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Ma J, Zhang H, Zheng R, Wang S, Ding L. Radiotherapy with targeted and immunotherapy improved overall survival and progression-free survival for hepatocellular carcinoma with portal vein tumor thrombosis. Oncologist 2025; 30:oyae209. [PMID: 39231443 PMCID: PMC11883153 DOI: 10.1093/oncolo/oyae209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 07/16/2024] [Indexed: 09/06/2024] Open
Abstract
BACKGROUND The efficacy of radiotherapy (RT) combined with targeted therapy and immunotherapy in treating hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) is still unclear. This study investigated the efficacy and safety of RT combined with targeted therapy and immunotherapy in HCC with PVTT. MATERIALS AND METHODS Seventy-two patients with HCC with PVTT treated with tyrosine kinase inhibitor (TKI) plus programmed cell death protein-1 (PD-1) inhibitor with or without RT from December 2019 to December 2023 were included. After propensity score matching (PSM) for adjusting baseline differences, 32 pairs were identified in RT + TKI + PD-1 group (n = 32) and TKI + PD-1 group (n = 32). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS Median OS (mOS) in RT + TKI + PD-1 group was significantly longer than TKI + PD-1 group (15.6 vs. 8.2 months, P = .008). Median PFS (mPFS) in RT + TKI + PD-1 group was dramatically longer than TKI + PD-1 group (8.1 vs. 5.2 months, P = .011). Patients in TKI + PD-1 + RT group showed favorable ORR and DCR compared with TKI + PD-1 group (78.1% vs. 56.3%, P = .055; 93.8% vs. 81.3%, P = .128). Subgroup analysis demonstrated a remarkable OS and PFS benefit with TKI + PD-1 + RT for patients with main PVTT (type III/IV) and those of Child-Pugh class A. Multivariate analysis confirmed RT + TKI + PD-1 as an independent prognostic factor for longer OS (HR 0.391, P = .024) and longer PFS (HR 0.487, P = .013), with no mortality or severe TRAEs. CONCLUSION RT combined with TKI and PD-1 inhibitor could significantly improve mOS and mPFS without inducing severe TRAEs or mortality.
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Affiliation(s)
- Jianing Ma
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China
| | - Haifeng Zhang
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China
| | - Ruipeng Zheng
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China
| | - Shudong Wang
- Department of Cardiology, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China
| | - Lijuan Ding
- Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China
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Sui WF, Li JY, Fu JH. Transarterial chemoembolization plus stent placement for hepatocellular carcinoma with main portal vein tumor thrombosis: A meta-analysis. World J Clin Oncol 2024; 15:447-455. [PMID: 38576592 PMCID: PMC10989260 DOI: 10.5306/wjco.v15.i3.447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 01/05/2024] [Accepted: 02/04/2024] [Indexed: 03/22/2024] Open
Abstract
BACKGROUND Portal vein tumor thrombus is an important indicator of poor prognosis in patients with hepatocellular carcinoma. Transarterial chemoembolization is recommended as the standard first-line therapy for unresectable hepatocellular carcinoma. Portal vein stent placement is a safe and effective therapy for promptly restoring flow and relieving portal hypertension caused by tumor thrombus. AIM To assess the clinical significance of transarterial chemoembolization plus stent placement for the treatment of hepatocellular carcinoma with main portal vein tumor thrombosis. METHODS We searched English and Chinese databases, assessed the quality of the included studies, analyzed the characteristic data, tested heterogeneity, explored heterogeneity, and tested publication bias. RESULTS In total, eight clinical controlled trials were included. The results showed that the pressure in the main portal vein after stent placement was significantly lower than that with no stent placement. The cumulative stent patency and survival rates at 6 and 12 months were lower in the transarterial chemoembolization + stent placement group than in the transarterial chemoembolization + stent placement + brachytherapy/radiotherapy group. The survival rates of patients treated with transarterial chemoembolization + stent placement for 6 and 12 months were higher than those of patients treated with transarterial chemoembolization alone. CONCLUSION For Chinese patients with hepatocellular carcinoma with main portal vein tumor thrombosis, transarterial chemoembolization plus stenting is effective. Transarterial chemoembolization + stent placement is more effective than transarterial chemoembolization alone. Transarterial chemoembolization + stent placement + brachytherapy/radiotherapy is more effective than transarterial chemoembolization + stenting.
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Affiliation(s)
- Wei-Fan Sui
- Department of Interventional Radiology, Zhenjiang First People's Hospital, Zhenjiang 212000, Jiangsu Province, China
| | - Jian-Yun Li
- Department of Interventional Radiology, Zhenjiang First People's Hospital, Zhenjiang 212000, Jiangsu Province, China
| | - Jian-Hua Fu
- Department of Interventional Radiology, Zhenjiang First People's Hospital, Zhenjiang 212000, Jiangsu Province, China
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Zhao Y, He GS, Li G. Triplet regimen as a novel modality for advanced unresectable hepatocellular carcinoma: A case report and review of literature. World J Clin Cases 2023; 11:6558-6564. [PMID: 37900216 PMCID: PMC10601001 DOI: 10.12998/wjcc.v11.i27.6558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 08/22/2023] [Accepted: 08/31/2023] [Indexed: 09/20/2023] Open
Abstract
BACKGROUND Portal vein tumor thrombus (PVTT) is a common complication, accounting for 44%-62.2% of Hepatocellular carcinoma (HCC), and often indicates the poor prognosis. There is no global consensus for the treatment of unresectable HCC with PVTT. In the present case, we reported a novel strategy of radiotherapy-antiangiogenesis-immune checkpoint blockade combination, which showed better response and prolonged survival. CASE SUMMARY A 51-year-old male diagnosed with HCC (Child-Pugh class A), chronic hepatitis B virus infection and Cheng's type III PVTT, was given radiotherapy to part of the lesion plus targeted therapy as the first-line therapy, and achieved partial remission. After radiotherapy, lenvatinib plus pembrolizumab was used as maintenance therapy, and complete remission was achieved. The patient remains alive 46 months after the diagnosis of the HCC with PVTT. CONCLUSION This case of unresectable HCC patient with PVTT treated by radiation-lenvatinib-pembrolizumab combination therapy shows apparent clinical efficacy, which demonstrates that local radiotherapy plus antiangiogenesis and immune checkpoint blockad could also benefit patients with advanced HCC.
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Affiliation(s)
- Ying Zhao
- Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Guo-Sheng He
- Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Gong Li
- Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
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Sidhu MS, Ramandeep, Sood S, Aggarwal R, Singh K, Sood D. Role of rapid arc-image-guided radiotherapy in hepatocellular carcinoma with portal vein tumor thrombosis: A study from tertiary care center in Punjab, India. J Cancer Res Ther 2023; 19:639-643. [PMID: 37470587 DOI: 10.4103/jcrt.jcrt_365_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Background and Objectives Treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is very challenging with poor outcome. In this situation, radiotherapy has become an alternative treatment modality, more precisely due to advances in radiation techniques. The goal of our study is to do analysis of these patients treated with rapid arc image-guided technology (RA-IGRT) at our institution. Materials and Methods Thirteen patients were included in the study. As per intuition policy, patient set up, contouring, and treatment plans were generated. Radiological response assessment was done 1-month post-radiotherapy. Survival analysis curve along with Chi-square test for prognostic factors assessment was done using SPSS. Results With median dose of 45 Gy in 20 fractions, we were able to achieve 27.3% objective response rate with median survival of 5 months in eligible patients. Conclusions One-year overall survival up to 30% can be achieved in HCC with PVTT, especially in patients with objective response to radiotherapy with Japan Integrated Staging score 2, provided it is precisely hit by RA-IGRT.
