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Journal of Cancer Therapy, 2020, 11, 115-123
https://www.scirp.org/journal/jct
ISSN Online: 2151-1942
ISSN Print: 2151-1934
DOI:
10.4236/jct.2020.113010 Mar. 6, 2020 115
Journal of Cancer Therapy
Treatment of Hepatocellular Carcinoma with
Portal Vein Tumor Thrombosis
Junyi Shi1, Ai Shen2,3, Tong Mou3, Zhongjun Wu3*
1Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
2Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China
3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Abstract
The prognosis of hepatocellular carcinoma (HCC) with
portal vein tumor
throm
bosis (PVTT) is very poor although sorafenib is recommended as the
first-
line treatment. Therefore, an effective treatment regime is needed for
treating HCC with PVTT. This review summarized seven potential treatment
regimes which in
cluding transarterial chemoembolization (TACE), TACE
combined with sorafenib, TACE combined with radiotherapy (RT), hepa-
tectomy, hepatic arterial infusion chemotherapy (HAIC), HAIC combined
with sorafenib and HAIC combined with RT in the treatment of HCC w
ith
PVTT. In conclusion, hepatectomy or the combination of HAIC and sorafe-
nib may be a more effective modality in the treatment of HCC patients with
type I - II PVTT. HAIC combined with or without sorafenib/RT or the com-
bination of RT and TACE is an alternative treatment choice
for HCC patients
with type III - IV PVTT. Further randomized controlled studies are war-
ranted.
Keywords
Hepatocellular Carcinoma, Portal Vein Tumor Thrombosis, Hepatic Arterial
Infusion Chemotherapy
1. Introduction
Hepatocellular carcinoma (HCC) is one of the seven leading cancer in the world
and the third leading cause of cancer related death [1]. HCC is asymptomatic
during the early stage, most HCC are diagnosed in intermediate or advanced
stage so that it is not candidate for surgery and thus affects the prognosis of pa-
tients. According to the American Association for the Study of Liver Diseases
How to cite this paper:
Shi, J.Y., Shen, A.,
Mou,
T. and Wu, Z.J. (2020)
Treatment of
Hepatocellular Carcinoma with Portal Vein
Tumor Thrombosis
.
Journal of Cancer The
r-
apy
,
11
, 115-123.
https://doi.org/10.4236/jct.2020.113010
Received:
February 20, 2020
Accepted:
March 3, 2020
Published:
March 6, 2020
Copyright © 20
20 by author(s) and
Scientific
Research Publishing Inc.
This work is
licensed under the Creative
Commons Attribution International
License (CC BY
4.0).
http://creativecommons.org/licenses/by/4. 0/
Open Access
J. Y. Shi et al.
DOI:
10.4236/jct.2020.113010 116
Journal of Cancer Therapy
(AASLD) guidelines, only 10% of HCC patients are suitable for surgical treat-
ment [2]. In terms of AASLD, European Association for the Study of the liver
and Asian Pacific Association for the Study of the Liver guidelines, transarterial
chemoembolization (TACE）is the first choice of intermediate stage HCC pa-
tients and sorafenib is the first-line treatment of advanced HCC [2] [3] [4].
However, approximately 35% - 45% of advanced HCC accompanied by portal
vein tumor thrombosis (PVTT) [2] [5] [6] which can cause several severe prog-
nosis-related complications such as portal hypertension, upper gastrointestinal
hemorrhage and hepatic encephalopathy. A systematic review has shown that
the median overall survival (mOS) of advanced HCC patients with PVTT is only
about 2.7 months, significantly lower than that of patients without PVTT in
which mOS is 24.4 months [7]. According to current guidelines, sorafenib is still
recommended as the first-line treatment for HCC with PVTT [2], and this rec-
ommendation is based on two phase III clinical trials (SHARP and ORIENTAL)
[5] [8]. However, Although the two trials showed a statistical significantly dif-
ference in survival between sorafenib and placebo (Harzard ratio(HR): 0.69, 90%
Confidence interval (CI): 0.53 - 0.89), the mOS of patients in sorafenib group
was only 47 days longer than that in placebo group (184 vs. 137 days) [9]. So, the
efficacy of sorafenib in the treatment of HCC patients with PVTT is limited.
