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1
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Dupuis M, Dupont A, Pizza S, Vilgrain V, Bando Delaunay A, Lebtahi R, Bouattour M, Ronot M, Grégory J. Prognostic value of early response in predicting survival in hepatocellular carcinoma patients treated with selective internal radiation therapy. Eur Radiol 2025; 35:3181-3191. [PMID: 39702632 DOI: 10.1007/s00330-024-11253-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 11/04/2024] [Accepted: 11/19/2024] [Indexed: 12/21/2024]
Abstract
OBJECTIVES This study evaluates the prognostic value of tumor response on CT at 3 months, assessed by Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and Liver Imaging Reporting and Data System Treatment Response Algorithm (LR-TRA) in patients with hepatocellular carcinoma (HCC) treated with selective internal radiation therapy (SIRT). MATERIALS AND METHODS A retrospective analysis was conducted on 102 HCC patients treated with SIRT between 2018 and 2020. RECIST, mRECIST, and LR-TRA were assessed at 3 months post-SIRT. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier analysis and Cox proportional-hazards models. RESULTS The median age was 71 years, and most patients (90%) had advanced-stage tumors (Barcelona Clinic Liver Cancer-C). After a median follow-up of 32.0 months (95% CI: 16.8-60.9), 60/102 patients died (59%), and 90/102 patients showed tumor progression (88%). Median OS was 20.4 months (95% CI: 15.4-33.0), and median PFS was 14.5 months (95% CI: 6.5-24.5); 1-year OS and PFS rates were 65.6% and 50.7%. Multivariable analysis revealed that early response according to RECIST 1.1 (HR 1.66, p = 0.30), mRECIST (HR 1.40, p = 0.215), and LR-TRA (HR 0.67, p = 0.30) were not predictors of OS. Disease progression evaluated by RECIST (HR 2.55, p < 0.001) and mRECIST (HR 2.53, p < 0.001), bilirubin levels (HR 1.03, p < 0.001), and prothrombin time (HR 0.98, p = 0.005) were predictors of OS. For PFS, neither RECIST nor mRECIST response, disease progression, nor LR-TRA viability were predictors. CONCLUSION In this advanced-stage HCC population, early response assessed by RECIST, mRECIST, and LR-TRA criteria did not predict OS or PFS after SIRT. However, early disease progression and liver function indicators were prognostic factors for OS. KEY POINTS QuestionHow well does early tumor response, assessed at 3 months post-selective internal radiation therapy (SIRT), predict survival in advanced hepatocellular carcinoma (HCC) patients? Findings Early response, assessed by RECIST, mRECIST, and LR-TRA, did not predict overall or progression-free survival; disease progression and liver function indicators were significant predictors. Clinical relevance This study highlights the limitations of early imaging criteria in predicting survival outcomes in advanced HCC post-SIRT, suggesting the need for alternative or complementary prognostic indicators to guide treatment decisions.
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Affiliation(s)
- Michel Dupuis
- Department of Radiology, Beaujon Hospital, AP-HP.Nord, Clichy, France
| | - Axelle Dupont
- Clinical Research, Biostatistics and Epidemiology Department, AP-HP Nord-Université Paris Cité, HUPNVS, Paris, France
| | - Silvia Pizza
- Department of Radiology, Beaujon Hospital, AP-HP.Nord, Clichy, France
| | - Valérie Vilgrain
- Department of Radiology, Beaujon Hospital, AP-HP.Nord, Clichy, France
- Université Paris Cité, FHU MOSAIC, INSERM U1149 "Centre de Recherche sur l'Inflammation", CRI, Paris, France
| | - Aurélie Bando Delaunay
- Department of Nuclear Medicine, Beaujon Hospital, AP-HP.Nord, Clichy, France
- Université Paris Cité, INSERM U1149 "Centre de Recherche sur l'Inflammation", CRI, Paris, France
| | - Rachida Lebtahi
- Department of Nuclear Medicine, Beaujon Hospital, AP-HP.Nord, Clichy, France
- Université Paris Cité, INSERM U1149 "Centre de Recherche sur l'Inflammation", CRI, Paris, France
| | | | - Maxime Ronot
- Department of Radiology, Beaujon Hospital, AP-HP.Nord, Clichy, France
- Université Paris Cité, FHU MOSAIC, INSERM U1149 "Centre de Recherche sur l'Inflammation", CRI, Paris, France
| | - Jules Grégory
- Department of Radiology, Beaujon Hospital, AP-HP.Nord, Clichy, France.
- Université Paris Cité, FHU MOSAIC, INSERM U1149 "Centre de Recherche sur l'Inflammation", CRI, Paris, France.
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2
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Vogel A, Chan SL, Dawson LA, Kelley RK, Llovet JM, Meyer T, Ricke J, Rimassa L, Sapisochin G, Vilgrain V, Zucman-Rossi J, Ducreux M. Hepatocellular carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2025; 36:491-506. [PMID: 39986353 DOI: 10.1016/j.annonc.2025.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 02/10/2025] [Accepted: 02/11/2025] [Indexed: 02/24/2025] Open
Affiliation(s)
- A Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Division of Hepatology, Toronto General Hospital, Toronto, Canada; Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada
| | - S L Chan
- State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Sir YK Pao Centre for Cancer, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - L A Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - R K Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, USA
| | - J M Llovet
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, USA; Liver Cancer Translational Research Group, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
| | - T Meyer
- Department of Oncology, Royal Free Hospital, London, UK; UCL Cancer Institute, University College London, London, UK
| | - J Ricke
- Klinik und Poliklinik für Radiologie, Ludwig-Maximilians-Universität München, Munich, Germany
| | - L Rimassa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - G Sapisochin
- Department of Surgery, University of Toronto, Toronto, Canada
| | - V Vilgrain
- Centre de Recherche sur l'Inflammation U 1149, Université Paris Cité, Paris, France; Department of Radiology, Beaujon Hospital, APHP Nord, Clichy, France
| | - J Zucman-Rossi
- Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, INSERM, Paris, France
| | - M Ducreux
- INSERM U1279, Université Paris-Saclay, Villejuif, France; Department of Cancer Medicine, Gustave Roussy, Villejuif, France
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3
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Chen H, Xiong Y, Teng M, Li Y, Zhang D, Ren Y, Li Z, Liu H, Wen X, Li Z, Zhang Y, Askari Rizvi SF, Zhuang R, Huang J, Li S, Mao J, Cheng H, Liu G. A preclinical and first-in-human study of superstable homogeneous radiolipiodol for revolutionizing interventional diagnosis and treatment of hepatocellular carcinoma. Acta Pharm Sin B 2025. [DOI: 10.1016/j.apsb.2025.02.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2025] Open
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4
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Susman S, Santoso B, Makary MS. Locoregional Therapies for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease. Biomedicines 2024; 12:2226. [PMID: 39457538 PMCID: PMC11504147 DOI: 10.3390/biomedicines12102226] [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: 09/01/2024] [Revised: 09/17/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with an average five-year survival rate in the US of 19.6%. With the advent of HBV and HCV treatment and prevention, along with the rising rates of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are set to overtake infectious causes as the most common cause of HCC. While surgical resection and transplantation can be curative when amenable, the disease is most commonly unresectable on presentation, and other treatment approaches are the mainstay of therapy. In these patients, locoregional therapies have evolved as a vital tool in both palliation for advanced disease and as a bridge to surgical resection and transplantation. In this review, we will be exploring the primary locoregional therapies for HCC in patients with NAFLD, including transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial radioembolization (TARE), and percutaneous ablation.
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Affiliation(s)
- Stephen Susman
- Department of Radiology, Yale University Medical Center, New Haven, CT 06510, USA
| | - Breanna Santoso
- Heritage College of Osteopathic Medicine, Ohio University, Dublin, OH 43016, USA
| | - Mina S. Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43202, USA
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5
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Zhou MT, Zhang P, Mao Q, Wei XQ, Yang L, Zhang XM. Current research status of transarterial therapies for hepatocellular carcinoma. World J Gastrointest Oncol 2024; 16:3752-3760. [PMID: 39350995 PMCID: PMC11438772 DOI: 10.4251/wjgo.v16.i9.3752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 05/22/2024] [Accepted: 05/30/2024] [Indexed: 09/09/2024] Open
Abstract
With continuous advancements in interventional radiology, considerable progress has been made in transarterial therapies for hepatocellular carcinoma (HCC) in recent years, and an increasing number of research papers on transarterial therapies for HCC have been published. In this editorial, we comment on the article by Ma et al published in the recent issue of the World Journal of Gastro intestinal Oncology: "Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC". We focus specifically on the current research status and future directions of transarterial therapies. In the future, more studies are needed to determine the optimal transarterial local treatment for HCC. With the emergence of checkpoint immunotherapy modalities, it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.
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Affiliation(s)
- Mao-Ting Zhou
- Department of Radiology, Interventional Medical Center, Science and Technology Innovation Center, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Peng Zhang
- Department of Radiology, Interventional Medical Center, Science and Technology Innovation Center, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Qi Mao
- Department of Radiology, Interventional Medical Center, Science and Technology Innovation Center, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Xiao-Qin Wei
- School of Medical Imaging, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Lin Yang
- Department of Radiology, Interventional Medical Center, Science and Technology Innovation Center, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Xiao-Ming Zhang
- Department of Radiology, Interventional Medical Center, Science and Technology Innovation Center, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
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Hadjivassiliou A, Hou X, Cardarelli-Leite L, Klyuzhin IS, Bénard F, Klass D, Ho SGF, Rahmim A, Liu D. Contralateral Hypertrophy Post Yttrium-90 Transarterial Radioembolization in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombus. Cureus 2024; 16:e59260. [PMID: 38813339 PMCID: PMC11135002 DOI: 10.7759/cureus.59260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/28/2024] [Indexed: 05/31/2024] Open
Abstract
Objectives Contralateral hypertrophy of non-irradiated liver following Yttrium-90 (90Y) transarterial radioembolization (TARE) is increasingly recognized as an option to facilitate curative surgical resection in patients that would otherwise not be surgical candidates due to a small future liver remnant (FLR). This study aimed to investigate the correlation between patient features and liver hypertrophy and identify potential predictors for liver growth in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) undergoing TARE. Methodology Twenty-three patients with HCC and PVTT were included. Contralateral liver hypertrophy was assessed at six months posttreatment based on CT or MRI imaging. Thirteen patient features were selected for statistical and prediction analysis. Univariate Spearman correlation and analysis of variance (ANOVA) tests were performed. Subsequently, four feature-selection methods based on multivariate analysis were used to improve model generalization performance. The selected features were applied to train linear regression models, with fivefold cross-validation to assess the performance of the predicted models. Results The ratio of disease-free target liver volume to spared liver volume and total liver volume showed the highest correlations with contralateral hypertrophy (P-values = 0.03 and 0.05, respectively). In three out of four feature-selection methods, the feature of disease-free target liver volume to total liver volume ratio was selected, having positive correlations with the outcome and suggesting that more hypertrophy may be expected when more volume of disease-free liver is irradiated. Conclusions Contralateral hypertrophy post-90Y TARE can be an option for facilitating surgical resection in patients with otherwise small FLR.
