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Tabrizian P, Pero A, Schwartz M. Hepatic Resection for Hepatocellular Carcinoma. Clin Liver Dis 2025; 29:59-72. [PMID: 39608958 DOI: 10.1016/j.cld.2024.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2024]
Abstract
Hepatic resection has long been considered the preferred treatment for hepatocellular carcinoma (HCC) when feasible, but its role, as well as the outcomes is evolving rapidly. This article explores the impact of the changing demographics of HCC, reviews current criteria for resection, considers the roles of liver transplantation and nonsurgical locoregional therapies vis-a-vis resection, highlights the potential of new systemic therapies (particularly immune checkpoint inhibitors) to improve outcomes, details the common complications associated with resection, and discusses recurrence of HCC after resection and its management.
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Affiliation(s)
- Parissa Tabrizian
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, New York, NY 10029, USA
| | - Adriana Pero
- Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, New York, NY 10029, USA
| | - Myron Schwartz
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, New York, NY 10029, USA.
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Fazlollahi F, Makary MS. Precision oncology: The role of minimally-invasive ablation therapy in the management of solid organ tumors. World J Radiol 2025; 17:98618. [PMID: 39876886 PMCID: PMC11755905 DOI: 10.4329/wjr.v17.i1.98618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 12/16/2024] [Accepted: 01/18/2025] [Indexed: 01/21/2025] Open
Abstract
Solid organ tumors present a significant healthcare challenge, both economically and logistically, due to their high incidence and treatment complexity. In 2023, out of the 1.9 million new cancer cases in the United States, over 73% were solid organ tumors. Ablative therapies offer minimally invasive solutions for malignant tissue destruction in situ, often with reduced cost and morbidity compared to surgical resection. This review examines the current Food and Drug Administration-approved locoregional ablative therapies (radiofrequency, microwave, cryogenic, high-intensity focused ultrasound, histotripsy) and their evolving role in cancer care. Data were collected through a comprehensive survey of the PubMed-indexed literature on tumor ablation techniques, their clinical indications, and outcomes. Over time, emerging clinical data will help establish these therapies as the standard of care in solid organ tumor treatment, supported by improved long-term outcomes and progression-free survival.
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Affiliation(s)
- Farbod Fazlollahi
- College of Medicine, The Ohio State University, Columbus, OH 43210, United States
| | - Mina S Makary
- Department of Radiology, The Ohio State University Medical Center, Columbus, OH 43210, United States
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Li J, Liu Y, Qiu Y, Qu C, Li J. Comparison of adjuvant treatment regimens for high-risk hepatocellular carcinoma: a Bayesian network meta analysis and systematic review. Front Immunol 2024; 15:1487353. [PMID: 39588371 PMCID: PMC11586331 DOI: 10.3389/fimmu.2024.1487353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 10/17/2024] [Indexed: 11/27/2024] Open
Abstract
Background The five-year recurrence rate for patients with hepatocellular carcinoma (HCC) is as high as 70%. Patients with high-risk recurrence factors experience significantly poorer prognosis. Local regional therapies, including transarterial chemoembolisation (TACE), hepatic arterial infusion chemotherapy (HAIC), radiotherapy, and emerging immunotherapy, are commonly used adjuvant treatment options. We conducted an indirect comparison of these adjuvant therapies for such patients. Methods We conducted a systematic search in public databases for relevant studies and assessed the efficacy and safety of the corresponding therapies by consolidating disease-free survival (DFS), overall survival (OS), and adverse events (AEs). Results A total of eight randomised controlled trials were ultimately included. The Gelman-Rubin plot and kernel density estimation indicate that the stability of the combined model is satisfactory. Conclusion immunotherapy is not inferior to local regional therapies in delaying tumour recurrence, however, the higher incidence of AEs remains a significant concern. Adjuvant radiotherapy demonstrated superior efficacy in delaying tumour recurrence compared to adjuvant TACE, although further support from phase III clinical trial evidence is required. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024576316.