Other more effective treatment regimes are warranted. Therefore, this review
will summarize and discuss the potential treatment modality in the treatment of
HCC with PVTT. This view was conducted based on an online search on Pubmed
by using the search items “hepatocelluar carcinoma” and “portal vein tumor
thrombosis” combined with “sorafenib” or “transaterial chemoembolization/trasa-
terial embolization” or “radiotherapy” or “hepatectomy/hepatic resection” or “he-
patic aterial infusion chemotherapy” with language limited to English, before
February 5, 2020.
2. TACE
Although TACE is recommended as the first-line treatment of intermediate
HCC [2] [3] [4], it is also effective for advanced HCC with PVTT. A prospective
study conducted by Luo et al. included 164 patients showed that the mOS of
HCC patients with PVTT in TACE treatment group was 7.1 months, signifi-
cantly longer than that in the conservative treatment group which was 4.1
months, especially for patients with type I - II PVTT which mOS was 10.2 and
5.2 months in TACE group and conservative group, respectively. Additionally,
the benefit of TACE for type III - IV PVTT was also better than that of conserv-
ative treatment (mOS: 5.3 vs 3.4 months) [10]. Niu’s study demonstrated that
the mOS of HCC patients with PVTT treated with TACE was 8.67 months,
much longer than that of conservative treatment which was only 1.4 months
[11]. A multicenter study showed that the mOS of patients in TACE group was 9
months and 6 months, respectively, compared with that in conservative treat-
ment group. For type I, II, III and IV PVTT, the mOS of TACE and conservative
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treatment group was 19, 12, 9, 6 and 12, 7, 7, 5 months, respectively. It showed
that TACE was significantly better than conservative group for treating type I, II
and III PVTT, but the benefit of TACE in type IV PVTT is not significant [12].
In addition, Pinter’s study shows that TACE is as effective as sorafenib in the
treatment of HCC with PVTT, and can be used as an alternative to sorafenib
[13]. However, TACE is only a locoregional therapy and it may lead to severe
liver dysfunction for type III - IV PVTT [14], so the usefulness of TACE in type
III - IV PVTT is controversial.
3. TACE Combined with Sorafenib
Due to that TACE is a locoregional therapy, so combined with a systematic
agent may improve the treatment efficacy. Choi’s study showed that TACE
combined with sorafenib was superior to sorafenib with respect to OS (HR: 0.64
and 0.48, 95% CI: 0.44, 0.92, P = 0.02), but, there was a significant difference in
the proportion of type III - IV PVTT patients between the two groups (24.5% vs.
36.2%) [15]. Although Yuan’s study showed that TACE combined with sorafenib
was superior to TACE alone in the treatment of hepatitis B-related HCC with
PVTT (mOS was 13.0 and 7.0 months, respectively), the study did not report the
complications after treatment [16]. In addition, a phase III randomized con-
trolled trial in Japan showed that TACE combined with sorafenib had no signif-
icant advantage over TACE alone in the treatment of unresectable advanced
HCC [17]. Also, TACE treatment may lead to severe liver dysfunction in the
treatment of type III - IV PVTT [14], so the combination treatment should be
further evaluated.