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Affiliation(s)
| | - Xinchi Hou
- Department of Functional Imaging, BC Cancer Research Institute, Vancouver, CAN
| | | | - Ivan S Klyuzhin
- Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, CAN
| | - François Bénard
- Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, CAN
- Department of Radiology, University of British Columbia, Vancouver, CAN
- Department of Functional Imaging, BC Cancer, Vancouver, CAN
| | - Darren Klass
- Department of Radiology, University of British Columbia, Vancouver, CAN
| | - Stephen G F Ho
- Department of Radiology, University of British Columbia, Vancouver, CAN
| | - Arman Rahmim
- Department of Radiology, University of British Columbia, Vancouver, CAN
- Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, CAN
| | - David Liu
- Department of Radiology, University of British Columbia, Vancouver, CAN
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Cabibbo G, Daniele B, Borzio M, Casadei-Gardini A, Cillo U, Colli A, Conforti M, Dadduzio V, Dionisi F, Farinati F, Gardini I, Giannini EG, Golfieri R, Guido M, Mega A, Cinquini M, Piscaglia F, Rimassa L, Romanini L, Pecorelli A, Sacco R, Scorsetti M, Viganò L, Vitale A, Trevisani F. Multidisciplinary treatment of hepatocellular carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part II - Non-surgical treatments. Dig Liver Dis 2024; 56:394-405. [PMID: 38052656 DOI: 10.1016/j.dld.2023.10.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 10/13/2023] [Accepted: 10/30/2023] [Indexed: 12/07/2023]
Abstract
Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of its management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the second part of guidelines, focused on the multidisciplinary tumor board of experts and non-surgical treatments of HCC.
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Affiliation(s)
- Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Gastroenterology Unit, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone", Palermo, Italy.
| | - Bruno Daniele
- Oncology Unit, Ospedale del Mare, ASL Napoli 1 Centro, Napoli, Italy
| | - Mauro Borzio
- Centro Diagnostico Italiano (CDI), Milano, Italy
| | - Andrea Casadei-Gardini
- Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
| | - Umberto Cillo
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Agostino Colli
- Dipartimento di Medicina Trasfusionale ed Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | | | - Vincenzo Dadduzio
- Medical Oncology Unit, "Mons. A.R.Dimiccoli" Hospital, Barletta, ASL BT, Italy
| | - Francesco Dionisi
- Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute - Rome, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; Gastroenterology Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy
| | - Ivan Gardini
- EpaC Onlus, Italian Liver Patient Association, Turin, Italy
| | - Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Rita Golfieri
- Alma Mater Studiorum" Bologna University, Bologna, Italy; Radiology Unit Madre Fortunata Toniolo Private Hospital, coordinator of Radiology centers Medipass Bologna, Bologna, Italy
| | - Maria Guido
- Department of Medicine, University of Padova, Padova - Italy
| | - Andrea Mega
- Department of Gastronterology, Regional Hospital Bolzano, Italy
| | - Michela Cinquini
- Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milano, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Laura Romanini
- Radiology Unit, Ospedale di Cremona, ASST Cremona, Cremona, Italy
| | - Anna Pecorelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, Italy
| | - Marta Scorsetti
- Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Milan, Italy; Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Luca Viganò
- Hepatobiliary Unit, Department of Minimally Invasive General & Oncologic Surgery, Humanitas Gavazzeni University Hospital, Viale M. Gavazzeni 21, 24125 Bergamo, Italy; Department of Biomedical Sciences, Humanitas University, Viale Rita Levi Montalcini 4, 20090 Milan, Italy
| | - Alessandro Vitale
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
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Busse NC, Al‐Ghazi MSAL, Abi‐Jaoudeh N, Alvarez D, Ayan AS, Chen E, Chuong MD, Dezarn WA, Enger SA, Graves SA, Hobbs RF, Jafari ME, Kim SP, Maughan NM, Polemi AM, Stickel JR. AAPM Medical Physics Practice Guideline 14.a: Yttrium-90 microsphere radioembolization. J Appl Clin Med Phys 2024; 25:e14157. [PMID: 37820316 PMCID: PMC10860558 DOI: 10.1002/acm2.14157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 06/19/2023] [Accepted: 08/25/2023] [Indexed: 10/13/2023] Open
Abstract
Radioembolization using Yttrium-90 (90 Y) microspheres is widely used to treat primary and metastatic liver tumors. The present work provides minimum practice guidelines for establishing and supporting such a program. Medical physicists play a key role in patient and staff safety during these procedures. Products currently available are identified and their properties and suppliers summarized. Appropriateness for use is the domain of the treating physician. Patient work up starts with pre-treatment imaging. First, a mapping study using Technetium-99m (Tc-99m ) is carried out to quantify the lung shunt fraction (LSF) and to characterize the vascular supply of the liver. An MRI, CT, or a PET-CT scan is used to obtain information on the tumor burden. The tumor volume, LSF, tumor histology, and other pertinent patient characteristics are used to decide the type and quantity of 90 Y to be ordered. On the day of treatment, the appropriate dose is assayed using a dose calibrator with a calibration traceable to a national standard. In the treatment suite, the care team led by an interventional radiologist delivers the dose using real-time image guidance. The treatment suite is posted as a radioactive area during the procedure and staff wear radiation dosimeters. The treatment room, patient, and staff are surveyed post-procedure. The dose delivered to the patient is determined from the ratio of pre-treatment and residual waste exposure rate measurements. Establishing such a treatment modality is a major undertaking requiring an institutional radioactive materials license amendment complying with appropriate federal and state radiation regulations and appropriate staff training commensurate with their respective role and function in the planning and delivery of the procedure. Training, documentation, and areas for potential failure modes are identified and guidance is provided to ameliorate them.
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Affiliation(s)
| | | | - Nadine Abi‐Jaoudeh
- Department of Radiological SciencesUniversity of CaliforniaIrvineCaliforniaUSA
| | - Diane Alvarez
- Baptist HospitalMiami Cancer InstituteMiamiFloridaUSA
| | - Ahmet S. Ayan
- Department of Radiation OncologyOhio State UniversityColumbusOhioUSA
| | - Erli Chen
- Department of Radiation OncologyCheshire Medical CenterKeeneNew HampshireUSA
| | - Michael D. Chuong
- Department of Radiation OncologyMiami Cancer InstituteMiamiFloridaUSA
| | - William A. Dezarn
- Department of Radiation OncologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | | | | | - Robert F. Hobbs
- Department of Radiation OncologyJohns Hopkins UniversityBaltimoreMarylandUSA
| | - Mary Ellen Jafari
- Diagnostic Physics, Atlantic Health SystemMorristown Medical CenterMorristownNew JerseyUSA
| | - S. Peter Kim
- Medical Physics UnitMcGill UniversityMontrealCanada
| | - Nichole M. Maughan
- Department of Radiation OncologyWashington University in St. LouisSaint LouisMissouriUSA
| | - Andrew M. Polemi
- Department of RadiologyUniversity of VirginiaCharlottesvilleVirginiaUSA
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9
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Ozen M, Patel RK. Ablation versus Radiation Segmentectomy for Small Liver Tumors. Semin Intervent Radiol 2023; 40:511-514. [PMID: 38274221 PMCID: PMC10807957 DOI: 10.1055/s-0043-1777714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Abstract
Hepatocellular carcinoma (HCC) is a liver malignancy that affects more than a million people worldwide with a complex multifactorial etiology. After the diagnosis of HCC is made, physicians establish management using the Barcelona Clinic Liver Cancer (BCLC) guidelines revolving around tumor stage, liver function, performance status, and patient preferences. According to recent updates to these guidelines, thermal ablation is the second-best curative option apart from surgical resection for small HCC (< 2 cm). While thermal ablation is standard of care, recent studies have suggested that radiation segmentectomy (RS) has similar outcomes, limited hepatotoxicity, and ultimately a cost-efficient approach. Although there is limited literature on RS, this article compares ablation techniques against radiation segmentectomy for small HCC tumors.
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Affiliation(s)
- Merve Ozen
- Department of Radiology, University of Kentucky College of Medicine, Lexington, Kentucky
| | - Ronak K. Patel
- University of Kentucky College of Medicine, Lexington, Kentucky
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10
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Serhal M, Gordon AC, Brown DB, Toskich BB, Lewandowski RJ. Transarterial Radioembolization: Overview of Radioembolic Devices. Semin Intervent Radiol 2023; 40:461-466. [PMID: 37927522 PMCID: PMC10622244 DOI: 10.1055/s-0043-1772814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2023]
Affiliation(s)
- Muhamad Serhal
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
| | - Andrew C. Gordon
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
| | - Daniel B. Brown
- Division of Interventional Radiology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Beau B. Toskich
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, Florida
| | - Robert J. Lewandowski
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
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11
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Zeng H, Zhou C, Chen X, Hu L, Su K, Guo L, Han Y. Comparison of the efficacy and safety of selective internal radiotherapy and sorafenib alone or combined for hepatocellular carcinoma: a systematic review and Bayesian network meta-analysis. Clin Exp Med 2023; 23:2141-2150. [PMID: 36737488 PMCID: PMC10543878 DOI: 10.1007/s10238-023-00997-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 01/12/2023] [Indexed: 02/05/2023]
Abstract
BACKGROUND Selective internal radiation therapy (SIRT) is a developing technique and its efficacy and modality of application in hepatocellular carcinoma (HCC) are still controversial. This network meta-analysis aims to determine whether the efficacy and safety of SIRT alone and in combination are superior to that of sorafenib. METHODS Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched before August 2022. Cochrane Randomized Trial Risk of Bias Assessment Tool and the Newcastle-Ottawa scale were used to assess the quality. The outcomes of interest included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). RESULTS A total of 9 eligible trials involving 1954 patients were included, and SIRT ranked first among the three treatment modalities in terms of both OS (probability, 52.3%) and PFS (probability, 68.6%). The combination of SIRT and sorafenib did not improve OS or PFS in patients with HCC. Although the combination of SIRT and sorafenib did not raise the risk of grade 3 or higher AEs, it may have introduced more AEs than either alone. CONCLUSIONS SIRT alone was found to be superior to sorafenib and the combination of the two in improving OS or PFS in patients with non-surgical HCC, especially in patients with combined portal vein tumor thrombus. The AEs induced by SIRT were different from those of sorafenib, but the overall toxicity was manageable, the combination of the two may cause an increase in the types of AEs that occur.
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Affiliation(s)
- Hao Zeng
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | | | - Xiaojing Chen
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Lanxin Hu
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Ke Su
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Lu Guo
- Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yunwei Han
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
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12
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Shi L, Li D, Tong Q, Jia G, Li X, Zhang L, Han Q, Li R, Zuo C, Zhang W, Li X. Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials. J Nanobiotechnology 2023; 21:278. [PMID: 37598140 PMCID: PMC10439629 DOI: 10.1186/s12951-023-02032-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 07/29/2023] [Indexed: 08/21/2023] Open
Abstract
BACKGROUND The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate the performance of drug loading and releasing. Embolization efficiency was evaluated in rat caudal artery and rabbit auricular artery, and the in vivo distribution of iodinated SFMS (125I/131I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with 131I-SFMS was performed on rat models with liver cancer. The whole procedure of selective internal radiation was recorded with SPECT/CT, and the therapeutic effects were evaluated with 18 F-FDG PET/CT. Lastly, the enzymatic degradation was recorded and followed with the evaluation of particle size on clearance of sub-micron silk fibroin. RESULTS SFMS were of smooth surface and regular shape with pervasive pores on the surface and inside the microspheres, and of suitable size range for TAE. Drug-loading functionalized SFMS with chemotherapy or radio-sensitization, and the enhanced therapeutic effects were proved in treating HUH-7 cells as lasting doxorubicin release or more lethal radiation. For artery embolization, SFMS effectively blocked the blood supply; when 131I-SFMS serving as the embolic agent, the good labeling stability and embolization performance guaranteed the favorable therapeutic effects in treating in situ liver tumor. At the 5th day post TARE with 37 MBq/3 mg 131I-SFMS per mice, tumor activity was quickly inhibited to a comparable glucose metabolism level with surrounding normal liver. More importantly, for the fragments of biodegradable SFMS, smaller sized SF (< 800 nm) metabolized in gastrointestinal tract and excreted by the urinary system, while SF (> 800 nm) entered the liver within 72 h for further metabolism. CONCLUSION The feasibility of SFMS as degradable TARE agent for liver cancer was primarily proved as providing multiple therapeutic potentials.
