Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study

Takuya Nagano; Akihiko Hoshi; Masayuki Kurosaki; Kazuma Sasamura; Kaoru Tsuchiya; Kazuma Toda; Hirofumi Kuwabara; Meika Namba; Daigoro Matsubara; Sayako Oota; Yasuo Yoshioka; Ryoichi Yoshimura; Namiki Izumi

doi:doi:10.11648/j.ijcocr.20200503.13

Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study

Takuya Nagano, Akihiko Hoshi, Masayuki Kurosaki, Kazuma Sasamura, Kaoru Tsuchiya, Kazuma Toda, Hirofumi Kuwabara, Meika Namba, Daigoro Matsubara, Sayako Oota, Yasuo Yoshioka, Ryoichi Yoshimura, Namiki Izumi

Published in International Journal of Clinical Oncology and Cancer Research (Volume 5, Issue 3)

Received: 16 September 2020 Accepted: 27 September 2020 Published: 7 October 2020

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Abstract

Background: The aim of this multicenter study was to evaluate the outcome of radiotherapy (RT) that targeted for tumor thrombi (TT) from hepatocellular carcinoma (HCC), including the portal vein, hepatic vein, inferior vena cava, and bile duct TT. Methods: Patients who received RT for the treatment of TT between 2005 and 2020 were retrospectively reviewed. We compared patient characteristics, overall survival (OS), the combined chemotherapy regimen, and objective response rates (ORRs) between the treatment modalities and analyzed cumulative incidence formula (CIF) for the deterioration in the Child-Pugh class and the progression of intrahepatic tumors. Results: We evaluated 64 patients, 39 of whom received combined chemotherapy with RT. Multivariate analysis showed that the Child-Pugh class, primary tumor size and the response of TT were significant prognostic factors for OS and the total equivalent dose in 2 Gy fractions (EQD2) of more than 48.75 Gy significantly contributed to ORRs (p=0.04). In the multivariate analysis of CIF, only acute liver damage was the significant factor for the deterioration in the Child-Pugh class (p=0.01) and the length of TT was significant for the progression of intrahepatic tumors (p=0.03). Conclusion: High doses should be delivered to TT, but long tumor thrombi are difficult to control. Tumor thrombus length is more important in predicting intrahepatic progression than the location of the tumor thrombus.

Published in	International Journal of Clinical Oncology and Cancer Research (Volume 5, Issue 3)
DOI	10.11648/j.ijcocr.20200503.13
Page(s)	65-77
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2020. Published by Science Publishing Group

Keywords

Combined Chemotherapy, Radiation Therapy, Hepatocellular Carcinoma, Macroscopic Vascular Invasion, Tumor Thrombosis

