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Soni L, Soopramanien J, Acharya A, Ashrafian H, Giannarou S, Fotiadis N, Darzi A. The use of machine learning in transarterial chemoembolisation/transarterial embolisation for patients with intermediate-stage hepatocellular carcinoma: a systematic review. LA RADIOLOGIA MEDICA 2025:10.1007/s11547-025-02013-y. [PMID: 40317437 DOI: 10.1007/s11547-025-02013-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 03/25/2025] [Indexed: 05/07/2025]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Intermediate-stage HCC is often treated with either transcatheter arterial chemoembolisation (TACE) or transcatheter arterial embolisation (TAE). Integrating machine learning (ML) offers the possibility of improving treatment outcomes through enhanced patient selection. This systematic review evaluates the effectiveness of ML models in improving the precision and efficacy of both TACE and TAE for intermediate-stage HCC. A comprehensive search of PubMed, EMBASE, Web of Science, and Cochrane Library databases was conducted for studies applying ML models to TACE and TAE in patients with intermediate-stage HCC. Seven studies involving 4,017 patients were included. All included studies were from China. Various ML models, including deep learning and radiomics, were used to predict treatment response, yielding a high predictive accuracy (AUC 0.90). However, study heterogeneity limited comparisons. While ML shows potential in predicting treatment outcomes, further research with standardised protocols and larger, multi-centre trials is needed for clinical integration.
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Affiliation(s)
- Lakshya Soni
- Institute of Global Health Innovation, Imperial College London, London, UK.
- Royal Marsden Hospital, London, UK.
| | | | - Amish Acharya
- Institute of Global Health Innovation, Imperial College London, London, UK
| | - Hutan Ashrafian
- Institute of Global Health Innovation, Imperial College London, London, UK
| | | | - Nicos Fotiadis
- Royal Marsden Hospital, London, UK.
- Institute of Cancer Research, London, UK.
| | - Ara Darzi
- Institute of Global Health Innovation, Imperial College London, London, UK
- Institute of Cancer Research, London, UK
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Schmidt R, Rueger C, Xu H, He Y, Yilmaz EY, Heidemann L, Sulejmani O, Liu Y, Noack L, Hesse F, Ruppel R, Abosabie SA, Hamm CA, Penzkofer T, Gebauer B, Savic LJ. Comparing the Prognostic Value of Quantitative Response Assessment Tools and LIRADS Treatment Response Algorithm in Patients with Hepatocellular Carcinoma Following Interstitial High-Dose-Rate Brachytherapy and Conventional Transarterial Chemoembolization. Cancers (Basel) 2025; 17:1275. [PMID: 40282451 PMCID: PMC12025668 DOI: 10.3390/cancers17081275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives: The aim of this study was to investigate the prognostic value of established response assessment tools for hepatocellular carcinoma (HCC) treated with high-dose-rate interstitial brachytherapy (iBT) alone or with transarterial chemoembolization (cTACE). Methods: (Non-)responders were categorized using size-based RECIST 1.1 and WHO criteria, enhancement-based mRECIST and EASL criteria, and the LI-RADS Treatment Response Algorithm (LR-TRA). The outcomes were the overall survival (OS), progression-free survival (PFS), and time to progression (TTP). The statistics used included Fisher's exact test, a t-test, the Mann-Whitney-U test, and a Kaplan-Meier analysis. The median OS, PFS, and TTP were higher in patients following iBT (26.3, 9.1, and 13.0 months) than following cTACE/iBT (23.3, 7.6, and 9.2 months). Results: The enhancement-based criteria identified more responders and predicted PFS and TTP better compared to the size-based criteria. At two months, the cTACE/iBT responders showed improved PFS (mRECIST and EASL: 11.3 vs. 2.3 and 11.0 vs. 2.3, p < 0.01) and TTP (mRECIST and EASL: 11.9 vs. 2.4 months, p < 0.01) by the enhancement-based criteria. An EASL assessment at five months predicted improved survival following both cTACE/iBT (PFS: 11.9 vs. 5.1 months, p = 0.03; TTP: 12.4 vs. 5.0, p < 0.01) and iBT (11.1 vs. 5.1 months, p = 0.04; 13.0 vs. 5.3, p < 0.01). The LR-TRA showed OS benefits at five months for cTACE/iBT responders. Size-based criteria were not prognostic. Conclusions: Extending follow-up post-iBT or post-iBT/cTACE may improve responder stratification and prognostication.
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Affiliation(s)
- Robin Schmidt
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Experimental Clinical Research Center (ECRC) at Charité-Universitätsmedizin Berlin and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany
| | - Christopher Rueger
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Han Xu
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Yubei He
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Experimental Clinical Research Center (ECRC) at Charité-Universitätsmedizin Berlin and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany
| | - Emine Yaren Yilmaz
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Experimental Clinical Research Center (ECRC) at Charité-Universitätsmedizin Berlin and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany
| | - Luisa Heidemann
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Experimental Clinical Research Center (ECRC) at Charité-Universitätsmedizin Berlin and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany
| | - Ornela Sulejmani
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Experimental Clinical Research Center (ECRC) at Charité-Universitätsmedizin Berlin and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany
| | - Yu Liu
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Experimental Clinical Research Center (ECRC) at Charité-Universitätsmedizin Berlin and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany
| | - Lasse Noack
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Friederike Hesse
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Richard Ruppel
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Sara A. Abosabie
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Charlie Alexander Hamm
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Tobias Penzkofer
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Bernhard Gebauer
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Lynn Jeanette Savic
- Department of Radiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Experimental Clinical Research Center (ECRC) at Charité-Universitätsmedizin Berlin and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Straße 10, 13125 Berlin, Germany
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
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Mortezaei A, Taghlabi KM, Al-Saidi N, Amasa S, Whitehead RE, Hoang A, Yaeger K, Faraji AH, Kadirvel R, Ghozy S. Advanced targeted microsphere embolization for arteriovenous malformations: state-of-the-art and future directions. Neuroradiology 2025; 67:1009-1022. [PMID: 40088307 DOI: 10.1007/s00234-025-03584-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 03/04/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Arteriovenous malformations (AVMs) present a significant therapeutic challenge, as current treatment modalities frequently fail to achieve complete and rapid obliteration and are associated with substantial morbidity in both the short and long term. This underscores the critical need for innovative therapeutic strategies that enable efficient AVM obliteration while minimizing patient risk. The current review aims to comprehensively assess the role of ATME in AVM management, examining its clinical efficacy, associated risks and benefits, and the economic and ethical implications to provide valuable foundation for future studies and guiding development in treatment strategies for AVMs. RESULTS Advanced targeted microsphere embolization (ATME) has emerged as a promising therapeutic option, initially developed for the localized treatment of AVMs and unresectable tumors, including liver cancer. By providing targeted delivery, ATME offers potential advantages over conventional approaches in achieving effective local control. CONCLUSIONS ATME are safe and effective for vascular disease and cancer. Although evidence for microspheres in AVMs is scarce, results are promising. Future research could refine eligibility criteria, evaluate treatment techniques, and optimize ATME.
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Affiliation(s)
- Ali Mortezaei
- Gonabad University of Medical Sciences, Gonabad, Iran
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA
| | - Khaled M Taghlabi
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA.
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA.
| | - Nadir Al-Saidi
- College of Medicine, Central Michigan University, Mt Pleasant, MI, USA.
| | - Saketh Amasa
- Department of Neurosurgery, The University of Texas Medical Branch, Galveston, TX, USA
| | - Rachael E Whitehead
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Alex Hoang
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Kurt Yaeger
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Amir H Faraji
- Clinical Innovations Laboratory, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX, USA
- Department of Neurological Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Ramanathan Kadirvel
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Sherief Ghozy
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.
- Department of Radiology, Mayo Clinic, Rochester, MN, USA.
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Kodama Y, Ueshima K, Moriguchi M, Inaba Y, Yamashita T, Iwamoto H, Ueno M, Ogasawara S, Kuzuya T, Kodama T, Sato Y, Tada T, Tsuchiya K, Nishiofuku H, Yamakado K, Sone M, Ikeda M, Takehara T, Hamano T, Kudo M. Protocol of the IMPACT study: randomized, multicenter, phase 3 study evaluating the efficacy of immunotherapy (Atezolizumab) plus anti-VEGF therapy (Bevacizumab) in combination with transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma. BMC Cancer 2025; 25:434. [PMID: 40069616 PMCID: PMC11895279 DOI: 10.1186/s12885-025-13648-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 02/05/2025] [Indexed: 03/15/2025] Open
Abstract
BACKGROUND Atezolizumab plus bevacizumab is recommended as a first-line treatment for unresectable hepatocellular carcinoma (uHCC). A subgroup analysis of the IMbrave150 trial showed shorter overall survival (OS) in uHCC patients with stable disease (SD) than patients with complete response (CR) or partial response (PR) after atezolizumab plus bevacizumab. Improving OS in patients with SD is an unmet medical need. Transcatheter arterial chemoembolization (TACE) may enhance treatment efficacy by controlling intrahepatic lesions and activating anti-tumor immunity. The IMPACT study aims to evaluate whether combining atezolizumab plus bevacizumab with TACE improves OS in patients with SD. METHODS IMPACT is a multicenter, phase 3 study being conducted in Japan, recruiting uHCC patients aged ≥ 18 years with Barcelona Clinic Liver Cancer stage A (single tumor ≥ 5 cm only, TACE unsuitable), stage B (TACE unsuitable) or stage C (excluding Vp3 or 4), Child-Pugh A liver function, and no prior systemic therapy. After 12 weeks of atezolizumab plus bevacizumab treatment as induction therapy, patients are being divided into two cohorts based on response: a randomized cohort for patients who achieve SD, or an atezolizumab plus bevacizumab followed by curative conversion (ABC-conversion) cohort for patients who achieve CR or PR. Patients in the randomized cohort are receiving atezolizumab plus bevacizumab and intrahepatic control TACE (Group A), or continuing atezolizumab plus bevacizumab (Group B). Patients in the ABC-conversion cohort are receiving atezolizumab plus bevacizumab. All cohorts can be considered for curative conversion therapies for residual tumors if these therapies are considered curative, in the patient's best interests, and deemed necessary by the investigator. The primary endpoint is OS for the randomized cohort and conversion rate for the ABC-conversion cohort. Secondary endpoints in both cohorts include progression-free survival, objective response rate, duration of response, time to CR, and safety. The study is expected to last 6.5 years from June 2023. DISCUSSION IMPACT is evaluating the efficacy of combination therapy with atezolizumab plus bevacizumab and TACE, as well as exploring the efficacy of curative conversion therapy. The results should contribute to establishing a response-guided treatment strategy for uHCC by determining optimal treatment according to the therapeutic effect of atezolizumab plus bevacizumab. TRIAL REGISTRATION Japan Registry of Clinical Trials (jRCT), identifier: jRCTs051230037. Registered 13 June 2023. PROTOCOL VERSION 8 May 2024; version 1.4.