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Affiliation(s)
- Linlin Shi
- Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, 310005, Zhejiang, China
| | - Danni Li
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, 200433, China
| | - Qianqian Tong
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, 200433, China
| | - Guorong Jia
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, 200433, China
| | - Xiaohong Li
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, 200433, China
| | - Lan Zhang
- Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China
| | - Qingqing Han
- Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, 310005, Zhejiang, China
| | - Rou Li
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, 200433, China.
| | - Changjing Zuo
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, 200433, China.
| | - Wei Zhang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| | - Xiao Li
- Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, 200433, China.
- Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.
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13
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Posa A, Contegiacomo A, Ponziani FR, Punzi E, Mazza G, Scrofani A, Pompili M, Goldberg SN, Natale L, Gasbarrini A, Sala E, Iezzi R. Interventional Oncology and Immuno-Oncology: Current Challenges and Future Trends. Int J Mol Sci 2023; 24:ijms24087344. [PMID: 37108507 PMCID: PMC10138371 DOI: 10.3390/ijms24087344] [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: 03/27/2023] [Revised: 04/07/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
Personalized cancer treatments help to deliver tailored and biologically driven therapies for cancer patients. Interventional oncology techniques are able to treat malignancies in a locoregional fashion, with a variety of mechanisms of action leading to tumor necrosis. Tumor destruction determines a great availability of tumor antigens that can be recognized by the immune system, potentially triggering an immune response. The advent of immunotherapy in cancer care, with the introduction of specific immune checkpoint inhibitors, has led to the investigation of the synergy of these drugs when used in combination with interventional oncology treatments. The aim of this paper is to review the most recent advances in the field of interventional oncology locoregional treatments and their interactions with immunotherapy.
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Affiliation(s)
- Alessandro Posa
- Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
| | - Andrea Contegiacomo
- Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy
| | - Ernesto Punzi
- Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
| | - Giulia Mazza
- Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
| | - Annarita Scrofani
- Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
| | - Maurizio Pompili
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy
| | - Shraga Nahum Goldberg
- Division of Image-Guided Therapy, Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem 12000, Israel
| | - Luigi Natale
- Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy
| | - Evis Sala
- Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy
| | - Roberto Iezzi
- Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy
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Portal Vein Embolization: Rationale, Techniques, and Outcomes to Maximize Remnant Liver Hypertrophy with a Focus on Contemporary Strategies. Life (Basel) 2023; 13:life13020279. [PMID: 36836638 PMCID: PMC9959051 DOI: 10.3390/life13020279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/11/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
Hepatectomy remains the gold standard for curative therapy for patients with limited primary or metastatic hepatic tumors as it offers the best survival rates. In recent years, the indication for partial hepatectomy has evolved away from what will be removed from the patient to the volume and function of the future liver remnant (FLR), i.e., what will remain. With this regard, liver regeneration strategies have become paramount in transforming patients who previously had poor prognoses into ones who, after major hepatic resection with negative margins, have had their risk of post-hepatectomy liver failure minimized. Preoperative portal vein embolization (PVE) via the purposeful occlusion of select portal vein branches to promote contralateral hepatic lobar hypertrophy has become the accepted standard for liver regeneration. Advances in embolic materials, selection of treatment approaches, and PVE with hepatic venous deprivation or concurrent transcatheter arterial embolization/radioembolization are all active areas of research. To date, the optimal combination of embolic material to maximize FLR growth is not yet known. Knowledge of hepatic segmentation and portal venous anatomy is essential before performing PVE. In addition, the indications for PVE, the methods for assessing hepatic lobar hypertrophy, and the possible complications of PVE need to be fully understood before undertaking the procedure. The goal of this article is to discuss the rationale, indications, techniques, and outcomes of PVE before major hepatectomy.
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15
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Couillard AB, Knott EA, Zlevor AM, Mezrich JD, Cristescu MM, Agarwal P, Ziemlewicz TJ, Longhurst C, Lubner MG, Hinshaw JL, Said A, Laeseke PF, Lucey MR, Rice JP, Foley D, Al-Adra D, Lee FT. Microwave ablation as bridging to liver transplant for patients with hepatocellular carcinoma: a single-center retrospective analysis. J Vasc Interv Radiol 2022; 33:1045-1053. [PMID: 35667580 DOI: 10.1016/j.jvir.2022.05.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 05/03/2022] [Accepted: 05/27/2022] [Indexed: 11/28/2022] Open
Abstract
PURPOSE To evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant. MATERIALS AND METHODS This retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and listed for liver transplantation at a single medical center between 2011 and 2019. Overall survival rate status-post liver transplant, waitlist retention and disease progression were evaluated using Kaplan-Meier techniques. RESULTS Of 88 patients (72M, 16F, mean age 60 years, MELD=11.2) listed for transplant, median waitlist time was 9.4 months (IQR: 5.5 - 18.9). Seventy-one patients (80.7%) received transplant after median wait time of 8.5 months. Seventeen patients (19.3%) were removed from the waitlist, four (4.5%) due to tumors outside of the Milan criteria (HCC-specific dropout). No difference in tumor size or AFP was seen in transplanted vs. non-transplanted patients at time of ablation (2.1 vs. 2.1 cm and 34.4 vs. 34.7 ng/mL for transplanted vs. non-transplanted, respectively, p>0.05). Five of 88 patients (5.1%) experienced adverse events after ablation; however, all recovered. There were no cases of tract seeding. The local tumor progression (LTP) rate was 7.2%. The overall survival status-post liver transplant at 5-years was 76.7% and the disease-specific survival after LT was 89.6% with a median follow-up of 61 months for all patients. CONCLUSION MW ablation appears to be safe and effective for bridging patients with HCC to liver transplant without waitlist removal from seeding, adverse events, or local tumor progression.
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Affiliation(s)
| | - Emily A Knott
- University of Wisconsin-Madison: Department of Radiology
| | - Annie M Zlevor
- University of Wisconsin-Madison: Department of Radiology
| | | | | | | | | | - Colin Longhurst
- Department of Carbone Cancer Center; Department of Biostatistics and Medical Informatics
| | | | - J Louis Hinshaw
- University of Wisconsin-Madison: Department of Radiology; Department of Urology
| | | | - Paul F Laeseke
- University of Wisconsin-Madison: Department of Radiology
| | | | | | | | | | - Fred T Lee
- University of Wisconsin-Madison: Department of Radiology; Department of Urology; Department of Biomedical Engineering.
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16
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Wu X, Ge L, Shen G, He Y, Xu Z, Li D, Mu C, Zhao L, Zhang W. 131I-Labeled Silk Fibroin Microspheres for Radioembolic Therapy of Rat Hepatocellular Carcinoma. ACS APPLIED MATERIALS & INTERFACES 2022; 14:21848-21859. [PMID: 35507826 DOI: 10.1021/acsami.2c00211] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Transarterial radioembolization (TARE) is a promising technology in hepatocellular carcinoma (HCC) therapy, which utilizes radionuclide-labeled microspheres to achieve arterial embolization and internal irradiation. However, the therapeutic effect of liver cancer can be affected by low radionuclide labeling rate and stability, as well as poor biocompatibility, and non-biodegradability of microspheres. Here, 131I-labeled silk fibroin microspheres (131I-SFMs) were developed as radioembolization material for effective TARE therapy against HCC. Silk fibroin rich in 10.03% of tyrosine was extracted from silkworm cocoons and then emulsified and genipin-crosslinked to prepare SFMs. SFMs show a good settlement rate, biodegradability, hemocompatibility, and low cytotoxicity. Afterward, 131I-SFMs were obtained by radiolabeling 131I onto the SFMs through the chloramine-T method. 131I-SFMs possess a high 131I labeling rate of over 84% and good radioactive stability and are thus conducive to internal radiotherapy. Significantly, 131I-SFMs with diameters around 11 μm were successfully radioembolized at the hepatic artery. 131I-SFMs were diffused in the liver, indicating the favorable biodistribution and biosafety in vivo. Based on the combination of embolization and local radiotherapy, the administration of 131I-SFMs shows a favorable inhibitive effect against the progression of HCC. Overall, the newly developed 131I-SFMs as radioembolization microspheres provide a promising application for effective TARE therapy against liver cancer.
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Affiliation(s)
- Xiao Wu
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, P. R. China
| | - Liming Ge
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, P. R. China
| | - Guohua Shen
- Laboratory of Clinical Nuclear Medicine, Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, P. R. China
| | - Ying He
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu 610041, P. R. China
| | - Zhilang Xu
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, P. R. China
| | - Defu Li
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, P. R. China
| | - Changdao Mu
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, P. R. China
| | - Lei Zhao
- Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P. R. China
| | - Wenjie Zhang
- Laboratory of Clinical Nuclear Medicine, Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, P. R. China
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17
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Cazzato RL, Hubelé F, De Marini P, Ouvrard E, Salvadori J, Addeo P, Garnon J, Kurtz JE, Greget M, Mertz L, Goichot B, Gangi A, Imperiale A. Liver-Directed Therapy for Neuroendocrine Metastases: From Interventional Radiology to Nuclear Medicine Procedures. Cancers (Basel) 2021; 13:cancers13246368. [PMID: 34944988 PMCID: PMC8699378 DOI: 10.3390/cancers13246368] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/16/2021] [Accepted: 12/17/2021] [Indexed: 12/25/2022] Open
Abstract
Neuroendocrine neoplasms (NENs) are rare and heterogeneous epithelial tumors most commonly arising from the gastroenteropancreatic (GEP) system. GEP-NENs account for approximately 60% of all NENs, and the small intestine and pancreas represent two most common sites of primary tumor development. Approximately 80% of metastatic patients have secondary liver lesions, and in approximately 50% of patients, the liver is the only metastatic site. The therapeutic strategy depends on the degree of hepatic metastatic invasion, ranging from liver surgery or percutaneous ablation to palliative treatments to reduce both tumor volume and secretion. In patients with grade 1 and 2 NENs, locoregional nonsurgical treatments of liver metastases mainly include percutaneous ablation and endovascular treatments, targeting few or multiple hepatic metastases, respectively. In the present work, we provide a narrative review of the current knowledge on liver-directed therapy for metastasis treatment, including both interventional radiology procedures and nuclear medicine options in NEN patients, taking into account the patient clinical context and both the strengths and limitations of each modality.
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Affiliation(s)
- Roberto Luigi Cazzato
- Interventional Radiology, University Hospitals of Strasbourg, Strasbourg University, 67000 Strasbourg, France; (R.L.C.); (P.D.M.); (J.G.); (M.G.); (A.G.)
- Oncology, Institut de Cancérologie de Strasbourg Europe (ICANS), Strasbourg University, 67200 Strasbourg, France;
| | - Fabrice Hubelé
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie de Strasbourg Europe (ICANS), University Hospitals of Strasbourg, Strasbourg University, 67200 Strasbourg, France; (F.H.); (E.O.)
| | - Pierre De Marini
- Interventional Radiology, University Hospitals of Strasbourg, Strasbourg University, 67000 Strasbourg, France; (R.L.C.); (P.D.M.); (J.G.); (M.G.); (A.G.)
| | - Eric Ouvrard
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie de Strasbourg Europe (ICANS), University Hospitals of Strasbourg, Strasbourg University, 67200 Strasbourg, France; (F.H.); (E.O.)
| | - Julien Salvadori
- Radiophysics, Institut de Cancérologie de Strasbourg Europe (ICANS), 67200 Strasbourg, France;
| | - Pietro Addeo
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Hospitals of Strasbourg, 67200 Strasbourg, France;
| | - Julien Garnon
- Interventional Radiology, University Hospitals of Strasbourg, Strasbourg University, 67000 Strasbourg, France; (R.L.C.); (P.D.M.); (J.G.); (M.G.); (A.G.)
| | - Jean-Emmanuel Kurtz
- Oncology, Institut de Cancérologie de Strasbourg Europe (ICANS), Strasbourg University, 67200 Strasbourg, France;
| | - Michel Greget
- Interventional Radiology, University Hospitals of Strasbourg, Strasbourg University, 67000 Strasbourg, France; (R.L.C.); (P.D.M.); (J.G.); (M.G.); (A.G.)
| | - Luc Mertz
- Radiophysics, University Hospitals of Strasbourg, 67000 Strasbourg, France;
| | - Bernard Goichot
- Internal Medicine, Diabetes and Metabolic Disorders, University Hospitals of Strasbourg, Strasbourg University, 67200 Strasbourg, France;
| | - Afshin Gangi
- Interventional Radiology, University Hospitals of Strasbourg, Strasbourg University, 67000 Strasbourg, France; (R.L.C.); (P.D.M.); (J.G.); (M.G.); (A.G.)
