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14 "Immunotherapy"
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Case Report
Durable complete response after discontinuation of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma with portal vein tumor thrombosis: the first report
Pramod Kumar, Pradeep Krishna, Rohit Maidur, Naveen Chandrashekhar, Suresh Raghavaiah
Received June 14, 2024  Accepted September 26, 2024  Published online November 5, 2024  
DOI: https://doi.org/10.17998/jlc.2024.09.26    [Accepted]
  • 819 Views
  • 118 Downloads
AbstractAbstract PDF
Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with a dismal prognosis. Atezolizumab plus bevacizumab (atezo-bev) is the recommended palliative treatment, and approximately 10% of the patients may experience a complete response (CR), according to the mRECIST criteria. The treatment duration is until disease progression or unacceptable side effects occur. Long-term continuation can cause potential toxicities and a substantial financial burden, making early treatment discontinuation a viable option. This report describes durable CR after discontinuing atezo-bev treatment in three patients with HCC and PVTT.
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Review Articles
Multidisciplinary approaches to downstaging hepatocellular carcinoma: present and future
Sang-Youn Hwang, Hyunwook Choi, Wan Jeon, Ryoung-Go Kim
J Liver Cancer. 2024;24(2):171-177.   Published online September 5, 2024
DOI: https://doi.org/10.17998/jlc.2024.08.30
  • 1,244 Views
  • 123 Downloads
AbstractAbstract PDF
Downstaging of hepatocellular carcinoma (HCC) is typically defined as the reduction in size or number of viable tumors through locoregional therapy (LRT), aiming to meet the established criteria for liver transplantation (LT). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, a subgroup of patients with BCLC-B may benefit most from downstaging therapies. The United Network Organ Sharing downstaging protocol identifies potential candidates for downstaging by setting out ‘inclusion criteria’ and defining ‘successful downstaging.’ Additionally, the protocol considers factors related to tumor biology, such as an alphafetoprotein level <500 ng/mL after LRT. Reports indicate that successful downstaging rates following LRT are about 50%, with post- LT recurrence rates comparable to those of patients within the Milan criteria. A comprehensive multicenter US study on 10-year outcomes post-LT after downstaging showed 10-year post-LT survival and recurrence rates of 52.1% and 20.6%, respectively, for patients whose disease was downstaged; this compares to 61.5% and 13.3% for those consistently within the Milan criteria. Recently, the development of effective systemic treatments for HCC, such as immuno-oncologic agents, has provided additional opportunities for downstaging. Numerous clinical trials are exploring a multidisciplinary approach (MDA) combining LRT and systemic therapy. Although concrete evidence of the superiority of MDA for HCC downstaging is lacking, some retrospective studies and phase I and II trials have shown promising results regarding the efficacy and safety of MDA for this purpose. In this review, we will also discuss the future of MDA protocols in downstaging for improved clinical outcomes.
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New systemic treatment options for advanced cholangiocarcinoma
Valentina Zanuso, Giulia Tesini, Elena Valenzi, Lorenza Rimassa
J Liver Cancer. 2024;24(2):155-170.   Published online August 8, 2024
DOI: https://doi.org/10.17998/jlc.2024.08.07
  • 3,436 Views
  • 188 Downloads
  • 4 Citations
AbstractAbstract PDF
Cholangiocarcinoma (CCA) is a rare and aggressive cancer, mostly diagnosed at advanced or metastatic stage, at which point systemic treatment represents the only therapeutic option. Chemotherapy has been the backbone of advanced CCA treatment. More recently, immunotherapy has changed the therapeutic landscape, as immune checkpoint inhibitors have yielded the first improvement in survival and currently, the addition of either durvalumab or pembrolizumab to standard of care cisplatin plus gemcitabine represents the new first-line treatment option. However, the use of immunotherapy in subsequent lines has not demonstrated its efficacy and therefore, it is not approved, except for pembrolizumab in the selected microsatellite instability-high population. In addition, advances in comprehensive genomic profiling have led to the identification of targetable genetic alterations, such as isocitrate dehydrogenase 1 (IDH1), fibroblast growth factor receptor 2 (FGFR2), human epidermal growth factor receptor 2 (HER2), proto-oncogene B-Raf (BRAF), neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), and mouse double minute 2 homolog (MDM2), thus favoring the development of a precision medicine approach in previously treated patients. Despite these advances, the use of molecularly driven agents is limited to a subgroup of patients. This review aims to provide an overview of the newly approved systemic therapies, the ongoing studies, and future research challenges in advanced CCA management.

