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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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Stocker D, King MJ, Homsi ME, Gnerre J, Marinelli B, Wurnig M, Schwartz M, Kim E, Taouli B. Early post-treatment MRI predicts long-term hepatocellular carcinoma response to radiation segmentectomy. Eur Radiol 2024; 34:475-484. [PMID: 37540318 PMCID: PMC10791774 DOI: 10.1007/s00330-023-10045-z] [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: 02/21/2023] [Revised: 05/29/2023] [Accepted: 06/20/2023] [Indexed: 08/05/2023]
Abstract
OBJECTIVES Radiation segmentectomy using yttrium-90 plays an emerging role in the management of early-stage HCC. However, the value of early post-treatment MRI for response assessment is uncertain. We assessed the value of response criteria obtained early after radiation segmentectomy in predicting long-term response in patients with HCC. MATERIALS AND METHODS Patients with HCC who underwent contrast-enhanced MRI before, early, and 12 months after radiation segmentectomy were included in this retrospective single-center study. Three independent radiologists reviewed images at baseline and 1st follow-up after radiation segmentectomy and assessed lesion-based response according to mRECIST, LI-RADS treatment response algorithm (TRA), and image subtraction. The endpoint was response at 12 months based on consensus readout of two separate radiologists. Diagnostic accuracy for predicting complete response (CR) at 12 months based on the 1st post-treatment MRI was calculated. RESULTS Eighty patients (M/F 60/20, mean age 67.7 years) with 80 HCCs were assessed (median size baseline, 1.8 cm [IQR, 1.4-2.9 cm]). At 12 months, 74 patients were classified as CR (92.5%), 5 as partial response (6.3%), and 1 as progressive disease (1.2%). Diagnostic accuracy for predicting CR was fair to good for all readers with excellent positive predictive value (PPV): mRECIST (range between 3 readers, accuracy: 0.763-0.825, PPV: 0.966-1), LI-RADS TRA (accuracy: 0.700-0.825, PPV: 0.983-1), and subtraction (accuracy: 0.775-0.825, PPV: 0.967-1), with no difference in accuracy between criteria (p range 0.053 to > 0.9). CONCLUSION mRECIST, LI-RADS TRA, and subtraction obtained on early post-treatment MRI show similar performance for predicting long-term response in patients with HCC treated with radiation segmentectomy. CLINICAL RELEVANCE STATEMENT Response assessment extracted from early post-treatment MRI after radiation segmentectomy predicts complete response in patients with HCC with high PPV (≥ 0.96). KEY POINTS • Early post-treatment response assessment on MRI predicts response in patients with HCC treated with radiation segmentectomy with fair to good accuracy and excellent positive predictive value. • There was no difference in diagnostic accuracy between mRECIST, LI-RADS, and subtraction for predicting HCC response to radiation segmentectomy.
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Affiliation(s)
- Daniel Stocker
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
| | - Michael J King
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Maria El Homsi
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jeffrey Gnerre
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Brett Marinelli
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Interventional Radiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Moritz Wurnig
- Institute of Radiology, Spital Lachen AG, Lachen, Switzerland
| | - Myron Schwartz
- Recanati Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Edward Kim
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Bachir Taouli
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Khan F, Jones K, Lyon P. Immune checkpoint inhibition: a future guided by radiology. Br J Radiol 2023; 96:20220565. [PMID: 36752570 PMCID: PMC10321249 DOI: 10.1259/bjr.20220565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 01/04/2023] [Accepted: 01/29/2023] [Indexed: 02/09/2023] Open
Abstract
The limitation of the function of antitumour immune cells is a common hallmark of cancers that enables their survival. As such, the potential of immune checkpoint inhibition (ICI) acts as a paradigm shift in the treatment of a range of cancers but has not yet been fully capitalised. Combining minimally and non-invasive locoregional therapies offered by radiologists with ICI is now an active field of research with the aim of furthering therapeutic capabilities in medical oncology. In parallel to this impending advancement, the "imaging toolbox" available to radiologists is also growing, enabling more refined tumour characterisation as well as greater accuracy in evaluating responses to therapy. Options range from metabolite labelling to cellular localisation to immune checkpoint screening. It is foreseeable that these novel imaging techniques will be integrated into personalised treatment algorithms. This growth in the field must include updating the current standardised imaging criteria to ensure they are fit for purpose. Such criteria is crucial to both appropriately guide clinical decision-making regarding next steps of treatment, but also provide reliable prognosis. Quantitative approaches to these novel imaging techniques are also already being investigated to further optimise personalised therapeutic decision-making. The therapeutic potential of specific ICIs and locoregional therapies could be determined before administration thus limiting unnecessary side-effects whilst maintaining efficacy. Several radiological aspects of oncological care are advancing simultaneously. Therefore, it is essential that each development is assessed for clinical use and optimised to ensure the best treatment decisions are being offered to the patient. In this review, we discuss state of the art advances in novel functional imaging techniques in the field of immuno-oncology both pre-clinically and clinically.
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Affiliation(s)
- Faraaz Khan
- Foundation Doctor, Buckinghamshire Hospitals NHS Trust, Amersham, Buckinghamshire, United Kingdom
| | - Keaton Jones
- Academic Clinical Lecturer Nuffield Department of Surgical Sciences University of Oxford, Wellington Square, Oxford, United Kingdom
| | - Paul Lyon
- Consultant Radiologist, Department of Radiology, Oxford University Hospitals, Headington, Oxford, United Kingdom
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Taiji R, Lin YM, Chintalapani G, Lin EY, Huang SY, Mahvash A, Avritscher R, Liu CA, Lee RC, Resende V, Nishiofuku H, Tanaka T, Kichikawa K, Klotz E, Gupta S, Odisio BC. A novel method for predicting hepatocellular carcinoma response to chemoembolization using an intraprocedural CT hepatic arteriography-based enhancement mapping: a proof-of-concept analysis. Eur Radiol Exp 2023; 7:4. [PMID: 36717474 PMCID: PMC9886747 DOI: 10.1186/s41747-022-00315-8] [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: 05/12/2022] [Accepted: 12/01/2022] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND To evaluate the feasibility of a novel approach for predicting hepatocellular carcinoma (HCC) response to drug-eluting beads transarterial chemoembolization (DEB-TACE) using computed tomography hepatic arteriography enhancement mapping (CTHA-EM) method. METHODS This three-institution retrospective study included 29 patients with 46 HCCs treated with DEB-TACE between 2017 and 2020. Pre- and posttreatment CTHA-EM images were generated using a prototype deformable registration and subtraction software. Relative tumor enhancement (TPost/pre-RE) defined as the ratio of tumor enhancement to normal liver tissue was calculated to categorize tumor response as residual (TPost-RE > 1) versus non-residual (TPost-RE ≤ 1) enhancement, which was blinded compared to the response assessment on first follow-up imaging using modified RECIST criteria. Additionally, for tumors with residual enhancement, CTHA-EM was evaluated to identify its potential feeding arteries. RESULTS CTHA-EM showed residual enhancement in 18/46 (39.1%) and non-residual enhancement in 28/46 (60.9%) HCCs, with significant differences on TPost-RE (3.05 ± 2.4 versus 0.48 ± 0.23, respectively; p < 0.001). The first follow-up imaging showed non-complete response (partial response or stable disease) in 19/46 (41.3%) and complete response in 27/46 (58.7%) HCCs. CTHA-EM had a response prediction sensitivity of 94.7% (95% CI, 74.0-99.9) and specificity of 100% (95% CI, 87.2-100). Feeding arteries to the residual enhancement areas were demonstrated in all 18 HCCs (20 arteries where DEB-TACE was delivered, 2 newly developed collaterals following DEB-TACE). CONCLUSION CTHA-EM method was highly accurate in predicting initial HCC response to DEB-TACE and identifying feeding arteries to the areas of residual arterial enhancement.
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Affiliation(s)
- Ryosuke Taiji
- grid.240145.60000 0001 2291 4776Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 USA ,grid.410814.80000 0004 0372 782XDepartment of Radiology and Nuclear Medicine, Nara Medical University, Kashihara, Nara, 634-8521 Japan
| | - Yuan-Mao Lin
- grid.240145.60000 0001 2291 4776Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 USA
| | - Gouthami Chintalapani
- Siemens Medical Solutions USA Inc, 501 North Barrington Road, Hoffman Estates, IL 60192 USA
| | - Ethan Y. Lin
- grid.240145.60000 0001 2291 4776Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 USA
| | - Steven Y. Huang
- grid.240145.60000 0001 2291 4776Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 USA
| | - Armeen Mahvash
- grid.240145.60000 0001 2291 4776Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 USA
| | - Rony Avritscher
- grid.240145.60000 0001 2291 4776Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 USA
| | - Chien-An Liu
- grid.278247.c0000 0004 0604 5314Department of Radiology, Taipei Veterans General Hospital, Taipei, 112 Taiwan ,grid.260539.b0000 0001 2059 7017College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Rheun-Chuan Lee
- grid.278247.c0000 0004 0604 5314Department of Radiology, Taipei Veterans General Hospital, Taipei, 112 Taiwan ,grid.260539.b0000 0001 2059 7017College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Vivian Resende
- grid.8430.f0000 0001 2181 4888Department of Surgery, Federal University of Minas Gerais, Belo Horizonte, MG Brazil
| | - Hideyuki Nishiofuku
- grid.410814.80000 0004 0372 782XDepartment of Radiology and Nuclear Medicine, Nara Medical University, Kashihara, Nara, 634-8521 Japan
| | - Toshihiro Tanaka
- grid.410814.80000 0004 0372 782XDepartment of Radiology and Nuclear Medicine, Nara Medical University, Kashihara, Nara, 634-8521 Japan
| | - Kimihiko Kichikawa
- grid.410814.80000 0004 0372 782XDepartment of Radiology and Nuclear Medicine, Nara Medical University, Kashihara, Nara, 634-8521 Japan
| | - Ernst Klotz
- grid.481749.70000 0004 0552 4145Siemens Healthineers, Siemensstraße 3, 91301 Forchheim, Germany
| | - Sanjay Gupta
- grid.240145.60000 0001 2291 4776Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 USA
| | - Bruno C. Odisio
- grid.240145.60000 0001 2291 4776Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 USA
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Vallati G, Trobiani C. Follow-Up (Response to Treatment, Clinical Management). TRANSARTERIAL CHEMOEMBOLIZATION (TACE) 2023:131-141. [DOI: 10.1007/978-3-031-36261-3_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Zhu W, Zhong Z, Yan H, Guo H, Xiao M, He X, Gao F, Zhang F. Clinical efficacy of CT-guided 125I brachytherapy in patients with local residual or recurrent hepatocellular carcinoma after thermal ablation. Insights Imaging 2022; 13:185. [PMID: 36471084 PMCID: PMC9723008 DOI: 10.1186/s13244-022-01327-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 11/09/2022] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES Treatment methods of local residual or recurrent hepatocellular carcinoma (HCC) after thermal ablation are limited. Therefore, our study aimed to explore the efficacy and prognostic factors of 125I brachytherapy for local residual or recurrent lesion after thermal ablation. METHODS A total of 114 patients with 212 local residual or recurrent HCC tumors after thermal ablation underwent 125I brachytherapy. Local progression-free survival (LPFS) and prognostic factors were analyzed by Kaplan-Meier curves and the Cox model. RESULTS After a 6-month follow-up, the percentage of patients who achieved complete response (CR), partial response (PR), and stable disease (SD) was 57%, 13.2%, and 5.2%, respectively. The 1-, 2-, and 3-year LPFS rates were 58.7%, 50.0%, and 41.2%, respectively. Portal vein tumor thrombus (PVTT) (p = 0.03), the number of intrahepatic tumors (p = 0.01), and AFP level (p = 0.02) were independent risk factors for local tumor progression (LTP). The median LPFS in patients without PVTT (22 months) was much longer compared to those with PVTT (10 months). The median LPFS in patients with less than three intrahepatic lesions improved from 17 to 24 months. The median LPFS was only 5 months in the high AFP group, but was prolonged with a decrease in AFP level (24 months). No severe complications were recorded. All complications were controllable and treatable. CONCLUSIONS CT-guided 125I brachytherapy was a safe and effective treatment for patients with local residual or recurrent HCC after thermal ablation to improve local control rate.
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Affiliation(s)
- Wenliang Zhu
- grid.488530.20000 0004 1803 6191Department of Minimally Invasive and Interventional Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road, East, Guangzhou, 510060 People’s Republic of China
| | - Zhihui Zhong
- grid.488530.20000 0004 1803 6191Department of Minimally Invasive and Interventional Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road, East, Guangzhou, 510060 People’s Republic of China
| | - Huzheng Yan
- grid.12981.330000 0001 2360 039XDepartment of Interventional Radiology, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630 People’s Republic of China
| | - Huanqing Guo
- grid.488530.20000 0004 1803 6191Department of Minimally Invasive and Interventional Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road, East, Guangzhou, 510060 People’s Republic of China
| | - Meigui Xiao
- grid.488530.20000 0004 1803 6191Department of Minimally Invasive and Interventional Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road, East, Guangzhou, 510060 People’s Republic of China
| | - Xu He
- grid.452930.90000 0004 1757 8087ZhuHai Interventional Medical Center, ZhuHai People’s Hospital (ZhuHai Hospital Affiliated With Jinan University), Jinan University, ZhuHai, 519000 Guangdong People’s Republic of China
| | - Fei Gao
- grid.488530.20000 0004 1803 6191Department of Minimally Invasive and Interventional Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road, East, Guangzhou, 510060 People’s Republic of China
| | - Fujun Zhang
- grid.488530.20000 0004 1803 6191Department of Minimally Invasive and Interventional Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road, East, Guangzhou, 510060 People’s Republic of China
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Giuffrida P, Celsa C, Antonucci M, Peri M, Grassini MV, Rancatore G, Giacchetto CM, Cannella R, Incorvaia L, Corsini LR, Morana P, La Mantia C, Badalamenti G, Brancatelli G, Cammà C, Cabibbo G. The Evolving Scenario in the Assessment of Radiological Response for Hepatocellular Carcinoma in the Era of Immunotherapy: Strengths and Weaknesses of Surrogate Endpoints. Biomedicines 2022; 10:2827. [PMID: 36359347 PMCID: PMC9687474 DOI: 10.3390/biomedicines10112827] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/02/2022] [Indexed: 08/30/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a challenging malignancy characterised by clinical and biological heterogeneity, independent of the stage. Despite the application of surveillance programs, a substantial proportion of patients are diagnosed at advanced stages when curative treatments are no longer available. The landscape of systemic therapies has been rapidly growing over the last decade, and the advent of immune-checkpoint inhibitors (ICIs) has changed the paradigm of systemic treatments. The coexistence of the tumour with underlying cirrhosis exposes patients with HCC to competing events related to tumour progression and/or hepatic decompensation. Therefore, it is relevant to adopt proper clinical endpoints to assess the extent of treatment benefit. While overall survival (OS) is the most accepted endpoint for phase III randomised controlled trials (RCTs) and drug approval, it is affected by many limitations. To overcome these limits, several clinical and radiological outcomes have been used. For instance, progression-free survival (PFS) is a useful endpoint to evaluate the benefit of sequential treatments, since it is not influenced by post-progression treatments, unlike OS. Moreover, radiological endpoints such as time to progression (TTP) and objective response rate (ORR) are frequently adopted. Nevertheless, the surrogacy between these endpoints and OS in the setting of unresectable HCC (uHCC) remains uncertain. Since most of the surrogate endpoints are radiology-based (e.g., PFS, TTP, ORR), the use of standardised tools is crucial for the evaluation of radiological response. The optimal way to assess the radiological response has been widely debated, and many criteria have been proposed over the years. Furthermore, none of the criteria have been validated for immunotherapy in advanced HCC. The coexistence of the underlying chronic liver disease and the access to several lines of treatments highlight the urgent need to capture early clinical benefit and the need for standardised radiological criteria to assess cancer response when using ICIs in mono- or combination therapies. Here, we review the most commonly used clinical and radiological endpoints for trial design, as well as their surrogacy with OS. We also review the criteria for radiological response to treatments for HCC, analysing the major issues and the potential future perspectives.