- School of Biomedical Engineering and Imaging Science, King’s College London, Strand, London WC2R 2LS, UK
| | - Alessio Imperiale
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie de Strasbourg Europe (ICANS), University Hospitals of Strasbourg, Strasbourg University, 67200 Strasbourg, France; (F.H.); (E.O.)
- Molecular Imaging—DRHIM, IPHC, UMR 7178, CNRS/Unistra, 67037 Strasbourg, France
- Correspondence: ; Tel.: +33-3-68-76-74-48; Fax: +33-3-68-76-72-56
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18
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Karamchandani DM, Hammad H, Chetty R, Arnold CA. New Kids on the Block. Arch Pathol Lab Med 2021; 145:1569-1584. [PMID: 33571357 DOI: 10.5858/arpa.2020-0535-ra] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2020] [Indexed: 12/31/2022]
Abstract
CONTEXT.— With the increasing development and use of iatrogenic agents, pathologists are encountering more novel foreign materials in retrieved gastrointestinal specimens. These colorful and unusual-appearing foreign materials can pose a diagnostic dilemma to those unaware of their morphology, especially if the relevant clinical history is lacking. OBJECTIVE.— To discuss the histopathologic features, clinical scenarios and significance, and differential diagnosis of relatively recently described, yet quickly expanding, family of iatrogenic agents that can present as foreign materials in gastrointestinal specimens-pharmaceutical fillers (crospovidone and microcrystalline cellulose), submucosal lifting agents (Eleview and ORISE), lanthanum carbonate, hydrophilic polymers, OsmoPrep, yttrium 90 microspheres (SIR-Sphere and TheraSphere), and resins (sodium polystyrene sulfonate, sevelamer, and bile acid sequestrants). DATA SOURCES.— We collate the findings of published literature, including recently published research papers, and authors' personal experiences from clinical sign-out and consult cases. CONCLUSIONS.— Correct identification of these iatrogenic agents is important because the presence of some novel agents can explain the histopathologic findings seen in the background specimen, and specific novel agents can serve as diagnostic clues to prompt the pathologist to consider other important and related diagnoses. Awareness of even biologically inert agents is important for accurate diagnosis and to avoid unnecessary and expensive diagnostic studies.
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Affiliation(s)
- Dipti M Karamchandani
- From the Department of Pathology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania (Karamchandani)
| | - Hazed Hammad
- The Department of Internal Medicine, Division of Gastroenterology and Hepatology (Hammad), University of Colorado, Anschutz Medical Center, Denver
| | - Runjan Chetty
- The Histopathology Department, Brighton & Sussex University Hospitals, Brighton, United Kingdom (Chetty)
| | - Christina A Arnold
- The Department of Pathology (Arnold), University of Colorado, Anschutz Medical Center, Denver
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19
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Updated Survival and Secondary Safety and Efficacy Analyses From CA 209-678: A Phase 2, Open-Label, Single-Center Study of Y90-Radioembolization in Combination With Nivolumab in Asian Patients With Advanced Hepatocellular Carcinoma. Gastroenterol Hepatol (N Y) 2021; 17:18-19. [PMID: 35611266 PMCID: PMC9122048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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20
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Kim GH, Kim JH, Kim PH, Chu HH, Gwon DI, Ko HK. Emerging Trends in the Treatment of Advanced Hepatocellular Carcinoma: A Radiological Perspective. Korean J Radiol 2021; 22:1822-1833. [PMID: 34431250 PMCID: PMC8546136 DOI: 10.3348/kjr.2021.0229] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/17/2021] [Accepted: 06/03/2021] [Indexed: 01/10/2023] Open
Abstract
This is a narrative review of various treatment modalities for advanced hepatocellular carcinoma (HCC), with a focus on recent updates in radiological treatments, as well as novel treatment concepts related to immune checkpoint inhibitors and combination therapies with locoregional treatments. Interventional radiologists have made efforts toward developing alternative and/or combination treatments for first-line systemic treatment of patients with advanced HCC. Locoregional treatments with or without systemic therapy may be considered in the selected patients. Various treatment modalities for advanced HCC are emerging, and several randomized controlled trials, including those of combination treatments with immunotherapy, are ongoing.
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Affiliation(s)
- Gun Ha Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
| | - Pyeong Hwa Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Hee Ho Chu
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Dong Il Gwon
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Heung-Kyu Ko
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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21
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Ness JR, Molvar C. Radioembolization of Intrahepatic Cholangiocarcinoma: Patient Selection, Outcomes, and Competing Therapies. Semin Intervent Radiol 2021; 38:438-444. [PMID: 34629711 DOI: 10.1055/s-0041-1735526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Intrahepatic cholangiocarcinoma is the second most common primary hepatic malignancy and poses a therapeutic challenge owing to its late-stage presentation and treatment-resistant outcomes. Most patients are diagnosed with locally advanced, unresectable disease and are treated with a combination of systemic and local regional therapies. Transarterial radioembolization offers a survival benefit and a favorable side effect profile, with a growing body of evidence to support its use. Herein, we review patient selection and detail outcomes of radioembolization for intrahepatic cholangiocarcinoma, together with mention of competing treatments.
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Affiliation(s)
- Joseph Ray Ness
- Division of Diagnostic Radiology, Department of Radiology, Loyola University Medical Center, Maywood, Illinois
| | - Christopher Molvar
- Division of Diagnostic Radiology, Department of Radiology, Loyola University Medical Center, Maywood, Illinois
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22
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Abstract
Radiation segmentectomy is an yttrium-90 transarterial radioembolization treatment where a high radiation dose is administered to a small volume of liver to achieve a high tumoricidal dose to a target with anatomic surgical precision while sparing surrounding parenchyma. This therapeutic modality is often used to treat hepatocellular carcinoma, and recent studies have demonstrated that radiation segmentectomy is an effective treatment as a neoadjuvant to transplant, resection, or as a standalone treatment. This article provides a review of radiation segmentectomy, indications for treatment, recent outcome data, and guidelines for postprocedural management.
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Affiliation(s)
- Kristina Prachanronarong
- Department of Interventional Radiology, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York
| | - Edward Kim
- Department of Interventional Radiology, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York
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23
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Aramburu J, Antón R, Rodríguez-Fraile M, Sangro B, Bilbao JI. Computational Fluid Dynamics Modeling of Liver Radioembolization: A Review. Cardiovasc Intervent Radiol 2021; 45:12-20. [PMID: 34518913 PMCID: PMC8716346 DOI: 10.1007/s00270-021-02956-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 08/25/2021] [Indexed: 12/16/2022]
Abstract
Yttrium-90 radioembolization (RE) is a widely used transcatheter intraarterial therapy for patients with unresectable liver cancer. In the last decade, computer simulations of hepatic artery hemodynamics during RE have been performed with the aim of better understanding and improving the therapy. In this review, we introduce the concept of computational fluid dynamics (CFD) modeling with a clinical perspective and we review the CFD models used to study RE from the fluid mechanics point of view. Finally, we show what CFD simulations have taught us about the hemodynamics during RE, the current capabilities of CFD simulations of RE, and we suggest some future perspectives.
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Affiliation(s)
- Jorge Aramburu
- Universidad de Navarra, TECNUN Escuela de Ingeniería, 20018, Donostia-San Sebastián, Spain.
| | - Raúl Antón
- Universidad de Navarra, TECNUN Escuela de Ingeniería, 20018, Donostia-San Sebastián, Spain.,IdiSNA, Instituto de Investigación Sanitaria de Navarra, 31008, Pamplona, Spain
| | - Macarena Rodríguez-Fraile
- IdiSNA, Instituto de Investigación Sanitaria de Navarra, 31008, Pamplona, Spain.,Department of Nuclear Medicine, Clínica Universidad de Navarra, 31008, Pamplona, Spain
| | - Bruno Sangro
- IdiSNA, Instituto de Investigación Sanitaria de Navarra, 31008, Pamplona, Spain.,Liver Unit, Clínica Universidad de Navarra and CIBEREHD, 31008, Pamplona, Spain
| | - José Ignacio Bilbao
- IdiSNA, Instituto de Investigación Sanitaria de Navarra, 31008, Pamplona, Spain.,Department of Radiology, Clínica Universidad de Navarra, 31008, Pamplona, Spain
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24
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Delaney LJ, Tantawi M, Wessner CE, Machado P, Forsberg F, Lyshchik A, O'Kane P, Liu JB, Civan J, Tan A, Anton K, Shaw CM, Eisenbrey JR. Predicting Long-Term Hepatocellular Carcinoma Response to Transarterial Radioembolization Using Contrast-Enhanced Ultrasound: Initial Experiences. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:2523-2531. [PMID: 34130880 PMCID: PMC8355136 DOI: 10.1016/j.ultrasmedbio.2021.05.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 02/26/2021] [Accepted: 05/06/2021] [Indexed: 05/12/2023]
Abstract
Conventional cross-sectional imaging done shortly after radioembolization of hepatocellular carcinoma (HCC) does not reliably predict long-term response to treatment. This study evaluated whether quantitative contrast-enhanced ultrasound (CEUS) can predict the long-term response of HCC to yttrium-90 (Y-90) treatment. Fifteen patients underwent CEUS at three time points: immediately following treatment and 1 and 2 wk post-treatment. Response 3-6 mo after treatment was categorized on contrast-enhanced magnetic resonance imaging by two experienced radiologists using the Modified Response Evaluation Criteria in Solid Tumors. CEUS data were analyzed by quantifying tumor perfusion and residual fractional vascularity using time-intensity curves. Patients with stable disease on magnetic resonance imaging had significantly greater fractional vascularity 2 wk post-treatment (65.15%) than those with partial or complete response (13.8 ± 9.9%, p = 0.007, and 14.9 ± 15.4%, p = 0.009, respectively). Complete responders had lower tumor vascularity at 2 wk than at post-operative examination (-38.3 ± 15.4%, p = 0.045). Thus, this pilot study suggests CEUS may provide an earlier indication of Y-90 treatment response than cross-sectional imaging.
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Affiliation(s)
- Lauren J Delaney
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Mohamed Tantawi
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Corinne E Wessner
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Priscilla Machado
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Flemming Forsberg
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Andrej Lyshchik
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Patrick O'Kane
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Ji-Bin Liu
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Jesse Civan
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Allison Tan
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Kevin Anton
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Colette M Shaw
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - John R Eisenbrey
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
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25
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Decoteau MA, Steuterman S, Kurian SM, Case J, Lewis PR, Fisher JS, Schaffer RL, Marsh CL. Mitigation of radiation exposure during surgical hepatectomy after yttrium-90 radioembolization. JOURNAL OF RADIOLOGICAL PROTECTION : OFFICIAL JOURNAL OF THE SOCIETY FOR RADIOLOGICAL PROTECTION 2021; 41:N1-N11. [PMID: 34107455 DOI: 10.1088/1361-6498/ac09c0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 06/09/2021] [Indexed: 06/12/2023]
Abstract
Yttrium-90 (Y-90) radioembolization for the treatment of hepatocellular carcinoma can present safety challenges when transplanting recently treated Y-90 patients. To reduce surgeons' contact with radioactive tissue and remain within occupational dose limits, current guidelines recommend delaying transplants at least 14 days, if possible. We wanted to determine the level of radiation exposure to the transplant surgeon when explanting an irradiated liver before the recommended decay period. Anex-vivoradiation exposure analysis was conducted on the explanted liver of a patient who received Y-90 therapy 46 h prior to orthotopic liver transplant. To estimate exposure to the surgeon's hands, radiation dosimeter rings were placed inside three different surgical glove configurations and exposed to the explanted liver. Estimated radiation doses corrected for Y-90 decay were calculated. Radiation safety gloves performed best, with an average radiation exposure rate of 5.36 mSV h-1in the static hand position, an 83% reduction in exposure over controls with no glove (31.31 mSv h-1). Interestingly, non-radiation safety gloves also demonstrated reduced exposure rates, well below occupational regulation limits. Handling of Y-90 radiated organs within the immediate post-treatment period can be done safely and does not exceed federal occupational dose limits if appropriate gloves and necessary precautions are exercised.
