Advertisement

Journal of Radiation Oncology

, Volume 3, Issue 2, pp 179–184 | Cite as

Association between changes in serum α-fetoprotein level and patterns of recurrence in patients undergoing carbon-ion radiotherapy for hepatocellular carcinoma

  • Takeshi Yanagi
  • Shigeo Yasuda
  • Hiroshi Imada
  • Shigeru Yamada
  • Hirotoshi Kato
  • Yuta Shibamoto
  • Tadashi Kamada
Original Research Article
  • 110 Downloads

Abstract

Objective

This study aims to assess the usefulness of monitoring serum α-fetoprotein (AFP) levels for predicting recurrence patterns in patients with hepatocellular carcinoma (HCC) treated with carbon-ion radiotherapy.

Methods

Consecutive 157 HCCs treated with definitive carbon-ion radiotherapy between April 1995 and March 2003 were evaluated. Serum AFP levels were measured before and at 3, 6, 12, and 18 months after treatment. Patterns of recurrence were categorized as local (in field), intrahepatic, or distant. Associations between clinical data and onset of recurrence were analyzed. Patients with AFP level of >20 ng/ml were defined as AFP positive.

Results

Follow-up periods were 4.1–66 months (median 35.4 months). Only in the AFP-positive patients, AFP reelevation was associated with the development of recurrence (p = 0.00). Although not statistically significant, patterns of AFP change tended to differ between intrahepatic failure and local failure; AFP levels tended to reelevate earlier in patients developing local failure. Pretreatment AFP of >50 ng/ml (p = 0.00) and total bilirubin of >1.6 mg/dl (p = 0.04) were predictive of development of intrahepatic recurrence within 6 months. AFP of >60 ng/ml (p = 0.00) and platelet of <70,000/mm3 (p = 0.01) were predictive of development of distant metastasis.

Conclusion

AFP monitoring was useful for patients with HCC treated with carbon-ion radiotherapy. Early AFP reelevation was suggestive of in-field local recurrence.

Keywords

Carbon-ion radiotherapy Hepatocellular carcinoma α-Fetoprotein Charged particle 

Notes

Conflict of interest

Takeshi Yanagi, Shigeo Yasuda, Hiroshi Imada, Shigeru Yamada, Hirotoshi Kato, Yuta Shibamoto, and Tadashi Kamada declare that they have no conflict of interest.

Ethical standards

This retrospective study was approved by the IRB of the NIRS. All three clinical trials involved have been approved by the IRB and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All patients gave their informed consent prior to their inclusion in the study.

