DOI QR코드

DOI QR Code

Hypofractionated Radiotherapy for Small-sized Hepatocellular Carcinoma as Salvage Therapy: Sustained Local Control and Safety

작은 크기의 재발성 간세포암에 대한 구제치료로 소분할 방사선치료: 국소 제어율과 안전성

  • Bae, Sun-Hyun (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) ;
  • Lim, Do-Hoon (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Jung-Ae (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Choi, Moon-Seok (Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Joon-Hyoek (Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Koh, Kwang-Cheol (Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Paik, Seung-Woon (Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Yoo, Byung-Chul (Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 배선현 (성균관대학교 의과대학 삼성서울병원 방사선종양학교실) ;
  • 박희철 (성균관대학교 의과대학 삼성서울병원 방사선종양학교실) ;
  • 임도훈 (성균관대학교 의과대학 삼성서울병원 방사선종양학교실) ;
  • 이정애 (성균관대학교 의과대학 삼성서울병원 방사선종양학교실) ;
  • 최문석 (성균관대학교 의과대학 삼성서울병원 내과학교실) ;
  • 이준혁 (성균관대학교 의과대학 삼성서울병원 내과학교실) ;
  • 고광철 (성균관대학교 의과대학 삼성서울병원 내과학교실) ;
  • 백승운 (성균관대학교 의과대학 삼성서울병원 내과학교실) ;
  • 유병철 (성균관대학교 의과대학 삼성서울병원 내과학교실)
  • Received : 2010.04.29
  • Accepted : 2010.06.03
  • Published : 2010.06.30

Abstract

Purpose: To evaluate the rate of tumor response, local control, and treatment-related complications after hypofractionated radiotherapy for recurrent hepatocelluar carcinoma (HCC) less than 5 cm in size. Materials and Methods: Among the HCC patients who were treated by radiotherapy (RT) between 2006 and 2007 after the failure of previous treatment, a total of 12 patients were treated with hypofractionated RT. The criteria for hypofractionated RT was as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to a critical organ, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that irradiated 50% of the prescribed dose. Hypofractionated RT was performed with 50 Gy delivered in 10 fractions, at a rate of 5 fractions per week. The evaluation of tumor response was determined by CT scans performed at 3 months after the cessation of RT, followed by the evaluation of toxicity by Common Terminology Criteria for Adverse Events version 3.0. The median follow-up period after radiotherapy was 18 months. Results: A complete response (CR) was achieved in 5 of 12 lesions (41.7%) at CT performed at 3 months after the cessation, whereas the overall complete response was observed in 7 of 12 cases (58.3%). In-field local control rate was sustained in 83.3% of patients. All patients developed intra-hepatic metastases except for 2 patients. The overall survival rate was 90.0% at 1 year and 67.5% at 2 years, respectively. Three patients developed Grade 1 nausea during RT and 1 patient showed a progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusion: Hypofractionated RT for small-sized HCC as a salvage therapy showed a 58.3% CR rate and 83.3% of local control. Fifty Gy administered in 10 fractions of partial liver irradiation is considered as a tolerable dose that does not cause severe complications.

목 적: 크기가 작은 5 cm 미만의 재발성 간세포암 환자를 대상으로 소분할 방사선치료 후 종양의 반응, 국소제어율 및 소분할 방사선치료와 연관된 부작용을 평가하였다. 대상 및 방법: 2006년부터 2007년까지 국소요법으로 치료한 후 재발한 간세포암 환자 중 구제치료로 소분할 방사선치료를 받은 12명의 환자를 대상으로 후향적 분석을 시행하였다. 소분할 방사선치료의 적용기준은 종양의 크기가 5 cm 미만이고, 중요 정상조직에 인접하지 않으면서, 간세포암에 의한 간문맥 종양 혈전증이 없으며, 처방된 방사선량의 50%가 조사되는 정상 간 용적이 15% 미만인 경우로 제한하였다. 소분할 방사선치료의 1회 조사량은 5 Gy였고, 주 5회 치료하여 2주 동안 총 50 Gy를 조사하였다. 종양의 반응도는 방사선치료 종료 후 3개월에 시행된 간 컴퓨터단층촬영으로 평가하였다. 치료와 연관된 부작용은 Common Terminology Criteria for Adverse Events version 3.0으로 평가하였다. 방사선치료 종료 후 추적관찰기간은 8~33개월(중앙값 18개월)이었다. 결 과: 방사선치료 후 3개월에 시행한 간 컴퓨터단층촬영에서 완전관해율은 41.7%였고 추적관찰기간에 확인한 전체 완전관해율은 58.3%였다. 방사선치료 부위 내 국소제어율은 83.3%였다. 두 명을 제외한 모든 환자에서 간 내 재발이 발생하였다. 전체 환자의 1년 및 2년 생존율은 각각 90.0%, 67.5%였다. 치료와 연관된 부작용은 3명의 환자가 치료 중 1도의 오심, 식욕부진이 발생하였고 방사선치료 종료 후 복수가 진행한 환자가 1명 있었다. 3도 이상의 중대한 부작용은 없었다. 결 론: 작은 크기의 재발성 간세포암의 구제 치료로서 소분할 방사선치료는 58.3%의 완전관해율과 83.3%의 국소 제어율을 보여주었다. 소분할 방사선치료로 5 Gy씩 총 50 Gy를 조사하는 것은 치료와 연관된 심각한 독성 없이 비교적 안전하고 효과적인 방법으로 판단된다.