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Affiliation(s)
- Mary A Decoteau
- Scripps Center for Organ and Cell Transplantation, Scripps Clinic and Scripps Green Hospital, 10666 N Torrey Pines Road, 200N, La Jolla, CA 92037, United States of America
- Department of General Surgery, Naval Medical Center San Diego, San Diego, CA, United States of America
| | - Steven Steuterman
- Scripps Center for Organ and Cell Transplantation, Scripps Clinic and Scripps Green Hospital, 10666 N Torrey Pines Road, 200N, La Jolla, CA 92037, United States of America
- Department of Medical Physics and Radiation Safety, Scripps Clinic and Scripps Green Hospital, La Jolla, CA, United States of America
| | - Sunil M Kurian
- Scripps Center for Organ and Cell Transplantation, Scripps Clinic and Scripps Green Hospital, 10666 N Torrey Pines Road, 200N, La Jolla, CA 92037, United States of America
- Scripps Clinic Bio-Repository and Bio-Informatics Core, Scripps Green Hospital, La Jolla, CA, United States of America
| | - Jamie Case
- Scripps Center for Organ and Cell Transplantation, Scripps Clinic and Scripps Green Hospital, 10666 N Torrey Pines Road, 200N, La Jolla, CA 92037, United States of America
- Scripps Clinic Bio-Repository and Bio-Informatics Core, Scripps Green Hospital, La Jolla, CA, United States of America
| | - Paul R Lewis
- Scripps Center for Organ and Cell Transplantation, Scripps Clinic and Scripps Green Hospital, 10666 N Torrey Pines Road, 200N, La Jolla, CA 92037, United States of America
- Department of General Surgery, Naval Medical Center San Diego, San Diego, CA, United States of America
| | - Jonathan S Fisher
- Scripps Center for Organ and Cell Transplantation, Scripps Clinic and Scripps Green Hospital, 10666 N Torrey Pines Road, 200N, La Jolla, CA 92037, United States of America
| | - Randolph L Schaffer
- Scripps Center for Organ and Cell Transplantation, Scripps Clinic and Scripps Green Hospital, 10666 N Torrey Pines Road, 200N, La Jolla, CA 92037, United States of America
| | - Christopher L Marsh
- Scripps Center for Organ and Cell Transplantation, Scripps Clinic and Scripps Green Hospital, 10666 N Torrey Pines Road, 200N, La Jolla, CA 92037, United States of America
- Scripps Clinic Bio-Repository and Bio-Informatics Core, Scripps Green Hospital, La Jolla, CA, United States of America
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26
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HCC: role of pre- and post-treatment tumor biology in driving adverse outcomes and rare responses to therapy. Abdom Radiol (NY) 2021; 46:3686-3697. [PMID: 34195886 DOI: 10.1007/s00261-021-03192-8] [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] [Received: 04/17/2021] [Revised: 06/19/2021] [Accepted: 06/21/2021] [Indexed: 12/12/2022]
Abstract
Liver cancer is the fastest-growing cause of cancer deaths in the United States and is a complex disease. The response of hepatocellular carcinoma (HCC) to treatment can be variable. Predicting response to determine the most effective therapy is an active area of research. Our understanding of underlying factors which drive response to therapy is continually increasing. As more therapies for the treatment of this disease evolve, it is crucial to identify and match the ideal therapy for a particular tumor and patient. The potential predicative imaging features of tumor behavior, while of research interest, have not been validated for clinical use and do not currently inform treatment planning. If further validated though, prognostic features may be used in the future to personalize treatment plans according to individual patients and tumors. Unexpected post-treatment responses such as potential tumor biology changes and abscopal effect which are important to be aware of. This review is intended for radiologists who routinely interpret post treatment HCC imaging and is designed to increase their cognizance about how HCC tumor biology drives response to therapy and explore rare responses to therapy.
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27
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Vogel A, Bathon M, Saborowski A. Advances in systemic therapy for the first-line treatment of unresectable HCC. Expert Rev Anticancer Ther 2021; 21:621-628. [PMID: 33499684 DOI: 10.1080/14737140.2021.1882855] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Hepatocellular carcinoma (HCC) is one of the most common and deadliest cancers worldwide. In recent years, several drugs have been approved in first- and second-line setting. Currently, several phase-III trials are ongoing with combinations of checkpoint inhibitors, tyrosine kinase inhibitors (TKI) and anti-angiogenic antibodies, which will most likely increase therapeutic options in frontline therapy in the near future.Areas covered: This review summarizes the standard of care in first-line systemic therapy for patients with advanced HCC and provides an outlook on the most promising combinations currently tested in prospective trials.Expert opinion: The recent approval of novel substances has substantially changed the field of palliative treatment strategies in patients with advanced HCC. Immuno-oncology (IO)-based combination therapies will become the next standard of care in frontline HCC. The potent anti-tumor efficacy and good tolerability of these therapies will increase the use of upfront systemic therapy in patients with intermediate stage HCC.
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Affiliation(s)
- Arndt Vogel
- Department of Gastroenterology, Hepatology & Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Melanie Bathon
- Department of Gastroenterology, Hepatology & Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology & Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany
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28
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Llovet JM, De Baere T, Kulik L, Haber PK, Greten TF, Meyer T, Lencioni R. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2021; 18:293-313. [PMID: 33510460 DOI: 10.1038/s41575-020-00395-0] [Citation(s) in RCA: 549] [Impact Index Per Article: 137.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/25/2020] [Indexed: 12/14/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality and has an increasing incidence worldwide. Locoregional therapies, defined as imaging-guided liver tumour-directed procedures, play a leading part in the management of 50-60% of HCCs. Radiofrequency is the mainstay for local ablation at early stages and transarterial chemoembolization (TACE) remains the standard treatment for intermediate-stage HCC. Other local ablative techniques (microwave ablation, cryoablation and irreversible electroporation) or locoregional therapies (for example, radioembolization and sterotactic body radiation therapy) have been explored, but have not yet modified the standard therapies established decades ago. This understanding is currently changing, and several drugs have been approved for the management of advanced HCC. Molecular therapies dominate the adjuvant trials after curative therapies and combination strategies with TACE for intermediate stages. The rationale for these combinations is sound. Local therapies induce antigen and proinflammatory cytokine release, whereas VEGF inhibitors and tyrosine kinase inhibitors boost immunity and prime tumours for checkpoint inhibition. In this Review, we analyse data from randomized and uncontrolled studies reported with ablative and locoregional techniques and examine the expected effects of combinations with systemic treatments. We also discuss trial design and benchmarks to be used as a reference for future investigations in the dawn of a promising new era for HCC treatment.
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Affiliation(s)
- Josep M Llovet
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .,Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Catalonia, Spain. .,Institució Catalana d'Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
| | - Thierry De Baere
- Radiology Department Gustave Roussy Cancer Center, Vilejuif, France.,University Paris-Saclay, Saint-Aubin, France
| | - Laura Kulik
- Division of Gastroenterology and Hepatology, Surgery and Interventional Radiology in Northwestern University, Chicago, IL, USA
| | - Philipp K Haber
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Tim F Greten
- Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Tim Meyer
- Deptartment of Oncology, University College London Cancer Institute, London, UK.,Deptartment of Oncology, Royal Free Hospital, London, UK
| | - Riccardo Lencioni
- Department of Radiology, University of Pisa School of Medicine, Pisa, Italy.,Miami Cancer Institute, Miami, FL, USA
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29
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Complete response of a hepatocellular carcinoma with complex macrovascular invasion after combined treatment with chemoembolization and immunotherapy: a case report. Acta Gastroenterol Belg 2021; 84:371-374. [PMID: 34217191 DOI: 10.51821/84.2.371] [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] [Indexed: 11/21/2022]
Abstract
Hepatocellular carcinoma accounts for 90% of primary liver cancers and represents a growing health problem worldwide. We report the complex case of a 71 year-old patient diagnosed with a large hepatocellular carcinoma and presenting an extensive vascular invasion of the middle hepatic vein and the inferior caval vein ascending to the right atrium with no extrahepatic spread. Due to several comorbidities, a systemic treatment by tyrosine kinase inhibitors was contraindicated. After discussion at the multidisciplinary hepatology tumor board, he was referred for selective internal radiation therapy. Unfortunately, the work-up showed an important lung shunt not allowing radioembolization. No clear recommendations are available in this situation. The decision was made to propose a combination treatment by transarterial chemoembolization, that was performed using a new generation of radio-opaque microspheres loaded with doxorubicin, followed by immunotherapy. This allowed a complete response with a very good quality of life.
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30
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Role of Locoregional Therapies in Patients With Hepatocellular Cancer Awaiting Liver Transplantation. Am J Gastroenterol 2021; 116:57-67. [PMID: 33110015 DOI: 10.14309/ajg.0000000000000999] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 09/14/2020] [Indexed: 02/08/2023]
Abstract
Hepatocellular cancer (HCC) is the fifth most common cancer in the world and the third most common cause of cancer-related deaths. The United Network for Organ Sharing has its own staging criteria for organ allocation, which is a modification of tumor-node-metastasis staging of American Joint Committee on Cancer. For the purpose of clarity, United Network for Organ Sharing staging will be described as uT1, uT2 (Milan criteria), and uT3 (eligible for downstaging) in this review. For those with unresectable HCC or those with advanced liver disease and HCC but within the Milan criteria, liver transplantation is the treatment of choice. Because of prolonged waiting period on the liver transplant list in many parts of the world for deceased donor liver transplantation, there is a serious risk of dropout from the liver transplant list because of tumor progression. For those patients, locoregional therapies might need to be considered, and moreover, there is circumstantial evidence to suggest that tumor progression after locoregional therapies might be a surrogate marker of unfavorable tumor biology. There is no consensus on the role or type of locoregional therapies in the management of patients with uT1 and uT2 eligible for liver transplant and of those with lesions larger than uT2 but eligible for downstaging protocol (uT3 lesions). In this review, we examine the role of locoregional therapies in these patients stratified by staging and propose treatment options based on the current evidence of tumor progression rates while awaiting liver transplantation and tumor recurrence rates after liver transplantation.
