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Cappelli A, Golfieri R, Mulas V, De Cinque A, Cocozza MA, Mosconi C. The Current Situation Regarding TACE-Specific Scores. TRANSARTERIAL CHEMOEMBOLIZATION (TACE) 2023:83-88. [DOI: 10.1007/978-3-031-36261-3_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Kegasawa T, Sakamori R, Maesaka K, Yamada R, Tahata Y, Urabe A, Kodama T, Hikita H, Imanaka K, Ohkawa K, Hiramatsu N, Oshita M, Yamada Y, Inada M, Yakushijin T, Imai Y, Tatsumi T, Takehara T. Lower Serum Sodium Levels Are Associated with the Therapeutic Effect of Sorafenib on Hepatocellular Carcinoma. Dig Dis Sci 2021; 66:1720-1729. [PMID: 32556820 DOI: 10.1007/s10620-020-06380-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 05/30/2020] [Indexed: 01/22/2023]
Abstract
BACKGROUND AND AIM Although the serum sodium level has been reported to be a prognostic and predictive marker for the therapeutic effects of lung cancer and renal cell carcinoma treated with molecular targeted therapy, the serum sodium level has not been investigated in hepatocellular carcinoma (HCC) patients treated with sorafenib. The aim of our analysis was to assess the prognostic role of serum sodium levels in these patients. METHODS We retrospectively analyzed 341 HCC patients treated with sorafenib between 2009 and 2012 in our hospital and other related institutions. RESULTS A total of 178 patients were enrolled in this study. The median age was 72 years (44-88), and 148 patients (83%) were male. The median overall survival (OS) was 12.9 months, and the median time to progression (TTP) was 3.1 months. Hyponatremia (hazard ratio (HR) 1.78, 95% confidence interval (CI) 1.26-2.52), a lower sodium level (HR 1.57, 95% CI 1.07-2.80), and a high level of α-fetoprotein (AFP) (≥ 200 ng/mL) (HR 1.78, 95% CI 1.26-2.52) were independent prognostic factors for TTP. We also categorized the patients into three groups according to serum sodium and AFP levels: Group A (n = 39) (serum sodium > 140 mEq/L, AFP < 200 ng/mL), Group C (n = 58) (serum sodium ≤ 140 mEq/L, AFP ≥ 200 ng/mL), and Group B (n = 81) (other patients). Significantly longer TTP and OS were observed in the following order: Groups A, C, and B. CONCLUSION Serum sodium levels are associated with the effectiveness of sorafenib. The serum sodium level can predict the therapeutic effect of sorafenib in advanced HCC patients.
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Affiliation(s)
- Tadashi Kegasawa
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kazuki Maesaka
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Ryoko Yamada
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Ayako Urabe
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takahiro Kodama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | | | | | | | | | | | - Masami Inada
- Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan
| | | | | | - Tomohide Tatsumi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
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Mao J, Tan Z, Pan X, Meng F. ASPP2 expression predicts the prognosis of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization. Exp Ther Med 2021; 21:397. [PMID: 33680119 PMCID: PMC7918402 DOI: 10.3892/etm.2021.9828] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 12/19/2019] [Indexed: 12/14/2022] Open
Abstract
Transcatheter arterial chemoembolization (TACE) induces ischemia-hypoxia and local chemotherapy-induced cytotoxicity which destroys cancerous cells. However, some patients do not respond to TACE. The causes for such a lack of response remain unclear. Recent studies have revealed that self-regulation of apoptosis-stimulating p53 protein 2 (ASPP2) may play an important role in promoting cell survival under hypoxic conditions as well as chemotherapy resistance via autophagy in various types of cancer. We measured the expression of ASPP2, autophagy-related proteins and apoptotic proteins by western blot assays. Multivariate logistic regression analysis was used to identify the independent risk factor. The present study found that ASPP2 expression was negatively correlated with that of BECN-1 (Beclin-1) in hepatocellular carcinoma (HCC) tissues. The expression of ASPP-1 was lower while that of Beclin-1 was higher in patients who underwent recurrence of HCC following TACE, than in those who do not undergo such a relapse. ASPP2 expression was also lower in cancerous tissues subjected to TACE, compared with that of directly resected cancerous tissue. The expression of LC3-II was also higher in patients with post-operative recurrence of HCC than in those without relapse. In vitro experiments showed that administration of an autophagy inhibitor, together with hypoxia activation and 5-FU treatment, promoted apoptosis in HepG2 liver cancer cells and primary HCC cells. Multivariate logistic regression analysis revealed that ASPP2 expression in cancer tissue following TACE is an independent risk factor for HCC recurrence as well as overall survival. Higher levels of ASPP2 expression were notably associated with higher objective responses evaluated via mRECIST. Thus, patients with resectable HCC showing high levels of ASPP2 expression may benefit from neoadjuvant TACE prior to resection. Our study provided a novel biomarker for HCC prognosis following TACE, based on cell survival mechanisms related to autophagy.
