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Li L, Li ZZ, Pan LX, Su JY, Huang S, Ma L, Zhong JH. Adjuvant Therapy for Hepatocellular Carcinoma After Curative Treatment: Several Unanswered Questions. J Clin Transl Hepatol 2024; 12:525-533. [PMID: 38779519 PMCID: PMC11106350 DOI: 10.14218/jcth.2024.00030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 03/31/2024] [Accepted: 04/09/2024] [Indexed: 05/25/2024] Open
Abstract
Most patients with hepatocellular carcinoma (HCC) have a poor prognosis. Hepatectomy and local ablation are the main curative treatments for HCC. Nevertheless, the recurrence rate after hepatectomy or ablation is up to 70%, which seriously affects patient prognosis. Several adjuvant therapies have been explored to reduce postoperative recurrence. However, although a variety of adjuvant therapies have been shown to reduce the recurrence rate and improve overall survival, a standard consensus of national HCC guidelines for adjuvant treatment is lacking. Therefore, there are significant differences in the recommendations for adjuvant therapy for HCC between the Eastern and Western guidelines. A variety of adjuvant treatment methods, such as antiviral therapy, transarterial chemoembolization or traditional Chinese medicine, are recommended by the Chinese HCC guidelines. However, Western guidelines make few recommendations other than antiviral therapy. Adjuvant immune checkpoint inhibitors are recommended only in the recently updated American Association for the Study of Liver Diseases guidelines. This review summarized the existing adjuvant therapy options after curative hepatectomy or ablation and discusses several important dilemmas of adjuvant treatments.
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Affiliation(s)
- Le Li
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
- Guangxi Academy of Medical Sciences, Emergency Department, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
| | - Zhen-Zhen Li
- Pathology Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Li-Xin Pan
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Jia-Yong Su
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Shan Huang
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Liang Ma
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Jian-Hong Zhong
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi, China
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Shu Q, Zhang N, Han J, Yan X, Sha B, Zhao L, Yi Y, Zhang Y. Novel predictive nomograms based on aspartate aminotransferase‑to‑platelet ratio index for hepatocellular carcinoma with post‑operative adjuvant transarterial chemoembolization. Oncol Lett 2024; 27:3. [PMID: 38028181 PMCID: PMC10665988 DOI: 10.3892/ol.2023.14137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 10/05/2023] [Indexed: 12/01/2023] Open
Abstract
The clinical significance of systemic inflammation assessed with laboratory analysis of blood samples has been validated in a variety of cancers. The present study was conducted to investigate prognostic significance of preoperative aspartate aminotransferase-to-platelet ratio index (APRI) for the outcome of hepatocellular carcinoma (HCC) patients receiving post-operative adjuvant transarterial chemoembolization (PATACE). A total of 201 patients who underwent PATACE were retrospectively analyzed. A nomogram for HCC was developed using predictors based on multivariate Cox models, and bootstrapping was performed for validation. According to the ROC curve, which was used to divide patients into two cohorts: High APRI group (APRI>1.02) and Low APRI group (APRI≤1.02). In subgroup survival analysis, patients with a relatively low APRI had significantly longer disease-free survival (DFS) and overall survival (OS) than patients with a relatively high APRI, regardless of Barcelona Clinic Liver Cancer (BCLC) stages (BCLC 0/A or BCLC B/C, both P<0.05); while in China liver cancer staging I/II and TNM I/II stage patients, relatively low APRI was associated with improved DFS and OS (both P<0.05). Multivariate Cox models demonstrated that APRI and BCLC stages were independent prognostic factors of DFS and OS (both P<0.05). Nomograms for DFS and OS were constructed, respectively. Calibration curve analysis showed that the standard curve fitted well with the predicted curve. Time-receiver operating characteristic curve analysis revealed that the nomogram had high efficiency. Decision curve analysis demonstrated the high clinical value of the nomogram. APRI is an independent prognostic factor of DFS and OS in HCC patients receiving PATACE, and the combination of APRI with the HCC staging system can refine risk stratification to provide a more accurate prognostic assessment for the outcome of patients receiving PATACE.
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Affiliation(s)
- Qinghua Shu
- Department of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210003, P.R. China
| | - Nannan Zhang
- Department of Gastroenterology, Jiangsu Geriatric Hospital/Jiangsu Official Hospital, Nanjing, Jiangsu 210024, P.R. China
| | - Jianbo Han
- Department of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210003, P.R. China
| | - Xiaopeng Yan
- Department of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210003, P.R. China
| | - Bowen Sha
- Department of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210003, P.R. China
| | - Liang Zhao
- Department of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210003, P.R. China
| | - Yongxiang Yi
- Department of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210003, P.R. China
| | - Yufeng Zhang
- Department of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210003, P.R. China
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Elderkin J, Al Hallak N, Azmi AS, Aoun H, Critchfield J, Tobon M, Beal EW. Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management. Cancers (Basel) 2023; 15:5118. [PMID: 37958294 PMCID: PMC10647678 DOI: 10.3390/cancers15215118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 10/11/2023] [Accepted: 10/13/2023] [Indexed: 11/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) ranks fourth in cancer-related deaths worldwide. Semiannual surveillance of the disease for patients with cirrhosis or hepatitis B virus allows for early detection with more favorable outcomes. The current underuse of surveillance programs demonstrates the need for intervention at both the patient and provider level. Mail outreach along with navigation provision has proven to increase surveillance follow-up in patients, while provider-targeted electronic medical record reminders and compliance reports have increased provider awareness of HCC surveillance. Imaging is the primary mode of diagnosis in HCC with The Liver Imaging Reporting and Data System (LI-RADS) being a widely accepted comprehensive system that standardizes the reporting and data collection for HCC. The management of HCC is complex and requires multidisciplinary team evaluation of each patient based on their preference, the state of the disease, and the available medical and surgical interventions. Staging systems are useful in determining the appropriate intervention for HCC. Early-stage HCC is best managed by curative treatment modalities, such as liver resection, transplant, or ablation. For intermediate stages of the disease, transarterial local regional therapies can be applied. Advanced stages of the disease are treated with systemic therapies, for which there have been recent advances with new drug combinations. Previously sorafenib was the mainstay systemic treatment, but the recent introduction of atezolizumab plus bevacizumab proves to have a greater impact on overall survival. Although there is a current lack of improved outcomes in Phase III trials, neoadjuvant therapies are a potential avenue for HCC management in the future.
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Affiliation(s)
- Jessica Elderkin
- Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Asfar S. Azmi
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Hussein Aoun
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Jeffrey Critchfield
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Miguel Tobon
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Eliza W. Beal
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
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Operational nuclear research reactors in the Asia-Pacific with potential for medical radionuclide production. Nucl Med Commun 2023; 44:227-243. [PMID: 36808108 DOI: 10.1097/mnm.0000000000001665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2023]
Abstract
Personalised cancer treatment is of growing importance and can be achieved via targeted radionuclide therapy. Radionuclides with theranostic properties are proving to be clinically effective and are widely used because diagnostic imaging and therapy can be accomplished using a single formulation that avoids additional procedures and unnecessary radiation burden to the patient. For diagnostic imaging, single photon emission computed tomography (SPECT) or positron emission tomography (PET) is used to obtain functional information noninvasively by detecting the gamma (γ) rays emitted from the radionuclide. For therapeutics, high linear energy transfer (LET) radiations such as alpha (α), beta (β - ) or Auger electrons are used to kill cancerous cells in close proximity, whereas sparing the normal tissues surrounding the malignant tumour cells. One of the most important factors that lead to the sustainable development of nuclear medicine is the availability of functional radiopharmaceuticals. Nuclear research reactors play a vital role in the production of medical radionuclides for incorporation into clinical radiopharmaceuticals. The disruption of medical radionuclide supplies in recent years has highlighted the importance of ongoing research reactor operation. This article reviews the current status of operational nuclear research reactors in the Asia-Pacific region that have the potential for medical radionuclide production. It also discusses the different types of nuclear research reactors, their operating power, and the effects of thermal neutron flux in producing desirable radionuclides with high specific activity for clinical applications.
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Guo B, Chen Q, Liu Z, Chen X, Zhu P. Adjuvant therapy following curative treatments for hepatocellular carcinoma: current dilemmas and prospects. Front Oncol 2023; 13:1098958. [PMID: 37139151 PMCID: PMC10149944 DOI: 10.3389/fonc.2023.1098958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 04/04/2023] [Indexed: 05/05/2023] Open
Abstract
Curative surgical treatments, mainly liver resection, are still one of the optimal options for patients with early-, mid-, and even progression-stage hepatocellular carcinoma (HCC). However, the recurrence rate within 5 years after surgery is as high as 70%, especially in patients with high risk factors for recurrence, most of whom experience early recurrence within 2 years. Effective adjuvant therapy may improve prognosis, previous studies found that adjuvant transarterial chemoembolization, antiviral, and traditional Chinese medicine et al. were helpful in preventing HCC recurrence. Nevertheless, due to controversial results or lack of high-level evidence, there is no standardized postoperative management protocol worldwide at present. Continued exploration of effective postoperative adjuvant treatments to improve surgical prognosis is necessary.
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Affiliation(s)
- Bin Guo
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qian Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hepatobiliary Surgery Department, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, China
| | - Zhicheng Liu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Peng Zhu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- *Correspondence: Peng Zhu,
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Nevarez NM, Chang GY, Yopp AC. An Overview of Clinical Trials in the Treatment of Resectable Hepatocellular Carcinoma. Surg Oncol Clin N Am 2023; 32:101-117. [PMID: 36410911 DOI: 10.1016/j.soc.2022.07.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Partial hepatectomy, one of a few curative therapeutic modalities, is plagued by high recurrence rate of up to 70% at 5 years. Throughout the past 3 decades, many clinical trials have attempted to improve HCC recurrence rate following partial hepatectomy using adjuvant and neoadjuvant treatment modalities such as antiviral therapy, brachytherapy, systemic chemotherapy, immunotherapy, transarterial chemoembolization and radioembolization, and radiotherapy. The goal of this review is to discuss the clinical trials pertaining to resectable HCC including surgical technique considerations, adjuvant, and neoadjuvant treatment modalities.
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Affiliation(s)
- Nicole M Nevarez
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
| | - Gloria Y Chang
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
| | - Adam C Yopp
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
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Jokar N, Moradhaseli F, Ahmadzadehfar H, Jafari E, Nikeghbalian S, Rasekhi AR, Assadi M. Theranostic approach in liver cancer: an emerging paradigm to optimize personalized medicine. Clin Transl Imaging 2022. [DOI: 10.1007/s40336-022-00525-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Zeng ZM, Mo N, Zeng J, Ma FC, Jiang YF, Huang HS, Liao XW, Zhu GZ, Ma J, Peng T. Advances in postoperative adjuvant therapy for primary liver cancer. World J Gastrointest Oncol 2022; 14:1604-1621. [PMID: 36187393 PMCID: PMC9516643 DOI: 10.4251/wjgo.v14.i9.1604] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 05/13/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly heterogeneous, invasive, and conventional chemotherapy-insensitive tumor with unique biological characteristics. The main methods for the radical treatment of HCC are surgical resection or liver transplantation. However, recurrence rates are as high as 50% and 70% at 3 and 5 years after liver resection, respectively, and even in Milan-eligible recipients, the recurrence rate is approximately 20% at 5 years after liver transplantation. Therefore, reducing the postoperative recurrence rate is key to improving the overall outcome of liver cancer. This review discusses the risk factors for recurrence in patients with HCC radical surgical resection and adjuvant treatment options that may reduce the risk of recurrence and improve overall survival, including local adjuvant therapy (e.g., transcatheter arterial chemoembolization), adjuvant systemic therapy (e.g., molecular targeted agents and immunotherapy), and other adjuvant therapies (e.g., antiviral and herbal therapy). Finally, potential research directions that may change the paradigm of adjuvant therapy for HCC are analyzed.