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Affiliation(s)
- Paolo Giuffrida
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Ciro Celsa
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
- Department of Surgical, Oncological, and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
| | - Michela Antonucci
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
| | - Marta Peri
- Department of Surgical, Oncological, and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
| | - Maria Vittoria Grassini
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Gabriele Rancatore
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Carmelo Marco Giacchetto
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Roberto Cannella
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
| | - Lorena Incorvaia
- Department of Surgical, Oncological, and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
| | - Lidia Rita Corsini
- Department of Surgical, Oncological, and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
| | - Piera Morana
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Claudia La Mantia
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Giuseppe Badalamenti
- Department of Surgical, Oncological, and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
| | - Giuseppe Brancatelli
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
| | - Calogero Cammà
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Giuseppe Cabibbo
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
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Liu CH, Peng CM, Hwang JI, Liang PC, Chen PJ, Abi-Jaoudeh N, Giiang LH, Tyan YS. Phase I Dose-Escalation Study of Tirapazamine Chemoembolization for Unresectable Early- and Intermediate-Stage Hepatocellular Carcinoma. J Vasc Interv Radiol 2022; 33:926-933.e1. [PMID: 35504436 DOI: 10.1016/j.jvir.2022.04.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 04/03/2022] [Accepted: 04/21/2022] [Indexed: 11/16/2022] Open
Abstract
PURPOSE To investigate the safety of replacing doxorubicin with tirapazamine in conventional transarterial chemoembolization (TACE) in an Asian population with hepatocellular carcinoma (HCC), and to determine the optimal tirapazamine dose for phase II studies. MATERIALS AND METHODS This was a phase I, 3 + 3 dose-escalation study for patients with unresectable early- and intermediate-stage HCC who received 5, 10, or 20 mg/m2 of intra-arterial (IA) tirapazamine followed by ethiodized oil/gelatin sponge-based embolization. Key eligibilities included HCCs no more than 10 cm in diameter, prior embolization allowed, Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh score of 5-7, and platelet count of ≥60,000 μL. Dose-limiting toxicity (DLT) was defined as any grade 3 nonhematological or grade 4 hematological toxicity, with the exception of transient elevation of aminotransferase levels after the procedure. RESULTS Seventeen patients were enrolled, 59% of whom had progression from a prior HCC therapy and 35% of whom had progression or recurrence after TACE. All patients tolerated the tirapazamine TACE well without any DLT or serious adverse event. Using the modified Response Evaluation Criteria in Solid Tumors, the complete response (CR) rate was 47%, and the CR + partial response rate was 65%. The median duration of response was not reached. The median time to progression was 12.6 months (95% confidence interval, 5.1-not reached). The median overall survival was 29.3 months. The selected phase II dose was set at a fixed dose of 35 mg of IA tirapazamine. CONCLUSIONS IA tirapazamine with transarterial embolization was well tolerated and showed promising efficacy signals in intermediate-stage HCC, justifying pursuit of a phase II study.
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Affiliation(s)
- Chang-Hsien Liu
- Department of Medical Imaging, China Medical University Hsinchu Hospital and China Medical University, Hsinchu, Taiwan, Republic of China; Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, Republic of China; Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
| | - Cheng-Ming Peng
- Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China
| | - Jen-I Hwang
- Department of Radiology, Taichung Veteran General Hospital, and Department of Medical Imaging, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan, Republic of China
| | - Po-Chin Liang
- Department of Medical Imaging, National Taiwan University Hospital Hsin-Chu Branch, and National Taiwan University Hospital, Taipei, Taiwan, Republic of China
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
| | - Nadine Abi-Jaoudeh
- Department of Radiology, University of California, Irvine Medical Center, Orange, California, USA
| | - Lung-Hui Giiang
- Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Yu-Shen Tyan
- Department of Radiology, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China
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Nayak G, Bhuyan SK, Bhuyan R, Sahu A, Kar D, Kuanar A. Global emergence of Enterovirus 71: a systematic review. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2022; 11:78. [PMID: 35730010 PMCID: PMC9188855 DOI: 10.1186/s43088-022-00258-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 05/29/2022] [Indexed: 02/06/2023] Open
Abstract
Background Hand, foot, and mouth disease (HFMD) is a viral infection caused by a virus from the enterovirus genus of picornavirus family that majorly affects children. Though most cases of HFMD do not cause major problems, the outbreaks of Enterovirus 71 (EV71) can produce a high risk of neurological sequelae, including meningoencephalitis, lung difficulties, and mortality. In Asia, HFMD caused by EV71 has emerged as an acutely infectious disease of highly pathogenic potential, which demands the attention of the international medical community.
Main body of the abstract Some online databases including NCBI, PubMed, Google Scholar, ProQuest, Scopus, and EBSCO were also accessed using keywords relating to the topic for data mining. The paid articles were accessed through the Centre Library facility of Siksha O Anusandhan University. This work describes the structure, outbreak, molecular epidemiology of Enterovirus 71 along with different EV71 vaccines. Many vaccines have been developed such as inactivated whole-virus live attenuated, subviral particles, and DNA vaccines to cure the patients. In Asia–Pacific nations, inactivated EV71 vaccination still confronts considerable obstacles in terms of vaccine standardization, registration, price, and harmonization of pathogen surveillance and measurements. Short conclusion HFMD has emerged as a severe health hazard in Asia–Pacific countries in recent decades. In Mainland China and other countries with high HFMD prevalence, the inactivated EV71 vaccination will be a vital tool in safeguarding children's health. When creating inactivated EV71 vaccines, Mainland China ensured maintaining high standards of vaccine quality. The Phase III clinical studies were used to confirm the safety and effectiveness of vaccinations. Graphical Abstract ![]()
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Affiliation(s)
- Gayatree Nayak
- Centre for Biotechnology, Siksha O Anusandhan (Deemed to Be) University, Kalinga Nagar, Ghatikia, Bhubaneswar, Odisha 751003 India
| | - Sanat Kumar Bhuyan
- Institute of Dental Sciences, Siksha 'O' Anusandhan (Deemed to Be) University, Bhubaneswar, Odisha 751003 India
| | - Ruchi Bhuyan
- Department of Medical Research, Health Science, IMS and SUM Hospital, Siksha O Anusandhan (Deemed to Be) University, Bhubaneswar, Odisha 751003 India
| | - Akankshya Sahu
- Centre for Biotechnology, Siksha O Anusandhan (Deemed to Be) University, Kalinga Nagar, Ghatikia, Bhubaneswar, Odisha 751003 India
| | - Dattatreya Kar
- Department of Medical Research, Health Science, IMS and SUM Hospital, Siksha O Anusandhan (Deemed to Be) University, Bhubaneswar, Odisha 751003 India
| | - Ananya Kuanar
- Centre for Biotechnology, Siksha O Anusandhan (Deemed to Be) University, Kalinga Nagar, Ghatikia, Bhubaneswar, Odisha 751003 India
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10
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Xia D, Wang Q, Bai W, Wang E, Wang Z, Mu W, Sun J, Huang M, Yin G, Li H, Zhao H, Zhang C, Li J, Wu J, Zhu X, Yang S, Pan X, Li J, Li Z, Xu G, Shi H, Zhang H, Zhang Y, Ding R, Yu H, Zheng L, Yang X, Wang G, You N, Feng L, Zhang S, Huang W, Xu T, Fan W, Li X, Yang X, Zhou W, Wang W, Li X, Wang Z, Luo B, Niu J, Yuan J, Lv Y, Li K, Guo W, Yin Z, Fan D, Xia J, Han G. Optimal time point of response assessment for predicting survival is associated with tumor burden in hepatocellular carcinoma receiving repeated transarterial chemoembolization. Eur Radiol 2022; 32:5799-5810. [PMID: 35381853 DOI: 10.1007/s00330-022-08716-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 02/08/2022] [Accepted: 03/05/2022] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Objective response rate (ORR) under mRECIST criteria after transarterial chemoembolization (TACE) is a well-perceived surrogate endpoint of overall survival (OS). However, its optimal time point remains controversial and may be influenced by tumor burden. We aim to investigate the surrogacy of initial/best ORR in relation to tumor burden. METHODS A total of 1549 eligible treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh score ≤ 7, and performance status score ≤ 1 undergoing TACE between January 2010 and May 2016 from 17 academic hospitals were retrospectively analyzed. Based on "six-and-twelve" criteria, tumor burden was graded as low, intermediate, and high if the sum of the maximum tumor diameter and tumor number was ≤ 6, > 6 but ≤ 12, and > 12, respectively. RESULTS Both initial and best ORRs interacted with tumor burden. Initial and best ORRs could equivalently predict and correlate with OS in low (adjusted HR, 2.55 and 2.95, respectively, both p < 0.001; R = 0.84, p = 0.035, and R = 0.97, p = 0.002, respectively) and intermediate strata (adjusted HR, 1.81 and 2.22, respectively, both p < 0.001; R = 0.74, p = 0.023, and R = 0.9, p = 0.002, respectively). For high strata, only best ORR exhibited qualified surrogacy (adjusted HR, 2.61, p < 0.001; R = 0.70, p = 0.035), whereas initial ORR was not significant (adjusted HR, 1.08, p = 0.357; R = 0.22, p = 0.54). CONCLUSIONS ORR as surrogacy of OS is associated with tumor burden. For patients with low/intermediate tumor burden, initial ORR should be preferred in its early availability upon similar sensitivity, whereas for patients with high tumor burden, best ORR has optimal sensitivity. Timing of OR assessment should be tailored according to tumor burden. KEY POINTS • This is the first study utilizing individual patient data to comprehensively analyze the surrogacy of ORR with a long follow-up period. • Optimal timing of ORR assessment for predicting survival should be tailored according to tumor burden. • For patients with low and intermediate tumor burden, initial ORR is optimal for its timeliness upon similar sensitivity with best ORR. For patients with high tumor burden, best ORR has optimal sensitivity.
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Affiliation(s)
- Dongdong Xia
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Qiuhe Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Wei Bai
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Enxin Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,Department of Medical Affairs, Air Force Hospital of Western Theater Command, Chengdu, Sichuan Province, China
| | - Zhexuan Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Wei Mu
- Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Junhui Sun
- Department of Hepatobiliary and Pancreatic Interventional Cancer, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ming Huang
- Department of Minimally Invasive International Therapy, The Third Affiliated Hospital of Kunming University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Guowen Yin
- Department of Interventional Radiology, Jiangsu Provincial Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Hailiang Li
- Department of Interventional Radiology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Hui Zhao
- Department of Interventional Radiology, The Affiliated Hospital of Nantong University, Nantong, China
| | - Chunqing Zhang
- Department of Gastroenterology and Hepatology, Shandong Province Hospital Affiliated to Shandong University, Jinan, China
| | - Jing Li
- Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Jianbing Wu
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xiaoli Zhu
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Shufa Yang
- Department of Interventional Radiology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China
| | - Xingnan Pan
- Clinical Liver Diseases Research Center, Nanjing Military Command, 180th Hospital of PLA, Quanzhou, China
| | - Jiaping Li
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zixiang Li
- Interventional Medical Center of The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Guohui Xu
- Department of Interventional Radiology, Sichuan Cancer Hospital & Institute, Chengdu, China
| | - Haibin Shi
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hui Zhang
- Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Yuelin Zhang
- Department of Hepatobiliary and Pancreatic Interventional Cancer, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Rong Ding
- Department of Minimally Invasive International Therapy, The Third Affiliated Hospital of Kunming University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Hui Yu
- Department of Interventional Radiology, Jiangsu Provincial Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Lin Zheng
- Department of Interventional Radiology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiaohu Yang
- Department of Interventional Radiology, The Affiliated Hospital of Nantong University, Nantong, China
| | - Guangchuan Wang
- Department of Gastroenterology and Hepatology, Shandong Province Hospital Affiliated to Shandong University, Jinan, China
| | - Nan You
- Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Long Feng
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Shuai Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Wukui Huang
- Department of Interventional Radiology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China
| | - Tao Xu
- Clinical Liver Diseases Research Center, Nanjing Military Command, 180th Hospital of PLA, Quanzhou, China
| | - Wenzhe Fan
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xueda Li
- Interventional Medical Center of The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xuegang Yang
- Department of Interventional Radiology, Sichuan Cancer Hospital & Institute, Chengdu, China
| | - Weizhong Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wenjun Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Xiaomei Li
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Zhengyu Wang
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Bohan Luo
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Jing Niu
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Jie Yuan
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Yong Lv
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Kai Li
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Wengang Guo
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Zhanxin Yin
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Jielai Xia
- Department of Health Statistics, Fourth Military Medical University, Xi'an, China
| | - Guohong Han
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China. .,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
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11
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Weber M, Lam M, Chiesa C, Konijnenberg M, Cremonesi M, Flamen P, Gnesin S, Bodei L, Kracmerova T, Luster M, Garin E, Herrmann K. EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds. Eur J Nucl Med Mol Imaging 2022; 49:1682-1699. [PMID: 35146577 PMCID: PMC8940802 DOI: 10.1007/s00259-021-05600-z] [Citation(s) in RCA: 106] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 10/19/2021] [Indexed: 12/15/2022]
Abstract
Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.