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Affiliation(s)
- Jiaren Mao
- Department of Radiology, The People's Hospital of Danyang, Danyang, Jiangsu 212300, P.R. China
| | - Zhongjun Tan
- Department of Radiology, The People's Hospital of Danyang, Danyang, Jiangsu 212300, P.R. China
| | - Xiaoqi Pan
- Department of Radiology, The People's Hospital of Danyang, Danyang, Jiangsu 212300, P.R. China
| | - Feijian Meng
- Department of Radiology, The People's Hospital of Danyang, Danyang, Jiangsu 212300, P.R. China
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Elshaarawy O, Gomaa A, Omar H, Rewisha E, Waked I. Intermediate stage hepatocellular carcinoma: a summary review. J Hepatocell Carcinoma 2019; 6:105-117. [PMID: 31372364 PMCID: PMC6628956 DOI: 10.2147/jhc.s168682] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 06/14/2019] [Indexed: 12/12/2022] Open
Abstract
It is well known that intermediate stage hepatocellular carcinoma (HCC) encompasses the widest class of patients with this disease. The main characteristic of this special sub-group of patients is that it is extensively heterogenous. This substantial heterogeneity is due to the wide range of liver functions of such patients and variable tumor numbers and sizes. Real world clinical data show huge support for transarterial chemo-embolization (TACE) as a therapeutic modality for intermediate stage HCC, applied in 50%-60% of those class of patients. There are special considerations in various international guidelines regarding treatment allocation in intermediate stage HCC. There is an epidemiological difference in HCC in eastern and western cohorts, and various guidelines have been proposed. In patients with HCC, it has frequently been reported that there is poor correlation between the clinical benefit and real gain in patient condition and the conventional way of tumor response assessment after locoregional treatments. This is due to the evaluation criteria in addition to the scoring systems used for treatment allocation in those patients. It became clear that intermediate stage HCC patients receiving TACE need a proper prognostic score that offers valid clinical prediction and supports proper decision-making. Also, it is the proper time to study more treatment options beyond TACE, such as multimodal regimens for this class of patients. In this review, we tried to provide a summary of the challenges and future directions in managing patients with intermediate stage HCC.
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Affiliation(s)
- Omar Elshaarawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Asmaa Gomaa
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Hazem Omar
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Eman Rewisha
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Imam Waked
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
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Wang E, Xia D, Bai W, Yuan J, Li X, Niu J, Yin Z, Xia J, Cai H, Fan D, Han G, Liu L. Tumor Hypervascularity and hand-foot-skin reaction predict better outcomes in combination treatment of TACE and Sorafenib for intermediate hepatocellular carcinoma. BMC Cancer 2019; 19:409. [PMID: 31039750 PMCID: PMC6492437 DOI: 10.1186/s12885-019-5570-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Accepted: 04/02/2019] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND To validate the robust predictive values of tumor vascularity and hand-foot-skin reaction (HFSR) in combination treatment of transarterial chemoembolization (TACE) and sorafenib for patients with intermediate hepatocellular carcinoma (HCC), and then select the potential candidates who would survive best from such treatment. METHODS A total of 132 treatment-naive patients with intermediate HCC undergoing combination therapy of TACE and sorafenib were recruited between January 2010 and December 2014. The tumor vascularity was defined according to digital subtraction angiography (DSA) and HFSR was assessed by the national cancer institute common terminology criteria for adverse events (NCI-CTCAE). The Mann-Whitney U test was used to assess the correlation between vascularity and radiologic response; time to radiologic progression (TTP) and overall survival (OS) were evaluated using Kaplan-Meier techniques and compared by log-rank test; factors associated with them were evaluated using multivariate Cox regression analysis. RESULTS During a median follow up of 17.3 months, it was revealed that hypervascularity and development of ≥2 grade of HFSR within 60 days after sorafenib initiation were favorable predictors for TTP (HR 0.378, p < 0.001; HR 0.627, p = 0.018) and OS (HR 0.499, p = 0.002; HR 0.555, p = 0.004). The median TTP and OS for patients with both were 12.2 and 29.1 months, which were better than patients with either of them (6.0 months, HR 1.74, p = 0.012; 16.5 months, HR 1.73, p = 0.021), as well as those with neither (2.9 months, HR 3.74, p < 0.001; 11.9 months, HR 3.17, p < 0.001). CONCLUSIONS Tumor hypervascularity and development of ≥2 grade of HFSR within 60 days were favorable predictive factors for the combination treatment of TACE and sorafenib, with both of which the patients survived longest and might be the potential candidates.