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Affiliation(s)
- Zhi-Ming Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ning Mo
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Fu-Chao Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yan-Feng Jiang
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hua-Sheng Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xi-Wen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guang-Zhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Wang L, Qiu L, Ke Q, Ji H, Wu J. Systematic review of adjuvant external beam radiotherapy for hepatocellular carcinoma following radical hepatectomy. Radiother Oncol 2022; 175:101-111. [PMID: 35998838 DOI: 10.1016/j.radonc.2022.08.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 08/11/2022] [Accepted: 08/16/2022] [Indexed: 10/15/2022]
Abstract
BACKGROUND AND AIM Recurrence remains the main bottleneck hindering outcomes of hepatectomy for hepatocellular carcinoma (HCC). Owing to technological advances, external beam radiotherapy (EBRT) is being increasingly used in the management of HCC; however, there is no consensus on the role of adjuvant EBRT following hepatectomy. METHODS A systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. PubMed, MedLine, Embase, the Cochrane Library, Web of Knowledge were used to screen eligible studies (published as of May 1st, 2022) that evaluated the clinical safety and efficacy of EBRT for HCC receiving hepatectomy. The endpoints were disease-free survival (DFS), overall survival (OS), and adverse events (AEs). RESULTS A total of ten studies were eligible (three randomized controlled trials, one phase II trial, and six retrospective comparative studies). The pooled hazard ratio (HR) for median DFS and OS were both in favor of adjuvant EBRT compared with surgery alone (all P<0.05), and the advantage of adjuvant EBRT was also confirmed in subgroups stratified by different populations (narrow margin, P<0.05; microvascular invasion, P<0.05; portal vein tumor thrombus, P<0.05) and study designs (prospective studies, P<0.05; retrospective studies, P<0.05). Adjuvant EBRT was also found to be superior to adjuvant TACE (P<0.05). Pooled rates of overall AEs and severe AEs were 65.3% and 12.2%, but no fatal AEs were reported. CONCLUSION Adjuvant EBRT can be considered for HCC patients, especially those with a high risk of recurrence. Further studies are required for validation of these findings.
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Affiliation(s)
- Lei Wang
- College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, Fujian, China; Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Lu Qiu
- Department of Radiation Oncology, Zhangzhou Affiliated Hospital of Fujian medical University, Fuzhou, Zhangzhou, China
| | - Qiao Ke
- College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, Fujian, China; Department of Hepatopancreatobiliary Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Hongbing Ji
- Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China.
| | - Junxin Wu
- College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, Fujian, China; Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China.
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Zhang Y, Lei X, Xu L, Lv X, Xu M, Tang H. Preoperative and postoperative nomograms for predicting early recurrence of hepatocellular carcinoma without macrovascular invasion after curative resection. BMC Surg 2022; 22:233. [PMID: 35715787 PMCID: PMC9205542 DOI: 10.1186/s12893-022-01682-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 06/06/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Postoperative early recurrence (ER) is a major obstacle to long-term survival after curative liver resection (LR) in patients with hepatocellular carcinoma (HCC). This study aimed to establish preoperative and postoperative nomograms to predict ER in HCC without macrovascular invasion. METHODS Patients who underwent curative LR for HCC between January 2012 and December 2016 were divided into training and internal prospective validation cohorts. Nomograms were constructed based on independent risk factors derived from the multivariate logistic regression analyses in the training cohort. The predictive performances of the nomograms were validated using the internal prospective validation cohort. RESULTS In total, 698 patients fulfilled the eligibility criteria. Among them, 265 of 482 patients (55.0%) in the training cohort and 120 of 216 (55.6%) patients in the validation cohort developed ER. The preoperative risk factors associated with ER were age, alpha-fetoprotein, tumor diameter, and tumor number, and the postoperative risk factors associated with ER were age, tumor diameter, tumor number, microvascular invasion, and differentiation. The pre- and postoperative nomograms based on these factors showed good accuracy, with concordance indices of 0.712 and 0.850 in the training cohort, respectively, and 0.754 and 0.857 in the validation cohort, respectively. The calibration curves showed optimal agreement between the predictions by the nomograms and actual observations. The area under the receiver operating characteristic curves of the pre- and postoperative nomograms were 0.721 and 0.848 in the training cohort, respectively, and 0.754 and 0.844 in the validation cohort, respectively. CONCLUSIONS The nomograms constructed in this study showed good performance in predicting ER for HCC without macrovascular invasion before and after surgery. These nomograms would be helpful for doctors when determining treatments and selecting patients for regular surveillance or administration of adjuvant therapies.
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Affiliation(s)
- Yanfang Zhang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xuezhong Lei
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Liangliang Xu
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoju Lv
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Mingqing Xu
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China.
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
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Subramanian S, Mallia MB, Shinto AS, Mathew AS. Clinical Management of Liver Cancer in India and Other Developing Nations: A Focus on Radiation Based Strategies. Oncol Ther 2021; 9:273-295. [PMID: 34046873 PMCID: PMC8593115 DOI: 10.1007/s40487-021-00154-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 05/12/2021] [Indexed: 11/28/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a global killer with preponderance in Asian and African countries. It poses a challenge for successful management in less affluent or developing nations like India, with large populations and limited infrastructures. This review aims to assess the available options and future directions for management of HCC applicable to such countries. While summarizing current and emerging clinical strategies for detection, staging and therapy of the disease, it highlights radioisotope- and radioactivity-based strategies as part of an overall program. Using the widely accepted Barcelona Clinic Liver Cancer (BCLC) staging system as a base, it evaluates the applicability of different therapeutic approaches and their synergistic combination(s) in the context of a patient-specific dynamic results-based strategy. It distills the conclusions of multiple HCC management-focused consensus recommendations to provide a picture of clinical strategies, especially radiation-related approaches. Additionally, it discusses the logistical and economic feasibility of these approaches in the context of the limitations of the burdened public health infrastructure in India (and like nations) and highlights possible strategies both at the clinical level and in terms of an administrative health policy on HCC to provide the maximum possible benefit to the widest swathe of the affected population.
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Affiliation(s)
- Suresh Subramanian
- Radiopharmaceuticals Division, RLG Building, Bhabha Atomic Research Centre, Trombay, Mumbai, Maharashtra, 400085, India.
| | - Madhava B Mallia
- Radiopharmaceuticals Division, RLG Building, Bhabha Atomic Research Centre, Trombay, Mumbai, Maharashtra, 400085, India
| | - Ajit S Shinto
- Apollo Proton Cancer Centre, Chennai, 600096, Tamil Nadu, India
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Rodriguez S, Skeet K, Mehmetoglu-Gurbuz T, Goldfarb M, Karri S, Rocha J, Shahinian M, Yazadi A, Poudel S, Subramani R. Phytochemicals as an Alternative or Integrative Option, in Conjunction with Conventional Treatments for Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:cancers13225753. [PMID: 34830907 PMCID: PMC8616323 DOI: 10.3390/cancers13225753] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 11/10/2021] [Accepted: 11/15/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is globally ranked as the sixth most diagnosed cancer, and the second most deadly cancer. To worsen matters, there are only limited therapeutic options currently available; therefore, it is necessary to find a reservoir from which new HCC treatments may be acquired. The field of phytomedicine may be the solution to this problem, as it offers an abundance of plant-derived molecules, which show capabilities of being effective against HCC proliferation, invasion, migration, and metastasis. In our review, we collect and analyze current evidence regarding these promising phytochemical effects on HCC, and delve into their potential as future chemotherapies. Additionally, information on the signaling behind these numerous phytochemicals is provided, in an attempt to understand their mechanisms. This review makes accessible the current body of knowledge pertaining to phytochemicals as HCC treatments, in order to serve as a reference and inspiration for further research into this subject. Abstract Hepatocellular carcinoma (HCC) is the most abundant form of liver cancer. It accounts for 75–85% of liver cancer cases and, though it ranks globally as the sixth most common cancer, it ranks second in cancer-related mortality. Deaths from HCC are usually due to metastatic spread of the cancer. Unfortunately, there are many challenges and limitations with the latest HCC therapies and medications, making it difficult for patients to receive life-prolonging care. As there is clearly a high demand for alternative therapy options for HCC, it is prudent to turn to plants for the solution, as their phytochemicals have long been used and revered for their many medicinal purposes. This review explores the promising phytochemical compounds identified from pre-clinical and clinical trials being used either independently or in conjunction with already existing cancer therapy treatments. The phytochemicals discussed in this review were classified into several categories: lipids, polyphenols, alkaloids, polysaccharides, whole extracts, and phytochemical combinations. Almost 80% of the compounds failed to progress into clinical studies due to lack of information regarding the toxicity to normal cells and bioavailability. Although large obstacles remain, phytochemicals can be used either as an alternative or integrative therapy in conjunction with existing HCC chemotherapies. In conclusion, phytochemicals have great potential as treatment options for hepatocellular carcinoma.
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Affiliation(s)
- Sheryl Rodriguez
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
| | - Kristy Skeet
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Tugba Mehmetoglu-Gurbuz
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
| | - Madeline Goldfarb
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (M.G.); (S.K.)
| | - Shri Karri
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (M.G.); (S.K.)
| | - Jackelyn Rocha
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Mark Shahinian
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Abdallah Yazadi
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
| | - Seeta Poudel
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
| | - Ramadevi Subramani
- Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (S.R.); (T.M.-G.); (S.P.)
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; (K.S.); (J.R.); (M.S.); (A.Y.)
- Correspondence: ; Tel.: +1-915-215-6851
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13
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Zhang W, Zhang B, Chen XP. Adjuvant treatment strategy after curative resection for hepatocellular carcinoma. Front Med 2021; 15:155-169. [PMID: 33754281 DOI: 10.1007/s11684-021-0848-3] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 02/20/2021] [Indexed: 01/27/2023]
Abstract
Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.
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Affiliation(s)
- Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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14
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Li TE, Zhang Z, Wang Y, Xu D, Dong J, Zhu Y, Wang Z. A Novel Immunotype-based Risk Stratification Model Predicts Postoperative Prognosis and Adjuvant TACE Benefit in Chinese Patients with Hepatocellular Carcinoma. J Cancer 2021; 12:2866-2876. [PMID: 33854587 PMCID: PMC8040877 DOI: 10.7150/jca.54408] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 02/28/2021] [Indexed: 12/11/2022] Open
Abstract
Background and Aims: The tumor microenvironment can be divided into inflamed, immune-excluded and immune-desert phenotypes according to CD8+ T cell categories with differential programmed cell death protein 1 (PD-L1) expression. The study aims to construct a novel immunotype-based risk stratification model to predict postsurgical survival and adjuvant trans-arterial chemoembolization (TACE) response in patients with hepatocellular carcinoma (HCC). Methods: A total of 220 eligible HCC patients participated in this study. CD8+ T cell infiltration and PD-L1 expression mode were estimated by immunohistochemical staining. A risk stratification model was developed and virtualized by a nomogram that integrated these independent prognostic factors. The postoperative prognosis and adjuvant TACE benefits were evaluated with a novel immunotype-based risk stratification model. Results: A total of 220 patients were finally identified. Immune-desert, immune-excluded, and inflamed immunotypes represented 45%, 24%, and 31% of HCC, respectively. Univariate and multivariate analyses identified immunotype and PD-L1 expression mode as independent prognostic factors for overall survival time (OS) and recurrence-free survival time (RFS). The nomogram was constructed by integrating immunotype, PD-L1 expression, Barcelona Clinic Liver Cancer (BCLC) stage and tumor grade. The C-index was 0.794 in the training cohort and 0.813 in the validation cohort. A risk stratification system was constructed based on the nomogram classifying HCC patients into 3 risk groups. The average OS times in the low-risk, intermediate-risk and high-risk groups in all cohorts were 77.1 months (95% CI 71.4-82.9), 53.7 months (95% CI 48.2-59.2), and 25.6 months (95% CI 21.4-29.7), respectively. Further analysis showed that OS was significantly improved by adjuvant TACE in the low- and intermediate-risk groups (P=0.041 and P=0.010, respectively) but not in the high-risk group (P=0.398). Conclusion: A novel immunotype-based risk stratification model was built to predict postoperative prognosis and adjuvant TACE benefit in HCC patients. These tools can assist in building a more customized method of HCC treatment.