Citations

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  • Genomic and transcriptomic signatures of sequential carcinogenesis from papillary neoplasm to biliary tract cancer
    Taek Chung, Seungho Oh, Jeongsoo Won, Jiho Park, Jeong Eun Yoo, Ho Kyoung Hwang, Gi Hong Choi, Chang Moo Kang, Dai Hoon Han, Sangwoo Kim, Young Nyun Park
    Journal of Hepatology.2025;[Epub]     CrossRef
  • Is 26S proteasome non-ATPase regulatory subunit 6 a potential molecular target for intrahepatic cholangiocarcinoma?
    Yong-Zhi Zhuang, Li-Quan Tong, Xue-Ying Sun
    World Journal of Hepatology.2024; 16(11): 1219.     CrossRef
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    Jun Gu Kang, Taek Chung, Dong Kyu Kim, Hyungjin Rhee
    The Ewha Medical Journal.2024;[Epub]     CrossRef
  • Resectability and survival outcome in real world practice of 720 cholangiocarcinoma patients: intrahepatic, perihilar and distal cholangiocarcinoma.
    Poowanai Sarkhampee, Weeris Ouransatien, Nithi Lertsawatvicha, Satsawat Chansitthichock, Paiwan Wattanarath
    World Journal of Surgical Oncology.2024;[Epub]     CrossRef
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Original Articles
Downstaging with atezolizumab-bevacizumab: a case series
Anand V. Kulkarni, Parthasarathy Kumaraswamy, Balachandran Menon, Anuradha Sekaran, Anuhya Rambhatla, Sowmya Iyengar, Manasa Alla, Shantan Venishetty, Sumana Kolar Ramachandra, Giri V. Premkumar, Mithun Sharma, P. Nagaraja Rao, Duvvur Nageshwar Reddy, Amit G. Singal
J Liver Cancer. 2024;24(2):224-233.   Published online May 27, 2024
DOI: https://doi.org/10.17998/jlc.2024.05.12
  • 2,515 Views
  • 233 Downloads
  • 3 Citations
AbstractAbstract PDFSupplementary Material
Backgrounds/Aims
Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezo-bev remains unknown.
Methods
In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging.
Results
Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age, 58.5 years; women, 17%; Barcelona Clinic Liver Cancer stage system B/C, 5/7) had received 3-12 cycles of atezo- bev, and four of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 days (range, 54-114) following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 months (range, 4-30), none of the alive patients developed HCC recurrence or graft rejection.
Conclusions
Surgical therapy, including LT, is possible after atezo-bev therapy in well-selected patients after downstaging.