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Affiliation(s)
- Jiahao Li
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yingnan Liu
- Department of Radiology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yuqi Qiu
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Chao Qu
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Jiarui Li
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin, China
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Hao K, Paik AJ, Han LH, Makary MS. Yttrium-90 radioembolization treatment strategies for management of hepatocellular carcinoma. World J Radiol 2024; 16:512-527. [PMID: 39494134 PMCID: PMC11525828 DOI: 10.4329/wjr.v16.i10.512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 10/14/2024] [Accepted: 10/21/2024] [Indexed: 10/28/2024] Open
Abstract
As the third leading cause of cancer-related deaths worldwide, hepatocellular carcinoma (HCC) represents a significant global health challenge. This paper provides an introduction and comprehensive review of transarterial radioembolization (TARE) with Yttrium-90 (Y90), a widely performed transcatheter procedure for HCC patients who are not suitable candidates for surgery. TARE involves the targeted delivery of radioactive microspheres to liver tumors, offering a promising treatment option for managing HCC across various stages of the disease. By evaluating Y90 TARE outcomes across early, intermediate, and advanced stages of HCC, the review aims to present a thorough understanding of its efficacy and safety. Additionally, this paper highlights future research directions focusing on the potential of combination therapies with systemic and immunotherapies, as well as personalized treatments. The exploration of these innovative approaches aims to improve treatment outcomes, reduce adverse events, and provide new therapeutic opportunities for HCC patients. The review underscores the importance of ongoing research and clinical trials to optimize TARE further and integrate it into comprehensive HCC treatment paradigms.
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Affiliation(s)
- Kelly Hao
- College of Medicine, The Ohio State University, Columbus, OH 43210, United States
| | - Andrew J Paik
- College of Medicine, The Ohio State University, Columbus, OH 43210, United States
| | - Lauren H Han
- College of Medicine, The Ohio State University, Columbus, OH 43210, United States
| | - Mina S Makary
- Department of Radiology, The Ohio State University Medical Center, Columbus, OH 43210, United States
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Fite EL, Makary MS. Transarterial Chemoembolization Treatment Paradigms for Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:2430. [PMID: 39001491 PMCID: PMC11240648 DOI: 10.3390/cancers16132430] [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: 06/01/2024] [Revised: 06/27/2024] [Accepted: 06/27/2024] [Indexed: 07/16/2024] Open
Abstract
Hepatocellular carcinoma (HCC) accounts for 90% of liver cancer cases worldwide and is currently the most quickly increasing cause of cancer-related deaths in the United States. The 5-year survival rate for primary liver cancer is estimated to be below 20%, and HCC mortality is expected to increase by 41% by 2040. Currently, surgical resection is the first-line approach to definitive treatment of early-stage HCC. However, the majority of patients present with late-stage, unresectable disease due to the asymptomatic nature of early HCC. For patients who present with unresectable HCC, locoregional therapies such as transarterial chemoembolization (TACE) represent an alternative approach to HCC treatment. TACE is a minimally invasive, catheter-based technique that allows for targeted delivery of chemotherapy to tumor sites while occluding tumor-feeding blood vessels. In appropriately selected patients, outcomes for TACE therapy have been shown to be more favorable than supportive care or conservative management. The increasing incidence and mortality of HCC, in addition to the late-stage presentation of most HCC patients, demonstrates the need to expand the role of locoregional therapies in the treatment of HCC. TACE represents an appealing approach to HCC management, including disease control, palliation, and potentially curative-intent strategies. In this review, we will describe the current utility of TACE in the treatment of HCC, characterize the outcomes of patients treated with TACE across different HCC stages, and outline future applications of TACE in the treatment paradigm.