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Affiliation(s)
- Tian-En Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Ze Zhang
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai 200040, China
| | - Yi Wang
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai 200040, China
| | - Da Xu
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai 200040, China
| | - Jian Dong
- Institute of Advanced Surgical Technology and Engineering, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Ying Zhu
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai 200040, China
| | - Zheng Wang
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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15
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Wang W, Guo Y, Zhong J, Wang Q, Wang X, Wei H, Li J, Xiu P. The clinical significance of microvascular invasion in the surgical planning and postoperative sequential treatment in hepatocellular carcinoma. Sci Rep 2021; 11:2415. [PMID: 33510294 PMCID: PMC7843639 DOI: 10.1038/s41598-021-82058-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 01/12/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and most lethal malignant tumors in the world. Microvascular invasion (MVI) is a major risk factor for survival outcomes and intrahepatic metastasis after resection in patients with HCC. Relevant English literatures retrieved using PubMed on the research progress of MVI in patients with HCC were reviewed. For HCC patients, especially those with MVI, it is very important to develop a comprehensive and sequential treatment plan to support the long-term survival of patients. This manuscript reviewed and analyzed the risk factors for MVI; the preoperative prediction of MVI, which informs the selection of surgical strategies; and the current situation and future direction of comprehensive postoperative treatment strategies; to provide a basis for the comprehensive treatment of HCC patients with MVI. For HCC patients with MVI, the preoperative prediction of MVI may play a certain guiding role in planning procedures, and the comprehensive sequential postoperative pathological detection of HCC MVI may provide a basis for treatment decisions.
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Affiliation(s)
- Wentao Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Yaxun Guo
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jingtao Zhong
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Qi Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
| | - Xin Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Honglong Wei
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jie Li
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Peng Xiu
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China.
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China.
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16
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Llovet JM, Villanueva A, Marrero JA, Schwartz M, Meyer T, Galle PR, Lencioni R, Greten TF, Kudo M, Mandrekar SJ, Zhu AX, Finn RS, Roberts LR. Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference. Hepatology 2021; 73 Suppl 1:158-191. [PMID: 32430997 DOI: 10.1002/hep.31327] [Citation(s) in RCA: 260] [Impact Index Per Article: 65.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 03/31/2020] [Accepted: 04/02/2020] [Indexed: 12/13/2022]
Affiliation(s)
- Josep M Llovet
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.,Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain.,Institució Catalana d'Estudis Avançats (ICREA), Barcelona, Spain
| | - Augusto Villanueva
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | | | - Myron Schwartz
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Tim Meyer
- Department Oncology, University College London Cancer Institute, London, UK
| | - Peter R Galle
- Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany
| | - Riccardo Lencioni
- Department of Radiology, University of Pisa School of Medicine, Pisa, Italy.,Miami Cancer Institute, Miami, FL
| | - Tim F Greten
- Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | | | - Andrew X Zhu
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.,Jiahui International Cancer Center, Shanghai, China
| | | | - Lewis R Roberts
- Gastroenterology & Hepatology Department, Mayo Clinic, Rochester, MN
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17
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Zhu XD, Li KS, Sun HC. Adjuvant therapies after curative treatments for hepatocellular carcinoma: Current status and prospects. Genes Dis 2020; 7:359-369. [PMID: 32884990 PMCID: PMC7452398 DOI: 10.1016/j.gendis.2020.02.002] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 02/20/2020] [Indexed: 02/07/2023] Open
Abstract
Tumor recurrence rate after surgery or ablation of hepatocellular carcinoma (HCC) is as high as 70%. However, there are no widely accepted adjuvant therapies; therefore, no treatment has been recommended by guidelines from the American Association for the Study of Liver Disease or the European Association for the Study of the Liver. All the registered trials failed to find any treatment to prolong recurrence-free survival, which is the primary outcome in most studies, including sorafenib. Some investigator-initiated studies revealed that anti-hepatitis B virus agents, interferon-α, transcatheter chemoembolization, chemokine-induced killer cells, and other treatments prolonged patient recurrence-free survival or overall survival after curative therapies. In this review, we summarize the current status of adjuvant treatments for HCC and explain the challenges associated with designing a clinical trial for adjuvant therapy. Promising new treatments being used as adjuvant therapy, especially anti-PD-1 antibodies, are also discussed.
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Key Words
- Adjuvant therapy
- Anti-PD-1 antibody
- CIK, chemokine-induced killer cells
- CR, complete response
- Clinical trial
- HCC, hepatocellular carcinoma
- Hepatocellular carcinoma
- ICI, immune checkpoint inhibitor
- Molecular targeted therapy
- ORR, objective response rate
- OS, overall survival
- PD-1, program death-1
- PD-L1, program death-1 ligand
- PR, partial response
- RCT, randomized clinical trial
- RECIST, Response Evaluation Criteria in Solid Tumors
- RFS, recurrence-free survival
- Recurrence-free survival
- TACE, transcatheter chemoembolization
- TKI, tyrosine kinase inhibitor
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Affiliation(s)
- Xiao-Dong Zhu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Kang-Shuai Li
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Hui-Chuan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China
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18
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Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov 2020; 19:589-608. [PMID: 32728208 PMCID: PMC7390460 DOI: 10.1038/s41573-020-0073-9] [Citation(s) in RCA: 464] [Impact Index Per Article: 92.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/08/2020] [Indexed: 12/25/2022]
Abstract
Radiopharmaceutical therapy (RPT) is emerging as a safe and effective targeted approach to treating many types of cancer. In RPT, radiation is systemically or locally delivered using pharmaceuticals that either bind preferentially to cancer cells or accumulate by physiological mechanisms. Almost all radionuclides used in RPT emit photons that can be imaged, enabling non-invasive visualization of the biodistribution of the therapeutic agent. Compared with almost all other systemic cancer treatment options, RPT has shown efficacy with minimal toxicity. With the recent FDA approval of several RPT agents, the remarkable potential of this treatment is now being recognized. This Review covers the fundamental properties, clinical development and associated challenges of RPT.
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Affiliation(s)
- George Sgouros
- Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - Lisa Bodei
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Jessie R Nedrow
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
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19
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Hirokawa F, Komeda K, Taniguchi K, Asakuma M, Shimizu T, Inoue Y, Kagota S, Tomioka A, Yamamoto K, Uchiyama K. Is Postoperative Adjuvant Transcatheter Arterial Infusion Therapy Effective for Patients with Hepatocellular Carcinoma who Underwent Hepatectomy? A Prospective Randomized Controlled Trial. Ann Surg Oncol 2020; 27:4143-4152. [PMID: 32500344 DOI: 10.1245/s10434-020-08699-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND The effectiveness of adjuvant transcatheter arterial chemo- or/and chemoembolization therapy after curative hepatectomy of initial hepatocellular carcinoma (HCC) is controversial. This study aimed to evaluate whether hepatectomy combined with adjuvant transcatheter arterial infusion therapy (TAI) for initial HCC has better long-term survival outcomes than hepatectomy alone. METHODS From January 2012 to December 2014, a prospective randomized controlled trial of patients with initial HCC was conducted. Then, 114 initial HCC patients were recruited to undergo hepatectomy with adjuvant TAI (TAI group, n = 55) or hepatectomy alone (control group, n = 59) at our institution. The TAI therapy was performed twice, at 3 and 6 months after curative hepatectomy (UMIN 000011900). RESULTS The patients treated with TAI had no serious side effects, and operative outcomes did not differ between the two groups. No significant differences were found in the pattern of intrahepatic recurrence or time until recurrence between the two groups. Moreover, no significant differences were found in the relapse-free survival or overall survival. Low cholinesterase level (< 200) had been identified as a risk factor affecting relapse-free survival. Furthermore, compared with surgery alone, adjuvant TAI with hepatectomy improved the overall survival for lower-cholinesterase patients. CONCLUSIONS Adjuvant TAI is safe and feasible, but it cannot reduce the incidence of postoperative recurrence or prolong survival for patients who underwent curative hepatectomy for initial HCC.
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Affiliation(s)
- Fumitoshi Hirokawa
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan.
| | - Koji Komeda
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Kohei Taniguchi
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan.,Translational Research Program, Osaka Medical College, Osaka, Japan
| | - Mitsuhiro Asakuma
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Tetsunosuke Shimizu
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Yoshihiro Inoue
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Shuji Kagota
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Atsushi Tomioka
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | | | - Kazuhisa Uchiyama
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
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20
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Lu SD, Li L, Liang XM, Chen W, Chen FL, Fan LL, Ahir BK, Zhang WG, Zhong JH. Updates and advancements in the management of hepatocellular carcinoma patients after hepatectomy. Expert Rev Gastroenterol Hepatol 2019; 13:1077-1088. [PMID: 31648568 DOI: 10.1080/17474124.2019.1684898] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 10/21/2019] [Indexed: 02/07/2023]
Abstract
Introduction: The 5-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection or local ablation is up to 70%. Adjuvant therapies to prevent HCC recurrence have been reported but are not currently recommended by EASL or AASLD guidelines. This review examined evidence from randomized controlled trials, meta-analyses and systematic reviews on the safety and efficacy of adjuvant therapies and chemotherapies in HCC patients after resection or local ablation.Areas covered: PubMed was searched through 15 June 2019. Available evidence was assessed based on the GRADE system.Expert commentary: Transarterial chemoembolization is the best adjuvant therapy for HCC patients at high risk of recurrence, antiviral therapy with nucleoside analogs is effective for preventing recurrence of HBV-related HCC, and interferon-α is effective for preventing recurrence of HCV-related HCC. Further studies are needed to clarify the efficacy of adjuvant immune checkpoint inhibitors. Adjuvant sorafenib appears to offer negligible clinical benefit and high risk of adverse effects.
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Affiliation(s)
- Shi-Dong Lu
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Lin Li
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xin-Min Liang
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Wu Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Fu-Li Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Lang-Lin Fan
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Bhavesh K Ahir
- Section of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Wan-Guang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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21
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Akateh C, Black SM, Conteh L, Miller ED, Noonan A, Elliott E, Pawlik TM, Tsung A, Cloyd JM. Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma. World J Gastroenterol 2019; 25:3704-3721. [PMID: 31391767 PMCID: PMC6676544 DOI: 10.3748/wjg.v25.i28.3704] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/13/2019] [Accepted: 06/22/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.
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Affiliation(s)
- Clifford Akateh
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Sylvester M Black
- Division of Transplant Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Lanla Conteh
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric D Miller
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Anne Noonan
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric Elliott
- Division of Diagnostic Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Allan Tsung
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
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22
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Chen ZH, Zhang XP, Zhou TF, Wang K, Wang H, Chai ZT, Shi J, Guo WX, Cheng SQ. Adjuvant transarterial chemoembolization improves survival outcomes in hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis. Eur J Surg Oncol 2019; 45:2188-2196. [PMID: 31256949 DOI: 10.1016/j.ejso.2019.06.031] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 04/28/2019] [Accepted: 06/24/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The benefits of adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remain controversial. We compared the efficacy and safety of adjuvant TACE and hepatic resection (HR) alone for HCC patients with MVI. METHODS The PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare adjuvant TACE and HR alone for the treatment of HCC with MVI from inception to January 1, 2019. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors. RESULTS 12 trials involving 2190 patients were evaluated. A meta-analysis of 11 studies suggested that the 1-, 3-, and 5-year overall survival (OS) rates (OR = 0.33, P < 0.001; OR = 0.49, P < 0.001; and OR = 0.59, P < 0.01; respectively), favored adjuvant TACE over HR alone. 11 studies were included in the meta-analysis of DFS, and adjuvant TACE showed better 1-, 3-, and 5-DFS (OR = 0.45, P < 0.001; OR = 0.50, P < 0.001; and OR = 0.58, P < 0.001; respectively) compared to HR alone. Subgroup analysis demonstrated that adjuvant TACE could benefit HCC patients with MVI with tumor diameter >5 cm or multinodular tumors. CONCLUSION Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI. However, these results need to be validated through further high-quality clinical studies. LAY SUMMARY The benefits of adjuvant TACE in HCC patients with microvascular invasion remain controversial. Twelve studies involving 2190 patients were include in our meta-analysis. Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI.
