Journal of Liver Cancer

Case Reports

Favorable response of hepatocellular carcinoma with portal vein tumor thrombosis after radiotherapy combined with atezolizumab plus bevacizumab: Yong Tae Kim, Jina Kim, Jinsil Seong; Received January 11, 2023 Accepted February 27, 2023 Published online March 16, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.27 [Epub ahead of print]

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Abstract PDF: Recently, the superiority of atezolizumab plus bevacizumab (AteBeva) over sorafenib was proven in the IMbrave150 trial, and AteBeva became the first-line systemic treatment for untreated, unresectable hepatocellular carcinoma (HCC). While the results are encouraging, more than half of patients with advanced HCC are still being treated in a palliative setting. Radiotherapy (RT) is known to induce immunogenic effects that may enhance the therapeutic efficacy of immune checkpoint inhibitors. Herein, we report the case of a patient with advanced HCC with massive portal vein tumor thrombosis treated with a combination of RT and AteBeva, who showed near complete response in tumor thrombosis and favorable response to HCC. Although this is a rare case, it shows the importance of reducing the tumor burden via RT to combination immunotherapy in patients with advanced HCC.

A case of successful surgical treatment for peritoneal seeding of hepatocellular carcinoma after radiotherapy and atezolizumab plus bevacizumab combination treatment: Yuri Cho, Bo Hyun Kim, Tae Hyun Kim, Young Hwan Koh, Joong-Won Park; Received January 12, 2023 Accepted February 9, 2023 Published online February 24, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.09 [Epub ahead of print]

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Abstract PDF: Peritoneal seeding of hepatocellular carcinoma (HCC) is incurable and has poor prognosis. A 68-year-old man underwent surgical resection for a 3.5 cm single nodular HCC at the tip of segment 3 and transarterial chemoembolization for a 1.5 cm-sized recurrent HCC at the tip of segment 6. 3 months later, an increasing 1 cm pelvic nodule on the rectovesical pouch warranted radiotherapy. Although it stabilized, a new 2.7 cm-sized peritoneal nodule in the right upper quadrant (RUQ) omentum appeared 3.5 years after radiotherapy. Hence, omental mass and small bowel mesentery mass excision were performed. 3 years later, recurrent peritoneal metastases in the RUQ omentum and rectovesical pouch progressed. 33 cycles of atezolizumab and bevacizumab treatment elicited stable disease response. Finally, laparoscopic left pelvic peritonectomy was performed without tumor recurrence. Herein, we present a case of HCC with peritoneal seeding that was successfully treated with surgery after radiotherapy and systemic therapy, leading to complete remission.

Original Article

Diagnostic performance of the 2022 KLCA-NCC criteria for hepatocellular carcinoma on magnetic resonance imaging with extracellular contrast and hepatobiliary agents: comparison with the 2018 KLCA-NCC criteria: Ja Kyung Yoon, Sunyoung Lee, Jeong Ah Hwang, Ji Eun Lee, Seung-seob Kim, Myeong-Jin Kim; Received December 27, 2022 Accepted February 7, 2023 Published online February 23, 2023; DOI: https://doi.org/10.17998/jlc.2023.02.07 [Epub ahead of print]

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Abstract PDF Supplementary Material: Background
/Aim: This study aimed to determine the diagnostic performance of 2022 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) imaging criteria compared with the 2018 KLCA-NCC for hepatocellular carcinoma (HCC) in high-risk patients using magnetic resonance imaging (MRI).
Methods
This retrospective study included 415 treatment-naïve patients (152 patients who underwent extracellular contrast agent [ECA]-MRI and 263 who underwent hepatobiliary agent [HBA]-MRI; 535 lesions, including 412 HCCs) with a high risk of HCC who underwent contrast-enhanced MRI. Two readers evaluated all lesions according to the 2018 and 2022 KLCA-NCC imaging diagnostic criteria, and the per-lesion diagnostic performances were compared.
Results
In “definite” HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI showed a significantly higher sensitivity for the diagnosis of HCC than ECA-MRI (77.0% vs. 64.3%, P=0.006) without a significant difference in specificity (94.7% vs. 95.7%, P=0.801). On ECAMRI, “definite” or “probable” HCC categories of the 2022 KLCA-NCC had significantly higher sensitivity than those of the 2018 KLCA-NCC (85.3% vs. 78.3%, P=0.002) with identical specificity (93.6%). On HBA-MRI, the sensitivity and specificity of “definite” or “probable” HCC categories of both 2018 and 2022 KLCA-NCC were not significantly different (83.3% vs. 83.6%, P>0.999 and 92.1% vs. 90.8%, P>0.999, respectively).
Conclusions
In “definite” HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI provides better sensitivity than ECA-MRI without compromising specificity. On ECA-MRI, “definite” or “probable” HCC categories of the 2022 KLCA-NCC may improve sensitivity in the diagnosis of HCC compared with the 2018 KLCA-NCC.

