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Arar A, Heglin A, Veluri S, Alnablsi MW, Benjamin JL, Choudhary M, Pillai A. Radioembolization of HCC and secondary hepatic tumors: a comprehensive review. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2024; 68:270-287. [PMID: 39088238 DOI: 10.23736/s1824-4785.24.03572-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
Transarterial radioembolization (TARE), also called Selective Internal Radiation Therapy (SIRT), has emerged as an effective locoregional therapy for primary and secondary hepatic tumors, utilizing yttrium-90 (Y90) microspheres and other agents such as holmium-166 and rhenium-188. TARE has various applications in the management of HCC across different BCLC stages. Radiation segmentectomy, which involves administering high doses of Y90 (>190 Gy), can be both curative and ablative, achieving complete necrosis of the tumor. In contrast, radiation lobectomy involves administering a lower dose of Y90 (80-120 Gy) as a neoadjuvant treatment modality to improve local control and induce future liver remnant (FLR) hypertrophy in patients who are planned to undergo surgery but have insufficient FLR. Modified radiation lobectomy combines both techniques and offers several advantages over portal vein embolization (PVE). Y90 is also used in downstaging HCC patients outside liver transplantation criteria, as well as bridging those awaiting liver transplantation (LT). Multiple studies and combined analyses were described to highlight the outcomes of TARE and compare it with other treatment modalities, including TACE and sorafenib. Additionally, the review delves into the efficacy and safety of radioembolization in managing metastatic colorectal cancer and other metastatic tumors to the liver. Recent studies have emphasized the role of personalized dosimetry for improved outcomes, and thus we described the different methods used for this purpose. Pretherapy imaging, estimating lung shunt, selection of therapeutic radionuclides, adverse effects, and cost-effectiveness were all discussed as well.
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Affiliation(s)
- Ahmad Arar
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA -
| | - Alex Heglin
- Division of Nuclear Medicine, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Shriya Veluri
- The University of Texas Health Science Center, San Antonio, TX, USA
| | - Mhd Wisam Alnablsi
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jamaal L Benjamin
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Moaz Choudhary
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Anil Pillai
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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2
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Franzè MS, Vigneron P, Sessa A, Saitta C, Chalaye J, Tacher V, Luciani A, Regnault H, Bejan A, Rhaiem R, Sommacale D, Leroy V, Brustia R, Raimondo G, Amaddeo G. Prognostic factors influencing outcomes in hepatocellular carcinoma patients undergoing selective internal radiation therapy. Ann Hepatol 2024; 30:101539. [PMID: 39179159 DOI: 10.1016/j.aohep.2024.101539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 07/06/2024] [Indexed: 08/26/2024]
Abstract
Selective internal radiation therapy (SIRT) has emerged as a viable endovascular treatment strategy for hepatocellular carcinoma (HCC). According to the Barcelona Clinic Liver Cancer (BCLC) classification, SIRT is currently recommended for early- and intermediate-stage HCC that is unsuitable for alternative locoregional therapies. Additionally, SIRT remains a recommended treatment for patients with advanced-stage HCC and portal vein thrombosis (PVT) without extrahepatic metastasis. Several studies have shown that SIRT is a versatile and promising treatment with a wide range of applications. Consequently, given its favourable characteristics in various scenarios, SIRT could be an encouraging treatment option for patients with HCC across different BCLC stages. Over the past decade, an increasing number of studies have focused on better understanding the prognostic factors associated with SIRT to identify patients who derive the most benefit from this treatment or to refine the optimal technical procedures of SIRT. Several variables can influence treatment decisions, with a growing emphasis on a personalised approach. This review, based on the literature, will focus on the prognostic factors associated with the effectiveness of radioembolization and related complications. By comprehensively analysing these factors, we aimed to provide a clearer understanding of how to optimise the use of SIRT in managing HCC patients, thereby enhancing outcomes across various clinical scenarios.
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Affiliation(s)
- Maria Stella Franzè
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Paul Vigneron
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Anna Sessa
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Carlo Saitta
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Julia Chalaye
- Department of Nuclear Medicine, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Vania Tacher
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Medical Imaging, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Alain Luciani
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Medical Imaging, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Hélène Regnault
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Ancuta Bejan
- Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Rami Rhaiem
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatobiliary, Pancreatic and Digestive Surgery, Robert Debré University Hospital, Reims, France; University Reims Champagne-Ardenne, France
| | - Daniele Sommacale
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Digestive and Hepatobiliary Surgery, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Vincent Leroy
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Raffaele Brustia
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Digestive and Hepatobiliary Surgery, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Giuliana Amaddeo
- Université Paris-Est Créteil, UPEC, Créteil, France; INSERM, U955, Team "Virus Hépatologie Cancer", Créteil, France; Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France.
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3
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Thornton LM, Abi-Jaoudeh N, Lim HJ, Malagari K, Spieler BO, Kudo M, Finn RS, Lencioni R, White SB, Kokabi N, Jeyarajah DR, Chaudhury P, Liu D. Combination and Optimal Sequencing of Systemic and Locoregional Therapies in Hepatocellular Carcinoma: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel. J Vasc Interv Radiol 2024; 35:818-824. [PMID: 38789204 DOI: 10.1016/j.jvir.2024.02.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 02/07/2024] [Accepted: 02/19/2024] [Indexed: 05/26/2024] Open
Abstract
Hepatocellular carcinoma, historically, has had a poor prognosis with very few systemic options. Furthermore, most patients at diagnosis are not surgical candidates. Therefore, locoregional therapy (LRT) has been widely used, with strong data supporting its use. Over the last 15 years, there has been progress in the available systemic agents. This has led to the updated Barcelona Clinic Liver Cancer (BCLC) algorithm's inclusion of these new systemic agents, with advocacy of earlier usage in those who progress on LRT or have tumor characteristics that make them less likely to benefit from LRT. However, neither the adjunct of LRT nor the specific sequencing of combination therapies is addressed directly. This Research Consensus Panel sought to highlight research priorities pertaining to the combination and optimal sequencing of LRT and systemic therapy, assessing the greatest needs across BCLC stages.
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Affiliation(s)
- Lindsay M Thornton
- Department of Interventional Radiology, University of Miami, Leonard M. Miller School of Medicine Miami, Florida.
| | - Nadine Abi-Jaoudeh
- Division of Interventional Radiology, University of California Irvine, Irvine, California
| | - Howard J Lim
- Department of Oncology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Katerina Malagari
- Department of Radiology, National and Kapodistrian University of Athens, Athens, Greece
| | - Benjamin Oren Spieler
- Department of Radiation Oncology, University of Miami, Leonard M Miller School of Medicine, Miami, Florida
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
| | - Richard S Finn
- Department of Medicine, Division of Hematology/ Oncology, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California
| | - Riccardo Lencioni
- Department of Radiology, Pisa University Hospital and School of Medicine, Pisa, Italy
| | - Sarah B White
- Department of Radiology and Surgical Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Nima Kokabi
- Division of Interventional Radiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - D Rohan Jeyarajah
- Department of Surgery, Texas Christian University, Burnett School of Medicine, Fort Worth, Texas
| | - Prosanto Chaudhury
- Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - David Liu
- Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; School of Biomedical Engineering, Faculty of Applied Sciences, University of British Columbia, Vancouver, British Columbia, Canada; Department of Interventional Radiology, University of Miami, Leonard M Miller School of Medicine, Miami, Florida
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Bellendorf A, Mader N, Mueller SP, Ezziddin S, Bockisch A, Grafe H, Best J, Goebel J, Pöppel TD, Sabet A. Safety and Efficacy of Selective Internal Radionuclide Therapy with 90Y Glass Microspheres in Patients with Progressive Hepatocellular Carcinoma after the Failure of Repeated Transarterial Chemoembolization. Pharmaceuticals (Basel) 2024; 17:101. [PMID: 38256934 PMCID: PMC10819448 DOI: 10.3390/ph17010101] [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: 10/29/2023] [Revised: 01/04/2024] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
Transarterial chemoembolization (TACE) is currently the standard of care in patients with unresectable hepatocellular carcinoma (HCC), and selective internal radionuclide therapy (SIRT) with 90Y microspheres is mainly used as an alternative modality in patients considered poor candidates for TACE. Treatment with sorafenib is the recommended option for patients with progressive disease after TACE. This study aims to evaluate the safety and efficacy of SIRT with glass microspheres in patients with progressive HCC after repeated TACE who are not eligible for treatment with sorafenib. Forty-seven patients with progressive HCC after a median of three TACE sessions (range 2-14) underwent SIRT (3.5 ± 1.5 GBq; liver target dose 110-120 Gy). Toxicity was recorded 4 and 12 weeks after treatment and reported according to the Common Terminology Criteria for Adverse Events Version 5.0. Treatment response was assessed three months after SIRT using multiphase computed tomography and modified criteria in solid tumors (mRECIST). Survival analyses were performed using Kaplan-Meier curves and a Cox proportional hazards model for uni- and multivariate analyses. Significant but reversible hepatotoxicity (≥grade 3) occurred in five patients (11%). No radioembolization-induced liver disease (REILD) was observed. The number of previous TACE sessions and cumulative administered activity did not predict the incidence of post-SIRT significant hepatotoxicity. Treatment responses consisted of partial responses in 26 (55%), stable disease in 12 (26%), and progressive disease in 9 (19%) patients. The median overall survival (OS) was 11 months (95% confidence interval (CI), 9-13), and objective responses to SIRT were associated with a longer OS (p = 0.008). Significant hepatotoxicity (≥grade 3) after SIRT was a contributor to impaired survival (median OS 6 months (95% CI, 4-8) vs. 12 months (95% CI, 10-14), p < 0.001). SIRT with glass microspheres is a safe and effective salvage treatment for patients with progressive HCC refractory to TACE who are considered poor candidates for sorafenib treatment.
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Affiliation(s)
- Alexander Bellendorf
- Department of Nuclear Medicine, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (A.B.); (S.P.M.); (A.B.); (H.G.)
- MVZ Radiologie, Nuklearmedizin und Strahlentherapie Essen GmbH, Ruüttenscheider Str. 191, 45131 Essen, Germany
| | - Nicolai Mader
- Department of Nuclear Medicine, Clinic for Radiology and Nuclear Medicine, University Hospital, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany;
| | - Stefan P. Mueller
- Department of Nuclear Medicine, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (A.B.); (S.P.M.); (A.B.); (H.G.)
| | - Samer Ezziddin
- Department of Nuclear Medicine, Saarland University Medical Center, Kirrberger Straße, 66421 Homburg, Germany;
| | - Andreas Bockisch
- Department of Nuclear Medicine, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (A.B.); (S.P.M.); (A.B.); (H.G.)
| | - Hong Grafe
- Department of Nuclear Medicine, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (A.B.); (S.P.M.); (A.B.); (H.G.)
| | - Jan Best
- Department of Internal Medicine, University Hospital Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany;
- Department of Internal Medicine, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
| | - Juliane Goebel
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany;
| | - Thorsten D. Pöppel
- Department of Nuclear Medicine, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (A.B.); (S.P.M.); (A.B.); (H.G.)