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Affiliation(s)
| | - Ramandeep
- Department of Radiology, SPS Hospital, Ludhiana, Punjab, India
| | - Sandhya Sood
- Department of Radiation Oncology, DMCH Cancer Center, Ludhiana, Punjab, India
| | - Ritu Aggarwal
- Department of Radiation Oncology, DMCH Cancer Center, Ludhiana, Punjab, India
| | - Kulbir Singh
- Department of Medical Physics, DMCH Cancer Center, Ludhiana, Punjab, India
| | - Divyanshi Sood
- Department of Radiation Oncology, DMCH Cancer Center, Ludhiana, Punjab, India
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Park HJ, Choi G, Ha S, Kim Y, Choi MJ, Kim M, Islam MK, Chang Y, Kwon TJ, Kim D, Jang E, Kim TH, Chang SJ, Kim YH. MBP-11901 Inhibits Tumor Growth of Hepatocellular Carcinoma through Multitargeted Inhibition of Receptor Tyrosine Kinases. Cancers (Basel) 2022; 14:cancers14081994. [PMID: 35454900 PMCID: PMC9030223 DOI: 10.3390/cancers14081994] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 12/02/2022] Open
Abstract
Simple Summary Although various treatments such as surgery and chemotherapy exist for advanced or unresectable HCC, most patients suffer from intractable diseases, having a poor prognosis. While immunotherapy using immune checkpoint inhibitors was recently proposed for HCC, only a small percentage of patients respond. Thus, there remains an unmet need for the development of therapeutic agents for the treatment of liver cancer. Here, we presented multi-RTKi MBP-11901, an innovative targeted anticancer agent for HCC, suggesting it as a new therapeutic strategy for the treatment of liver cancer. Abstract Hepatocellular carcinomas (HCCs) are aggressive tumors with a poor prognosis. Approved first-line treatments include sorafenib, lenvatinib, and a combination of atezolizumab and bevacizumab; however, they do not cure HCC. We investigated MBP-11901 as a drug candidate for HCC. Cell proliferation and cytotoxicity were evaluated using normal and cancer human liver cell lines, while Western blotting and flow cytometry evaluated apoptosis. The anticancer effect of MBP-11901 was verified in vitro through migration, invasion, colony formation, and JC-1 MMP assays. In mouse models, the tumor volume, tumor weight, and bodyweight were measured, and cancer cell proliferation and apoptosis were analyzed. The toxicity of MBP-11901 was investigated through GOT/GPT and histological analyses in the liver and kidney. The signaling mechanism of MBP-11901 was investigated through kinase assays, phosphorylation analysis, and in silico docking simulations. Results. MBP-11901 was effective against various human HCC cell lines, leading to the disappearance of most tumors when administered orally in animal models. This effect was dose-dependent, with no differences in efficacy according to administration intervals. MBP-11901 induced anticancer effects by targeting the signaling mechanisms of FLT3, VEGFR2, c-KIT, and PDGFRβ. MBP-11901 is suggested as a novel therapeutic agent for the treatment of advanced or unresectable liver cancer.
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Affiliation(s)
- Hyun Jin Park
- R&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, Korea; (H.J.P.); (G.C.); (Y.K.); (M.-J.C.); (S.J.C.)
| | - Garam Choi
- R&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, Korea; (H.J.P.); (G.C.); (Y.K.); (M.-J.C.); (S.J.C.)
| | - Seongmin Ha
- Institute of Biomedical Engineering Research, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu 41944, Korea; (S.H.); (M.K.I.); (Y.C.)
| | - Yesl Kim
- R&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, Korea; (H.J.P.); (G.C.); (Y.K.); (M.-J.C.); (S.J.C.)
| | - Min-Jin Choi
- R&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, Korea; (H.J.P.); (G.C.); (Y.K.); (M.-J.C.); (S.J.C.)
| | - Minsup Kim
- InCerebro Drug Discovery Institute, Seoul 01811, Korea;
| | - Md. Kamrul Islam
- Institute of Biomedical Engineering Research, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu 41944, Korea; (S.H.); (M.K.I.); (Y.C.)
| | - Yongmin Chang
- Institute of Biomedical Engineering Research, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu 41944, Korea; (S.H.); (M.K.I.); (Y.C.)
| | - Tae-Jun Kwon
- Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation, 80, Cheombok-ro, Dong-gu, Daegu 41061, Korea; (T.-J.K.); (D.K.)
| | - Dongkyu Kim
- Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation, 80, Cheombok-ro, Dong-gu, Daegu 41061, Korea; (T.-J.K.); (D.K.)
| | - Eunbee Jang
- College of Pharmacy, Daegu Catholic University, 13-13, Hayang-ro, Hayang-eup, Gyeongsan-si 38430, Korea; (E.J.); (T.H.K.)
| | - Tae Hwan Kim
- College of Pharmacy, Daegu Catholic University, 13-13, Hayang-ro, Hayang-eup, Gyeongsan-si 38430, Korea; (E.J.); (T.H.K.)
| | - Sha Joung Chang
- R&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, Korea; (H.J.P.); (G.C.); (Y.K.); (M.-J.C.); (S.J.C.)
| | - Yeoun-Hee Kim
- R&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, Korea; (H.J.P.); (G.C.); (Y.K.); (M.-J.C.); (S.J.C.)
- Correspondence: ; Tel.: +82-31-776-3403
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Srivastava A, Parambath HK, Ramdulari AV, Saxena H, Kumar R, Pandey S, Shalimar, Gupta S, Jee B. Is hepatocellular carcinoma complicated with portal vein tumor thrombosis potentially curable by radiotherapy in the form of stereotactic body radiation therapy? Int J Radiat Biol 2022; 98:1495-1509. [PMID: 35311612 DOI: 10.1080/09553002.2022.2055800] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
PURPOSE The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal. Despite best treatment and care, the patients with this malignancy only showed 2.7-4 months of overall survival. It is debatable whether liver transplantation helps PVTT sufferers. The effectiveness of radiation therapy in treating HCC patients with PVTT should not be undervalued. By limiting the high dosage region to a small planning target volume, stereotactic radiation delivery has shifted toward hypofractionation, limiting the radiation exposure to healthy organs and tissues. Stereotactic body radiotherapy (SBRT) has a local control rate of 75-100%, depending on the treatment. The major limitation in SBRT for hepatocellular carcinoma with PVTT is the paucity of prospective evidence for longer periods beyond the first two years after treatment. More prospective studies/randomized clinical trials with a longer follow-up, larger sample size, and adequate statistical power are the dire need of the present situation to ascertain the curative effect of SBRT as primary therapy for advanced HCC with PVTT. CONCLUSION SBRT can improve survival, particularly for patients receiving multidisciplinary treatment. This review sums up our most current understanding of how radiation therapy, notably SBRT, can be used to treat hepatocellular carcinoma when combined with PVTT. Recent research has led us to believe that irradiation in the form of SBRT may cure hepatocellular carcinoma complicated by PVTT.