Citations

Citations to this article as recorded by  
  • Immunotherapy Prior to a Liver Transplant: Literature Review and a Case Report of Hepatocellular Carcinoma With BRCA1 Mutation
    N. E. Kostrygin, D. S. Chumachenko
    Innovative Medicine of Kuban.2024; (3): 61.     CrossRef
  • Combining liver-directed and immunotherapy in advanced hepatocellular carcinoma: A review and future directions
    Pranav Kumar, Chase J. Wehrle, Keyue Sun, Chunbao Jiao, Rebecca Panconesi, Mingyi Zhang, Noah X. Tocci, Hanna Hong, Abby Gross, Erlind Allkushi, Maureen Whitsett Linganna, Andrea Schlegel, Toms Augustin, Charles Miller, David CH Kwon, Kazunari Sasaki, Fed
    Surgical Oncology Insight.2024; 1(4): 100100.     CrossRef
  • Prognostic significance of combined PD-L1 expression in malignant and infiltrating cells in hepatocellular carcinoma treated with atezolizumab and bevacizumab
    Jaejun Lee, Jae-Sung Yoo, Ji Hoon Kim, Dong Yeup Lee, Keungmo Yang, Bohyun Kim, Joon-Il Choi, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Ji Won Han, Pil Soo Sung
    Frontiers in Immunology.2024;[Epub]     CrossRef
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Comparison of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis
Jeayeon Park, Yun Bin Lee, Yunmi Ko, Youngsu Park, Hyunjae Shin, Moon Haeng Hur, Min Kyung Park, Dae-Won Lee, Eun Ju Cho, Kyung-Hun Lee, Jeong-Hoon Lee, Su Jong Yu, Tae-Yong Kim, Yoon Jun Kim, Tae-You Kim, Jung-Hwan Yoon
J Liver Cancer. 2024;24(1):81-91.   Published online January 19, 2024
DOI: https://doi.org/10.17998/jlc.2023.12.25
  • 3,604 Views
  • 226 Downloads
  • 3 Citations
AbstractAbstract PDFSupplementary Material
Background/Aim
Atezolizumab plus bevacizumab and lenvatinib are currently available as first-line therapy for the treatment of unresectable hepatocellular carcinoma (HCC). However, comparative efficacy studies are still limited. This study aimed to investigate the effectiveness of these treatments in HCC patients with portal vein tumor thrombosis (PVTT).
Methods
We retrospectively included patients who received either atezolizumab plus bevacizumab or lenvatinib as first-line systemic therapy for HCC with PVTT. Primary endpoint was overall survival (OS), and secondary endpoints included progressionfree survival (PFS) and disease control rate (DCR) determined by response evaluation criteria in solid tumors, version 1.1.
Results
A total of 52 patients were included: 30 received atezolizumab plus bevacizumab and 22 received lenvatinib. The median follow-up duration was 6.4 months (interquartile range, 3.9-9.8). The median OS was 10.8 months (95% confidence interval [CI], 5.7 to not estimated) with atezolizumab plus bevacizumab and 5.8 months (95% CI, 4.8 to not estimated) with lenvatinib (P=0.26 by log-rank test). There was no statistically significant difference in OS (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.34-1.49; P=0.37). The median PFS was similar (P=0.63 by log-rank test), with 4.1 months (95% CI, 3.3-7.7) for atezolizumab plus bevacizumab and 4.3 months (95% CI, 2.6-5.8) for lenvatinib (aHR, 0.93; 95% CI, 0.51-1.69; P=0.80). HRs were similar after inverse probability treatment weighting. The DCRs were 23.3% and 18.2% in patients receiving atezolizumab plus bevacizumab and lenvatinib, respectively (P=0.74).
Conclusion
The effectiveness of atezolizumab plus bevacizumab and lenvatinib was comparable for the treatment of HCC with PVTT.

Citations

Citations to this article as recorded by  
  • Portal vein tumor thrombosis in hepatocellular carcinoma patients: Is it the end?
    Walaa Abdelhamed, Hend Shousha, Mohamed El-Kassas
    Liver Research.2024;[Epub]     CrossRef
  • Reappraisal of transarterial radioembolization for liver-confined hepatocellular carcinoma with portal vein tumor thrombosis: Editorial on “Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein throm
    Jin Hyoung Kim, Gun Ha Kim, Dong Il Gwon
    Clinical and Molecular Hepatology.2024; 30(4): 659.     CrossRef
  • Current perspectives on the pharmacological treatment of advanced hepatocellular carcinoma: a narrative review
    Hye-Jin Yoo, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
    The Ewha Medical Journal.2024;[Epub]     CrossRef
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Review Articles
Complications of immunotherapy in advanced hepatocellular carcinoma
Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
J Liver Cancer. 2024;24(1):9-16.   Published online November 29, 2023
DOI: https://doi.org/10.17998/jlc.2023.11.21
  • 3,290 Views
  • 186 Downloads
  • 9 Citations
AbstractAbstract PDF
Immune checkpoint inhibitors (ICIs) are highly effective in cancer treatment. However, the risks associated with the treatment must be carefully balanced against the therapeutic benefits. Immune-related adverse events (irAEs) are generally unpredictable and may persist over an extended period. In this review, we analyzed common irAEs reported in highly cited original articles and systematic reviews. The prevalent adverse reactions include fatigue, pyrexia, rash, pruritus, diarrhea, decreased appetite, nausea, abdominal pain, constipation, hepatitis, and hypothyroidism. Therefore, it is crucial to conduct evaluations not only of gastrointestinal organs but also of cardiac, neurologic, endocrine (including the frequently affected thyroid), and ophthalmic systems before commencing ICIs. This review further explores commonly reported types of irAEs, specific irAEs associated with each ICI agent, rare yet potentially fatal irAEs, and available treatment options for managing them.