4. TACE Combined with Radiotherapy
Because the poor prognosis of patients with PVTT is mainly due to intrahepatic
dissemination or complications resulting from portal hypertension, rather than
the progression of the tumor itself, some researchers focused on treating PVTT
to improve the prognosis of HCC. Radiotherapy (RT) was used for treating solid
tumors for years, and it combined with TACE showed advantages in the treat-
ment of HCC with PVTT. The combination of the two therapeutic methods has
the following advantages: TACE can reduce the volume of tumor target so that
increase the radiation dose of RT to PVTT and reduce the damage of normal
liver tissue. RT can inhibit or kill the residual tumor after TACE. DSA can found
the tumor lesions that CT or MRI cannot found, which is convenient for RT to
sketching the target area [18]. A retrospective study of Lu showed that TACE
combined with 3D-RT significantly prolonged the survival time of HCC patients
with PVTT compared with TACE alone (mOS: 13.0 vs. 9.0 months, respectively)
[19]. Li’s propensity matching score study showed that TACE combined with
3D-RT was superior to TACE in the treatment of type II and III PVTT, with
mOS of 12.5, 8.9 and 4.4, 4.0 months, respectively. However, there was no sig-
nificant difference between the two treatment regime when treating HCC with
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type I and IV PVTT，with mOS of 23.7, 4.8 and 22.8, and 3.1 months, respec-
tively [18]. Wang’s study also showed that TACE combined with 3D-RT was
significantly better than hepatectomy, TACE, TACE combined with sorafenib
for type III PVTT, with mOS of 8.9, 6.0, 4.9 and 7.0 months, respectivey [20]. In
addition, stereotactic body radiotherapy (SBRT) is regarded superior to 3D-RT
due to its advantages of high accuracy, high dosage, high conformability and less
treatment times. A study showed that the combination of SBRT and TACE can
have some survival benefits compared with SBRT alone, but the combination
may also damage the liver function [21]. Moreover, these studies are all retros-
pective studies, and the sample size is small. Prospective studies are still needed
to verify the efficacy of TACE combined RT.
5. Hepatectomy
According to the guidelines, patients with HCC beyond Milan criteria are not
suitable for hepatectomy. However, studies have shown that if the tumor can be
completely removed, the patients can benefit from hepatectomy although HCC
beyond Milan criteria [22] [23]. If the tumor and PVTT can be completely re-
moved, patients can also obtain longer survival time and higher quality of life
[7]. Peng’s study showed that the 1-, 3-, 5-year survival rate of PVTT patients in
hepatectomy and TACE group were 42.0%, 14.1%, 11.1% and 37.8%, 7.3%, 0.5%,
respectively. Subgroup analysis showed that for type I (P < 0.001) and type II
(P = 0.002) PVTT, single tumor (P < 0.001) and tumor diameter > 5 cm (P <
0.001), the result favors hepatectomy [24]. Zheng’s study showed that the 1 -, 3 -,
and 5-year survival rates of PVTT patients in the hepatectomy group were
86.5%, 60.4%, and 33.3%, respectively, while those in the TACE group were
77.6%, 47.8%, and 20.9%, respectively (P = 0.021). Univariate and multivariate
analysis showed that the efficacy of hepatectomy was superior to that of TACE
[25]. Lee’s study showed that for HCC patients with PVTT, the survival time of
patients in hepatectomy group was significantly longer than that in TACE or
sorafenib group (mOS: 19.9, 6.6 and 6.2 months, respectively, P < 0.001) [26]. A
large case series study showed that hepatectomy (mOS: 15.9, and 12.5 months,
respectively) was significantly prong the survival than TACE (mOS: 9.3 and 4.9
months, respectively), TACE combined with sorafenib (mOS: 12.0 and 8.9
months, respectively), TACE combined with RT (12.2 and 10.6 months, respec-
tively) in the treatment of HCC patients with type I and II PVTT [20]. These
studies showed hepatectomy is beneficial in the treatment of HCC with PVTT,
especially in type I - II PVTT.
6. Hepatic Arterial Infusion Chemotherapy
Hepatic arterial infusion chemotherapy (HAIC) is considered as an effective
treatment for PVTT, which is widely used in Japan and Korea [27] [28] [29].
HAIC can increase and maintain the concentration of chemotherapeutic drugs
in tumor cells. Theoretically, HAIC can treat HCC and PVTT. Compared with
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systemic chemotherapy, the incidence of adverse events can be significantly re-
duced due to the decrease of systemic distribution of chemotherapeutic drugs.
Some retrospective studies showed that HAIC can improve the survival of HCC
patients with PVTT, which is significantly better than sorafenib [28] [29]. The
study of Nanako showed that continuous infusion of lipiodol and chemothera-
peutics via hepatic artery could significantly prolong the survival period of HCC
patients with type II - IV PVTT than sorafenib, and the mOS was 30.4 and 13.2
months, respectively [29]. A small randomized controlled trial involving only 58
patients showed that HAIC significantly prolong the survival time of HCC pa-
tients with type III - IV PVTT (mOS: 14.9 months vs 7.2 months) compared
with sorafenib [27]. These studies showed the advantages of HAIC in the treat-
ment of HCC with PVTT, but still need large scale clinical trials to verify because
most of these studies were retrospective or small sample size studies.