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Affiliation(s)
- Astha Srivastava
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Haresh Kunhi Parambath
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Anjali V Ramdulari
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Harsh Saxena
- Department of Medicine Trauma, All India Institute of Medical Sciences, New Delhi, India
| | - Rishabh Kumar
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Suyash Pandey
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Subhash Gupta
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Babban Jee
- Department of Health Research, Ministry of Health and Family Welfare, Government of India, New Delhi, India
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7
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Li S, Guo JH, Lu J, Wang C, Wu H, Wang H, Zha J, Fan R. I 125 irradiation stent for treatment of hepatocellular carcinoma with portal vein thrombosis: A meta-analysis. Cancer Radiother 2021; 25:340-349. [PMID: 33455874 DOI: 10.1016/j.canrad.2020.12.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 11/10/2020] [Accepted: 12/14/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE A meta-analysis aimed to systematically evaluate the safety and efficiency of I125 irradiation stent placement for patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS The Cochrane library, PubMed/Medline, EMBASE, CNKI, Wanfang Data and CQVIP were systematically screened out from the earliest to December 2019. The qualities of all included studies were assessed. The primary endpoints were the 6-month, 12-month stent cumulative patency rate and 6-month, 12-month, 24-month overall survival rate while the secondary endpoints were the objective response rate of PVTT, main portal venous pressure changes and treatment-related adverse events. Our meta-analysis was conducted using Stata 12.0 software. RESULTS Totally seven studies with 1018 patients were included in the final analysis, in which 602 patients received TACE and I125 irradiation stent placement, and 416 patients in control group underwent TACE and stent placement without endovascular brachytherapy (EVBT). Meta-analysis showed that the I125 irradiation stent improved the cumulative stent patency rates in 6months [OR=1.65, 95% CI (1.32-2.05), P<0.001] and 12months [OR=2.55, 95% CI (1.90-3.42), P<0.001] and the survival rates in 6months [OR=1.77, 95% CI (1.41-2.22), P<0.001], 12months [OR=3.14, 95% CI (2.24-4.40), P<0.001] and 24months [OR=7.39, 95% CI (3.55-15.41), P<0.001]. However, there was no difference in the objective response rate of PVTT [OR=1.13, 95% CI (0.87-1.48), P=0.365], main portal venous pressure and the occurrence adverse event [OR=0.88, CI=0.72-1.08, P=0.212] between two groups. CONCLUSION I125 irradiation stent seems to be more effective in treating hepatocellular carcinoma with portal vein tumor thrombosis. The usage of portal vein stent combined endovascular brachytherapy has the potential to act as an alternative therapy for HCC with PVTT. On account of the limitation of studies included, more studies with high-level evidence, such as RCTs, are requisite to support the above promising results.
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Affiliation(s)
- S Li
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - J-H Guo
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - J Lu
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - C Wang
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - H Wu
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - H Wang
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - J Zha
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - R Fan
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
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Park J, Park JW, Kang MK. Current status of stereotactic body radiotherapy for the treatment of hepatocellular carcinoma. Yeungnam Univ J Med 2019; 36:192-200. [PMID: 31620633 PMCID: PMC6784649 DOI: 10.12701/yujm.2019.00269] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 07/22/2019] [Accepted: 07/30/2019] [Indexed: 12/19/2022] Open
Abstract
Stereotactic body radiotherapy (SBRT) is an advanced form of radiotherapy (RT) with a growing interest on its application in the treatment of hepatocellular carcinoma (HCC). It can deliver ablative radiation doses to tumors in a few fractions without excessive doses to normal tissues, with the help of advanced modern RT and imaging technologies. Currently, SBRT is recommended as an alternative to curative treatments, such as surgery and radiofrequency ablation. This review discusses the current status of SBRT to aid in the decision making on how it is incorporated into the HCC management.
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Affiliation(s)
- Jongmoo Park
- Department of Radiation Oncology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jae Won Park
- Department of Radiation Oncology, Yeungnam University College of Medicine, Daegu, Korea
| | - Min Kyu Kang
- Department of Radiation Oncology, School of Medicine, Kyungpook National University, Daegu, Korea
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9
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Wang L, Chen B, Li Z, Yao X, Liu M, Rong W, Wu F, Lin S, Liu Y, Zheng Y, Li Y, Wang W, Wu J. Optimal postoperative adjuvant treatment strategy for HBV-related hepatocellular carcinoma with microvascular invasion: a propensity score analysis. Onco Targets Ther 2019; 12:1237-1247. [PMID: 30863091 PMCID: PMC6388954 DOI: 10.2147/ott.s179247] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Microvascular invasion (MVI) is the most important risk factor associated with early postoperative recurrence in patients with hepatocellular carcinoma (HCC). However, the efficacy of postoperative adjuvant treatment for preventing recurrence in HCC patients with MVI has not been assessed. This study investigated the efficacy of postoperative adjuvant radiotherapy (RT) and transcatheter arterial chemoembolization (TACE) in HCC patients with MVI. Materials and methods From July 2008 to December 2016, 117 hepatitis B virus (HBV)-related HCC patients with MVI were retrospectively divided into two groups based on postoperative adjuvant treatments. Propensity score matching (PSM) was performed to adjust for significant differences in baseline characteristics. Relapse-free survival (RFS) and overall survival (OS) of the two groups were analyzed before and after PSM. Results Of all patients, the RT group had significantly smaller tumor size and milder MVI classification. PSM analysis created 46 pairs of patients. After matching, the two groups of patients were similar in baseline characteristics. Multivariate analysis indicated that tumor size, MVI classification, and postoperative treatment strategies were independently associated with RFS; tumor size and MVI classification were independently associated with OS. Similar multivariate analysis results were demonstrated after matching propensity score. Survival analysis revealed that the estimated median RFS and OS of patients with RT and TACE were 25.74±8.12 vs 9.18±1.67 months (P=0.003) and 60.69±7.36 vs 36.53±5.34 months (P=0.262), respectively. The RT group had significantly longer RFS than the TACE group. Conclusion Postoperative adjuvant RT offers better RFS for HCC patients with MVI than TACE.
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Affiliation(s)
- Liming Wang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhuo Li
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xuesong Yao
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mei Liu
- Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiqi Rong
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Fan Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Shengtao Lin
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Yunhe Liu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Yiling Zheng
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Yexiong Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weihu Wang
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China,
| | - Jianxiong Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
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Transarterial chemoembolization combined with computed tomography-guided 125iodine implantation enhances survival in hepatocellular carcinoma patients with portal vein tumor thrombus. Oncotarget 2018; 8:29258-29268. [PMID: 28418927 PMCID: PMC5438728 DOI: 10.18632/oncotarget.16491] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 02/14/2017] [Indexed: 12/16/2022] Open
Abstract
We conducted a retrospective study to evaluate the safety and efficacy of transarterial chemoembolization (TACE) combined with computed tomography-guided 125iodine implantation (TACE-125iodine) in hepatocellular carcinoma (HCC) patients with type B portal vein tumor thrombus (PVTT). From medical records, we determined that 50 patients who received 125iodine implantation 4-7 days after the first TACE session showed better survival than 50 patients who received only TACE (median survival, 13.1 vs. 6.0 months; P<0.01). Moreover, the PVTT control rate was higher in the TACE-125iodine than TACE alone group (78% vs. 18%; P<0.01). Multivariate analysis demonstrated that the TACE-125iodine procedure was an independent prognostic factor for overall survival. We also observed that bilirubin levels were increased at 4 weeks, indicating that 125iodine seeding in the PVTT beneficially impacted the small bile duct, which is proximal to the portal vein. No severe adverse events were observed in patients that received 125iodine seed implantation, and the mild adverse events were successfully treated. This study shows that TACE-125iodine therapy enhances patient survival with minimal adverse events. It is also more affordable than sorafenib, which is currently the recommended therapy for advanced HCC patients with PVTT.
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Tan T, Xiao Y, Zhou S, Ma C, Zhang Z. Y-configuration stent combined with iodine-125 seeds strand for the treatment of hepatocellular carcinoma with tumor thrombosis in portal vein branches: A case report. Medicine (Baltimore) 2017; 96:e8660. [PMID: 29145293 PMCID: PMC5704838 DOI: 10.1097/md.0000000000008660] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
RATIONALE Currently, the treatment of hepatocellular carcinoma (HCC) associated with portal vein tumor thrombosis (PVTT) is a challenge. Percutaneous puncture endovascular placement of iodine-125 (I) seeds strand and stent is reported to treat HCC with tumor thrombus effectively. However, it is proved to be only suitable for the main portal vein (MPV) thrombus. PATIENT CONCERNS A 42-year-old male patient was referred to our institution after experiencing right upper abdominal distention without abdominal pain, nausea, or vomiting for 2 weeks. The patient had a history of hepatitis B virus infection over a 20 year period. DIAGNOSIS After a full evaluation, the patient was diagnosed with primary HCC with a tumor thrombus in both main and branch portal veins. INTERVENTIONS We used a Y-configuration stent combined with I seeds strand to treat the tumor thrombus in both main and branch portal veins. OUTCOMES The patient's liver function and the stent patency period were improved. More importantly, the patient had an acceptable survival time. LESSONS A Y-configuration stent makes it possible to treat tumor thrombosis in portal vein branches (PVBs). However, the long-term curative effects of Y-configuration stents need to be verified.