References

[1]	Yoon SM, Lim YS, Won HJ, et al. Radiotherapy plus transarterial chemoembolization for hepatocellular carcinoma invading the portal vein: long-term patient outcomes. Int J Radiat Oncol Biol Phys 2012; 82: 2004–11.
[2]	Pao TH, Hsueh WT, Chang WL, et al. Radiotherapy for inferior vena cava tumor thrombus in patients with hepatocellular carcinoma. BMC Cancer (2019) 19: 560.
[3]	Nakazawa T, Shibuya A, Okuwaki Y, et al. Overall survival in response to sorafenib versus radiotherapy in unresectable hepatocellular carcinoma with major portal vein tumor thrombosis: propensity score analysis BMC Gastroenterology 2014, 14: 84.
[4]	Kudo M, Matsui O, Izumi N, et al. Japanese Society of Hepatology Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. Liver Cancer 2014; 3: 458–468.
[5]	Bruix J, Qin S, Merie P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 389: 56–66.
[6]	Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med 2008; 359, 378–390.
[7]	Luo J, Guo RP, Lai EC, et al. Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: A Prospective Comparative Study. Ann Surg Oncol (2011) 18: 413–420.
[8]	Nouso K, Miyahara K, Uchida D, et al. Effect of hepatic arterial infusion chemotherapy of 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma in the Nationwide Survey of Primary Liver Cancer in Japan. British Journal of Cancer (2013) 109, 1904–1907.
[9]	Wang K, GuoWX, Chen MS, et al. Multimodality Treatment for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus. Medicine Volume 95, Number 11, March 2016 1-10.
[10]	Bai H, Gao P, Gao H, et al. Improvement of Survival Rate for Patients with Hepatocellular Carcinoma Using Transarterial Chemoembolization in Combination with Three-Dimensional Conformal Radiation Therapy: A Meta-Analysis. Med Sci Monit, 2016; 22: 1773-1781.
[11]	Kondo Y, Kimura O, Kogure T, et al. Radiation Therapy Is a Reasonable Option for Improving the Prognosis in Hepatocellular Carcinoma. Tohoku J. Exp. Med., 2015, 237, 249-257.
[12]	Meng MB, Cui YL, Lu Y, et al. Transcatheter arterial chemoembolization in combination with radiotherapy for unresectable hepatocellular carcinoma: A systematic review and meta-analysis. Radiotherapy and Oncology 92 (2009) 184–194.
[13]	Zou LQ, Zhang BL, Chang Q, et al. 3D conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma. World J Gastroenterol 2014 December 7; 20 (45): 17227-17234.
[14]	Cheng AL, Kang YK, Chen Z, et al. 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 2009; 10: 25–34.
[15]	Chen AL, Finn RS, Qin S, et al. Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in firstline treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC). J Clin Oncol 2017; 35: abstract 4001.
[16]	Kokudo T, Hasegawa K, Matsuyama Y, et al. Liver Resection for Hepatocellular Carcinoma Associated With Hepatic Vein Invasion: A Japanese Nationwide Survey. HEPATOLOGY, VOL. 66, NO. 2, 2017 510-517.
[17]	Pawlik T, Poon R, Abdalla E, et al. Hepatectomy for hepatocellular carcinoma with major portal or hepatic vein invasion: Results of a multicenter study. Surgery. 2005; 137: 403-10.
[18]	Torzilli G, Belghiti J, Kokudo N, et al. A Snapshot of the Effective Indications and Results of Surgery for Hepatocellular Carcinoma in Tertiary Referral Centers: Is It Adherent to the EASL/AASLD Recommendations? Annals of Surgery. Volume 257, Number 5, May 2013.
[19]	Im JH, Yoon SM, Park HC, et al. Radiotherapeutic strategies for hepatocellular carcinoma with portal vein tumour thrombosis in a hepatitis B endemic area. Liver Int 2017; 37: 90–100.
[20]	Yoon SM, Ryoo BY, Lee SJ, et al. Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion. A Randomized Clinical Trial. JAMA Oncol. 2018; 4 (5): 661-669.
[21]	Choi Y, Kim JW, Cha H, et al. Overall response of both intrahepatic tumor and portal vein tumor thrombosis is a good prognostic factor for hepatocellular carcinoma patients receiving concurrent chemoradiotherapy. Journal of Radiation Research, 2014, 55, 113–120.
[22]	Matsuo Y, Yoshida K, Nishimura H, et al. Efficacy of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis/inferior vena cava tumor thrombosis: evaluation by comparison with conventional three-dimensional conformal radiotherapy. Journal of Radiation Research, Vol. 57, No. 5, 2016, pp. 512–523.
[23]	Xi M, Zhang L, Zhao L, et al. Effectiveness of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma with Portal Vein and/or Inferior Vena Cava Tumor Thrombosis. PLoS ONE, 2013, 8 (5): e63864.
[24]	Marks LB, Yorke ED, Jackson A, Haken RKT, Constine LS, Eisbruch A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 76 (3 Suppl): S10-19, 2010.
[25]	Sugahara S, Nakayama H, Fukuda K, et al. Proton-Beam Therapy for Hepatocellular Carcinoma Associated with Portal Vein Tumor Thrombosis. Strahlenther Onkol 2009; 185: 782–8.
[26]	Lee SU, Park JW, Kim TH, et al. Effectiveness and safety of proton beam therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis. Strahlenther Onkol, 2014, 190, 806–814.
[27]	Sekino Y, Okumura T, Fukumitsu N, et al. Proton beam therapy for hepatocellular carcinoma associated with inferior vena cava tumor thrombus. Journal of Cancer Research and Clinical Oncology (2020) 146: 711–720.