7. HAIC Combined with Sorafenib
Because HAIC is a locoregional treatment, and advanced HCC may have poten-
tial metastasis, a systematic treatment drug is needed for comprehensive treat-
ment. HAIC combined with sorafenib was used in many studies, and the result
favors the combination regime. Nagai’s study included 38 HCC patients with
type III - IV PVTT. The mOS of the patients treated with HAIC and sorafenib
was 315 days, which was significantly longer than that treated with HAIC alone
(197days) [30]. A prospective randomized controlled trial recruited 247 HCC
patients with PVTT showed that HAIC combined with sorafenib could signifi-
cantly prolong the survival time (mOS: 13.37 vs. 7.13 months, respectively), and
the progression-free survival time (median: 7.03 vs 2.6 months, respectively) of
patients compared with sorafenib alone [31]. The mOS of patients in combina-
tion therapy group and sorafenib monotherapy group was 18.17 and 10.87
months, respectively in type I - II PVTT subgroup, 13.47 and 6.27 months re-
spectively in type III PVTT subgroup, 9.47 and 5.5 months respectively in type
IV PVTT subgroup [31]. These studies indicate the effectiveness and feasibility
of HAIC combined with sorafenib in the treatment of HCC with PVTT.
8. HAIC Combined with RT
The purpose of HAIC combined with RT is to inhibit the growth of PVTT by
RT, protect the portal vein blood flow and prevent the deterioration of residual
liver function, so as to achieve the maximum therapeutic effect of HAIC. Oni-
shi’s retrospective study showed that HAIC combined with RT can significantly
improve the objective response rate of liver tumor (52% vs. 18%, P < 0.01) and
PVTT (45% vs. 18%, P = 0.01) compared with HAIC monotherapy in the treat-
ment of HCC patients with type III - IV PVTT, and its survival period is signifi-
cantly prolonged (mOS: 12.4 vs. 5.7 months) [32]. Kodama’s retrospective study
showed that HAIC combined with RT is superior to sorafenib in the treatment
of HCC with type III - IV PVTT with respect to PFS (median: 3.9 vs. 2.1 months)
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and OS (median: 9.9 vs. 5.3 months) [33]. However, these conclusions need to be
verified by further well-designed clinical studies.
9. Conclusion
Current studies showed that hepatectomy or the combination of HAIC and so-
rafenib may be a more effective modality in the treatment of HCC patients with
type I - II PVTT. HAIC combined with or without sorafenib/RT or, the combi-
nation of RT and TACE are potential beneficial regimens for the treatment of
HCC with type III - IV PVTT. Further studies are warranted to verify these con-
clusions.
Acknowledgements
Junyi Shi and Ai Shen contributed equally to this review.
Funding
This review was funding from the graduate tutor team construction project of
Chongqing Municipal Education Commission Foundation, China (No. dstd
201801).
Conflicts of Interest
The authors declare no conflicts of interest regarding the publication of this pa-
per.
References
[1] Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018)
Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality
Worldwide for 36 Cancers in 185 Countries.
CA
:
A Cancer Journal for Clinicians
,
68, 394-424. https://doi.org/10.3322/caac.21492
[2] Heimbach, J.K., Kulik, L.M., Finn, R.S., Sirlin, C.B., Abecassis, M.M., Roberts, L.R.,
et al.
(2018) AASLD Guidelines for the Treatment of Hepatocellular Carcinoma.
Hepatology
, 67, 358-380. https://doi.org/10.1002/hep.29086
[3] European Association for the Study of the Liver. Electronic Address EEE, Eu ropean
Association for the Study of the L (2018) EASL Clinical Practice Guidelines: Man-
agement of Hepatocellular Carcinoma.
Journal of Hepatology
, 69, 182-236.
[4] Omata, M., Cheng, A.L., Kokudo, N., Kudo, M., Lee, J.M., Jia, J.,
et al.
(2017) Asia-
Pacific Clinical Practice Guidelines on the Management of Hepatocellular Carci-
noma: A 2017 Update.