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Affiliation(s)
- Enxin Wang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Dongdong Xia
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Wei Bai
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Jie Yuan
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Xiaomei Li
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Jing Niu
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Zhanxin Yin
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Jielai Xia
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, 710032, China
| | - Hongwei Cai
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, 710032, China
| | - Daiming Fan
- Xijing Hospital of Digestive Diseases & State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, 710032, China
| | - Guohong Han
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Lei Liu
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
- Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle Road, Xi'an, 710032, China.
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Escudier B, Worden F, Kudo M. Sorafenib: key lessons from over 10 years of experience. Expert Rev Anticancer Ther 2018; 19:177-189. [PMID: 30575405 DOI: 10.1080/14737140.2019.1559058] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Introduction: In 2005, sorafenib was the first targeted therapy approved for advanced renal cell carcinoma (RCC), transforming treatment. In hepatocellular carcinoma (HCC), for more than a decade, sorafenib remained the only approved systemic therapy to have demonstrated a survival benefit in first-line unresectable HCC. In 2013, sorafenib was the first targeted agent approved for patients with differentiated thyroid cancer (DTC) refractory to radioactive iodine treatment. Areas covered: This review discusses the development, advances, and challenges associated with sorafenib use in RCC, HCC, and DTC over the past decade. A search was performed on PubMed and key congresses as required, with no time limits. Expert commentary: Sorafenib has had a lasting impact on the therapeutic landscape of RCC, HCC, and DTC, and remains an important treatment option despite a rapidly evolving treatment landscape. Extensive clinical and real-world experience has been invaluable in improving patient management and maximizing benefit from treatment. Ongoing clinical trials continue to evaluate sorafenib in different settings, and in combination with other therapies in HCC and DTC. We have no doubt that sorafenib will continue to be an important treatment option in the coming years.
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Affiliation(s)
- Bernard Escudier
- a Department of Medical Oncology , Institut Gustave Roussy , Paris , France
| | - Francis Worden
- b Department of Internal Medicine, Division of Hematology and Oncology, Comprehensive Cancer Center , University of Michigan , Ann Arbor , MI , USA
| | - Masatoshi Kudo
- c Department of Gastroenterology and Hepatology , Kindai University Faculty of Medicine , Osaka , Japan
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Jin PP, Shao SY, Wu WT, Zhao XY, Huang BF, Fu QH, Que RS, Hu QD. Combination of transarterial chemoembolization and sorafenib improves outcomes of unresectable hepatocellular carcinoma: an updated systematic review and meta-analysis. Jpn J Clin Oncol 2018; 48:1058-1069. [PMID: 30272196 DOI: 10.1093/jjco/hyy138] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Accepted: 09/18/2018] [Indexed: 12/28/2022] Open
Affiliation(s)
- Piao-Piao Jin
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Shi-Yi Shao
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wang-Teng Wu
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xin-Yu Zhao
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Bing-Feng Huang
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qi-Han Fu
- Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ri-Sheng Que
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qi-Da Hu
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Wang E, Xia D, Bai W, Wang Z, Wang Q, Liu L, Wang W, Yuan J, Li X, Chen H, Lv Y, Niu J, He C, Guo W, Yin Z, Luo B, Han N, Wang Z, Yu T, Yuan X, Li K, Tie J, Li C, Cai H, Xia J, Fan D, Han G. Hand-foot-skin reaction of grade ≥ 2 within sixty days as the optimal clinical marker best help predict survival in sorafenib therapy for HCC. Invest New Drugs 2018; 37:401-414. [PMID: 30019101 DOI: 10.1007/s10637-018-0640-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Accepted: 07/09/2018] [Indexed: 12/31/2022]
Abstract
Background & Aims Sorafenib-related adverse events have been reported as clinical surrogates for treatment response in hepatocellular carcinoma (HCC); however, no consensus has been reached regarding the definition of responders. We evaluated the predictive abilities of different definitions for sorafenib response based on treatment-emergent adverse events, aiming to identify the most discriminatory one as a clinical marker. Methods From January 2010 to December 2014, 435 consecutive HCC patients treated with sorafenib were enrolled. Considering the type, severity and timing of adverse events, twelve different categories of sorafenib response were defined. By comparing their discriminatory abilities for survival, an indicative criterion was defined, the prognostic value of which was evaluated by time-dependent multivariate analysis, validated in various subsets and confirmed by landmark analysis. Results Using concordance (C)-index analysis and time-dependent receiver operating characteristic curves, the development of a hand-foot-skin reaction ≥ grade 2 within 60 days of sorafenib initiation (2HFSR60) showed the highest discriminating value. Based on this criterion, 161 (37.0%) sorafenib responders achieved decreased risk of death by 47% (adjusted HR 0.53, 95%CI 0.43-0.67, P < 0.001) and likelihood of progression by 26% (adjusted HR 0.74, 95%CI 0.58-0.96, P = 0.020) compared with non-responders. Notably, 2HFSR60 remained an effective discriminator among most subgroups and had superior predictive ability to previous definitions, even according to the landmark analysis. Conclusions Our study demonstrated that 2HFSR60, with the best discriminatory ability compared to currently available definitions of sorafenib-related adverse events, could be the optimal clinical marker to identify sorafenib responders with decreased risk of death by half.