Citations

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  • METTL3-mediated SMPDL3A promotes cell growth, metastasis and immune process of hepatocellular carcinoma by regulating LRPPRC
    Weixin Xu, Miaomiao Tao, Yeqiong Liu, Jun Yan, Jiali Hu, Lei Wang
    Cellular Signalling.2025; 127: 111543.     CrossRef
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    Hepatology.2024; 80(5): 1074.     CrossRef
  • Risk of Bleeding in Hepatocellular Carcinoma Patients Treated with Atezolizumab/Bevacizumab: A Systematic Review and Meta-Analysis
    Young-Gi Song, Kyeong-Min Yeom, Eun Ae Jung, Sang Gyune Kim, Young Seok Kim, Jeong-Ju Yoo
    Liver Cancer.2024; : 1.     CrossRef
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    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Atezolizumab-Induced Ulcerative Colitis in Patient with Hepatocellular Carcinoma: Case Report and Literature Review
    Hyuk Kim, Yoon E Shin, Hye-Jin Yoo, Jae-Young Kim, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
    Medicina.2024; 60(9): 1422.     CrossRef
  • A Potential Pneumothorax Induced by Immune Checkpoint Inhibitors: A Case Report and Literature Review
    Yoon-E Shin, Hyuk Kim, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
    Medicina.2024; 60(10): 1634.     CrossRef
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    The Ewha Medical Journal.2024;[Epub]     CrossRef
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    Han Ah Lee
    The Ewha Medical Journal.2024;[Epub]     CrossRef
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Combination of interventional oncology local therapies and immunotherapy for the treatment of hepatocellular carcinoma
Dong-Hyun Kim
J Liver Cancer. 2022;22(2):93-102.   Published online April 22, 2022
DOI: https://doi.org/10.17998/jlc.2022.03.28
  • 7,261 Views
  • 213 Downloads
  • 12 Citations
AbstractAbstract PDF
Interventional oncology (IO) local therapies of hepatocellular carcinoma (HCC) can activate anti-cancer immunity and it is potentially leading to an anti-cancer immunity throughout the body. For the development of an effective HCC treatment regime, great emphasis has been dedicated to different IO local therapy mediated immune modulation and possible combinations with immune checkpoint inhibitor immunotherapy. In this review paper, we summarize the status of combination of IO local therapy and immunotherapy, as well as the prospective role of therapeutic carriers and locally administered immunotherapy in advanced HCC.