Hepatology International
, 11, 317-370.
https://doi.org/10.1007/s12072-017-9799-9
[5] Llovet, J.M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J.F.,
et al.
(2008)
Sorafenib in Advanced Hepatocellular Carcinoma.
The New England Journal of
Medicine
, 359, 378-390. https://doi.org/10.1056/NEJMoa0708857
[6] Llovet, J.M., Bustamante, J., Castells, A., Vilana, R., Ayuso Mdel, C., Sala, M.,
et al.
(1999) Natural History of Untreated Nonsurgical Hepatocellular Carcinoma: Ra-
tionale for the Design and Evaluation of Therapeutic Trials.
Hepatology
, 29, 62-67.
https://doi.org/10.1002/hep.510290145
J. Y. Shi et al.
DOI:
10.4236/jct.2020.113010 121
Journal of Cancer Therapy
[7] Zhang, Z.Y., Dong, K.S., Zhang, E.L., Zhang, L.W., Chen, X.P. and Dong, HH.
(2019) Resection Might Be a Meaningful Choice for Hepatocellular Carcinoma with
Portal Vein Thrombosis: A Systematic Review and Meta-Analysis.
Medicine
, 98,
e18362. https://doi.org/10.1097/MD.0000000000018362
[8] Cheng, A.L., Kang, Y.K., Chen, Z., Tsao, C.J., Qin, S., Kim, J.S.,
et al.
(2009) Efficacy
and Safety of Sorafenib in Patients in the Asia-Pacific Region with Advanced Hepa-
tocellular Carcinoma: A Phase III Randomised, Double-Blind, Placebo-Controlled
Trial.
The Lancet Oncology
, 10, 25-34.
https://doi.org/10.1016/S1470-2045(08)70285-7
[9] Bruix, J., Cheng, A.L., Meinhardt, G., Nakajima, K., De Sanctis, Y. and Llovet, J.
(2017) Prognostic Factors and Predictors of Sorafenib Benefit in Patients with He-
patocellular Carcinoma: Analysis of Two Phase III Studies.
Journal of Hepatology
,
67, 999-1008. https://doi.org/10.1016/j.jhep.2017.06.026
[10] Luo, J., Guo, R.P., Lai, E.C., Zhang, Y.J., Lau, W.Y., Chen, M.S.,
et al.
(2011) Trans-
arterial Chemoembolization for Unresectable Hepatocellular Carcinoma with Portal
Vein Tumor Thrombosis: A Prospective Comparative Study.
Annals of Surgical
Oncology
, 18, 413-420. https://doi.org/10.1245/s10434-010-1321-8
[11] Niu, Z.J., Ma, Y.L., Kang, P., Ou, S.Q., Meng, Z.B., Li, Z.K.,
et al.
(2012) Transar-
terial Chemoembolization Compared with Conservative Treatment for Advanced
Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: Using a New Classi-
fication.
Medical Oncology
, 29, 2992-2997.
https://doi.org/10.1007/s12032-011-0145-0
[12] Xiang, X., Lau, W.Y., Wu, Z.Y., Zhao, C., Ma, Y.L., Xiang, B.D.,
et al.
(2019) Trans-
arterial Chemoembolization versus Best Supportive Care for Patients with Hepato-
cellular Carcinoma with Portal Vein Tumor Thrombusa Multicenter Study.
Euro-
pean Journal of Surgical Oncology
, 45, 1460-1467.
https://doi.org/10.1016/j.ejso.2019.03.042
[13] Pinter, M., Hucke, F., Graziadei, I., Vogel, W., Maieron, A., Konigsberg, R.,
et al.
(2012) Advanced-Stage Hepatocellular Carcinoma: Transarterial Chemoemboliza-
tion versus Sorafenib.
Radiology
, 263, 590-599.
https://doi.org/10.1148/radiol.12111550
[14] Chung, J.W., Park, J.H., Han, J.K., Choi, B.I., Han, M.C., Lee, H.S.,
et al.
(1996) He-
patic Tumors: Predisposing Factors for Complications of Transcatheter Oily Che-
moembolization.
Radiology
, 198, 33-40.
https://doi.org/10.1148/radiology.198.1.8539401
[15] Choi, G.H., Shim, J.H., Kim , M.J., Ryu, M.H., Ryoo, B.Y., Kang, Y.K.,
et al.