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Affiliation(s)
- Enxin Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Dongdong Xia
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Wei Bai
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Zhexuan Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Qiuhe Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Lei Liu
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Wenjun Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Jie Yuan
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Xiaomei Li
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Hui Chen
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Yong Lv
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Jing Niu
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Chuangye He
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Wengang Guo
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Zhanxin Yin
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Bohan Luo
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Na Han
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Zhengyu Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Tianlei Yu
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Xulong Yuan
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Kai Li
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Jun Tie
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Chanjuan Li
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, China
| | - Hongwei Cai
- Information Center, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Jielai Xia
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, China
| | - Daiming Fan
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
- Xijing Hospital of Digestive Diseases & State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - Guohong Han
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China.
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Lei XF, Ke Y, Bao TH, Tang HR, Wu XS, Shi ZT, Lin J, Zhang ZX, Gu H, Wang L. Effect and safety of sorafenib in patients with intermediate hepatocellular carcinoma who received transarterial chemoembolization: A retrospective comparative study. World J Clin Cases 2018; 6:74-83. [PMID: 29774219 PMCID: PMC5955731 DOI: 10.12998/wjcc.v6.i5.74] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Revised: 03/04/2018] [Accepted: 03/20/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To evaluate the safety and efficacy of sorafenib plus transarterial chemoembolization (TACE) treatment for intermediate hepatocellular carcinoma (HCC).
METHODS Sixty-seven patients with intermediate-stage [Barcelona Clinic liver cancer stage B (BCLC-B)] HCC who were treated with sorafenib plus TACE or TACE alone between 2009 and 2011 were included in the study. Follow-up was until 2014 or patient death. Two groups were defined in the experiment: The experimental group, treated with sorafenib plus TACE, and the control group, treated with standard TACE alone.
RESULTS The Kaplan-Meier survival analysis showed that the median overall survival (mOS) of the experimental group was 35.2 mo, while that of the control group was 22.0 mo (P < 0.05). Sorafenib plus TACE showed higher incidence rates of rash, hand-foot syndrome (HFS), and hypertension (P < 0.05) than TACE treatment alone.
CONCLUSION Sorafenib plus TACE treatment for BCLC-B HCC significantly prolonged the mOS of patients compared to TACE treatment alone. The most common toxicities with sorafenib were rash (31.6%), HFS (39.5%) and hypertension (31.6%), but there were no intolerable adverse events. The Cox multivariate analysis showed that the survival of patients with BCLC-B HCC depended on the Child-Pugh classification, tumor diameter, and treatment with sorafenib plus TACE compared to TACE alone.
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Affiliation(s)
- Xue-Fen Lei
- Department of Medical Oncology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
| | - Yang Ke
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
| | - Tian-Hao Bao
- The Mental Health Center of Kunming Medical University, Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
| | - Hao-Ran Tang
- Department of Gastroenterological Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
| | - Xue-Song Wu
- Department of Gastroenterological Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
| | - Zhi-Tian Shi
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University; Kunming 650101, Yunnan Province, China
| | - Jie Lin
- Department of Medical Oncology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
| | - Zhi-Xian Zhang
- Department of Medical Oncology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
| | - Hou Gu
- Department of Medical Oncology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
| | - Lin Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University; Kunming 650101, Yunnan Province, China
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Meng XC, Chen BH, Huang JJ, Huang WS, Cai MY, Zhou JW, Guo YJ, Zhu KS. Early prediction of survival in hepatocellular carcinoma patients treated with transarterial chemoembolization plus sorafenib. World J Gastroenterol 2018; 24:484-493. [PMID: 29398869 PMCID: PMC5787783 DOI: 10.3748/wjg.v24.i4.484] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Revised: 12/10/2017] [Accepted: 12/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To identify clinical biomarkers that could early predict improved survival in patients with advanced-stage hepatocellular carcinoma (HCC) treated with transarterial chemoembolization combined with sorafenib (TACE-S).