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    Kyeong-Min Yeom, Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
    Medicina.2024; 60(1): 157.     CrossRef
  • CT-guided high dose rate brachytherapy can induce multiple systemic proteins of proliferation and angiogenesis predicting outcome in HCC
    Lukas Salvermoser, Shraga Nahum Goldberg, Marianna Alunni-Fabbroni, Philipp Maximilian Kazmierczak, Moritz Nikolaus Gröper, Jan Niklas Schäfer, Elif Öcal, Tanja Burkard, Stefanie Corradini, Najib Ben Khaled, Agnese Petrera, Moritz Wildgruber, Jens Ricke,
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    Jing-shun Zhang, Yuan-dong Sun, Yuan-min Li, Jian-jun Han
    Heliyon.2024; 10(16): e36388.     CrossRef
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    Sang-Youn Hwang, Hyunwook Choi, Wan Jeon, Ryoung-Go Kim
    Journal of Liver Cancer.2024; 24(2): 171.     CrossRef
  • Current Status of Immunotherapy in Management of Small Bowel Neuroendocrine Tumors
    Brittany C. Fields, Reed I. Ayabe, Y. David Seo, Jessica E. Maxwell, Daniel M. Halperin
    Current Oncology Reports.2024; 26(11): 1530.     CrossRef
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    Han Ah Lee
    The Ewha Medical Journal.2024;[Epub]     CrossRef
  • Hepatotoxicity in Cancer Immunotherapy: Diagnosis, Management, and Future Perspectives
    Alberto Savino, Alberto Rossi, Stefano Fagiuoli, Pietro Invernizzi, Alessio Gerussi, Mauro Viganò
    Cancers.2024; 17(1): 76.     CrossRef
  • Syngeneic N1-S1 Orthotopic Hepatocellular Carcinoma in Sprague Dawley Rat for the Development of Interventional Oncology-Based Immunotherapy: Survival Assay and Tumor Immune Microenvironment
    Bongseo Choi, Jason Pe, Bo Yu, Dong-Hyun Kim
    Cancers.2023; 15(3): 913.     CrossRef
  • Preclinical Development and Validation of Translational Temperature Sensitive Iodized Oil Emulsion Mediated Transcatheter Arterial Chemo‐Immuno‐Embolization for the Treatment of Hepatocellular Carcinoma
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    Advanced Healthcare Materials.2023;[Epub]     CrossRef
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    Won Il Jang, Sunmi Jo, Ji Eun Moon, Sun Hyun Bae, Hee Chul Park
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  • Inducing the Abscopal Effect in Liver Cancer Treatment: The Impact of Microwave Ablation Power Levels and PD-1 Antibody Therapy
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Advances in immune checkpoint inhibitors for hepatocellular carcinoma
Ji Won Han, Su-Hyung Park
J Liver Cancer. 2021;21(2):139-145.   Published online September 30, 2021
DOI: https://doi.org/10.17998/jlc.2021.09.24
  • 4,828 Views
  • 109 Downloads
  • 5 Citations
AbstractAbstract PDF
Hepatocellular carcinoma (HCC) is the fifth most common cancer, and the second leading cause of cancer-related death worldwide. Although recent advances in immune checkpoint inhibitor-based immunotherapy have initiated a new era for advanced HCC treatment, the majority of HCC patients receiving immune checkpoint blockades do not derive clinical benefit. Thus, there remains an urgent need for novel immunotherapeutic strategies with improved therapeutic efficacy. Here we review recent studies of immune checkpoint blockade in HCC, providing the necessary basis for the rational design of immunotherapy.