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Wang L, Wang W, Yao X, Rong W, Wu F, Chen B, Liu M, Lin S, Liu Y, Wu J. Postoperative adjuvant radiotherapy is associated with improved survival in hepatocellular carcinoma with microvascular invasion. Oncotarget 2017; 8:79971-79981. [PMID: 29108379 PMCID: PMC5668112 DOI: 10.18632/oncotarget.20402] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 08/04/2017] [Indexed: 01/27/2023] Open
Abstract
Purpose Limited studies have compared the efficacy of postoperative adjuvant therapies in HCC patients with microvascular invasion (MVI). In this study we assess the efficacy of postoperative adjuvant conservative therapy (CT), trans-catheter arterial chemoembolization (TACE) and radiotherapy (RT) in HCC patients with MVI. Results Kaplan-Meier survival analysis revealed that patients in the RT group have significantly improved RFS (RT vs TACE: p = 0.011; RT vs CT: p < 0.001) and OS (RT vs. TACE: p = 0.034; RT vs CT: P < 0.001) compared to TACE and CT groups. Further, subgroup analysis based on the degree of MVI and surgical margin width showed that patients with narrow surgical margin have significantly longer RFS and OS after adjuvant RT than the TACE and CT, independent of degree of MVI. Multivariate analysis indicated that MVI classification is the independent prognostic factor associated with RFS and OS. Materials and Methods Between July 2008 and December 2015, 136 HCC patients with MVI were divided into three groups according to their adjuvant therapies. Survival outcomes namely relapse-free survival (RFS) and overall survival (OS) of the three groups were analyzed. Conclusions Adjuvant radiotherapy following hepatectomy could result in better survival outcomes for HCC patients with MVI than TACE or CT.
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Affiliation(s)
- Liming Wang
- Department of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weihu Wang
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
| | - Xuesong Yao
- Department of Interventional Therapy, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiqi Rong
- Department of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Wu
- Department of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mei Liu
- Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shengtao Lin
- Department of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yunhe Liu
- Department of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianxiong Wu
- Department of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Kong XQ, Dong YP, Wu JX, He JY, Le YY, Du KX, Peng QQ, Li JL. High-biologically effective dose palliative radiotherapy for a tumor thrombus might improve the long-term prognosis of hepatocellular carcinoma: a retrospective study. Radiat Oncol 2017; 12:92. [PMID: 28569169 PMCID: PMC5452386 DOI: 10.1186/s13014-017-0831-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 05/25/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND This study aimed to highlight the type of tumor thrombus and identify the prognostic factors influencing the long-term survival outcomes in patients with hepatocellular carcinoma (HCC) having a tumor thrombus. A tumor thrombus in HCC is associated with poor prognosis. METHODS Eighty patients diagnosed with HCC having a tumor thrombus between May 2006 and April 2014 were enrolled in this study. Age, gender, clinical characteristics, laboratory findings, Child-Pugh classification, performance status (ECOG), types of tumor thrombi, radiotherapy method, biologically effective dose (BED), and primary treatment method were analyzed to identify the prognostic factors associated with the overall survival (OS) rates. Statistical analyses were performed using SPSS version 19.0. RESULTS The median follow-up duration was 24 months (range 6-90). The 1-, 3-, and 5-year OS rates of the patients were 77.6%, 37.6%, and 18.8%, respectively. On univariate analysis, gender, radiotherapy method, BED, types of tumor thrombi, Child-Pugh classification, ECOG, and total bilirubin were associated with OS (P < 0.001, P = 0.001, P = 0.016, P = 0.003, P < 0.001, P < 0.001, P = 0.039, respectively). The prognostic factors for OS in multi-variate analyses were gender (P < 0.001), BED (P = 0.044), Child Pugh classification (P = 0.020), performance status (ECOG) (P = 0.004), and types of tumor thrombi (P = 0.001). The median OS for the high-BED group was better than that for the low-BED groups (42 months vs. 19 months, P = 0.016). CONCLUSIONS Gender, BED, performance status (ECOG), Child-Pugh classification, and types of tumor thrombi seemed to affect OS, and a stepwise decrease in survival was observed with the types of tumor thrombi ranging from I to IV. High-BED palliative radiotherapy might improve the long-term outcomes for patients with HCC having a tumor thrombus.
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Affiliation(s)
- Xiang-quan Kong
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, 420 Fuma Rd, Jinan District, Fuzhou, 350014 China
| | - Ya-ping Dong
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, 420 Fuma Rd, Jinan District, Fuzhou, 350014 China
| | - Jun-xin Wu
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, 420 Fuma Rd, Jinan District, Fuzhou, 350014 China
| | - Jun-yan He
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, 420 Fuma Rd, Jinan District, Fuzhou, 350014 China
| | - Yu-yin Le
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, 420 Fuma Rd, Jinan District, Fuzhou, 350014 China
| | - Kai-xin Du
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, 420 Fuma Rd, Jinan District, Fuzhou, 350014 China
| | - Qing-qin Peng
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, 420 Fuma Rd, Jinan District, Fuzhou, 350014 China
| | - Jin-luan Li
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, 420 Fuma Rd, Jinan District, Fuzhou, 350014 China
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Yang S, Liu G. Targeting the Ras/Raf/MEK/ERK pathway in hepatocellular carcinoma. Oncol Lett 2017; 13:1041-1047. [PMID: 28454211 DOI: 10.3892/ol.2017.5557] [Citation(s) in RCA: 158] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2015] [Accepted: 09/28/2016] [Indexed: 12/12/2022] Open
Abstract
Although the biological basis of hepatocellular carcinoma (HCC) remains unclear, effective treatments and improvement of the survival rate remain worthwhile research goals. Abnormal protein signaling pathways contributing to uncontrolled cell proliferation, differentiation, survival and apoptosis are biomarkers of the carcinogenic process. Certain mutated components or overexpression of the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway are increasingly being studied in HCC carcinogenesis. The present review addresses the effect of the Ras/Raf/MEK/ERK signaling pathway on the pathogenesis of HCC, and provides an update on the preclinical and clinical development of various inhibitors targeting this core signaling pathway, which include various Ras inhibitors, Raf inhibitors and MEK inhibitors for HCC.
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Affiliation(s)
- Sufang Yang
- Department of Pharmacy, The First Affiliated Hospital of Shantou University Medical Collage, Shantou, Guangdong 515041, P.R. China
| | - Guohua Liu
- Department of Pharmacy, The First Affiliated Hospital of Shantou University Medical Collage, Shantou, Guangdong 515041, P.R. China
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Portal Vein Stenting Combined with Iodine-125 Seeds Endovascular Implantation Followed by Transcatheter Arterial Chemoembolization for Treatment of Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus. BIOMED RESEARCH INTERNATIONAL 2016; 2016:3048261. [PMID: 27999793 PMCID: PMC5143688 DOI: 10.1155/2016/3048261] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 11/03/2016] [Indexed: 12/20/2022]
Abstract
Aim was to assess the therapeutic value of portal vein stenting (PVS) combined with iodine-125 seed (125I seed) strand endovascular implantation followed by transcatheter arterial chemoembolization (TACE) for treating patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). This was a retrospective study of 34 patients aged 29–81 years, diagnosed HCC with PVTT, and treated with PVS combined with 125I seed strand endovascular implantation followed by TACE between January 2012 and August 2014. Survival, stent patency, technical success rate, complications related to the procedure, and adverse events were recorded. The technical success rate was 100%. No serious procedure-related adverse event was recorded. The median survival was 147 days. The cumulative survival rates and stent patency rates at 90, 180, and 360 days were 94.1%, 61.8%, and 32.4% and 97.1% (33/34), 76.9% (24/34), and 29.4% (10/34), respectively. PVS combined with 125I seed strand endovascular implantation followed by TACE is feasible for patients with HCC and PVTT. It resulted in appropriate survival and stent patency, with no procedure-related adverse effects.