METHODS We retrospectively evaluated the medical records of consecutive patients with advanced-stage HCC who underwent TACE-S from January 2012 to December 2015. At the first follow-up 4-6 wk after TACE-S (median, 38 d; range, 33-45 d), patients exhibiting the modified Response Evaluation Criteria in Solid Tumors (mRECIST)-evaluated complete response, partial response, and stable disease were categorized as early disease control. At this time point, multiple variables were analyzed to identify the related factors affecting survival.
RESULTS Ninety-five patients were included in this study, and 60 of these patients achieved early disease control, with an overall disease control rate (DCR) of 63.2%. Patients who got sorafenib at the first TACE (no previous TACE) and patients without portal vein tumor thrombus (PVTT) had a higher DCR than those who underwent previous TACE before TACE-S (72.4% vs 48.6%, P = 0.019) and those with PVTT (75.5% vs 50.0%, P = 0.010). Early disease control after TACE-S, no previous TACE, and no PVTT were the independent prognostic factors for survival in the uni- and multivariate analyses.
CONCLUSION The first follow-up 4-6 wk after TACE-S can be used as the earliest time point to assess the response to TACE-S, and patients with mRECIST-evaluated early disease control, no previous TACE, and no PVTT had better survival.
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Affiliation(s)
- Xiao-Chun Meng
- Department of Radiology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Bing-Hui Chen
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
| | - Jing-Jun Huang
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Wen-Sou Huang
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Ming-Yue Cai
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Jing-Wen Zhou
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Yong-Jian Guo
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
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MEIS-1 level in unresectable hepatocellular carcinoma can predict the post-treatment outcomes of radiofrequency ablation. Oncotarget 2018; 9:15252-15265. [PMID: 29632641 PMCID: PMC5880601 DOI: 10.18632/oncotarget.24165] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 12/01/2017] [Indexed: 02/06/2023] Open
Abstract
Radiofrequency ablation (RFA) is a local-ablative therapy for unresectable hepatocellular carcinoma (HCC). At present, there is no predictive marker for RFA treatment outcomes. This work aimed to valuate myeloid ecotropic viral integration site 1 (MEIS-1) in predicting post-RFA treatment outcomes of unresectable HCC patients. The time to progression (TTP) and overall survival (OS) of 81 HCC patients who received RFA treatment were measured. The protein level of MEIS-1 in tumor specimens was measured by western blot. The role of MEIS-1 in RFA-treating HCC in vivo growth nude mouse model was examined via PET/CT imaging. Higher level of MEIS-1 in tumor tissue is associated with better RFA treatment outcomes. The median TTP was 9.0 (95% confidence interval [CI]: 6.8–11.3) months in patients with high MEIS-1 expression (n = 43) versus 6.0 (95% CI: 4.6–7.4) months in patients with low MEIS-1 expression (n = 38). Moreover, in rodent HCC model we found overexpression of MEIS-1 enhanced the anti-tumor effect of RFA treatment. We conclude that high level of MEIS-1 expression predicts better RFA treatment outcome in HCC.
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12
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Abstract
Hepatocellular carcinoma (HCC), also called malignant hepatoma, is one of the deadliest cancers due to its complexities, reoccurrence after surgical resection, metastasis and heterogeneity. Incidence and mortality of HCC are increasing in Western countries and are expected to rise as a consequence of the obesity epidemic. Multiple factors trigger the initiation and progression of HCC including chronic alcohol consumption, viral hepatitis B and C infection, metabolic disorders and age. Although Sorafenib is the only FDA approved drug for the treatment of HCC, numerous treatment modalities such as transcatheter arterial chemoembolization/transarterial chemoembolization (TACE), radiotherapy, locoregional therapy and chemotherapy have been tested in the clinics. Polymeric nanoparticles, liposomes, and micelles carrying small molecules, proteins, peptides and nucleic acids have attracted great attention for the treatment of various cancers including HCC. Herein, we discuss the pathogenesis of HCC in relation to its various recent treatment methodologies using nanodelivery of monoclonal antibodies (mAbs), small molecules, miRNAs and peptides. Synopsis of recent clinical trials of mAbs and peptide drugs has been presented with a broad overview of the pathogenesis of the disease and treatment efficacy.
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Affiliation(s)
- Rinku Dutta
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Ram I Mahato
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States.
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