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MESH Headings
- Humans
- Liver Neoplasms/therapy
- Liver Neoplasms/pathology
- Liver Neoplasms/mortality
- Liver Neoplasms/drug therapy
- Carcinoma, Hepatocellular/therapy
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/drug therapy
- Bevacizumab/administration & dosage
- Bevacizumab/therapeutic use
- Chemoembolization, Therapeutic/methods
- Antibodies, Monoclonal, Humanized/administration & dosage
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Male
- Female
- Vascular Endothelial Growth Factor A/antagonists & inhibitors
- Immunotherapy/methods
- Multicenter Studies as Topic
- Clinical Trials, Phase III as Topic
- Treatment Outcome
- Randomized Controlled Trials as Topic
- Combined Modality Therapy
- Middle Aged
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Affiliation(s)
- Yoshihisa Kodama
- Department of Radiology, Teine Keijinkai Hospital, 1-12-1-40, Maeda, Teine-Ku, Sapporo, Hokkaido, 006-8555, Japan
| | - Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
| | - Michihisa Moriguchi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan
| | - Yoshitaka Inaba
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-Ku, Nagoya, Aichi, 464-8681, Japan
| | - Tatsuya Yamashita
- Department of Gastroenterology, Kanazawa University Hospital, 13-1, Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Hideki Iwamoto
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-Machi, Kurume, Fukuoka, 830-0011, Japan
| | - Makoto Ueno
- Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2, Nakao, Asahi-Ku, Yokohama, Kanagawa, 241-8515, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-Ku, Chiba, 260-8677, Japan
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-Cho, Toyoake, Aichi, 470-1192, Japan
| | - Takahiro Kodama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yozo Sato
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-Ku, Nagoya, Aichi, 464-8681, Japan
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, 1-12-1, Shimoteno, Himeji, Hyogo, 670-8540, Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Japanese Red Cross Musashino Hospital, 1-26-1, Kyonan-Cho, Musashino, Tokyo, 180-8610, Japan
| | - Hideyuki Nishiofuku
- Department of Diagnostic and Interventional Radiology, Nara Medical University, 840, Shijo-Cho, Kashihara, Nara, 634-8522, Japan
| | - Koichiro Yamakado
- Department of Radiology, Hyogo Medical University, 1-1, Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Miyuki Sone
- Department of Diagnostic Radiology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tetsutaro Hamano
- Head office, P4 Statistics Co. Ltd., 5-11-14, Todoroki, Setagaya-Ku, Tokyo, 158-0082, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
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Huang T, Chen J, Zhang L, Wang R, Liu Y, Lu C. Diagnostic performance of microRNAs for predicting response to transarterial chemoembolization in hepatocellular carcinoma: a meta-analysis. Front Oncol 2025; 14:1483196. [PMID: 39876897 PMCID: PMC11773618 DOI: 10.3389/fonc.2024.1483196] [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: 08/19/2024] [Accepted: 12/18/2024] [Indexed: 01/31/2025] Open
Abstract
Purpose To provide a detailed pooled analysis of the diagnostic accuracy of microRNAs (miRNAs) in predicting the response to transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). Methods A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and Web of Science to identify studies assessing the diagnostic performance of miRNAs in predicting TACE response in HCC. Two independent reviewers performed quality assessment and data extraction using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristic (SROC) curve were calculated using a bivariate random-effects model. Subgroup analyses and meta-regression were performed to explore potential sources of heterogeneity, including sample size, response criteria, specimen source, response evaluation methods, TACE efficacy interval window, and geographical location. Results Seven studies, comprising 320 HCC responders and 187 non-responders, were included in this meta-analysis. The miRNAs studied included miR-373, miR-210, miR-4492, miR-1271, miR-214, miR-133b, and miR-335. The pooled sensitivity of miRNAs in predicting recurrence after TACE was 0.79 [95% CI: 0.72-0.84], and the pooled specificity was 0.82 [95% CI: 0.74-0.88]. The DOR was 17 [95% CI: 9-33], and the pooled area under the SROC curve (AUC) was 0.85 [95% CI: 0.81-0.88], indicating excellent diagnostic accuracy. Subgroup analyses revealed significant differences in diagnostic performance based on response criteria and geographical location. Meta-regression did not identify any significant sources of interstudy heterogeneity. Conclusion MiRNAs show promise as diagnostic tools for predicting TACE response in HCC patients. However, their clinical application requires further validation in larger cohorts. Future research should focus on standardizing RNA extraction methods, selecting consistent endogenous controls, and adopting uniform response evaluation criteria to improve reliability and reduce variability.
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Affiliation(s)
- Tianyi Huang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
- Medical School of Nantong University, Nantong, China
| | - Jing Chen
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
- Medical School of Nantong University, Nantong, China
| | - Lu Zhang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
- Medical School of Nantong University, Nantong, China
| | - Rui Wang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
- Medical School of Nantong University, Nantong, China
| | - Yiheng Liu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
- Medical School of Nantong University, Nantong, China
| | - Cuihua Lu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
- Medical School of Nantong University, Nantong, China
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6
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Huang JX, Zhang WH, Wu YM, Hu JY, Long H, Zhu HD, Zhang JQ, Teng GJ, Xiong F. A Study on Overcoming Post-TACE Drug Resistance in HCC Based on Controllable Oxygen Release-Magnetic Hyperthermia Therapy. Adv Healthc Mater 2024; 13:e2402253. [PMID: 39319494 DOI: 10.1002/adhm.202402253] [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: 07/18/2024] [Revised: 08/12/2024] [Indexed: 09/26/2024]
Abstract
Drug-eluting bead transcatheter arterial chemoembolization (D-TACE) is one of the first-line treatment for intermediate hepatocellular carcinoma (HCC). However, the dual hypoxia microenvironment, due to inherent tumor hypoxia and TACE-induced hypoxia, triggers drug resistance in HCC. To address this challenge, the study develops multicavitary microspheres capable of encapsulating oxygen and harnessing magnetic hyperthermia to enhance oxygen permeability. The novel multicavitary oxygen-encapsulated magnetothermal drug-eluting microspheres (OTD-Ms) effectively reduce hypoxia-related proteins (HIF-1α, VEGF-A) and drug resistance (P-gp) both in vitro and in vivo. Moreover, these microspheres demonstrate improved TACE efficacy and enhance survival rates in a rabbit VX-2 tumor model, suggesting their potential for HCC treatment.
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Affiliation(s)
- Jin-Xin Huang
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210009, P. R. China
| | - Wei-Hua Zhang
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210009, P. R. China
- Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, P. R. China
- National Innovation Platform for Integration of Medical Engineering Education (NMEE) (Southeast University), Nanjing, 210009, P. R. China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, 210009, P. R. China
| | - Ye-Ming Wu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210009, P. R. China
- Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, P. R. China
- National Innovation Platform for Integration of Medical Engineering Education (NMEE) (Southeast University), Nanjing, 210009, P. R. China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, 210009, P. R. China
| | - Jian-Yu Hu
- Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, P. R. China
| | - Huan Long
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210009, P. R. China
- Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, P. R. China
| | - Hai-Dong Zhu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210009, P. R. China
- Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, P. R. China
- National Innovation Platform for Integration of Medical Engineering Education (NMEE) (Southeast University), Nanjing, 210009, P. R. China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, 210009, P. R. China
| | - Jian-Qiong Zhang
- Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, P. R. China
- Department of Microbiology and Immunology, School of Medicine, Southeast University, Nanjing, 210009, P. R. China
| | - Gao-Jun Teng
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210009, P. R. China
- Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, P. R. China
- National Innovation Platform for Integration of Medical Engineering Education (NMEE) (Southeast University), Nanjing, 210009, P. R. China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, 210009, P. R. China
| | - Fei Xiong
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210009, P. R. China
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7
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Osman A, Patel S, Gonsalves M, Renani S, Morgan R. Vascular Interventions in Oncology. Clin Oncol (R Coll Radiol) 2024; 36:473-483. [PMID: 37805354 DOI: 10.1016/j.clon.2023.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 07/21/2023] [Accepted: 09/13/2023] [Indexed: 10/09/2023]
Abstract
Vascular interventions are an important and established tool in the management of the oncology patient. The goal of these procedures may be curative, palliative or adjunctive in nature. Some of the common vascular interventions used in oncology include transarterial embolisation or chemoembolisation, selective internal radiation therapy, chemosaturation, venous access lines, superior vena cava stenting and portal vein embolisation. We provide an overview of the principles, technology and approach of vascular techniques for tumour therapy in both the arterial and venous systems. Arterial interventions are currently mainly used in the management of hepatocellular carcinoma. Transarterial embolisation, chemoembolisation and selective internal radiation therapy deliver targeted catheter-delivered treatments with the aim of reducing tumour burden, controlling tumour growth or increasing survival in patients not eligible for transplantation. Chemosaturation is a regional chemotherapy technique that delivers high doses of chemotherapy directly to the liver via the hepatic artery, while reducing the risks of systemic effects. Venous interventions are more adjunctive in nature. Venous access lines are used to provide a means of delivering chemotherapy and other medications directly into the bloodstream. Superior vena cava stenting is a palliative procedure that is used to relieve symptoms of superior vena cava obstruction. Portal vein embolisation is a procedure that allows hypertrophy of a healthy portion of the liver in preparation for liver resection. Interventional radiology-led vascular interventions play an essential part of cancer management. These procedures are minimally invasive and provide a safe and effective adjunct to traditional cancer treatment methods. Appropriate work-up and discussion of each patient-specific problem in a multidisciplinary setting with interventional radiology is essential to provide optimum patient-centred care.
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Affiliation(s)
- A Osman
- St George's Hospital University Hospitals NHS Foundation Trust, London, UK.
| | - S Patel
- St George's Hospital University Hospitals NHS Foundation Trust, London, UK
| | - M Gonsalves
- St George's Hospital University Hospitals NHS Foundation Trust, London, UK
| | - S Renani
- St George's Hospital University Hospitals NHS Foundation Trust, London, UK
| | - R Morgan
- St George's Hospital University Hospitals NHS Foundation Trust, London, UK
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8
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Wong K, Davis S, Partridge G, McWhinney B, Mott N, Klages P, Bain R, Cheung N. Stability of doxorubicin in radiocontrast medium for use in conventional transarterial chemo-embolisation procedures. J Med Imaging Radiat Oncol 2024; 68:434-439. [PMID: 38437190 DOI: 10.1111/1754-9485.13628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 02/21/2024] [Indexed: 03/06/2024]
Affiliation(s)
- Kennedy Wong
- Department of Medical Imaging, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Samuel Davis
- Department of Medical Imaging, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Grant Partridge
- Cancer Care Services, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Brett McWhinney
- Department of Chemical Pathology, Pathology Queensland, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Nigel Mott
- Department of Medical Imaging, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Paul Klages
- Cancer Care Services, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Roger Bain
- Department of Medical Imaging, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Nicholas Cheung
- Department of Medical Imaging, Launceston General Hospital, Launceston, Tasmania, Australia
- University of Tasmania, College of Health and Medicine, Hobart, Tasmania, Australia
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9
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Moschovaki-Zeiger O, Arkoudis NA, Giannakis A, Grigoriadis S, Anagnostopoulos F, Spiliopoulos S. Biodegradable Microspheres for Transarterial Chemoembolization in Malignant Liver Disease. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:678. [PMID: 38674324 PMCID: PMC11051965 DOI: 10.3390/medicina60040678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/10/2024] [Accepted: 04/17/2024] [Indexed: 04/28/2024]
Abstract
Transarterial chemoembolization (TACE) has revolutionized the treatment landscape for malignant liver disease, offering localized therapy with reduced systemic toxicity. This manuscript delves into the use of degradable microspheres (DMS) in TACE, exploring its potential advantages and clinical applications. DMS-TACE emerges as a promising strategy, offering temporary vessel occlusion and optimized drug delivery. The manuscript reviews the existing literature on DMS-TACE, emphasizing its tolerability, toxicity, and efficacy. Notably, DMS-TACE demonstrates versatility in patient selection, being suitable for both intermediate and advanced stages. The unique properties of DMS provide advantages over traditional embolic agents. The manuscript discusses the DMS-TACE procedure, adverse events, and tumor response rates in HCC, ICC, and metastases.
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Affiliation(s)
- Ornella Moschovaki-Zeiger
- 2nd Department of Radiology, School of Medicine, “Attikon” University General Hospital, National and Kapodistrian University of Athens, GR-124 62 Chaidari, Greece; (O.M.-Z.); (N.-A.A.); (A.G.); (S.G.); (F.A.)
| | - Nikolaos-Achilleas Arkoudis
- 2nd Department of Radiology, School of Medicine, “Attikon” University General Hospital, National and Kapodistrian University of Athens, GR-124 62 Chaidari, Greece; (O.M.-Z.); (N.-A.A.); (A.G.); (S.G.); (F.A.)
- Research Unit of Radiology and Medical Imaging, 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, GR-115 28 Athens, Greece
| | - Athanasios Giannakis
- 2nd Department of Radiology, School of Medicine, “Attikon” University General Hospital, National and Kapodistrian University of Athens, GR-124 62 Chaidari, Greece; (O.M.-Z.); (N.-A.A.); (A.G.); (S.G.); (F.A.)
| | - Stavros Grigoriadis
- 2nd Department of Radiology, School of Medicine, “Attikon” University General Hospital, National and Kapodistrian University of Athens, GR-124 62 Chaidari, Greece; (O.M.-Z.); (N.-A.A.); (A.G.); (S.G.); (F.A.)
| | - Fotis Anagnostopoulos
- 2nd Department of Radiology, School of Medicine, “Attikon” University General Hospital, National and Kapodistrian University of Athens, GR-124 62 Chaidari, Greece; (O.M.-Z.); (N.-A.A.); (A.G.); (S.G.); (F.A.)
| | - Stavros Spiliopoulos
- 2nd Department of Radiology, School of Medicine, “Attikon” University General Hospital, National and Kapodistrian University of Athens, GR-124 62 Chaidari, Greece; (O.M.-Z.); (N.-A.A.); (A.G.); (S.G.); (F.A.)