(2013)
Sorafenib Alone versus Sorafenib Combined with Transarterial Chemoembolization
for Advanced-Stage Hepatocellular Carcinoma: Results of Propensity Score Analys-
es.
Radiology
, 269, 603-611. https://doi.org/10.1148/radiol.13130150
[16] Yuan, J., Yin, X., Tang, B., Ma, H., Zhang, L., Li, L.,
et al.
(2019) Transarterial Che-
moembolization (TACE) Combined with Sorafenib in Treatment of HBV Back-
ground Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Propen-
sity Score Matching Study.
BioMed Research International
, 2019, Article ID:
2141859. https://doi.org/10.1155/2019/2141859
[17] Kudo, M., Imanaka, K., Chida, N., Nakachi, K., Tak, W.Y., Takayama, T.,
et al.
(2011) Phase III Study of Sorafenib after Transarterial Chemoembolisation in Japa-
nese and Korean Patients with Unresectable Hepatocellular Carcinoma.
European
Journal of Cancer
, 47, 2117-2127. https://doi.org/10.1016/j.ejca.2011.05.007
[18] Li, X.L., Guo, W.X., Hong, X.D., Yang, L., Wang, K., Shi, J.,
et al.
(2016) Efficacy of
J. Y. Shi et al.
DOI:
10.4236/jct.2020.113010 122
Journal of Cancer Therapy
the Treatment of Transarterial Chemoembolization Combined with Radiotherapy
for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Propensity
Score Analysis.
Hepatology Research
, 46, 1088-1098.
https://doi.org/10.1111/hepr.12657
[19] Lu, D.H., Fei, Z.L., Zhou, J.P., Hu Z.T. and Hao, W.S. (2015) A Comparison be-
tween Three-Dimensional Conformal Radiotherapy Combined with Interventional
Treatment and Interventional Treatment Alone for Hepatocellular Carcinoma with
Portal Vein Tumour Thrombosis.
Journal of Medical Imaging and Radiation On-
cology
, 59, 109-114. https://doi.org/10.1111/1754-9485.12207
[20] Wang, K., Guo, W.X., Chen, M.S., Mao, Y.L., Sun, B.C., Shi, J.,
et al.
(2016) Multi-
modality Treatment for Hepatocellular Carcinoma with Portal Vein Tumor
Thrombus: A Large-Scale, Multicenter, Propensity Mathching Score Analysis.
Medicine
, 95, e3015. https://doi.org/10.1097/MD.0000000000003015
[21] Kang, J., Nie, Q., Du, R., Zhang, L., Zhang, J., Li, Q.,
et al.
(2014) Stereotactic Body
Radiotherapy Combined with Transarterial Chemoembolization for Hepatocellular
Carcinoma with Portal Vein Tumor Thrombosis.
Molecular and Clinical Oncology
,
2, 43-50. https://doi.org/10.3892/mco.2013.196
[22] Liu, P.H., Lee, Y.H., Hsu, C.Y., Hsia, C.Y., Huang, Y.H., Chiou, Y.Y.,
et al.
(2014)
Surgical Resection Is Better than Transarterial Chemoembolization for Hepatocel-
lular Carcinoma beyond Milan Criteria Independent of Performance Status.
The
Journal of Gastrointestinal Surgery
, 18, 1623-1631.
https://doi.org/10.1007/s11605-014-2546-9
[23] Zhao, Y.N., Zhang, Y.Q., Ye, J.Z., Liu, X., Yang, H.Z., Cong, F.Y.,
et al.
(2016) He-
patic Resection versus Transarterial Chemoembolization for Patients with Barcelo-
na Clinic Liver Cancer Intermediate Stage Child-Pugh A Hepatocellular Carcinoma.
Experimental and Therapeutic Medicine
, 12, 3813-3819.
https://doi.org/10.3892/etm.2016.3810
[24] Peng, Z.W., Guo, R.P., Zhang, Y.J., Lin, X.J., Chen, M.S. and Lau, W.Y. (2012) He-
patic Resection versus Transcatheter Arterial Chemoembolization for the Treat-
ment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.
