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Erschienen in: Strahlentherapie und Onkologie 9/2014

01.09.2014 | Original article

Effectiveness and safety of proton beam therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis

verfasst von: Sung Uk Lee, Joong-Won Park, M.D., Tae Hyun Kim, M.D., Yeon-Joo Kim, M.D., Sang Myung Woo, M.D., Young-Hwan Koh, M.D., Woo Jin Lee, M.D., Sang-Jae Park, M.D., Dae Yong Kim, M.D., Chang-Min Kim, M.D.

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 9/2014

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Abstract

Purpose

To evaluate the clinical effectiveness and safety of proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT).

Patients and methods

Twenty-seven HCC patients with PVTT underwent PBT, including 22 patients with modified International Union Against Cancer (mUICC) stage IVA,five patients with stage IVB primary tumors, and 16 with main PVTT. A median dose of 55 GyE (range, 50–66 GyE) in 20–22 fractions was delivered to a target volume encompassing both the PVTT and primary tumor.

Results

Overall, treatment was well tolerated, with no toxicity of grade ≥ 3. Median overall survival (OS) times in all patients and in stage IVA patients were 13.2 months and 16 months, respectively. Assessments of PVTT response showed complete response in 0 of 27 (0 %) patients, partial response in 15 (55.6 %), stable disease in 10 (37 %), and progressive disease in 2 (7.4 %) patients, with an objective response rate of 55.6 %. PVTT responders showed significantly higher actuarial 1-year local progression-free survival (LPFS; 85.6 % vs. 51.3 %), relapse-free survival (RFS; 20 % vs. 0 %) and OS (80 % vs. 25 %) rates than nonresponders (p < 0.05 each). Multivariate analysis showed that PVTT response and mUICC stage were independent prognostic factors for OS.