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Affiliation(s)
- Zhen-Hua Chen
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xiu-Ping Zhang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | | | - Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Hang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Zong-Tao Chai
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
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He S, Fan X, Ma H, Xiaerfuhazi H, Rehato A, Feng J, Shi X, He F. Effect of prophylactic TACE on 5-year survival of patients with hepatocellular carcinoma after hepatectomy. Oncol Lett 2019; 18:1824-1830. [PMID: 31423250 PMCID: PMC6614664 DOI: 10.3892/ol.2019.10517] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 04/15/2019] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to establish a prediction index (PI) model for the 5-year survival rate of patients with hepatitis B-related hepatocellular carcinoma (HCC) after radical resection, and to evaluate the effect of prophylactic transcatheter arterial chemoembolization (TACE). A total of 201 patients with hepatitis B-related HCC who had undergone radical hepatic resection at The First Affiliated Hospital of Xinjiang Medical University (Xinjiang, China) were enrolled, and the clinical, pathological and complete follow-up data were collected. Univariate and multivariate Cox regression analyses were performed to identify which clinicopathological factors were considered significant risk factors and the PI model was established based on these factors. The receiver operating characteristic curve was generated, and the area under the curve (0.841) and the cut-off value for PI were calculated. A Kaplan-Meier plot was used for survival analysis and the log-rank test was used to determine differences in survival. Cox regression analysis demonstrated that there were seven independent factors that may have affected the 5-year survival of HCC patients: Neutrophil-to-lymphocyte ratio (NLR), maximum size of tumor (MTS), tumor histological grade (HG), positive resection margin (PRM), microvascular invasion (MVI), the amount of tumor (AT), and antivirus therapy (AVT). A PI model on 5-year survival was established based on these factors, which was PI=0.32 × NLR + 0.39 × HG (high=1, medium=2, low=3) + 0.92 × PRM (yes=1, no=0) + 0.87 × MVI (yes=1, no=0) + 0.73 × AT (single=0, many=1) + 0.53 × MTS (≥5 cm=1, <5 cm=0)-0.87 × AVT (yes=1, no=0). PI was an independent predictor for survival, with a cut-off value of 2.75. For low-risk patients (PI <2.75), there was no significant difference in cumulative survival between TACE and non-TACE. For high-risk patients (PI >2.75), the cumulative survival rates showed significant differences among patients who had received ≥3 TACE procedues, patients who had received <3 TACE procedures, and patients who had not undergone TACE. The PI model predicts the 5-year survival rate of patients with hepatitis B-related HCC. For high-risk patients with a PI >2.75, if they had received ≥3 prophylactic TACE procedures, they demonstrated a more favorable outcome. For low-risk patients (PI <2.75) with 1 or 2 risk factors, TACE is recommended 1-2 times after surgery. TACE treatment is not required for low-risk patients without any risk fctors. These results may contribute to the decision-making process for whether prophylactic intervention is recommended after radical resection of HCC.
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Affiliation(s)
- Shasha He
- Department of Infectious Diseases, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong 518000, P.R. China
| | - Xiaotang Fan
- Department of Hepatology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Hailin Ma
- Department of Hepatology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Hali Xiaerfuhazi
- Department of Hepatology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Aliya Rehato
- Department of Hepatology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Juan Feng
- Department of Hepatology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Xiujiang Shi
- Department of Hepatology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
| | - Fangping He
- Department of Infectious Diseases, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong 518000, P.R. China
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Moran A, Ramos LF, Picado O, Pendola F, Sleeman D, Dudeja V, Merchant N, Yakoub D. Hepatocellular carcinoma: resection with adjuvant hepatic artery infusion therapy vs resection alone. A systematic review and meta-analysis. J Surg Oncol 2018; 119:455-463. [PMID: 30575028 DOI: 10.1002/jso.25338] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Accepted: 11/25/2018] [Indexed: 12/14/2022]
Abstract
Hepatocellular carcinoma (HCC) has a recurrence rate of up to 70% in 5 years after resection, detrimentally lowering survival. The role of adjuvant therapy remains controversial; therefore, the aim of this study was to evaluate the disease-free and overall survival of patients with HCC, not candidates for transplantation, undergoing resection and adjuvant hepatic artery infusion therapy vs resection alone. Our meta-analysis showed that adjuvant HAIC improves overall and disease-free survival after resection, especially in tumors ≥7 cm.
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Affiliation(s)
- Alexandra Moran
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Lorena Flor Ramos
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Omar Picado
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Fiorella Pendola
- Department of Medicine, Blake Medical Center, Bradenton, Florida
| | - Danny Sleeman
- Division of General Surgery, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.,Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Vikas Dudeja
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.,Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Nipun Merchant
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.,Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Danny Yakoub
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.,Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
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25
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Zhu GQ, Wang K, Wang B, Zhou YJ, Yang Y, Chen EB, Zhou ZJ, Zhou SL, Shi YH, Zhou J, Dai Z. Aspartate aminotransferase-to-platelet ratio index predicts prognosis of hepatocellular carcinoma after postoperative adjuvant transarterial chemoembolization. Cancer Manag Res 2018; 11:63-79. [PMID: 30588111 PMCID: PMC6305141 DOI: 10.2147/cmar.s186150] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIM To investigate the value of the aspartate aminotransferase-to-platelet ratio index (APRI) and build a new nomogram for hepatocellular carcinoma (HCC) patients undergoing postoperative adjuvant transarterial chemoembolization (PATACE). METHODS We retrospectively reviewed 351 patients with HCC undergoing PATACE. We collected baseline HCC patient characteristics to obtain the risk factors for determining poor disease-free survival (DFS) and early time to recurrence (TTR) after PATACE. The multivariate Cox proportional hazards model was used to build new nomogram based on significant prognostic factors of outcomes. RESULTS We generated the cutoff value of the APRI as 0.50 using the X-tile to distinguish patients with different outcomes in the whole cohort. Two hundred seventeen patients with high APRI had poorer survival (P<0.001) than did 134 patients with low APRI. Furthermore, a nomogram, including tumor size, alanine aminotransferase (ALT) level, white blood cell counts, Barcelona Clinic Liver Cancer grade, and APRI was built for DFS, while factors including hepatitis B surface antigen, tumor size, ALT, microvascular invasion, and APRI was built for TTR. Internal validation with 500 bootstrapped sample sets had a good concordance index of 0.729 for DFS and 0.730 for TTR. Additionally, nomogram based on APRI conferred more prognostic value than previous biomarkers. CONCLUSION High APRI was associated with worse survival and shorter TTR for HCC patients undergoing PATACE. This simple nomogram based on APRI conferred personalized survival and recurrence data for HCC patients undergoing PATACE.
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Affiliation(s)
- Gui-Qi Zhu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China,
- State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China,
| | - Kang Wang
- Department of Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, 400016, China
| | - Biao Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China,
- State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China,
| | - Yu-Jie Zhou
- Department of Gastroenterology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Yi Yang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China,
- State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China,
| | - Er-Bao Chen
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zheng-Jun Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China,
- State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China,
| | - Shao-Lai Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China,
- State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China,
| | - Ying-Hong Shi
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China,
- State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China,
| | - Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China,
- State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China,
| | - Zhi Dai
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China,
- State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China,
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26
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Liu S, Guo L, Li H, Zhang B, Sun J, Zhou C, Zhou J, Fan J, Ye Q. Postoperative Adjuvant Trans-Arterial Chemoembolization for Patients with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus. Ann Surg Oncol 2018; 25:2098-2104. [DOI: 10.1245/s10434-018-6438-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Indexed: 12/23/2022]
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27
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Adjuvant I-131 Lipiodol After Resection or Radiofrequency Ablation for Hepatocellular Carcinoma. World J Surg 2017; 40:1941-50. [PMID: 27098539 DOI: 10.1007/s00268-016-3502-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND OBJECTIVES High rates of recurrence have been observed after curative treatment for hepatocellular carcinoma (HCC). The main aim of this study was to establish the influence of adjuvant transarterial radioembolization-based I-131 lipiodol on survival and recurrence. METHODS Between 2004 and 2010, 38 patients were treated with adjuvant I-131 lipiodol therapy, at a dosage of 2220 MBq, within 4 months after surgery. This treated cohort was compared to a control cohort consisting of 42 consecutive patients operated prior to the time the I-131 lipiodol treatment became available. RESULTS Recurrence-free survival in the control and in the I-131 lipiodol cohort was 12.6 and 18.7 months, respectively (HR = 1.871, p = 0.025). At 2 and 5 years, the cumulative incidence of a first recurrence or death was, respectively, 50 % and 61 % in the treated cohort versus 69 % and 74 % in the control cohort. Median overall survival was 55 and 29 months, respectively (p = 0.051). Among patients with a recurrence at 2 years, more patients had already experienced such recurrence at 1 year in the control cohort (70 % vs 33 %, p = 0.014). CONCLUSIONS Adjuvant I-131 lipiodol improves disease-free survival in patients with HCC.
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28
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Jiang J, Hu H, Liu R, Wang JH, Long XR, Fan J, Yan ZP. Nomogram for individualized prediction of recurrence after postoperative adjuvant TACE for hepatitis B virus-related hepatocellular carcinoma. Medicine (Baltimore) 2017; 96:e7390. [PMID: 28796032 PMCID: PMC5556198 DOI: 10.1097/md.0000000000007390] [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: 02/06/2023] Open
Abstract
This study sought to develop an effective and reliable nomogram for predictions of recurrence for postoperative adjuvant transarterial chemoembolization (PA-TACE) in patients with hepatitis B virus-related (HBV) hepatocellular carcinoma (HCC).The nomogram was established based on data obtained from a retrospective study on 235 consecutive patients with HBV HCC who received PA-TACE as an initial therapy from 2006 to 2010 in our center. Eighty-four patients who were collected at another institution between 01/2008 and 12/2010 served as an external validation set. Recurrence-free survival (RFS) was collected. The nomogram for tumor recurrence was developed based on the data obtained before the PA-TACE procedure. Predictive accuracy and discriminative ability of the nomogram were assessed by concordance index (C-index), calibration curves, and validation set.The 1, 2, 3-year RFS rates were 55.5%, 27.0%, and 14.1%, respectively, in the patients from the derivation set and 60.7%, 33.2%, and 23.8% in those from the validation set. Four risk factors (HBV-DNA level, vascular invasion, change of Child-Pugh score, and tumor diameter) in the multivariate analysis were significantly associated with RFS. The statistical nomogram incorporated these 4 factors achieved good calibration and discriminatory abilities with the c-index of 0.74 (95% CI 0.66-0.82). The findings were supported by the independent external validation set (c-index, 0.70; 95% CI 0.58-0.83). The area under the receiver operating characteristic curve in our model was greater than those of conventional staging systems in the validation patients (corresponding c-indices, 0.56-0.64).The novel nomogram may achieve an optimal prediction for recurrence outcome in HBV-related HCC with PA-TACE.
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Affiliation(s)
- Jiang Jiang
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai
| | - Hao Hu
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai
| | - Rong Liu
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai
| | - Jian Hua Wang
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai
| | | | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhi Ping Yan
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai
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Yu WB, Rao A, Vu V, Xu L, Rao JY, Wu JX. Management of centrally located hepatocellular carcinoma: Update 2016. World J Hepatol 2017; 9:627-634. [PMID: 28539990 PMCID: PMC5424292 DOI: 10.4254/wjh.v9.i13.627] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 03/24/2017] [Accepted: 04/10/2017] [Indexed: 02/06/2023] Open
Abstract
Centrally located hepatocellular carcinoma (HCC) is sited in the central part of the liver and adjacent to main hepatic vascular structures. This special location is associated with an increase in the difficulty of surgery, aggregation of the recurrence disease, and greater challenge in disease management. This review summarizes the evolution of our understanding for centrally located HCC and discusses the development of treatment strategies, surgical approaches and recurrence prevention methods. To improve patient survival, a multi-disciplinary modality is greatly needed throughout the whole treatment period.