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Affiliation(s)
- M Weber
- Department of Nuclear medicine, University clinic Essen, Essen, Germany.
| | - M Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - C Chiesa
- Nuclear Medicine, Foundation IRCCS National Tumour Institute, Milan, Italy
| | - M Konijnenberg
- Nuclear Medicine Department, Erasmus MC, Rotterdam, The Netherlands
| | - M Cremonesi
- Radiation Research Unit, IEO European Institute of Oncology IRCCS, Via Giuseppe Ripamonti, 435, 20141, Milan, MI, Italy
| | - P Flamen
- Department of Nuclear Medicine, Institut Jules Bordet-Université Libre de Bruxelles (ULB), 1000, Brussels, Belgium
| | - S Gnesin
- Institute of Radiation physics, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - L Bodei
- Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - T Kracmerova
- Department of Medical Physics, Motol University Hospital, Prague, Czech Republic
| | - M Luster
- Department of Nuclear medicine, University hospital Marburg, Marburg, Germany
| | - E Garin
- Department of Nuclear Medicine, Cancer, Institute Eugène Marquis, Rennes, France
| | - K Herrmann
- Department of Nuclear medicine, University clinic Essen, Essen, Germany
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12
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Li B, Zhou L, Xu A, Li Q, Xiang H, Huang Y, Peng L, Xiang K, Zhang M, Wang N. Apparent Diffusion Coefficient as a Noninvasive Biomarker for the Early Response in Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization using Drug-Eluting Beads. Curr Med Imaging 2022; 18:1186-1194. [PMID: 35249499 DOI: 10.2174/1573405618666220304141632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/03/2021] [Accepted: 12/28/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Prognostic evaluation for hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) using drug-eluting beads (DEBs) is essential for guiding the personalized treatment and follow-up strategy. Apparent diffusion coefficient (ADC) has been reported as a biomarker in conventional TACE. OBJECTIVE To evaluate the diagnostic value of ADCbaseline, ADC change, and ADCratio in predicting the early objective response for HCC after DEB-TACE. METHODS This prospective single-center study included 32 consecutive patients undergoing dynamic contrast-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging before and 1 month after DEB-TACE. After DEB-TACE, patients were grouped based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria into responders (complete response [CR], partial response [PR] ) and nonresponders (stable disease [SD], progressive disease [PD]). The Mann-Whitney U test and receiver operating characteristic (ROC) curves were performed to assess the statistical differences in ADCbaseline, ADC change, and ADCratio between responders and nonresponders. RESULTS At post-DEB-TACE follow-up MRI, 62.5% (n = 20, 11 CRs, and 9 PRs) of patients showed objective response, and 37.5% (n = 12, 7 SDs, and 5 PDs) did not respond to chemoembolization. Nonresponders had a significantly higher ADCbaseline value than responders (p < 0.001). The ROC for identifying the response to chemoembolization demonstrated that the threshold ADCbaseline value of 0.920 × 10-3 mm2/s had 100% sensitivity and 70% specificity. The ADC change and ADCratio of responders were higher than that of nonresponders (p < 0.001). CONCLUSION ADCbaseline, ADC change, and ADCratio may be utilized as a noninvasive biomarker for predicting the early response of HCC to DEB-TACE.
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Affiliation(s)
- Basen Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Zhou
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Anhui Xu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qin Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huihua Xiang
- Department of Radiology, Minda Hospital of Hubei Minzu University, Enshi, China
| | - Yanrong Huang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ling Peng
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kun Xiang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mingfeng Zhang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Nan Wang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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13
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Liver MRI and clinical findings to predict response after drug eluting bead transarterial chemoembolization in hepatocellular carcinoma. Sci Rep 2021; 11:24076. [PMID: 34911966 PMCID: PMC8674226 DOI: 10.1038/s41598-021-01839-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 11/01/2021] [Indexed: 12/24/2022] Open
Abstract
To identify the gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI) and laboratory findings that enable prediction of treatment response and disease-free survival (DFS) after the first session of drug eluting bead transarterial chemoembolization (DEB-TACE) in patients with hepatocellular carcinoma (HCC). A total of 55 patients who underwent GA-enhanced MRI and DEB-TACE from January 2014 to December 2018 were included. All MRI features were reviewed by two radiologists. Treatment response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Univariate and multivariate logistic regression analyses were used to determine predictive factors of treatment response and DFS, respectively. A total of 27 patients (49.1%) achieved complete response (CR) after one session of treatment. There were no significant differences between the two groups in terms of clinical and laboratory characteristics. Heterogeneous signal intensity in the hepatobiliary phase (HBP) was the only independent predictor of non-CR (odds ratio, 4.807; p = 0.048). Recurrent HCC was detected in 19 patients (70.4%) after CR. In the multivariate analysis, elevated serum alpha-fetoprotein (AFP) level (≥ 30 ng/mL) was the only significant parameter associated with DFS (hazard ratio, 2.916; p = 0.040). This preliminary study demonstrated that heterogeneous signal intensity in the HBP and high serum AFP were useful predictive factors for poor treatment response and short DFS after DEB-TACE, respectively.
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14
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Svecic A, Mansour R, Tang A, Kadoury S. Prediction of post transarterial chemoembolization MR images of hepatocellular carcinoma using spatio-temporal graph convolutional networks. PLoS One 2021; 16:e0259692. [PMID: 34874934 PMCID: PMC8651128 DOI: 10.1371/journal.pone.0259692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 10/24/2021] [Indexed: 11/25/2022] Open
Abstract
Magnetic resonance imaging (MRI) plays a critical role in the planning and monitoring of hepatocellular carcinomas (HCC) treated with locoregional therapies, in order to assess disease progression or recurrence. Dynamic contrast-enhanced (DCE)-MRI sequences offer temporal data on tumor enhancement characteristics which has strong prognostic value. Yet, predicting follow-up DCE-MR images from which tumor enhancement and viability can be measured, before treatment of HCC actually begins, remains an unsolved problem given the complexity of spatial and temporal information. We propose an approach to predict future DCE-MRI examinations following transarterial chemoembolization (TACE) by learning the spatio-temporal features related to HCC response from pre-TACE images. A novel Spatial-Temporal Discriminant Graph Neural Network (STDGNN) based on graph convolutional networks is presented. First, embeddings of viable, equivocal and non-viable HCCs are separated within a joint low-dimensional latent space, which is created using a discriminant neural network representing tumor-specific features. Spatial tumoral features from independent MRI volumes are then extracted with a structural branch, while dynamic features are extracted from the multi-phase sequence with a separate temporal branch. The model extracts spatio-temporal features by a joint minimization of the network branches. At testing, a pre-TACE diagnostic DCE-MRI is embedded on the discriminant spatio-temporal latent space, which is then translated to the follow-up domain space, thus allowing to predict the post-TACE DCE-MRI describing HCC treatment response. A dataset of 366 HCC's from liver cancer patients was used to train and test the model using DCE-MRI examinations with associated pathological outcomes, with the spatio-temporal framework yielding 93.5% classification accuracy in response identification, and generating follow-up images yielding insignificant differences in perfusion parameters compared to ground-truth post-TACE examinations.
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Affiliation(s)
- Andrei Svecic
- Department of Computer Engineering, MedICAL, Polytechnique Montréal, Montréal, Québec, Canada
| | | | - An Tang
- CHUM Research Center, Montréal, Québec, Canada
- Department of Radiology, CHUM, Montréal, Québec, Canada
| | - Samuel Kadoury
- Department of Computer Engineering, MedICAL, Polytechnique Montréal, Montréal, Québec, Canada
- CHUM Research Center, Montréal, Québec, Canada
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15
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Greten TF, Abou-Alfa GK, Cheng AL, Duffy AG, El-Khoueiry AB, Finn RS, Galle PR, Goyal L, He AR, Kaseb AO, Kelley RK, Lencioni R, Lujambio A, Mabry Hrones D, Pinato DJ, Sangro B, Troisi RI, Wilson Woods A, Yau T, Zhu AX, Melero I. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma. J Immunother Cancer 2021; 9:e002794. [PMID: 34518290 PMCID: PMC8438858 DOI: 10.1136/jitc-2021-002794] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/02/2021] [Indexed: 12/11/2022] Open
Abstract
Patients with advanced hepatocellular carcinoma (HCC) have historically had few options and faced extremely poor prognoses if their disease progressed after standard-of-care tyrosine kinase inhibitors (TKIs). Recently, the standard of care for HCC has been transformed as a combination of the immune checkpoint inhibitor (ICI) atezolizumab plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was shown to offer improved overall survival in the first-line setting. Immunotherapy has demonstrated safety and efficacy in later lines of therapy as well, and ongoing trials are investigating novel combinations of ICIs and TKIs, in addition to interventions earlier in the course of disease or in combination with liver-directed therapies. Because HCC usually develops against a background of cirrhosis, immunotherapy for liver tumors is complex and oncologists need to account for both immunological and hepatological considerations when developing a treatment plan for their patients. To provide guidance to the oncology community on important concerns for the immunotherapeutic care of HCC, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for HCC, including diagnosis and staging, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with HCC.
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Affiliation(s)
- Tim F Greten
- Thoracic and GI Malignancies Branch, National Cancer Institute, Bethesda, Maryland, USA
| | - Ghassan K Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Weill Medical College at Cornell University, New York, New York, USA
| | - Ann-Lii Cheng
- Department of Medical Oncology, National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan
| | - Austin G Duffy
- The Mater Hospital/University College Dublin, Dublin, Ireland
| | - Anthony B El-Khoueiry
- Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA
| | - Richard S Finn
- David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
| | | | - Lipika Goyal
- Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Aiwu Ruth He
- Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Ahmed O Kaseb
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Robin Kate Kelley
- Department of Medicine (Hematology/Oncology), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA
| | - Riccardo Lencioni
- Department of Radiology, University of Pisa School of Medicine, Pisa, Italy
- Miami Cancer Institute, Miami, Florida, USA
| | - Amaia Lujambio
- Oncological Sciences Department, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Donna Mabry Hrones
- Thoracic and GI Malignancies Branch, National Cancer Institute, Bethesda, Maryland, USA
| | - David J Pinato
- Department of Surgery & Cancer, Imperial College London, London, UK
| | - Bruno Sangro
- Clinica Universidad de Navarra-Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | | | - Andrea Wilson Woods
- Blue Faery: The Adrienne Wilson Liver Cancer Association, Birmingham, Alabama, USA
| | - Thomas Yau
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong
| | - Andrew X Zhu
- Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
- Jiahui Health, Jiahui International Cancer Center, Shanghai, China
| | - Ignacio Melero
- Clinica Universidad de Navarra-Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain
- Foundation for Applied Medical Research (FIMA), Pamplona, Spain
- Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain
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Pirasteh A, Sorra EA, Marquez H, Sibley RC, Fielding JR, Vij A, Rich NE, Arroyo A, Yopp AC, Khatri G, Singal AG, Yokoo T. LI-RADS treatment response algorithm after first-line DEB-TACE: reproducibility and prognostic value at initial post-treatment CT/MRI. Abdom Radiol (NY) 2021; 46:3708-3716. [PMID: 33755735 DOI: 10.1007/s00261-021-03043-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/17/2021] [Accepted: 03/05/2021] [Indexed: 02/06/2023]
Abstract
PURPOSE To evaluate the inter-reader reproducibility and prognostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (LR-TR) at the time of initial post-treatment evaluation following drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC). METHODS This retrospective study included patients with HCC who underwent first-line DEB-TACE between January 2011 and December 2015. Six readers (three fellowship-trained radiologists and three radiology trainees) independently assessed lesion-level response in up to two treated lesions per LR-TR and modified Response Evaluation Criteria in Solid Tumors (mRECIST)-target criteria, as well as patient-level response per mRECIST-overall criteria, on the initial post-treatment CT/MRI. Inter-reader agreement was calculated by Fleiss' multi-reader κ. We tested whether LR-TR, mRECIST-target, and mRECIST-overall response were associated with overall survival using Kaplan-Meier and Cox proportional hazard model analyses. RESULTS A total of 82 patients with 113 treated target lesions were included. Inter-reader agreement was moderate for LR-TR and mRECIST-overall (κ range 0.42-0.57), and substantial for mRECIST-target (κ range 0.62-0.66), among all three reader-groups: all readers, experienced readers, and less-experienced readers. LR-TR and mRECIST-target response were not significantly associated with overall survival regardless of reader experience (P > 0.05). In contrast, mRECIST-overall response was significantly associated with overall survival when assessed by all readers (P = 0.02) and experienced readers (P = 0.03), but not by the less-experienced readers (P = 0.35). CONCLUSION Although LR-TR algorithm has moderate inter-reader reproducibility, it alone may not predict overall survival on the initial post-treatment CT/MRI after first-line DEB-TACE for HCC.
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Affiliation(s)
- Ali Pirasteh
- Radiology, University of Wisconsin-Madison, 1111 Highland Ave, WIMR II, Room 2423, Madison, WI, 53705, USA.
- Medical Physics, University of Wisconsin-Madison, Madison, WI, USA.
- Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
| | - E Aleks Sorra
- Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Hector Marquez
- Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Robert C Sibley
- Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Julia R Fielding
- Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Abhinav Vij
- Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Nicole E Rich
- Digestive and Liver Diseases, Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ana Arroyo
- Digestive and Liver Diseases, Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Adam C Yopp
- Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Gaurav Khatri
- Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Amit G Singal
- Digestive and Liver Diseases, Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Takeshi Yokoo
- Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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Transarterial Chemoembolization of Hepatocellular Carcinoma with Oncozene Microspheres: An Initial, Short-Term Clinical Experience-A Retrospective, Matched, Comparison Study. Life (Basel) 2021; 11:life11070600. [PMID: 34201468 PMCID: PMC8305898 DOI: 10.3390/life11070600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/24/2021] [Accepted: 06/15/2021] [Indexed: 11/16/2022] Open
Abstract
Background: The purpose of this study is to describe a single institution's experience using Oncozene (OZ) microspheres for transarterial chemoembolization (OZ-TACE) of hepatocellular carcinoma (HCC), and to compare tolerability, safety, short-term radiographic tumor response, progression-free survival (PFS), and overall survival (OS) of these procedures to TACE (LC-TACE) performed with LC beads (LC). Methods: A retrospective, matched cohort study of patients undergoing DEB-TACE (drug-eluting bead transarterial chemoembolization) with OZ or LC was performed. The cohort comprised 23 patients undergoing 29 TACE with 75 or 100 μm OZ and 24 patients undergoing 29 TACE with 100-300 μm LC. Outcome measures were changes in liver function tests, complications, treatment tolerability, short-term radiographic tumor response according to modified RECIST criteria for HCC, PFS, and 1-year OS. The Mann-Whitney U test, Fisher exact test, and log rank test were used to compare the groups. Results: The BCLC or Child-Pugh scores were similar between the OZ and LC group. However, the two groups differed with respect to the etiology of background cirrhosis (p = 0.02). All other initial demographic and tumor characteristics were similar between the two groups. OZ-TACE used less doxorubicin per treatment compared to LC-TACE (median 50 vs. 75 mg; p = 0.0005). Rates of pain, nausea, and postembolization syndrome were similar, irrespective of the embolic agent used. OZ-TACE resulted in an overall complication rate comparable to LC-TACE (20.7% vs. 10.3%; p = 0.47). LC-TACE resulted in a higher percent increase in total bilirubin on post-procedure day 1 (median 18.8 vs. 0%; p = 0.05), but this difference resolved at 1 month. Both OZ-TACE and LC-TACE resulted in similar complete (31% vs. 24%) and objective (66% vs. 79%) target lesion response rates on 1-month post-TACE imaging. Both OZ-TACE and LC-TACE had similar median progression-free survival (283 vs. 209 days; p = 0.14) and 1-year overall survival rates (85% vs. 76%; p = 0.30). Conclusion: With a significantly reduced dose of doxorubicin, TACE performed with Oncozene microspheres in a heterogeneous patient population is well-tolerated, safe, and produces a similar radiological response and survival rate when compared to LC Bead TACE.