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10
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Choi JW, Kim HC, Han J, Jang MJ, Chung JW. Transarterial Chemoembolization Using Idarubicin Versus Doxorubicin Chemoemulsion in Patients with Hepatocellular Carcinoma (IDADOX): Protocol for a Randomized, Non-inferiority, Double-Blind Trial. Cardiovasc Intervent Radiol 2024; 47:372-378. [PMID: 38147153 DOI: 10.1007/s00270-023-03621-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 11/07/2023] [Indexed: 12/27/2023]
Abstract
PURPOSE This study aims to test the hypothesis that idarubicin-based transarterial chemoembolization (IDA-TACE), using one of the most potent chemotherapeutic agents, could yield oncologic outcomes equivalent to or marginally improved over doxorubicin-based TACE (DOX-TACE). MATERIALS AND METHODS This single-center, prospective, phase II, randomized controlled, non-inferiority, double-blind trial will enroll 128 treatment-naïve patients with HCC (≤ 5 tumors, 1-5 cm in diameter) for conventional TACE. Participants will be randomly assigned (1:1) to either IDA-TACE or DOX-TACE, with stratification by Child-Pugh class. Superselective conventional TACE will be performed using cone-beam CT and small-bore microcatheters. Patient evaluations, including dynamic imaging and blood tests, will occur at 1, 3, and 6 months post-initial treatment. The primary outcome measure is the objective response rate (ORR) according to mRECIST at 6 months. Secondary outcomes include 3-month and 6-month tumor responses, time-to-progression, the incidence of treatment-related serious adverse events within 30 days, and the incidence and severity of any adverse events. STATISTICS Non-inferiority will be claimed if the upper limit of a one-sided 97.5% confidence interval for the proportion difference (i.e., "6-month ORR of DOX-TACE" - "6-month ORR of IDA-TACE") falls below 0.15 in both intention-to-treat and per-protocol analyses. The proportion difference and its confidence interval will be calculated by the Cochran-Mantel-Haenszel method to obtain a weighted average of stratum-specific proportion differences. EXPECTED GAIN OF KNOWLEDGE If IDA-TACE demonstrates outcomes comparable to DOX-TACE, this study could provide compelling evidence that various cytotoxic agents yield similar contributions in TACE, considering the minor role of chemotherapeutic agents in TACE. TRIAL REGISTRATION ClinicalTrials.gov ( https://clinicaltrials.gov/ ). Identifier: NCT06114082. World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) ( https://trialsearch.who.int/Default.aspx ). Identifier: KCT0008166.
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Affiliation(s)
- Jin Woo Choi
- Department of Radiology, Seoul National University Hospital, #101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University Hospital, #101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jiyeon Han
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea
| | - Myoung-Jin Jang
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea
| | - Jin Wook Chung
- Department of Radiology, Seoul National University Hospital, #101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
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11
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Shaha S, Rodrigues D, Mitragotri S. Locoregional drug delivery for cancer therapy: Preclinical progress and clinical translation. J Control Release 2024; 367:737-767. [PMID: 38325716 DOI: 10.1016/j.jconrel.2024.01.072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 01/26/2024] [Accepted: 01/31/2024] [Indexed: 02/09/2024]
Abstract
Systemic drug delivery is the current clinically preferred route for cancer therapy. However, challenges associated with tumor localization and off-tumor toxic effects limit the clinical effectiveness of this route. Locoregional drug delivery is an emerging viable alternative to systemic therapies. With the improvement in real-time imaging technologies and tools for direct access to tumor lesions, the clinical applicability of locoregional drug delivery is becoming more prominent. Theoretically, locoregional treatments can bypass challenges faced by systemic drug delivery. Preclinically, locoregional delivery of drugs has demonstrated enhanced therapeutic efficacy with limited off-target effects while still yielding an abscopal effect. Clinically, an array of locoregional strategies is under investigation for the delivery of drugs ranging in target and size. Locoregional tumor treatment strategies can be classified into two main categories: 1) direct drug infusion via injection or implanted port and 2) extended drug elution via injected or implanted depot. The number of studies investigating locoregional drug delivery strategies for cancer treatment is rising exponentially, in both preclinical and clinical settings, with some approaches approved for clinical use. Here, we highlight key preclinical advances and the clinical relevance of such locoregional delivery strategies in the treatment of cancer. Furthermore, we critically analyze 949 clinical trials involving locoregional drug delivery and discuss emerging trends.
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Affiliation(s)
- Suyog Shaha
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Allston, MA 02134, USA; Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA
| | - Danika Rodrigues
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Allston, MA 02134, USA; Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA
| | - Samir Mitragotri
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Allston, MA 02134, USA; Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
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12
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Behzadi AH, Haghani L, D'Souza DL, Flanagan S, Jones C. Practical Considerations When Choosing Chemoembolization versus Radioembolization for Hepatocellular Carcinoma. Semin Intervent Radiol 2024; 41:48-55. [PMID: 38495267 PMCID: PMC10940042 DOI: 10.1055/s-0044-1779714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are common liver-directed therapies (LDTs) for unresectable HCC. While both deliver intra-arterial treatment directly to the site of the tumor, they differ in mechanisms of action and side effects. Several studies have compared their side effect profile, time to progression, and overall survival data, but often these lack practical considerations when choosing which treatment modality to use. Many factors can impact operator's choice for treatment, and the choice depends on treatment availability, cost, insurance coverage, operator's comfort level, patient-specific factors, tumor location, tumor biology, and disease stage. This review discusses survival data, time to progression data, as well as more practical patient and tumor characteristics for personalized LDT with TACE or TARE.
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Affiliation(s)
- Ashkan Heshmatzadeh Behzadi
- Division of Interventional Radiology, Department of Radiology, University of Minnesota, Minneapolis, Minnesota
| | - Leila Haghani
- Department of Interventional Radiology, Memorial Sloan Kettering, New York City, New York
| | - Donna L. D'Souza
- Division of Interventional Radiology, Department of Radiology, University of Minnesota, Minneapolis, Minnesota
| | - Siobhan Flanagan
- Division of Interventional Radiology, Department of Radiology, University of Minnesota, Minneapolis, Minnesota
| | - Christopher Jones
- Division of Interventional Radiology, Department of Radiology, University of Minnesota, Minneapolis, Minnesota
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13
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Lu H, Liang B, Xia X, Zheng C. Efficacy Analysis of PTCD + TACE vs PTCD + Apatinib in the Treatment of HCC with Obstructive Jaundice: A Retrospective Study. Anticancer Agents Med Chem 2024; 24:1241-1252. [PMID: 39034727 DOI: 10.2174/0118715206313132240712101607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/15/2024] [Accepted: 06/26/2024] [Indexed: 07/23/2024]
Abstract
PURPOSE The aim was to evaluate the safety and effectiveness of PTCD combined with TACE in the treatment of hepatocellular carcinoma with obstructive jaundice and to compare the efficacy of TACE in patients with different levels of bilirubin after PTCD. METHODS The clinical data of 141 patients with HCC complicated with obstructive jaundice were analyzed retrospectively. The patients underwent PTCD first. When the total bilirubin decreased, the patients received TACE or Apatinib treatment. They were divided into two groups: (1) PTCD+TACE group, N=68; (2) PTCD+Apatinib group, N=73. RESULTS The PTCD+TACE group had higher ORR and DCR than the PTCD+Apatinib group (57.4% vs 12.3%, p < 0.001; 80.9% vs 60.3%, p = 0.010). The mPFS of the PTCD+TACE group was longer than that of the PTCD+Apatinib group (7.1 months vs 3.8 months, p < 0.001). The mOS of the PTCD+TACE group was longer than that of the PTCD+Apatinib group(11.5 months vs 7.7 months, p < 0.001). In the subgroup analysis of the PTCD+TACE group, the results showed that the survival benefits of the groups with total bilirubin <2 times and 2-3 times were greater. CONCLUSION In patients with HCC and obstructive jaundice, superselective TACE(lipiodol+epirubicin emulsion) significantly prolonged OS and PFS compared with Apatinib after using PTCD to reduce total bilirubin to <100 μmol/L. Patients whose total bilirubin dropped to .3 times of the upper limit of normal value after PTCD had longer OS and PFS than patients >3 times.
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Affiliation(s)
- Haohao Lu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Xiangwen Xia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
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14
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Lu H, Zheng C, Liang B, Xia X. Analysis of the Efficacy and Safety of Palonosetron Hydrochloride in Preventing Nausea And Vomiting After TACE: A Retrospective Analysis. Curr Radiopharm 2024; 17:46-54. [PMID: 38037910 DOI: 10.2174/0118744710261186231026062257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 09/11/2023] [Accepted: 09/22/2023] [Indexed: 12/02/2023]
Abstract
PURPOSE To investigate the mechanism of nausea and vomiting after TACE, and analyze the efficacy and safety of palonosetron hydrochloride in the prevention of nausea and vomiting after TACE. METHODS The data of 221 patients who underwent TACE in the Department of Intervention Therapy from August 2018 to August 2020 were collected. The patients were divided into two groups: those who did not use palonosetron hydrochloride before TACE (TACE group, N=116); and those who used palonosetron hydrochloride before TACE (TACE+palonosetron group, N=105). Primary study endpoint: The control rate of nausea and vomiting in the two groups at 0-24 h (acute), 24-120 h (delayed), and 0-120 h. Secondary Study Endpoints: Adverse events of palonosetron hydrochloride. RESULTS TACE group vs TACE+palonosetron group: 0-24 h, 74 vs. 44 patients with nausea (63.8% vs. 41.9%); 24-120 h, 50 vs. 16 patients with nausea (43.1% vs. 15.2%); 0-120 h after TACE, 81 vs. 50 patients with nausea (69.8% vs. 47.6%). 0-24 h, 52 vs. 26 patients with vomiting (44.8% vs. 24.8%); 24-120 h, 24 vs. 8 patients with vomiting (20.7% vs. 7.6%); 0-120 h after TACE, 64 vs. 26 patients with vomiting (55.2% vs. 24.8%). The incidence of nausea and vomiting after TACE was significantly lower in the TACE+palonosetron group than in the TACE group (p < 0.05). CONCLUSION Palonosetron hydrochloride can significantly reduce the incidence of nausea and vomiting in patients after TACE, with exact effect and high safety.
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Affiliation(s)
- Haohao Lu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Xiangwen Xia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
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15
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Burasakarn P, Hongjinda S, Thienhiran A, Phancharoenkit N, Fuengfoo P. Preoperative transarterial chemoembolization does not improve the outcomes of resectable hepatocellular carcinoma: A propensity score-matched study. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2023; 12:169-175. [DOI: 10.18528/ijgii230025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 10/03/2023] [Accepted: 10/03/2023] [Indexed: 01/07/2025] Open
Affiliation(s)
- Pipit Burasakarn
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Phramongkutklao Hospital, Bangkok, Thailand
| | - Sermsak Hongjinda
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Phramongkutklao Hospital, Bangkok, Thailand
| | - Anuparp Thienhiran
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Phramongkutklao Hospital, Bangkok, Thailand
| | - Nichaphat Phancharoenkit
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Phramongkutklao Hospital, Bangkok, Thailand
| | - Pusit Fuengfoo
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Phramongkutklao Hospital, Bangkok, Thailand
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16
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Chen Q, Shu L, Sun Y, Guo P, Wang D, Sha X. In Vitro Drug Loading, Releasing Profiles, and In Vivo Embolic Efficacy and Safety Evaluation of a Novel Drug-Eluting Microsphere (CalliSpheres). Cancer Biother Radiopharm 2023; 38:512-520. [PMID: 33493417 DOI: 10.1089/cbr.2020.3766] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Background: To investigate morphology, physical property, loadability, stability, and release profiles of a novel drug-eluting microsphere, CalliSpheres, in vitro and to explore its embolic efficacy and safety in vivo. Materials and Methods: CalliSpheres (50-150 μm, 100-300 μm, and 300-500 μm) and doxorubicin in different amounts (20, 40, 80, and 100 mg) and concentrations (5 and 10 mg/mL) were prepared for experiments. Dynamic light scattering and an Agilent 1260 high-performance liquid chromatography system were used to quantify bead diameters and the efficiency of drug loading and release, respectively. Twelve New Zealand rabbits were treated with catheter-aided hepatic embolization using CalliSpheres. Results: CalliSpheres displayed a red color after loading with doxorubicin, and the mean diameters decreased by 20.7-25.8%. Almost 100% of the drug was incorporated with CalliSpheres in different sizes immersed with doxorubicin 20 mg, while loading efficiency ranged from 75.8% to 100.0% with doxorubicin at 40, 80, and 100 mg dependent on CalliSpheres sizes (smaller sizes, higher loading efficiency). Elevated loading efficiency was observed at higher concentration of doxorubicin solutions. Regarding release profiles, doxorubicin was released from CalliSpheres quickly at the very beginning, and doxorubicin release percentage was increased in the 50-150 μm group (39.2% ± 1.2%) compared with the 100-300 μm group (31.3% ± 1.3%) and 300-500 μm group (31.7% ± 2.5%). Digital subtraction angiography, computed tomography, and histopathologic emanation results proved in vivo safety and embolic efficacy of CalliSpheres. Conclusions: CalliSpheres present with good physical characteristics and satisfactory loading and releasing profiles in vitro and are well tolerated and efficient in embolization in vivo.