Citations

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  • Role of transarterial chemoembolization for hepatocellular carcinoma with extrahepatic metastases in the era of advancing systemic therapy
    Byeong Geun Song, Myung Ji Goh, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Moon Seok Choi
    Journal of Liver Cancer.2024; 24(2): 243.     CrossRef
  • Dynamic Peripheral T-Cell Analysis Identifies On-Treatment Prognostic Biomarkers of Atezolizumab plus Bevacizumab in Hepatocellular Carcinoma
    Ji Won Han, Min Woo Kang, Soon Kyu Lee, Hyun Yang, Ji Hoon Kim, Jae-Sung Yoo, Hee Sun Cho, Eun Ji Jang, Deok Hwa Seo, Jung Hyun Kwon, Soon Woo Nam, Si Hyun Bae, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Pil Soo Sung
    Liver Cancer.2024; : 1.     CrossRef
  • Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies
    Logan Muzyka, Nicolas K. Goff, Nikita Choudhary, Michael T. Koltz
    International Journal of Molecular Sciences.2023; 24(13): 10456.     CrossRef
  • Integrative analysis of lactylation-related genes and establishment of a novel prognostic signature for hepatocellular carcinoma
    Diankui Cai, Xiaoqing Yuan, D. Q. Cai, Ang Li, Sijia Yang, Weibang Yang, Jinxin Duan, Wenfeng Zhuo, Jun Min, Li Peng, Jinxing Wei
    Journal of Cancer Research and Clinical Oncology.2023; 149(13): 11517.     CrossRef
  • Editorial on Immune Checkpoint Inhibitors in the Treatment of Hepatocellular Carcinoma
    Samantha M Ruff, Timothy M Pawlik
    Immunotherapy.2023; 15(16): 1323.     CrossRef
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Systemic therapy for advanced hepatocellular carcinoma: consideration for selecting second-line treatment
Bo Hyun Kim, Joong-Won Park
J Liver Cancer. 2021;21(2):124-138.   Published online September 30, 2021
DOI: https://doi.org/10.17998/jlc.2021.09.23
  • 5,027 Views
  • 125 Downloads
  • 2 Citations
AbstractAbstract PDF
Several molecular-targeted agents have been tested as first- or second-line therapies for hepatocellular carcinoma (HCC) but failed to improve clinical outcomes; sorafenib has been the only approved systemic agent for treating HCC for almost 10 years. Regorafenib resulted in a significant improvement in overall survival and thus was approved for HCC patients previously treated with sorafenib. Subsequently, cabozantinib and ramucirumab demonstrated superior overall survival compared with placebos in phase III clinical trials. Immune checkpoint inhibitors such as nivolumab with or without ipilimumab and pembrolizumab are also available in some countries for patients who are unresponsive to sorafenib. Some second-line agents are available for patients who are unresponsive to sorafenib; however, little is known about the considerations for selecting appropriate secondline systemic agents. Hence, this study aimed to review the current and future perspectives of second-line systemic agents.

Citations

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  • Expression of Peptidyl Arginine Deiminase 2 Is Closely Associated with Recurrence in Patients with Hepatocellular Carcinoma
    Sunho Uhm, Yoon Cho, Ji-Young Choe, Ji Park, Min-Jeong Kim, Won-Ho Han, Junyong Lee, Jung Lee, Dong Shin, Jae Soh, Hyun Lim, Ho Kang, Sung-Hoon Moon, Sung-Eun Kim
    Diagnostics.2023; 13(4): 659.     CrossRef
  • Expert consensus on the management of adverse events in patients receiving lenvatinib for hepatocellular carcinoma
    Bo Hyun Kim, Su Jong Yu, Wonseok Kang, Sung Bum Cho, Soo Young Park, Seung Up Kim, Do Young Kim
    Journal of Gastroenterology and Hepatology.2022; 37(3): 428.     CrossRef
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Case Report
Nivolumab for Advanced Hepatocellular Carcinoma with Multiple Lung Metastases after Sorafenib Failure
Jaewoong Kim, Jin Won Chang, Jun Yong Park
J Liver Cancer. 2020;20(1):72-77.   Published online March 31, 2020
DOI: https://doi.org/10.17998/jlc.20.1.72
  • 5,398 Views
  • 147 Downloads
  • 1 Citation
AbstractAbstract PDF
Over the past decade, standard first-line systemic treatment of advanced hepatocellular carcinoma (HCC) has been based on sorafenib, a multi-kinase inhibitor. Regorafenib, another tyrosine kinase inhibitor, is the only second-line therapy that has been globally approved after progression under sorafenib treatment. Recently, immunotherapeutic agents have emerged as promising treatment options in many different malignancies, including advanced HCC. Nivolumab is the first immunotherapy approved by the Food and Drug Administration for use in HCC patients with advanced-stage second-line after sorafenib failure. In this report, a case of advanced HCC with multiple lung metastases in which a complete response and maintained progression-free status was achieved with nivolumab, following the failure of transarterial chemoembolization and sorafenib is presented. We hope this report may help expand the clinical application of second-line treatment.