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Xu L, Wang S, Wang S, Wang Y, Li W, Lin G, Yuan Z. Baseline apparent diffusion coefficients: Validation study of new predictor of survival in patients with unresectable hepatocellular carcinoma following chemoembolization. JOURNAL OF X-RAY SCIENCE AND TECHNOLOGY 2021; 29:507-516. [PMID: 33814481 DOI: 10.3233/xst-200827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
OBJECTIVES To investigate whether the baseline apparent diffusion coefficient (ADC) can predict survival in the hepatocellular carcinoma (HCC) patients receiving chemoembolization. MATERIALS AND METHODS Diffusion-weighted MR imaging of HCC patients is performed within 2 weeks before chemoembolization. The ADC of the largest index lesion is recorded. Responses are assessed by mRECIST after the start of the second course of chemoembolization. Receiver operating characteristic (ROC) curve analysis is performed to evaluate the diagnostic performance and determine optimal cut-off values. Cox regression and Kaplan-Meier survival analyses are used to explore the differences in overall survival (OS) between the responders and non-responders. RESULTS The difference is statistically significant in the baseline ADC between the responders and non-responders (P < 0.001). ROC analyses indicate that the baseline ADC value is a good predictor of response to treatment with an area under the ROC curve (AUC) of 0.744 and the optimal cut-off value of 1.22×10-3 mm2/s. The Cox regression model shows that the baseline ADC is an independent predictor of OS, with a 57.2% reduction in risk. CONCLUSION An optimal baseline ADC value is a functional imaging response biomarker that has higher discriminatory power to predict tumor response and prolonged survival following chemoembolization in HCC patients.
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Affiliation(s)
- Lichao Xu
- Department of Interventional Radiology and Image Guided Medicine, Shanghai Cancer Hospital, Fudan University, Shanghai, China
| | - Shiqin Wang
- Department of Radiology, Huadong Hospital, Fudan University, Shanghai, China
| | - Shengping Wang
- Department of Radiology, Shanghai Cancer Hospital, Fudan University, Shanghai, China
| | - Ying Wang
- Department of Interventional Radiology and Image Guided Medicine, Shanghai Cancer Hospital, Fudan University, Shanghai, China
| | - Wentao Li
- Department of Interventional Radiology and Image Guided Medicine, Shanghai Cancer Hospital, Fudan University, Shanghai, China
| | - Guangwu Lin
- Department of Radiology, Huadong Hospital, Fudan University, Shanghai, China
| | - Zheng Yuan
- Department of Radiology, Huadong Hospital, Fudan University, Shanghai, China
- Department of Radiology, Shanghai No. 85 Hospital, Shanghai, China
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19
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Kim BH. Selecting the Right Tool for the Right Job: Which Response Criteria Better Predicts Survival of Patients Treated with Transarterial Radioembolization? Gut Liver 2020; 14:671-672. [PMID: 33191309 PMCID: PMC7667919 DOI: 10.5009/gnl20324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Affiliation(s)
- Bo Hyun Kim
- Division of Gastroenterology, Department of Internal Medicine, Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
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20
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Domaratius C, Settmacher U, Malessa C, Teichgräber U. Transarterial chemoembolization with drug-eluting beads in patients with hepatocellular carcinoma: response analysis with mRECIST. Diagn Interv Radiol 2020; 27:85-93. [PMID: 33135664 DOI: 10.5152/dir.2020.19439] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE According to the Barcelona Clinic Liver Cancer (BCLC) staging classification, transarterial chemoembolization (TACE) is the treatment of choice for intermediate hepatocellular carcinoma (HCC). Thereby, the use of drug-eluting beads (DEB) as embolic agents has been recently established in clinical practice. The aim of this study was to evaluate tumor response after DEB-TACE. METHODS This retrospective study was approved by the institutional ethics committee. Overall, 89 patients with HCC (Child Pugh A or B) receiving DEB-TACE as palliative treatment option or as bridging before liver transplantation were included in the study. Tumor response was assessed by modified response evaluation criteria in solid tumors (mRECIST) and a tumor growth rate. Survival analysis was performed using Kaplan-Meier estimator with log-rank testing and Cox proportional hazards. RESULTS A total of 188 TACE procedures were performed between 2006 and 2010. After the last intervention, 18% achieved complete response, 45% achieved partial response, 28% had stable disease and 9% had progressive disease. Using the tumor growth rate, 90% of all patients showed a tumor reduction between first and final response evaluation. The 6-month, 1-, 2- and 3-year overall survival rates were 86.5%, 67.4%, 47.2%, and 33.7%, with a median survival of 45, 24, 15, and 14 months for complete response, partial response, stable disease, and progressive disease, respectively. Tumor reduction showed a positive effect on survival. CONCLUSION DEB-TACE offers conclusive response results with mRECIST and proves a strong tendency of tumor reduction on survival benefits. Therefore, tumor growth rate represents a possible parameter to predict survival.
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Affiliation(s)
- Claudia Domaratius
- Department of Radiology, University Hospital Jena, Friedrich Schiller University, Jena, Germany
| | - Utz Settmacher
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Friedrich Schiller University, Jena, Germany
| | - Christina Malessa
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Friedrich Schiller University, Jena, Germany
| | - Ulf Teichgräber
- Department of Radiology, University Hospital Jena, Friedrich Schiller University, Jena, Germany
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21
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Pollock RF, Brennan VK, Peters R, Paprottka PM. Association between objective response rate and overall survival in metastatic neuroendocrine tumors treated with radioembolization: a systematic literature review and regression analysis. Expert Rev Anticancer Ther 2020; 20:997-1009. [PMID: 32930618 DOI: 10.1080/14737140.2020.1814748] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES Neuroendocrine tumors (NETs) are a heterogeneous group of cancers arising from neuroendocrine cells. The aim was to evaluate objective response rate (ORR) as a predictor of overall survival (OS) in patients with metastatic NETs (mNETs) treated with radioembolization (RE). METHODS Randomized controlled trials and observational studies of RE treatment of mNETs were identified by systematic literature review (SLR). Pooled ORR and OS estimates were calculated and a weighted generalized linear model (GLM) of ORR as a predictor of OS was derived, stratified by ORR assessment criteria and RE type (Yttrium-90 resin or glass microspheres). RESULTS The SLR identified 32 observational studies. Mean ORR was 41% (95% confidence interval 38-45%). The Yttrium-90 resin and glass microsphere GLMs accounted for 59% and 57% of OS deviance, respectively. ORR was a significant predictor of OS in the resin microspheres model (p < 0.001), but not the glass microspheres model (p = 0.11). CONCLUSIONS A weighted GLM showed a significant relationship between ORR and OS in patients with mNETs treated with Yttrium-90 resin microspheres. ORR could therefore potentially be an OS surrogate in future trials of Yttrium-90 resin microspheres. Further research is needed to confirm the relationship between ORR and OS and the difference between resin and glass microspheres.
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Affiliation(s)
- Richard F Pollock
- Department of Health Economics and Outcomes Research, Covalence Research Ltd , London, UK
| | - Victoria K Brennan
- Health Economics, Pricing, Reimbursement & Market Access, Sirtex Medical United Kingdom Ltd , London, UK
| | - Ralph Peters
- Health Economics, Pricing, Reimbursement & Market Access, Sirtex Medical United Kingdom Ltd , London, UK
| | - Philipp M Paprottka
- Department of Interventional Radiology, Klinikum Rechts der Isar der Technischen Universität München , Munich, Germany
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22
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Ou HY, Cheng YF, Chuang YH, Hsu HW, Chen CL, Lazo MZ, Weng CC, Yu CY, Tsang LLC, Huang TL, Tong YS. Quantification of Functional MR Predicts Early Response in Post-doxorubicin Drug-Eluting Beads Chemoembolization for Hepatocellular Carcinoma. Dig Dis Sci 2020; 65:2433-2441. [PMID: 31732907 DOI: 10.1007/s10620-019-05951-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 11/07/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND The purpose of this study was to assess the value of functional MRI (fMRI) of post-doxorubicin drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) as an early imaging biomarker of response to therapy. METHODS This prospective analysis included 21 consecutive patients undergoing fMRI before and after DEB-TACE at a single medical center from January 2013 to December 2014. Functional MRI, including relative changes in apparent diffusion coefficient (ADC) and choline levels measured at hydrogen-1 magnetic resonance spectroscopy (MRS) of treated lesions, was recorded at baseline before DEB-TACE, and at 1, 2, and 4 weeks after DEB-TACE therapy. Assessment of tumor response was based on dynamic contrast-enhanced computer tomography imaging response according to modified response evaluation criteria in solid tumors. RESULTS At post-therapy, 76% (n = 16) of patients demonstrated objective tumor response, 10% (n = 2) had stable disease, and 3 (14%) had progressive disease. Stable disease and progressive disease were designated as non-response. At week 2, the mean change in ADC value of responsive tumors was 0.35 ± 0.24 mm2/s, which was greater than that of non-response tumors (mean 0.01 ± 0.13 × 10-3 mm2/s) (P = 0.006). Significant differences were found in mean choline/water ratio between responsive (7.8 ± 4.9 × 10-3) and non-responsive (17.2 ± 4.9 × 10-3) tumors (P = 0.005). Composite scores of choline/water ratio and relative change of ADC showed significantly better diagnostic accuracy in non-responsive tumors than responsive tumors (area under the curve = 1.0; P < 0.001). CONCLUSIONS Combined DWI and MRS may be used as an early imaging biomarker of therapy response in HCC patients after chemoembolization therapy.
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Affiliation(s)
- Hsin-You Ou
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan.
| | - Yu-Fan Cheng
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Yi-Hsuan Chuang
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Hsien-Wen Hsu
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Chao-Long Chen
- Liver Transplantation Program and Departments of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Marirose Zingapan Lazo
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Ching-Chun Weng
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Chun-Yen Yu
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Leo Leung-Chit Tsang
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Tung-Liang Huang
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Yu-Shun Tong
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
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Han G, Berhane S, Toyoda H, Bettinger D, Elshaarawy O, Chan AWH, Kirstein M, Mosconi C, Hucke F, Palmer D, Pinato DJ, Sharma R, Ottaviani D, Jang JW, Labeur TA, van Delden OM, Pirisi M, Stern N, Sangro B, Meyer T, Fateen W, García‐Fiñana M, Gomaa A, Waked I, Rewisha E, Aithal GP, Travis S, Kudo M, Cucchetti A, Peck‐Radosavljevic M, Takkenberg R, Chan SL, Vogel A, Johnson PJ. Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach. Hepatology 2020; 72:198-212. [PMID: 31698504 PMCID: PMC7496334 DOI: 10.1002/hep.31022] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 10/28/2019] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND AIMS The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. APPROACH AND RESULTS Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. CONCLUSIONS A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognostication.
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Affiliation(s)
- Guohong Han
- Department of Liver Disease and Digestive Interventional RadiologyXijing Hospital of Digestive DiseaseFourth Military Medical UniversityXi’anChina
| | - Sarah Berhane
- Department of BiostatisticsUniversity of LiverpoolLiverpoolUnited Kingdom
| | - Hidenori Toyoda
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiJapan
| | - Dominik Bettinger
- Department of Medicine IIFaculty of MedicineMedical Center University of FreiburgUniversity of FreiburgFreiburgGermany
| | - Omar Elshaarawy
- National Liver InstituteMenoufia UniversityShebeen El‐KomEgypt
| | | | - Martha Kirstein
- Department of Gastroenterology, Hepatology and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Cristina Mosconi
- Radiology UnitDepartment of SpecializedDiagnostic and Experimental MedicineAlma Mater Studiorum ‐ University of BolognaItaly University Hospital of Bologna Sant'Orsola‐Malpighi PolyclinicBolognaItaly
| | - Florian Hucke
- Department of Internal Medicine and GastroenterologyKlinikum Klagenfurt am WörtherseeKlagenfurtAustria
| | - Daniel Palmer
- Department of Molecular and Clinical Cancer MedicineUniversity of LiverpoolLiverpoolUnited Kingdom
| | - David J. Pinato
- Department of Surgery and CancerImperial College LondonLondonUnited Kingdom
| | - Rohini Sharma
- Department of Surgery and CancerImperial College LondonLondonUnited Kingdom
| | - Diego Ottaviani
- UCL Cancer InstituteUniversity College LondonLondonUnited Kingdom
| | - Jeong W. Jang
- Department of Internal MedicineThe Catholic University of KoreaSeoul St. Mary’s HospitalSeoulRepublic of Korea
| | - Tim A. Labeur
- Department of Gastroenterology and HepatologyAmsterdam University Medical CenterAmsterdamthe Netherlands
| | - Otto M. van Delden
- Department of RadiologyAmsterdam University Medical CentersAmsterdamthe Netherlands
| | - Mario Pirisi
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | - Nick Stern
- Department of Gastroenterology and HepatologyAintree University HospitalLiverpoolUnited Kingdom
| | - Bruno Sangro
- Liver UnitClínica Universidad de Navarra IDISNA and CIBEREHDPamplonaSpain
| | - Tim Meyer
- Research Department of OncologyUCL Cancer InstituteUniversity College LondonLondonUnited Kingdom
| | - Waleed Fateen
- National Institute for Health Research Nottingham Biomedical Research CentreNottingham University Hospitals National Health Service Trust and the University of NottinghamNottinghamUnited Kingdom
- Nottingham Digestive Diseases CentreSchool of MedicineUniversity of NottinghamNottinghamUnited Kingdom
| | | | - Asmaa Gomaa
- National Liver InstituteMenoufia UniversityShebeen El‐KomEgypt
| | - Imam Waked
- National Liver InstituteMenoufia UniversityShebeen El‐KomEgypt
| | - Eman Rewisha
- National Liver InstituteMenoufia UniversityShebeen El‐KomEgypt
| | - Guru P. Aithal
- National Institute for Health Research Nottingham Biomedical Research CentreNottingham University Hospitals National Health Service Trust and the University of NottinghamNottinghamUnited Kingdom
- Nottingham Digestive Diseases CentreSchool of MedicineUniversity of NottinghamNottinghamUnited Kingdom
| | - Simon Travis
- Department of RadiologyNottingham University Hospitals National Health Service TrustNottinghamUnited Kingdom
| | - Masatoshi Kudo
- Department of Gastroenterology and HepatologyKinki University School of MedicineOsaka‐SayamaOsakaJapan
| | | | - Markus Peck‐Radosavljevic
- Department of Internal Medicine and GastroenterologyKlinikum Klagenfurt am WörtherseeKlagenfurtAustria
| | - R.B. Takkenberg
- Department of Gastroenterology and HepatologyAmsterdam University Medical CenterAmsterdamthe Netherlands
| | - Stephen L. Chan
- Department of Clinical OncologyChinese University of Hong KongShatinHong Kong
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Philip J. Johnson
- Department of Molecular and Clinical Cancer MedicineUniversity of LiverpoolLiverpoolUnited Kingdom
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Gregory J, Dioguardi Burgio M, Corrias G, Vilgrain V, Ronot M. Evaluation of liver tumour response by imaging. JHEP Rep 2020; 2:100100. [PMID: 32514496 PMCID: PMC7267412 DOI: 10.1016/j.jhepr.2020.100100] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/10/2020] [Accepted: 03/10/2020] [Indexed: 12/12/2022] Open
Abstract
The goal of assessing tumour response on imaging is to identify patients who are likely to benefit - or not - from anticancer treatment, especially in relation to survival. The World Health Organization was the first to develop assessment criteria. This early score, which assessed tumour burden by standardising lesion size measurements, laid the groundwork for many of the criteria that followed. This was then improved by the Response Evaluation Criteria in Solid Tumours (RECIST) which was quickly adopted by the oncology community. At the same time, many interventional oncology treatments were developed to target specific features of liver tumours that result in significant changes in tumours but have little effect on tumour size. New criteria focusing on the viable part of tumours were therefore designed to provide more appropriate feedback to guide patient management. Targeted therapy has resulted in a breakthrough that challenges conventional response criteria due to the non-linear relationship between response and tumour size, requiring the development of methods that emphasize the appearance of tumours. More recently, research into functional and quantitative imaging has created new opportunities in liver imaging. These results have suggested that certain parameters could serve as early predictors of response or could predict later tumour response at baseline. These approaches have now been extended by machine learning and deep learning. This clinical review focuses on the progress made in the evaluation of liver tumours on imaging, discussing the rationale for this approach, addressing challenges and controversies in the field, and suggesting possible future developments.