- MVZ CDT Strahleninstitut GmbH, Turiner Straße 2, 50668 Cologne, Germany
| | - Amir Sabet
- Department of Nuclear Medicine, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (A.B.); (S.P.M.); (A.B.); (H.G.)
- Department of Nuclear Medicine, Clinic for Radiology and Nuclear Medicine, University Hospital, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany;
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Dalzell CG, Taylor AC, White SB. New Insights on Liver-Directed Therapies in Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:5749. [PMID: 38136295 PMCID: PMC10741466 DOI: 10.3390/cancers15245749] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/01/2023] [Accepted: 12/05/2023] [Indexed: 12/24/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) has been increasing over the past decades, but improvements in systemic and locoregional therapies is increasing survival. Current locoregional treatment options include ablation, transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and stereotactic body radiotherapy (SBRT). There is ongoing research regarding the combination of systemic and local therapies to maximize treatment effect as well as in new non-invasive, image-guided techniques such as histotripsy. There is also active research in optimizing the delivery of therapy to tumors via nanostructures and viral-vector-mediated gene therapies. In many cases, patients require a combination of therapies to achieve tumor control and prolong survival. This article provides an overview of the most common liver-directed therapies for HCC as well as insight into more recent advances in personalized medicine and emerging techniques.
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Affiliation(s)
- Christina G. Dalzell
- Department of Radiology and Medical Imaging, Division of Vascular and Interventional Radiology, University of Virginia Health System, Charlottesville, VA 22903, USA
| | - Amy C. Taylor
- Department of Radiology and Medical Imaging, Division of Vascular and Interventional Radiology, University of Virginia Health System, Charlottesville, VA 22903, USA
| | - Sarah B. White
- Department of Radiology, Division of Vascular and Interventional Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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Wu X, Lokken RP, Mehta N. Optimal treatment for small HCC (<3 cm): Resection, liver transplantation, or locoregional therapy? JHEP Rep 2023; 5:100781. [PMID: 37456674 PMCID: PMC10339255 DOI: 10.1016/j.jhepr.2023.100781] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 03/30/2023] [Indexed: 07/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains the most common form of liver cancer, accounting for 90% of all primary liver cancers. Up to 30% of HCC cases could be small (2-3 cm in diameter) at the time of diagnosis with advances in imaging techniques and surveillance programmes. Treating patients with early-stage HCC can be complex and often requires interdisciplinary care, owing to the wide and increasing variety of treatment options, which include liver resection, liver transplantation, and various locoregional therapies offered by interventional radiology and radiation oncology. Decisions regarding the optimal management strategy for a patient involve many considerations, including patient- and tumour-specific characteristics, as well as socioeconomic factors. In this review, we aim to comprehensively summarise the commonly used therapies for single, small HCC (<3 cm), with a focus on the impact of tumour size (<2 cm vs. 2-3 cm), as well as a brief discussion on the cost-effectiveness of the different treatment options.
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Affiliation(s)
- Xiao Wu
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Ryan Peter Lokken
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Neil Mehta
- Department of General Hepatology and Liver Transplantation, University of California, San Francisco, CA, USA
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7
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Piwowarska-Bilska H, Kurkowska S, Birkenfeld B. Individualization of Radionuclide Therapies: Challenges and Prospects. Cancers (Basel) 2022; 14:cancers14143418. [PMID: 35884478 PMCID: PMC9316481 DOI: 10.3390/cancers14143418] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 07/04/2022] [Accepted: 07/12/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Currently, patient-specific treatment plans and dosimetry calculations are not routinely performed for radionuclide therapies. In external beam radiotherapy, it is quite the opposite. As a result, a small fraction of patients receives optimal radioactivity. This conservative approach provides “radiation safety” to healthy tissues but delivers a lower than indicated absorbed dose to the tumors, resulting in a lower response rate and a higher disease relapse rate. Evidence shows that better and more predictable outcomes can be achieved with patient-individualized dose assessment. Therefore, the incorporation of individual planning into radionuclide therapies is a high priority for nuclear medicine physicians and medical physicists alike. Internal dosimetry is used in tumor therapy to optimize the absorbed dose to the target tissue. The main reasons for the difficulties in incorporating patients’ internal dosimetry into routine clinical practice are discussed. The article presents the prospects for the routine implementation of personalized radionuclide therapies. Abstract The article presents the problems of clinical implementation of personalized radioisotope therapy. The use of radioactive drugs in the treatment of malignant and benign diseases is rapidly expanding. Currently, in the majority of nuclear medicine departments worldwide, patients receive standard activities of therapeutic radiopharmaceuticals. Intensively conducted clinical trials constantly provide more evidence of a close relationship between the dose of radiopharmaceutical absorbed in pathological tissues and the therapeutic effect of radioisotope therapy. Due to the lack of individual internal dosimetry (based on the quantitative analysis of a series of diagnostic images) before or during the treatment, only a small fraction of patients receives optimal radioactivity. The vast majority of patients receive too-low doses of ionizing radiation to the target tissues. This conservative approach provides “radiation safety” to healthy tissues, but also delivers lower radiopharmaceutical activity to the neoplastic tissue, resulting in a low level of response and a higher relapse rate. The article presents information on the currently used radionuclides in individual radioisotope therapies and on radionuclides newly introduced to the therapeutic market. It discusses the causes of difficulties with the implementation of individualized radioisotope therapies as well as possible changes in the current clinical situation.
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Ytrrium-90 transarterial radioembolization in patients with gastrointestinal malignancies. Clin Transl Oncol 2022; 24:796-808. [PMID: 35013882 DOI: 10.1007/s12094-021-02745-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 11/29/2021] [Indexed: 10/19/2022]
Abstract
Transarterial radioembolization (TARE) with yttrium-90 (Y90) is a promising alternative strategy to treat liver tumors and liver metastasis from colorectal cancer (CRC), as it selectively delivers radioactive isotopes to the tumor via the hepatic artery, sparring surrounding liver tissue. The landscape of TARE indications is constantly evolving. This strategy is considered for patients with hepatocellular carcinoma (HCC) with liver-confined disease and preserved liver function in whom neither TACE nor systemic therapy is possible. In patients with liver metastases from CRC, TARE is advised when other chemotherapeutic options have failed. Recent phase III trials have not succeeded to prove benefit in overall survival; however, it has helped to better understand the patients that may benefit from TARE based on subgroup analysis. New strategies and treatment combinations are being investigated in ongoing clinical trials. The aim of this review is to summarize the clinical applications of TARE in patients with gastrointestinal malignancies.
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Waddell JJ, Townsend PH, Collins ZS, Walter C. Liver-Directed Therapy for Metastatic Colon Cancer: Update. CURRENT COLORECTAL CANCER REPORTS 2022. [DOI: 10.1007/s11888-022-00474-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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10
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Guiu B, Garin E, Allimant C, Edeline J, Salem R. TARE in Hepatocellular Carcinoma: From the Right to the Left of BCLC. Cardiovasc Intervent Radiol 2022; 45:1599-1607. [PMID: 35149884 DOI: 10.1007/s00270-022-03072-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 01/23/2022] [Indexed: 02/06/2023]
Abstract
The Barcelona Clinic Liver Cancer (BCLC) system is the most commonly used staging system for hepatocellular carcinoma (HCC) in Western countries. BCLC aims to categorize patients into five stages with different prognoses and to allocate treatment according to these stages based on the best possible contemporary evidence. Transarterial radioembolization (TARE) has recently entered at the left of the BCLC algorithm (i.e., BCLC 0-A), mainly because of negative phase III trials in BCLC C stage. TARE has shown a steady increase in nationwide studies over the past 20 years and has even been adopted in some tertiary centers as the primary HCC treatment across all BCLC stages. We aimed to review the history of TARE in HCC, starting from advanced HCC and gradually expanding to earlier stages at the left of the BCLC system.
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Affiliation(s)
- Boris Guiu
- Department of Radiology, St-Eloi University Hospital, 80 Avenue Augustin Fliche, 34295, Montpellier, France.
| | - Etienne Garin
- Department of Nuclear Medicine, Centre de Lutte Contre le Cancer Eugène Marquis, 35000, Rennes, France
| | - Carole Allimant
- Department of Radiology, St-Eloi University Hospital, 80 Avenue Augustin Fliche, 34295, Montpellier, France
| | - Julien Edeline
- Department of Oncology, Centre de Lutte Contre le Cancer Eugène Marquis, 35000, Rennes, France
| | - Riad Salem
- Section of Interventional Radiology, Department of Radiology, Northwestern University, Chicago, IL, 60611, USA
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Dosimetry in radionuclide therapy: the clinical role of measuring radiation dose. Lancet Oncol 2022; 23:e75-e87. [DOI: 10.1016/s1470-2045(21)00657-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 11/03/2021] [Accepted: 11/05/2021] [Indexed: 12/22/2022]
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12
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Bertolet A, Wehrenberg-Klee E, Bobić M, Grassberger C, Perl J, Paganetti H, Schuemann J. Pre- and post-treatment image-based dosimetry in 90Y-microsphere radioembolization using the TOPAS Monte Carlo toolkit. Phys Med Biol 2021; 66:10.1088/1361-6560/ac43fd. [PMID: 34915451 PMCID: PMC8729171 DOI: 10.1088/1361-6560/ac43fd] [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: 10/04/2021] [Accepted: 12/16/2021] [Indexed: 12/31/2022]
Abstract
Objective. To evaluate the pre-treatment and post-treatment imaging-based dosimetry of patients treated with 90Y-microspheres, including accurate estimations of dose to tumor, healthy liver and lung. To do so, the Monte Carlo (MC) TOPAS platform is in this work extended towards its utilization in radionuclide therapy.Approach. Five patients treated at the Massachusetts General Hospital were selected for this study. All patients had data for both pre-treatment SPECT-CT imaging using 99mTc-MAA as a surrogate of the 90Y-microspheres treatment and SPECT-CT imaging immediately after the 90Y activity administration. Pre- and post-treatment doses were computed with TOPAS using the SPECT images to localize the source positions and the CT images to account for tissue inhomoegeneities. We compared our results with analytical calculations following the voxel-based MIRD scheme.Main results. TOPAS results largely agreed with the MIRD-based calculations in soft tissue regions: the average difference in mean dose to the liver was 0.14 Gy GBq-1(2.6%). However, dose distributions in the lung differed considerably: absolute differences in mean doses to the lung ranged from 1.2 to 6.3 Gy GBq-1and relative differences from 153% to 231%. We also found large differences in the intra-hepatic dose distributions between pre- and post-treatment imaging, but only limited differences in the pulmonary dose.Significance. Doses to lung were found to be higher using TOPAS with respect to analytical calculations which may significantly underestimate dose to the lung, suggesting the use of MC methods for 90Y dosimetry. According to our results, pre-treatment imaging may still be representative of dose to lung in these treatments.