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Bai T, Chen J, Xie ZB, Wu FX, Wang SD, Liu JJ, Li LQ. The efficacy and safety of postoperative adjuvant transarterial embolization and radiotherapy in hepatocellular carcinoma patients with portal vein tumor thrombus. Onco Targets Ther 2016; 9:3841-8. [PMID: 27390524 PMCID: PMC4930237 DOI: 10.2147/ott.s104307] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Objective This study aims to find out the safety and efficiency of postoperative adjuvant transarterial chemoembolization (TACE) and radiotherapy (RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Methods From 2009 to 2010, a total of 92 HCC patients with PVTT were enrolled in this retrospective study. Patients were divided into three groups according to their adjuvant therapies (conservative group, n=51; TACE group, n=31; RT group, n=10). Results In our analysis, median survival in patients with postoperative adjuvant TACE (21.91±3.60 months) or RT (14.53±1.61 months) was significantly longer than patients with hepatectomy alone (8.99±1.03 months). But the difference between adjuvant TACE and RT was of no significance (P=0.716). Also a similar result could be observed in median disease-free survival: conservative group (6.51±1.44 months), TACE group (13.98±3.38 months), and RT group (14.03±2.40 months). Treatment strategies (hazard ratio [HR] =0.411, P<0.001) and PVTT type (HR =4.636, P<0.001) were the independent prognostic factors for overall survival. Similarly, the risk factors were the same when multivariate analysis was conducted in disease-free survival (treatment strategies, HR =0.423, P<0.001; PVTT type, HR =4.351, P<0.001) and recurrence (treatment strategies, HR =0.459, P=0.030; PVTT type, HR =2.908, P=0.047). Patients with PVTT type I had longer overall survival than patients with PVTT type II (median survival: 18.43±2.88 months vs 11.59±1.45 months, P=0.035). Conclusion Postoperative adjuvant TACE and RT may be a choice for HCC patients with PVTT.
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Affiliation(s)
- Tao Bai
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University; Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning
| | - Jie Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University; Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning
| | - Zhi-Bo Xie
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University; Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning
| | - Si-Da Wang
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning; Department of Ultrasound Diagnosis, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Jun-Jie Liu
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning; Department of Ultrasound Diagnosis, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University; Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning
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Okazaki E, Yamamoto A, Nishida N, Hamuro M, Ogino R, Hosono M, Shimatani Y, Tsutsumi S, Hamamoto S, Sohgawa E, Jogo A, Miki Y. Three-dimensional conformal radiotherapy for locally advanced hepatocellular carcinoma with portal vein tumour thrombosis: evaluating effectiveness of the model for end-stage liver disease (MELD) score compared with the Child-Pugh classification. Br J Radiol 2016; 89:20150945. [PMID: 27164029 DOI: 10.1259/bjr.20150945] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE The purpose of this study was to retrospectively evaluate the effectiveness of the model for end-stage liver disease (MELD) score compared with the Child-Pugh classification in patients who received three-dimensional conformal radiotherapy (3D CRT) for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) by analyzing toxicity and prognostic factors. METHODS 56 consecutive patients who had locally advanced HCC with PVTT treated by 3D CRT between September 2007 and April 2013 were retrospectively reviewed. RESULTS The median survival time of all patients was 6.4 months. Receiver-operating characteristic (ROC) analysis identified MELD score = 7.5 [area under the curve (AUC) 0.81] and Child-Pugh score = 6.5 (AUC 0.86) as the best cut-off values for predicting the incidence of complications over Common Terminology Criteria for Adverse Events grade 2. There was no significant difference in the discrimination power between the MELD score and the Child-Pugh score on comparison of the two ROC curves (p = 0.17). On multivariate analysis, age, MELD score and radiotherapy dose were significant prognostic factors for overall survival (p = 0.021, 0.038 and 0.006, respectively). In contrast, the Child-Pugh classification, tumour response, PVTT response and the number of prior interventional radiologic treatments were not significant on multivariate analysis. CONCLUSION This study showed that the best MELD score cut-off value is 7.5 and that the MELD score is a better prognostic factor than the Child-Pugh classification in 3D CRT for HCC with PVTT. ADVANCES IN KNOWLEDGE The MELD score is useful for predicting the risk of severe toxicities and the prognosis of patients treated with 3D CRT for PVTT.
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Affiliation(s)
- Eiichiro Okazaki
- 1 Department of Diagnostic and Interventional Radiology/Radiation Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Akira Yamamoto
- 1 Department of Diagnostic and Interventional Radiology/Radiation Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Norifumi Nishida
- 2 Department of Radiology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
| | - Masao Hamuro
- 1 Department of Diagnostic and Interventional Radiology/Radiation Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Ryo Ogino
- 3 Department of Radiation Oncology, Tane General Hospital, Osaka, Japan
| | - Masako Hosono
- 1 Department of Diagnostic and Interventional Radiology/Radiation Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuhiko Shimatani
- 1 Department of Diagnostic and Interventional Radiology/Radiation Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shinichi Tsutsumi
- 1 Department of Diagnostic and Interventional Radiology/Radiation Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shinichi Hamamoto
- 1 Department of Diagnostic and Interventional Radiology/Radiation Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Etsuji Sohgawa
- 1 Department of Diagnostic and Interventional Radiology/Radiation Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Atsushi Jogo
- 1 Department of Diagnostic and Interventional Radiology/Radiation Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yukio Miki
- 1 Department of Diagnostic and Interventional Radiology/Radiation Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Qi X, Ng KTP, Lian QZ, Liu XB, Li CX, Geng W, Ling CC, Ma YY, Yeung WH, Tu WW, Fan ST, Lo CM, Man K. Clinical significance and therapeutic value of glutathione peroxidase 3 (GPx3) in hepatocellular carcinoma. Oncotarget 2015; 5:11103-20. [PMID: 25333265 PMCID: PMC4294380 DOI: 10.18632/oncotarget.2549] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Accepted: 09/30/2014] [Indexed: 12/22/2022] Open
Abstract
AIMS We aimed to investigate the clinical significance of GPx3 in hepatocellular carcinoma (HCC) and to characterize its tumor suppressive role. METHODS HCC patients (113) who underwent hepatectomy were recruited to examine the clinical relevance of GPx3. The tumor suppressive role of GPx3 was studied by administration of recombinant GPx3 (rGPx3) or over-expression of GPx3 in HCC cells in vitro and in vivo. The therapeutic value of GPx3 for HCC was further investigated using human induced pluripotent stem cell derived mesenchymal stem cells (hiPSC-MSCs) as its delivery vehicle. RESULTS Down-regulation of GPx3 significantly correlated with advanced tumor stage (P = 0.024), venous infiltration (P = 0.043) and poor overall survival (P = 0.007) after hepatectomy. Lower plasma GPx3 in HCC patients was significantly associated with larger tumor size (P = 0.011), more tumor nodules (P = 0.032) and higher recurrence (P = 0.016). Over-expression of GPx3 or administration of rGPx3 significantly inhibited proliferation and invasiveness of HCC cells in vitro and in vivo. Tumor suppressive activity of GPx3 was mediated through Erk-NFκB-SIP1 pathway. GPx3 could be delivered by hiPSC-MSCs into the tumor and exhibited tumor suppressive activity in vivo. CONCLUSIONS GPx3 is a tumor suppressor gene in HCC and may possess prognostic and therapeutic value for HCC patients.