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Key Words
- (c)TACE, (conventional) transarterial chemoembolisation
- (m)RECIST, (modified) Response Evaluation Criteria in Solid Tumours
- 18F-FDG, 18F-fluorodeoxyglucose
- 90Y, yttrium-90
- ADC, apparent diffusion coefficient
- APHE, arterial phase hyperenhancement
- CEUS, contrast-enhanced ultrasound
- CRLM, colorectal liver metastases
- DWI, diffusion-weighted imaging
- EASL
- EASL, European Association for the Study of the Liver criteria
- GIST, gastrointestinal stromal tumours
- HCC, hepatocellular carcinoma
- HU, Hounsfield unit
- Imaging
- LI-RADS
- LI-RADS, Liver Imaging Reporting And Data System
- Liver
- Metastases
- PD, progressive disease
- PET, positron emission tomography
- PR, partial response
- RECIST
- SD, stable disease
- SIRT, selective internal radiotherapy
- TR, treatment response
- Tumours
- WHO, World Health Organization
- mRECIST
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Affiliation(s)
- Jules Gregory
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France
- University of Paris, Paris, France
- INSERM U1149, CRI, Paris, France
| | - Marco Dioguardi Burgio
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France
- University of Paris, Paris, France
- INSERM U1149, CRI, Paris, France
| | - Giuseppe Corrias
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France
- University of Paris, Paris, France
- INSERM U1149, CRI, Paris, France
| | - Valérie Vilgrain
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France
- University of Paris, Paris, France
- INSERM U1149, CRI, Paris, France
| | - Maxime Ronot
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France
- University of Paris, Paris, France
- INSERM U1149, CRI, Paris, France
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Xu H, Min X, Ren Y, Yang L, Liu F. Comparative Study of Drug-eluting Beads versus Conventional Transarterial Chemoembolization for Treating Peculiar Anatomical Sites of Gastric Cancer Liver Metastasis. Med Sci Monit 2020; 26:e922988. [PMID: 32474569 PMCID: PMC7566229 DOI: 10.12659/msm.922988] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 03/14/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND This study aimed to assess the relative safety and short-term efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (c-TACE) for treating peculiar anatomical sites of gastric cancer liver metastasis. MATERIAL AND METHODS Of the 68 patients with gastric cancer liver metastases confirmed by imaging and pathology, 35 were treated with DEB-TACE and 33 with c-TACE. The DEB-TACE group comprised 26 males and 9 females aged 28-75 years (56.8±6.3), and the c-TACE group included 19 males and 14 females aged 33-77 (60.2±9.4) years. Liver functions of the 2 groups were compared between pre-TACE and 1-week and 1-month after TACE. Computed tomography and magnetic resonance imaging were reexamined at 1, 3, and 6 months after TACE, and short-term efficacy was assessed based on modified response evaluation criteria in solid tumors. RESULTS One month following DEB-TACE and c-TACE, the number of cases with objective response (OR) was 29 cases (29 out of 35 cases, 82.9%) and 20 cases (20 out of 33 cases, 60.6%) and disease control (DC) in the 2 groups was 33 cases (33 out of 35 cases, 94.3%) and 26 cases (26 out of 33 cases, 78.8%) respectively (P=0.041, P=0.031). Alanine transaminase (ALT) and Aspartate transaminase (AST) significantly increased in the DEB-TACE and c-TACE groups 1 week later (P<0.001). There were no serious complications in the 2 groups; incidences of nausea and vomiting were significantly lower, but instances of fever were markedly elevated in the DEB-TACE group (P=0.023, P=0.016, respectively). CONCLUSIONS The safety, feasibility, and short-term efficacy of DEB-TACE and c-TACE in the treatment of gastric cancer liver metastasis are clear. DEB-TACE leads to less incidences of nausea and vomiting but more incidences of fever than c-TACE.
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Affiliation(s)
- Hao Xu
- Sichuan Key Laboratory of Medical Imaging, Department of Interventional Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P.R. China
| | - Xuli Min
- Sichuan Key Laboratory of Medical Imaging, Department of Interventional Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P.R. China
| | - Yongjun Ren
- Sichuan Key Laboratory of Medical Imaging, Department of Interventional Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P.R. China
| | - Lin Yang
- Sichuan Key Laboratory of Medical Imaging, Department of Interventional Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P.R. China
| | - Fang Liu
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P.R. China
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Luo J, Zheng J, Shi C, Fang J, Peng Z, Huang J, Sun J, Zhou G, Li T, Zhu D, Xu H, Hou Q, Ying S, Sun Z, Du H, Xie X, Cao G, Ji W, Han J, Gu W, Guo X, Shao G, Yu Z, Zhou J, Yu W, Zhang X, Li L, Hu H, Hu T, Wu X, Chen Y, Ji J, Hu W. Drug-eluting beads transarterial chemoembolization by CalliSpheres is effective and well tolerated in treating intrahepatic cholangiocarcinoma patients: A preliminary result from CTILC study. Medicine (Baltimore) 2020; 99:e19276. [PMID: 32195932 PMCID: PMC7220404 DOI: 10.1097/md.0000000000019276] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
This study aimed to investigate the efficacy and safety of drug-eluting beads (DEB) transarterial chemoembolization (TACE) treatment in Chinese intrahepatic cholangiocarcinoma (ICC) patients.37 ICC patients underwent DEB-TACE treatment in CTILC study (registered on clinicaltrials.gov with registry No. NCT03317483) were included in this present study. Treatment response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Overall survival (OS) was calculated from the time of DEB-TACE operation until the date of death from any causes. Liver function change and adverse events (AEs) were recorded during and after DEB-TACE operation.3 (8.1%) patients achieved complete response (CR) and 22 (59.5%) patients achieved partial response (PR), with objective response rate (ORR) of 67.6%. After DEB-TACE treatment, mean OS was 376 days (95%CI: 341-412 days). Multivariate logistic regression analysis revealed that Bilobar disease (P = .040, OR: 0.105, 95% CI: 0.012-0.898) and portal vein invasion (P = .038, OR: 0.104, 95% CI: 0.012-0.881) could independently predict less possibility of ORR. Patients with ALB abnormal, TP abnormal, ALT abnormal and AST abnormal were increased at 1-week post DEB-TACE treatment (P = .034, P = .001, P < .001, P = .006, respectively), while returned to the levels at baseline after 1 to 3 months (all P > .050). Besides, most of the AEs were mild including pain, fever, vomiting, and nausea in this study.DEB-TACE was effective and well tolerated in treating ICC patients, and bilobar disease as well as portal vein invasion were independently correlated with less probability of ORR achievement.
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Affiliation(s)
- Jun Luo
- Department of Intervention, Zhejiang Cancer Hospital, Hangzhou
| | - Jiaping Zheng
- Department of Intervention, Zhejiang Cancer Hospital, Hangzhou
| | - Changsheng Shi
- Department of Intervention, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, China
| | - Jian Fang
- Department of Hepatobiliary Surgery, Quzhou People's Hospital, Quzhou
| | - Zhiyi Peng
- Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou
| | - Jing Huang
- Department of Hepatobiliary Surgery, Ningbo Medical Center, Lihuili Eastern Hospital, Ningbo
| | - Junhui Sun
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou
| | - Guanhui Zhou
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou
| | - Tiefeng Li
- Department of Radiology, Beilun District People's Hospital of Ningbo, Ningbo
| | - Dedong Zhu
- Department of Liver Oncology, Ningbo No.2 Hospital, Ningbo, China
| | - Huanhai Xu
- Division of Digestive Endoscopy, Yueqing City People's Hospital, Yueqing
| | - Qinming Hou
- Department of Radiology, Xixi Hospital of Hangzhou, Hangzhou 6th People's Hospital, Hangzhou
| | - Shihong Ying
- Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou
| | - Zhichao Sun
- Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou
| | - Haijun Du
- Department of Intervention, Dong Yang people's Hospital, Dongyang
| | - Xiaoxi Xie
- Interventional Center, Xinchang People's Hospital, Shaoxing
| | - Guohong Cao
- Department of Radiology, Shulan (Hangzhou) Hospital, Zhejiang University International Hospital, Hangzhou
| | - Wenbin Ji
- Department of Radiology, Taizhou Hospital of Zhejiang Province, Linhai
| | - Jun Han
- Department of Intervention, Jiaxing First Hospital, Jiaxing
| | - Wenjiang Gu
- Department of Intervention, Jiaxing Second Hospital, Jiaxing
| | - Xiaohua Guo
- Department of Intervention, Jinhua Central Hospital, Jinhua
| | - Guoliang Shao
- Department of Intervention, Zhejiang Cancer Hospital, Hangzhou
| | - Zhihai Yu
- Department of Vascular and Interventional Radiology, The Affiliated Hospital of Medical College of Ningbo University, Ningbo
| | - Jian Zhou
- Department of Radiology, Hangzhou Cancer Hospital
| | - Wenqiang Yu
- Department of Intervention, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Xin Zhang
- Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou
| | - Ling Li
- Department of Liver Oncology, Ningbo No.2 Hospital, Ningbo, China
| | - Hongjie Hu
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine, Hangzhou
| | - Tingyang Hu
- Department of Intervention, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Xia Wu
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine, Hangzhou
| | - Yutang Chen
- Department of Intervention, Zhejiang Cancer Hospital, Hangzhou
| | - Jiansong Ji
- Department of Radiology, Lishui Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui
| | - Wenhao Hu
- Department of Intervention, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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27
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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: 159] [Impact Index Per Article: 31.8] [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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mRECIST for HCC: Performance and novel refinements. J Hepatol 2020; 72:288-306. [PMID: 31954493 DOI: 10.1016/j.jhep.2019.09.026] [Citation(s) in RCA: 408] [Impact Index Per Article: 81.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 09/27/2019] [Accepted: 09/28/2019] [Indexed: 02/06/2023]
Abstract
In 2010, modified RECIST (mRECIST) criteria were proposed as a way of adapting the RECIST criteria to the particularities of hepatocellular carcinoma (HCC). We intended to overcome some limitations of RECIST in measuring tumour shrinkage with local and systemic therapies, and also to refine the assessment of progression that could be misinterpreted with conventional RECIST 1.1, due to clinical events related to the natural progression of chronic liver disease (development of ascites, enlargement of lymph nodes, etc.). mRECIST has served its purpose since being adopted or included in clinical practice guidelines (European, American and Asian) for the management of HCC; it has also been instrumental for assessing response and time-to-event endpoints in several phase II and III investigations. Nowadays, mRECIST has become the standard tool for measurement of radiological endpoints at early/intermediate stages of HCC. At advanced stages, guidelines recommend both methods. mRECIST has been proven to capture higher objective response rates in tumours treated with molecular therapies and those responses have shown to be independently associated with better survival. With the advent of novel treatment approaches (i.e. immunotherapy) and combination therapies there is a need to further refine and clarify some concepts around the performance of mRECIST. Similarly, changes in the landscape of standard of care at advanced stages of the disease are pointing towards progression-free survival as a potential primary endpoint in some phase III investigations, as effective therapies applied beyond progression might mask overall survival results. Strict recommendations for adopting this endpoint have been reported. Overall, we review the performance of mRECIST during the last decade, incorporating novel clarifications and refinements in light of emerging challenges in the study and management of HCC.
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Yoon JS, Sinn DH, Lee JH, Kim HY, Lee CH, Kim SW, Lee HY, Nam JY, Chang Y, Lee YB, Cho EJ, Yu SJ, Kim HC, Chung JW, Kim YJ, Yoon JH. Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study. Cancers (Basel) 2019; 11:cancers11111721. [PMID: 31689972 PMCID: PMC6896068 DOI: 10.3390/cancers11111721] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 10/31/2019] [Accepted: 11/01/2019] [Indexed: 02/07/2023] Open
Abstract
Background: For patients with hepatocellular carcinoma (HCC), the definition of refractoriness to transarterial chemoembolization (TACE), which might make them a candidate for systemic therapy, is still controversial. We aimed to derive and validate a tumor marker-based algorithm to define the refractoriness to TACE in patients with intermediate-stage HCC. Methods: This multi-cohort study was comprised of patients who underwent TACE for treatment-naïve intermediate-stage HCC. We derived a prediction model for overall survival (OS) using the pre- and post-TACE model to predict tumor recurrence after living donor liver transplantation (MoRAL) (i.e., MoRAL score = 11×√protein induced by vitamin K absence-II + 2×√alpha-fetoprotein), which was proven to reflect both tumor burden and biologic aggressiveness of HCC in the explant liver, from a training cohort (n = 193). These results were externally validated in both an independent hospital cohort (from two large-volume centers, n = 140) and a Korean National Cancer Registry sample cohort (n = 149). Results: The changes in MoRAL score (ΔMoRAL) after initial TACE was an independent predictor of OS (MoRAL-increase vs. MoRAL-non-increase: adjusted hazard ratio (HR) = 2.18, 95% confidence interval (CI) = 1.37–3.46, p = 0.001; median OS = 18.8 vs. 37.8 months). In a subgroup of patients with a high baseline MoRAL score (≥89.5, 25th percentile and higher), the prognostic impact of ΔMoRAL was more pronounced (MoRAL-increase vs. MoRAL-non-increase: HR = 3.68, 95% CI = 1.54–8.76, p < 0.001; median OS = 9.9 vs. 37.4 months). These results were reproduced in the external validation cohorts. Conclusion: The ΔMoRAL after the first TACE, a simple and objective index, provides refined prognostication for patients with intermediate-stage HCC. Proceeding to a second TACE may not provide additional survival benefits in cases of a MoRAL-increase after the first TACE in patients with a high baseline MoRAL score (≥89.5), who might be candidates for systemic therapy.