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Affiliation(s)
- Alejandro Bertolet
- Department of Radiation Oncology, Massachusetts General Hospital
and Harvard Medical School, Boston, MA, USA
| | - Eric Wehrenberg-Klee
- Department of Radiology, Division of Interventional Radiology,
Massachusetts General Hospital, Boston, MA, USA
| | - Mislav Bobić
- Department of Radiation Oncology, Massachusetts General Hospital
and Harvard Medical School, Boston, MA, USA & Department of Physics, ETH
Zürich, Zürich, Switzerland
| | - Clemens Grassberger
- Department of Radiation Oncology, Massachusetts General Hospital
and Harvard Medical School, Boston, MA
| | - Joseph Perl
- SLAC National Accelerator Laboratory, Menlo Park, CA, USA
| | - Harald Paganetti
- Department of Radiation Oncology, Massachusetts General Hospital
and Harvard Medical School, Boston, MA, USA
| | - Jan Schuemann
- Department of Radiation Oncology, Massachusetts General Hospital
and Harvard Medical School, Boston, MA, USA
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13
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Swersky A, Kulik L, Kalyan A, Grace K, Caicedo JC, Lewandowski RJ, Salem R. Contemporary Algorithm for the Management of Hepatocellular Carcinoma in 2021: The Northwestern Approach. Semin Intervent Radiol 2021; 38:432-437. [PMID: 34629710 DOI: 10.1055/s-0041-1735528] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major cause of cancer-related morbidity and mortality around the world. Frequently, concurrent liver dysfunction and variations in tumor burden make it difficult to design effective and standardized treatment pathways. Contemporary treatment guidelines designed for an era of personalized medicine should consider these features in a more clinically meaningful way to improve outcomes for patients across the HCC spectrum. Given the heterogeneity of HCC, we propose a detailed clinical algorithm for selecting optimal treatment using an evidence-based and practical approach, incorporating liver function, tumor burden, the extent of disease, and ultimate treatment intent, with the goal of individualizing clinical decision making.
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Affiliation(s)
- Adam Swersky
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Laura Kulik
- Division of Hepatology, Department of Medicine, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Aparna Kalyan
- Division of Medical Oncology, Department of Medicine, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Karen Grace
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Juan Carlos Caicedo
- Division of Transplantation, Department of Surgery, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Robert J Lewandowski
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Riad Salem
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
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14
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Murali N, Mouli SK, Riaz A, Lewandowski RJ, Salem R. Extrahepatic Applications of Yttrium-90 Radioembolization. Semin Intervent Radiol 2021; 38:479-481. [PMID: 34629717 DOI: 10.1055/s-0041-1735573] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
While initially described and now accepted as treatment for primary and secondary malignancies in the liver, radioembolization therapy has expanded to include treatment for other disease pathologies and other organ systems. Advantages and limitations for these treatments exist and must be compared against more traditional treatments for these processes. This article provides an overview of the current applications for radioembolization outside of the liver, for both malignant and nonmalignant disease.
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Affiliation(s)
- Nikitha Murali
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Samdeep K Mouli
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Ahsun Riaz
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Robert J Lewandowski
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Riad Salem
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
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15
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Kwee SA, Wong LL, Sato MM, Acoba JD, Rho YS, Srivastava A, Landsittel DP. Transarterial Radioembolization for Hepatocellular Carcinoma with Major Vascular Invasion: A Nationwide Propensity Score-Matched Analysis with Target Trial Emulation. J Vasc Interv Radiol 2021; 32:1258-1266.e6. [PMID: 34242775 DOI: 10.1016/j.jvir.2021.07.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 06/25/2021] [Accepted: 07/01/2021] [Indexed: 12/24/2022] Open
Abstract
PURPOSE To examine National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between patients undergoing transarterial radioembolization (TARE) and those undergoing systemic therapy for hepatocellular carcinoma with major vascular invasion (HCC-MVI). METHODS One thousand five hundred fourteen patients with HCC-MVI undergoing first-line TARE or systemic therapy were identified from the NCDB. OS was compared using propensity score-matched Cox regression and landmark analysis. Efficacy was also compared within a target trial framework. RESULTS TARE usage doubled between 2010 and 2015. Intervals before treatment were longer for TARE than for systemic therapy (mean [median], 66.5 [60] days vs 46.8 (35) days, respectively, P < .0001). In propensity-score-matched and landmark-time-adjusted analyses, TARE was found to be associated with a hazard ratio of 0.74 (95 % CI, 0.60-0.91; P = .005) and median OS of 7.1 months (95 % CI, 5.0-10.5) versus 4.9 months (95 % CI, 3.9-6.5) for systemically treated patients. In an emulated target trial involving 236 patients with unilobular HCC-MVI, a low number of comorbidities, creatinine levels <2.0 mg/dL, bilirubin levels <2.0 mg/dL, and international normalized ratio <1.7, TARE was found to be associated with a hazard ratio of 0.57 (95 % CI, 0.39-0.83; P = .004) and a median OS of 12.9 months (95 % CI, 7.6-19.2) versus 6.5 months (95 % CI, 3.6-11.1) for the systemic therapy arm. CONCLUSIONS In propensity-score-matched analyses involving pragmatic and target trial HCC-MVI cohorts, TARE was found to be associated with significant survival benefits compared with systemic therapy. Although not a substitute for prospective trials, these findings suggest that the increasing use of TARE for HCC-MVI is accompanied by improved OS. Further trials of TARE in patients with HCC-MVI are needed, especially to compare with newer systemic therapies.
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Affiliation(s)
- Sandi A Kwee
- Queen's Medical Center, Honolulu, Hawaii; Clinical and Translational Science Section, Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
| | - Linda L Wong
- Clinical and Translational Science Section, Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii
| | | | - Jared D Acoba
- Queen's Medical Center, Honolulu, Hawaii; Clinical and Translational Science Section, Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii
| | | | - Avantika Srivastava
- Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Douglas P Landsittel
- Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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16
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Zhang JW, Yu ZY, Li HB, Yi SH, Liu W, Yang Y, Wang GY. Severe bile duct complication after yttrium-90 radioembolization therapy in a patient with recurrent hepatocellular carcinoma after liver transplantation: A case report. LIVER RESEARCH 2021; 5:33-35. [PMID: 39958925 PMCID: PMC11791838 DOI: 10.1016/j.livres.2020.10.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 08/01/2020] [Accepted: 10/22/2020] [Indexed: 01/10/2023]
Abstract
Patients with recurrent hepatocellular carcinoma (HCC) following liver transplantation (LT) have a poor prognosis owing to rapid tumor progression. Yttrium-90 radioembolization (90Y-RE) has been shown to be a safe and efficacious transarterial radioembolization treatment for patients with advanced HCC. However, to our knowledge, no data are available for patients with recurrent HCC following LT. Here we report a case of severe bile duct complication after transarterial radioembolization with yttrium-90 in a patient who experienced HCC recurrence following LT. The present case suggests that 90Y-RE should be cautiously performed in patients with recurrent HCC following LT.
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Affiliation(s)
- Jian-Wen Zhang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Organ Transplantation Institute of Sun Yat-sen University, Guangzhou, China
| | - Zhen-Yu Yu
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Organ Transplantation Research Center of Guangdong Province, Guangzhou, China
| | - Hai-Bo Li
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shu-Hong Yi
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wei Liu
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Organ Transplantation Institute of Sun Yat-sen University, Guangzhou, China
| | - Guo-Ying Wang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Organ Transplantation Research Center of Guangdong Province, Guangzhou, China
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17
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Nabrinsky E, James E. Highlighting Survival with Yttrium-90 Radioembolization Therapy in Unresectable Hepatocellular Carcinoma. Cureus 2020; 12:e8163. [PMID: 32550079 PMCID: PMC7296880 DOI: 10.7759/cureus.8163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Unresectable hepatocellular carcinoma has several different therapeutic options, including targeted agents as well as locoregional therapy. Yttrium-90 (Y90) radioembolization therapy is an established treatment for unresectable disease and has been compared to other locoregional options as well as different targeted therapies. Newer case series are also reporting a potential benefit to the addition of immunotherapy to Y90 radioembolization. Here we report a case of prolonged survival in a patient whose treatment course included Y90 radioembolization along with sorafenib and nivolumab.
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Affiliation(s)
- Edward Nabrinsky
- Internal Medicine, Advocate Lutheran General Hospital, Park Ridge, USA
| | - Edward James
- Medical Oncology, Advocate Lutheran General Hospital, Park Ridge, USA
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18
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Advances in resection and transplantation for hepatocellular carcinoma. J Hepatol 2020; 72:262-276. [PMID: 31954491 DOI: 10.1016/j.jhep.2019.11.017] [Citation(s) in RCA: 116] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 11/25/2019] [Accepted: 11/26/2019] [Indexed: 02/08/2023]
Abstract
It would be impossible to summarise all of the significant developments in the surgical management of hepatocellular carcinoma (HCC), even just over the past year, in a manuscript of this scope. Thus, we have selected topics for discussion that are the subject of current controversy and have attempted to present balanced points of view. Hepatic resection and transplantation are both mature modalities, and for the most part technical advances and improvements in candidate selection are incremental. The ability to readily cure hepatitis C stands out as the most impactful development in the field over recent years, especially in Western countries where hepatitis C has long been the chief aetiology underlying HCC and a predictor of poor outcomes after surgery, but its full implications remain to be clarified. The rising incidence of non-alcoholic steatohepatitis-related HCC and what it means with regard to surgical HCC management is an area of great current interest. With advancing technology, non-surgical locoregional treatments are gaining increasing application as potentially curative therapies. In addition, the advances in molecular and genomic assessment of HCC hold promise for personalising treatment and prognostication. The possible role of immunotherapy as an adjuvant to resection is being aggressively investigated. While liver surgery maintains an important role, the care of patients with HCC is more and more a team effort and needs to take place in the context of a well-integrated interdisciplinary programme to achieve the best outcomes for patients.