Keywords

References

  1. Okuda K, Ohtsuki T, Obata H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment: study of 850 patients. Cancer 1985;56:918-928 https://doi.org/10.1002/1097-0142(19850815)56:4<918::AID-CNCR2820560437>3.0.CO;2-E
  2. Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma: conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001;35:421-430 https://doi.org/10.1016/S0168-8278(01)00130-1
  3. Liver Cancer Study Group of Japan. Primary liver cancer in Japan: clinicopathologic features and results of surgical treatment. Ann Surg 1990;211:277-287
  4. Yamanaka N, Okamoto E, Toyosaka A, et al. Prognostic factors after hepatectomy for hepatocellular carcinomas: a univariate and multivariate analysis. Cancer 1990;65:1104-1110 https://doi.org/10.1002/1097-0142(19900301)65:5<1104::AID-CNCR2820650511>3.0.CO;2-G
  5. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005;42:1208-1236 https://doi.org/10.1002/hep.20933
  6. Korean Liver Cancer Study Group and National Cancer Center, Korea. Practice guidelines for management of hepatocellular carcinoma 2009. Korean J Hepatol 2009;15: 391-423 https://doi.org/10.3350/kjhep.2009.15.3.391
  7. 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
  8. Ingold JA, Reed GB, Kaplan HS, Bagshaw MA. Radiation Hepatitis. Am J Roentgenol Radium Ther Nucl Med 1965;93:200-208
  9. Lawrence TS, Robertson JM, Anscher MS, Jirtle RL, Ensminger WD, Fajardo LF. Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 1995;31: 1237-1248 https://doi.org/10.1016/0360-3016(94)00418-K
  10. Seong J. Challenge and hope in radiotherapy of hepatocellular carcinoma. Yonsei Med J 2009;50:601-612 https://doi.org/10.3349/ymj.2009.50.5.601
  11. Seong J, Lee IJ, Shim SJ, et al. A multicenter retrospective cohort study of practice patterns and clinical outcome on radiotherapy for hepatocellular carcinoma in Korea. Liver Int 2009;29:147-152 https://doi.org/10.1111/j.1478-3231.2008.01873.x
  12. Choi BO, Jang HS, Kang KM, et al. Fractionated stereotactic radiotherapy in patients with primary hepatocellular carcinoma. Jpn J Clin Oncol 2006;36:154-158 https://doi.org/10.1093/jjco/hyi236
  13. Choi BO, Kang KM, Jang HS, et al. Effects of fractionated stereotactic radiotherapy for primary hepatocellular carcinoma. J Korean Soc Ther Radiol Oncol 2005;23:92-97
  14. Herfarth KK, Debus J, Lohr F, et al. Stereotactic singledose radiation therapy of liver tumors: results of a phase I/II trial. J Clin Oncol 2001;19:164-170
  15. Leksell L. The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 1951;102:316-319
  16. Takeda A, Takahashi M, Kunieda E, et al. Hypofractionated stereotactic radiotherapy with and without transarterial chemoembolization for small hepatocellular carcinoma not eligible for other ablation therapies: preliminary results for efficacy and toxicity. Hepatol Res 2008;38:60-69 https://doi.org/10.1111/j.1872-034X.2007.00084.x
  17. Tse RV, Hawkins M, Lockwood G, et al. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol 2008;26:657-664 https://doi.org/10.1200/JCO.2007.14.3529
  18. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981;47:207-214 https://doi.org/10.1002/1097-0142(19810101)47:1<207::AID-CNCR2820470134>3.0.CO;2-6
  19. Krishnan S, Dawson LA, Seong J, et al. Radiotherapy for hepatocellular carcinoma: an overview. Ann Surg Oncol 2008; 15:1015-1024 https://doi.org/10.1245/s10434-007-9729-5
  20. Dawson LA, Eccles C, Craig T. Individualized image guided iso-NTCP based liver cancer SBRT. Acta Oncol 2006; 45:856-864 https://doi.org/10.1080/02841860600936369
  21. Lax I, Blomgren H, Naslund I, Svanstrom R. Stereotactic radiotherapy of malignancies in the abdomen: methodological aspects. Acta Oncol 1994;33:677-683 https://doi.org/10.3109/02841869409121782
  22. Lencioni RA, Allgaier HP, Cioni D, et al. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 2003;228:235-240 https://doi.org/10.1148/radiol.2281020718
  23. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma ${\leq}4$ cm. Gastroenterology 2004;127:1714-1723 https://doi.org/10.1053/j.gastro.2004.09.003
  24. Livraghi T, Lazzaroni S, Meloni F. Radiofrequency thermal ablation of hepatocellular carcinoma. Eur J Ultrasound 2001;13:159-166 https://doi.org/10.1016/S0929-8266(01)00128-8
  25. Kim H, Rhim H, Choi D, et al. Recurrence and treatment pattern in long-term survivors with hepatocellular carcinoma: a comparison between radiofrequency ablation and surgery as a first-line treatment. World J Surg 2010 Apr 8 [Epub]. DOI: 10.1007/s00268-010-0533-1
  26. Oh D, Lim DH, Park HC, et al. Early three-dimensional conformal radiotherapy for patients with unresectable hepatocellular carcinoma after incomplete transcatheter arterial chemoembolization: a prospective evaluation of efficacy and toxicity. Am J Clin Oncol 2010 Apr 15 [Epub]. DOI: 10.1097/ COC.0b013e3181b0c298