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Affiliation(s)
- Jun Sik Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
- Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan 47392, Korea.
| | - Dong Hyun Sinn
- Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Korea.
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Hwi Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07804, Korea.
| | - Cheol-Hyung Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Sun Woong Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Hyo Young Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
- Department of Internal Medicine, Eulji General Hospital, Eulji University School of Medicine, Seoul 01830, Korea.
| | - Joon Yeul Nam
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07804, Korea.
| | - Young Chang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea.
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Jin Wook Chung
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
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Lim TS, Rhee H, Kim GM, Kim SU, Kim BK, Park JY, Ahn SH, Han KH, Choi JY, Kim DY. Alpha-Fetoprotein, Des-Gamma-Carboxy Prothrombin, and Modified RECIST Response as Predictors of Survival after Transarterial Radioembolization for Hepatocellular Carcinoma. J Vasc Interv Radiol 2019; 30:1194-1200.e1. [PMID: 31235408 DOI: 10.1016/j.jvir.2019.03.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Revised: 03/25/2019] [Accepted: 03/29/2019] [Indexed: 02/07/2023] Open
Abstract
PURPOSE To evaluate the prognostic role of alpha-fetoprotein (AFP), des-gamma-carboxy protein (DCP), and modified Response Evaluation Criteria in Solid Tumors (mRECIST) in patients with hepatocellular carcinoma after transarterial radioembolization (TARE). MATERIALS AND METHODS During 2009-2016, 63 patients with AFP >20 ng/mL, DCP >20 mAU/mL, and Child-Pugh class A who were treated with TARE were evaluated using landmark and risk-of-death method after TARE. Both resin microspheres (n = 46) and glass microspheres (n = 17) were used. AFP or DCP response was defined as more than 50% decrease from baseline. mRECIST response was defined as complete or partial response. Median age was 60 years, and the proportion of male sex was 77.8% (n = 49). The proportions of patients with Barcelona Clinic Liver Cancer stages A, B, and C were 7.9% (n = 5), 46.0% (n = 29), and 46.0% (n = 29), respectively. RESULTS At the 3-month landmark, AFP, DCP, and mRECIST responders lived longer than nonresponders (median overall survival, 75.8 vs 7.6 months for AFP; 75.8 vs 7.1 months for DCP; and 75.8 vs 10.0 months for mRECIST; all P < .05). The 6-month risk of death at the 3-month landmark was statistically different only between DCP responders and nonresponders (P = .002). In multivariate analysis, age less than 70 years (P = .024), absence of distant metastasis (P = .049), DCP response (P = .003), and mRECIST response (P = .003) were independent predictors for overall survival at the 3-month landmark after TARE. CONCLUSIONS AFP, DCP, and mRECIST responders showed better prognosis than nonresponders after TARE, and DCP response was a more potent predictor than AFP response. Tumor marker response, as well as radiologic response, may be useful to predict post-TARE survival.
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Affiliation(s)
- Tae Seop Lim
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodeamun-gu, Seoul, 120-752, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea; Division of Gastroenterology, Department of Internal Medicine, Mediplex Sejong Hospital, Incheon, Republic of Korea
| | - Hyungjin Rhee
- Department of Radiology, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodeamun-gu, Seoul, 120-752, Republic of Korea
| | - Gyoung Min Kim
- Department of Radiology, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodeamun-gu, Seoul, 120-752, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodeamun-gu, Seoul, 120-752, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodeamun-gu, Seoul, 120-752, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodeamun-gu, Seoul, 120-752, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodeamun-gu, Seoul, 120-752, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodeamun-gu, Seoul, 120-752, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Jin-Young Choi
- Department of Radiology, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodeamun-gu, Seoul, 120-752, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodeamun-gu, Seoul, 120-752, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
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Llovet JM, Montal R, Villanueva A. Randomized trials and endpoints in advanced HCC: Role of PFS as a surrogate of survival. J Hepatol 2019; 70:1262-1277. [PMID: 30943423 DOI: 10.1016/j.jhep.2019.01.028] [Citation(s) in RCA: 162] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 12/21/2018] [Accepted: 01/29/2019] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Around half of patients with HCC will receive systemic therapies during their life span. The pivotal positive sorafenib trial and regulatory approval in 2007 was followed by a decade of negative studies with drugs leading to marginal antitumoral efficacy, toxicity, or trials with a lack of enrichment strategies. This trend has changed over the last 2 years with several compounds, such as lenvatinib (in first-line) and regorafenib, cabozantinib, ramucirumab and nivolumab (in second-line), showing clinical benefit. These successes came at a cost of increasing the complexity of decision-making, and ultimately, impacting the design of future clinical trials. Nowadays, life expectancy with single active agents has surpassed the threshold of 1 year and sequential strategies have provided encouraging outcomes. Overall survival (OS) remains the main endpoint in phase III investigations, but as in other solid tumours, there is a clear need to define surrogate endpoints that both reliably recapitulate survival benefits and can be assessed before additional efficacious drugs are administered. A thorough analysis of 21 phase III trials published in advanced HCC demonstrated a moderate correlation between progression-free survival (PFS) or time to progression (TTP) and OS (R = 0.84 and R = 0.83, respectively). Nonetheless, the significant differences in PFS identified in 7 phase III studies only correlated with differences in OS in 3 cases. In these cases, the hazard ratio (HR) for PFS was ≤0.6. Thus, this threshold is herein proposed as a potential surrogate endpoint of OS in advanced HCC. Conversely, PFS with an HR between 0.6-0.7, despite significance, was not associated with better survival, and thus these magnitudes are considered uncertain surrogates. In the current review, we discuss the reasons for positive or negative phase III trials in advanced HCC, and the strengths and limitations of surrogate endpoints (PFS, TTP and objective response rate [ORR]) to predict survival.
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Affiliation(s)
- Josep M Llovet
- Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Catalonia, Spain; Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
| | - Robert Montal
- Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Catalonia, 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, USA; Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Patella F, Pesapane F, Fumarola E, Zannoni S, Brambillasca P, Emili I, Costa G, Anderson V, Levy EB, Carrafiello G, Wood BJ. Assessment of the response of hepatocellular carcinoma to interventional radiology treatments. Future Oncol 2019; 15:1791-1804. [PMID: 31044615 DOI: 10.2217/fon-2018-0747] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
According to Barcelona Clinic Liver Cancer (BCLC) guidelines, interventional radiology procedures are valuable treatment options for many hepatocellular carcinomas (HCCs) that are not amenable to resection or transplantation. Accurate assessment of the efficacy of therapies at earlier stages enables completion of treatment, optimal follow-up and to prevent potentially unnecessary treatments, side effects and costly failure. The goal of this review is to summarize and describe the radiological strategies that have been proposed to predict survival and to stratify HCC responses after interventional radiology therapies. New techniques currently in development are also described.
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Affiliation(s)
- Francesca Patella
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy.,Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Filippo Pesapane
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy.,Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Enrico Fumarola
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy.,Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Stefania Zannoni
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy
| | | | - Ilaria Emili
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy
| | - Guido Costa
- Università degli Studi di Milano, Postgraduate School of General Surgery, Milan, Italy
| | - Victoria Anderson
- Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Elliot B Levy
- Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
| | | | - Bradford J Wood
- Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
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Transarterial Chemoembolization of Hepatocellular Carcinoma Using Radiopaque Drug-Eluting Embolics: How to Pursue Periprocedural Cross-Sectional Imaging? J Vasc Interv Radiol 2019; 30:380-389.e4. [PMID: 30819480 DOI: 10.1016/j.jvir.2018.09.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Revised: 08/31/2018] [Accepted: 09/01/2018] [Indexed: 12/22/2022] Open
Abstract
PURPOSE To compare different imaging techniques (volume perfusion CT, cone-beam CT, and dynamic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced dynamic contrast-enhanced MR imaging with golden-angle radial sparse parallel MR imaging) in evaluation of transarterial chemoembolization of hepatocellular carcinoma (HCC) using radiopaque drug-eluting embolics (DEE). MATERIALS AND METHODS MR imaging and CT phantom investigation of radiopaque DEE was performed. In the clinical portion of the study, 13 patients (22 HCCs) were prospectively enrolled. All patients underwent cross-sectional imaging before and after transarterial chemoembolization using 100-300 μm radiopaque DEE. Qualitative assessment of images using a Likert scale was performed. RESULTS In the phantom study, CT-related beam-hardening artifacts were markedly visible at a concentration of 12% (v/v) radiopaque DEE; MR imaging demonstrated no significant detectable signal intensity changes. Imaging obtained before transarterial chemoembolization showed no significant difference regarding tumor depiction. Visualization of tumor feeding arteries was significantly improved with volume perfusion CT (P < .001) and cone-beam CT (P = .002) compared with MR imaging. Radiopaque DEE led to significant decrease in tumor depiction (P = .001) and significant increase of beam-hardening artifacts (P = .012) using volume perfusion CT before versus after transarterial chemoembolization. Greater residual arterial tumor enhancement was detected with MR imaging (10 HCCs) compared with volume perfusion CT (8 HCCs) and cone-beam CT (6 HCCs). CONCLUSIONS Using radiopaque DEE, the imaging modalities provided comparable early treatment assessment. In HCCs with dense accumulation of radiopaque DEE, treatment assessment using volume perfusion CT or cone-beam CT may be impaired owing to resulting beam-hardening artifacts and contrast stasis. Dynamic contrast-enhanced MR imaging may add value in detection of residual arterial tumor enhancement.
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Rimola J, Davenport MS, Liu PS, Brown T, Marrero JA, McKenna BJ, Hussain HK. Diagnostic accuracy of MRI with extracellular vs. hepatobiliary contrast material for detection of residual hepatocellular carcinoma after locoregional treatment. Abdom Radiol (NY) 2019; 44:549-558. [PMID: 30218239 DOI: 10.1007/s00261-018-1775-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE To compare the diagnostic accuracy of extracellular gadolinium-based contrast-enhanced MRI (Gd-MRI) and gadoxetic acid-enhanced MRI (EOB-MRI) for the assessment of hepatocellular carcinoma (HCC) response to locoregional therapy (LRT) using explant correlation as the reference standard. METHODS Forty-nine subjects with cirrhosis and HCC treated with LRT who underwent liver MRI using either Gd-MRI (n = 26) or EOB-MRI (n = 23) within 90 days of liver transplantation were included. Four radiologists reviewed the MR images blinded to histology to determine the size and percentage of viable residual HCC using a per-lesion explant reference standard. Sensitivities, specificities, accuracies, and agreement with histology for the detection residual HCC were calculated. RESULTS Gd-MRI had greater agreement with histology (ICC: 0.98 [0.95-0.99] vs. 0.80 [0.63-0.90]) and greater sensitivity for viable HCC (76% [13/17 50-93%] vs. 58% [7/12; 28-85%]) than EOB-MRI; specificities were similar (84% [16/19; 60-97%] vs. 85% [23/27; 66-96%]). Areas under ROC curves for detecting residual viable tumor were 0.80 (0.64-0.92) for Gd-MRI and 0.72 (0.55-0.85) for EOB-MRI. Gd-MRI had greater inter-rater agreement than EOB-MRI for determining the size of residual viable HCC (ICC: 0.96 [0.92-0.98] vs. 0.85 [0.72-0.92]). CONCLUSION Gd-MRI may be more accurate and precise than EOB-MRI for the assessment of viable HCC following LRT.
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Vogel A, Cervantes A, Chau I, Daniele B, Llovet JM, Meyer T, Nault JC, Neumann U, Ricke J, Sangro B, Schirmacher P, Verslype C, Zech CJ, Arnold D, Martinelli E. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018; 29:iv238-iv255. [PMID: 30285213 DOI: 10.1093/annonc/mdy308] [Citation(s) in RCA: 713] [Impact Index Per Article: 101.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- A Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany
| | - A Cervantes
- Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain
| | - I Chau
- Department of Medicine, Royal Marsden Hospital, Surrey, UK
| | - B Daniele
- Direttore Dipartimento di Oncologia e U.O.C. Oncologia Medica A.O., Benevento, Italy
| | - J M Llovet
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, Mount Sinai Liver Cancer Program, New York, USA
- Barcelona-Clínic Liver Cancer Group (BCLC), Unitat d'Hepatologia, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona
- Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
| | - T Meyer
- Oncology, Royal Free Hospital, London
- UCL Cancer Institute, University College London, London, UK
| | - J-C Nault
- Service d'hépatologie, Hôpital Jean Verdier, Bondy, France
| | - U Neumann
- Klinik für Allgemein- und Viszeralchirurgie, Medizinische Fakultät der RWTH Aachen
| | - J Ricke
- Klinik und Poliklinik für Radiologie, Ludwig-Maximilians-Universität München, Munich, Germany
| | - B Sangro
- Liver Unit, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain
| | - P Schirmacher
- Institute of Pathology, University Hospital, Heidelberg, Germany
| | - C Verslype
- Campus Gasthuisberg, UZ Leuven, Leuven, Belgium
| | - C J Zech
- Klinik für Radiologie und Nuklearmedizin Universität Basel, Basel, Switzerland
| | - D Arnold
- Department Oncology, Section Hematology and Palliative Care AK Altona, Asklepios Tumorzentrum Hamburg, Hamburg, Germany
| | - E Martinelli
- Faculty of Medicine, Università della Campania L. Vanvitelli Naples, Caserta, Italy
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Vande Lune P, Abdel Aal AK, Klimkowski S, Zarzour JG, Gunn AJ. Hepatocellular Carcinoma: Diagnosis, Treatment Algorithms, and Imaging Appearance after Transarterial Chemoembolization. J Clin Transl Hepatol 2018; 6:175-188. [PMID: 29951363 PMCID: PMC6018317 DOI: 10.14218/jcth.2017.00045] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 11/02/2017] [Accepted: 12/02/2017] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, with incidence increasing worldwide. Unfortunately, the overall prognosis for patients with HCC is poor and many patients present with advanced stages of disease that preclude curative therapies. Diagnostic and interventional radiologists play a key role in the management of patients with HCC. Diagnostic radiologists can use contrast-enhanced computed tomography (CT), magnetic resonance imaging, and ultrasound to diagnose and stage HCC, without the need for pathologic confirmation, by following established criteria. Once staged, the interventional radiologist can treat the appropriate patients with percutaneous ablation, transarterial chemoembolization, or radioembolization. Follow-up imaging after these liver-directed therapies for HCC can be characterized according to various radiologic response criteria; although, enhancement-based criteria, such as European Association for the Study of the Liver and modified Response Evaluation Criteria in Solid Tumors, are more reflective of treatment effect in HCC. Newer imaging technologies like volumetric analysis, dual-energy CT, cone beam CT and perfusion CT may provide additional benefits for patients with HCC.