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31
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Llovet JM, Villanueva A, Marrero JA, Schwartz M, Meyer T, Galle PR, Lencioni R, Greten TF, Kudo M, Mandrekar SJ, Zhu AX, Finn RS, Roberts LR. Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference. Hepatology 2021; 73 Suppl 1:158-191. [PMID: 32430997 DOI: 10.1002/hep.31327] [Citation(s) in RCA: 260] [Impact Index Per Article: 65.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 03/31/2020] [Accepted: 04/02/2020] [Indexed: 12/13/2022]
Affiliation(s)
- Josep M Llovet
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.,Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain.,Institució Catalana d'Estudis Avançats (ICREA), Barcelona, Spain
| | - Augusto Villanueva
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | | | - Myron Schwartz
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Tim Meyer
- Department Oncology, University College London Cancer Institute, London, UK
| | - Peter R Galle
- Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany
| | - Riccardo Lencioni
- Department of Radiology, University of Pisa School of Medicine, Pisa, Italy.,Miami Cancer Institute, Miami, FL
| | - Tim F Greten
- Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | | | - Andrew X Zhu
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.,Jiahui International Cancer Center, Shanghai, China
| | | | - Lewis R Roberts
- Gastroenterology & Hepatology Department, Mayo Clinic, Rochester, MN
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32
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King MJ, Tong A, Dane B, Huang C, Zhan C, Shanbhogue K. Response assessment of hepatocellular carcinoma treated with yttrium-90 radioembolization: inter-reader variability, comparison with 3D quantitative approach, and role in the prediction of clinical outcomes. Eur J Radiol 2020; 133:109351. [DOI: 10.1016/j.ejrad.2020.109351] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/05/2020] [Accepted: 10/11/2020] [Indexed: 12/26/2022]
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33
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Shehta A, Lee JM, Suh KS, Kim HC, Hong SK, Cho JH, Yi NJ, Lee KW. Bridging and downstaging role of trans-arterial radio-embolization for expected small remnant volume before liver resection for hepatocellular carcinoma. Ann Hepatobiliary Pancreat Surg 2020; 24:421-430. [PMID: 33234744 PMCID: PMC7691198 DOI: 10.14701/ahbps.2020.24.4.421] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 07/13/2020] [Accepted: 07/13/2020] [Indexed: 02/06/2023] Open
Abstract
Backgrounds/Aims To evaluate our initial experience of bridging role of trans-arterial radio-embolization (TARE) before major hepatectomy for hepatocellular carcinoma (HCC) in risky patients with small expected remnant liver volume (ERLV). Methods We reviewed the data of patients with HCC who underwent major hepatectomy after TARE during the period between March and December 2017. Patients included had uni-lobar large HCC (>5 cm) requiring major hepatectomy with small ERLV. Results Five patients were included in our study. All patients were Child Pugh class A. A single session of TARE was applied in all patients. None developed any adverse events related to irradiation. The mean tumor size at baseline was 8.4 cm and 6.1 cm after TARE (p=0.077). The mean % of tumor shrinkage was 24.5%. ERLV improved from 354.6 ml at baseline to 500.8 ml after TARE (p=0.012). ERLV percentage improved from 27.2% at baseline to 38.1% after TARE (p=0.004). The mean % of ERLV was 39.5%. The mean interval time between TARE and resection was 99.6 days. Four patients (80%) underwent right hemi-hepatectomy and one patient (20%) underwent extended right hemi-hepatectomy. The mean operation time was 151 minutes, and mean blood loss was 56 ml. The mean hospital stay was 13.8 days, and one patient (20%) developed postoperative morbidity. After a mean follow-up of 15 months, all patients were alive with no recurrence. Conclusions Yttrium-90 TARE can play a bridging role before major hepatectomy for borderline resectable HCC in risky patients with small ERLV.
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Affiliation(s)
- Ahmed Shehta
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.,Liver Transplantation Unit, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jae-Hyung Cho
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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34
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Millardet M, Moussaoui S, Mateus D, Idier J, Carlier T. Local-Mean Preserving Post-Processing Step for Non-Negativity Enforcement in PET Imaging: Application to 90Y-PET. IEEE TRANSACTIONS ON MEDICAL IMAGING 2020; 39:3725-3736. [PMID: 32746117 DOI: 10.1109/tmi.2020.3003428] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
In a low-statistics PET imaging context, the positive bias in regions of low activity is a burning issue. To overcome this problem, algorithms without the built-in non-negativity constraint may be used. They allow negative voxels in the image to reduce, or even to cancel the bias. However, such algorithms increase the variance and are difficult to interpret since the resulting images contain negative activities, which do not hold a physical meaning when dealing with radioactive concentration. In this paper, a post-processing approach is proposed to remove these negative values while preserving the local mean activities. Its original idea is to transfer the value of each voxel with negative activity to its direct neighbors under the constraint of preserving the local means of the image. In that respect, the proposed approach is formalized as a linear programming problem with a specific symmetric structure, which makes it solvable in a very efficient way by a dual-simplex-like iterative algorithm. The relevance of the proposed approach is discussed on simulated and on experimental data. Acquired data from an yttrium-90 phantom show that on images produced by a non-constrained algorithm, a much lower variance in the cold area is obtained after the post-processing step, at the price of a slightly increased bias. More specifically, when compared with the classical OSEM algorithm, images are improved, both in terms of bias and of variance.
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35
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Downstaging to Liver Transplant: Success Involves Choosing the Right Patient. Clin Liver Dis 2020; 24:665-679. [PMID: 33012452 DOI: 10.1016/j.cld.2020.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatocellular carcinoma is a rising indication for liver transplantation in the United States. Downstaging, defined as the reduction of tumor burden using local-regional therapy into Milan criteria, opens an avenue to access cure through transplant for patients who traditionally would not qualify. Approaching the selection of downstaging candidates through an assessment of hepatic function, staying within a modest expansion of tumor burden, and incorporation of serologic/imaging markers for tumor biology provide the best chance for successful downstaging. Following well-defined downstaging protocols with built-in failure criteria ensures excellent post-transplant outcomes.
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Chen L, Sun T, Kan X, Chen S, Ren Y, Cao Y, Yan L, Liang B, Xiong B, Zheng C. Transarterial chemoembolization combined with iodine-125 seed implantation for patients with hepatocellular carcinoma: a retrospective controlled study. J Int Med Res 2020; 48:300060520944309. [PMID: 33050765 PMCID: PMC7570795 DOI: 10.1177/0300060520944309] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective To determine if iodine-125 seed implantation improved the efficacy of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) (≤5 cm). Methods We retrospectively reviewed the medical records of 83 consecutive patients with HCC (≤5 cm) who underwent TACE or TACE–iodine-125 from January 2014 to July 2017. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS) and objective response rate (ORR) at 3 months after the first TACE treatment. PFS and OS were calculated using the Kaplan–Meier method and compared using log-rank tests. Independent risk factors for PFS and OS were analyzed using a Cox proportional hazards model. Results Thirty-five patients received TACE–iodine-125 and 48 received TACE alone. The median OS and PFS were both significantly longer in the TACE–iodine-125 compared with the TACE-alone group (42 vs 23 months and 16 vs 8 months, respectively). The ORR was significantly higher in the TACE–iodine-125 compared with the TACE-alone group. There was no significant difference in adverse events, apart from decreased white cell count, between the two groups. Conclusion TACE–iodine-125 might be an effective and safe alternative treatment for patients with HCC (≤5 cm).
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Affiliation(s)
- Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Xuefeng Kan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Shi Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Yanyan Cao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Liangliang Yan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Bin Xiong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
- Chuansheng Zheng, 1277 Jiefang Avenue, Jianghan District, Wuhan 430022, China.
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Clinical Application of Trans-Arterial Radioembolization in Hepatic Malignancies in Europe: First Results from the Prospective Multicentre Observational Study CIRSE Registry for SIR-Spheres Therapy (CIRT). Cardiovasc Intervent Radiol 2020; 44:21-35. [PMID: 32959085 PMCID: PMC7728645 DOI: 10.1007/s00270-020-02642-y] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 09/02/2020] [Indexed: 01/27/2023]
Abstract
Purpose To address the lack of prospective data on the real-life clinical application of trans-arterial radioembolization (TARE) in Europe, the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) initiated the prospective observational study CIRSE Registry for SIR-Spheres® Therapy (CIRT). Materials and Methods Patients were enrolled from 1 January 2015 till 31 December 2017. Eligible patients were adult patients treated with TARE with Y90 resin microspheres for primary or metastatic liver tumours. Patients were followed up for 24 months after treatment, whereas data on the clinical context of TARE, overall survival (OS) and safety were collected. Results Totally, 1027 patients were analysed. 68.2% of the intention of treatment was palliative. Up to half of the patients received systemic therapy and/or locoregional treatments prior to TARE (53.1%; 38.3%). Median overall survival (OS) was reported per cohort and was 16.5 months (95% confidence interval (CI) 14.2–19.3) for hepatocellular carcinoma, 14.6 months (95% CI 10.9–17.9) for intrahepatic cholangiocarcinoma. For liver metastases, median OS for colorectal cancer was 9.8 months (95% CI 8.3–12.9), 5.6 months for pancreatic cancer (95% CI 4.1–6.6), 10.6 months (95% CI 7.3–14.4) for breast cancer, 14.6 months (95% CI 7.3–21.4) for melanoma and 33.1 months (95% CI 22.1–nr) for neuroendocrine tumours. Statistically significant prognostic factors in terms of OS include the presence of ascites, cirrhosis, extra-hepatic disease, patient performance status (Eastern Cooperative Oncology Group), number of chemotherapy lines prior to TARE and tumour burden. Thirty-day mortality rate was 1.0%. 2.5% experienced adverse events grade 3 or 4 within 30 days after TARE. Conclusion In the real-life clinical setting, TARE is largely considered to be a part of a palliative treatment strategy across indications and provides an excellent safety profile. Level of evidence Level 3. Trial registration ClinicalTrials.gov NCT02305459. Electronic supplementary material The online version of this article (10.1007/s00270-020-02642-y) contains supplementary material, which is available to authorized users.
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Dixon M, Cruz J, Sarwani N, Gusani N. The Future Liver Remnant : Definition, Evaluation, and Management. Am Surg 2020; 87:276-286. [PMID: 32931301 DOI: 10.1177/0003134820951451] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
When considering patients for a major hepatectomy, one must carefully consider the volume of liver to be left behind and if additional procedures are necessary to augment its volume. This review considers the optimal volume of the future liver remnant (FLR) and analyzes the techniques of augmenting this volume, the various growth parameters to assess adequate growth of the FLR, as well as further management when there has been inadequate growth of the FLR.
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Affiliation(s)
- Matthew Dixon
- Division of Surgical Oncology, Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA
| | - Jeffrey Cruz
- Division of Surgical Oncology, Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA.,Department of Radiology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA.,Department of Medicine, The Pennsylvania State University, College of Medicine, Hershey, PA, USA
| | - Nabeel Sarwani
- Department of Radiology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA
| | - Niraj Gusani
- Division of Surgical Oncology, Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA.,Department of Medicine, The Pennsylvania State University, College of Medicine, Hershey, PA, USA.,Department of Public Health Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, USA
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Lee JM, Lee KW, Kim HC, Yi NJ, Suh KS. No touch isolation technique for the prevention of postoperative recurrence of hepatocellular carcinoma after liver transplantation-combined with trans-arterial radioembolization. Surg Oncol 2020; 35:189-190. [PMID: 32890956 DOI: 10.1016/j.suronc.2020.08.024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 05/06/2020] [Accepted: 08/19/2020] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Transarterial radioembolization (TARE) is recently emerging treatment modality using radiation from Yttrium-90 through the transarterial approach. It usually is used in the intermediate stage and unresectable hepatocellular carcinoma (HCC). No touch isolation technique is a way to prevent the spread of tumors by pre-ligating the vessels around the tumor with minimal touch during surgery. We hoped that if we were to use these techniques, we would be able to control all viable tumors before liver transplantation. Then we could get better outcomes even in the advanced hepatocellular carcinoma patients. METHODS We performed living donor liver transplantation using no touch isolation technique in the patients who had multinodular hepatocellular carcinoma and extremely high AFP, PIVKA-II level after TARE and conventional TACE. RESULTS 36 years old female patient had liver cirrhosis with hepatitis B virus infection and multiple hepatocellular carcinoma in both lobes. Hepatologist decided to do TARE and additional conventional TACE for viable tumors. After that treatment, AFP and PIVKA-II level were dramatically decreased, we decided to proceed of living donor liver transplantation because the patient's treatment response was extremely good. CONCLUSIONS No touch isolation technique combined with TARE for recipient hepatectomy might be helpful in advanced stage hepatocellular carcinoma patients.