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19
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Saini A, Wallace A, Alzubaidi S, Knuttinen MG, Naidu S, Sheth R, Albadawi H, Oklu R. History and Evolution of Yttrium-90 Radioembolization for Hepatocellular Carcinoma. J Clin Med 2019; 8:jcm8010055. [PMID: 30621040 PMCID: PMC6352151 DOI: 10.3390/jcm8010055] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 12/18/2018] [Accepted: 12/31/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and affects millions worldwide. Due to the lack of effective systemic therapies for HCC, researchers have been investigating the use of locoregional tumor control with Yttrium-90 (Y90) radioembolization since the 1960s. Following the development of glass and resin Y90 microspheres in the early 1990s, Y90 radioembolization has been shown to be a safe and efficacious treatment for patients with HCC across Barcelona Clinic Liver Cancer (BCLC) stages. By demonstrating durable local control, good long term outcomes, and equivalent if not superior tumor responses and tolerability when compared to alternative therapies including transarterial chemoembolization (TACE) and sorafenib, Y90 radioembolization is being increasingly used in HCC treatment. More recently, investigations into variations in Y90 radioembolization technique including radiation segmentectomy and radiation lobectomy have further expanded its clinical utility. Here, we discuss the history and evolution of Y90 use in HCC. We outline key clinical trials that have established the safety and efficacy of Y90 radioembolization, and also summarize trials comparing its efficacy to existing HCC treatments. We conclude by reviewing the techniques of radiation segmentectomy and lobectomy, and by discussing dosimetry.
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Affiliation(s)
- Aman Saini
- Division of Vascular and Interventional Radiology, Laboratory for Minimally Invasive Therapeutics, Mayo Clinic, Phoenix, AZ 85054, USA.
| | - Alex Wallace
- Division of Vascular and Interventional Radiology, Laboratory for Minimally Invasive Therapeutics, Mayo Clinic, Phoenix, AZ 85054, USA.
| | - Sadeer Alzubaidi
- Division of Vascular and Interventional Radiology, Laboratory for Minimally Invasive Therapeutics, Mayo Clinic, Phoenix, AZ 85054, USA.
| | - M Grace Knuttinen
- Division of Vascular and Interventional Radiology, Laboratory for Minimally Invasive Therapeutics, Mayo Clinic, Phoenix, AZ 85054, USA.
| | - Sailendra Naidu
- Division of Vascular and Interventional Radiology, Laboratory for Minimally Invasive Therapeutics, Mayo Clinic, Phoenix, AZ 85054, USA.
| | - Rahul Sheth
- Department of Interventional Radiology, MD Anderson Cancer Center, Houston, TX 77054, USA.
| | - Hassan Albadawi
- Division of Vascular and Interventional Radiology, Laboratory for Minimally Invasive Therapeutics, Mayo Clinic, Phoenix, AZ 85054, USA.
| | - Rahmi Oklu
- Division of Vascular and Interventional Radiology, Laboratory for Minimally Invasive Therapeutics, Mayo Clinic, Phoenix, AZ 85054, USA.
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20
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Krishan S, Dhiman RK, Kalra N, Sharma R, Baijal SS, Arora A, Gulati A, Eapan A, Verma A, Keshava S, Mukund A, Deva S, Chaudhary R, Ganesan K, Taneja S, Gorsi U, Gamanagatti S, Madhusudan KS, Puri P, Shalimar, Govil S, Wadhavan M, Saigal S, Kumar A, Thapar S, Duseja A, Saraf N, Khandelwal A, Mukhopadyay S, Gulati A, Shetty N, Verma N. Joint Consensus Statement of the Indian National Association for Study of the Liver and Indian Radiological and Imaging Association for the Diagnosis and Imaging of Hepatocellular Carcinoma Incorporating Liver Imaging Reporting and Data System. J Clin Exp Hepatol 2019; 9:625-651. [PMID: 31695253 PMCID: PMC6823668 DOI: 10.1016/j.jceh.2019.07.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 07/12/2019] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the 6th most common cancer and the second most common cause of cancer-related mortality worldwide. There are currently no universally accepted practice guidelines for the diagnosis of HCC on imaging owing to the regional differences in epidemiology, target population, diagnostic imaging modalities, and staging and transplant eligibility. Currently available regional and national guidelines include those from the American Association for the Study of Liver Disease (AASLD), the European Association for the Study of the Liver (EASL), the Asian Pacific Association for the Study of the Liver, the Japan Society of Hepatology, the Korean Liver Cancer Study Group, Hong Kong, and the National Comprehensive Cancer Network in the United States. India with its large population and a diverse health infrastructure faces challenges unique to its population in diagnosing HCC. Recently, American Association have introduced a Liver Imaging Reporting and Data System (LIRADS, version 2017, 2018) as an attempt to standardize the acquisition, interpretation, and reporting of liver lesions on imaging and hence improve the coherence between radiologists and clinicians and provide guidance for the management of HCC. The aim of the present consensus was to find a common ground in reporting and interpreting liver lesions pertaining to HCC on imaging keeping LIRADSv2018 in mind.
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Affiliation(s)
- Sonal Krishan
- Department of Radiology, Medanta Hospital, Gurgaon, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India,Address for correspondence: Radha Krishan Dhiman, MD, DM, FACG, FRCP, FAASLD, Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Navin Kalra
- Department of Radiology, Postgraduate Institute Of Medical Education and Research, Chandigarh, India
| | - Raju Sharma
- Department of Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Sanjay S. Baijal
- Department of Diagnostic and Intervention Radiology, Medanta Hospital, Gurgaon, India
| | - Anil Arora
- Institute Of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Gangaram Hospital, New Delhi, India
| | - Ajay Gulati
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Anu Eapan
- Department of Radiology, Christian Medical College, Vellore, India
| | - Ashish Verma
- Department of Radiology, Banaras Hindu University, Varanasi, India
| | - Shyam Keshava
- Department of Radiology, Christian Medical College, Vellore, India
| | - Amar Mukund
- Department of Intervention Radiology, Institute of liver and biliary Sciences, New Delhi, India
| | - S. Deva
- Department of Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Ravi Chaudhary
- Department of Radiology, Medanta Hospital, Gurgaon, India
| | | | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ujjwal Gorsi
- Department of Radiology, Postgraduate Institute Of Medical Education and Research, Chandigarh, India
| | | | - Kumble S. Madhusudan
- Department of Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Pankaj Puri
- Institute Of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Gangaram Hospital, New Delhi, India
| | - Shalimar
- Department of GastroEnterology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Manav Wadhavan
- Institute of Digestive and Liver Diseases, BLK Hospital, Delhi, India
| | - Sanjiv Saigal
- Department of Hepatology, Medanta Hospital, Gurgaon, India
| | - Ashish Kumar
- Institute Of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Gangaram Hospital, New Delhi, India
| | - Shallini Thapar
- Department of Radiology, Institute of liver and biliary Sciences, New Delhi, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Neeraj Saraf
- Department of Hepatology, Medanta Hospital, Gurgaon, India
| | | | | | - Ajay Gulati
- Department of Radiology, Postgraduate Institute Of Medical Education and Research, Chandigarh, India
| | - Nitin Shetty
- Department of Radiology, Tata Memorial Hospital, Kolkata, India
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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21
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Toesca DAS, Barry A, Sapisochin G, Beecroft R, Dawson L, Owen D, Mouli S, Lewandowski R, Salem R, Chang DT. Clinical Case Panel: Treatment Alternatives for Inoperable Hepatocellular Carcinoma. Semin Radiat Oncol 2018; 28:295-308. [PMID: 30309640 DOI: 10.1016/j.semradonc.2018.08.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Surgical resection or liver transplantation offers the best chance of cure for patients with hepatocellular carcinoma (HCC). Unfortunately, most patients are not good candidates for liver resection due to locally advanced disease or compromised liver function. Moreover, liver transplantation waiting lists are long. For those cases not amenable for resection, a variety of local treatment modalities are available, such as image-guided ablative procedures, transarterial chemoembolization, and radioembolization, as well as external beam radiation. HCC presentation can vary considerably in size, number, and location of lesions. The management of inoperable HCC is, therefore, quite complex, and there is a lack of consensus on the best local treatment modality for each type tumor presentation. Here, we present 4 clinical case scenarios representative of commonly seen cases in the clinical setting, with different therapeutic perspectives from institutions with high expertise in the management of HCC.
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Affiliation(s)
- Diego A S Toesca
- Department of Radiation Oncology, Stanford Cancer Institute, Stanford, CA
| | - Aisling Barry
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant, Toronto General Surgery, Department of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Robert Beecroft
- Division of Interventional Radiology, University of Toronto, Toronto, Ontario, Canada
| | - Laura Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | - Dawn Owen
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
| | - Samdeep Mouli
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL
| | - Robert Lewandowski
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL
| | - Daniel T Chang
- Department of Radiation Oncology, Stanford Cancer Institute, Stanford, CA.
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22
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Mantaka A, Augoustaki A, Kouroumalis EA, Samonakis DN. Portal vein thrombosis in cirrhosis: diagnosis, natural history, and therapeutic challenges. Ann Gastroenterol 2018; 31:315-329. [PMID: 29720857 PMCID: PMC5924854 DOI: 10.20524/aog.2018.0245] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 11/26/2017] [Indexed: 12/13/2022] Open
Abstract
Portal vein thrombosis (PVT) is a frequent complication in cirrhosis and its prevalence increases with disease severity. Several factors are involved in the development and progression of PVT. The challenge for the management of PVT is the precise evaluation of the bleeding risk as opposed to life-threatening extension of thrombosis. Nevertheless, the impact on the progression and outcome of liver disease is unclear. A critical evaluation of the available data discloses that treating PVT in cirrhotics is safe and effective. However, there are open issues, such as which anticoagulant could represent a safer therapeutic option, and when and for how long this treatment should be administered to cirrhotic patients with PVT.