Citations

Citations to this article as recorded by  
  • Infiltrative hepatocellular carcinoma with multiple lung metastasis completely cured using nivolumab: a case report
    Ji Eun Han, Hyo Jung Cho, Soon Sun Kim, Jae Youn Cheong
    Journal of Liver Cancer.2021; 21(2): 169.     CrossRef
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Review Articles
Deciphering and Reversing Immunosuppressive Cells in the Treatment of Hepatocellular Carcinoma
Su Jong Yu, Tim F. Greten
J Liver Cancer. 2020;20(1):1-16.   Published online March 31, 2020
DOI: https://doi.org/10.17998/jlc.20.1.1
  • 8,085 Views
  • 201 Downloads
  • 3 Citations
AbstractAbstract PDF
Use of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) has been partially successful. However, most HCC patients do not respond to immunotherapy. HCC has been shown to induce several immune suppressor mechanisms in patients. These suppressor mechanisms include involvement of myeloid-derived suppressor cells, regulatory T-cells, functionally impaired dendritic cells (DCs), neutrophils, monocytes, and tumor associated macrophages. The accumulation of immunosuppressive cells may lead to an immunosuppressive tumor microenvironment as well as the dense fibrotic stroma which may contribute to immune tolerance. Our laboratory has been investigating different cellular mechanisms of immune suppression in HCC patients. In vitro as well as in vivo studies have demonstrated that abrogation of the suppressor cells enhances or unmasks tumor-specific antitumor immune responses. Two or three effective systemic therapies including ICIs and/or molecular targeted therapies and the addition of innovative combination therapies targeting immune suppressor cells may lead to increased immune recognition with a greater tumor response. We reviewed the literature for the latest research on immune suppressor cells in HCC, and here we provide a comprehensive summary of the recent studies in this field.

Citations

Citations to this article as recorded by  
  • Higher Number of Tumor-Infiltrating PD-L1+ Cells Is Related to Better Response to Multikinase Inhibitors in Hepatocellular Carcinoma
    Ji Won Han, Ji Hoon Kim, Dong Hyun Kim, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Jaegyoon Ahn, Hyun Yang, Pil Soo Sung
    Diagnostics.2023; 13(8): 1453.     CrossRef
  • Immune checkpoint inhibitors in HCC: Cellular, molecular and systemic data
    Uasim Harkus, Miriam Wankell, Pranavan Palamuthusingam, Craig McFarlane, Lionel Hebbard
    Seminars in Cancer Biology.2022; 86: 799.     CrossRef
  • Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma
    Pil Soo Sung
    Clinical and Molecular Hepatology.2022; 28(3): 333.     CrossRef
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Recent Advances and Future Directions in Immunotherapeutics for Hepatocellular Carcinoma
Yuri Cho, Jimin Han, Won Kim
J Liver Cancer. 2019;19(1):1-11.   Published online March 31, 2019
DOI: https://doi.org/10.17998/jlc.19.1.1
  • 6,010 Views
  • 150 Downloads
  • 5 Citations
AbstractAbstract PDF
Systemic target therapeutic drugs, such as sorafenib, lenvatinib, or regorafenib are the only drugs that are known to be effective against advanced hepatocellular carcinoma (HCC). However, these agents show a limited efficacy in killing residual tumors. Immunotherapy is an alternative approach to this treatment and has been used to successfully treat different cancers, including HCC. HCC is an inflammation-induced cancer and represents a very interesting target for immunotherapeutics. Immunotherapies aim to reverse the immune tolerance and suppression found in tumor microenvironments and include approaches, such as adoptive cell therapy, immune checkpoint inhibition, and cancer vaccination. Adoptive cell therapy uses autologous natural killer or cytokine-induced killer cells by cultivating them ex vivo and subsequently reinfusing them into the patient. Immune checkpoint inhibitors reactivate tumorspecific T cells by suppressing checkpoint-mediated inhibitory signaling. Cancer vaccination induces a tumor-specific immune response by activating effector T lymphocytes. A wide range of potential immunotherapy-related adverse events occur; therefore, a multidisciplinary collaborative management is required across the clinical spectrum. This review summarizes the current status of immunotherapy for HCC and provides a perspective on its future applications.