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APA Style

Takuya Nagano, Akihiko Hoshi, Masayuki Kurosaki, Kazuma Sasamura, Kaoru Tsuchiya, et al. (2020). Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study. International Journal of Clinical Oncology and Cancer Research, 5(3), 65-77. https://doi.org/10.11648/j.ijcocr.20200503.13

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ACS Style

Takuya Nagano; Akihiko Hoshi; Masayuki Kurosaki; Kazuma Sasamura; Kaoru Tsuchiya, et al. Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study. Int. J. Clin. Oncol. Cancer Res. 2020, 5(3), 65-77. doi: 10.11648/j.ijcocr.20200503.13

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AMA Style

Takuya Nagano, Akihiko Hoshi, Masayuki Kurosaki, Kazuma Sasamura, Kaoru Tsuchiya, et al. Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study. Int J Clin Oncol Cancer Res. 2020;5(3):65-77. doi: 10.11648/j.ijcocr.20200503.13

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@article{10.11648/j.ijcocr.20200503.13,
  author = {Takuya Nagano and Akihiko Hoshi and Masayuki Kurosaki and Kazuma Sasamura and Kaoru Tsuchiya and Kazuma Toda and Hirofumi Kuwabara and Meika Namba and Daigoro Matsubara and Sayako Oota and Yasuo Yoshioka and Ryoichi Yoshimura and Namiki Izumi},
  title = {Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study},
  journal = {International Journal of Clinical Oncology and Cancer Research},
  volume = {5},
  number = {3},
  pages = {65-77},
  doi = {10.11648/j.ijcocr.20200503.13},
  url = {https://doi.org/10.11648/j.ijcocr.20200503.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcocr.20200503.13},
  abstract = {Background: The aim of this multicenter study was to evaluate the outcome of radiotherapy (RT) that targeted for tumor thrombi (TT) from hepatocellular carcinoma (HCC), including the portal vein, hepatic vein, inferior vena cava, and bile duct TT. Methods: Patients who received RT for the treatment of TT between 2005 and 2020 were retrospectively reviewed. We compared patient characteristics, overall survival (OS), the combined chemotherapy regimen, and objective response rates (ORRs) between the treatment modalities and analyzed cumulative incidence formula (CIF) for the deterioration in the Child-Pugh class and the progression of intrahepatic tumors. Results: We evaluated 64 patients, 39 of whom received combined chemotherapy with RT. Multivariate analysis showed that the Child-Pugh class, primary tumor size and the response of TT were significant prognostic factors for OS and the total equivalent dose in 2 Gy fractions (EQD2) of more than 48.75 Gy significantly contributed to ORRs (p=0.04). In the multivariate analysis of CIF, only acute liver damage was the significant factor for the deterioration in the Child-Pugh class (p=0.01) and the length of TT was significant for the progression of intrahepatic tumors (p=0.03). Conclusion: High doses should be delivered to TT, but long tumor thrombi are difficult to control. Tumor thrombus length is more important in predicting intrahepatic progression than the location of the tumor thrombus.},
 year = {2020}
}