Conclusion

Our data suggest that PBT could improve LPFS, RFS, and OS in advanced HCC patients with PVTT and it is feasible and safe for these patients.
Literatur
1.
Zurück zum Zitat Cheng AL, Kang YK, Chen Z et al (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10:25–34 Cheng AL, Kang YK, Chen Z et al (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10:25–34
2.
Zurück zum Zitat Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390 Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390
3.
Zurück zum Zitat Korean Liver Cancer Study G, National Cancer Center K (2009) [Practice guidelines for management of hepatocellular carcinoma 2009]. Korean J Hepatol 15:391–423 Korean Liver Cancer Study G, National Cancer Center K (2009) [Practice guidelines for management of hepatocellular carcinoma 2009]. Korean J Hepatol 15:391–423
4.
Zurück zum Zitat Ueno S, Tanabe G, Nuruki K et al (2002) Prognostic performance of the new classification of primary liver cancer of Japan (4th edition) for patients with hepatocellular carcinoma: a validation analysis. Hepatol Res 24:395–403 Ueno S, Tanabe G, Nuruki K et al (2002) Prognostic performance of the new classification of primary liver cancer of Japan (4th edition) for patients with hepatocellular carcinoma: a validation analysis. Hepatol Res 24:395–403
5.
Zurück zum Zitat Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247 Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247
6.
Zurück zum Zitat Ishikura S, Ogino T, Furuse J et al (2002) Radiotherapy after transcatheter arterial chemoembolization for patients with hepatocellular carcinoma and portal vein tumor thrombus. Am J Clin Oncol 25:189–193 Ishikura S, Ogino T, Furuse J et al (2002) Radiotherapy after transcatheter arterial chemoembolization for patients with hepatocellular carcinoma and portal vein tumor thrombus. Am J Clin Oncol 25:189–193
7.
Zurück zum Zitat Yamada K, Izaki K, Sugimoto K et al (2003) Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 57:113–119 Yamada K, Izaki K, Sugimoto K et al (2003) Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 57:113–119
8.
Zurück zum Zitat Toya R, Murakami R, Baba Y et al (2007) Conformal radiation therapy for portal vein tumor thrombosis of hepatocellular carcinoma. Radiother Oncol 84:266–271 Toya R, Murakami R, Baba Y et al (2007) Conformal radiation therapy for portal vein tumor thrombosis of hepatocellular carcinoma. Radiother Oncol 84:266–271
9.
Zurück zum Zitat Huang YJ, Hsu HC, Wang CY et al (2009) The treatment responses in cases of radiation therapy to portal vein thrombosis in advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 73:1155–1163 Huang YJ, Hsu HC, Wang CY et al (2009) The treatment responses in cases of radiation therapy to portal vein thrombosis in advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 73:1155–1163
10.
Zurück zum Zitat Zeng ZC, Fan J, Tang ZY et al (2005) A comparison of treatment combinations with and without radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombus. Int J Radiat Oncol Biol Phys 61:432–443 Zeng ZC, Fan J, Tang ZY et al (2005) A comparison of treatment combinations with and without radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombus. Int J Radiat Oncol Biol Phys 61:432–443
11.
Zurück zum Zitat Kim DY, Park W, Lim DH et al (2005) Three-dimensional conformal radiotherapy for portal vein thrombosis of hepatocellular carcinoma. Cancer 103:2419–2426 Kim DY, Park W, Lim DH et al (2005) Three-dimensional conformal radiotherapy for portal vein thrombosis of hepatocellular carcinoma. Cancer 103:2419–2426
12.
Zurück zum Zitat Kim TH, Kim DY, Park JW et al (2007) Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys 67:225–231 Kim TH, Kim DY, Park JW et al (2007) Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys 67:225–231
13.
Zurück zum Zitat Yoon SM, Lim YS, Won HJ et al (2012) Radiotherapy plus transarterial chemoembolization for hepatocellular carcinoma invading the portal vein: long-term patient outcomes. Int J Radiat Oncol Biol Phys 82:2004–2011 Yoon SM, Lim YS, Won HJ et al (2012) Radiotherapy plus transarterial chemoembolization for hepatocellular carcinoma invading the portal vein: long-term patient outcomes. Int J Radiat Oncol Biol Phys 82:2004–2011
14.
Zurück zum Zitat Han KH, Seong J, Kim JK et al (2008) Pilot clinical trial of localized concurrent chemoradiation therapy for locally advanced hepatocellular carcinoma with portal vein thrombosis. Cancer 113:995–1003 Han KH, Seong J, Kim JK et al (2008) Pilot clinical trial of localized concurrent chemoradiation therapy for locally advanced hepatocellular carcinoma with portal vein thrombosis. Cancer 113:995–1003
15.
Zurück zum Zitat Kim JY, Yoo EJ, Jang JW et al (2013) Hypofractionated radiotheapy using helical tomotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis. Radiat Oncol 8:15 Kim JY, Yoo EJ, Jang JW et al (2013) Hypofractionated radiotheapy using helical tomotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis. Radiat Oncol 8:15
16.
