Abstract
Although the lung is the most common site of extrahepatic metastases from hepatocellular carcinoma (HCC), the optimal treatment for such metastases has’nt been established. External beam radiotherapy (EBRT) is becoming a useful local control therapy for lung cancer. To evaluated the efficacy of EBRT treatment for such metastases, we retrospectively studied 13 patients (11 men and 2 women; mean age, 52.6 years) with symptomatic pulmonary metastases from HCC who had been treated with EBRT in our institution. The palliative radiation dose delivered to the lung lesions ranged from 47 to 60 Gy (median 50) in conventional fractions, while the intrahepatic lesions were treated with surgery or transarterial chemoembolization, and/or EBRT. Follow-up period from radiotherapy ranged from 3.7 to 49.1 months (median, 16.7). Among the 13 patients, 23 out of a total of 31 pulmonary metastatic lesions received EBRT. In 12/13(92.3%) patients, significant symptoms were completely or partially relieved. An objective response was observed in 10/13(76.9%) of the subjects by computed tomography imaging. The median progression-free survival for all patients was 13.4 months. The 2-year survival rate from pulmonary metastasis was 70.7%. Adverse effects were mild and consisted of bone marrow suppression in three patients and pleural effusion in one patient (all CTCAE Grade II). In conclusion, EBRT with ≤60 Gy appears to be a good palliative therapy with reasonable safety for patients with pulmonary metastases from HCC. However, large-scale randomized clinical trials will be necessary to confirm the therapeutic role of this method.
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Abbreviations
- HCC:
-
Hepatocellular carcinoma
- EBRT:
-
External beam radiotherapy
- CT:
-
Computed tomography
- BACE:
-
Bronchial arterial chemoembolization
- AFP:
-
α-Fetoprotein
- CEA:
-
Carcinoembryonic antigen
- CA19-9:
-
Carbohydrate antigen 19-9
- PmFI:
-
Pulmonary metastases-free interval
- TACE:
-
Transarterial chemoembolization
- 3D-CRT:
-
Three-dimensional conformal radiation therapy
- GTV:
-
Gross tumor volume
- CTV:
-
Clinical target volume
- PTV:
-
Planning target volume
- DVH:
-
Dose–volume histogram
- OARs:
-
Organs at risk
- BED:
-
Biologic effective dose
- RECIST:
-
Response evaluation criteria in solid tumors
- CR:
-
Complete response
- PR:
-
Partial response
- SD:
-
Stable disease
- PD:
-
Progression of disease
- CTCAE:
-
Common terminology criteria for adverse events
- PFS:
-
Progression-free survival time
- CI:
-
Confidence interval
- WBC:
-
Whiter blood cell counts
References
Ikai I, Arii S, Kojiro M, Ichida T, Makuuchi M, Matsuyama Y, Nakanuma Y, Okita K, Omata M, Takayasu K, Yamaoka Y (2004) Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey. Cancer 101:796–802. doi:10.1002/cncr.20426
Yoon YS, Kim HK, Kim J, Choi YS, Shim YM, Paik SW, Kim K (2010) Long-term survival and prognostic factors after pulmonary metastasectomy in hepatocellular carcinoma. Ann Surg Oncol 17:2795–2801. doi:10.1245/s10434-010-1073-5
Chen F, Sato K, Fujinaga T, Sonobe M, Shoji T, Sakai H, Miyahara R, Bando T, Okubo K, Hirata T, Date H (2008) Pulmonary resection for metastases from hepatocellular carcinoma. World J Surg 32:2213–2217. doi:10.1007/s00268-008-9684-8
Tomimaru Y, Sasaki Y, Yamada T, Eguchi H, Takami K, Ohigashi H, Higashiyama M, Ishikawa O, Kodama K, Imaoka S (2006) The significance of surgical resection for pulmonary metastasis from hepatocellular carcinoma. Am J Surg 192:46–51. doi:10.1016/j.amjsurg
Hiraki T, Gobara H, Takemoto M, Mimura H, Mukai T, Himei K, Hase S, Iguchi T, Fujiwara H, Yagi T, Tanaka N, Kanazawa S (2006) Percutaneous radiofrequency ablation combined with previous bronchial arterial chemoembolization and followed by radiation therapy for pulmonary metastasis from hepatocellular carcinoma. J Vasc Interv Radiol 17:1189–1193. doi:10.1097/01.RVI.0000228370.09886.66