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Affiliation(s)
- Xiang Qi
- Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Kevin Tak Pan Ng
- Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Qi Zhou Lian
- Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Xiao Bing Liu
- Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Chang Xian Li
- Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Wei Geng
- Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Chang Chun Ling
- Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Yuen Yuen Ma
- Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Wai Ho Yeung
- Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Wen Wei Tu
- Department of Paediatrics & Adolescent Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Sheung Tat Fan
- Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Kwan Man
- Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China
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Yeh SA, Chen YS, Perng DS. The role of radiotherapy in the treatment of hepatocellular carcinoma with portal vein tumor thrombus. JOURNAL OF RADIATION RESEARCH 2015; 56:325-31. [PMID: 25411553 PMCID: PMC4380051 DOI: 10.1093/jrr/rru104] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
The aim of this study was to evaluate the role of radiotherapy in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVT) and to determine the prognostic factors for overall survival. Altogether, 106 patients with HCC and PVT referred for radiotherapy between 2004 and 2009 were retrospectively reviewed. A total of 60 Gy in 30 daily fractions was delivered with intensity-modulated radiotherapy techniques. Patient-related and treatment-related factors were analyzed to evaluate their prognostic significance for the overall survival rate. Complete response was noted in 10 patients and partial response in 55 patients. The liver lesions had become resectable after the completion of radiotherapy in 12 patients, and surgery was subsequently performed. One or two courses of transarterial chemoembolization (TACE) were administered to 19 patients following radiotherapy. The 1-year and 2-year overall survival rates were 34.7% and 11%, respectively, and the median survival was 7 months for the entire cohort of patients. Post-radiotherapy treatment modality, response to radiotherapy and JIS score were demonstrated as independent prognostic factors for overall survival (P = 0.003, P < 0.001, P < 0.001, respectively). For patients who received surgical intervention after radiotherapy, the median survival was 30 months and the 2-year overall survival rate was 67%. Radiotherapy achieved a 61.5% objective response rate and prolonged survival in patients with PVT. The liver tumors had become resectable after radiotherapy in 11% of patients. Our results suggested that radiotherapy could offer survival benefits and should be considered as a treatment option for patients with PVT. Radiotherapy could also be considered as a preoperative treatment modality in patients with HCC and PVT.
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Affiliation(s)
- Shyh-An Yeh
- Department of Radiation Oncology, E-DA Hospital, Kaohsiung City, Taiwan Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung City, Taiwan
| | - Yaw-Sen Chen
- Department of General Surgery, E-DA Hospital, Kaohsiung City, Taiwan
| | - Daw-Shyong Perng
- Department of Gastroenterology, E-DA Hospital, Kaohsiung City, Taiwan
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Xu JF, Liu XY, Wang S, Wen HX. Surgical treatment for hepatocellular carcinoma with portal vein tumor thrombus: a novel classification. World J Surg Oncol 2015; 13:86. [PMID: 25889711 PMCID: PMC4352541 DOI: 10.1186/s12957-015-0493-x] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Accepted: 02/01/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The hepatic resection for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) which is not uncommon at clinic continues to be debated. Our study introduced a novel classification of HCC with PVTT and compared the outcomes of surgical treatment between different groups. METHODS From January 2008 to December 2012, a total of 56 cases of HCC with PVTT underwent liver resection combined with thrombectomy. Clinical pathological features and surgical data of these patients were retrospectively studied. The patients were divided into two groups. Cumulative overall and disease-free survival curves of the patients were compared according to different groups. RESULTS Sixteen patients (28.6%) belonging to group A were compared to 40 patients (71.4%) belonging to group B. The rates of capsular formation and tumor number showed differences between the two groups (P = 0.047, P = 0.032). Group A had more liver cirrhosis than group B (P = 0.047). The patients with large blood loss (≥1,000) were more in group A, as well. There was no significant difference in complications between the two groups except the ascites (P = 0.028). The 1-year overall survival rate of group A after liver resection was 31.5%. The 1-, 3-, and 5-year overall survival rates of group B were 62.3%, 16.1%, and 5.2%, respectively. For further study, group B had significantly better overall survival than group A (P = 0.033). Group A had significantly higher incidence of recurrence than group B (P = 0.021). CONCLUSIONS Liver resection combined with thrombectomy for HCC with PVTT can get better outcome in the HCC patients with PVTT involving only one branch (left/right) of portal vein (group B) compared to patients with PVTT involving the main portal vein trunk or both the left and right portal veins (group A).
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Affiliation(s)
- Jiang-feng Xu
- Department of Surgery, The Fourth Affiliated Hospital of Zhejiang, University School of Medicine, East building in Huajiachi campus, Kaixuan road 268, Hangzhou, Zhejiang, 310020, China.
| | - Xi-yu Liu
- Department of Surgery, The Fourth Affiliated Hospital of Zhejiang, University School of Medicine, East building in Huajiachi campus, Kaixuan road 268, Hangzhou, Zhejiang, 310020, China.
| | - Shuai Wang
- Department of Surgery, The Fourth Affiliated Hospital of Zhejiang, University School of Medicine, East building in Huajiachi campus, Kaixuan road 268, Hangzhou, Zhejiang, 310020, China.
| | - Huai-xi Wen
- Department of Surgery, The Fourth Affiliated Hospital of Zhejiang, University School of Medicine, East building in Huajiachi campus, Kaixuan road 268, Hangzhou, Zhejiang, 310020, China.
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21
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Kang TW, Lim HK, Lee MW, Kim YS, Rhim H, Lee WJ, Gwak GY, Paik YH, Lim HY, Kim MJ. Aggressive Intrasegmental Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation: Risk Factors and Clinical Significance. Radiology 2015; 276:274-85. [PMID: 25734550 DOI: 10.1148/radiol.15141215] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE To evaluate the frequency, risk factors, and clinical significance of aggressive intrasegmental recurrence (AIR) found after radiofrequency (RF) ablation for hepatocellular carcinoma (HCC). MATERIALS AND METHODS Institutional review board approval was obtained for this retrospective study. Between March 2005 and December 2010, 539 patients (414 men, 125 women; mean age, 57.91 years; age range, 30-82 years) underwent ultrasonography-guided percutaneous RF ablation as a first-line treatment for a single HCC classified as Barcelona Clinic Liver Cancer (BCLC) stage 0 or A. AIR of HCC was defined as (a) initial tumor recurrence with disease-free status at least 6 months after initial RF ablation and (b) the simultaneous development of multiple nodular (at least three) or infiltrative tumor recurrence in the treated segment. Patients were stratified into two groups: those with AIR (n = 20) and those without AIR (n = 519) during follow-up. Risk factors for AIR were assessed with logistic regression analysis, and risk factors for long-term overall survival were assessed with time-dependent Cox proportional hazard models. RESULTS In a median follow-up period of 49 months (range, 6-95 months), AIR was observed in 3.7% of the patients (20 of 539 patients), with the frequency increasing to 15% in the subgroup with periportal HCC (11 of 72 patients). AIRs manifested as either multiple nodular type (n = 14, BCLC stage A or B) or diffusely infiltrative type with tumor thrombus formation (n = 6, BCLC stage C). At multivariate analysis, periportal tumor location and younger patient age were significant risk factors for AIR. The presence of AIR during the follow-up period has a significant effect on the overall survival rate (hazard ratio = 5.72, P = .002). CONCLUSION The overall frequency of AIR after RF ablation for HCC was low, with periportal location and patient age showing a significant relationship to the development of AIR. The occurrence of AIR had an adverse effect on overall survival rate.