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Affiliation(s)
- Qinyue Chen
- Key Laboratory of Smart Drug Delivery, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China
| | - Lan Shu
- Key Laboratory of Smart Drug Delivery, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China
| | - Yali Sun
- Key Laboratory of Smart Drug Delivery, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China
| | - Ping Guo
- Jiangsu Hengrui Medicine Co., Ltd., Shanghai, China
| | - Dong Wang
- Jiangsu Hengrui Medicine Co., Ltd., Shanghai, China
| | - Xianyi Sha
- Key Laboratory of Smart Drug Delivery, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China
- The Institutes of Integrative Medicine of Fudan University, Shanghai, China
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17
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Gorji L, Aoun H, Critchfield J, Al Hallak N, Beal EW. Locoregional Therapy for Intrahepatic Cholangiocarcinoma: The Role of Intra-Arterial Therapies. Cancers (Basel) 2023; 15:4727. [PMID: 37835420 PMCID: PMC10571998 DOI: 10.3390/cancers15194727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 09/18/2023] [Accepted: 09/22/2023] [Indexed: 10/15/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a rare disease with a rising incidence. While surgical resection is the only curative option, the disease process is often identified in advanced stages, as this malignancy often remains clinically silent in early development. Only one-third of patients are eligible for resection at the time of diagnosis. For patients who cannot undergo resection, intra-arterial therapies are reasonable palliative treatment options; in rare occasions, these may be bridging therapies, as well. The premise of bland embolization and most chemoembolization intra-arterial therapies is that the arterial supply of the tumor is occluded to induce tumor necrosis, while radioembolization utilizes the arterial flow of the tumor to deliver radiation therapy. In this review, we discuss the use of transarterial embolization, transarterial chemoembolization, and selective internal radiation therapy for the treatment of ICC. Phase III randomized controlled clinical trials are difficult to tailor to this extremely rare and aggressive disease, but ultimately, further investigation should be pursued to define the patient population that will derive the greatest benefit from each modality.
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Affiliation(s)
- Leva Gorji
- Department of Surgery, Kettering Health, Dayton, OH 45402, USA;
| | - Hussein Aoun
- Department of Interventional Radiology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Jeffrey Critchfield
- Department of Interventional Radiology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA;
| | - Eliza W. Beal
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA;
- Department of Surgery, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA
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18
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Su GA, Wadsworth OJ, Muller HS, Archer WR, Hetts SW, Schulz MD. Polymer-nucleobase composites for chemotherapy drug capture. J Mater Chem B 2023; 11:8449-8455. [PMID: 37580990 DOI: 10.1039/d3tb00819c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Abstract
Intravenous chemotherapy (e.g., doxorubicin (DOX)) is standard treatment for many cancers but also leads to side effects due to off-target toxicity. To address this challenge, devices for removing off-target chemotherapy agents from the bloodstream have been developed, but the efficacy of such devices relies on the ability of the underlying materials to specifically sequester small-molecule drugs. Anion-exchange materials, genomic DNA, and DNA-functionalized iron oxide particles have all been explored as drug-capture materials, but cost, specificity, batch-to-batch variation, and immunogenicity concerns persist as challenges. Here, we report a new class of fully synthetic drug-capture materials. We copolymerized methacrylic acid and ethylene glycol dimethacrylate in the presence of several nucleobases and derivatives (adenine, cytosine, xanthine, and thymine) to yield a crosslinked resin with nucleobases integrated into the material. These materials demonstrated effective DOX capture: up to 27 mg of DOX per g of material over 20 minutes from a phosphate-buffered saline solution with an initial concentration of 0.05 mg mL-1 of DOX. These materials use only the individual nucleobases for DOX capture and exhibit competitive capture efficacy compared to previous materials that used genomic DNA, making this approach more cost-effective and reducing potential immunological concerns.
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Affiliation(s)
- Gillian A Su
- Department of Chemistry and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA 24061, USA.
| | - Ophelia J Wadsworth
- Department of Chemistry and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA 24061, USA.
| | - H Suzanne Muller
- Department of Chemistry and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA 24061, USA.
| | - William R Archer
- Department of Chemistry and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA 24061, USA.
| | - Steven W Hetts
- Departments of Radiology, Biomedical Imaging, and Neurological Surgery, University of California, San Francisco, CA 94143-0628, USA
| | - Michael D Schulz
- Department of Chemistry and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA 24061, USA.
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Selzman J, Gajendran M, El Kurdi B, Katabathina V, Wright R, Umapathy C, Echavarria J. Transarterial Chemoembolization-Induced Ischemic Colitis: A Rare Complication Due to Nontarget Embolization. ACG Case Rep J 2023; 10:e01140. [PMID: 37753099 PMCID: PMC10519514 DOI: 10.14309/crj.0000000000001140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 07/31/2023] [Accepted: 08/02/2023] [Indexed: 09/28/2023] Open
Abstract
Nontarget embolization is a rare complication that may occur after a patient undergoes transarterial chemoembolization as a localized treatment of hepatocellular carcinoma. This phenomenon can occur because of variations in arterial blood supply to the liver and ultimately can lead to ischemic complications in unintended locations. We describe a case of nontarget embolization during transarterial chemoembolization causing ischemic colitis because of anatomic variation in the origin of the right hepatic artery. This case highlights the importance of recognizing rare side effects associated with this procedure and the need for comprehensive imaging to assess for anatomical variation to avoid poor outcomes.
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Affiliation(s)
- Jonathan Selzman
- Department of Internal Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX
| | - Mahesh Gajendran
- Department of Gastroenterology and Hepatology, The University of Texas Health Science Center at San Antonio, San Antonio, TX
| | - Bara El Kurdi
- Department of Gastroenterology and Hepatology, The University of Texas Health Science Center at San Antonio, San Antonio, TX
| | - Venkata Katabathina
- Department of Radiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX
| | - Randy Wright
- Department of Gastroenterology and Hepatology, The University of Texas Health Science Center at San Antonio, San Antonio, TX
| | - Chandraprakash Umapathy
- Department of Gastroenterology and Hepatology, The University of Texas Health Science Center at San Antonio, San Antonio, TX
| | - Juan Echavarria
- Department of Gastroenterology and Hepatology, The University of Texas Health Science Center at San Antonio, San Antonio, TX
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20
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Alawyia B, Constantinou C. Hepatocellular Carcinoma: a Narrative Review on Current Knowledge and Future Prospects. Curr Treat Options Oncol 2023; 24:711-724. [PMID: 37103744 DOI: 10.1007/s11864-023-01098-9] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2023] [Indexed: 04/28/2023]
Abstract
OPINION STATEMENT Hepatocellular carcinoma is the fourth leading cause of cancer-related deaths worldwide and its associated mortality rate is expected to rise within the next decade. The incidence rate of hepatocellular carcinoma varies significantly across countries and the latter can be attributed to the differences in risk factors that are prevalent across different countries. Some of the risk factors associated with hepatocellular carcinoma include hepatitis B and C infections, non-alcoholic fatty liver disease, and alcoholic liver disease. Regardless of the underlying aetiology, the end result is liver fibrosis and cirrhosis that ultimately progress into carcinoma. The treatment and management of hepatocellular carcinoma is complicated by treatment resistance and high tumor recurrence rates. Early stages of hepatocellular carcinoma are treated with liver resection and other forms of surgical therapy. Advanced stages of hepatocellular carcinoma can be treated with chemotherapy, immunotherapy, and the use of oncolytic viruses and these treatment options can be combined with nanotechnology to improve efficacy and reduce side effects. Moreover, chemotherapy and immunotherapy can be combined to further improve treatment efficacy and overcome resistance. Despite the treatment options available, the high mortality rates provide evidence that current treatment options for advanced-stage hepatocellular carcinoma are not achieving the desired therapeutic goals. Various clinical trials are ongoing to improve treatment efficacy, reduce recurrence rates, and ultimately prolong survival. This narrative review aims to provide an update on our current knowledge and future direction of research on hepatocellular carcinoma.
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Affiliation(s)
- Basil Alawyia
- University of Nicosia Medical School, Nicosia, Cyprus
| | - Constantina Constantinou
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, P.O. Box 24005, 21 Ilia Papakyriakou, 2414 Engomi, CY-1700, Nicosia, Cyprus.
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21
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Andreozzi G, Lorenzoni V, Bargellini I, Cioni R, Turchetti G. Drug-eluting Microspheres Compared to Conventional Transarterial Chemoembolization as First Line Treatment for Unresectable Hepatocellular Carcinoma: A Single-center Retrospective Cost-utility Analysis. Cardiovasc Intervent Radiol 2023; 46:319-326. [PMID: 36599950 PMCID: PMC10014672 DOI: 10.1007/s00270-022-03335-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 11/30/2022] [Indexed: 01/05/2023]
Abstract
PURPOSE To assess the cost-utility of initial treatment with drug-eluting microspheres (DEM) transarterial chemoembolization (TACE) versus conventional (C)-TACE in patients with hepatocellular carcinoma considering the perspective of a Local Healthcare Authority in Italy. MATERIALS AND METHODS The economic evaluation is based on a retrospective single-center study and individual patients' data whose details have been previously reported. The impact of initial treatment with DEM-TACE or C-TACE on disease progression, mortality, and direct health costs over a lifetime horizon were simulated and compared in terms of incremental cost-utility ratio expressed as costs per quality adjusted life years (QALY). Costs included direct health costs related to the first chemoembolization procedure and all subsequent follow-up costs associated with health care resources used for disease management. Probabilistic (PSA) sensitivity analysis was used to assess the robustness of the results. RESULTS A total of 101 patients in each treatment group were considered. All over the time-horizon median costs were €3,145.14 and €2,158.32 in the DEM-TACE and C-TACE group, respectively (p < 0.001); while mean costs were € 24,619 and € 17,001, respectively (p < 0.001). The ICUR was 6,461.86 €/QALY when using median costs derived from the study population as input for the health-economic evaluation and 49,932.15 €/QALY when the mean costs were considered. Results from PSA highlighted that using median costs DEM-TACE was always cost-effective, while using mean costs, it was preferable only 24.7% of times. CONCLUSIONS The higher prices of DEMs are counterbalanced by the positive impact on QALY.
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Affiliation(s)
- G Andreozzi
- Institute of Management, Scuola Superiore Sant'Anna, Piazza Martiri Della Libertà, 33, 56127, Pisa, Italy
| | - V Lorenzoni
- Institute of Management, Scuola Superiore Sant'Anna, Piazza Martiri Della Libertà, 33, 56127, Pisa, Italy.
| | - I Bargellini
- Department of Interventional Radiology, Pisa University Hospital, Pisa, Italy
| | - R Cioni
- Department of Interventional Radiology, Pisa University Hospital, Pisa, Italy
| | - G Turchetti
- Institute of Management, Scuola Superiore Sant'Anna, Piazza Martiri Della Libertà, 33, 56127, Pisa, Italy
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22
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Zhang L, Zhang X, Li Q, Makamure J, Liu Z, Zhao D, Li X, Shi H, Zheng C, Liu F, Liang B. Transarterial chemoembolization failure in patients with hepatocellular carcinoma: Incidence, manifestation and risk factors. Clin Res Hepatol Gastroenterol 2023; 47:102071. [PMID: 36539181 DOI: 10.1016/j.clinre.2022.102071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 11/16/2022] [Accepted: 12/16/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND To identify the incidence, manifestation and risk factors of transarterial chemoembolization (TACE) failure defined as untreatable progression (UP) in patients with hepatocellular carcinoma (HCC) on short-term observation. METHODS Patients from two hospitals with HCC treated with TACE were considered. According to the definition of UP, TACE failure was considered to be present in at least one of the following situations: situation I, failure to achieve objective response in the targeted tumor after at least two initial TACE treatments; situation II, failure to achieve objective response in local tumor progression or new intrahepatic tumor after another TACE session; situation III, presence of major progression; and situation IV, presence of impaired liver function or performance status that contraindicates TACE treatment. Patients were assessed for TACE failure on follow-up visits after two or three TACE sessions. Risk factors for TACE failure were evaluated with logistic regression analysis. RESULTS A total of 206 patients were included. TACE failure occurred in 42 (42/206, 20.4%) patients, of whom 21, 1, 4, 0 and 16 patients manifested as situation I, II, III, IV alone, and combination of situation I with the others, respectively. Multivariate analysis showed that tumor without complete capsule (P < .001) and non-smooth margin (P = .004) were independent predictors of the presence of TACE failure. CONCLUSIONS TACE failure was uncommon in patients with HCC, which manifested predominantly as failure of treatment response of the initial intrahepatic tumor. Non-smooth tumor margin and tumors without complete capsule were associated with the presence of TACE failure.