Li C, Zhang F, Zhang W, Zhang L, Huang Z, Wu P (2010) Feasibility of (125)I brachytherapy combined with sorafenib treatment in patients with multiple lung metastases after liver transplantation for hepatocellular carcinoma. J Cancer Res Clin Oncol 136:1633–1640. doi:10.1007/s00432-010-0821-z
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216. doi:10.1093/jnci/92.3.205
Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. (2006) DCTDN, NIH, NHHS. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed August 9, 2006
Ikai I, Arii S, Okazaki M, Okita K, Omata M, Kojiro M, Takayasu K, Nakanuma Y, Makuuchi M, Matsuyama Y, Monden M, Kudo M (2007) Report of the 17th nationwide follow-up survey of primary liver cancer in Japan. Hepatol Res 37:676–691. doi:10.1111/j.1872-034X.2007.00119.x
Chua TC, Morris DL (2011) Exploring the role of resection of extrahepatic metastases from hepatocellular carcinoma. Surg Oncol. doi:10.1016/j.suronc.2011.01.005
Zhang SM, Zeng ZC, Tang ZY, Sun J, Cheng JM, Liu R, Wang P, Zhang BH (2008) Prognostic analysis of pulmonary metastases from hepatocellular carcinoma. Hepatol Int 2:237–243. doi:10.1007/s12072-008-9052-7
The International Registry of Lung Metastases, Writing Committee, Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, Johnston M, McCormack P, Pass H, Putnam JB Jr (1997) Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 113:37–49
He J, Zeng ZC, Tang ZY, Fan J, Zhou J, Zeng MS, Wang JH, Sun J, Chen B, Yang P, Pan BS (2009) Clinical features and prognostic factors in patients with bone metastases from hepatocellular carcinoma receiving external beam radiotherapy. Cancer 115:2710–2720. doi:10.1002/cncr.24300
Zeng ZC, Tang ZY, Fan J, Zhou J, Qin LX, Ye SL, Sun HC, Wang BL, Zhang JY, Yu Y, Cheng JM, Wang XL, Guo W (2005) Radiation therapy for adrenal gland metastases from hepatocellular carcinoma. Jpn J Clin Oncol 35:61–67. doi:10.1093/jjco/hyi020
Cheng JC, Chou CH, Kuo ML, Hsieh CY (2006) Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-kappaB signal transduction pathway. Oncogene 25:7009–7018. doi:10.1038/sj.onc.1209706
Jia JB, Wang WQ, Sun HC, Liu L, Zhu XD, Kong LQ, Chai ZT, Zhang W, Zhang JB, Xu HX, Zeng ZC, Wu WZ, Wang L, Tang ZY (2010) A novel tripeptide, tyroserleutide, inhibits irradiation-induced invasiveness and metastasis of hepatocellular carcinoma in nude mice. Invest New Drugs 29:861–872. doi:10.1007/s10637-010-9435-1
Tsuchiya A, Imai M, Kamimura H, Togashi T, Watanabe K, Seki K, Ishikawa T, Ohta H, Yoshida T, Kamimura T (2009) Successful treatment of multiple lung metastases of hepatocellular carcinoma by combined chemotherapy with docetaxel, cisplatin and tegafur/uracil. World J Gastroenterol 15:1779–1781. doi:10.3748/wjg.15.1779
Girard N, Mornex F (2011) Sorafenib and radiotherapy association for hepatocellular carcinoma. Cancer Radiother 15:77–80. doi:10.1016/j.canrad.2010.11.012
Jang JW, Kay CS, You CR, Kim CW, Bae SH, Choi JY, Yoon SK, Han CW, Jung HS, Choi IB (2009) Simultaneous multitarget irradiation using helical tomotherapy for advanced hepatocellular carcinoma with multiple extrahepatic metastases. Int J Radiat Oncol Biol Phys 74:412–418. doi:10.1016/j.ijrobp.2008.08.034
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Jiang, W., Zeng, ZC., Zhang, JY. et al. Palliative radiation therapy for pulmonary metastases from hepatocellular carcinoma. Clin Exp Metastasis 29, 197–205 (2012). https://doi.org/10.1007/s10585-011-9442-4
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DOI: https://doi.org/10.1007/s10585-011-9442-4