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Affiliation(s)
- Tae Wook Kang
- From the Department of Radiology and Center for Imaging Science (T.W.K., H.K.L., M.W.L., Y.S.K., H.R., W.J.L.), Division of Hepatology, Department of Medicine (G.Y.G., Y.H.P.), Division of Hematology-Oncology, Department of Medicine (H.Y.L.), and Biostatics Unit, Samsung Biomedical Research Institute (M.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Irwonro 81, Seoul 135-710, Republic of Korea; and Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul Republic of Korea (H.K.L., W.J.L., Y.H.P., H.Y.L.)
| | - Hyo Keun Lim
- From the Department of Radiology and Center for Imaging Science (T.W.K., H.K.L., M.W.L., Y.S.K., H.R., W.J.L.), Division of Hepatology, Department of Medicine (G.Y.G., Y.H.P.), Division of Hematology-Oncology, Department of Medicine (H.Y.L.), and Biostatics Unit, Samsung Biomedical Research Institute (M.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Irwonro 81, Seoul 135-710, Republic of Korea; and Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul Republic of Korea (H.K.L., W.J.L., Y.H.P., H.Y.L.)
| | - Min Woo Lee
- From the Department of Radiology and Center for Imaging Science (T.W.K., H.K.L., M.W.L., Y.S.K., H.R., W.J.L.), Division of Hepatology, Department of Medicine (G.Y.G., Y.H.P.), Division of Hematology-Oncology, Department of Medicine (H.Y.L.), and Biostatics Unit, Samsung Biomedical Research Institute (M.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Irwonro 81, Seoul 135-710, Republic of Korea; and Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul Republic of Korea (H.K.L., W.J.L., Y.H.P., H.Y.L.)
| | - Young-Sun Kim
- From the Department of Radiology and Center for Imaging Science (T.W.K., H.K.L., M.W.L., Y.S.K., H.R., W.J.L.), Division of Hepatology, Department of Medicine (G.Y.G., Y.H.P.), Division of Hematology-Oncology, Department of Medicine (H.Y.L.), and Biostatics Unit, Samsung Biomedical Research Institute (M.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Irwonro 81, Seoul 135-710, Republic of Korea; and Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul Republic of Korea (H.K.L., W.J.L., Y.H.P., H.Y.L.)
| | - Hyunchul Rhim
- From the Department of Radiology and Center for Imaging Science (T.W.K., H.K.L., M.W.L., Y.S.K., H.R., W.J.L.), Division of Hepatology, Department of Medicine (G.Y.G., Y.H.P.), Division of Hematology-Oncology, Department of Medicine (H.Y.L.), and Biostatics Unit, Samsung Biomedical Research Institute (M.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Irwonro 81, Seoul 135-710, Republic of Korea; and Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul Republic of Korea (H.K.L., W.J.L., Y.H.P., H.Y.L.)
| | - Won Jae Lee
- From the Department of Radiology and Center for Imaging Science (T.W.K., H.K.L., M.W.L., Y.S.K., H.R., W.J.L.), Division of Hepatology, Department of Medicine (G.Y.G., Y.H.P.), Division of Hematology-Oncology, Department of Medicine (H.Y.L.), and Biostatics Unit, Samsung Biomedical Research Institute (M.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Irwonro 81, Seoul 135-710, Republic of Korea; and Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul Republic of Korea (H.K.L., W.J.L., Y.H.P., H.Y.L.)
| | - Geum-Youn Gwak
- From the Department of Radiology and Center for Imaging Science (T.W.K., H.K.L., M.W.L., Y.S.K., H.R., W.J.L.), Division of Hepatology, Department of Medicine (G.Y.G., Y.H.P.), Division of Hematology-Oncology, Department of Medicine (H.Y.L.), and Biostatics Unit, Samsung Biomedical Research Institute (M.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Irwonro 81, Seoul 135-710, Republic of Korea; and Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul Republic of Korea (H.K.L., W.J.L., Y.H.P., H.Y.L.)
| | - Yong Han Paik
- From the Department of Radiology and Center for Imaging Science (T.W.K., H.K.L., M.W.L., Y.S.K., H.R., W.J.L.), Division of Hepatology, Department of Medicine (G.Y.G., Y.H.P.), Division of Hematology-Oncology, Department of Medicine (H.Y.L.), and Biostatics Unit, Samsung Biomedical Research Institute (M.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Irwonro 81, Seoul 135-710, Republic of Korea; and Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul Republic of Korea (H.K.L., W.J.L., Y.H.P., H.Y.L.)
| | - Ho Yeong Lim
- From the Department of Radiology and Center for Imaging Science (T.W.K., H.K.L., M.W.L., Y.S.K., H.R., W.J.L.), Division of Hepatology, Department of Medicine (G.Y.G., Y.H.P.), Division of Hematology-Oncology, Department of Medicine (H.Y.L.), and Biostatics Unit, Samsung Biomedical Research Institute (M.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Irwonro 81, Seoul 135-710, Republic of Korea; and Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul Republic of Korea (H.K.L., W.J.L., Y.H.P., H.Y.L.)
| | - Min Ji Kim
- From the Department of Radiology and Center for Imaging Science (T.W.K., H.K.L., M.W.L., Y.S.K., H.R., W.J.L.), Division of Hepatology, Department of Medicine (G.Y.G., Y.H.P.), Division of Hematology-Oncology, Department of Medicine (H.Y.L.), and Biostatics Unit, Samsung Biomedical Research Institute (M.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Irwonro 81, Seoul 135-710, Republic of Korea; and Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul Republic of Korea (H.K.L., W.J.L., Y.H.P., H.Y.L.)
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22
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Radiation Oncology in the Treatment of Hepatocellular Carcinoma. AN INFORMATION TECHNOLOGY FRAMEWORK FOR PREDICTIVE, PREVENTIVE AND PERSONALISED MEDICINE 2015. [DOI: 10.1007/978-3-319-12166-6_11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Lu DH, Fei ZL, Zhou JP, Hu ZT, Hao WS. A comparison between three-dimensional conformal radiotherapy combined with interventional treatment and interventional treatment alone for hepatocellular carcinoma with portal vein tumour thrombosis. J Med Imaging Radiat Oncol 2014; 59:109-14. [PMID: 25088249 DOI: 10.1111/1754-9485.12207] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Accepted: 06/15/2014] [Indexed: 12/12/2022]
Abstract
INTRODUCTION We investigated the therapeutic effects of three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolisation (TACE) for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT). METHODS Sixty-three HCC patients with PVTT were divided into two groups. Group A (30 patients) was treated with three-dimensional conformal radiotherapy followed by 2-3 series of TACE, while group B (33 patients) was only treated with TACE. RESULTS The 1- and 2-year survival rates of group A were 62.40% and 20.81%, respectively, with a mean survival time of 13.0 months. The 1- and 2-year survival rates of group B were 56.49% and 18.83%, respectively, with a mean survival time of 9.0 months. There were significant differences between the two groups (log-rank chi-square value = 3.950, P = 0.047). CONCLUSION Three-dimensional conformal radiotherapy combined with TACE can significantly improve clinical outcomes in patients with HCC and PVTT compared with TACE alone.
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Affiliation(s)
- Dong-Hui Lu
- Tumor Diagnosis and Treatment Center, 105th Hospital of PLA, Hefei, China
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24
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Tanaka Y, Nakazawa T, Komori S, Hidaka H, Okuwaki Y, Takada J, Watanabe M, Shibuya A, Minamino T, Yamamoto H, Kokubu S, Hayakawa K, Koizumi W. Radiotherapy for patients with unresectable advanced hepatocellular carcinoma with invasion to intrahepatic large vessels: efficacy and outcomes. J Gastroenterol Hepatol 2014; 29:352-7. [PMID: 23869689 DOI: 10.1111/jgh.12333] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/03/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM To examine the efficacy and outcomes of radiotherapy (RT) in patients who have hepatocellular carcinoma with invasion to intrahepatic large vessels (IHLVs). METHODS Sixty-seven patients who had advanced hepatocellular carcinoma with invasion to IHLVs received three-dimensional conformal RT. IHLV invasion was associated with portal venous tumor thrombosis in 40 patients, tumor thrombosis involving the hepatic vein in 17, and both findings in 10. A daily radiation dose of 1.8-2 Gy was administered using 6 or 10 MV X-rays to deliver a total dose of 30-56 Gy. RESULTS The overall objective response rate (complete response plus partial response) was 45% (n = 30). The median survival time was 13.7 months in the responder group and 5.9 months in the nonresponder group. An objective response was observed in 28 (56%) of 50 patients with Child-Pugh (C-P) class A and in 2 (12%) of 17 patients with C-P class B. Hepatic function of C-P class A was an independent factor for both RT responder and overall survival on Cox regression analysis (hazard ratio = 9.5, 95% confidence interval = 1.97-46.2, P = 0.005; and hazard ratio = 0.39, 95% confidence interval = 0.2-0.77, P = 0.007, respectively). CONCLUSION RT is an effective treatment option without serious adverse events. RT should be considered for the patients with better hepatic function who have invasion to IHLVs.