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Affiliation(s)
- Aikaterini Mantaka
- Department of Gastroenterology and Hepatology, University Hospital of Crete, Heraklion, Crete, Greece
| | - Aikaterini Augoustaki
- Department of Gastroenterology and Hepatology, University Hospital of Crete, Heraklion, Crete, Greece
| | - Elias A Kouroumalis
- Department of Gastroenterology and Hepatology, University Hospital of Crete, Heraklion, Crete, Greece
| | - Dimitrios N Samonakis
- Department of Gastroenterology and Hepatology, University Hospital of Crete, Heraklion, Crete, Greece
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23
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Peterson RA, Buck EC, Chun J, Daniel RC, Herting DL, Ilton ES, Lumetta GJ, Clark SB. Review of the Scientific Understanding of Radioactive Waste at the U.S. DOE Hanford Site. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2018; 52:381-396. [PMID: 29215277 DOI: 10.1021/acs.est.7b04077] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
This Critical Review reviews the origin and chemical and rheological complexity of radioactive waste at the U.S. Department of Energy Hanford Site. The waste, stored in underground tanks, was generated via three distinct processes over decades of plutonium extraction operations. Although close records were kept of original waste disposition, tank-to-tank transfers and conditions that impede equilibrium complicate our understanding of the chemistry, phase composition, and rheology of the waste. Tank waste slurries comprise particles and aggregates from nano to micro scales, with varying densities, morphologies, heterogeneous compositions, and complicated responses to flow regimes and process conditions. Further, remnant or changing radiation fields may affect the stability and rheology of the waste. These conditions pose challenges for transport through conduits or pipes to treatment plants for vitrification. Additionally, recalcitrant boehmite degrades glass quality and the high aluminum content must be reduced prior to vitrification for the manufacture of waste glass of acceptable durability. However, caustic leaching indicates that boehmite dissolves much more slowly than predicted given surface normalized rates. Existing empirical models based on ex situ experiments and observations generally only describe material balances and have not effectively predicted process performance. Recent advances in the areas of in situ microscopy, aberration-corrected transmission electron microscopy, theoretical modeling across scales, and experimental methods for probing the physics and chemistry at mineral-fluid and mineral-mineral interfaces are being implemented to build robustly predictive physics-based models.
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Affiliation(s)
| | | | | | | | - Daniel L Herting
- Washington River Protection Solutions , Richland, Washington 99354, United States
| | | | | | - Sue B Clark
- Chemistry Department, Washington State University , Pullman, Washington 99164, United States
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Abouchaleh N, Gabr A, Ali R, Al Asadi A, Mora RA, Kallini JR, Mouli S, Riaz A, Lewandowski RJ, Salem R. 90Y Radioembolization for Locally Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Long-Term Outcomes in a 185-Patient Cohort. J Nucl Med 2017; 59:1042-1048. [DOI: 10.2967/jnumed.117.199752] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 11/13/2017] [Indexed: 12/23/2022] Open
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25
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Quencer KB, Friedman T, Sheth R, Oklu R. Tumor thrombus: incidence, imaging, prognosis and treatment. Cardiovasc Diagn Ther 2017; 7:S165-S177. [PMID: 29399520 PMCID: PMC5778532 DOI: 10.21037/cdt.2017.09.16] [Citation(s) in RCA: 113] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 09/12/2017] [Indexed: 12/11/2022]
Abstract
Intravascular tumor extension, also known as tumor thrombus, can occur in many different types of cancer. Those with the highest proclivity include Wilm's tumor, renal cell carcinoma (RCC), adrenal cortical carcinoma (ACC) and hepatocellular carcinoma (HCC). The presence of tumor thrombus markedly worsens prognosis and impacts treatment approach. Imaging plays a key role in its diagnosis. Endovascular methods also play a large role in treatment.
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Affiliation(s)
| | - Tamir Friedman
- Division of Interventional Radiology, Department of Radiology, Cornell University, New York, NY, USA
| | - Rahul Sheth
- Division of Interventional Radiology, Department of Radiology, MD Anderson Cancer, Houston, TX, USA
| | - Rahmi Oklu
- Division of Interventional Radiology, Department of Radiology, Mayo Clinic-Arizona, Phoenix, AZ, USA
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26
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Maher B, Ryan E, Little M, Boardman P, Stedman B. The management of colorectal liver metastases. Clin Radiol 2017; 72:617-625. [DOI: 10.1016/j.crad.2017.05.016] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Accepted: 05/30/2017] [Indexed: 02/07/2023]
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Ye JZ, Wang YY, Bai T, Chen J, Xiang BD, Wu FX, Li LQ. Surgical resection for hepatocellular carcinoma with portal vein tumor thrombus in the Asia-Pacific region beyond the Barcelona Clinic Liver Cancer treatment algorithms: a review and update. Oncotarget 2017; 8:93258-93278. [PMID: 29190996 PMCID: PMC5696262 DOI: 10.18632/oncotarget.18735] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Accepted: 04/25/2017] [Indexed: 01/27/2023] Open
Abstract
Portal vein tumor thrombus (PVTT) usually worsens prognosis of hepatocellular carcinoma (HCC), as characterized by aggressive disease progression, impaired liver function and tolerance to treatment. Conventionally, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) accepted the Barcelona Clinical Liver Cancer (BCLC) treatment algorithms, identifying PVTT as an absolute contra-indication of surgical resection for HCC. HCC-PVTT patients are offered sorafenib as the standard treatment. Evidently, SHARP and Asia-Pacific trials demonstrated that sorafenib only improves overall survival by approximately 3 months in patients with advanced HCC. Besides, BCLC treatment algorithm does not provide different therapeutic recommendations for different degree of PVTT, and only supports single treatment option for each stage of HCC rather than a combination of comprehensive treatments, which limited individual and best care for every HCC-PVTT patients. In the past few years, many surgeons do not restrict surgical resection to HCC with PVTT. There have been new reports demonstrated that surgical treatment is feasible for selected HCC-PVTT patients with resectable tumor and moderate liver function to prolong survival period and elevate life quality as long as PVTT limited to the first-order branch, whereas non-surgical treatments fail to provide comparable therapeutic effects. At present, guidelines on HCC management from mainland China, Japan, and Hong Kong have been updated and a consensus of Asia-Pacific experts has established that portal venous invasion is not an absolute contradiction of surgical resection for HCC. This review summarized the emerging data on surgical resection for HCC-PVTT patients beyond the BCLC treatment algorithms and discussed recent therapeutic conceptualchanges in the Asia-Pacific region.
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Affiliation(s)
- Jia-Zhou Ye
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Yan-Yan Wang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Tao Bai
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Jie Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
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Comparison of the Adverse Event Profile of TheraSphere® with SIR-Spheres® for the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review. Cardiovasc Intervent Radiol 2017; 40:1033-1043. [DOI: 10.1007/s00270-017-1594-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Accepted: 01/31/2017] [Indexed: 12/16/2022]
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29
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Kouri BE, Abrams RA, Al-Refaie WB, Azad N, Farrell J, Gaba RC, Gervais DA, Gipson MG, Kolbeck KJ, Marshalleck FE, Pinchot JW, Small W, Ray CE, Hohenwalter EJ. ACR Appropriateness Criteria Radiologic Management of Hepatic Malignancy. J Am Coll Radiol 2016; 13:265-73. [PMID: 26944037 DOI: 10.1016/j.jacr.2015.12.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 12/04/2015] [Indexed: 12/18/2022]
Abstract
Management of primary and secondary hepatic malignancy is a complex problem. Achieving optimal care for this challenging population often requires the involvement of multiple medical and surgical disciplines. Because of the wide variety of potential therapies, treatment protocols for various malignancies continue to evolve. Consequently, development of appropriate therapeutic algorithms necessitates consideration of medical options, such as systemic chemotherapy; surgical options, such as resection or transplantation; and loco-regional therapies, such as thermal ablation and transarterial embolization techniques. This article provides a review of treatment strategies for the three most common subtypes of hepatic malignancy treated with loco-regional therapies: hepatocellular carcinoma, neuroendocrine metastases, and colorectal metastases. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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Affiliation(s)
- Brian E Kouri
- Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina.
| | | | - Waddah B Al-Refaie
- Georgetown University Hospital, Washington, District of Columbia, American College of Surgeons
| | - Nilofer Azad
- Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore, Maryland, American Society of Clinical Oncology
| | - James Farrell
- Interventional Endoscopy and Pancreatic Diseases, New Haven, Connecticut, American Gastroenterological Association
| | - Ron C Gaba
- University of Illinois Hospital, Chicago, Illinois
| | | | - Matthew G Gipson
- University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | | | | | | | - William Small
- Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois
| | - Charles E Ray
- University of Illinois Hospital and Health Science System, Chicago, Illinois
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Hsieh TC, Wu YC, Sun SS, Yen KY, Kao CH. Treating hepatocellular carcinoma with 90Y-bearing microspheres: a review. Biomedicine (Taipei) 2016; 6:19. [PMID: 27848114 PMCID: PMC5138159 DOI: 10.7603/s40681-016-0019-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2016] [Accepted: 08/06/2016] [Indexed: 12/21/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a disease usually diagnosed in its advanced-stage, and is frequently not amenable to curative surgical treatment. Also, HCC is resistant to chemotherapy and less vulnerable to radiation therapy compared to normal hepatic parenchyma. Both of these facts render the efficacy of adjuvant and palliative treatments problematic. Selective internal radiation therapy (SIRT) with 90Y-bearing microspheres is characterized by preferentially delivering substantially high doses of radiation to a liver tumor dose simultaneously limiting the damage to its non-tumorous cells, providing an opportunity for effective local tumor control and even tumor regression therapy. The current article reviews the specific characters, dosimetry, possible applications, and special considerations toward the pre-existing radiation therapy of 90Y microsphere SIRT in treating HCC.
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Affiliation(s)
- Te-Chun Hsieh
- Department of Nuclear Medicine and PET Center, China Medical University Hospital, No. 2, Yuh-Der Rd., North Dist., Taichung, 404, Taiwan.,Department of Biomedical Imaging and Radiological Science, China Medical University, 404, Taichung, Taiwan
| | - Yu-Chin Wu
- Department of Nuclear Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu Branch, No. 25, Ln. 442. Sec. 1, Jingguo Rd., East Dist.,, Hsinchu City, 300, Taiwan.
| | - Shung-Shung Sun
- Department of Nuclear Medicine and PET Center, China Medical University Hospital, No. 2, Yuh-Der Rd., North Dist., Taichung, 404, Taiwan.,Department of Biomedical Imaging and Radiological Science, China Medical University, 404, Taichung, Taiwan
| | - Kuo-Yang Yen
- Department of Nuclear Medicine and PET Center, China Medical University Hospital, No. 2, Yuh-Der Rd., North Dist., Taichung, 404, Taiwan.,Department of Biomedical Imaging and Radiological Science, China Medical University, 404, Taichung, Taiwan
| | - Chia-Hung Kao
- Department of Nuclear Medicine and PET Center, China Medical University Hospital, No. 2, Yuh-Der Rd., North Dist., Taichung, 404, Taiwan. .,School of Medicine, China Medical University, 404, Taichung, Taiwan.