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30
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Olesinski J, Mithieux F, Guillaud O, Hilleret MN, Lombard-Bohas C, Henry L, Boillot O, Walter T, Partensky C, Paliard P, Valette PJ, Vuillez JP, Borson-Chazot F, Scoazec JY, Dumortier J. Survival and prognostic factors after adjuvant 131iodine-labeled lipiodol for hepatocellular carcinoma: a retrospective analysis of 106 patients over 20 years. Ann Nucl Med 2017; 31:379-389. [PMID: 28342103 DOI: 10.1007/s12149-017-1165-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Accepted: 03/14/2017] [Indexed: 01/27/2023]
Abstract
OBJECTIVE Hepatocellular carcinoma (HCC) has high recurrence rate after curative treatment. The aim of the present study was to report our experience with adjuvant use of 131I-lipiodol after curative treatment of HCC in terms of recurrence and survival in a large cohort of patients with a long follow-up. METHODS All patients treated with 131I-lipiodol after curative treatment of HCC in two French centers from 1991 to 2009 were included in a retrospective cohort study. RESULTS One hundred and six patients were included. The median (range) follow-up was 6 years (0.3-22). Forty-three patients (41%) had cirrhosis. Recurrence-free survival rates at 1, 2, 5, 10, and 20 years were 73, 57, 40, 30, and 14%, respectively. Cirrhosis was an independent predictive factor of recurrence [RR = 1.18, 95% CI (1.11-3.02), p = 0.019]. Overall, survival rates at 1, 2, 5, 10, and 20 years were 90, 83, 59, 37, and 23%, respectively. Prognostic factors were recurrence [RR = 2.73, 95% CI (1.35-5.54); p = 0.005], age over 60 years (RR = 1.91, 95% CI [1.02-3.61]; p = 0.044), and tumor number over 3 [RR = 3.31, 95% CI (1.25-8.77); p = 0.016]. CONCLUSION Our results suggest that the effect of 131I-lipiodol after curative treatment of HCC could be related to a beneficial impact on risk factors of early tumor recurrence. This could be evaluated in further studies using modern radioembolization methods.
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Affiliation(s)
- Jonathan Olesinski
- Hospices civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, pavillon L, 69437, Lyon Cedex 03, France
| | - François Mithieux
- Hospices civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, pavillon L, 69437, Lyon Cedex 03, France
| | - Olivier Guillaud
- Hospices civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, pavillon L, 69437, Lyon Cedex 03, France
| | - Marie-Noëlle Hilleret
- Service d'hépato-gastro-entérologie, CHU de Grenoble, Hôpital A. Michallon, La Tronche, France
| | - Catherine Lombard-Bohas
- Hospices civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, pavillon L, 69437, Lyon Cedex 03, France
| | - Luc Henry
- Hospices civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, pavillon L, 69437, Lyon Cedex 03, France
| | - Olivier Boillot
- Hospices civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, pavillon L, 69437, Lyon Cedex 03, France.,Université Claude Bernard Lyon 1, Lyon, France
| | - Thomas Walter
- Hospices civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, pavillon L, 69437, Lyon Cedex 03, France.,Université Claude Bernard Lyon 1, Lyon, France
| | - Christian Partensky
- Hospices civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, pavillon L, 69437, Lyon Cedex 03, France.,Université Claude Bernard Lyon 1, Lyon, France
| | - Pierre Paliard
- Hospices civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, pavillon L, 69437, Lyon Cedex 03, France.,Université Claude Bernard Lyon 1, Lyon, France
| | - Pierre-Jean Valette
- Hospices civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, pavillon L, 69437, Lyon Cedex 03, France.,Université Claude Bernard Lyon 1, Lyon, France
| | - Jean-Philippe Vuillez
- Service de Médecine nucléaire, CHU de Grenoble, Hôpital A. Michallon, La Tronche, France.,Université Joseph Fourier, Grenoble, France
| | - Françoise Borson-Chazot
- Service de Médecine Nucléaire, Hospices civils de Lyon, Hôpital Cardiologique Louis Pradel, Lyon, France
| | - Jean-Yves Scoazec
- Université Claude Bernard Lyon 1, Lyon, France.,Service Central d'Anatomie et Cytologie Pathologiques, Hospices civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Jérôme Dumortier
- Hospices civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, pavillon L, 69437, Lyon Cedex 03, France. .,Service de Médecine nucléaire, CHU de Grenoble, Hôpital A. Michallon, La Tronche, France.
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Majumdar A, Roccarina D, Thorburn D, Davidson BR, Tsochatzis E, Gurusamy KS. Management of people with early- or very early-stage hepatocellular carcinoma: an attempted network meta-analysis. Cochrane Database Syst Rev 2017; 3:CD011650. [PMID: 28351116 PMCID: PMC6464490 DOI: 10.1002/14651858.cd011650.pub2] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (primary liver cancer) is classified in many ways. The Barcelona Clinic Liver Cancer (BCLC) group staging classifies the cancer based on patient's life expectancy. People with very early- or early-stage hepatocellular carcinoma have single tumour or three tumours of maximum diameter of 3 cm or less, Child-Pugh status A to B, and performance status 0 (fully functional). Management of hepatocellular carcinoma is uncertain. OBJECTIVES To assess the comparative benefits and harms of different interventions used in the treatment of early or very early hepatocellular carcinoma through a network meta-analysis and to generate rankings of the available interventions according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis and instead assessed the benefits and harms of different interventions versus each other or versus sham or no intervention using standard Cochrane methodology. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and trials registers to September 2016 to identify randomised clinical trials (RCTs) on hepatocellular carcinoma. SELECTION CRITERIA We included only RCTs, irrespective of language, blinding, or publication status, in participants with very early- or early-stage hepatocellular carcinoma, irrespective of the presence of cirrhosis, portal hypertension, aetiology of hepatocellular carcinoma, size and number of the tumours, and future remnant liver volume. We excluded trials including participants who were previously liver transplanted. We considered interventions compared with each other, sham, or no intervention. DATA COLLECTION AND ANALYSIS We calculated the odds ratio, mean difference, rate ratio, or hazard ratio with 95% confidence intervals using both fixed-effect and random-effects models based on available-participant analysis with Review Manager 5. We assessed the risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis using Stata, and the quality of the evidence using GRADE. MAIN RESULTS Eighteen trials met the inclusion criteria for this review. Four trials (593 participants; 574 participants included for one or more analyses) compared surgery versus radiofrequency ablation in people with early hepatocellular carcinoma, eligible to undergo surgery. Fourteen trials (2533 participants; 2494 participants included for various analyses) compared different non-surgical interventions in people with early hepatocellular carcinoma, not eligible to undergo surgery. Overall, the quality of evidence was low or very low for all outcomes for both comparisons. Surgery versus radiofrequency ablationThe majority of participants had cirrhotic livers, and the hepatocellular carcinoma was of viral aetiology. The trials did not report the participants' portal hypertension status or whether they received adjuvant antiviral treatment or adjuvant immunotherapy. The average follow-up ranged from 29 months to 42 months (3 trials).There was no evidence of a difference in all-cause mortality at maximal follow-up for surgery versus radiofrequency ablation (hazard ratio 0.80, 95% confidence interval (CI) 0.60 to 1.08; 574 participants; 4 trials; I2 = 68). Cancer-related mortality was lower in the surgery group (20/115 (17.4%)) than in the radiofrequency ablation group (43/115 (37.4%)) (odds ratio 0.35, 95% CI 0.19 to 0.65; 230 participants; 1 trial). Serious adverse events (number of participants) was higher in the surgery group (14/60 (23.3%)) than in the radiofrequency ablation group (1/60 (1.7%)) (odds ratio 17.96, 95% CI 2.28 to 141.60; 120 participants; 1 trial). The number of serious adverse events was higher in the surgery group (adjusted rate 11.3 events per 100 participants) than in the radiofrequency ablation group (3/186 (1.6 events per 100 participants)) (rate ratio 7.02, 95% CI 2.29 to 21.46; 391 participants; 2 trials; I2 = 0%). None of the trials reported health-related quality of life. One trial was funded by a party with vested interests; three trials were funded by parties without any vested. Non-surgical interventionsThe majority of participants had cirrhotic livers, and the hepatocellular carcinoma was of viral aetiology. Most trials did not report the portal hypertension status of the participants, and none of the trials reported whether the participants received adjuvant antiviral treatment or adjuvant immunotherapy. The average follow-up ranged from 6 months to 37 months (11 trials). Trial participants, who were not eligible for surgery, were treated with radiofrequency ablation, laser ablation, microwave ablation, percutaneous acetic acid injection, percutaneous alcohol injection, a combination of radiofrequency ablation with systemic chemotherapy, a combination of radiofrequency ablation with percutaneous alcohol injection, a combination of transarterial chemoembolisation with percutaneous alcohol injection, or a combination of transarterial chemoembolisation with radiofrequency ablation.The mortality at maximal follow-up was higher in the percutaneous acetic acid injection (hazard ratio 1.77, 95% CI 1.12 to 2.79; 125 participants; 1 trial) and percutaneous alcohol injection (hazard ratio 1.49, 95% CI 1.18 to 1.88; 882 participants; 5 trials; I2 = 57%) groups compared with the radiofrequency ablation group. There was no evidence of a difference in all-cause mortality at maximal follow-up for any of the other comparisons. The proportion of people with cancer-related mortality at maximal follow-up was higher in the percutaneous alcohol injection group (adjusted proportion 16.8%) compared with the radiofrequency ablation group (20/232 (8.6%)) (odds ratio 2.18, 95% CI 1.22 to 3.89; 458 participants; 3 trials; I2 = 0%). There was no evidence of a difference in any of the comparisons that reported serious adverse events (number of participants or number of events). None of the trials reported health-related quality of life. Five trials were funded by parties without any vested interest; the source of funding was not available in the remaining trials. AUTHORS' CONCLUSIONS The evidence was of low or very low quality. There was no evidence of a difference in all-cause mortality at maximal follow-up between surgery and radiofrequency ablation in people eligible for surgery. All-cause mortality at maximal follow-up was higher with percutaneous acetic acid injection and percutaneous alcohol injection than with radiofrequency ablation in people not eligible for surgery. There was no evidence of a difference in all-cause mortality at maximal follow-up for the other comparisons. High-quality RCTs designed to assess clinically important differences in all-cause mortality and health-related quality of life, and having an adequate follow-up period (approximately five years) are needed.
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Affiliation(s)
- Avik Majumdar
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, Pond Street, London, UK, NW3 2QG
| | - Davide Roccarina
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, Pond Street, London, UK, NW3 2QG
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, Pond Street, London, UK, NW3 2QG
| | - Brian R Davidson
- Department of Surgery, Royal Free Campus, UCL Medical School, Pond Street, London, UK, NW3 2QG
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, Pond Street, London, UK, NW3 2QG
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Gavriilidis P, Askari A, Azoulay D. Survival following redo hepatectomy vs radiofrequency ablation for recurrent hepatocellular carcinoma: a systematic review and meta-analysis. HPB (Oxford) 2017; 19:3-9. [PMID: 28341429 DOI: 10.1016/j.hpb.2016.10.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2016] [Revised: 09/24/2016] [Accepted: 10/02/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Redo hepatic resection (RHR) and radiofrequency ablation (RFA) are salvage treatment choices for recurrent hepatocellular carcinoma (RHCC). As yet, it is unclear as to which treatment modality is superior in terms of long term survival. The aim of this study was to compare the survival benefits and treatment efficacy of RHR and RFA for recurrent HCC. METHODS A literature review using the EMBASE, Medline, Google scholar, and Cochrane databases was performed. Meta-analyses were performed using an inference of variance, random effects model for 1, 3 and 5-year Disease Free Survival (DFS) and Overall Survival (OS). Secondary outcomes were major morbidity and mortality. RESULTS Five retrospective studies including 639 patients were eligible. Overall, there were no differences in 1, 3 and 5-year DFS or OS for patients undergoing RHR or RFA for recurrent HCC. Comparison between the two groups demonstrated similar 5-year DFS (HR 0.86, 95% CI 0.67-1.11, p = 0.250) and 5-year OS (HR 1.03, 95% CI 0.83-1.27, p = 0.082). However, RFA had a lower morbidity rate (2%) compared with RHR (17%, p < 0.001). CONCLUSION This study demonstrates, neither RHR nor RFA appeared to be superior in terms of DFS and OS. Well-constructed, randomised, multicenter trials will be required to determine if a true difference exists.
