimada M, Takenaka K, Gion T, Fujiwara Y, Kajiyama K, Maeda T et al. Prognosis of recurrent hepatocellular carcinoma: a 10-year surgical experience in Japan. Gastroenterology. 1996 Sep;111(3):720-726.
  24. Itamoto, T. Nakahara, H, Amano, H; Kohashi, T. Ohdan, H. Tashiro, H et al. Repeat hepatectomy for recurrent hepatocellular carcinoma. 2007;141(5):589-597.
  25. Matsuda, M, Fujii, H. Kono, H, Matsumoto, Y. Surgical treatment of recurrent hepatocellular carcinoma based on the mode of recurrence: repeat hepatic resection or ablation are good choices for patients with recurrent multicentric cancer. Journal of Hepato-biliary-pancreatic Surgery. 2001;8(4):353-359.
  26. Sugimachi K, Maehara S, Tanaka S, Shimada M, Sugimachi K. Repeat hepatectomy is the most useful treatment for recurrent hepatocellular carcinoma. Journal of Hepato-biliary-pancreatic Surgery, 2001;8(5):410-416.
  27. Tralhão JG, Dagher I, Lino T, Roudie J, Franco D. Treatment of tumour recurrence after resection of hepatocellular carcinoma. Analysis of 97 consecutive patients. Eur J Surg Oncol. 2007;33(6):746-751.
  28. Wu CC, Cheng SB, Yeh DC, Wang J, P'eng FK. Second and third hepatectomies for recurrent hepatocellular carcinoma are justified. Br J Surg. 2009;96(9):1049-1057
  29. Zhou Y, Sui C, Li B, Yin Z, Tan Y, Yang J et al. Repeat hepatectomy for recurrent hepatocellular carcinoma: a local experience and a systematic review. World Journal of Surgical Oncology. 2010;8:55. doi: 10.1186/1477-7819-8-55.
  30. Okazaki M, Yamasaki S, Ono H, et al. Chemoembolotherapy for recurrent hepatocellular carcinoma in the residual liver after hepatectomy. Hepatogastroenterology. 1993;40:320-323.
  31. Takayasu K, Wakao F, Moriyama N, et al. Postresection recurrence of hepatocellular carcinoma treated by arterial embolization: analysis of prognostic factors. Hepatology. 1992;16:906-911.
  32. Poon RT, Fan ST, Lo CM, et al. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg. 1999;229:216-222.
  33. Nakao N, Kamino K, Miura K, et al. Recurrent hepatocellular carcinoma after partial hepatectomy: value of treatment with transcatheter arterial chemoembolization. AJR Am J Roentgenol. 1991;156:1177-1179.
  34. Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006;24:4293-4300.
  35. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al. Josep M. Sorafenib in Advanced Hepatocellular Carcinoma. N Engl J Med. 2008;359:378-390.
  36. 김달호, 이종성. 황제내경소문(전). 의성당. 2001. p.255-258.
  37. 이정행, 이은식, 박원희. 신세포암세포주의 성장에 대한 온열요법의 효과. 대한비뇨기과학회지. 1998;39(4):333-338.
  38. 박병섭. 암 치료에 있어 온열요법 (hyperthermia)의 적용에 관한 문헌적 고찰. 김천대학교 논문집. 1998;19:33-53.
  39. Gibbs FA Jr. Regional hyperthermia: a clinical appraisal of noninvasive deep-heating methods. Cancer Res. 1984;44(10):4765-4770.
  40. Kainuma O, Asano T, Aoyama H, Takayama W, Nakagohri T, Kenmochi T et al. Combined therapy with radiofrequency thermal ablation and intra-arterial infusion chemotherapy for hepatic metastases from colorectal cancer. Hepatogastroenterology. 1999;46(26):1071-1077.
  41. Sun J, Guo M, Pang H, Qi J, Zhang J, Ge Y. Treatment of malignant glioma using hyperthermia. Neural Regen Res. 2013 Oct 15;8(29):2775-2782.
  42. Abe M, Hiraoka M, Takahashi M, Egawa S, Matsuda C, Onoyama Y et al. Multi-institutional studies on hyperthermia using an 8-MHz radiofrequency capacitive heating device (Thermotron RF-8) in combination with radiation for cancer therapy. Cancer. 1986;15;58(8):1589-1595.<1589::AID-CNCR2820580802>3.0.CO;2-B
  43. Piotrkowicz N, Zielinski J, Jonska J, Roszkowska K, Debicki P, Lyczek J. Intracavitary 500KHZ hyperthermia treatment of patients with endometrial and cervical cancer-preliminary clinical and pathological results. Ginekol Pol. 2003 ;74(9):824-829.
  44. Piotrkowicz N, Zielinski J, Jonska J, Debicki P. 500 kHz hyperthermia assisted HDR brachytherapy in the treatment of recurrent cervical and endometrial cancer in previously irradiated fields. Reports of Practical Oncology & Radiotherapy. 2005;10(3):131-134.
  45. T Takeda, T Takahashi, I Yamamoto, T Hasegawa, T Takeda, H Takeda. Hyperthermia Enhances Immunotherapy in Cancer Patients : Clinical and Experimental Analyses. Thermal Medicine. 2012;28(1):11-16.
  46. 윤해창, 강지영, 김준영, 정진용, 손창규, 이남헌 외. 암 환자에 대한 구법의 치료와 메커니즘에 대한 최신 국내외 연구 현황. 대한한방내과학회지. 2015;36(3):361-379.
  47. Hiraoka M, Nishimura Y, Masunaga S, Nagata Y, Mitsumori M, Koishi M et al. Current status of thermoradiotherapy in cancer therapy. Gan To Kagaku Ryoho. 1993 ;20(5):591-596.
  48. Nishimura Y, Hiraoka M, Jo S, Abe M, Terashima H, Tsuchiya T et al. Clinical results of hyperthermia alone in the treatment of refractory human tumors. Nihon Gan Chiryo Gakkai Shi. 1989;24(10):2436-2440.