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Affiliation(s)
- Lijie Zhang
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China; Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, PR China
| | - Xin Zhang
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Qing Li
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Joyman Makamure
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Ziyi Liu
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Dan Zhao
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Xin Li
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Heshui Shi
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Chuansheng Zheng
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Fengyong Liu
- Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, PR China.
| | - Bin Liang
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
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23
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Zhang H, Ren Y, Li H, Zheng C, Qian K. Renal and hepatic artery embolization with Pickering gel emulsion of lipiodol in rabbit. BMC Cancer 2022; 22:1300. [PMID: 36510170 PMCID: PMC9743509 DOI: 10.1186/s12885-022-10337-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 11/18/2022] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE This research aimed to evaluate the feasibility of a novel liquid embolic agent Pickering gel emulsion of lipiodol (PGEL) for renal and hepatic artery embolization in the rabbit experimental model. METHODS Embolization was performed in the right renal artery of 24 adult New Zealand White rabbits and 24 VX2 tumors in the left liver lobe. The rabbits were randomly allocated to four treatment groups (n = 6 per group): (A) normal saline (NS), (B) lipiodol, (C) 180-300 μm polyvinyl alcohol (PVA), and (D) PGEL. RESULTS Renal artery embolization in normal rabbits and transarterial embolization (TAE) in VX2 tumor-bearing rabbits indicated that PGEL achieved a better embolization effect for a longer time than lipiodol and PVA. The tumor growth ratio of the PGEL group was significantly lower than that of the NS, lipiodol, and PVA groups at 3 (P < 0.001) and 7 (P < 0.001) days after embolization. In addition, hematoxylin and eosin and immunohistochemical staining revealed that the tumor necrosis ratio was higher in the PGEL group than in the NS, lipiodol, and PVA groups (P < 0.01), and the expression levels of HIF-1α, VEGF, and CD31 decreased after PGEL embolization compared with the lipiodol and PVA treatments. CONCLUSION PGEL is an effective embolic material that provides immediate and total occlusion of the renal artery and may be a potential therapeutic embolic agent for TAE of HCC.
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Affiliation(s)
- Hongsen Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Han Li
- National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of Ministry of Education, Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, College of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, 430074, Wuhan City, China
- The GBA National Institute for Nanotechnology Innovation, 136 Kaiyuan Avenue, Guangzhou, PR China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China.
| | - Kun Qian
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China.
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Impact of the COVID-19 Pandemic on the Outcomes of Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma: A Single Center Experience from a Developing Country. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58121701. [PMID: 36556903 PMCID: PMC9786879 DOI: 10.3390/medicina58121701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/05/2022] [Accepted: 11/15/2022] [Indexed: 11/24/2022]
Abstract
Background and Objectives: Treatment of cancer patients during the COVID-19 pandemic has been a challenge worldwide. In accordance with the current recommendations for hepatocellular carcinoma (HCC) management during the COVID-19 pandemic, loco-regional therapy such as transarterial chemoembolization (TACE) was proposed with the purpose of achieving local tumor control and improving overall survival. The aim of this prospective cohort study was to evaluate the outcomes of TACE treatment in patients with HCC during the COVID-19 pandemic in comparison with the outcomes of patients treated in the pre-pandemic period. Materials and Methods: Between September 2018 and December 2021, 154 patients were managed by serial TACE procedures for different liver tumors. Ninety-seven patients met the study criteria and were divided into two groups: the study group n = 49 (patients treated from May 2020 to December 2021); the control group n = 48 (patients treated from September 2018 to May 2020). Results: The mean waiting time for TACE was significantly longer in the study group compared to the control group (p < 0.001). No significant difference in survival between the groups is noted (log-rank test p = 0.823). In multivariate analysis, the MELD score (HR 1.329, 95% CI 1.140−1.548, p < 0.001) remained a significant predictor of mortality. Conclusions: COVID-19 pandemic did not affect the final outcome of TACE treatment.
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Gupta P, Kalra N, Chaluvashetty SB, Gamangatti S, Mukund A, Abdul R, Shyam VS, Baijal SS, Mohan C. Indian College of Radiology and Imaging Guidelines on Interventions in Hepatocellular Carcinoma. Indian J Radiol Imaging 2022; 32:540-554. [DOI: 10.1055/s-0042-1754361] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022] Open
Abstract
AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies and a significant cause of cancer-related death. Treatment of HCC depends on the stage of the tumor. As many patients with HCC are not deemed fit for surgical resection or liver transplantation, locoregional therapies play an essential role in the management. Image-guided locoregional treatments include percutaneous ablative therapies and endovascular therapies. The choice of an individual or a combination of therapies is guided by the tumor and patient characteristics. As the outcomes of image-guided locoregional treatments depend on the ability to achieve necrosis of the entire tumor along with a safety margin around it, it is mandatory to follow standard guidelines. In this manuscript, we discuss in detail the various aspects of image-guided locoregional therapies to guide interventional radiologists involved in the care of patients with HCC.
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Affiliation(s)
- Pankaj Gupta
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Naveen Kalra
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sreedhara B. Chaluvashetty
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Amar Mukund
- Department of Interventional Radiology, ILBS, New Delhi, India
| | - Razik Abdul
- Department of Radiodiagnosis, AIIMS, New Delhi, India
| | - VS Shyam
- Department of Interventional Radiology, ILBS, New Delhi, India
| | | | - Chander Mohan
- Department of Interventional Radiology, BLK Superspeciality Hospital, New Delhi, India
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Hong J, Cai X. Construction of a Novel Oxidative Stress Response-Related Gene Signature for Predicting the Prognosis and Therapeutic Responses in Hepatocellular Carcinoma. DISEASE MARKERS 2022; 2022:6201987. [PMID: 36133439 PMCID: PMC9484914 DOI: 10.1155/2022/6201987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 08/24/2022] [Accepted: 08/25/2022] [Indexed: 11/17/2022]
Abstract
Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with poor outcomes, and the assessment of its prognosis as well as its response to therapy is still challenging. In this study, we aimed to construct an oxidative stress response-related genes-(OSRGs-) based gene signature for predicting prognosis and estimating treatment response in patients with HCC. We integrated the transcriptomic data and clinicopathological information of HCC patients from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. LASSO Cox regression analysis was utilized to establish an integrated multigene signature in the TCGA cohort, and its prediction performance was validated in the ICGC cohort. The CIBERSORT algorithm was employed to evaluate immune cell infiltration. The response rate to immune checkpoint inhibition (ICI) therapy was assessed using a TIDE platform. Drug activity data from the Cancer Genome Project and NCI-60 human cancer cell lines were used to predict sensitivity to chemotherapy. We successfully established a gene signature comprising G6PD, MT3, CBX2, CDKN2B, CCNA2, MAPT, EZH2, and SLC7A11. The risk score of each patient, which was determined by the multigene signature, was identified as an independent prognostic marker. The immune cell infiltration patterns, response rates to ICI therapy, and the estimated sensitivity of 89 chemotherapeutic drugs were associated with risk scores. Individual prognostic genes were also associated with susceptibility to various FDA-approved drugs. Our study indicates that a comprehensive transcriptomic analysis of OSRGs can provide a reliable molecular model to predict prognosis and therapeutic response in patients with HCC.
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Affiliation(s)
- Junjie Hong
- Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
| | - Xiujun Cai
- Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
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27
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Yawalkar AN, Pawar MA, Vavia PR. Microspheres for targeted drug delivery- A review on recent applications. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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28
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Manjunatha N, Ganduri V, Rajasekaran K, Duraiyarasan S, Adefuye M. Transarterial Chemoembolization and Unresectable Hepatocellular Carcinoma: A Narrative Review. Cureus 2022; 14:e28439. [PMID: 36176866 PMCID: PMC9509692 DOI: 10.7759/cureus.28439] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/26/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive tumor, and even with the breakthrough in preventive strategies, and new diagnostic and treatment modalities, incidence and fatality rates continue to climb. Patients with HCC are most commonly diagnosed in the later stage, where the disease has already advanced, making it impossible to undertake potentially curative surgery. Transarterial chemoembolization (TACE) is a locoregional therapy regarded as a first-line treatment in patients with intermediate-stage HCC (Barcelona clinical liver cancer {BCLC}-B). TACE is a minimally invasive and non-surgical procedure that combines local chemotherapeutic drug administration with embolization to treat HCC. It helps limit tumor growth, preserve liver function, and increase overall and progression-free survival in patients with intermediate-stage HCC. This article has reviewed the efficacy, survival, limitations, and overall benefit of TACE in patients with unresectable HCC. This article has also discussed the effectiveness of TACE for neoadjuvant chemoembolization and the use of TACE with combination therapies.
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Affiliation(s)
- Nisha Manjunatha
- Research, Our Lady of Fatima University College of Medicine, Metro Manila, PHL
| | | | | | | | - Mayowa Adefuye
- Research, University of Ibadan College of Medicine, Ibadan, NGA
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29
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Bai H, Meng S, Xiong C, Liu Z, Shi W, Ren Q, Xia W, Zhao X, Jian J, Song Y, Ni C, Gao X, Li Z. Preoperative CECT-based Radiomic Signature for Predicting the Response of Transarterial Chemoembolization (TACE) Therapy in Hepatocellular Carcinoma. Cardiovasc Intervent Radiol 2022; 45:1524-1533. [PMID: 35896687 DOI: 10.1007/s00270-022-03221-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 06/30/2022] [Indexed: 12/24/2022]
Abstract
PURPOSE To evaluate the efficiency of radiomics signatures in predicting the response of transarterial chemoembolization (TACE) therapy based on preoperative contrast-enhanced computed tomography (CECT). MATERIALS This study consisted of 111 patients with intermediate-stage hepatocellular carcinoma who underwent CECT at both the arterial phase (AP) and venous phase (VP) before and after TACE. According to mRECIST 1.1, patients were divided into an objective-response group (n = 38) and a non-response group (n = 73). Among them, 79 patients were assigned as the training dataset, and the remaining 32 cases were assigned as the test dataset. METHODS Radiomics features were extracted from CECT images. Two feature ranking methods and three classifiers were used to find the best single-phase radiomics signatures for both AP and VP on the training set. Meanwhile, multi-phase radiomics signatures were built upon integration of images from two CECT phases by decision-level fusion and feature-level fusion. Finally, multivariable logistic regression was used to develop a nomogram by combining radiomics signatures and clinic-radiologic characteristics. The prediction performance was evaluated by AUC on the test dataset. RESULTS The multi-phase radiomics signature (AUC = 0.883) performed better in predicting TACE therapy response compared to the best single-phase radiomics signature (AUC = 0.861). The nomogram (AUC = 0.913) showed better performance than any radiomics signatures. CONCLUSION The radiomics signatures and nomogram were developed and validated for predicting responses to TACE therapy, and the radiomics model may play a positive role in identifying patients who may benefit from TACE therapy in clinical practice.
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Affiliation(s)
- Honglin Bai
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, No. 88 Keling Road, Suzhou, 215163, Jiangsu, China.,School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Suzhou, 215163, China
| | - Siyu Meng
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, No. 88 Keling Road, Suzhou, 215163, Jiangsu, China
| | - Chuanfeng Xiong
- Tandon School of Engineering, New York University, 6 MetroTech Center, Brooklyn, NY, USA
| | - Zhao Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Wei Shi
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, No. 88 Keling Road, Suzhou, 215163, Jiangsu, China
| | - Qimeng Ren
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Wei Xia
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, No. 88 Keling Road, Suzhou, 215163, Jiangsu, China
| | - XingYu Zhao
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, No. 88 Keling Road, Suzhou, 215163, Jiangsu, China.,School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Suzhou, 215163, China
| | - Junming Jian
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, No. 88 Keling Road, Suzhou, 215163, Jiangsu, China
| | - Yizhi Song
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, No. 88 Keling Road, Suzhou, 215163, Jiangsu, China
| | - Caifang Ni
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
| | - Xin Gao
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, No. 88 Keling Road, Suzhou, 215163, Jiangsu, China.
| | - Zhi Li
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China. .,People's Hospital of Xinjiang Kizilsu Kirgiz Autonomous Prefecture, West Pamir Road 5, Atush, Xinjiang, 845350, China.
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Ghosh A, Gupta V, Al Khalifah A, Akhter NM. Transradial versus transfemoral arterial access in DEB-TACE for hepatocellular carcinoma. J Clin Imaging Sci 2022; 12:38. [PMID: 36128344 PMCID: PMC9479582 DOI: 10.25259/jcis_47_2022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/24/2022] [Indexed: 11/04/2022] Open
Abstract
Objectives
Transradial access has become increasingly popular in body interventional procedures but has not been ubiquitously adapted. This retrospective study compares the efficacy of this approach versus transfemoral access in hepatocellular carcinoma (HCC) patients who underwent drug-eluting bead transarterial chemoembolization (DEB-TACE).