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Affiliation(s)
- Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University Hospital, Seoul, South Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
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Pasciak AS, Manupipatpong S, Hui FK, Gainsburg L, Krimins R, Zink MC, Brayton CF, Morris M, Sage J, Donahue DR, Dreher MR, Kraitchman DL, Weiss CR. Yttrium-90 radioembolization as a possible new treatment for brain cancer: proof of concept and safety analysis in a canine model. EJNMMI Res 2020; 10:96. [PMID: 32804262 PMCID: PMC7431501 DOI: 10.1186/s13550-020-00679-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 07/28/2020] [Indexed: 12/22/2022] Open
Abstract
Purpose To evaluate the safety, feasibility, and preliminary efficacy of yttrium-90 (90Y) radioembolization (RE) as a minimally invasive treatment in a canine model with presumed spontaneous brain cancers. Materials Three healthy research dogs (R1–R3) and five patient dogs with spontaneous intra-axial brain masses (P1–P5) underwent cerebral artery RE with 90Y glass microspheres (TheraSphere). 90Y-RE was performed on research dogs from the unilateral internal carotid artery (ICA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) while animals with brain masses were treated from the ICA. Post-treatment 90Y PET/CT was performed along with serial neurological exams by a veterinary neurologist. One month after treatment, research dogs were euthanized and the brains were extracted and sent for microdosimetric and histopathologic analyses. Patient dogs received post-treatment MRI at 1-, 3-, and 6-month intervals with long-term veterinary follow-up. Results The average absorbed dose to treated tissue in R1–R3 was 14.0, 30.9, and 73.2 Gy, respectively, with maximum doses exceeding 1000 Gy. One month after treatment, research dog pathologic analysis revealed no evidence of cortical atrophy and rare foci consistent with chronic infarcts, e.g., < 2-mm diameter. Absorbed doses to masses in P1–P5 were 45.5, 57.6, 58.1, 45.4, and 64.1 Gy while the dose to uninvolved brain tissue was 15.4, 27.6, 19.2, 16.7, and 33.3 G, respectively. Among both research and patient animals, 6 developed acute neurologic deficits following treatment. However, in all surviving dogs, the deficits were transient resolving between 7 and 33 days post-therapy. At 1 month post-therapy, patient animals showed a 24–94% reduction in mass volume with partial response in P1, P3, and P4 at 6 months post-treatment. While P2 initially showed a response, by 5 months, the mass had advanced beyond pre-treatment size, and the dog was euthanized. Conclusion This proof of concept demonstrates the technical feasibility and safety of 90Y-RE in dogs, while preliminary, initial data on the efficacy of 90Y-RE as a potential treatment for brain cancer is encouraging.
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Affiliation(s)
- Alexander S Pasciak
- School of Medicine, The Johns Hopkins University School of Medicine, 1800 Orleans St, Baltimore, MD, 21287, USA.
| | - Sasicha Manupipatpong
- School of Medicine, The Johns Hopkins University School of Medicine, 1800 Orleans St, Baltimore, MD, 21287, USA
| | - Ferdinand K Hui
- Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Larry Gainsburg
- Mid-Atlantic Veterinary Neurology and Neurosurgery, Baltimore, MD, USA
| | - Rebecca Krimins
- Department of Molecular and Comparative Pathobiology, The Johns Hopkins University, Baltimore, MD, USA.,Department of Radiology and Radiological Science, Express Radiology Research Lab, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Radiology and Radiological Science, Veterinary Clinical Trials Network, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - M Christine Zink
- Department of Molecular and Comparative Pathobiology, The Johns Hopkins University, Baltimore, MD, USA
| | - Cory F Brayton
- Department of Molecular and Comparative Pathobiology, The Johns Hopkins University, Baltimore, MD, USA
| | - Meaghan Morris
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Danielle R Donahue
- Mouse Imaging Facility, National Institutes of Health, Bethesda, MD, USA
| | - Matthew R Dreher
- Biocompatibles UK Ltd., a BTG International group company, Farnham, Surrey, UK
| | - Dara L Kraitchman
- Department of Molecular and Comparative Pathobiology, The Johns Hopkins University, Baltimore, MD, USA.,Department of Radiology and Radiological Science, Center for Image-Guided Animal Therapy, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Clifford R Weiss
- Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department Biomedical Engineering, The Johns Hopkins Whiting School of Engineering, Baltimore, MD, USA
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Roncali E, Taebi A, Foster C, Vu CT. Personalized Dosimetry for Liver Cancer Y-90 Radioembolization Using Computational Fluid Dynamics and Monte Carlo Simulation. Ann Biomed Eng 2020; 48:1499-1510. [PMID: 32006268 PMCID: PMC7160004 DOI: 10.1007/s10439-020-02469-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2019] [Accepted: 01/25/2020] [Indexed: 12/14/2022]
Abstract
Yttrium-90 (Y-90) transarterial radioembolization uses radioactive microspheres injected into the hepatic artery to irradiate liver tumors internally. One of the major challenges is the lack of reliable dosimetry methods for dose prediction and dose verification. We present a patient-specific dosimetry approach for personalized treatment planning based on computational fluid dynamics (CFD) simulations of the microsphere transport combined with Y-90 physics modeling called CFDose. The ultimate goal is the development of a software to optimize the amount of activity and injection point for optimal tumor targeting. We present the proof-of-concept of a CFD dosimetry tool based on a patient's angiogram performed in standard-of-care planning. The hepatic arterial tree of the patient was segmented from the cone-beam CT (CBCT) to predict the microsphere transport using multiscale CFD modeling. To calculate the dose distribution, the predicted microsphere distribution was convolved with a Y-90 dose point kernel. Vessels as small as 0.45 mm were segmented, the microsphere distribution between the liver segments using flow analysis was predicted, the volumetric microsphere and resulting dose distribution in the liver volume were computed. The patient was imaged with positron emission tomography (PET) 2 h after radioembolization to evaluate the Y-90 distribution. The dose distribution was found to be consistent with the Y-90 PET images. These results demonstrate the feasibility of developing a complete framework for personalized Y-90 microsphere simulation and dosimetry using patient-specific input parameters.
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Affiliation(s)
- Emilie Roncali
- Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA.
| | - Amirtahà Taebi
- Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA
| | - Cameron Foster
- Department of Radiology, UC Davis Medical Center, Sacramento, CA, 95817, USA
| | - Catherine Tram Vu
- Department of Radiology, UC Davis Medical Center, Sacramento, CA, 95817, USA
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Satiya J, Schwartz I, Tabibian JH, Kumar V, Girotra M. Ablative therapies for hepatic and biliary tumors: endohepatology coming of age. Transl Gastroenterol Hepatol 2020; 5:15. [PMID: 32258519 PMCID: PMC7063520 DOI: 10.21037/tgh.2019.10.17] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 10/23/2019] [Indexed: 12/12/2022] Open
Abstract
Ablative therapies refer to minimally invasive procedures performed to destroy abnormal tissue that may arise with many conditions, and can be achieved clinically using chemical, thermal, and other techniques. In this review article, we explore the different ablative therapies used in the management of hepatic and biliary malignancies, namely hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), with a particular focus on radiofrequency ablation (RFA) and photodynamic therapy (PDT) techniques.
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Affiliation(s)
- Jinendra Satiya
- Internal Medicine, University of Miami/JFK Medical Center Palm Beach Regional GME Consortium, West Palm Beach, FL, USA
| | - Ingrid Schwartz
- Internal Medicine, University of Miami Miller School of Medicine/Jackson Memorial Hospital, Miami, FL, USA
| | - James H. Tabibian
- Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - Vivek Kumar
- Gastroenterology and Hepatology, UPMC Susquehanna, Williamsport, PA, USA
| | - Mohit Girotra
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, Miami, FL, USA
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43
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Chen LT, Martinelli E, Cheng AL, Pentheroudakis G, Qin S, Bhattacharyya GS, Ikeda M, Lim HY, Ho GF, Choo SP, Ren Z, Malhotra H, Ueno M, Ryoo BY, Kiang TC, Tai D, Vogel A, Cervantes A, Lu SN, Yen CJ, Huang YH, Chen SC, Hsu C, Shen YC, Tabernero J, Yen Y, Hsu CH, Yoshino T, Douillard JY. Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO. Ann Oncol 2020; 31:334-351. [PMID: 32067677 DOI: 10.1016/j.annonc.2019.12.001] [Citation(s) in RCA: 151] [Impact Index Per Article: 30.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 11/18/2019] [Accepted: 12/11/2019] [Indexed: 02/06/2023] Open
Abstract
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.
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Affiliation(s)
- L-T Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan; Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - E Martinelli
- Department of Clinical and Experimental Medicine 'F Magrassi' - Medical Oncology, Università degli Studi della Campania L Vanvitelli, Naples, Italy
| | - A-L Cheng
- Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - G Pentheroudakis
- Department of Medical Oncology, University of Ioannina, Ioannina, Greece
| | - S Qin
- Chinese PLA Cancer Center, Jinling Hospital, Nanjing, China
| | | | - M Ikeda
- Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Japan
| | - H-Y Lim
- Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - G F Ho
- Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - S P Choo
- Curie Oncology, Singapore; National Cancer Centre Singapore, Singapore, Singapore
| | - Z Ren
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - H Malhotra
- Department of Medical Oncology, Sri Ram Cancer Center, Mahatma Gandhi Medical College Hospital, Jaipur, India
| | - M Ueno
- Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
| | - B-Y Ryoo
- Department of Oncology, Asan Medical Center University of Ulsan College of Medicine, Seoul, South Korea
| | - T C Kiang
- Hospital Umum Sarawak, Kuching, Sarawak, Malaysia
| | - D Tai
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - A Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany
| | - A Cervantes
- CIBERONC, Department of Medical Oncology, Institute of Health Research, INCLIVIA, University of Valencia, Valencia, Spain
| | - S-N Lu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - C-J Yen
- Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Y-H Huang
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - S-C Chen
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - C Hsu
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Y-C Shen
- Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
| | - J Tabernero
- Medical Oncology Department, Vall d' Hebron University Hospital and Institute of Oncology (VHIO), UVic, IOB-Quiron, Barcelona, Spain
| | - Y Yen
- Taipei Medical University, Taipei, Taiwan
| | - C-H Hsu
- Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - T Yoshino
- Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Japan
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Craciun L, de Wind R, Demetter P, Lucidi V, Bohlok A, Michiels S, Bouazza F, Vouche M, Tancredi I, Verset G, Garaud S, Naveaux C, Galdon MG, Gallo KW, Hendlisz A, Derijckere ID, Flamen P, Larsimont D, Donckier V. Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy. BMC Cancer 2020; 20:135. [PMID: 32075608 PMCID: PMC7032008 DOI: 10.1186/s12885-020-6613-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 02/07/2020] [Indexed: 02/08/2023] Open
Abstract
Background Immunotherapy represents a promising option for treatment of hepatocellular carcinoma (HCC) in cirrhotic patients but its efficacy is currently inconsistent and unpredictable. Locoregional therapies inducing immunogenic cell death, such as transarterial chemoembolization (TACE) or selective internal radiation therapy (SIRT), have the potential to act synergistically with immunotherapy. For the development of new approaches combining locoregional treatments with immunotherapy, a better understanding of the respective effects of TACE and SIRT on recruitment and activation of immune cells in HCC is needed. To address this question, we compared intra-tumor immune infiltrates in resected HCC after preoperative treatment with TACE or SIRT. Methods Data fromr patients undergoing partial hepatectomy for HCC, without preoperative treatment (SURG, n = 32), after preoperative TACE (TACE, n = 16), or preoperative SIRT (n = 12) were analyzed. Clinicopathological factors, tumor-infiltrating lymphocytes (TILs), CD4+ and CD8+ T cells, and granzyme B (GZB) expression in resected HCC, and postoperative overall and progression-free survival were compared between the three groups. Results Clinicopathological and surgical characteristics were similar in the three groups. A significant increase in TILs, CD4+ and CD8+ T cells, and GZB expression was observed in resected HCC in SIRT as compared to TACE and SURG groups. No difference in immune infiltrates was observed between TACE and SURG patients. Within the SIRT group, the dose of irradiation affected the type of immune infiltrate. A significantly higher ratio of CD3+ cells was observed in the peri-tumoral area in patients receiving < 100 Gy, whereas a higher ratio of intra-tumoral CD4+ cells was observed in patients receiving > 100 Gy. Postoperative outcomes were similar in all groups. Irrespective of the preoperative treatment, the type and extent of immune infiltrates did not influence postoperative survival. Conclusions SIRT significantly promotes recruitment/activation of intra-tumor effector-type immune cells compared to TACE or no preoperative treatment. These results suggest that SIRT is a better candidate than TACE to be combined with immunotherapy for treatment of HCC. Evaluation of the optimal doses for SIRT for producing an immunogenic effect and the type of immunotherapy to be used require further evaluation in prospective studies.