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31
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Park HC, Yu JI, Cheng JCH, Zeng ZC, Hong JH, Wang MLC, Kim MS, Chi KH, Liang PC, Lee RC, Lau WY, Han KH, Chow PKH, Seong J. Consensus for Radiotherapy in Hepatocellular Carcinoma from The 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014): Current Practice and Future Clinical Trials. Liver Cancer 2016; 5:162-74. [PMID: 27493892 PMCID: PMC4960352 DOI: 10.1159/000367766] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
A consensus meeting to develop practice guidelines and to recommend future clinical trials for radiation therapy (RT), including external beam RT (EBRT), and selective internal RT (SIRT) in hepatocellular carcinoma (HCC) was held at the 5th annual meeting of the Asia-Pacific Primary Liver Cancer Expert consortium. Although there is no randomized phase III trial evidence, the efficacy and safety of RT in HCC has been shown by prospective and retrospective studies using modern RT techniques. Based on these results, the committee came to a consensus on the utility and efficacy of RT in the management of HCC according to each disease stage as follows: in early and intermediate stage HCC, if standard treatment is not compatible, RT, including EBRT and SIRT can be considered. In locally advanced stage HCC, combined EBRT with transarterial chemoembolization or hepatic arterial infusion chemotherapy, and SIRT can be considered. In terminal stage HCC, EBRT can be considered for palliation of symptoms and reduction of morbidity caused by the primary tumor or its metastases. Despite the currently reported benefits of RT in HCC, the committee agreed that there is a compelling need for large prospective studies, including randomized phase III trial evidence evaluating the role of RT. Specifically studies evaluating the efficacy and safety of sequential combination of EBRT and SIRT are strongly recommended.
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Affiliation(s)
- Hee Chul Park
- Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea,Medical Device Management and Research, SAIHST, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jeong Il Yu
- Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jason Chia-Hsien Cheng
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan (ROC)
| | - Zhao Chong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ji Hong Hong
- Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (ROC)
| | | | - Mi Sook Kim
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea
| | - Kwan Hwa Chi
- Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (ROC)
| | - Po-Ching Liang
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan (ROC)
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan (ROC)
| | - Wan-Yee Lau
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Kwang Hyub Han
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Pierce Kah-Hoe Chow
- Department of Surgical Oncology, National Cancer Center; Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital; Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore,*Pierce K. H. Chow, MD, PhD, Department of Surgical Oncology, National Cancer, Center, Department of Hepatopancreatobiliary and, Transplant Surgery, Singapore General Hospital;, Office of Clinical Sciences, Duke-NUS Graduate, Medical School, Singapore (Singapore), Tel. +65 6326 6091, E-Mail
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea,*Jinsil Seong, MD, PhD, Department of Radiation Oncology, Yonsei Cancer, Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, (Republic of Korea), Tel. +82 2 2228 8111, E-Mail
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Lee EW, Alanis L, Cho SK, Saab S. Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review. Korean J Radiol 2016; 17:472-88. [PMID: 27390539 PMCID: PMC4936170 DOI: 10.3348/kjr.2016.17.4.472] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 03/20/2016] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.
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Affiliation(s)
- Edward Wolfgang Lee
- Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
| | - Lourdes Alanis
- Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
| | - Sung-Ki Cho
- Division of Interventional Radiology, Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
| | - Sammy Saab
- Division of Hepatology, Department of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles, CA 90024, USA
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Mohammadi H, Chuong MD, Moeslein FM, Sharma NK. Selective internal radiation therapy for the treatment of inoperable neuroendocrine tumor liver metastases. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2016. [DOI: 10.2217/ije.15.33] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Neuroendocrine tumor liver metastases are commonly present at the time of neuroendocrine tumor diagnosis. Surgical resection is potentially curative and achieves the best long-term results but is not feasible in many patients. Angiographic liver-directed treatment modalities such as transarterial embolization, transarterial chemoembolization and selective internal radiotherapy using Yttrium-90 ([90]Y)-labeled microspheres have been shown to be effective treatments with liver predominant disease. Here, we review the management of neuroendocrine tumor liver metastases including selective internal radiotherapy.
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Affiliation(s)
- Homan Mohammadi
- School of Medicine & Health Sciences, The George Washington University, 2300 Eye Street NW Washington, DC 20006, USA
| | - Michael D Chuong
- Department of Radiation Oncology, University of Maryland, 22 South Greene Street, Baltimore, MD 21201, USA
| | - Fred M Moeslein
- Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland, 22 South Greene Street, Baltimore, MD 21201, USA
| | - Navesh K Sharma
- Division of Radiation Oncology, Penn State Hershey Cancer Institute, 500 University Drive, Hershey, PA 17033, USA
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Wachsmann J, Peng F. Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma. World J Gastroenterol 2016; 22:221-31. [PMID: 26755872 PMCID: PMC4698487 DOI: 10.3748/wjg.v22.i1.221] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 10/18/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.
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Jia Z, Jiang G, Tian F, Zhu C, Qin X. A systematic review on the safety and effectiveness of yttrium-90 radioembolization for hepatocellular carcinoma with portal vein tumor thrombosis. Saudi J Gastroenterol 2016; 22:353-359. [PMID: 27748320 PMCID: PMC5051218 DOI: 10.4103/1319-3767.191139] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND/AIM Over the past two decades, several advances have been made in the management of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). Yttrium-90 ( 90 Y) radioembolization has recently been made a treatment option for patients with HCC and PVTT. However, there is still a need to systematicly evaluate the outcomes of 90 Y radioembolization for HCC and PVTT. We aimed to assess the safety and effectiveness of 90 Y radioembolization for HCC and PVTT. We performed a systematic review of clinical trials, clinical studies, and abstracts from conferences that qualified for analysis. MATERIALS AND METHODS PubMed, EMBASE, Cochrane Database of Systematic Review, CINAHL, and the "gray" literature (Google Scholar) were searched for all reports (1991-2016) related to 90 Y radioembolization for HCC and PVTT. RESULTS A total of 14 clinical studies and three abstracts from conferences including 722 patients qualified for the analysis. The median length of follow-up was 7.2 months; the median time to progression was 5.6 months, and median disease control rate was 74.3%. Radiological response data were reported in five studies, and the median reported value of patients with complete response, partial response, stable disease, and progressive disease were 3.2%, 16.5%, 31.3%, and 28%, respectively. The median survival was 9.7 months for all patients, including the median overall survival (OS) were 12.1, 6.1 months of Child-Pugh class A and B patients, and the median OS were 6.1, 13.4 months of main and branch PVTT patients, respectively. The common toxicities were fatigue, nausea/vomiting, abdominal pain, mostly not requiring medical intervention needed no medication intervention. CONCLUSIONS 90 Y radioembolization is a safe and effective treatment for HCC and PVTT.
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Affiliation(s)
- Zhongzhi Jia
- Department of Interventional Radiology, Changzhou No. 2 People's Hospital, Nanjing Medical University, Changzhou, 213003, Jiangsu Province, China
| | - Guomin Jiang
- Department of Interventional Radiology, Changzhou No. 2 People's Hospital, Nanjing Medical University, Changzhou, 213003, Jiangsu Province, China
| | - Feng Tian
- Department of Interventional Radiology, Changzhou No. 2 People's Hospital, Nanjing Medical University, Changzhou, 213003, Jiangsu Province, China
| | - Chunfu Zhu
- Department of General Surgery, Changzhou No. 2 People's Hospital, Nanjing Medical University, Changzhou, 213003, Jiangsu Province, China
| | - Xihu Qin
- Department of General Surgery, Changzhou No. 2 People's Hospital, Nanjing Medical University, Changzhou, 213003, Jiangsu Province, China,Address for correspondence: Dr. Xihu Qin, Department of General Surgery, Changzhou No. 2 People's Hospital, Nanjing Medical University, Xing Long Road 29#, Changzhou, 213003, Jiangsu Province, China. E-mail:
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Evaluation of factors affecting tumor response and survival in patients with primary and metastatic liver cancer treated with microspheres. Nucl Med Commun 2015; 36:340-9. [PMID: 25563137 DOI: 10.1097/mnm.0000000000000257] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Radioembolization with the yttrium-90 (Y-90) microspheres is being used increasingly more often in the treatment of patients with primary or metastatic liver cancer. Although technetium-99m macroaggregated albumin (Tc-99m MAA) scintigraphy performed following diagnostic angiography has an important role in predicting the effectiveness of treatment and in dose estimation, the number of studies using quantitative assessment of Tc-99m MAA scintigraphy is limited in this field. In the present study, the aim was to assess whether a tumor dose is required to obtain objective tumor response and to check whether this threshold value is predictive in terms of tumor response, survival, and liver toxicity by using Tc-99m MAA single-photon emission computed tomography (SPECT) images. MATERIALS AND METHODS Overall, 54 patients (20 women and 34 men; median age: 60 years) who underwent Y-90 Resin (SIR-Spheres) and Glass (TheraSphere) microsphere treatment with a diagnosis of unresectable liver cancer between August 2010 and April 2013 were included in the study. The mean doses to normal liver and tumor were estimated for each patient using Tc-99m MAA SPECT images and the medical internal radiation dosimetry method. The responses were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) and European Organisation for Research and Treatment of Cancer (EORTC) criteria. Kaplan-Meier survival curves and univariate Cox regression analysis were used in survival analysis. The relationship between treatment response and other parameters included was assessed using logistic regression analysis. The variables with a P value less than 0.01 in univariate analysis were assessed with multivariate analysis. RESULTS Fifty-four Y-90 microsphere treatments (eight by using a Y-90 glass microsphere and 46 by using a Y-90 resin microsphere) were performed. In the multivariate analysis, the only parameter related to response was tumor dose (P<0.01). With a tumor dose of 280 Gy or higher, objective tumor response was observed in 59 and 77% of the patients according to RECIST and EORTC criteria, respectively, and the tumor control rate was found to be 95% according to both criteria. In addition, it was found that only tumor dose was correlated with progression-free survival (PFS) (P<0.001) and overall survival (OS) (P=0.018). When the tumor dose was 280 Gy or higher, median PFS increased from 2 to 10.7 months (P<0.001), whereas median OS increased from 9 to 17.6 months (P=0.018). However, reversible ≥ G2 liver toxicity was observed in 3.7% (2/54) of the patients within 3 months after radioembolization with a median normal liver dose of 40 Gy (10-102 Gy). There was reversible ≥ G3 liver toxicity in 3.7% (2/54) of patients, but no G4 liver toxicity was observed. Clinical radiation hepatitis and treatment-induced liver failure were not observed in any of these patients. CONCLUSION Tc-99m MAA SPECT has a predictive value in terms of response to radioembolization, PFS, and OS. Dosimetry based on Tc-99m MAA SPECT images can be used in the selection of patients and, in particular, to adaptation of treatment plan in selected patients.