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Affiliation(s)
- Paschalis Gavriilidis
- Department of HPB Surgery and Liver Transplantation, Henri Mondor University Hospital, Créteil, France; Department of HPB and Transplant Surgery, St James's University Hospital, Beckett Str, Leeds LS9 7TF, UK
| | | | - Daniel Azoulay
- Department of HPB Surgery and Liver Transplantation, Henri Mondor University Hospital, Créteil, France; INSERM U 955, Créteil, France.
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Ma J, Wang JH. 131I-Labeled-Metuximab Plus Transarterial Chemoembolization in Combination Therapy for Unresectable Hepatocellular Carcinoma: Results from a Multicenter Phase IV Clinical Study. Asian Pac J Cancer Prev 2016; 16:7441-7. [PMID: 26625741 DOI: 10.7314/apjcp.2015.16.17.7441] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE This study evaluated the safety and objective response of combining 131I-labeled-metuximab (Licartin) with transarterial chemoembolization (TACE) in the treatment of unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS In a multicenter open-label clinical trial, 341 enrolled patients with stage III/IV HCC according to TNM criteria were nonrandomly assigned to a trial group (n=167) and a control group (n=174), undergoing TACE following hepatic intra-arterial injection of licartin or TACE alone from July 2007 to July 2009. Radiopharmaceutical distribution was evaluated. The primary endpoint was overall survival; secondary endpoints included time-to-progression (TTP), toxicity and adverse events (AEs). RESULTS The radiobiological distribution demonstrated better localization of licartin in liver tumors than other tissues (P<0.01). The organ absorbed doses to liver and red marrow were 3.19 ± 1.01 Gy and 0.55 ± 0.22 Gy, respectively. The 1-year survival rate was significantly higher [79.47% vs. 65.59%, hazard ratio (HR), 0.598, P=0.041] and TTP significantly improved (6.82 ± 1.28 vs. 4.7 ± 1.14 months, P=0.037) compared with the control group. Patients at stage III achieved more benefit of one year survival than stage IV in the trial group (86.9% vs. 53.8%, P<0.001). There were significant different toxicities in leukocytopenia, thrombocytopenia and increased total bilirubin level [P<0.001, P=0.013, P<0.01, relative risk (RR) 1.63, 1.33, 1.43], but no differences in severe AEs of upper GI hemorrhage and severe liver dysfunction between the groups (5.39% vs. 2.3%, P=0.136). CONCLUSIONS Owing to excellent tumor-targeting, promised efficacy and favourable toxicity profile, the novel combination therapy of licartin and TACE could be applied in patients with unresectable HCC.
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Affiliation(s)
- Jun Ma
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China E-mail :
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Yegin EG, Oymaci E, Karatay E, Coker A. Progress in surgical and nonsurgical approaches for hepatocellular carcinoma treatment. Hepatobiliary Pancreat Dis Int 2016; 15:234-56. [PMID: 27298100 DOI: 10.1016/s1499-3872(16)60097-8] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a complex and heterogeneous malignancy, frequently occurs in the setting of a chronically diseased organ, with multiple confounding factors making its management challenging. HCC represents one of the leading causes of cancer-related mortality globally with a rising trend of incidence in some of the developed countries, which indicates the need for better surgical and nonsurgical management strategies. DATA SOURCES PubMed database was searched for relevant articles in English on the issue of HCC management. RESULTS Surgical resection represents a potentially curative option for appropriate candidates with tumors detected at earlier stages and with well-preserved liver function. The long-term outcome of surgery is impaired by a high rate of recurrence. Surgical approaches are being challenged by local ablative therapies such as radiofrequency ablation and microwave ablation in selected patients. Liver transplantation offers potential cure for HCC and also correction of underlying liver disease, and minimizes the risk of recurrence, but is reserved for patients within a set of criteria proposed for a prudent allocation in the shortage of donor organs. Transcatheter locoregional therapies have become the palliative standard allowing local control for intermediate stage patients with noninvasive multinodular or large HCC who are beyond the potentially curative options. The significant survival benefit with the multikinase inhibitor sorafenib for advanced HCC has shifted the direction of research regarding systemic treatment toward molecular therapies targeting the disregulated pathways of hepatocarcinogenesis. Potential benefit is suggested from simultaneous or sequential multimodal therapies, and optimal combinations are being investigated. Despite the striking progress in preclinical studies of HCC immunotherapy and gene therapy, extensive clinical trials are required to achieve successful clinical applications of these innovative approaches. CONCLUSION Treatment decisions have become increasingly complex for HCC with the availability of multiple surgical and nonsurgical therapeutic options and require a comprehensive, multidisciplinary approach.
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Affiliation(s)
- Ender Gunes Yegin
- Department of Gastroenterology, Bozyaka Training and Research Hospital, Izmir 35170, Turkey.
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Kakuta A, Shibutani K, Ono S, Miura H, Tsushima F, Kakehata S, Basaki K, Fujita H, Seino H, Fujita T, Takai Y. Temporal variations in stump pressure and assessment of images obtained from cone-beam computed tomography during balloon-occluded transarterial chemoembolization. Hepatol Res 2016; 46:468-76. [PMID: 26333025 DOI: 10.1111/hepr.12579] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Revised: 07/29/2015] [Accepted: 08/20/2015] [Indexed: 12/20/2022]
Abstract
AIM Balloon-occluded transcatheter arterial chemoembolization (B-TACE) was used to show the optimized duration of balloon occlusion to start injection of lipiodol in order to maximize lipiodol deposition in the nodule, and to reveal the endpoint of lipiodol injection. METHODS Of 29 consecutive patients who underwent balloon-occluded TACE between November 2013 and February 2014, we were able to measure stump pressure for 219 nodules in 27 patients. Tumors were counted, measured and could be visually assessed in 20 of these patients at 26 sites. Tumors with multiple feeders were found in eight patients. Arterial blood pressure was measured before, immediately after and 5 min after balloon occlusion prior to intra-arterial injection, as well as before and after balloon deflation after intra-arterial injection. Images were assessed qualitatively by two radiologists as well as quantitatively by calculating the contrast-to-noise ratio. RESULTS We found no significant difference in pressure between immediately after and 5 min after balloon occlusion. Mean stump pressure before balloon deflation after intra-arterial injection was 70.4 mmHg. We observed a significant increase in qualitative scores after balloon occlusion (P < 0.001), and the mean score in the third-order branch was significantly higher than that in the first-order branch (P = 0.048). CONCLUSION Our results indicate that intra-arterial injection can be started at any time after balloon occlusion and that 70 mmHg may be considered as a possible indicator of the end-point for arterial injection.
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Affiliation(s)
- Akihisa Kakuta
- Department of Radiology and Radiation Oncology, Hirosaki University School of Medicine
| | - Koichi Shibutani
- Department of Radiology and Radiation Oncology, Hirosaki University School of Medicine
| | - Shuichi Ono
- Department of Radiology and Radiation Oncology, Hirosaki University School of Medicine
| | - Hiroyuki Miura
- Department of Radiology and Radiation Oncology, Hirosaki University School of Medicine
| | - Fumiyasu Tsushima
- Department of Radiology and Radiation Oncology, Hirosaki University School of Medicine
| | - Shinya Kakehata
- Department of Radiology, Aomori Prefectural Central Hospital, Hirosaki, Japan
| | - Kiyoshi Basaki
- Department of Radiology, Aomori Prefectural Central Hospital, Hirosaki, Japan
| | - Hiromasa Fujita
- Department of Radiology and Radiation Oncology, Hirosaki University School of Medicine
| | - Hiroko Seino
- Department of Radiology and Radiation Oncology, Hirosaki University School of Medicine
| | - Tamaki Fujita
- Department of Radiology and Radiation Oncology, Hirosaki University School of Medicine
| | - Yoshihiro Takai
- Department of Radiology and Radiation Oncology, Hirosaki University School of Medicine
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Qiao W, Yu F, Wu L, Li B, Zhou Y. Surgical outcomes of hepatocellular carcinoma with biliary tumor thrombus: a systematic review. BMC Gastroenterol 2016; 16:11. [PMID: 26822229 PMCID: PMC4730620 DOI: 10.1186/s12876-016-0427-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2015] [Accepted: 01/25/2016] [Indexed: 02/08/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) with biliary tumor thrombus (BTT) is rare and its impact on postoperative prognosis remains controversial. The aim of this study was to evaluate the published evidence concerning the outcome of surgical resection of HCC with BTT. Methods Eligible studies were identified by searching PubMed and reviewed systematically. Comparisons of the clinicopathologic features and surgical outcomes for HCC patients with or without BTT were analyzed using meta-analytical techniques. Results Twenty retrospective studies containing 598 patients that met the selection criteria were included for review. The perioperative mortality was 2.1 % (range, 0–10 %), and the median 5-year overall survival (OS) was 24 % (range, 0–48 %) with a recurrence rate of 63.9 % (range, 42–91 %). Pooled analysis of 13 comparative studies showed that HCC patients with BTT had a higher incidence of vascular invasion (odds ratio [OR]: 4.70, 95 % CI: 2.90–7.60; P <0.001), a higher frequency of poor differentiation (OR: 2.07, 95 % CI: 1.23–3.49; P = 0.006), and a shorter 5-year OS rate (OR: 0.31, 95 % CI: 0.21–0.64; P <0.001) than those without BTT. Conclusions Although HCC with BTT has more aggressive biological characteristics and is an indicator of poor prognosis, surgical resection can still provide long-term survival for some patients.
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Affiliation(s)
- Wenhui Qiao
- Department of General Surgery, First Hospital of Lanzhou University, Lanzhou, China.
| | - Feng Yu
- Department of Hepatobiliary Surgery, No.101 Hospital of CPLA, Wuxi, China.
| | - Lupeng Wu
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, First affiliated Hospital of Xiamen University, Xiamen, China.
| | - Bin Li
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, First affiliated Hospital of Xiamen University, Xiamen, China.
| | - Yanming Zhou
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, First affiliated Hospital of Xiamen University, Xiamen, China.
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Sun JJ, Wang K, Zhang CZ, Guo WX, Shi J, Cong WM, Wu MC, Lau WY, Cheng SQ. Postoperative Adjuvant Transcatheter Arterial Chemoembolization After R0 Hepatectomy Improves Outcomes of Patients Who have Hepatocellular Carcinoma with Microvascular Invasion. Ann Surg Oncol 2015; 23:1344-51. [PMID: 26714945 DOI: 10.1245/s10434-015-5008-z] [Citation(s) in RCA: 127] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Microvascular invasion (MiVI) is a major risk factor of survival outcomes after curative resection for patients with hepatocellular carcinoma (HCC). This study aimed to investigate the impact of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) on HCC patients with MiVI. METHODS From January 2004 to June 2013, HCC patients with histologically confirmed MiVI and well-tolerated liver function who underwent PA-TACE after R0 hepatectomy (RH) or RH alone were studied retrospectively. In the PA-TACE group, PA-TACE was given 4 weeks after RH. Uni- and multivariate analyses were used to identify the prognostic significance of PA-TACE. RESULTS Of the 322 HCC patients with MiVI included in the analysis, 185 entered into the RH group and 137 entered into the PA-TACE group. The baseline characteristics of the two groups were similar except for alanine aminotransferase (ALT) level (p = 0.037). The 1-, 2-, 3-, and 5-year recurrence-free survival (RFS) rates were respectively 69.3, 55.5, 46.7, and 35.0 % for the PA-TACE group and 47.0, 36.2, 34.1, and 30.3 % for the RH group (log-rank, χ(2) = 6.309; p = 0.012). The 1-, 2-, 3-, and 5-year overall survival (OS) rates were respectively 94.2, 78.8, 71.5, and 54.0 % for the PA-TACE group and 78.9, 62.2, 54.1, and 43.2 % for the RH group (log-rank, χ(2) = 7.537; p = 0.006). Multivariate Cox proportional hazards regression analysis showed PA-TACE to be an independent risk factor of postoperative RFS and OS. CONCLUSIONS This study showed that PA-TACE may be beneficial for HCC patients with MiVI.