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TY  - JOUR
T1  - Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study
AU  - Takuya Nagano
AU  - Akihiko Hoshi
AU  - Masayuki Kurosaki
AU  - Kazuma Sasamura
AU  - Kaoru Tsuchiya
AU  - Kazuma Toda
AU  - Hirofumi Kuwabara
AU  - Meika Namba
AU  - Daigoro Matsubara
AU  - Sayako Oota
AU  - Yasuo Yoshioka
AU  - Ryoichi Yoshimura
AU  - Namiki Izumi
Y1  - 2020/10/07
PY  - 2020
N1  - https://doi.org/10.11648/j.ijcocr.20200503.13
DO  - 10.11648/j.ijcocr.20200503.13
T2  - International Journal of Clinical Oncology and Cancer Research
JF  - International Journal of Clinical Oncology and Cancer Research
JO  - International Journal of Clinical Oncology and Cancer Research
SP  - 65
EP  - 77
PB  - Science Publishing Group
SN  - 2578-9511
UR  - https://doi.org/10.11648/j.ijcocr.20200503.13
AB  - Background: The aim of this multicenter study was to evaluate the outcome of radiotherapy (RT) that targeted for tumor thrombi (TT) from hepatocellular carcinoma (HCC), including the portal vein, hepatic vein, inferior vena cava, and bile duct TT. Methods: Patients who received RT for the treatment of TT between 2005 and 2020 were retrospectively reviewed. We compared patient characteristics, overall survival (OS), the combined chemotherapy regimen, and objective response rates (ORRs) between the treatment modalities and analyzed cumulative incidence formula (CIF) for the deterioration in the Child-Pugh class and the progression of intrahepatic tumors. Results: We evaluated 64 patients, 39 of whom received combined chemotherapy with RT. Multivariate analysis showed that the Child-Pugh class, primary tumor size and the response of TT were significant prognostic factors for OS and the total equivalent dose in 2 Gy fractions (EQD2) of more than 48.75 Gy significantly contributed to ORRs (p=0.04). In the multivariate analysis of CIF, only acute liver damage was the significant factor for the deterioration in the Child-Pugh class (p=0.01) and the length of TT was significant for the progression of intrahepatic tumors (p=0.03). Conclusion: High doses should be delivered to TT, but long tumor thrombi are difficult to control. Tumor thrombus length is more important in predicting intrahepatic progression than the location of the tumor thrombus.
VL  - 5
IS  - 3
ER  -

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Author Information

Takuya Nagano

Department of Radiation Therapeutics and Oncology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
Akihiko Hoshi

Department of Radiology, Musashino Red Cross Hospital, Musashino-shi, Tokyo, Japan
Masayuki Kurosaki

Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino-shi, Tokyo, Japan
Kazuma Sasamura

Department of Radiation Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
Kaoru Tsuchiya

Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino-shi, Tokyo, Japan
Kazuma Toda

Department of Radiation Therapeutics and Oncology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
Hirofumi Kuwabara

Department of Radiology, Musashino Red Cross Hospital, Musashino-shi, Tokyo, Japan
Meika Namba

Department of Radiology, Musashino Red Cross Hospital, Musashino-shi, Tokyo, Japan
Daigoro Matsubara

Department of Radiology, Asahi General Hospital, Asahi-shi, Chiba, Japan
Sayako Oota

Department of Radiology, Asahi General Hospital, Asahi-shi, Chiba, Japan
Yasuo Yoshioka

Department of Radiation Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
Ryoichi Yoshimura

Department of Radiation Therapeutics and Oncology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
Namiki Izumi

Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino-shi, Tokyo, Japan

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APA Style

Takuya Nagano, Akihiko Hoshi, Masayuki Kurosaki, Kazuma Sasamura, Kaoru Tsuchiya, et al. (2020). Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study. International Journal of Clinical Oncology and Cancer Research, 5(3), 65-77. https://doi.org/10.11648/j.ijcocr.20200503.13

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ACS Style

Takuya Nagano; Akihiko Hoshi; Masayuki Kurosaki; Kazuma Sasamura; Kaoru Tsuchiya, et al. Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study. Int. J. Clin. Oncol. Cancer Res. 2020, 5(3), 65-77. doi: 10.11648/j.ijcocr.20200503.13

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AMA Style

Takuya Nagano, Akihiko Hoshi, Masayuki Kurosaki, Kazuma Sasamura, Kaoru Tsuchiya, et al. Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study. Int J Clin Oncol Cancer Res. 2020;5(3):65-77. doi: 10.11648/j.ijcocr.20200503.13