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Lee VHF, Leung DK, Luk MY, Tong CC, Law MW, Ng SC, Wong KK, Poon RT, Kwong DL, Leung TW. Yttrium-90 radioembolization for advanced inoperable hepatocellular carcinoma. Onco Targets Ther 2015; 8:3457-64. [PMID: 26640386 PMCID: PMC4662370 DOI: 10.2147/ott.s92473] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Advanced inoperable hepatocellular carcinoma (HCC) conferring a grave prognosis may benefit from yttrium-90 ((90)Y) radioembolization. METHODS Thirty patients with advanced inoperable HCC including those with any lesion >8 cm in maximal diameter or multiple bi-lobar lesions (totally more than five lesions), or portal vein thrombosis treated with radioembolization were reviewed. Treatment efficacy and safety were evaluated. Univariate and multivariate analyses were performed for identifying potential prognostic factors. RESULTS After a median follow-up of 18.3 months, the response rate was 30.0%, and the disease control rate was 50.0%. Median overall progression-free survival (PFS) and overall survival (OS) were 3.3 months and 13.2 months, respectively. Longer median PFS was noted in those who had transarterial chemoembolization before radioembolization (7.3 months vs 3.1 months; P=0.021) and duration of alfafeto protein (AFP) response ≥6 months (11.8 months vs 3.0 months; P<0.001). Longer median OS was also revealed in those without portal vein thrombosis (17.1 months vs 4.4 months; P=0.015) and those whose duration of AFP response was ≥6 months (21.2 months vs 8.6 months; P=0.001). Seventeen patients (56.7%) developed treatment-related complications including five (16.7%) grade 3 events. Multivariate analysis revealed that treatment responders (P=0.001) and duration of AFP response ≥6 months (P=0.006) were prognostic of PFS, whereas the absence of portal vein invasion (P=0.025), treatment responders (P=0.010), and duration of AFP response ≥6 months (P=0.001) were prognostic of OS. CONCLUSION (90)Y radioembolization is an alternative treatment with a promising outcome for poor-risk advanced inoperable HCC.
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Affiliation(s)
- Victor Ho-Fun Lee
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Dennis Kc Leung
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Mai-Yee Luk
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Chi-Chung Tong
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Martin Wm Law
- Department of Nuclear Medicine, The University of Hong Kong, Hong Kong
| | - Sherry Cy Ng
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Ka-Kin Wong
- Department of Radiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Ronnie Tp Poon
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Dora Lw Kwong
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - To-Wai Leung
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
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Abstract
METHODICAL INNOVATIONS Selective internal radiotherapy (SIRT) is a safe and efficacious, minimally invasive procedure to treat primary and secondary unresectable liver tumors. For hepatocellular carcinoma (HCC), SIRT has proven to be a well-tolerated therapy option even in advanced stages of disease. STANDARD RADIOLOGICAL METHODS In cases of portal vein thrombosis SIRT is the alternative to transarterial chemoembolization (TACE). PERFORMANCE The role of SIRT regarding downstaging and bridging to transplantation is promising and SIRT has also been shown to be highly effective and well-tolerated in metastastic liver disease. ACHIEVEMENTS The results of prospective randomized trials are awaited to prove the efficiency and safety of SIRT described in numerous retrospective and prospective non-randomized studies. PRACTICAL RECOMMENDATIONS The indications are established within the framework of a tumor board.
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Affiliation(s)
- H Duan
- Klinische Abteilung für Nuklearmedizin, Universitätsklinik für Radiologie und Nuklearmedizin, Medizinische Universität Wien, Wien, Österreich
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Rathi S, Dhiman RK. Hepatobiliary Quiz (Answers)-15 (2015). J Clin Exp Hepatol 2015; 5:269-71. [PMID: 26628847 PMCID: PMC4632104 DOI: 10.1016/j.jceh.2015.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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Kalantzis G, Leventouri T, Apte A, Shang C. A computational tool for patient specific dosimetry and radiobiological modeling of selective internal radiation therapy with (90)Y microspheres. Appl Radiat Isot 2015; 105:123-129. [PMID: 26296058 DOI: 10.1016/j.apradiso.2015.08.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Revised: 05/07/2015] [Accepted: 08/10/2015] [Indexed: 11/18/2022]
Abstract
In recent years we have witnessed tremendous progress in selective internal radiation therapy. In clinical practice, quite often, radionuclide therapy is planned using simple models based on standard activity values or activity administered per unit body weight or surface area in spite of the admission that radiation-dose methods provide more accurate dosimetric results. To address that issue, the authors developed a Matlab-based computational software, named Patient Specific Yttrium-90 Dosimetry Toolkit (PSYDT). PSYDT was designed for patient specific voxel-based dosimetric calculations and radiobiological modeling of selective internal radiation therapy with (90)Y microspheres. The developed toolkit is composed of three dimensional dose calculations for both bremsstrahlung and beta emissions. Subsequently, radiobiological modeling is performed on a per-voxel basis and cumulative dose volume histograms (DVHs) are generated. In this report we describe the functionality and visualization features of PSYDT.
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Affiliation(s)
- Georgios Kalantzis
- Florida Atlantic University, Department of Physics, Boca Raton, FL 33431, United States
| | - Theodora Leventouri
- Florida Atlantic University, Department of Physics, Boca Raton, FL 33431, United States
| | - Aditiya Apte
- Memorial Sloan Kettering Cancer Center, Department of Medical Physics, NY 10065, United States
| | - Charles Shang
- Florida Atlantic University, Department of Physics, Boca Raton, FL 33431, United States; Lynn Cancer Institute, Department of Radiation Oncology, Boca Raton, FL 33486, United States
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41
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Woo HY, Heo J. New perspectives on the management of hepatocellular carcinoma with portal vein thrombosis. Clin Mol Hepatol 2015; 21:115-21. [PMID: 26157747 PMCID: PMC4493353 DOI: 10.3350/cmh.2015.21.2.115] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Accepted: 05/17/2015] [Indexed: 02/06/2023] Open
Abstract
Despite advances in the treatment of hepatocellular carcinoma (HCC), managing HCC with portal vein thrombosis (PVT) remains challenging. PVT is present in 10-40% of HCC cases at the time of diagnosis and its therapeutic options are very limited. Current guidelines mainly recommend sorafenib for advanced HCC with PVT, but surgery, transarterial chemoemolization, external radiation therapy, radioembolization, transarterial infusion chemotherapy, and combination therapy are also still used. Furthermore, several new emerging therapies such as the administration of immunotherapeutic agents and oncolytic viruses are under investigation. This comprehensive literature review presents current and future management options with their relative advantages and disadvantages and summary data on overall survival.
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Affiliation(s)
- Hyun Young Woo
- Department of Internal Medicine, College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Jeong Heo
- Department of Internal Medicine, College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, Korea
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Chung SR, Kim JH, Yoon HK, Ko GY, Gwon DI, Shin JH, Song HY, Ko HK, Yoon SM. Combined Cisplatin-Based Chemoembolization and Radiation Therapy for Hepatocellular Carcinoma Invading the Main Portal Vein. J Vasc Interv Radiol 2015; 26:1130-8. [PMID: 26119202 DOI: 10.1016/j.jvir.2015.05.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Revised: 04/11/2015] [Accepted: 05/04/2015] [Indexed: 02/08/2023] Open
Abstract
PURPOSE To evaluate the safety and survival outcome of chemoembolization plus radiation therapy (RT) in patients with hepatocellular carcinoma (HCC) with main portal vein (PV) tumor thrombosis. MATERIALS AND METHODS This retrospective study evaluated 151 patients with HCC and main PV involvement (101 with Child-Pugh class A liver function and 50 with Child-Pugh class B liver function) treated with combined cisplatin-based chemoembolization and RT. Medical records, imaging, and laboratory studies were reviewed, and complications, survival, and mortality rates were determined. RESULTS After chemoembolization, major complications occurred in 19.9% of patients, with the rate of major complications significantly higher in Child-Pugh class B cases than in Child-Pugh class A cases (32% vs 13.9%; P = .016). The 30-day mortality rate was 0.7%. One hundred forty-seven patients received adjuvant RT an average of 17.4 days after chemoembolization for main PV tumor thrombosis. Adjuvant RT could not be performed in four patients because of intolerance of the initial chemoembolization. There were no major complications after RT. The objective tumor response at 6 months was 25.2%, with a median survival of 12 months (14 mo in Child-Pugh class A cases and 8 mo in Child-Pugh class B cases). Patients with Child-Pugh class B liver function with extrahepatic metastases, no tumor response, and absence of second-line sorafenib treatment had poor survival. CONCLUSIONS Chemoembolization combined with RT improves survival, with a median survival of 12 months in patients with HCC with main PV involvement.
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Affiliation(s)
- Sae Rom Chung
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Song pa-gu, Seoul 138-736, Republic of Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Song pa-gu, Seoul 138-736, Republic of Korea.
| | - Hyun-Ki Yoon
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Song pa-gu, Seoul 138-736, Republic of Korea
| | - Gi-Young Ko
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Song pa-gu, Seoul 138-736, Republic of Korea
| | - Dong Il Gwon
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Song pa-gu, Seoul 138-736, Republic of Korea
| | - Ji Hoon Shin
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Song pa-gu, Seoul 138-736, Republic of Korea
| | - Ho-Young Song
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Song pa-gu, Seoul 138-736, Republic of Korea
| | - Heung Kyu Ko
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Song pa-gu, Seoul 138-736, Republic of Korea
| | - Sang Min Yoon
- Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Song pa-gu, Seoul 138-736, Republic of Korea
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Roshan HR, Azarm A, Mahmoudian B, Islamian JP. Advances in SPECT for Optimizing the Liver Tumors Radioembolization Using Yttrium-90 Microspheres. World J Nucl Med 2015; 14:75-80. [PMID: 26097416 PMCID: PMC4455176 DOI: 10.4103/1450-1147.157120] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Radioembolization (RE) with Yttrium-90 ((90)Y) microspheres is an effective treatment for unresectable liver tumors. The activity of the microspheres to be administered should be calculated based on the type of microspheres. Technetium-99m macroaggregated albumin ((99m)Tc-MAA) single photon emission computed tomography/computed tomography (SPECT/CT) is a reliable assessment before RE to ensure the safe delivery of microspheres into the target. (90)Y bremsstrahlung SPECT imaging as a posttherapeutic assessment approach enables the reliable determination of absorbed dose, which is indispensable for the verification of treatment efficacy. This article intends to provide a review of the methods of optimizing (90)Y bremsstrahlung SPECT imaging to improve the treatment efficacy of liver tumor RE using (90)Y microspheres.