Materials and Methods
A total of 130 HCC patients underwent 146 DEB-TACE procedures within our institution from June 2015 to May 2020. About 90 and 56 procedures were logged for the transradial and transfemoral cohorts, respectively. Peak skin dose, fluoroscopy time, administered contrast volume, total procedure time, and equipment cost data for each procedure were reviewed to evaluate for statistical differences between the two groups.
Results
All 146 cases were technically successful without major complications or access failures in either group. No statistical differences were present between the two access groups in regards to peak skin dose or fluoroscopy time. Transradial access recorded a significantly higher contrast volume (P < 0.05), and a significantly longer procedural time than transfemoral access (P < 0.01). However, transradial access also displayed a significantly lower procedural equipment cost (P < 0.01) between the two groups.
Conclusion
Transradial DEB-TACE has similar trends to transfemoral DEB-TACE in several pertinent radiation parameters and is also significantly more cost-efficacious. The results of this investigation suggest the consideration of transradial access whenever viable as an alternative to transfemoral access in the DEB-TACE treatment of HCC patients.
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Affiliation(s)
- Abheek Ghosh
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
| | - Vikash Gupta
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
| | - Abdullah Al Khalifah
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
| | - Nabeel Mohsin Akhter
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
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Garg T, Shrigiriwar A, Habibollahi P, Cristescu M, Liddell RP, Chapiro J, Inglis P, Camacho JC, Nezami N. Intraarterial Therapies for the Management of Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:cancers14143351. [PMID: 35884412 PMCID: PMC9322128 DOI: 10.3390/cancers14143351] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 12/11/2022] Open
Abstract
Image-guided locoregional therapies play a crucial role in the management of patients with hepatocellular carcinoma (HCC). Transarterial therapies consist of a group of catheter-based treatments where embolic agents are delivered directly into the tumor via their supplying arteries. Some of the transarterial therapies available include bland embolization (TAE), transarterial chemoembolization (TACE), drug-eluting beads-transarterial chemoembolization (DEB-TACE), selective internal radioembolization therapy (SIRT), and hepatic artery infusion (HAI). This article provides a review of pre-procedural, intra-procedural, and post-procedural aspects of each therapy, along with a review of the literature. Newer embolotherapy options and future directions are also briefly discussed.
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Affiliation(s)
- Tushar Garg
- Division of Vascular and Interventional Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; (T.G.); (R.P.L.)
| | - Apurva Shrigiriwar
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
| | - Peiman Habibollahi
- Department of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Mircea Cristescu
- Vascular and Interventional Radiology Division, Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA;
| | - Robert P. Liddell
- Division of Vascular and Interventional Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; (T.G.); (R.P.L.)
| | - Julius Chapiro
- Section of Vascular and Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA;
| | - Peter Inglis
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Juan C. Camacho
- Department of Clinical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA;
- Vascular and Interventional Radiology, Radiology Associates of Florida, Sarasota, FL 34239, USA
| | - Nariman Nezami
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
- Experimental Therapeutics Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA
- Correspondence:
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Vardar BU, Meram E, Karaoglu K, Liang M, Yu M, Laeseke P, Ozkan OS. Radioembolization Followed by Transarterial Chemoembolization in Hepatocellular Carcinoma. Cureus 2022; 14:e23783. [PMID: 35518553 PMCID: PMC9063732 DOI: 10.7759/cureus.23783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/03/2022] [Indexed: 11/05/2022] Open
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Karagiannis E, Strouthos I, Leczynski A, Zamboglou N, Ferentinos K. Narrative Review of High-Dose-Rate Interstitial Brachytherapy in Primary or Secondary Liver Tumors. Front Oncol 2022; 12:800920. [PMID: 35299745 PMCID: PMC8920984 DOI: 10.3389/fonc.2022.800920] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 01/31/2022] [Indexed: 12/24/2022] Open
Abstract
The optimal management of intrahepatic malignancies involves a multidisciplinary approach. Although surgical resection has been considered the only curative approach, the use of several minimally invasive ablative techniques has dramatically increased the last two decades, mainly due to the fact that they provide similar oncological results with significantly decreased morbidity. Among these modalities, interstitial liver brachytherapy, probably the most flexible liver ablative method, with excellent clinical data on its safety and effectiveness, is frequently not even mentioned as an option in the current peer reviewed literature and guidelines. Brachytherapy is a type of radiotherapy utilizing radionuclides that are directly inserted into the tumor. Compared to external beam radiation therapy, brachytherapy has the potential to deliver an ablative radiation dose over a short period of time, with the advantage of a rapid dose fall-off, that allows for sparing of adjacent healthy tissue. For numerous malignancies such as skin, gynecological, breast, prostate, head and neck, bladder, liver and soft-tissue tumors, brachytherapy as a monotherapy or combined with external beam radiation therapy, has become a standard treatment for many decades. This review article aims to describe the high-dose-rate liver brachytherapy technique, its selection criteria, present its advantages and disadvantages, as well as the available clinical data, in order to help physicians to explore and hopefully introduce liver brachytherapy into their clinical routine.
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Affiliation(s)
- Efstratios Karagiannis
- Department of Radiation Oncology, German Oncology Center, Limassol, Cyprus.,Department of Medicine, School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Iosif Strouthos
- Department of Radiation Oncology, German Oncology Center, Limassol, Cyprus.,Department of Medicine, School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Agnes Leczynski
- Department of Radiation Oncology, German Oncology Center, Limassol, Cyprus
| | - Nikolaos Zamboglou
- Department of Radiation Oncology, German Oncology Center, Limassol, Cyprus.,Department of Medicine, School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Konstantinos Ferentinos
- Department of Radiation Oncology, German Oncology Center, Limassol, Cyprus.,Department of Medicine, School of Medicine, European University Cyprus, Nicosia, Cyprus
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Association of Frailty with Perioperative Outcomes Following Hepatic Resection: A National Study. J Am Med Dir Assoc 2022; 23:684-689.e1. [PMID: 35304129 DOI: 10.1016/j.jamda.2022.02.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 02/09/2022] [Accepted: 02/13/2022] [Indexed: 01/27/2023]
Abstract
OBJECTIVES Risk of mortality and major comorbidity remains high following hepatic resection. Given recent advancements in nonsurgical techniques to control hepatic malignancy, accurate assessment of surgical candidates, especially those considered frail, has become imperative. The present study aimed to characterize the impact of frailty on clinical and financial outcomes following hepatic resection in older individuals. DESIGN Retrospective cohort study. SETTING AND PARTICIPANTS All older adults (≥65 years) undergoing elective hepatic resection were identified from the 2012 to 2019 National Inpatient Sample. METHODS Frailty was defined by using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. Multivariable regression models were developed to assess the independent association of frailty with mortality, perioperative complications, and resource utilization. Marginal effects were tabulated to assess the impact of hospital volume on frailty-associated mortality. RESULTS Of an estimated 40,735 patients undergoing major hepatic resection, 9.0% were considered frail. After multivariable adjustment, frailty was associated with increased odds of mortality (adjusted odds ratio [AOR] 2.9; 95% confidence interval [CI] 2.0-4.3; P < .001) and perioperative complication (AOR 2.9; 95% CI 2.4-3.4; P < .001). Furthermore, frail patients incurred longer risk-adjusted length of stay (14.2 vs 6.7 days, P < .001) and greater hospitalization costs ($55,100 vs $29,300, P < .001). In assessing the impact of institutional expertise on perioperative outcomes, the marginal effect of frailty on mortality became less pronounced with increasing operative volume. CONCLUSIONS AND IMPLICATIONS As the population of the United States continues to age, surgeons are increasingly likely to encounter candidates for major hepatic resection who are frail. The present study associated frailty with inferior clinical and financial outcomes; however, frailty-associated mortality became less pronounced at centers with high hepatic resection operative volume. Coding-based instruments, such as the Johns Hopkins Adjusted Clinical Groups, may identify patients from electronic medical records who may benefit from further geriatric assessment and targeted treatments.
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35
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Trans-Arterial Chemoembolization with 50 μm Degradable Starch Microspheres Versus 300–500 μm Drug Eluting Beads in Hepatocellular Carcinoma: A Comparative Analysis of Initial Treatment Outcomes. J Belg Soc Radiol 2022; 106:10. [PMID: 35434518 PMCID: PMC8916059 DOI: 10.5334/jbsr.2594] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 01/31/2022] [Indexed: 11/20/2022] Open
Abstract
Background and Aims: Trans-arterial chemoembolization (TACE) has become a widely accepted treatment in unresectable hepatocellular carcinoma (HCC). We aimed at comparing the efficacy of Degradable Starch Microspheres (DSMs)-TACE with 50 ± 7 µm versus 300–500 μm Drug Eluting Beads (DEB)-TACE in terms of initial clinical and radiological treatment response parameters. Material and Methods: A total of 54 patients with unresectable HCC who underwent DEB-TACE (n = 25) or DSMs-TACE (n = 29) were included in this retrospective study. Baseline demographic and clinical characteristics, duration of follow-up, local recurrence and survival status, as well as treatment outcome including treatment response via modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, viable and total tumor diameter and serum alpha-fetoprotein (AFP) levels were analyzed in both study groups. Results: No significant difference was noted between the two groups in terms of local recurrence (31.6 vs. 16.7%) or mortality (73.9 vs. 85.7%) rates after 36-month and 12-month follow-up, respectively. DSMs-TACE vs. DEB-TACE was associated with significantly higher complete response rate (27.6 vs. 0.0%, p = 0.011) and significant decrease in serum AFP levels (p = 0.013). Conclusion: Both DSMs-TACE with 50 ± 7 µm microspheres and 300–500 μm DEB-TACE are effective for local control of unresectable HCC. Our findings revealed superiority of DSMs-TACE over DEB-TACEnin terms of initial clinical and radiological tumor response; though no significant difference was noted between the two patient groups in terms of local recurrence or mortality during follow up.
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36
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Mahmoud K, Swidan S, El-Nabarawi M, Teaima M. Lipid based nanoparticles as a novel treatment modality for hepatocellular carcinoma: a comprehensive review on targeting and recent advances. J Nanobiotechnology 2022; 20:109. [PMID: 35248080 PMCID: PMC8898455 DOI: 10.1186/s12951-022-01309-9] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Accepted: 02/12/2022] [Indexed: 12/12/2022] Open
Abstract
Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles-specifically lipid based nanoparticles-are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, phytosomes, lipid coated nanoparticles, and nanoassemblies. Multiple approaches are used to enhance the tumor uptake as well tumor specificity such as intratumoral injection, passive targeting, active targeting, and stimuli responsive nanoparticles. In this review, the effect of utilizing lipidic nanoparticles is being discussed as well as the different tumor uptake enhancement techniques used.
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Affiliation(s)
- Khaled Mahmoud
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt
- The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt
| | - Shady Swidan
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt.
- The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, 11837, Egypt.
| | - Mohamed El-Nabarawi
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
| | - Mahmoud Teaima
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
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37
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Murali M, Kumar AR, Nair B, Pavithran K, Devan AR, Pradeep GK, Nath LR. Antibody-drug conjugate as targeted therapeutics against hepatocellular carcinoma: preclinical studies and clinical relevance. Clin Transl Oncol 2022; 24:407-431. [PMID: 34595736 DOI: 10.1007/s12094-021-02707-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 08/29/2021] [Indexed: 02/05/2023]
Abstract
An antibody-drug conjugate (ADC) is an advanced chemotherapeutic option with immense promises in treating many tumor. They are designed to selectively attack and kill neoplastic cells with minimal toxicity to normal tissues. ADCs are complex engineered immunoconjugates that comprise a monoclonal antibody for site-directed delivery and cytotoxic payload for targeted destruction of malignant cells. Therefore, it enables the reduction of off-target toxicities and enhances the therapeutic index of the drug. Hepatocellular carcinoma (HCC) is a solid tumor that shows high heterogeneity of molecular phenotypes and is considered the second most common cause of cancer-related death. Studies show enormous potential for ADCs targeting GPC3 and CD24 and other tumor-associated antigens in HCC with their high, selective expression and show potential outputs in preclinical evaluations. The review mainly highlights the preclinical evaluation of different antigen-targeted ADCs such as MetFab-DOX, Anti-c-Met IgG-OXA, Anti CD 24, ANC-HN-01, G7mab-DOX, hYP7-DCand hYP7-PC, Anti-CD147 ILs-DOX and AC133-vcMMAF against hepatocellular carcinoma and its future relevance.
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Affiliation(s)
- M Murali
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P. O., Kochi, Kerala, 682041, India
| | - A R Kumar
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P. O., Kochi, Kerala, 682041, India
| | - B Nair
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P. O., Kochi, Kerala, 682041, India
| | - K Pavithran
- Department of Medical Oncology and Hematology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - A R Devan
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P. O., Kochi, Kerala, 682041, India
| | - G K Pradeep
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P. O., Kochi, Kerala, 682041, India
| | - L R Nath
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P. O., Kochi, Kerala, 682041, India.