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@article{10.11648/j.ijcocr.20200503.13,
  author = {Takuya Nagano and Akihiko Hoshi and Masayuki Kurosaki and Kazuma Sasamura and Kaoru Tsuchiya and Kazuma Toda and Hirofumi Kuwabara and Meika Namba and Daigoro Matsubara and Sayako Oota and Yasuo Yoshioka and Ryoichi Yoshimura and Namiki Izumi},
  title = {Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study},
  journal = {International Journal of Clinical Oncology and Cancer Research},
  volume = {5},
  number = {3},
  pages = {65-77},
  doi = {10.11648/j.ijcocr.20200503.13},
  url = {https://doi.org/10.11648/j.ijcocr.20200503.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcocr.20200503.13},
  abstract = {Background: The aim of this multicenter study was to evaluate the outcome of radiotherapy (RT) that targeted for tumor thrombi (TT) from hepatocellular carcinoma (HCC), including the portal vein, hepatic vein, inferior vena cava, and bile duct TT. Methods: Patients who received RT for the treatment of TT between 2005 and 2020 were retrospectively reviewed. We compared patient characteristics, overall survival (OS), the combined chemotherapy regimen, and objective response rates (ORRs) between the treatment modalities and analyzed cumulative incidence formula (CIF) for the deterioration in the Child-Pugh class and the progression of intrahepatic tumors. Results: We evaluated 64 patients, 39 of whom received combined chemotherapy with RT. Multivariate analysis showed that the Child-Pugh class, primary tumor size and the response of TT were significant prognostic factors for OS and the total equivalent dose in 2 Gy fractions (EQD2) of more than 48.75 Gy significantly contributed to ORRs (p=0.04). In the multivariate analysis of CIF, only acute liver damage was the significant factor for the deterioration in the Child-Pugh class (p=0.01) and the length of TT was significant for the progression of intrahepatic tumors (p=0.03). Conclusion: High doses should be delivered to TT, but long tumor thrombi are difficult to control. Tumor thrombus length is more important in predicting intrahepatic progression than the location of the tumor thrombus.},
 year = {2020}
}

Copy | Download

TY  - JOUR
T1  - Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study
AU  - Takuya Nagano
AU  - Akihiko Hoshi
AU  - Masayuki Kurosaki
AU  - Kazuma Sasamura
AU  - Kaoru Tsuchiya
AU  - Kazuma Toda
AU  - Hirofumi Kuwabara
AU  - Meika Namba
AU  - Daigoro Matsubara
AU  - Sayako Oota
AU  - Yasuo Yoshioka
AU  - Ryoichi Yoshimura
AU  - Namiki Izumi
Y1  - 2020/10/07
PY  - 2020
N1  - https://doi.org/10.11648/j.ijcocr.20200503.13
DO  - 10.11648/j.ijcocr.20200503.13
T2  - International Journal of Clinical Oncology and Cancer Research
JF  - International Journal of Clinical Oncology and Cancer Research
JO  - International Journal of Clinical Oncology and Cancer Research
SP  - 65
EP  - 77
PB  - Science Publishing Group
SN  - 2578-9511
UR  - https://doi.org/10.11648/j.ijcocr.20200503.13
AB  - Background: The aim of this multicenter study was to evaluate the outcome of radiotherapy (RT) that targeted for tumor thrombi (TT) from hepatocellular carcinoma (HCC), including the portal vein, hepatic vein, inferior vena cava, and bile duct TT. Methods: Patients who received RT for the treatment of TT between 2005 and 2020 were retrospectively reviewed. We compared patient characteristics, overall survival (OS), the combined chemotherapy regimen, and objective response rates (ORRs) between the treatment modalities and analyzed cumulative incidence formula (CIF) for the deterioration in the Child-Pugh class and the progression of intrahepatic tumors. Results: We evaluated 64 patients, 39 of whom received combined chemotherapy with RT. Multivariate analysis showed that the Child-Pugh class, primary tumor size and the response of TT were significant prognostic factors for OS and the total equivalent dose in 2 Gy fractions (EQD2) of more than 48.75 Gy significantly contributed to ORRs (p=0.04). In the multivariate analysis of CIF, only acute liver damage was the significant factor for the deterioration in the Child-Pugh class (p=0.01) and the length of TT was significant for the progression of intrahepatic tumors (p=0.03). Conclusion: High doses should be delivered to TT, but long tumor thrombi are difficult to control. Tumor thrombus length is more important in predicting intrahepatic progression than the location of the tumor thrombus.
VL  - 5
IS  - 3
ER  -

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