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Affiliation(s)
- Elliott L Fite
- College of Medicine, The Ohio State University, Columbus, OH 43210, USA
| | - Mina S Makary
- Department of Radiology, The Ohio State University Medical Center, Columbus, OH 43210, USA
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Jipa AM, Makary MS. Locoregional Therapies for Hepatobiliary Tumors: Contemporary Strategies and Novel Applications. Cancers (Basel) 2024; 16:1271. [PMID: 38610949 PMCID: PMC11010828 DOI: 10.3390/cancers16071271] [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: 02/18/2024] [Revised: 03/21/2024] [Accepted: 03/21/2024] [Indexed: 04/14/2024] Open
Abstract
A large majority of primary hepatobiliary tumors are hepatocellular carcinomas (HCC), with the remainer being cholangiocarcinoma. While surgical resection remains the gold standard treatment for hepatobiliary tumors, relatively few patients are operative candidates, and systemic treatments have limited effectiveness. Locoregional therapies offer significant promise in the management of HCC. Ablation and radioembolization may offer similar outcomes to surgery for early-stage hepatocellular carcinoma while radioembolization and chemoembolization are valuable in the management of advanced disease. There is significantly less evidence for the role of locoregional therapy in the treatment of cholangiocarcinoma, although it appears to be well tolerated.
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Affiliation(s)
| | - Mina S. Makary
- Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Medical Center, Columbus, OH 43210, USA;
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Zhang YB, Yang G, Bu Y, Lei P, Zhang W, Zhang DY. Development of a machine learning-based model for predicting risk of early postoperative recurrence of hepatocellular carcinoma. World J Gastroenterol 2023; 29:5804-5817. [PMID: 38074914 PMCID: PMC10701309 DOI: 10.3748/wjg.v29.i43.5804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 10/07/2023] [Accepted: 11/03/2023] [Indexed: 11/20/2023] Open
Abstract
BACKGROUND Surgical resection is the primary treatment for hepatocellular carcinoma (HCC). However, studies indicate that nearly 70% of patients experience HCC recurrence within five years following hepatectomy. The earlier the recurrence, the worse the prognosis. Current studies on postoperative recurrence primarily rely on postoperative pathology and patient clinical data, which are lagging. Hence, developing a new pre-operative prediction model for postoperative recurrence is crucial for guiding individualized treatment of HCC patients and enhancing their prognosis. AIM To identify key variables in pre-operative clinical and imaging data using machine learning algorithms to construct multiple risk prediction models for early postoperative recurrence of HCC. METHODS The demographic and clinical data of 371 HCC patients were collected for this retrospective study. These data were randomly divided into training and test sets at a ratio of 8:2. The training set was analyzed, and key feature variables with predictive value for early HCC recurrence were selected to construct six different machine learning prediction models. Each model was evaluated, and the best-performing model was selected for interpreting the importance of each variable. Finally, an online calculator based on the model was generated for daily clinical practice. RESULTS Following machine learning analysis, eight key feature variables (age, intratumoral arteries, alpha-fetoprotein, pre-operative blood glucose, number of tumors, glucose-to-lymphocyte ratio, liver cirrhosis, and pre-operative platelets) were selected to construct six different prediction models. The XGBoost model outperformed other models, with the area under the receiver operating characteristic curve in the training, validation, and test datasets being 0.993 (95% confidence interval: 0.982-1.000), 0.734 (0.601-0.867), and 0.706 (0.585-0.827), respectively. Calibration curve and decision curve analysis indicated that the XGBoost model also had good predictive performance and clinical application value. CONCLUSION The XGBoost model exhibits superior performance and is a reliable tool for predicting early postoperative HCC recurrence. This model may guide surgical strategies and postoperative individualized medicine.