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Affiliation(s)
- Yoshiaki Tanaka
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Tokyo, Japan
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Three-dimensional conformal radiotherapy for hepatocellular carcinoma in patients unfit for resection, ablation, or chemotherapy: a retrospective study. ScientificWorldJournal 2013; 2013:780141. [PMID: 24379750 PMCID: PMC3863543 DOI: 10.1155/2013/780141] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2013] [Accepted: 10/24/2013] [Indexed: 02/07/2023] Open
Abstract
PURPOSE The purpose is to evaluate the feasibility, efficacy, and the toxicity of three-dimensional conformal radiotherapy (3DCRT) in patients with advanced hepatocelluar carcinoma (HCC) and inferior vena cava tumor thrombosis (IVCTT). METHODS Between 2007 and 2012, in a retrospective way, 9 patients (median age 69 years) with advanced HCC and IVCTT unfit for surgery, radiofrequency ablation, embolization, or chemotherapy were treated with three-dimensional conformal radiotherapy (3DCRT). The radiotherapy volume included both primary tumor and IVTT. The radiotherapy schedule was 50-52 Gy in 2 Gy fractions. Overall survival (OS), response to radiotherapy, visual analogue scale (VAS), and toxicity were assessed. RESULTS All patients demonstrated a response rate up to 60%. During radiotherapy, 3 patients experienced grade 1 nausea/vomit toxicity. All patients demonstrated an elevation of the liver enzymes (3 patients with grade 1 and 6 patients with grade 2). The mean VAS-score was decreased from 6.11 to 3.11, while the median overall survival was 24 months. CONCLUSION 3DCRT achieves a very high local control rate and is suitable for patients with HCC and IVTT, while the documented radiation induced toxicity is moderate. It can be recommended for palliation in patients unable to undergo curative therapies.
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26
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Huang XY, Yao JG, Huang HD, Wang C, Ma Y, Xia Q, Long XD. MicroRNA-429 Modulates Hepatocellular Carcinoma Prognosis and Tumorigenesis. Gastroenterol Res Pract 2013; 2013:804128. [PMID: 24204382 PMCID: PMC3800573 DOI: 10.1155/2013/804128] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Accepted: 08/20/2013] [Indexed: 12/31/2022] Open
Abstract
MicroRNA-429 (miR-429) may modify the development and progression of cancers; however, the role of this microRNA in the hepatocellular carcinoma (HCC) has not been well elaborated. Here, we tested miR-429 expression in 138 pathology-diagnosed HCC cases and SMMC-7721 cells. We found that miR-429 was upregulated in HCC tumor tissues and that the high expression of miR-429 was significantly correlated with larger tumor size (odd ratio (OR), 2.70; 95% confidence interval (CI), 1.28-5.56) and higher aflatoxin B1-DNA adducts (OR = 3.13, 95% CI = 1.47-6.67). Furthermore, this microRNA overexpression modified the recurrence-free survival and overall survival of HCC patients. Functionally, miR-429 overexpression progressed tumor cells proliferation and inhibited cell apoptosis. These results indicate for the first time that miR-429 may modify HCC prognosis and tumorigenesis and may be a potential tumor therapeutic target.
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Affiliation(s)
- Xiao-Ying Huang
- Department of Pathology, Youjiang Medical College for Nationalities, Baise 533000, China
| | - Jin-Guang Yao
- Department of Pathology, Youjiang Medical College for Nationalities, Baise 533000, China
| | - Hong-Dong Huang
- Division of Nephrology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Chao Wang
- Department of Medicine, The Affiliated Hospital of Youjiang Medical College for Nationalities, Baise 533000, China
| | - Yun Ma
- Department of Pathology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China
| | - Qiang Xia
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Xi-Dai Long
- Department of Pathology, Youjiang Medical College for Nationalities, Baise 533000, China
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
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27
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Xi M, Zhang L, Zhao L, Li QQ, Guo SP, Feng ZZ, Deng XW, Huang XY, Liu MZ. Effectiveness of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombosis. PLoS One 2013; 8:e63864. [PMID: 23737955 PMCID: PMC3667854 DOI: 10.1371/journal.pone.0063864] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2013] [Accepted: 04/07/2013] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To report the feasibility, efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for the treatment of portal vein tumor thrombosis (PVTT) and/or inferior vena cava tumor thrombosis (IVCTT) in patients with advanced hepatocellular carcinoma (HCC). MATERIALS AND METHODS Forty-one patients treated with SBRT using volumetric modulated arc therapy (VMAT) for HCC with PVTT/IVCTT between July 2010 and May 2012 were analyzed. Of these, 33 had PVTT and 8 had IVCTT. SBRT was designed to target the tumor thrombosis and deliver a median total dose of 36 Gy (range, 30-48 Gy) in six fractions during two weeks. RESULTS The median follow-up was 10.0 months. At the time of analysis, 15 (36.6%) achieved complete response, 16 (39.0%) achieved partial response, 7 (17.1%) patients were stable, and three (7.3%) patients showed progressive disease. No treatment-related Grade 4/5 toxicity was seen within three months after SBRT. One patient had Grade 3 elevation of bilirubin. The one-year overall survival rate was 50.3%, with a median survival of 13.0 months. The only independent predictive factor associated with better survival was response to radiotherapy. CONCLUSIONS VMAT-based SBRT is a safe and effective treatment option for PVTT/IVCTT in HCC. Prospective randomized controlled trials are warranted to validate the role of SBRT in these patients.
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Affiliation(s)
- Mian Xi
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Li Zhang
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Lei Zhao
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Qiao-Qiao Li
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Su-Ping Guo
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Zi-Zhen Feng
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Xiao-Wu Deng
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Xiao-Yan Huang
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Meng-Zhong Liu
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
- * E-mail:
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Bae SH, Kim MS, Cho CK, Kim KB, Lee DH, Han CJ, Park SC, Kim YH. Feasibility and efficacy of stereotactic ablative radiotherapy for Barcelona Clinic Liver Cancer-C stage hepatocellular carcinoma. J Korean Med Sci 2013; 28:213-9. [PMID: 23400333 PMCID: PMC3565132 DOI: 10.3346/jkms.2013.28.2.213] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2012] [Accepted: 11/26/2012] [Indexed: 12/23/2022] Open
Abstract
The purpose of this study was to assess the feasibility and efficacy of stereotactic ablative radiotherapy (SABR) for liver tumor in patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). We retrospectively reviewed the medical records of 35 patients between 2003 and 2011. Vascular invasion was diagnosed in 32 patients, extrahepatic metastases in 11 and both in 8. Thirty-two patients were categorized under Child-Pugh (CP) class A and 3 patients with CP class B. The median SABR dose was 45 Gy (range, 30-60 Gy) in 3-5 fractions. The median survival time was 14 months. The 1- and 3-yr overall survival (OS) rate was 52% and 21%, respectively. On univariate analysis, CP class A and biologically equivalent dose ≥ 80 Gy(10) were significant determinants of better OS. Severe toxicity above grade 3, requiring prompt therapeutic intervention, was observed in 5 patients. In conclusion, SABR for BCLC-C stage HCC showed 1-yr OS rate of 52% but treatment related toxicity was moderate. We suggest that patients with CP class A are the best candidate and at least SABR dose of 80 Gy(10) is required for BCLC-C stage.
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Affiliation(s)
- Sun Hyun Bae
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Mi-Sook Kim
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Chul Koo Cho
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Kum Bae Kim
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Dong Han Lee
- CyberKnife Center, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Chul Ju Han
- Department of Internal Medicine, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Su Cheol Park
- Department of Internal Medicine, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Young Han Kim
- Department of Radiology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
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