References

  1. 1.
    Kayama T (2009) Cancer mortality rate by age and site 2008/2009. In: Foundation for Promotion of Cancer Research FPCR (ed) Cancer statistics in Japan 2010. FPCR, Tokyo, pp 66–69Google Scholar
  2. 2.
    Umemura T, Kiyosawa K (2006) Global epidemiology of liver cancer. In: Koike K (ed) Clinical gastroenterology. Hepatocellular carcinoma: update in diagnosis, treatment and prevention. Nihon Medical Center, Tokyo, pp 20–26Google Scholar
  3. 3.
    Khan K, Yatsuhashi H, Yamasaki K, Yamasaki M, Inoue O, Koga M et al (2000) Prospective analysis of risk factors for early intrahepatic recurrence of hepatocellular carcinoma following ethanol injection. J Hepatol 32:269–278PubMedCrossRefGoogle Scholar
  4. 4.
    Rossi S, Buscarini E, Garbagnati F, Di Stasi M, Quaretti P, Rago M et al (1998) Percutaneous treatment of small hepatic tumors by an expandable RF needle electrode. Am J Roentgenol 170:1015–1022CrossRefGoogle Scholar
  5. 5.
    Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Ierace T, Solbiati L et al (2000) Hepatocellular carcinoma: radiofrequency ablation of medium and large lesions. Radiology 214:761–768PubMedCrossRefGoogle Scholar
  6. 6.
    Kato H, Tsujii H, Miyamoto T, Mizoe JE, Kamada T, Tsuji H et al (2004) Results of first prospective study of carbon ion radiotherapy for hepatocellular carcinoma with liver cirrhosis. Int J Radiat Oncol Biol Phys 59:1468–1476PubMedCrossRefGoogle Scholar
  7. 7.
    Kato H, Yamada S, Yasuda S (2005) Phase II study of short-course carbon ion radiotherapy (52.8 GyE/4-fraction/1-week) for hepatocellular carcinoma. Hepatology 42(Suppl 1):381AGoogle Scholar
  8. 8.
    Imada H, Kato H, Yasuda S, Yamada S, Yanagi T, Kishimoto R et al (2010) Comparison of efficacy and toxicity of short-course carbon ion radiotherapy for hepatocellular carcinoma depending on their proximity to the porta hepatis. Radiother Oncol 96:231–235Google Scholar
  9. 9.
    Kanai T, Endo M, Minohara S, Miyahara N, Koyama-Ito H, Tomura H et al (1999) Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiotherapy. Int J Radiat Oncol Biol Phys 44:201–210PubMedCrossRefGoogle Scholar
  10. 10.
    Bergstrand CG, Czar B (1956) Demonstration of new protein fraction in serum from human fetus. Scand J Clin Lab Invest 8:174PubMedCrossRefGoogle Scholar
  11. 11.
    Halbrecht J, Klibanski C (1956) Identification of new normal embryonic haemoglobin. Nature 178:794PubMedCrossRefGoogle Scholar
  12. 12.
    Alpert E (1967) Human alpha-1 fetoprotein. In: Okuda K, Peters RL (eds) Hepatocellular carcinoma. Wiley, New York, pp 353–367Google Scholar
  13. 13.
    Chen DS, Sung JL (1977) Serum alpha-fetoprotein in hepatocellular carcinoma. Cancer 40:779–783PubMedCrossRefGoogle Scholar
  14. 14.
    Pompili M, Rapaccini GL, Luca F, Caturelli E, Astone A, Siena DA et al (1997) Risk factors for intrahepatic recurrence of hepatocellular carcinoma in cirrhotic patients treated by percutaneous ethanol injection. Cancer 79:1501–8PubMedCrossRefGoogle Scholar
  15. 15.
    Hsieh M, Lu S, Wang L, Su W, Lin Z, Chuang W et al (1992) Alpha-fetoprotein in patients with hepatocellular carcinoma after transcatheter arterial embolization. J Gastroenterol Hepatol 7:614–617PubMedCrossRefGoogle Scholar
  16. 16.
    Law AL, Ng WT, Lee MC, Chan AT, Fung KH, Li F et al (2012) Treatment of primary liver cancer using highly-conformal radiotherapy with kV-image guidance and respiratory control. Radiother Oncol 102:56–61PubMedCrossRefGoogle Scholar
  17. 17.
    Liang SX, Huang XB, Zhu XD, Zhang WD, Cai L, Huang HZ et al (2011) Dosimetric predictor identification for radiation-induced liver disease after hypofractionated conformal radiotherapy for primary liver carcinoma patients with Child-Pugh grade A cirrhosis. Radiother Oncol 98:265–269PubMedCrossRefGoogle Scholar
  18. 18.
    Fukumitsu N, Sugahara S, Nakayama H, Fukuda K, Mizumoto M, Abei M et al (2009) A prospective study of hypofractionated proton beam therapy for patients with hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 74:831–836PubMedCrossRefGoogle Scholar
  19. 19.
    The Liver Cancer Study Group of Japan (1994) Predictive factors for long term prognosis after partial hepatectomy for patients with hepatocellular carcinoma in Japan. Cancer 74:2772–2780CrossRefGoogle Scholar
  20. 20.
    Bisceglie AMD, Hoofnagle JH (1989) Elevations in serum alpha-fetoprotein levels in patients with chronic hepatitis B. Cancer 64:2117–2120PubMedCrossRefGoogle Scholar
  21. 21.
    Belghiti J, Panis Y, Farges O, Benhamou JP, Fekete F et al (1991) Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis. Ann Surg 214:114–117PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Livraghi T, Giorgio A, Marin G, Salmi A, de Sio I, Bolondi L et al (1995) Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection. Radiology 197:101–108PubMedGoogle Scholar
  23. 23.
    Yoshida H, Arakawa Y, Sata M, Nishiguchi S, Yano M, Fujiyama S (2002) Interferon therapy prolonged life expectancy among chronic hepatitis C patients. Gastroenterology 123:483–491PubMedCrossRefGoogle Scholar
  24. 24.
    Watanabe A, Miyazaki M, Taketa K (1976) Prompt elevation of rat serum α-fetoprotein by acute liver injury following a single injection of ethionine. Int J Cancer 17:518–524PubMedCrossRefGoogle Scholar
  25. 25.
    Imada H, Kato H, Yasuda S, Yamada S, Yanagi T, Hara R (2010) Compensatory enlargement of the liver after treatment of hepatocellular carcinoma with carbon ion radiotherapy—relation to prognosis and liver function. Radiother Oncol 96:236–242PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Takeshi Yanagi
    • 1
  • Shigeo Yasuda
    • 2
  • Hiroshi Imada
    • 2
  • Shigeru Yamada
    • 2
  • Hirotoshi Kato
    • 3
  • Yuta Shibamoto
    • 1
  • Tadashi Kamada
    • 2
  1. 1.Department of RadiologyNagoya City University Graduate School of Medical SciencesNagoya CityJapan
  2. 2.Research Center Hospital for Charged Particle TherapyNational Institute of Radiological SciencesChiba City, Chiba PrefectureJapan
  3. 3.Kato Medical ClinicTokyoJapan

Personalised recommendations