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Affiliation(s)
- Jing Jian Sun
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Kang Wang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Cun Zhen Zhang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Wei Xing Guo
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Jie Shi
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Wen Ming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Meng Chao Wu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Wan Yee Lau
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China.,Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Shu Qun Cheng
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China.
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Adjuvant Iodine (131) Lipiodol after Resection of Hepatocellular Carcinoma. JOURNAL OF ONCOLOGY 2015; 2015:746917. [PMID: 26713092 PMCID: PMC4680111 DOI: 10.1155/2015/746917] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2015] [Revised: 10/29/2015] [Accepted: 11/01/2015] [Indexed: 12/15/2022]
Abstract
Background. Survival after liver resection for HCC is compromised by a high rate of intrahepatic recurrence. Adjuvant treatment with a single, postoperative dose of intra-arterial I(131) lipiodol has shown promise, as a means of prolonging disease-free survival (DFS). Methodology. DFS and overall survival (OS) after a single dose of postoperative I(131) lipiodol were compared to liver resection alone, for treatment of hepatocellular carcinoma (HCC). Data were collected retrospectively for patients who had a curative resection for HCC between December 1993 and September 2011. Seventy-two patients were given I(131) lipiodol after surgery and 70 patients had surgery alone. Results. The DFS at 1, 3, and 5 years was 72%, 43%, and 26% in the surgery group and 70%, 39%, and 29% in the adjuvant I(131) lipiodol group (p = 0.75). The 1-, 3-, and 5-year OS was 83%, 64%, and 52% in the surgery group and 96%, 72%, and 61% in the adjuvant I(131) lipiodol group (p = 0.16). Conclusion. This retrospective study has found no significant benefit to survival, after adjuvant treatment with I(131) lipiodol.
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Faltermeier C, Busuttil RW, Zarrinpar A. A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma. Diseases 2015; 3:221-252. [PMID: 28943622 PMCID: PMC5548262 DOI: 10.3390/diseases3040221] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Revised: 09/15/2015] [Accepted: 09/21/2015] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%-30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC.
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Affiliation(s)
- Claire Faltermeier
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
| | - Ronald W Busuttil
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
| | - Ali Zarrinpar
- Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
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Xiao L, Wang M. Batimastat nanoparticles associated with transcatheter arterial chemoembolization decrease hepatocellular carcinoma recurrence. Cell Biochem Biophys 2015; 70:269-72. [PMID: 24639109 DOI: 10.1007/s12013-014-9893-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor characterized by easy metastasis and frequent recurrence. Transarterial chemoembolization (TACE) remains the routine treatment for patients with HCC who are not eligible for surgical resection or percutaneous tumor ablation; however, 5-year survival rates following interventional therapy are only 17-38.8 %, with liver recurrence due to incomplete embolization and tumor angiogenesis being a significant reason for treatment failure. Ischemia and hypoxia induced by TACE is correlated with an increased expression of angiogenic factor and stimulates an increase in angiogenesis, including endothelial cells (ECs) proliferation. Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic endopeptidases involved in tumor angiogenesis. In addition, MMPs stimulate tumor cell growth, migration and invasion, and metastasis. Hypoxia enhanced EC migration in a MMP-2-dependent manner while MMP inhibitors (MMPIs) significantly decreased the number of migrating cells in hypoxic cultures. We hypothesize batimastat (synthetic MMPI) nanoparticles associated with TACE could decrease HCC recurrence and metastasis. At first, batimastat nanoparticles were made from batimastat and poly(lactic-co-glycolic acid). Then, nanoparticles were mixed with lipiodol and chemotherapeutic drugs solution. The mixture was infused super-selectively into supplied artery of HCC through catheter. The disseminated area of batimastat might be same with TACE-induced hypoxia area. In the hypoxia area, batimastat inhibited the activity of MMPs, weakened the angiogenesis of tumor vascular system and migration of HCC cells. HCC cells could not escape from hypoxia area and tumor angiogenesis inhibited could not supply sufficient nutrients and O2 to residual HCC cells. With the help of batimastat, the killing effect of chemotherapeutic drugs might be enhanced. The rate of complete necrosis of HCC lesion might be increased and local recurrence and metastasis of HCC might be reduced. The hypothesis might increase the clinical efficacy of TACE and improve the prognosis of HCC patients.
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Affiliation(s)
- Liang Xiao
- The First Hospital of China Medical University, No. 155, St Nanjingbei, Dist Heping, Shenyang, 110001, Liaoning, People's Republic of China,
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On developing a pragmatic strategy for clinical trials: A case study of hepatocellular carcinoma. Contemp Clin Trials 2015; 43:252-9. [PMID: 26111924 DOI: 10.1016/j.cct.2015.06.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2015] [Revised: 06/19/2015] [Accepted: 06/20/2015] [Indexed: 12/18/2022]
Abstract
Randomised controlled trials (RCTs) with sufficiently high statistical power are not always feasible for patients when the administration of the treatment is burdensome. Nevertheless, useful information concerning the relative effectiveness of the Test and Standard therapies, may be gleaned from under powered trials, non-randomised comparative studies and/or clinician's beliefs: the latter possibly additionally providing some suggestion of the strength of evidence required in order to adopt the Test therapy into clinical practice. In such circumstances, a Bayesian synthesis may be useful in quantifying the evidence of treatment effectiveness. In this article, we aim to present a Bayesian approach for synthesizing the cumulative evidence of the use of adjuvant hepatic intra-arterial iodine-131-lipiodol (I131L) following curative resection in hepatocellular carcinoma (HCC) patients. We constructed a posterior distribution using the information from two small RCTs, three non-randomised comparative studies, three single arm studies and the views of investigators on the use of I131L. This distribution enables calculation of the probability that the Test therapy is more effective than the Standard by a pre-stipulated amount. If this is very high, then for example, one may conclude the Test may replace the Standard therapy. If it is not, then the Standard would be retained for clinical use. Despite a strong early indication of the effectiveness of I131L, the evolving evidence over a 10-year period became more sceptical of its value. Although highly recommended, difficulties of implementing a Bayesian approach in this context are highlighted.
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Hong Y, Wu LP, Ye F, Zhou YM. Adjuvant Intrahepatic Injection Iodine-131-Lipiodol Improves Prognosis of Patients with Hepatocellular Carcinoma After Resection: a Meta-Analysis. Indian J Surg 2015; 77:1227-32. [PMID: 27011542 DOI: 10.1007/s12262-015-1261-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Accepted: 03/09/2015] [Indexed: 02/07/2023] Open
Abstract
High incidence of intrahepatic recurrence is a major surgical limitation following hepatectomy of hepatocellular carcinoma (HCC). This study was intended to investigate the effects of adjuvant intrahepatic injection of iodine-131-lipiodol on disease recurrence and survival in patients with HCC who underwent resection. A computerized literature search was performed to identify relevant articles. Data synthesis was performed using Review Manager 5.0 software, and results are presented as odds ratio (OR) with 95 % confidence intervals. Two randomized controlled trials and three case-control studies with a total of 334 participants were analyzed. Iodine-131-lipiodol treatment achieved significantly lower rates of intrahepatic recurrence (OR = 0.48, 95 % confidence interval (95 % CI) = 0.30-0.74; P = 0.001) and early recurrence (<2 year) (OR = 0.45, 95 % CI = 0.23-0.89; P = 0.02). Likewise, iodine-131-lipiodol treatment improved both the 5-year disease-free survival and overall survival significantly (OR = 1.85, 95 % CI = 1.13-3.03; P = 0.01; OR = 2.00, 95 % CI = 0.99-4.04; P = 0.05, respectively). Adjuvant intrahepatic injection of iodine-131-lipiodol resulted in a preventive effect on recurrence and improved survival after resection of HCC. Further larger, multi-centred, randomized prospective trial is warranted.
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Affiliation(s)
- Ye Hong
- Department of Hepatobiliary & Pancreatovascular Surgery, First affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, 361003 China
| | - Lu-Peng Wu
- Department of Hepatobiliary & Pancreatovascular Surgery, First affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, 361003 China
| | - Feng Ye
- Department of Hepatobiliary & Pancreatovascular Surgery, First affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, 361003 China
| | - Yan-Ming Zhou
- Department of Hepatobiliary & Pancreatovascular Surgery, First affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, 361003 China
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Edeline J, Gilabert M, Garin E, Boucher E, Raoul JL. Yttrium-90 microsphere radioembolization for hepatocellular carcinoma. Liver Cancer 2015; 4:16-25. [PMID: 26020026 PMCID: PMC4439788 DOI: 10.1159/000343878] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Yttrium-90 (Y90) radioembolization is an emerging strategy to treat liver malignancies, and clinical data supporting its use have accumulated in recent years. Y90-radioembolization has shown clinical effectiveness in intermediate and advanced hepatocellular carcinoma, with a favorable safety profile. Retrospective data show similar levels of effectiveness to transarterial chemoembolization in intermediate hepatocellular carcinoma, with some evidence of better tolerance. While phase 3 studies comparing Y90-radioembolization to chemoembolization in intermediate hepatocellular carcinoma would be difficult to conduct, studies comparing or combining Y90-radioembolization with sorafenib are under way. Questions also remain about the most suitable modalities for defining the dose to administer. Phase 3 studies are under way to clarify the place of Y90-radioembolization in the algorithm of HCC treatment.
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Affiliation(s)
- Julien Edeline
- Medical Oncology, Eugene Marquis Comprehensive Cancer Center, Rennes, France
| | - Marine Gilabert
- Medical Oncology, Paoli Calmette Institute, Marseille, France
| | - Etienne Garin
- Nuclear Medicine, Eugene Marquis Comprehensive Cancer Center, Rennes, France
| | - Eveline Boucher
- Medical Oncology, Eugene Marquis Comprehensive Cancer Center, Rennes, France
| | - Jean-Luc Raoul
- Medical Oncology, Paoli Calmette Institute, Marseille, France,*Jean-Luc Raoul, MD, PhD, Institut Paoli Calmette, 232, boulevard Sainte Marguerite, BP 156, 13273 Marseille cedex9 (France), Tel. +33 4 9122 3679, E-Mail
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Yamamoto Y, Ikoma H, Morimura R, Konishi H, Murayama Y, Komatsu S, Shiozaki A, Kuriu Y, Kubota T, Nakanishi M, Ichikawa D, Fujiwara H, Okamoto K, Sakakura C, Ochiai T, Otsuji E. Optimal duration of the early and late recurrence of hepatocellular carcinoma after hepatectomy. World J Gastroenterol 2015; 21:1207-1215. [PMID: 25632194 PMCID: PMC4306165 DOI: 10.3748/wjg.v21.i4.1207] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2014] [Revised: 05/07/2014] [Accepted: 09/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the best cut-off value between the early and late recurrence periods after the initial recurrence of hepatocellular carcinoma (HCC).
METHODS: The clinical records of 404 patients who underwent macroscopic curative hepatectomy for HCC between 1980 and 2010 were retrospectively examined. We divided the 252 patients experienced a recurrence of HCC into two groups, the early and late recurrence groups using the “minimum P-value” approach. Factors for early recurrence were investigated using all 404 patients, and factors related to late recurrence were investigated in the patients who were confirmed to be recurrence free at the end of the early recurrence period.
RESULTS: For the 252 patients who experienced a recurrence, the optimal cut-off value for differentiating early and late recurrence based on the overall survival after initial recurrence was 17 mo (5-year overall survival after initial recurrence: 15.4% vs 36.3%, P = 0.000018). Cox proportional hazard analysis identified early recurrence (P = 0.003) as one of the independent prognostic factors associated with overall survival after initial recurrence. A logistic regression model showed that an alpha-fetoprotein level > 100 ng/mL (P < 0.001), multiple HCC (P < 0.001), serosal invasion (P = 0.031), and microvascular invasion (P = 0.012) were independent factors associated with early recurrence, whereas the only independent factor related to late recurrence was liver cirrhosis (P = 0.002).