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Evaluating Radioactive Analogs of Doxorubicin to Quantify ChemoFilter Binding and Whole Body PET/MR Drug Biodistribution. J Vasc Interv Radiol 2022; 33:687-694. [DOI: 10.1016/j.jvir.2022.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 01/20/2022] [Accepted: 03/06/2022] [Indexed: 11/23/2022] Open
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Mohr I, Vogeler M, Pfeiffenberger J, Sprengel SD, Klauss M, Radeleff B, Teufel A, Chang DH, Springfeld C, Longerich T, Merle U, Mehrabi A, Weiss KH, Mieth M. Clinical effects and safety of different transarterial chemoembolization methods for bridging and palliative treatments in hepatocellular carcinoma. J Cancer Res Clin Oncol 2022; 148:3163-3174. [PMID: 35076764 PMCID: PMC9508038 DOI: 10.1007/s00432-021-03900-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 12/24/2021] [Indexed: 01/09/2023]
Abstract
Purpose We assessed and compared clinical effects and safety endpoints of three methods of transarterial chemoembolization (TACE), conventional (cTACE), with drug-eluting beads (DEB-TACE), and with degradable starch microspheres (DSM-TACE), used in patients with hepatocellular carcinoma (HCC) in the bridging to liver transplant (LT) and the palliative setting. Methods In our center, 148 patients with HCC underwent 492 completed TACE procedures between 2008 and 2017 (158 for bridging to LT; 334 for palliative treatment) which we analyzed retrospectively. Of these procedures, 348 were DEB-TACE, 60 cTACE, and 84 DSM-TACE. Results The cTACE procedure revealed a significantly longer period of hospitalization (p = 0.02), increased occurrence of nausea (p = 0.025), and rise in alanine transaminase (ALT) levels (p = 0.001), especially in the palliative setting. In the bridging to LT cohort, these clinical endpoints did not reach statistical significance. Conclusions The clinical safety of different TACE methods for HCC in both the palliative and the bridging to LT setting was equivalent. In the palliative setting, the cTACE procedure revealed an increased risk for adverse clinical effects such as nausea, elevation of ALT, and a prolonged period of hospitalization what might either be related to the systemic effects of the chemotherapeutic agent or to the differences in both collectives. Thus, further studies must be conducted on a larger number of TACE procedures to effectively explore the clinical side effects of the various TACE variants.
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Affiliation(s)
- Isabelle Mohr
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Marie Vogeler
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Jan Pfeiffenberger
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | | | - Miriam Klauss
- Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Boris Radeleff
- Department of Diagnostic and Interventional Radiology, Sana Klinikum Hof, Hof, Germany
| | - Andreas Teufel
- Department of Gastroenterology and Hepatology, Mannheim University Hospital, Mannheim, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - De-Hua Chang
- Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Christoph Springfeld
- Department of Medical Oncology, Heidelberg University Hospital, National Center for Tumor Diseases (NCT), Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Thomas Longerich
- Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Uta Merle
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, INF 110, 69120, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Karl Heinz Weiss
- Internal Medicine, Salem Hospital Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, INF 110, 69120, Heidelberg, Germany.
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany.
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40
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Xu L, Chen L, Zhang W. Neoadjuvant treatment strategies for hepatocellular carcinoma. World J Gastrointest Surg 2021; 13:1550-1566. [PMID: 35070063 PMCID: PMC8727178 DOI: 10.4240/wjgs.v13.i12.1550] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/27/2021] [Accepted: 11/30/2021] [Indexed: 02/06/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) remains high globally. Surgical treatment is the best treatment for improving the prognosis of patients with HCC. Neoadjuvant therapy plays a key role in preventing tumor progression and even downstaging HCC. The liver transplantation rate and resectability rate have increased for neoadjuvant therapy. Neoadjuvant therapy is effective in different stages of HCC. In this review, we summarized the definition, methods, effects, indications and contraindications of neoadjuvant therapy in HCC, which have significance for guiding treatment.
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Affiliation(s)
- Lei Xu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Lin Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Natu A, Singh A, Gupta S. Hepatocellular carcinoma: Understanding molecular mechanisms for defining potential clinical modalities. World J Hepatol 2021; 13:1568-1583. [PMID: 34904030 PMCID: PMC8637668 DOI: 10.4254/wjh.v13.i11.1568] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 05/12/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
Liver cancer is the sixth most commonly occurring cancer and costs millions of lives per year. The diagnosis of hepatocellular carcinoma (HCC) has relied on scanning techniques and serum-based markers such as α-fetoprotein. These measures have limitations due to their detection limits and asymptomatic conditions during the early stages, resulting in late-stage cancer diagnosis where targeted chemotherapy or systemic treatment with sorafenib is offered. However, the aid of conventional therapy for patients in the advanced stage of HCC has limited outcomes. Thus, it is essential to seek a new treatment strategy and improve the diagnostic techniques to manage the disease. Researchers have used the omics profile of HCC patients for sub-classification of tissues into different groups, which has helped us with prognosis. Despite these efforts, a promising target for treatment has not been identified. The hurdle in this situation is genetic and epigenetic variations in the tumor, leading to disparities in response to treatment. Understanding reversible epigenetic changes along with clinical traits help to define new markers for patient categorization and design personalized therapy. Many clinical trials of inhibitors of epigenetic modifiers (also known as epi-drugs) are in progress. Epi-drugs like azacytidine or belinostat are already approved for other cancer treatments. Furthermore, epigenetic changes have also been observed in drug-resistant HCC tumors. In such cases, combinatorial treatment of epi-drugs with systemic therapy or trans-arterial chemoembolization might re-sensitize resistant cells.
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Affiliation(s)
- Abhiram Natu
- Epigenetics and Chromatin Biology Group, Gupta Laboratory, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India
- Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, Maharashtra, India
| | - Anjali Singh
- Epigenetics and Chromatin Biology Group, Gupta Laboratory, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India
- Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, Maharashtra, India
| | - Sanjay Gupta
- Epigenetics and Chromatin Biology Group, Gupta Laboratory, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India
- Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, Maharashtra, India
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42
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Nezami N, VAN Breugel JMM, Konstantinidis M, Chapiro J, Savic LJ, Miszczuk MA, Rexha I, Lin M, Hong K, Georgiades C. Lipiodol Deposition and Washout in Primary and Metastatic Liver Tumors After Chemoembolization. In Vivo 2021; 35:3261-3270. [PMID: 34697157 DOI: 10.21873/invivo.12621] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 08/18/2021] [Accepted: 09/06/2021] [Indexed: 12/26/2022]
Abstract
BACKGROUND/AIM Lipiodol is the key component of conventional trans-arterial chemoembolization. Our aim was to evaluate lipiodol deposition and washout rate after conventional trans-arterial chemoembolization in intrahepatic cholangiocarcinoma and hepatic metastases originating from neuroendocrine tumors and colorectal carcinoma. PATIENTS AND METHODS This was a retrospective analysis of 44 patients with intrahepatic cholangiocarcinoma and liver metastasis from neuroendocrine tumors or colorectal carcinoma who underwent conventional trans-arterial chemoembolization. Lipiodol volume (cm3) was analyzed on non-contrast computed tomography imaging obtained within 24 h post conventional trans-arterial chemoembolization, and 40-220 days after conventional trans-arterial chemoembolization using volumetric image analysis software. Tumor response was assessed on contrast-enhanced magnetic resonance imaging 1 month after conventional trans-arterial chemoembolization. RESULTS The washout rate was longer for neuroendocrine tumors compared to colorectal carcinoma, with half-lives of 54.61 days (p<0.00001) and 19.39 days (p<0.001), respectively, with no exponential washout among intrahepatic cholangiocarcinomas (p=0.83). The half-life for lipiodol washout was longer in tumors larger than 300 cm3 compared to smaller tumors (25.43 vs. 22.71 days). Lipiodol wash out half-life was 54.76 days (p<0.01) and 29.45 days (p<0.00001) for tumors with a contrast enhancement burden of 60% or more and less than 60%, respectively. A negative exponential relationship for lipiodol washout was observed in non-responders (p<0.00001). CONCLUSION Lipiodol washout is a time-dependent process, and occurs faster in colorectal carcinoma tumors, tumors smaller than 300 cm3, tumors with baseline contrast enhancement burden of less than 60%, and non-responding target lesions.
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Affiliation(s)
- Nariman Nezami
- Section of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, U.S.A.; .,Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, U.S.A
| | - Johanna Maria Mijntje VAN Breugel
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, U.S.A.,Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands.,Medical faculty, Utrecht University, Utrecht, the Netherlands
| | - Menelaos Konstantinidis
- Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Julius Chapiro
- Section of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, U.S.A.,Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, U.S.A
| | - Lynn Jeanette Savic
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, U.S.A.,Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Milena Anna Miszczuk
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, U.S.A
| | - Irvin Rexha
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, U.S.A.,Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Mingde Lin
- Visage Imaging, Inc., San Diego, CA, U.S.A
| | - Kelvin Hong
- Division of Vascular and Interventional Radiology, Russel H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A
| | - Christos Georgiades
- Division of Vascular and Interventional Radiology, Russel H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A
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43
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Zhang J, Feng GA, Li Y, Wang W. Drug-eluting bead transarterial chemoembolization with medium-sized versus small-sized CalliSpheres microspheres in unresectable primary liver cancer. Asia Pac J Clin Oncol 2021; 18:388-393. [PMID: 34708554 PMCID: PMC9543937 DOI: 10.1111/ajco.13660] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 07/29/2021] [Indexed: 12/01/2022]
Abstract
Purpose The optimal microparticle size for drug‐eluting beads transarterial chemoembolization (DEB‐TACE) remains unknown. This retrospective cohort study analyzed the efficacy and safety of CalliSpheres microsphere embolization in the treatment of unresectable hepatocellular carcinoma (HCC) to determine the influence of particle size on the results. Patients and methods Forty‐two patients with unresectable HCC were enrolled in this retrospective study from January 2018 to January 2020. Patients received DEB‐TACE with CalliSpheres of 100–300 μm (small‐size, n = 15) or 300–500 μm (medium‐size, n = 27). The tumor response was evaluated via enhanced CT or MRI at 1 month, 3 months, and 6 months after treatment, based on the Modified Response Evaluation Criteria in Solid Tumors. Adverse events after DEB‐TACE were recorded. Results Complete response, partial response, stable disease, and progressive disease were recorded in 20%, 20%, 33.3%, 26.7%, respectively, of patients in the small‐size group and 3.7%, 25.9%, 44.4%, 25.9% of patients in the medium‐size group, respectively. No significant difference was found between the two groups (p = 0.516). Major adverse events, including grade three liver toxicity (n = 4) and liver abscess (n = 3), occurred significantly more in the small‐size group, while none were reported in the medium size group (p < 0.05). Conclusion DEB‐TACE with medium‐size (300–500 μm) CalliSpheres microspheres had similar efficacy and a better safety profile than DEB‐TACE with small‐size (100–300 μm) CalliSpheres, indicating that medium‐size microspheres may be a better choice for unresectable primary liver cancer.
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Affiliation(s)
- Jiao Zhang
- Department of Health Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Guo-An Feng
- Department of Vascular Surgery, Juye County People' Hospital, Heze, Shandong Province, China
| | - Yuliang Li
- Department of Interventional Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Interventional Oncology Institute of Shandong University, Jinan, Shandong Province, China
| | - Wujie Wang
- Department of Interventional Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Interventional Oncology Institute of Shandong University, Jinan, Shandong Province, China
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44
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Lucatelli P, Burrel M, Guiu B, de Rubeis G, van Delden O, Helmberger T. CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation. Cardiovasc Intervent Radiol 2021; 44:1851-1867. [PMID: 34694454 DOI: 10.1007/s00270-021-02968-1] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 09/04/2021] [Indexed: 12/15/2022]
Abstract
This CIRSE Standards of Practice document is aimed at interventional radiologists and provides best practices for performing transarterial chemoembolisation. It has been developed by an expert writing group under the guidance of the CIRSE Standards of Practice Committee. It will encompass all technical details reflecting European practice of different TACE procedures (Lp-TACE, DEM-TACE, DSM-TACE, b-TACE) as well as revising the existing literature on the various clinical indications (HCC, mCRC, ICC, NET). Finally, new frontiers of development will also be discussed.