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Affiliation(s)
- Yu-Bo Zhang
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan 750003, Ningxia Hui Autonomous Region, China
| | - Gang Yang
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan 750003, Ningxia Hui Autonomous Region, China
| | - Yang Bu
- Department of Hepatobiliary Surgery, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750003, Ningxia Hui Autonomous Region, China
| | - Peng Lei
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan 750003, Ningxia Hui Autonomous Region, China
| | - Wei Zhang
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan 750003, Ningxia Hui Autonomous Region, China
| | - Dan-Yang Zhang
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan 750003, Ningxia Hui Autonomous Region, China
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Yan J, Wen Y, Deng M, Ye B, Liu X, Zhang L. Transarterial Chemoembolization Plus Sorafenib versus Transarterial Chemoembolization Alone for Advanced Hepatocellular Carcinoma: An Umbrella Review of Meta-Analyses and Systematic Reviews. J Hepatocell Carcinoma 2023; 10:1723-1733. [PMID: 37817915 PMCID: PMC10561755 DOI: 10.2147/jhc.s429352] [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: 07/06/2023] [Accepted: 09/27/2023] [Indexed: 10/12/2023] Open
Abstract
BACKGROUND Sorafenib is the standard treatment for most cases of advanced hepatocellular carcinoma (HCC), based on Western and Eastern clinical guidelines. Thus, an increasing number of transarterial chemoembolization (TACE) plus sorafenib combination therapies have been used in clinical practice. In addition, several systematic reviews and meta-analyses have explored the efficacy and safety of the combination of TACE and sorafenib. Therefore, we performed an umbrella review to summarize and evaluate these evidence-based studies. METHODS PubMed, Embase, Cochrane Library, and Web of Science databases were searched up to June 1, 2023. All meta-analyses that evaluated the effect of TACE plus sorafenib on HCC were considered eligible. The quality of the included meta-analyses was evaluated by AMSTAR2 (A Measurement Tool to Assess Systematic Reviews). The quality of evidence per association provided in the meta-analyses was rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). This study was registered with PROSPERO (Registration ID: CRD42023420417). RESULTS We included 12 meta-analyses, including randomized clinical trials, cohort studies, and observational studies. A total of 44 associations with overall survival, survival rate, time to disease progression, overall response rate, disease control rate, and adverse events were evaluated in this umbrella review. The quality of most associations ranged from low to very low, indicating that flaws were significant in the current meta-analyses. CONCLUSION This umbrella review identified beneficial associations between TACE and sorafenib combination therapy in advanced HCC. However, owing to the low certainty of the evidence, clinicians should interpret our results with caution when applying them in clinical practice, and high-quality studies are required in the future to confirm our results.
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Affiliation(s)
- Jingxin Yan
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, People’s Republic of China
- Qinghai Province Key Laboratory of Hydatid Disease Research, Xining, People’s Republic of China
| | - Yonghao Wen
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, People’s Republic of China
- Department of Postgraduate, Qinghai University, Xining, People’s Republic of China
| | - Manjun Deng
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, People’s Republic of China
- Qinghai Province Key Laboratory of Hydatid Disease Research, Xining, People’s Republic of China
| | - Bin Ye
- Department of General Surgery, Rongxian People’s Hospital, Zigong, People’s Republic of China
| | - Xinlian Liu
- Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, People’s Republic of China
| | - Lushun Zhang
- Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, People’s Republic of China
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Criss CR, Makary MS. Recent Advances in Image-Guided Locoregional Therapies for Primary Liver Tumors. BIOLOGY 2023; 12:999. [PMID: 37508428 PMCID: PMC10376862 DOI: 10.3390/biology12070999] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 07/09/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023]
Abstract
Primary liver cancer is the leading cause of cancer-related deaths worldwide. with incidences predicted to rise over the next several decades. Locoregional therapies, such as radiofrequency or microwave ablation, are described as image-guided percutaneous procedures, which offer either a curative intent for early-stage hepatocellular carcinoma or bridging/downstaging for surgical resection or transplantation. Catheter-driven locoregional therapies, such as transarterial chemoembolization and radioembolization, induce tumor hypoxia, can be palliative, and improve survival for early-to-intermediate hepatocellular carcinoma and unresectable intrahepatic cholangiocarcinoma. Herein, we provide a comprehensive overview of the antineoplastic mechanisms underpinning locoregional therapies, different treatment approaches, and the current state of the literature for the efficacy of locoregional therapies for primary liver cancer. We also discuss emerging advancements, such as the adjuvant use of immunotherapies and molecular targeting agents with locoregional therapy, for the treatment of primary liver cancer.
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Affiliation(s)
- Cody R. Criss
- OhioHealth Riverside Methodist Hospital, Columbus, OH 43214, USA;
| | - Mina S. Makary
- Department of Radiology, The Ohio State University Medical Center, Columbus, OH 43210, USA
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