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Affiliation(s)
- Hoda Rezaei Roshan
- Department of Medical Physics, Nuclear Medicine Unit, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahmadreza Azarm
- Department of Medical Physics, Nuclear Medicine Unit, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Babak Mahmoudian
- Department of Radiology, Nuclear Medicine Unit, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Jalil Pirayesh Islamian
- Department of Medical Physics, Nuclear Medicine Unit, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Mazzoccoli G, Tarquini R, Valoriani A, Oben J, Vinciguerra M, Marra F. Management strategies for hepatocellular carcinoma: old certainties and new realities. Clin Exp Med 2015; 16:243-56. [PMID: 26077653 DOI: 10.1007/s10238-015-0368-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 06/04/2015] [Indexed: 12/18/2022]
Abstract
Hepatocellular carcinoma (HCC) is a highly prevalent disease ranking among the ten most common cancers worldwide with increasing trend of incidence in most developed countries. The great healthcare costs and economic burden of HCC dictate proper preventive interventions as well as surveillance and screening programs to decrease disease incidence and allow early diagnosis. HCC treatment outcomes are affected by several variables, including liver function, patient's performance status, and tumor stage. In line with the Barcelona Clinic Liver Cancer (BCLC) staging curative treatments, such as surgery or radio-frequency ablation, are indicated in early-stage HCC (BCLC-A), and the noncurative treatments are indicated in intermediate and advanced stages of HCC (BCLC-B, C). Transarterial chemoembolization (TACE) represents the treatment of choice for intermediate-stage HCC with Child-Pugh A cirrhosis, and the long-term survival after liver transplantation is inferior to that of early-stage HCCs. In advanced-stage HCC or when complete necrosis is not achieved or early recurrence after TACE develops, individualized treatments such as systemic treatment or combined radiation therapy are indicated. The increasing knowledge of the genomic landscape of HCC and the development of molecular-targeted therapies is heading toward expanding the armamentarium for HCC management.
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Affiliation(s)
- Gianluigi Mazzoccoli
- Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
| | - Roberto Tarquini
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.,Inter-company Department for Continuity Assistance, School of Medicine, University of Florence, Florence, Italy.,San Giuseppe Hospital, Empoli, Italy
| | - Alice Valoriani
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.,Inter-company Department for Continuity Assistance, School of Medicine, University of Florence, Florence, Italy.,San Giuseppe Hospital, Empoli, Italy
| | - Jude Oben
- University College London (UCL) - Institute for Liver and Digestive Health, Division of Medicine, Royal Free Hospital, London, UK
| | - Manlio Vinciguerra
- University College London (UCL) - Institute for Liver and Digestive Health, Division of Medicine, Royal Free Hospital, London, UK.,Istituto EuroMEditerraneo di Scienza e Tecnologia (IEMEST), Palermo, Italy.,School of Science and Technology, Nottingham Trent University, Nottingham, UK
| | - Fabio Marra
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
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De Robertis R, Tinazzi Martini P, Demozzi E, Puntel G, Ortolani S, Cingarlini S, Ruzzenente A, Guglielmi A, Tortora G, Bassi C, Pederzoli P, D’Onofrio M. Prognostication and response assessment in liver and pancreatic tumors: The new imaging. World J Gastroenterol 2015; 21:6794-6808. [PMID: 26078555 PMCID: PMC4462719 DOI: 10.3748/wjg.v21.i22.6794] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/25/2015] [Accepted: 05/04/2015] [Indexed: 02/06/2023] Open
Abstract
Diffusion-weighted imaging (DWI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) are technical improvements of morphologic imaging that can evaluate functional properties of hepato-bilio-pancreatic tumors during conventional MRI or CT examinations. Nevertheless, the term “functional imaging” is commonly used to describe molecular imaging techniques, as positron emission tomography (PET) CT/MRI, which still represent the most widely used methods for the evaluation of functional properties of solid neoplasms; unlike PET or single photon emission computed tomography, functional imaging techniques applied to conventional MRI/CT examinations do not require the administration of radiolabeled drugs or specific equipments. Moreover, DWI and DCE-MRI can be performed during the same session, thus providing a comprehensive “one-step” morphological and functional evaluation of hepato-bilio-pancreatic tumors. Literature data reveal that functional imaging techniques could be proposed for the evaluation of these tumors before treatment, given that they may improve staging and predict prognosis or clinical outcome. Microscopic changes within neoplastic tissues induced by treatments can be detected and quantified with functional imaging, therefore these techniques could be used also for post-treatment assessment, even at an early stage. The aim of this editorial is to describe possible applications of new functional imaging techniques apart from molecular imaging to hepatic and pancreatic tumors through a review of up-to-date literature data, with a particular emphasis on pathological correlations, prognostic stratification and post-treatment monitoring.
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Abstract
Unresectable liver cancer presents a major problem in the treatment of solid tumors. Transarterial radioembolization is a modern approach toward primary and secondary liver malignancies. The mechanism of action is independent from other therapies that are based on ischemia or chemotoxicity. (90)Y-resin and (90)Y-glass microspheres are commercially available for transarterial radioembolization. Available data on the use of (90)Y-glass microspheres in hepatocellular carcinoma and metastatic disease indicate that this treatment is safe and effective. In hepatocellular carcinoma the results compare well with chemoembolization and might be considered more often. Current data in metastatic disease are promising, but there is a strong need for prospective randomized trials to identify the role of transarterial radioembolization with (90)Y-glass microspheres in metastatic liver disease.
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47
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Vilarinho S, Taddei T. Therapeutic strategies for hepatocellular carcinoma: new advances and challenges. ACTA ACUST UNITED AC 2015; 13:219-34. [PMID: 25791207 DOI: 10.1007/s11938-015-0049-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OPINION STATEMENT Hepatocellular carcinoma (HCC) is the fastest growing malignancy in the USA, and its prognosis remains poor with a 5-year survival around 12 %. Clinical data demonstrate that 85 % of cases occur in individuals with underlying cirrhosis and only 15 % develop in non-cirrhotic livers. Therefore, American and European guidelines recommend routine HCC screening for high-risk individuals (patients with cirrhosis) with abdominal ultrasound every 6 months. Once a lesion is identified or suspected on ultrasound, dynamic imaging is then indicated. The diagnosis of HCC is established in a patient with cirrhosis when a lesion measures at least 1 cm in diameter and demonstrates arterial enhancement and portal venous washout on contrast-enhanced computerized tomography or magnetic resonance imaging. Indeterminate lesions should be followed with surveillance imaging or further investigated with biopsy according to the level of suspicion for malignancy. Given the clinical, pathological, and molecular heterogeneity of HCC, there are multiple therapeutic modalities available. These may be curative, such as surgical resection, liver transplantation, and local ablation, or palliative, such as catheter-directed therapies (transarterial chemo, radio, or bland embolization), and systemic therapy (sorafenib). Patients with a single lesion, good performance status, and preserved liver synthetic function should be offered curative surgical resection or ablation therapy. Patients with HCC and decompensated liver disease should be evaluated and listed for liver transplantation. For unresectable disease or tumor burden precluding transplantation or curative ablation, palliative therapeutic modalities should be offered. Sorafenib is indicated for patients with vascular invasion and/or extra-hepatic metastasis if the estimated life expectancy is more than 3 months. Systemic internal radiation therapy using yttrium-90 microspheres in cases of multifocal bi-lobar disease and/or portal vein occlusion is an emerging therapy. Best supportive care is recommended for patients who lack the hepatic reserve to tolerate therapy.
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Affiliation(s)
- Sílvia Vilarinho
- Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, 1080 LMP, PO Box 208019, New Haven, CT, 06520-8019, USA,
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Keane FK, Tanguturi SK, Zhu AX, Dawson LA, Hong TS. Radiotherapy for liver tumors. Hepat Oncol 2015; 2:133-146. [PMID: 30190993 PMCID: PMC6095425 DOI: 10.2217/hep.15.7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Many patients with primary hepatic malignancies present with advanced disease that is not suitable for surgical resection, orthotopic liver transplantation, or radiofrequency ablation. Outcomes are particularly dismal in patients with large, unresectable tumors and/or tumor venous thrombosis. Liver-directed radiotherapy, including stereotactic body radiotherapy (SBRT), is able to treat a variety of tumor sizes and tumors with venous involvement and has demonstrated excellent safety and control outcomes. SBRT should be considered a standard option in patients with early-stage hepatocellular carcinoma who are not candidates for surgical resection, orthotopic liver transplantation or radiofrequency ablation. SBRT should be strongly considered in patients with larger tumors and/or tumors with tumor venous thrombosis who have adequate liver function. Radiotherapy should remain a focus of hepatocellular carcinoma research.
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Affiliation(s)
- Florence K Keane
- Harvard Radiation Oncology Program, Harvard Medical School, 75 Francis Street, Brigham & Women's Hospital, ASB1 L2, Boston, MA 02215, USA
| | - Shyam K Tanguturi
- Harvard Radiation Oncology Program, Harvard Medical School, 75 Francis Street, Brigham & Women's Hospital, ASB1 L2, Boston, MA 02215, USA
| | - Andrew X Zhu
- Massachusetts General Hospital, Division of Hematology-Oncology, Department of Medicine; 32 Fruit St, Yawkey 7, Boston, MA 02114, USA
| | - Laura A Dawson
- Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, 610 University Avenue, Toronto, ON M5G 2M9, USA
| | - Theodore S Hong
- Massachusetts General Hospital, Department of Radiation Oncology, 32 Fruit St, Yawkey 7, Boston, MA 02114, USA
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49
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Quirk M, Kim YH, Saab S, Lee EW. Management of hepatocellular carcinoma with portal vein thrombosis. World J Gastroenterol 2015; 21:3462-3471. [PMID: 25834310 PMCID: PMC4375567 DOI: 10.3748/wjg.v21.i12.3462] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2014] [Revised: 12/24/2014] [Accepted: 02/05/2015] [Indexed: 02/06/2023] Open
Abstract
Management of hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) is complex and requires an understanding of multiple therapeutic options. PVT is present in 10%-40% of HCC at the time of diagnosis, and is an adverse prognostic factor. Management options are limited, as transplantation is generally contraindicated, and surgical resection is only rarely performed in select centers. Systemic medical therapy with sorafenib has been shown to modestly prolong survival. Transarterial chemoembolization has been performed in select cases but has shown a high incidence of complications. Emerging data on treatment of PVT with Y-90 radioembolization suggest that this modality is well-tolerated and associated with favorable overall survival. Current society guidelines do not yet specifically recommend radioembolization for patients with PVT, but this may change with the development of newer staging systems and treatment algorithms. In this comprehensive literature review, we present current and available management options with the relative advantages, disadvantages and contraindications of these treatment options with summarized data on overall survival.
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50
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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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