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Affiliation(s)
- Pierleone Lucatelli
- Vascular and Interventional Radiology Unit, Department of Radiological Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy.
| | - Marta Burrel
- Radiology Department, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Boris Guiu
- Department of Radiology, Montpellier School of Medicine, St-Eloi University Hospital, Montpellier, France
| | - Gianluca de Rubeis
- Vascular and Interventional Radiology Unit, Department of Radiological Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy
- Department of Diagnostic Radiology, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Otto van Delden
- Department of Interventional Radiology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Thomas Helmberger
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, Bogenhausen Hospital, Munich, Germany
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45
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Wagner MG, Periyasamy S, Longhurst C, McLachlan MJ, Whitehead JF, Speidel MA, Laeseke PF. Real-time respiratory motion compensated roadmaps for hepatic arterial interventions. Med Phys 2021; 48:5661-5673. [PMID: 34431111 PMCID: PMC8568648 DOI: 10.1002/mp.15187] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 07/04/2021] [Accepted: 08/11/2021] [Indexed: 11/11/2022] Open
Abstract
PURPOSE During hepatic arterial interventions, catheter or guidewire position is determined by referencing or overlaying a previously acquired static vessel roadmap. Respiratory motion leads to significant discrepancies between the true position and configuration of the hepatic arteries and the roadmap, which makes navigation and accurate catheter placement more challenging and time consuming. The purpose of this work was to develop a dynamic respiratory motion compensated device guidance system and evaluate the accuracy and real-time performance in an in vivo porcine liver model. METHODS The proposed device navigation system estimates a respiratory motion model for the hepatic vasculature from prenavigational X-ray image sequences acquired under free-breathing conditions with and without contrast enhancement. During device navigation, the respiratory state is tracked based on live fluoroscopic images and then used to estimate vessel deformation based on the previously determined motion model. Additionally, guidewires and catheters are segmented from the fluoroscopic images using a deep learning approach. The vessel and device information are combined and shown in a real-time display. Two different display modes are evaluated within this work: (1) a compensated roadmap display, where the vessel roadmap is shown moving with the respiratory motion; (2) an inverse compensated device display, where the device representation is compensated for respiratory motion and overlaid on a static roadmap. A porcine study including seven animals was performed to evaluate the accuracy and real-time performance of the system. In each pig, a guidewire and microcatheter with a radiopaque marker were navigated to distal branches of the hepatic arteries under fluoroscopic guidance. Motion compensated displays were generated showing real-time overlays of the vessel roadmap and intravascular devices. The accuracy of the motion model was estimated by comparing the estimated vessel motion to the motion of the X-ray visible marker. RESULTS The median (minimum, maximum) error across animals was 1.08 mm (0.92 mm, 1.87 mm). Across different respiratory states and vessel branch levels, the odds of the guidewire tip being shown in the correct vessel branch were significantly higher (odds ratio = 3.12, p < 0.0001) for motion compensated displays compared to a noncompensated display (median probabilities of 86 and 69%, respectively). The average processing time per frame was 17 ms. CONCLUSIONS The proposed respiratory motion compensated device guidance system increased the accuracy of the displayed device position relative to the hepatic vasculature. Additionally, the provided display modes combine both vessel and device information and do not require the mental integration of different displays by the physician. The processing times were well within the range of conventional clinical frame rates.
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Affiliation(s)
- Martin G Wagner
- Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Sarvesh Periyasamy
- Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Colin Longhurst
- Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Matthew J McLachlan
- Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Joseph F Whitehead
- Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Michael A Speidel
- Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Paul F Laeseke
- Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA
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46
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Herold Z, Szasz AM, Dank M. Evidence based tools to improve efficiency of currently administered oncotherapies for tumors of the hepatopancreatobiliary system. World J Gastrointest Oncol 2021; 13:1109-1120. [PMID: 34616516 PMCID: PMC8465447 DOI: 10.4251/wjgo.v13.i9.1109] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/29/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatopancreatobiliary tumors are challenging to treat, and the advanced or metastatic forms have a very low 5-year survival rate. Several drug combinations have been tested, and new therapeutic approaches have been introduced in the last decades, including radiofrequency and heat based methods. Hyperthermia is the artificial heating of tumors by various biophysical methods that may possess immunostimulant, tumoricidal, and chemoradiotherapy sensitizer effects. Both whole-body and regional hyperthermia studies have been conducted since the 1980s after the introduction of deep-seated tumor hyperthermia techniques. Results of the effects of hyperthermia in hepatocellular and pancreatic cancer are known from several studies. Hyperthermia in biliary cancers is a less investigated area. High local and overall responses to treatment, increased progression-free and overall survival, and improved laboratory and quality-of-life results are associated with hyperthermia in all three tumor types. With the evolution of chemotherapeutic agents and the introduction of newer techniques, the combination of adjuvant hyperthermia with those therapies is advantageous and has not been associated with an increase in alarming adverse effects. However, despite the many positive effects of hyperthermia, its use is still only known at the experimental level, and its concomitant utilization in routine cancer treatment is not certain because of the lack of thorough clinical studies.
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Affiliation(s)
- Zoltan Herold
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest H-1083, Hungary
| | - A Marcell Szasz
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest H-1083, Hungary
| | - Magdolna Dank
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest H-1083, Hungary
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47
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Kong D, Jiang T, Liu J, Jiang X, Liu B, Lou C, Zhao B, Carroll SL, Feng G. Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal. Drug Deliv 2021; 27:1729-1740. [PMID: 33307843 PMCID: PMC7738295 DOI: 10.1080/10717544.2020.1856219] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Chemoembolization for hepatocellular carcinoma (HCC) is often suboptimal due to multiple involved signaling and lack of effective drugs. Arsenic trioxide (ATO) is a potent chemotherapeutic agent, which can target multiple signaling and have substantial efficacy on HCC. However, its usage is limited due to systemic toxicity. Using ATO-eluting beads/microspheres for chemoembolization can have locoregional drug delivery and avoid systemic exposure but will require high drug load, which has not been achieved due to low solubility of ATO. Through an innovative approach, we generated the transiently formed ATO microcrystals via micronization and stabilized these microcrystals by solvent exchange. By encapsulating ATO microcrystals, but not individual molecules, with poly(lactide-co-glycolic acid) (PLGA), we developed microspheres cored with extremely high dense ATO. The molar ratio between ATO and PLGA was 157.4:1 and drug load was 40.1%, which is 4–20 fold higher than that of reported ATO nano/microparticles. These microspheres sustainably induced reactive oxygen species, apoptosis, and cytotoxicity on HCC cells and reduced tumor growth by 80% via locoregional delivery. Chemoembolization on mice model showed that ATO-microcrystal loaded microspheres, but not ATO, inhibited HCC growth by 60–75%, which indicates ATO within these microspheres gains the chemoembolizing function via our innovative approach.
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Affiliation(s)
- Degang Kong
- Department of Hepatobiliary Surgery, The Second Hospital of Tianjin Medical University, Tianjin, China.,Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA
| | - Tao Jiang
- Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA.,Department of General Surgery, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, China
| | - Jian Liu
- Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA
| | - Xinyi Jiang
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China
| | - Bei Liu
- Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH, USA
| | - Cheng Lou
- Department of Hepatobiliary Surgery, Third Central Hospital of Tianjin, Tianjin, China
| | - Baobing Zhao
- Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China
| | - Steven L Carroll
- Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA
| | - Gong Feng
- Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA.,Department of Pathology and Laboratory Medicine Residency Program, Medical University of South Carolina, Charleston, SC, USA
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Chang WC, Hsu HH, Chiu SH, Huang WY, Lo CH, Lin HH, Huang PC, Shih YL, Wan YL. Transcatheter Arterial Chemoembolization with Drug-Eluting Beads for the Treatment of Hepatocellular Carcinoma: Recommended Selection for Small-Caliber (<100 μm) Beads. J Hepatocell Carcinoma 2021; 8:937-949. [PMID: 34422707 PMCID: PMC8373306 DOI: 10.2147/jhc.s319920] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 07/29/2021] [Indexed: 12/12/2022] Open
Abstract
Drug-eluting beads transarterial chemoembolization (DEB-TACE) is an alternative to conventional lipiodol-based TACE (cTACE) to treat hepatocellular carcinoma (HCC). With the advancement in pharmacology, small-caliber DEB-TACE (<100 μm) has been introduced since 2016. For the treatment of hepatic neoplasms or HCC, there is a tendency to use smaller beads by DEB-TACE to achieve more extensive tumor necrosis and a significant reduction in liver toxicity in comparison with that caused by cTACE. However, the indications and potential complications of small-caliber DEB-TACE remain uncertain and have not been well established, due to lack of randomized phase III clinical trials. Instead of systematic or meta-analysis review, this narrative review article describes the suggested indications and contraindications of DEB-TACE with small DEBs, benefit of super-selective embolization of the feeding arteries and the recommended selection of small-caliber DEB. This review was approved by the institutional review board (File Number: 1-105-05-158).
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Affiliation(s)
- Wei-Chou Chang
- Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan
| | - Hsian-He Hsu
- Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan
| | - Sung-Hua Chiu
- Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan
| | - Wen-Yen Huang
- Department of Radiation Oncology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan
| | - Cheng-Hsiang Lo
- Department of Radiation Oncology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan
| | - Hsuan-Hwai Lin
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan
| | - Pei-Ching Huang
- Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan
| | - Yu-Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan
| | - Yung-Liang Wan
- Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan
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Park C, Gwon DI, Chu HH, Kim JW, Kim JH, Ko GY. Correlation of tumor response on CT with pathologically proven necrosis in hepatocellular carcinoma treated by conventional transcatheter arterial chemoembolization: threshold value of intratumoral Lipiodol accumulation predicting tumor necrosis. Abdom Radiol (NY) 2021; 46:3729-3737. [PMID: 33141259 DOI: 10.1007/s00261-020-02845-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 10/24/2020] [Accepted: 10/29/2020] [Indexed: 12/12/2022]
Abstract
PURPOSE To evaluate associations between pathology and CT assessments made according to the mRECIST in HCC treated by conventional TACE (cTACE), and to identify predictors of complete tumor necrosis. METHODS From March 2016 to July 2018, 83 patients with a total of 100 masses were retrospectively included. Patients underwent sequential cTACE and portal vein embolization, and later hepatic surgery. Evaluation of treatment response and measurement of baseline lipiodol accumulation as mean HU was performed on CT at the time point closest to the time of operation (mean, 54.5 days after cTACE). Significant predictors associated with complete necrosis were identified by multivariate analysis. The optimal cut-off HU value of lipiodol accumulation for prediction of complete necrosis was determined using a ROC analysis. RESULTS According to mRECIST, complete response (CR, n = 70) and partial response (n = 30) were classified. 34.3% (24/70) masses classified as CR according to mRECIST were found to have viable lesions on pathology. On multivariate analysis, mean HU of lipiodol accumulation was the only significant predictor of complete necrosis (p = .003, odds ratio 1.746, 95% CI 1.201-2.539). On ROC analysis, 460 HU as a cut-off value was significantly associated with complete necrosis (67.4% sensitivity, 75.0% specificity). CONCLUSIONS A threshold value for lipiodol accumulation > 460 HU was highly sensitive and specific for complete necrosis, even in complete response according to mRECIST. Therefore, if lipiodol accumulation is insufficient in post-TACE CT, recurrence should be monitored more sensitively.
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Affiliation(s)
- Chan Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea
| | - Dong Il Gwon
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea.
| | - Hee Ho Chu
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea
| | - Jong Woo Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea
| | - Gi-Young Ko
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea
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Sawant A, Kamath S, KG H, Kulyadi GP. Solid-in-Oil-in-Water Emulsion: An Innovative Paradigm to Improve Drug Stability and Biological Activity. AAPS PharmSciTech 2021; 22:199. [PMID: 34212274 PMCID: PMC8249250 DOI: 10.1208/s12249-021-02074-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 06/14/2021] [Indexed: 12/13/2022] Open
Abstract
Abstract An emulsion is a biphasic dosage form comprising of dispersed phase containing droplets that are uniformly distributed into a surrounding liquid which forms the continuous phase. An emulsifier is added at the interface of two immiscible liquids to stabilize the thermodynamically unstable emulsion. Various types of emulsions such as water-in-oil (w-o), oil-in-water (o-w), microemulsions, and multiple emulsions are used for delivering certain drugs in the body. Water (aqueous) phase is commonly used for encapsulating proteins and several other drugs in water-in-oil-in-water (w-o-w) emulsion technique. But this method has posed certain problems such as decreased stability, burst release, and low entrapment efficiency. Thus, a novel “solid-in-oil-in-water” (s-o-w) emulsion system was developed for formulating certain drugs, probiotics, proteins, antibodies, and tannins to overcome these issues. In this method, the active ingredient is encapsulated as a solid and added to an oil phase, which formed a solid-oil dispersion. This dispersion was then mixed with water to form a continuous phase for enhancing the drug absorption. This article focuses on the various studies done to investigate the effectiveness of formulations prepared as solid-oil-water emulsions in comparison to conventional water-oil-water emulsions. A summary of the results obtained in each study is presented in this article. The s-o-w emulsion technique may become beneficial in near future as it has shown to improve the stability and efficacy of the entrapped active ingredient. Graphical abstract ![]()
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