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  • Exploring the potential of Toxoplasma gondii in drug development and as a delivery system
    Chanjin Yoon, Yu Seong Ham, Woo Jin Gil, Chul-Su Yang
    Experimental & Molecular Medicine.2024; 56(2): 289.     CrossRef
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    Jaewoong Kim, Jin Won Chang, Jun Yong Park
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Case Report
A Case of Management for Advanced Hepatocellular Carcinoma with Extrahepatic Metastasis by Autologous Natural Killer Cells Combined with Immune Checkpoint Inhibitor
Woo, Ara , Kim, Eun Ju , Shin, Sun Young , Jeon, Hong Jae , Park, Hana , Chon, Young Eun , Lee, Yun Bin , Hwang, Seong Gyu , Rim, Kyu Sung , Lee, Joo Ho
J Liver Cancer. 2018;18(1):67-74.   Published online March 31, 2018
DOI: https://doi.org/10.17998/jlc.18.1.67
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  • 70 Downloads
AbstractAbstract PDF
Hepatocellular carcinoma (HCC) has extremely poor prognosis. Immunotherapy has emerged as a new treatment for a number of cancers. Adoptive immunotherapy is one of the important cancer immunotherapy, which relies on the various lymphocytes including cytotoxic T lymphocytes, natural killer (NK) and cytokine induced killer cells. Also, there has been advance in techniques of NK cell activation to more effectively kill the cancer cells. Of note, recently the blocking antibodies targeting programmed cell death protein 1 (PD-1) have shown promising results in diverse cancers including HCC. We report our recent experience of a patient accompanying advanced HCC with extrahepatic metastases. Disease progression had occurred after sorafenib administration, while the patient showed local tumor control and tumor marker decrease by NK cell immunotherapy combined with PD-1 inhibitor therapy. Though, there was no definite survival advantage due to impaired liver function, which might be caused by treatment related toxicities as well as cancer progression.
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Review Article
Systemic Therapy for Advanced Hepatocellular Carcinoma: Targeted Therapy and Immunotherapy
Kim, Bo Hyun , Park, Joong Won
J Liver Cancer. 2018;18(1):17-22.   Published online March 31, 2018
DOI: https://doi.org/10.17998/jlc.18.1.17
  • 2,599 Views
  • 80 Downloads
  • 2 Citations
AbstractAbstract PDF
Systemic therapy for hepatocellular carcinoma (HCC) has markedly changed since 2007, with the approval of sorafenib. Sorafenib improved the overall survival of patients with advanced HCC; however, the modest efficacy and toxicity of this therapy present unmet needs. Subsequently, a variety of molecular targeted agents have been tested as first-line or secondline therapies but have failed, and sorafenib has remained the only approved systemic agent for almost 10 years. Recently, regorafenib significantly improved overall survival and was approved for patients with HCC who have been previously treated with sorafenib. Nivolumab, a programmed death protein-1 inhibitor, was also approved as second-line therapy, based on remarkable response rates.

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  • Sequential Use of Sorafenib and Regorafenib in Hepatocellular Cancer Recurrence After Liver Transplantation: Treatment Strategies and Outcomes
    Mehmet Fatih Ozbay, Hakan Harputluoglu, Mustafa Karaca, Omer Tekin, Mehmet Ali Nahit Şendur, Muhammed Ali Kaplan, Berksoy Sahin, Caglayan Geredeli, Fatih Teker, Deniz Tural, Sezer Saglam, Timuçin Çil, Ahmet Bilici, Cihan Erol, Ziya Kalkan, Ertugrul Bayram
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    The Journal of Internal Korean Medicine.2019; 40(1): 89.     CrossRef
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JLC : Journal of Liver Cancer
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