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Affiliation(s)
- Patrick Vande Lune
- University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA
| | - Ahmed K. Abdel Aal
- Division of Vascular and Interventional Radiology, Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sergio Klimkowski
- Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jessica G. Zarzour
- Division of Abdominal Imaging, Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Andrew J. Gunn
- Division of Vascular and Interventional Radiology, Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA
- *Correspondence to: Andrew J. Gunn, Division of Vascular and Interventional Radiology, Department of Radiology, University of Alabama at Birmingham, 619 19 St S, NHB 623, Birmingham, AL 35249, USA. Tel: +1-205-975-4850, Fax: +1-205-975-5257, E-mail:
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Transarterial Radioembolization Following Chemoembolization for Unresectable Hepatocellular Carcinoma: Response Based on Apparent Diffusion Coefficient Change is an Independent Predictor for Survival. Cardiovasc Intervent Radiol 2018; 41:1716-1726. [DOI: 10.1007/s00270-018-1991-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 05/19/2018] [Indexed: 12/22/2022]
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Fohlen A, Tasu JP, Kobeiter H, Bartoli JM, Pelage JP, Guiu B. Transarterial chemoembolization (TACE) in the management of hepatocellular carcinoma: Results of a French national survey on current practices. Diagn Interv Imaging 2018; 99:527-535. [PMID: 29609903 DOI: 10.1016/j.diii.2018.03.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Revised: 02/09/2018] [Accepted: 03/09/2018] [Indexed: 02/08/2023]
Abstract
PURPOSE To report current practices of transarterial chemoembolization (TACE) by interventional radiologists (IR) for hepatocellular carcinoma (HCC) through a French national survey. MATERIALS AND METHODS An electronic survey was sent by e-mail to 232 IRs performing TACE in 32 private or public centers. The survey included 66 items including indications for TACE, technical aspects of TACE, other locally available treatments for HCC, follow-up imaging and general aspects of interventional radiology practices. RESULTS A total of 64 IRs (64/232; 27%) answered the survey. Each IR performed a mean of 49±45 (SD) TACE procedures per year. Marked variations in indications for TACE in HCC were observed. Six percent of IRs (4/64) treated only patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC. Antibioprophylaxis was not used by 43/64 of IRs (67%). The number of HCC nodules was considered to select conventional TACE versus drug-eluting beadsTACE (DEB-TACE) by 17/49 IRs (35%) followed by patient performance status and Child-Pugh score by 6/49 IRs (12%). Seventy-three percent of IRs (45/62) treated nodules selectively in patients with unilobar disease with cTACE. Thirty-three percent of IRs (21/64) planned systematically a second TACE session. Doxorubicin was the most frequently used drug (52/64; 81%) and 15/64 IRs (23%) used gelatine sponge as the only embolic agent. For DEB-TACE, 100-300μm beads were used by 26/49 IRs (53%) and no additional embolization was performed by 19/48 IRs (39%). Monopolar radiofrequency technique was widely available (59/63; 94%) compared to selective internal radiation therapy (37/64; 58%). Magnetic resonance imaging was used for follow-up by 13/63 IRs (20%). CONCLUSION Current practices of TACE for HCC varied widely among IRs suggesting a need for more standardized practices.
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Affiliation(s)
- A Fohlen
- Department of Interventional and Diagnostic Imaging, University Hospital of Caen, Avenue de la Côte de Nacre, Caen Cedex 14033, France; Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, 14000 Caen, France.
| | - J P Tasu
- Diagnostic, Functional and Therapeutic Imaging Department, Poitiers University Hospital, Poitiers Cedex, France
| | - H Kobeiter
- Department of Medical Imaging, AP-HP, Groupe Henri-Mondor Albert-Chenevrier, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France; University of Medicine, Université Paris 12, 94000 Créteil, France
| | - J M Bartoli
- Department of Radiology, Hôpital Timone, 264, rue Saint-Pierre, 13385 Marseille Cedex 05, France
| | - J P Pelage
- Department of Interventional and Diagnostic Imaging, University Hospital of Caen, Avenue de la Côte de Nacre, Caen Cedex 14033, France; Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, 14000 Caen, France
| | - B Guiu
- Department of Radiology, St-Eloi University Hospital-Montpellier, 80, Avenue Augustin Fliche, 34295 Montpellier, France
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Otarigho B, Falade MO. Identification and characterization of sodium and chloride-dependent gamma-aminobutyric acid (GABA) transporters from eukaryotic pathogens as a potential drug target. Bioinformation 2018; 14:21-30. [PMID: 29497256 PMCID: PMC5818639 DOI: 10.6026/97320630014021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2017] [Revised: 12/10/2017] [Accepted: 12/10/2017] [Indexed: 12/22/2022] Open
Abstract
We explored 285 completed eukaryotic pathogen genomes for GABA transporter proteins as effective chemotherapy targets. We identified 8 GABA proteins that spread across 4 phyla with 5 different pathogen species; Eimeria mitis Houghton, Neospora caninum Liverpool, S. mansoni, S. haematobium and Trichinella spiralis. Sub-cellular localization prediction revealed that these proteins are integral membrane and are mostly insoluble. It is found that about 81% of these proteins are non-crystallizable and 15% are crystallizable. Transmembrane helices predictions show that the GABA transporters have 10, 11, 12 and 14 TMHs with 15, 23, 31 and 11%, respectively. It is further observed that most of these GABA transporters are from several parasites`genomes.
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Affiliation(s)
- Benson Otarigho
- Department of Biological Science, Edo University, Iyamho, Edo State
- Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 97239, USA
| | - Mofolusho O Falade
- Nigeria Cellular Parasitology Programme, Cell Biology and Genetics Unit, Department of Zoology, University of Ibadan, Ibadan, Nigeria
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Meng XC, Chen BH, Huang JJ, Huang WS, Cai MY, Zhou JW, Guo YJ, Zhu KS. Early prediction of survival in hepatocellular carcinoma patients treated with transarterial chemoembolization plus sorafenib. World J Gastroenterol 2018; 24:484-493. [PMID: 29398869 PMCID: PMC5787783 DOI: 10.3748/wjg.v24.i4.484] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Revised: 12/10/2017] [Accepted: 12/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To identify clinical biomarkers that could early predict improved survival in patients with advanced-stage hepatocellular carcinoma (HCC) treated with transarterial chemoembolization combined with sorafenib (TACE-S).
METHODS We retrospectively evaluated the medical records of consecutive patients with advanced-stage HCC who underwent TACE-S from January 2012 to December 2015. At the first follow-up 4-6 wk after TACE-S (median, 38 d; range, 33-45 d), patients exhibiting the modified Response Evaluation Criteria in Solid Tumors (mRECIST)-evaluated complete response, partial response, and stable disease were categorized as early disease control. At this time point, multiple variables were analyzed to identify the related factors affecting survival.
RESULTS Ninety-five patients were included in this study, and 60 of these patients achieved early disease control, with an overall disease control rate (DCR) of 63.2%. Patients who got sorafenib at the first TACE (no previous TACE) and patients without portal vein tumor thrombus (PVTT) had a higher DCR than those who underwent previous TACE before TACE-S (72.4% vs 48.6%, P = 0.019) and those with PVTT (75.5% vs 50.0%, P = 0.010). Early disease control after TACE-S, no previous TACE, and no PVTT were the independent prognostic factors for survival in the uni- and multivariate analyses.
CONCLUSION The first follow-up 4-6 wk after TACE-S can be used as the earliest time point to assess the response to TACE-S, and patients with mRECIST-evaluated early disease control, no previous TACE, and no PVTT had better survival.
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Affiliation(s)
- Xiao-Chun Meng
- Department of Radiology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Bing-Hui Chen
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
| | - Jing-Jun Huang
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Wen-Sou Huang
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Ming-Yue Cai
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Jing-Wen Zhou
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Yong-Jian Guo
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
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Raltitrexed plus oxaliplatin-based transarterial chemoembolization in patients with unresectable hepatocellular carcinoma. Anticancer Drugs 2017; 27:689-94. [PMID: 27145327 DOI: 10.1097/cad.0000000000000371] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Raltitrexed has shown efficacy and safety in many tumor types; however, the clinical data on the treatment of hepatocellular carcinoma is rare. In this report, we aim to assess the efficacy and safety of raltitrexed plus oxaliplatin (OXA)-based transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (uHCC). Patients with uHCC were recruited from multi-centers in China and assigned randomly to raltitrexed+OXA-based (n=76), fluorouracil+OXA-based (n=76), and doxorubicin+OXA-based (n=75) TACE treatment. The primary end point was overall survival (OS). Tumor response was assessed using response evaluation criteria in solid tumors (RECIST), modified response evaluation criteria in solid tumors (mRECIST), and European Association for the Study of the Liver criteria (EASL). Safety and toxicity were evaluated using the National Cancer Institute Common Toxicity Criteria. The raltitrexed group showed a better disease control rate evaluated using RECIST (raltitrexed vs. fluorouracil vs. doxorubicin: 96.1 vs. 84.2 vs. 86.7%, P=0.05) and a better overall response rate on the basis of mRECIST (67.1 vs. 47.4 vs. 50.7%, P=0.03) and EASL (67.1 vs. 47.4 vs. 49.3%, P=0.02). The median OS and median progression-free survival (PFS) were higher in the raltitrexed group (median OS: 13.4 vs. 9.6 vs. 8.5 months; median PFS: 6.7 vs 4.9 vs 4.6 months). The most common toxicities included elevated aspartate aminotransferase (78.9 vs. 86.8 vs. 81.3%) and abdominal nonspecific pain (68.4 vs. 81.6 vs. 78.7%). No significant differences were found in the overall number of patients who experienced any toxicity. Raltitrexed plus OXA-based TACE suggested a safe and efficacious regimen in uHCC patients. The results warrant further clinical investigation.
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Tovoli F, Renzulli M, Granito A, Golfieri R, Bolondi L. Radiologic criteria of response to systemic treatments for hepatocellular carcinoma. Hepat Oncol 2017; 4:129-137. [PMID: 30191059 PMCID: PMC6096444 DOI: 10.2217/hep-2017-0018] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Accepted: 10/16/2017] [Indexed: 02/07/2023] Open
Abstract
Sorafenib has been the only approved systemic therapy for hepatocellular carcinoma until very recently. However, the radiologic assessment of its biological activity is a disputed matter as at least five different criteria have been proposed. In this review, we describe the characteristic of the Response Evaluation Criteria In Solid Tumors (RECIST), European Association for the Study of The Liver (EASL), modified RECIST (mRECIST), Response Evaluation Criteria In the Cancer of the Liver (RECICL) and Choi criteria. The existing comparative studies are reported together with recent pieces of evidence, analyzing the reasons behind the split between recommendations of the scientific societies and regulatory agencies. Future perspectives in the wake of the impending results of the immunotherapy trials are also discussed.
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Affiliation(s)
- Francesco Tovoli
- Department of Medical & Surgical Sciences, University of Bologna, Italy
- *Author for correspondence: Tel.: +39 051 214 2214; Fax: +39 051 214 2725;
| | - Matteo Renzulli
- Radiology Unit, S.Orsola-Malpighi Bologna University Hospital, Italy
| | | | - Rita Golfieri
- Radiology Unit, S.Orsola-Malpighi Bologna University Hospital, Italy
| | - Luigi Bolondi
- Department of Medical & Surgical Sciences, University of Bologna, Italy
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Selective Internal Yttrium-90 Radioembolization Therapy (90Y-SIRT) Versus Best Supportive Care in Patients With Unresectable Metastatic Melanoma to the Liver Refractory to Systemic Therapy: Safety and Efficacy Cohort Study. Am J Clin Oncol 2017; 40:27-34. [PMID: 25089529 DOI: 10.1097/coc.0000000000000109] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES To investigate survival, efficacy, and safety of selective internal yttrium-90 radioembolization therapy (Y-SIRT) in patients with unresectable metastatic melanoma (MM) to liver refractory to systemic therapy. METHODS An IRB-approved retrospective review of 58 patients diagnosed with unresectable MM to the liver, refractory to systemic therapy, between February 2003 and March 2012 was conducted. Of these, 28 received resin-based Y-SIRT (group A), and 30 patients received best supportive care (group B). Survival was calculated using the Kaplan-Meier method and Cox proportional hazard models. RESULTS Groups A and B were similar for the Child-Pugh class, ECOG scores, age, sex, and race. Median overall survival (OS) from diagnosis of primary melanoma in groups A and B were 119.9 and 26.1 months, respectively (P<0.001). Median OS from hepatic metastasis in groups A and B were 19.9 and 4.8 months, respectively (P<0.0001). In group A, median OS from hepatic metastasis in the Child-Pugh A, B, and C patients was 37.7, 4.2, and 3.6 months, respectively (P<0.001). In group B, median OS from hepatic metastasis in the Child-Pugh A, B, and C patients was 7.8, 4.2, and 1.9 months, respectively (P=0.04). Within group A, median OS from first Y-SIRT was 10.1 months; median OS of the Child-Pugh A, B, and C patients from first Y-SIRT was 10.3, 1.2, and 0.9 months, respectively (P=0.04). Median OS from first Y-SIRT was significantly greater in the absence of diffuse (>10) liver metastases (15.1 vs. 4.7 mo, P=0.02), and in the absence of extrahepatic metastases (21.3 vs. 8.6 mo, P<0.001). Common clinical toxicities following Y-SIRT included abdominal pain (17.9%), fatigue (14.3%), and self-limiting grade III bilirubin toxicity (10.7%). CONCLUSION For patients with unresectable MM to the liver refractory to systemic therapy, resin-based Y was associated with longer survival from liver metastases than best supportive care. Child-Pugh A patients with <10 metastatic lesions and absence of extrahepatic metastases demonstrated greatest survival following Y-SIRT.
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Meyer T, Palmer DH, Cheng AL, Hocke J, Loembé AB, Yen CJ. mRECIST to predict survival in advanced hepatocellular carcinoma: Analysis of two randomised phase II trials comparing nintedanib vs sorafenib. Liver Int 2017; 37:1047-1055. [PMID: 28066978 DOI: 10.1111/liv.13359] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 01/02/2017] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Response Evaluation Criteria in Solid Tumors (RECIST) has been shown to be a poor surrogate for survival benefit with targeted therapy in advanced hepatocellular carcinoma (HCC). METHODS We investigated whether response evaluated using modified RECIST (mRECIST) predicted overall survival (OS) using data from two Phase II clinical trials. Analyses were conducted on pooled data from 188 patients with advanced HCC treated with nintedanib or sorafenib, of whom 180 were evaluable for response. Cox regression and Kaplan-Meier survival analyses were used to explore differences in OS between the responders and non-responders according to RECIST 1.0 and mRECIST criteria. Multivariate Cox proportional hazards models, including factors known to influence survival, were used to compare survival according to RECIST and mRECIST response. RESULTS Discordance between RECIST and mRECIST evaluation was most common for assessment of partial response (12.2%) and stable disease (13.3%). OS was significantly longer in patients with response compared to patients without response-RECIST: hazard ratio (HR) 0.325 (95% confidence interval [CI] 0.130-0.815), P=.0122; mRECIST: HR 0.544 (95% CI 0.335-0.881), P=.0122. HRs from the multivariate models used to evaluate response by RECIST or by mRECIST as predictors of OS approached significance for RECIST (0.40 [95% CI 0.16-1.01]; P=.053) and for mRECIST (0.62 [95% CI 0.38-1.01]; P=.053). CONCLUSIONS Response according to RECIST or mRECIST is associated with improved survival and should be considered as a valid endpoint for use in HCC clinical trials.