Cancer
,
118, 4725-4736. https://doi.org/10.1002/cncr.26561
[25] Zheng, N., Wei, X., Zhang, D., Chai, W., Che, M., Wang, J.,
et al.
(2016) Hepatic
Resection or Transarterial Chemoembolization for Hepatocellular Carcinoma with
Portal Vein Tumor Thrombus.
Medicine
, 95, e3959.
https://doi.org/10.1097/MD.0000000000003959
[26] Lee, J.M., Jang, B.K., Lee, Y.J., Choi, W.Y., Choi, S.M., Chung, W.J.,
et al.
(2016)
Survival Outcomes of Hepatic Resection Compared with Transarterial Chemoem-
bolization or Sorafenib for Hepatocellular Carcinoma with Portal Vein Tumor
Thrombosis.
Clinical and Molecular Hepatology
, 22, 160-167.
https://doi.org/10.3350/cmh.2016.22.1.160
[27] Choi, J.H., Chung, W.J., Bae, S.H., Song, D.S., Song, M.J., Kim, Y.S.,
et al.
(2018)
Randomized, Prospective, Comparative Study on the Effects and Safety of Sorafenib
vs. Hepatic Arterial Infusion Chemotherapy in Patients with Advanced Hepatocel-
lular Carcinoma with Portal Vein Tumor Thrombosis.
Cancer Chemotherapy and
Pharmacology
, 82, 469-478. https://doi.org/10.1007/s00280-018-3638-0
[28] Song, D.S., Song, M.J., Bae, S.H., Chung, W.J., Jang, J.Y., Kim, Y.S.,
et al.
(2015) A
Comparative Study between Sorafenib and Hepatic Arterial Infusion Chemotherapy
for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis.
The
Journal of Gastroenterology
, 50, 445-454.
J. Y. Shi et al.
DOI:
10.4236/jct.2020.113010 123
Journal of Cancer Therapy
https://doi.org/10.1007/s00535-014-0978-3
[29] Nakano, M., Niizeki, T., Nagamatsu, H., Tanaka, M., Kuromatsu, R., Satani, M.,
et
al.
(2017) Clinical Effects and Safety of Intra-Arterial Infusion Therapy of Cisplatin
Suspension in Lipiodol Combined with 5-Fluorouracil versus Sorafenib, for Ad-
vanced Hepatocellular Carcinoma with Macroscopic Vascular Invasion without Ex-
tra-Hepatic Spread: A Prospective Cohort Study.
Molecular and Clinical Oncology
,
7, 1013-1020. https://doi.org/10.3892/mco.2017.1442
[30] Nagai, H., Mukozu, T., Ogino, Y.U., Matsui, D., Matsu i, T., Wakui, N.,
et al.
(2015)
Sorafenib and Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellu-
lar Carcinoma with Portal Vein Tumor Thrombus.
Anticancer Research
, 35,
2269-2277.
[31] He, M., Li, Q., Zou, R., Shen, J., Fang, W., Tan, G.,
et al.
(2019) Sorafenib Plus He-
patic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib
alone for Hepatocellular Carcinoma with Portal Vein Invasion: A Randomized
Clinical Trial.
JAMA Oncology
, 5, 953-960.
https://doi.org/10.1001/jamaoncol.2019.0250
[32] Onishi, H., Nouso, K., Nakamura, S., Katsui, K., Wada, N., Morimoto, Y.,
et al.
(2015) Efficacy of Hepatic Arterial Infusion Chemotherapy in Combination with
Irradiation for Advanced Hepatocellular Carcinoma with Portal Vein Invasion.
Hepatology International
, 9, 105-112. https://doi.org/10.1007/s12072-014-9592-y
[33] Kodama, K., Kawaoka, T., Aikata, H., Uchikawa, S., Nishida, Y., Inagaki, Y.,
et al.
(2018) Comparison of Outcome of Hepatic Arterial Infusion Chemotherapy Com-
bined with Radiotherapy and Sorafenib for Advanced Hepatocellular Carcinoma
Patients with Major Portal Vein Tumor Thrombosis.
Oncology
, 94, 215-222.
https://doi.org/10.1159/000486483