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Affiliation(s)
- Ligia Craciun
- Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Roland de Wind
- Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Pieter Demetter
- Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium.,Pathology, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Valerio Lucidi
- Abdominal Surgery, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Ali Bohlok
- Surgery, Institut Jules Bordet, Université Libre de Bruxelles, Rue Héger-Bordet, 1, B-1000, Brussels, Belgium
| | - Sébastien Michiels
- Surgery, Institut Jules Bordet, Université Libre de Bruxelles, Rue Héger-Bordet, 1, B-1000, Brussels, Belgium
| | - Fikri Bouazza
- Surgery, Institut Jules Bordet, Université Libre de Bruxelles, Rue Héger-Bordet, 1, B-1000, Brussels, Belgium
| | - Michael Vouche
- Radiology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Ilario Tancredi
- Radiology, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Gontran Verset
- Gastroenterology and Medical Oncology, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Soizic Garaud
- Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Céline Naveaux
- Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Maria Gomez Galdon
- Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Karen Willard Gallo
- Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Alain Hendlisz
- Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Ivan Duran Derijckere
- Nuclear Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Patrick Flamen
- Nuclear Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Denis Larsimont
- Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Vincent Donckier
- Surgery, Institut Jules Bordet, Université Libre de Bruxelles, Rue Héger-Bordet, 1, B-1000, Brussels, Belgium.
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45
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Mehta N. Hepatocellular Carcinoma-How to Determine Therapeutic Options. Hepatol Commun 2020; 4:342-354. [PMID: 32140653 PMCID: PMC7049673 DOI: 10.1002/hep4.1481] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 12/31/2019] [Indexed: 02/06/2023] Open
Abstract
Deciding on specific treatment strategies involves not only tumor stage, performance status, and severity of underlying liver disease, but additional factors such as biomarkers, organ availability, and radiographic tumor response to treatment. In this review, we present hepatocellular carcinoma (HCC) cases to highlight how to determine therapeutic options for HCC in specific scenarios, including resection versus liver transplant, choice of initial local regional treatment, tumor downstaging, and systemic therapies for advanced HCC.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology Department of Medicine University of California San Francisco San Francisco CA
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46
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Voizard N, Cerny M, Assad A, Billiard JS, Olivié D, Perreault P, Kielar A, Do RKG, Yokoo T, Sirlin CB, Tang A. Assessment of hepatocellular carcinoma treatment response with LI-RADS: a pictorial review. Insights Imaging 2019; 10:121. [PMID: 31853668 PMCID: PMC6920285 DOI: 10.1186/s13244-019-0801-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 09/26/2019] [Indexed: 02/07/2023] Open
Abstract
Computed tomography (CT) and magnetic resonance imaging (MRI) play critical roles for assessing treatment response of hepatocellular carcinoma (HCC) after locoregional therapy. Interpretation is challenging because posttreatment imaging findings depend on the type of treatment, magnitude of treatment response, time interval after treatment, and other factors. To help radiologists interpret and report treatment response in a clear, simple, and standardized manner, the Liver Imaging Reporting and Data System (LI-RADS) has developed a Treatment Response (LR-TR) algorithm. Introduced in 2017, the system provides criteria to categorize response of HCC to locoregional treatment (e.g., chemical ablation, energy-based ablation, transcatheter therapy, and radiation therapy). LR-TR categories include Nonevaluable, Nonviable, Equivocal, and Viable. LR-TR does not apply to patients on systemic therapies. This article reviews the LR-TR algorithm; discusses locoregional therapies for HCC, treatment concepts, and expected posttreatment findings; and illustrates LI-RADS treatment response assessment with CT and MRI.
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Affiliation(s)
- Nicolas Voizard
- Department of Radiology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Québec, Canada
| | - Milena Cerny
- Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada
| | - Anis Assad
- Department of Radiology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Québec, Canada
| | - Jean-Sébastien Billiard
- Department of Radiology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Québec, Canada
| | - Damien Olivié
- Department of Radiology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Québec, Canada
| | - Pierre Perreault
- Department of Radiology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Québec, Canada
| | - Ania Kielar
- Joint Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Richard K G Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Takeshi Yokoo
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, CA, USA
| | - An Tang
- Department of Radiology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Québec, Canada.
- Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.
- Department of Radiology, Radio-oncology and Nuclear Medicine, University of Montreal, Montreal, Canada.
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47
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Vogel A, Saborowski A. Current strategies for the treatment of intermediate and advanced hepatocellular carcinoma. Cancer Treat Rev 2019; 82:101946. [PMID: 31830641 DOI: 10.1016/j.ctrv.2019.101946] [Citation(s) in RCA: 89] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 11/27/2019] [Indexed: 01/27/2023]
Abstract
Hepatocellular carcinoma (HCC) ranks among the most common cancers worldwide and remains to be a major global health care problem. Until 2007, no effective therapies were available for patients after failure of locoregional approaches, and the approval of sorafenib as the first systemic agent with efficacy in patients suffering from advanced HCC marked a new era in the treatment of this deadly disease. However, it took nearly 10 years until the portfolio of effective drugs finally expanded and additional substances showed activity in both first and further lines of treatment. Since their recent approval, these novel substances have substantially changed the field of palliative treatment strategies in patients with advanced HCC, and their sequential application has demonstrated their potential to significantly prolong patient survival in the palliative setting. With the recently communicated data from the first positive immuno-oncology trial in HCC, it appears highly likely that the implementation of IO concepts will result in a further improvement of patient prognosis. Although locoregional approaches remain an integral component of meaningful treatment concepts for patients with BCLC-B stage HCC, repetitive interventions bear the risk of a progressive deterioration of liver function. More than ever, in order to implement long-term therapeutic concepts and exploit the full potential of systemic treatment strategies, it is of utmost importance to maintain a fine balance between anti-tumor activity and toxicity. With an emphasis on the systemic treatment options, this review provides a summary of the most recent results from large phase III clinical trials and discusses their clinical implications.
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Affiliation(s)
- Arndt Vogel
- Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, Germany.
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, Germany
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48
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McKinley SK, Chawla A, Ferrone CR. Inoperable Biliary Tract and Primary Liver Tumors: Palliative Treatment Options. Surg Oncol Clin N Am 2019; 28:745-762. [PMID: 31472917 DOI: 10.1016/j.soc.2019.06.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Primary liver tumors are most commonly hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Although surgical resection offers a chance for cure, these tumors generally present at a late, inoperable stage, necessitating an understanding of noncurative and palliative treatment options. These options include ablative therapies, including radiofrequency ablation; intra-arterial therapies, including transcatheter chemoembolization; biliary decompression; radiotherapy; systemic therapies, including traditional chemotherapeutic agents; and molecular therapies, such as sorafenib. Selection of nonoperative treatment depends on patient and tumor factors as well as institutional resources and expertise.
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Affiliation(s)
- Sophia K McKinley
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRB-425, Boston, MA 02114, USA
| | - Akhil Chawla
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, WAC 4-460, Boston, MA 02114, USA
| | - Cristina R Ferrone
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, WAC 4-460, Boston, MA 02114, USA.
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49
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Zhan C, Ruohoniemi D, Shanbhogue KP, Wei J, Welling TH, Gu P, Park JS, Dagher NN, Taslakian B, Hickey RM. Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma. J Vasc Interv Radiol 2019; 31:25-34. [PMID: 31422022 DOI: 10.1016/j.jvir.2019.05.023] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 05/15/2019] [Accepted: 05/20/2019] [Indexed: 12/12/2022] Open
Abstract
PURPOSE To investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS This single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A-B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses. RESULTS The median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6-11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1-3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9-23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6-26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2-7.2), and progression-free survival was 5.7 months (95% CI, 4.3-7.1). CONCLUSIONS Radioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.
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Affiliation(s)
- Chenyang Zhan
- Division of Vascular Interventional Radiology, Department of Radiology, New York City, New York
| | - David Ruohoniemi
- New York University Langone Health, NYU School of Medicine, New York City, New York
| | - Krishna P Shanbhogue
- Division of Abdominal Imaging, Department of Radiology, NYU Langone Health, NYU School of Medicine, New York City, New York
| | - Jason Wei
- New York University Langone Health, NYU School of Medicine, New York City, New York
| | - Theodore H Welling
- Perlmutter Cancer Center and Department of Surgery, NYU Langone Health, NYU School of Medicine, New York City, New York
| | - Ping Gu
- Department of Hematology/Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - James S Park
- Hepatology Section, Division of Gastroenterology, Department of Medicine, NYU Langone Health, NYU School of Medicine, New York City, New York
| | - Nabil N Dagher
- Transplant Institute, NYU Langone Health, NYU School of Medicine, New York City, New York
| | - Bedros Taslakian
- Division of Vascular Interventional Radiology, Department of Radiology, New York City, New York
| | - Ryan M Hickey
- Division of Vascular Interventional Radiology, Department of Radiology, New York City, New York.
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50
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Lim C, Salloum C, Chalaye J, Lahat E, Costentin CE, Osseis M, Itti E, Feray C, Azoulay D. 18F-FDG PET/CT predicts microvascular invasion and early recurrence after liver resection for hepatocellular carcinoma: A prospective observational study. HPB (Oxford) 2019; 21:739-747. [PMID: 30401520 DOI: 10.1016/j.hpb.2018.10.007] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 09/17/2018] [Accepted: 10/10/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study assessed the prognostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in the prediction of MVI and early recurrence following resection. METHOD This prospective study (ClinicalTrials.gov ID: NCT02145013) included 78 consecutive HCC patients who underwent 18F-FDG PET/CT before curative-intent resection from 2014 to 2017. Prognostic factors available before surgery for predicting MVI and early recurrence (≤2 years) were identified by univariate and multivariate analyses. RESULTS The 18F-FDG PET/CT result was positive in 30 (38%) patients. MVI was present in 33% (26/78) of specimens. Early recurrence occurred in 19% (14/74) of surviving patients. PET/CT positivity was the sole independent predictor of MVI (odds ratio [OR] = 3.6, 95% confidence interval [CI] = 1.1-11.2; p = 0.03), with a specificity and sensitivity for predicting MVI of 73% and 62%, respectively. Analysis of variables available before surgery showed that PET/CT positivity (hazard ratio [HR] = 5.8, 95% CI = 1.6-20.4; p = 0.006) and the male sex (HR = 6.6; 95% CI = 1.8-24.2; p = 0.005) were independent predictors of early recurrence. CONCLUSION 18F-FDG PET/CT predicts MVI and early recurrence after surgery for HCC and could be used to select patients for neoadjuvant treatment.
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Affiliation(s)
- Chetana Lim
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil APHP, France
| | - Chady Salloum
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil APHP, France
| | - Julia Chalaye
- Department of Nuclear Medicine, Henri Mondor Hospital, Créteil APHP, France
| | - Eylon Lahat
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil APHP, France
| | | | - Michael Osseis
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil APHP, France
| | - Emmanuel Itti
- Department of Nuclear Medicine, Henri Mondor Hospital, Créteil APHP, France
| | - Cyrille Feray
- Department of Nuclear Medicine, Henri Mondor Hospital, Créteil APHP, France
| | - Daniel Azoulay
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil APHP, France.
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