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Affiliation(s)
- Tim Meyer
- UCL Cancer Institute, University College London, London, UK
| | - Daniel H Palmer
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.,Clatterbridge Cancer Centre, Bebington, UK
| | | | - Julia Hocke
- Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
| | | | - Chia-Jui Yen
- National Cheng Kung University Hospital, Tainan, Taiwan
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Lencioni R, Montal R, Torres F, Park JW, Decaens T, Raoul JL, Kudo M, Chang C, Ríos J, Boige V, Assenat E, Kang YK, Lim HY, Walters I, Llovet JM. Objective response by mRECIST as a predictor and potential surrogate end-point of overall survival in advanced HCC. J Hepatol 2017; 66:1166-1172. [PMID: 28131794 DOI: 10.1016/j.jhep.2017.01.012] [Citation(s) in RCA: 172] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Revised: 12/22/2016] [Accepted: 01/03/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was developed to overcome the limitations of standard RECIST criteria in response assessment of hepatocellular carcinoma (HCC). We aimed to investigate whether objective response by mRECIST accurately predicted overall survival (OS) in patients with advanced HCC treated with systemic targeted therapies and also to preliminarily assess this end-point as a potential surrogate of OS. METHODS Individual patient data from the BRISK-PS randomized phase III trial comparing brivanib vs. placebo (the first to prospectively incorporate mRECIST) were used to analyze objective response as a predictor of OS in a time-dependent covariate analysis. Patients with available imaging scans during follow-up were included (n=334; 85% of those randomized). Moreover, a correlation of the survival probability in deciles vs. the observed objective response was performed to evaluate its suitability as a surrogate end-point. RESULTS Objective response was observed in 11.5% and 1.9% of patients treated with brivanib and placebo respectively, and was associated with a better survival (median OS 15.0 vs. 9.4months, p<0.001). In addition, objective response had an independent prognostic value (HR=0.48; 95% confidence interval [CI], 0.26-0.91, p=0.025) along with known prognostic factors. Finally, objective response showed promising results as a surrogate of OS in this trial (R=-0.92; 95% CI, -1 to -0.73, p<0.001). It was an early indicator of the treatment effect (median time to objective response was 1.4months). CONCLUSIONS Objective response by mRECIST in advanced HCC predicts OS and thus can be considered as a candidate surrogate end-point. Further studies are needed to support this finding. LAY SUMMARY There is a need to identify surrogate end-points for overall survival in advanced hepatocellular carcinoma. We studied patients from the phase III BRISK trial, comparing brivanib treatment with placebo after sorafenib progression. We demonstrate that objective response is an independent predictor of survival and qualifies as a potential surrogate end-point for overall survival in this patient population. CLINICAL TRIAL NUMBER NCT00825955.
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Affiliation(s)
- Riccardo Lencioni
- Department of Interventional Radiology, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Robert Montal
- Liver Cancer Translational Research Laboratory, BCLC Group, IDIBAPS, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain
| | - Ferran Torres
- Medical Statistics Core Facility, IDIBAPS, Hospital Clinic, Barcelona, Spain; Biostatistics Unit, Faculty of Medicine, Autonomous University of Barcelona, Barcelona, Spain
| | - Joong-Won Park
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Thomas Decaens
- Service d'Hépato-gastro-entérologie, Hôpital Henri Mondor, Faculty of Medicine, University of Paris-Est, and INSERM, Creteil, France
| | - Jean-Luc Raoul
- Service d'Oncologie Médicale, Institut Paoli Calmette, Marseille, France
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Charissa Chang
- Liver Cancer Program, Division of Liver Diseases, Ichan School of Medicine at Mount Sinai, New York, NY, USA
| | - José Ríos
- Medical Statistics Core Facility, IDIBAPS, Hospital Clinic, Barcelona, Spain; Biostatistics Unit, Faculty of Medicine, Autonomous University of Barcelona, Barcelona, Spain
| | - Valerie Boige
- Service de Gastro-enterologie, Institut Gustave Roussy, Villejuif, France
| | - Eric Assenat
- Service d'Hépato-gastro-entérologie, Hôpital Saint Eloi, Montpellier Cedex, France
| | - Yoon-Koo Kang
- Department of Oncology, Asan Medical Center, Seoul, Republic of Korea
| | - Ho-Yeong Lim
- Division of Hematology-Oncology, Samsung Medical Center, Seoul, Republic of Korea
| | | | - Josep M Llovet
- Liver Cancer Translational Research Laboratory, BCLC Group, IDIBAPS, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain; Liver Cancer Program, Division of Liver Diseases, Ichan School of Medicine at Mount Sinai, New York, NY, USA; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain.
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Akinwande O, Dendy M, Ludwig JM, Kim HS. Hepatic intra-arterial injection of irinotecan drug eluting beads (DEBIRI) for patients with unresectable colorectal liver metastases: A systematic review. Surg Oncol 2017; 26:268-275. [PMID: 28807246 DOI: 10.1016/j.suronc.2017.05.003] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Revised: 04/30/2017] [Accepted: 05/19/2017] [Indexed: 12/22/2022]
Abstract
PURPOSE To systematically review the safety and efficacy of transarterial drug-eluting beads, irinotecan (DEBIRI) for the treatment of pretreated patients with unresectable colorectal liver metastases (CRLM). METHODS A systematic search of the current literature was conducted to extract publications reporting on the use of DEBIRI for CRLM. Data on the safety and efficacy was extracted and tabulated. Weighted average values (WAV) were calculated for each variable to provide a single value representing the pooled safety and efficacy data. RESULTS 13 studies (15 treatment arms) were evaluated, comprising a total of 850 patients. There were 6 prospective phase I/II trials, 5 retrospective trials and 2 randomized control trials. All papers involved patients previously treated with systemic chemotherapy. The weighted average all-grade toxicity rate was 35.2% (range; 6-100%). The high-grade WAV toxicity rate was 10.1% (range; 0-32%). Weighted average response rates were 56.2% and 51.1% according to RECIST (Response Evaluation Criteria in Solid Tumors) and modified RECIST/EASL (European Association for the Study of the Liver) response criteria respectively. The weighted average progression-free survival and overall survival were 8.1 months and 16.8 months, respectively. CONCLUSION Transarterial DEBIRI is safe and effective in the treatment of unresectable CRLM to the liver. Further studies are warranted to better define its role in the treatment algorithm of this patient subset.
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Affiliation(s)
- Olaguoke Akinwande
- Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, United States
| | - Meaghan Dendy
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States
| | - Johannes M Ludwig
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States
| | - Hyun S Kim
- Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States; Yale Cancer Center, Yale University, New Haven, CT, United States.
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Tumor Enhancement and Heterogeneity Are Associated With Treatment Response to Drug-Eluting Bead Chemoembolization for Hepatocellular Carcinoma. J Comput Assist Tomogr 2017; 41:289-293. [PMID: 27824665 DOI: 10.1097/rct.0000000000000509] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE Treatment response to drug-eluting bead chemoembolization (DEB-TACE) is well established for patients with hepatocellular carcinoma (HCC); however, few studies have evaluated tumor imaging characteristics associated with treatment responses. The aim of our study was to identify imaging characteristics associated with treatment responses and overall survival after DEB-TACE of HCC. METHODS This is a retrospective cohort study of 33 tumors in 32 patients who underwent DEB-TACE for inoperable HCC in a single, large academic medical center. Arterial phase computed tomography data were reviewed to assess tumor size, edge characteristics, tumor enhancement on pixel density histogram, and heterogeneity using coefficient of variation. We assessed correlation between these markers of tumor morphology and response to DEB-TACE using mRECIST criteria, progression-free survival, and overall survival. RESULTS Tumor heterogeneity (P = 0.01) and tumor enhancement greater than 50% (P = 0.05) were significantly associated with complete response to DEB-TACE in patients with HCC; however, neither was associated with overall or progression-free survival. Tumor size and edge characteristics were not associated with complete response to DEB-TACE, although tumor size greater than 6 cm was associated with worse overall survival (hazard ratio, 3.349; P = 0.02). CONCLUSIONS Tumor heterogeneity and enhancement on arterial phase imaging may be predictive markers of treatment response to DEB-TACE among patients with HCC.
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Wu L, Xu P, Rao S, Yang L, Chen C, Liu H, Fu C, Zeng M. ADC total ratio and D ratio derived from intravoxel incoherent motion early after TACE are independent predictors for survival in hepatocellular carcinoma. J Magn Reson Imaging 2017; 46:820-830. [PMID: 28276105 DOI: 10.1002/jmri.25617] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2016] [Accepted: 12/15/2016] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To explore the threshold of intravoxel incoherent motion (IVIM) parameters, apparent diffusion coefficient [ADCtotal and ADC(0,500) ] ratios 24-48 hours after transarterial chemoembolization (TACE) to assess early response in patients with unresectable hepatocellular carcinoma (HCC) and to compare the association between diffusion-weighted imaging with the intravoxel incoherent motion (IVIM-DWI) and mRECIST with survival. MATERIALS AND METHODS Institutional Review Board approval and informed consent were obtained for this prospective study. There were 30 patients undergoing 1.5T magnetic resonance imaging (MRI) with IVIM-DWI of 12 b values (0, 10, 20, 30, 40, 50, 70, 100, 200, 300, 500, 800 s/mm2 ) 1 week before and 24-48 hours after TACE. Response was assessed with the change of true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (PF), ADCtotal , and ADC(0,500) values relative to baseline and with mRECIST. Receiver operating characteristic (ROC) curve analysis was used to explore the threshold of these parameters ratios. Kaplan-Meier, log-rank tests, and the Cox hazard model were used to correlate the response variables with progression-free survival (PFS) and to assess the incidence and potential clinical risk factors for PFS. Mann-Whitney U-test was used to compare the difference in parameters between different groups with progression within and beyond median PFS prior to TACE. RESULTS Median PFS was 99 days, within which 16 patients progressed. The threshold of ADCtotal ratio, D ratio, and ADC(0,500) ratio were 13.1% (P = 0.001), 7.0% (P = 0.011), and 3.6% (P = 0.018) with sensitivity and specificity of 78.6% and 87.5%, 85.7% and 62.5%, 78.6% and 75%, respectively. The predictive utility of ADCtotal ratio, D ratio, and ADC(0,500) ratio for PFS were 0.848, 0.772, and 0.754, respectively. Survival analyses showed ADCtotal ratio, D ratio, ADC(0,500) ratio, liver cirrhosis, and mRECIST had a significant effect on PFS (P < 0.05). ADCtotal ratio and D ratio were independent predictors for 99-day PFS (P = 0.025, P = 0.036). There were no significant differences in pretreatment IVIM-DWI parameters between PFS > 99-day group and PFS ≤ 99-day group with P values of 0.547 for D, 0.394 for D*, 0.575 for PF, 0.901 for ADC(0,500) , and 0.506 for ADCtotal , respectively. CONCLUSION The ADCtotal ratio and D ratio 24-48 hours after TACE were independent predictors for response to TACE for HCC, and showed stronger association with PFS than mRECIST. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:820-830.
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Affiliation(s)
- Lifang Wu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, P.R. China
| | - Pengju Xu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, P.R. China.,Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Shengxiang Rao
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, P.R. China.,Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Li Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, P.R. China
| | - Caizhong Chen
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Hao Liu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Caixia Fu
- Siemens Healthcare, Shanghai, P.R. China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, P.R. China.,Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
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Tamandl D, Waneck F, Sieghart W, Unterhumer S, Kölblinger C, Baltzer P, Ba-Ssalamah A, Loewe C. Early response evaluation using CT-perfusion one day after transarterial chemoembolization for HCC predicts treatment response and long-term disease control. Eur J Radiol 2017; 90:73-80. [PMID: 28583650 DOI: 10.1016/j.ejrad.2017.02.032] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Revised: 02/17/2017] [Accepted: 02/20/2017] [Indexed: 02/07/2023]
Abstract
PURPOSE To determine the value of CT perfusion (CTP) for early response assessment after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS Between April 2013 and April 2015, 41 HCC (16 patients) were included in this study. CT perfusion was performed before and one day after TACE. Blood flow (BF), blood volume (BV), time to start (TTS), arterial liver perfusion (ALP), portal liver perfusion (PVP) and hepatic perfusion index (HPI) were measured. Quantitative perfusion values before and after TACE were compared to the response assessed using mRECIST criteria six weeks after TACE and long-term outcome was assessed. RESULTS Twenty-one lesions (51%) had complete remission (CR) and five (12%) had partial response (PR) six weeks after TACE. CTP parameters were significantly reduced after TACE in responders (PR, CR, p<0.001) while no difference was observed in non-responders. ALPpost was superior in the prediction of CR compared to BFpost and BVpost (p<0.001) with a sensitivity, specificity, PPV, NPV, and accuracy of 90%, 90%, 91%, 90%, and 91%, respectively. Only 3/21 lesions with CR recurred, with a mean local-recurrence-free survival of 19.6 months. CONCLUSION CT perfusion detects lesions with complete response one day after TACE, and is a feasible tool for early response assessment.
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Affiliation(s)
- Dietmar Tamandl
- Department of Biomedical Imaging and Image-Guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, Vienna, Austria
| | - Fredrik Waneck
- Department of Biomedical Imaging and Image-Guided Therapy, Division of Cardiovascular and Interventional Radiology, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Sieghart
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, Medical University of Vienna, Vienna, Austria
| | - Sylvia Unterhumer
- Department of Biomedical Imaging and Image-Guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-Guided Therapy, Division of Cardiovascular and Interventional Radiology, Medical University of Vienna, Vienna, Austria
| | | | - Pascal Baltzer
- Department of Biomedical Imaging and Image-Guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, Vienna, Austria
| | - Ahmed Ba-Ssalamah
- Department of Biomedical Imaging and Image-Guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, Vienna, Austria
| | - Christian Loewe
- Department of Biomedical Imaging and Image-Guided Therapy, Division of Cardiovascular and Interventional Radiology, Medical University of Vienna, Vienna, Austria.
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Subbiah V, Chuang HH, Gambhire D, Kairemo K. Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives. Diagnostics (Basel) 2017; 7:diagnostics7010010. [PMID: 28212290 PMCID: PMC5373019 DOI: 10.3390/diagnostics7010010] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 01/31/2017] [Accepted: 02/03/2017] [Indexed: 02/07/2023] Open
Abstract
In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for “go” versus “no go” decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords “response assessment” and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of “omics in radiology”—radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.
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Affiliation(s)
- Vivek Subbiah
- Departments of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
| | - Hubert H Chuang
- Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
| | | | - Kalevi Kairemo
- Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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