Effectiveness of Particle Radiotherapy in Various Stages of Hepatocellular Carcinoma: A Pilot Study

Overview

Journal Liver Cancer

Date 2018 Nov 30

PMID 30488022

Citations 4

Authors

Yushi Sorin

Kenji Ikeda

Yusuke Kawamura

Shunichiro Fujiyama

Masahiro Kobayashi

Tetsuya Hosaka

Hitomi Sezaki

Norio Akuta

Satoshi Saitoh

Fumitaka Suzuki

Yoshiyuki Suzuki

Yasuji Arase

Hiromitsu Kumada

Affiliations

Soon will be listed here.

Abstract

Aim: We analyzed the effectiveness of external particle radiotherapy (PRT) as an alternative therapy for various stages of hepatocellular carcinoma (HCC).

Methods: Eighty-three patients with HCC underwent PRT in our hospital from 2007 to 2015 (proton beam radiation in 58 patients and carbon ion radiation in 25 patients), including patients with early-stage HCC (single HCC measuring ≤3 cm, Barcelona Clinic Liver Cancer [BCLC] stage 0 or A) (group A, = 30), those with intermediate-stage HCC (HCCs measuring ≥3 cm but inoperable or multinodular and transcatheter arterial embolization [TACE]-refractory, BCLC stage B) (group B, = 31), and those with advanced-stage HCC (HCC with portal invasion or extrahepatic metastasis) (group C, = 22). The median radiation dose was 72.6 GyE (range 50-74) for proton beam radiation and 45.0 GyE (range 45-52.8) for carbon beam radiation. Local control ability was defined as continuous shrinkage of the tumor size without development of new lesions for ≥6 months after PRT.

Results: The rates of local control of the target tumor at 6 months, 1 year, and 2 years were 91.9, 86.3, and 84.8%, respectively. The overall survival rates at 1, 2, and 3 years were 83.0, 65.6, and 55.1%, respectively. Patients in group A showed the best survival rates (100.0% at 1 year and 85.9% at 2 years). The 1-year survival rate was poor in group C (63.6%) despite a good local tumor control rate of 74.7%. The overall survival rates were significantly better in groups A and B than in group C.

Conclusions: The local control rates after PRT were sufficiently high compared to TACE or sorafenib. Thus, PRT should be adopted for patients with difficult-to-treat HCC in the early and intermediate stages.

Citing Articles

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References

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

Komatsu S, Fukumoto T, Demizu Y, Miyawaki D, Terashima K, Sasaki R . Clinical results and risk factors of proton and carbon ion therapy for hepatocellular carcinoma. Cancer. 2011; 117(21):4890-904. DOI: 10.1002/cncr.26134. View

Blomgren H, Lax I, Naslund I, Svanstrom R . Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients. Acta Oncol. 1995; 34(6):861-70. DOI: 10.3109/02841869509127197. View

Bruix J, Sherman M . Management of hepatocellular carcinoma: an update. Hepatology. 2011; 53(3):1020-2. PMC: 3084991. DOI: 10.1002/hep.24199. View

Wang J, Li Q, Sun Y, Zheng H, Cui Y, Li H . Clinicopathologic features between multicentric occurence and intrahepatic metastasis of multiple hepatocellular carcinomas related to HBV. Surg Oncol. 2008; 18(1):25-30. DOI: 10.1016/j.suronc.2008.05.009. View

Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Nakashima O . Management of hepatocellular carcinoma in Japan: Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis. 2011; 29(3):339-64. DOI: 10.1159/000327577. View

Mizumoto M, Okumura T, Hashimoto T, Fukuda K, Oshiro Y, Fukumitsu N . Proton beam therapy for hepatocellular carcinoma: a comparison of three treatment protocols. Int J Radiat Oncol Biol Phys. 2010; 81(4):1039-45. DOI: 10.1016/j.ijrobp.2010.07.015. View

Bush D, Kayali Z, Grove R, Slater J . The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. Cancer. 2011; 117(13):3053-9. DOI: 10.1002/cncr.25809. View

Ueno S, Aoki D, Maeda T, Kubo F, Hokotate H, Fukukura Y . Preoperative assessment of multicentric occurrence in synchronous small and multiple hepatocellular carcinoma based on image-patterns and histological grading of non-cancerous region. Hepatol Res. 2004; 29(1):24-30. DOI: 10.1016/j.hepres.2004.02.003. View

10.

Feng K, Yan J, Li X, Xia F, Ma K, Wang S . A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol. 2012; 57(4):794-802. DOI: 10.1016/j.jhep.2012.05.007. View

11.

Kokudo N, Makuuchi M . Evidence-based clinical practice guidelines for hepatocellular carcinoma in Japan: the J-HCC guidelines. J Gastroenterol. 2009; 44 Suppl 19:119-21. DOI: 10.1007/s00535-008-2244-z. View

12.

Kato H, Tsujii H, Miyamoto T, Mizoe J, Kamada T, Tsuji H . Results of the first prospective study of carbon ion radiotherapy for hepatocellular carcinoma with liver cirrhosis. Int J Radiat Oncol Biol Phys. 2004; 59(5):1468-76. DOI: 10.1016/j.ijrobp.2004.01.032. View

13.

Sherman M . Hepatocellular carcinoma: epidemiology, surveillance, and diagnosis. Semin Liver Dis. 2010; 30(1):3-16. DOI: 10.1055/s-0030-1247128. View

14.

Sawrie S, Fiveash J, Caudell J . Stereotactic body radiation therapy for liver metastases and primary hepatocellular carcinoma: normal tissue tolerances and toxicity. Cancer Control. 2010; 17(2):111-9. DOI: 10.1177/107327481001700206. View

15.

Imada H, Kato H, Yasuda S, Yamada S, Yanagi T, Kishimoto R . Comparison of efficacy and toxicity of short-course carbon ion radiotherapy for hepatocellular carcinoma depending on their proximity to the porta hepatis. Radiother Oncol. 2010; 96(2):231-5. DOI: 10.1016/j.radonc.2010.05.019. View

16.

Zeng Z, Tang Z, Fan J, Qin L, Ye S, Zhou J . Consideration of role of radiotherapy for lymph node metastases in patients with HCC: retrospective analysis for prognostic factors from 125 patients. Int J Radiat Oncol Biol Phys. 2005; 63(4):1067-76. DOI: 10.1016/j.ijrobp.2005.03.058. View

17.

Wu F, Chen J, Bai T, Zhu S, Yang T, Qi L . The safety and efficacy of transarterial chemoembolization combined with sorafenib and sorafenib mono-therapy in patients with BCLC stage B/C hepatocellular carcinoma. BMC Cancer. 2017; 17(1):645. PMC: 5596482. DOI: 10.1186/s12885-017-3545-5. View

18.

Benson 3rd A, Abrams T, Ben-Josef E, Bloomston P, Botha J, Clary B . NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Canc Netw. 2009; 7(4):350-91. PMC: 4461147. DOI: 10.6004/jnccn.2009.0027. View

19.

El-Serag H, Siegel A, Davila J, Shaib Y, Cayton-Woody M, McBride R . Treatment and outcomes of treating of hepatocellular carcinoma among Medicare recipients in the United States: a population-based study. J Hepatol. 2005; 44(1):158-66. DOI: 10.1016/j.jhep.2005.10.002. View

20.

Wu J, Wong R, Johnston M, Bezjak A, Whelan T . Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys. 2003; 55(3):594-605. DOI: 10.1016/s0360-3016(02)04147-0. View