Zurück zum Zitat Choi Y, Kim JW, Cha H et al (2013) Overall response of both intrahepatic tumor and portal vein tumor thrombosis is a good prognostic factor for hepatocellular carcinoma patients receiving concurrent chemoradiotherapy. J Radiat Res 55:113–120 Choi Y, Kim JW, Cha H et al (2013) Overall response of both intrahepatic tumor and portal vein tumor thrombosis is a good prognostic factor for hepatocellular carcinoma patients receiving concurrent chemoradiotherapy. J Radiat Res 55:113–120
17.
Zurück zum Zitat Xi M, Zhang L, Zhao L et al (2013) Effectiveness of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombosis. PloS one 8:e63864 Xi M, Zhang L, Zhao L et al (2013) Effectiveness of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombosis. PloS one 8:e63864
18.
Zurück zum Zitat Lin CS, Jen YM, Chiu SY et al (2006) Treatment of portal vein tumor thrombosis of hepatoma patients with either stereotactic radiotherapy or three-dimensional conformal radiotherapy. Jpn J Clin Oncol 36:212–217 Lin CS, Jen YM, Chiu SY et al (2006) Treatment of portal vein tumor thrombosis of hepatoma patients with either stereotactic radiotherapy or three-dimensional conformal radiotherapy. Jpn J Clin Oncol 36:212–217
19.
Zurück zum Zitat Choi BO, Choi IB, Jang HS et al (2008) Stereotactic body radiation therapy with or without transarterial chemoembolization for patients with primary hepatocellular carcinoma: preliminary analysis. BMC Cancer 8:351 Choi BO, Choi IB, Jang HS et al (2008) Stereotactic body radiation therapy with or without transarterial chemoembolization for patients with primary hepatocellular carcinoma: preliminary analysis. BMC Cancer 8:351
20.
Zurück zum Zitat Bujold A, Massey CA, Kim JJ et al (2013) Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 31:1631–1639 Bujold A, Massey CA, Kim JJ et al (2013) Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 31:1631–1639
21.
Zurück zum Zitat Wang PM, Hsu WC, Chung NN et al (2013) Radiotherapy with volumetric modulated arc therapy for hepatocellular carcinoma patients ineligible for surgery or ablative treatments. Strahlenther Onkol 189:301–307 Wang PM, Hsu WC, Chung NN et al (2013) Radiotherapy with volumetric modulated arc therapy for hepatocellular carcinoma patients ineligible for surgery or ablative treatments. Strahlenther Onkol 189:301–307
22.
Zurück zum Zitat Gong GZ, Yin Y, Xing LG et al (2012) RapidArc combined with the active breathing coordinator provides an effective and accurate approach for the radiotherapy of hepatocellular carcinoma. Strahlenther Onkol 188:262–268 Gong GZ, Yin Y, Xing LG et al (2012) RapidArc combined with the active breathing coordinator provides an effective and accurate approach for the radiotherapy of hepatocellular carcinoma. Strahlenther Onkol 188:262–268
23.
Zurück zum Zitat Kim YI, Park HC, Lim do H et al (2012) Changes of the liver volume and the Child-Pugh score after high dose hypofractionated radiotherapy in patients with small hepatocellular carcinoma. Radiat Oncol J 30:189–196 Kim YI, Park HC, Lim do H et al (2012) Changes of the liver volume and the Child-Pugh score after high dose hypofractionated radiotherapy in patients with small hepatocellular carcinoma. Radiat Oncol J 30:189–196
24.
Zurück zum Zitat Sugahara S, Nakayama H, Fukuda K et al (2009) Proton-beam therapy for hepatocellular carcinoma associated with portal vein tumor thrombosis. Strahlenther Onkol 185:782–788 Sugahara S, Nakayama H, Fukuda K et al (2009) Proton-beam therapy for hepatocellular carcinoma associated with portal vein tumor thrombosis. Strahlenther Onkol 185:782–788
25.
Zurück zum Zitat Emami B, Lyman J, Brown A et al (1991) Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21:109–122 Emami B, Lyman J, Brown A et al (1991) Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21:109–122
26.
Zurück zum Zitat Lawrence TS, Ten Haken RK, Kessler ML et al (1992) The use of 3-D dose volume analysis to predict radiation hepatitis. Int J Radiat Oncol Biol Phys 23:781–788 Lawrence TS, Ten Haken RK, Kessler ML et al (1992) The use of 3-D dose volume analysis to predict radiation hepatitis. Int J Radiat Oncol Biol Phys 23:781–788
27.
Zurück zum Zitat Liang SX, Zhu XD, Lu HJ et al (2005) Hypofractionated three-dimensional conformal radiation therapy for primary liver carcinoma. Cancer 103:2181–2188 Liang SX, Zhu XD, Lu HJ et al (2005) Hypofractionated three-dimensional conformal radiation therapy for primary liver carcinoma. Cancer 103:2181–2188
28.
Zurück zum Zitat Yu W, Gu K, Yu Z et al (2013) Sorafenib potentiates irradiation effect in hepatocellular carcinoma in vitro and in vivo. Cancer Lett 329:109–117 Yu W, Gu K, Yu Z et al (2013) Sorafenib potentiates irradiation effect in hepatocellular carcinoma in vitro and in vivo. Cancer Lett 329:109–117
Metadaten
Titel
Effectiveness and safety of proton beam therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis
verfasst von
Sung Uk Lee
Joong-Won Park, M.D.
Tae Hyun Kim, M.D.
Yeon-Joo Kim, M.D.
Sang Myung Woo, M.D.
Young-Hwan Koh, M.D.
Woo Jin Lee, M.D.
Sang-Jae Park, M.D.
Dae Yong Kim, M.D.
Chang-Min Kim, M.D.
Publikationsdatum
01.09.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Strahlentherapie und Onkologie / Ausgabe 9/2014
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-014-0604-6

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