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.
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References
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 66–69
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 20–26
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 32:269–278
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 170:1015–1022
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 214:761–768
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 59:1468–1476
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):381A
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 96:231–235
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 44:201–210
Bergstrand CG, Czar B (1956) Demonstration of new protein fraction in serum from human fetus. Scand J Clin Lab Invest 8:174
Halbrecht J, Klibanski C (1956) Identification of new normal embryonic haemoglobin. Nature 178:794
Alpert E (1967) Human alpha-1 fetoprotein. In: Okuda K, Peters RL (eds) Hepatocellular carcinoma. Wiley, New York, pp 353–367
Chen DS, Sung JL (1977) Serum alpha-fetoprotein in hepatocellular carcinoma. Cancer 40:779–783
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 79:1501–8
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 7:614–617
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 102:56–61
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 98:265–269
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 74:831–836
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 74:2772–2780
Bisceglie AMD, Hoofnagle JH (1989) Elevations in serum alpha-fetoprotein levels in patients with chronic hepatitis B. Cancer 64:2117–2120
Belghiti J, Panis Y, Farges O, Benhamou JP, Fekete F et al (1991) Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis. Ann Surg 214:114–117
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 197:101–108
Yoshida H, Arakawa Y, Sata M, Nishiguchi S, Yano M, Fujiyama S (2002) Interferon therapy prolonged life expectancy among chronic hepatitis C patients. Gastroenterology 123:483–491
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 17:518–524
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 96:236–242
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.
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Yanagi, T., Yasuda, S., Imada, H. et al. Association between changes in serum α-fetoprotein level and patterns of recurrence in patients undergoing carbon-ion radiotherapy for hepatocellular carcinoma. J Radiat Oncol 3, 179–184 (2014). https://doi.org/10.1007/s13566-013-0124-5
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DOI: https://doi.org/10.1007/s13566-013-0124-5