CONCLUSION: Seventeen months after hepatectomy is a useful cut-off value between early and late recurrence of HCC based on the prognosis and different etiologies.
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Yamamoto Y, Ikoma H, Morimura R, Shoda K, Konishi H, Murayama Y, Komatsu S, Shiozaki A, Kuriu Y, Kubota T, Nakanishi M, Ichikawa D, Fujiwara H, Okamoto K, Sakakura C, Ochiai T, Otsuji E. Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein tumor thrombosis. World J Gastroenterol 2015; 21:246-253. [PMID: 25574098 PMCID: PMC4284342 DOI: 10.3748/wjg.v21.i1.246] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2014] [Revised: 06/07/2014] [Accepted: 07/11/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To analyze hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) using the tumor-node-metastasis (TNM) staging system.
METHODS: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009. We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system (7th edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center. Portal vein invasion (vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein, vp2 as an invasion or tumor thrombus in the second branch of the portal vein, vp3 as an invasion or tumor thrombus in the first branch of the portal vein, and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side.
RESULTS: The cumulative 5-year overall survival (5yrOS) and 5-year disease-free survival (5yrDFS) rates of the 372 patients were 58.3% and 31.3%, respectively. The 5yrDFS and 5yrOS of vp3-4 patients (n = 10) were 20.0%, and 30.0%, respectively, which was comparable with the corresponding survival rates of vp1-2 patients (P = 0.466 and 0.586, respectively). In the subgroup analysis of patients with macroscopic PVTT (vp2-4), the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not (P = 0.747). There was a significant difference in the DFS between patients with stage I HCC and those with stage II HCC (5yrDFS 39.2% vs 23.1%, P < 0.001); however, the DFS for stage II was similar to that for stage III (5yrDFS 23.1% vs 13.8%, P = 0.330). In the subgroup analysis of stage II-III HCC (n = 148), only alpha-fetoprotein (AFP) > 100 mg/dL was independently associated with DFS.
CONCLUSION: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2. AFP stratified the stage II-III HCC patients according to prognosis.
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Chen K, Chen G, Wang H, Li H, Xiao J, Duan X, He J, He K, Xiang G. Increased survival in hepatocellular carcinoma with iodine-125 implantation plus radiofrequency ablation: a prospective randomized controlled trial. J Hepatol 2014; 61:1304-11. [PMID: 25064436 DOI: 10.1016/j.jhep.2014.07.026] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2014] [Revised: 07/09/2014] [Accepted: 07/11/2014] [Indexed: 01/08/2023]
Abstract
BACKGROUND & AIMS The purpose of this study was to evaluate whether use of combined radiofrequency ablation (RFA) and percutaneous iodine-125 ((125)I) seed implantation results in better progression-free survival compared with the use of RFA alone in patients with hepatocellular carcinoma. METHODS 136 patients were randomly assigned to undergo HCC treatment with RFA and percutaneous iodine-125 seed implantation (RFA-(125)I, n=68) or RFA-only (n=68). A total of 91 patients had hepatitis B viral infection in both groups. Rates of tumour recurrence and overall survival were evaluated. RESULTS The probabilities of recurrence at 1-, 3-, and 5-years were 4.5%, 22.1%, and 39.8% in the RFA-(125)I group; and 14.8%, 35.3%, and 57.4% in the RFA-only group, respectively. The recurrence rate in the RFA-(125)I group was significantly lower than in the RFA-only group (HR, 0.508; 95% CI, 0.317-0.815; p=0.004 by log-rank test). Local and intrahepatic recurrence was significantly lower in the RFA-(125)I group than in the RFA-only group (7.3% vs. 22.0%, p=0.012 by log-rank test; 17.6% vs. 32.3%, p=0.041 by log-rank test). The probabilities of survival at 1-, 3-, and 5-years were 100%, 86.7%, and 66.1% in the RFA-(125)I group and 95.6%, 75.0%, and 47.0% in the RFA-only group, respectively. The survival rate in the RFA-(125)I group was significantly better than in the RFA-only group (HR, 0.502; 95% CI, 0.313-0.806; p=0.003 by log-rank test). Cox regression model indicated that the treatment group and tumour size were both recurrence-related and overall survival-related prognostic factors. CONCLUSIONS There were significant differences in overall survival and cumulative recurrence between RFA-(125)I and RFA-only for patients with small HCCs (⩽3 cm). Treatment with RFA-(125)I facilitated better local and intrahepatic tumour control and long-term survival compared with treatment of RFA alone. ClinicalTrials.gov Identifier: NCT01717729.
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Affiliation(s)
- Kaiyun Chen
- Department of General Surgery, The Second People's Hospital of Guangdong Province, Guangdong Provincial Emergency Hospital, South Medical University, Guangzhou, People's Republic of China; Department of Hepatology Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
| | - Guihua Chen
- Department of Hepatology Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Hanning Wang
- Department of General Surgery, The Second People's Hospital of Guangdong Province, Guangdong Provincial Emergency Hospital, South Medical University, Guangzhou, People's Republic of China
| | - Hua Li
- Department of Hepatology Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Jinfeng Xiao
- Department of General Surgery, The Second People's Hospital of Guangdong Province, Guangdong Provincial Emergency Hospital, South Medical University, Guangzhou, People's Republic of China
| | - Xiaopeng Duan
- Department of General Surgery, The Second People's Hospital of Guangdong Province, Guangdong Provincial Emergency Hospital, South Medical University, Guangzhou, People's Republic of China
| | - Jiwen He
- Department of General Surgery, The Second People's Hospital of Guangdong Province, Guangdong Provincial Emergency Hospital, South Medical University, Guangzhou, People's Republic of China
| | - Ke He
- Department of General Surgery, The Second People's Hospital of Guangdong Province, Guangdong Provincial Emergency Hospital, South Medical University, Guangzhou, People's Republic of China
| | - Guoan Xiang
- Department of General Surgery, The Second People's Hospital of Guangdong Province, Guangdong Provincial Emergency Hospital, South Medical University, Guangzhou, People's Republic of China.
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Comparative survival analysis of adjuvant therapy with iodine-131-labeled lipiodol to hepatic resection of primary hepatocellular carcinoma: a meta-analysis. Nucl Med Commun 2014; 35:484-92. [PMID: 24492679 DOI: 10.1097/mnm.0000000000000081] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Adjuvant therapies play an important role in delaying the recurrence of hepatocellular carcinoma (HCC) in patients with resectable tumor. Among the available options, use of radionuclides is an effective strategy. This meta-analysis aims to examine the evidence pertaining to the effectiveness of adjuvant therapy with intra-arterial iodine-131-labeled lipiodol ((131)I-lipiodol) to hepatic resection of HCC. METHODS A literature survey was conducted of multiple electronic databases including PubMed/Medline, Embase, CINAHL, Cochrane library, and Google Scholar using various combinations of the most relevant key terms. The odds ratio-based meta-analysis of recurrence and survival rates was performed with RevMan software (version 5.2) using a random-effect model. Heterogeneity was assessed by χ(2) and I(2) statistics. RESULTS When compared with the resection-only group, recurrence rates at 2 and 5 years were significantly lower in patients who received adjuvant therapy with intra-arterial I-lipiodol, with a corresponding odds ratio (95% confidence interval) of 0.45 (0.29-0.70) and 0.52 (0.32-0.85), respectively. The 3- and 5-year overall survival rates were found to be significantly higher in patients who received adjuvant therapy with (131)I-lipiodol than in patients who were not given any adjuvant therapy. Between-study statistical heterogeneity was moderate. CONCLUSION Postoperative adjuvant therapy with intra-arterial (131)I-lipiodol to hepatic resection of HCC significantly improves overall and disease-free survival rates and reduces recurrence rates. However, well-designed randomized trials are needed to arrive at conclusive evidence.
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Cauchy F, Soubrane O, Belghiti J. Liver resection for HCC: patient's selection and controversial scenarios. Best Pract Res Clin Gastroenterol 2014; 28:881-96. [PMID: 25260315 DOI: 10.1016/j.bpg.2014.08.013] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 08/06/2014] [Accepted: 08/19/2014] [Indexed: 02/07/2023]
Abstract
Liver resection is a valuable curative option for patients with hepatocellular carcinoma (HCC). Yet, the balance between the operative risk following hepatectomy for HCC occurring on chronic liver disease and the oncologic prognosis of advanced lesions have led treatment recommendations to limiting the place of liver resection to selected patients with preserved liver function harbouring early-stage tumours. However, better understanding of the natural history of both tumour and underlying liver disease, sophisticated assessment of the liver function, improvements in the preoperative management of the patients with the use of liver volume modulation, refinements in surgical technique including anatomic resection and laparoscopic approach along with tailored management of recurrences have led expert centres to better define and extend the indications for liver resection. In this setting, the reported favourable operative results and long-term outcomes following resection of HCC in a number of controversial scenarios support that current guidelines could be refined.
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Affiliation(s)
- François Cauchy
- Beaujon Hospital, Assistance Publique Hôpitaux de Paris, Clichy, France; University Denis Diderot, Paris 7, France
| | - Olivier Soubrane
- Beaujon Hospital, Assistance Publique Hôpitaux de Paris, Clichy, France; University Denis Diderot, Paris 7, France
| | - Jacques Belghiti
- Beaujon Hospital, Assistance Publique Hôpitaux de Paris, Clichy, France; University Denis Diderot, Paris 7, France.
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Chau GY. Resection of hepatitis B virus-related hepatocellular carcinoma: Evolving strategies and emerging therapies to improve outcome. World J Gastroenterol 2014; 20:12473-12484. [PMID: 25253947 PMCID: PMC4168080 DOI: 10.3748/wjg.v20.i35.12473] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2013] [Revised: 01/28/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing worldwide, largely due to hepatitis B virus (HBV), hepatitis C virus and liver cirrhosis. Chronic HBV infection is estimated to cause 55%-60% of the cases of HCC worldwide and over 70% in Asian countries. Liver resection is currently the mainstay of treatment due to the low surgical mortality, a wider treatment indication, and simplicity of post-treatment follow-up. There is an ever-increasing demand on surgeons to perform curative liver resection in HCC, with the hope of avoiding tumor recurrences. Hepatitis B-related-HCC has distinct clinicopathological features, which should be considered when treating the disease. The author presents a review of the recently evolving strategies and emerging therapies to improve HCC postresectional outcomes and focus on perioperative measures to improve patient outcome, with particular reference to the current status of adjuvant therapies in HCC patients after liver resection.
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MESH Headings
- Antiviral Agents/therapeutic use
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/secondary
- Carcinoma, Hepatocellular/surgery
- Carcinoma, Hepatocellular/virology
- Chemotherapy, Adjuvant
- Hepatectomy/adverse effects
- Hepatectomy/methods
- Hepatectomy/mortality
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Hepatitis B, Chronic/mortality
- Humans
- Liver Neoplasms/mortality
- Liver Neoplasms/pathology
- Liver Neoplasms/surgery
- Liver Neoplasms/virology
- Neoplasm Recurrence, Local
- Neoplasm Staging
- Neoplasm, Residual
- Treatment Outcome
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Tabrizian P, Roayaie S, Schwartz ME. Current management of hepatocellular carcinoma. World J Gastroenterol 2014; 20:10223-10237. [PMID: 25132740 PMCID: PMC4130831 DOI: 10.3748/wjg.v20.i30.10223] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Revised: 05/08/2014] [Accepted: 05/26/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and leading cause of death among patients with cirrhosis. Treatment guidelines are based according to the Barcelona Clinic Liver Cancer staging system. The choice among therapeutic options that include liver resection, liver transplantation, locoregional, and systemic treatments must be individualized for each patient. The aim of this paper is to review the outcomes that can be achieved in the treatment of HCC with the heterogeneous therapeutic options currently available in clinical practice.
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