Guideline

2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma: Received November 5, 2022 Accepted November 7, 2022 Published online December 9, 2022; DOI: https://doi.org/10.17998/jlc.2022.11.07 [Epub ahead of print]

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Abstract PDF: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.

Review Article

Liquid biopsy for early detection and therapeutic monitoring of hepatocellular carcinoma: Eun-Ji Choi, Young-Joon Kim; J Liver Cancer. 2022;22(2):103-114. Published online September 22, 2022; DOI: https://doi.org/10.17998/jlc.2022.09.08

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Abstract PDF Supplementary Material: Advances in our knowledge of the molecular characteristics of hepatocellular carcinoma (HCC) have enabled significant progress in the detection and therapeutic prediction of HCC. As a non-invasive alternative to tissue biopsy, liquid biopsy examines circulating cellular components such as exosomes, nucleic acids, and cell-free DNA found in body fluids (e.g., urine, saliva, ascites, and pleural effusions) and provides information about tumor characteristics. Technical advances in liquid biopsy have led to the increasing adoption of diagnostic and monitoring applications for HCC. This review summarizes the various analytes, ongoing clinical trials, and case studies of United States Food and Drug Administrationapproved in vitro diagnostic applications for liquid biopsy, and provides insight into its implementation in managing HCC.

Case Report

Fibrolamellar hepatocellular carcinoma that was successfully treated with surgical resection: a case report: Seong Kyun Na; J Liver Cancer. 2022;22(2):178-182. Published online June 22, 2022; DOI: https://doi.org/10.17998/jlc.2022.06.10

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Abstract PDF: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare malignant hepatic cancer with characteristics that differ from those of typical hepatocellular carcinoma (HCC). Unlike conventional HCC, FLHCC is common in young patients without any underlying liver disease and is known to be associated with a unique gene mutation. This cancer type is rare in Asia, with only a few cases being reported in Korea. We report a case of FLHCC in a young woman that successfully underwent surgical resection. The efficacy of alternative treatments, such as transarterial chemoembolization or systemic chemotherapies, has not yet been established. To conclude, early diagnosis and appropriate surgical resection are important for the treatment of FLHCC.

Review Article

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

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Abstract 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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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

Case Report

Concurrent transarterial radioembolization and combination atezolizumab/ bevacizumab treatment of infiltrative hepatocellular carcinoma with portal vein tumor thrombosis: a case report: Min Kyung Park, Su Jong Yu; J Liver Cancer. 2022;22(1):69-74. Published online March 21, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.09

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Abstract PDF

Treatment options for advanced hepatocellular carcinoma (HCC) have been rapidly evolving. Herein, we describe a patient with advanced HCC and portal vein tumor thrombosis (PVTT) who responded decisively to a multidisciplinary approach. The patient had an ill-defined infiltrative HCC (diffuse subtype), with several intrahepatic metastasis and tumor invasion of left portal vein. Concurrent use of transarterial radioembolization (TARE) and systemic therapeutics (atezolizumab + bevacizumab) ultimately proved successful. There was marked reduction in tumor volume after TARE and an additional three cycles of atezolizumab plus bevacizumab. This concurrent treatment was well tolerated, without adverse events during immunotherapy. The impressive results achieved suggest that concurrent TARE and combination atezolizumab/bevacizumab is a promising treatment approach for advanced HCC with PVTT.

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Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
Won Hyeok Choe
Journal of Liver Cancer.2022; 22(1): 1. CrossRef

Original Article

Diagnostic performance of serum exosomal miRNA-720 in hepatocellular carcinoma: Jeong Won Jang, Ji Min Kim, Hye Seon Kim, Jin Seoub Kim, Ji Won Han, Soon Kyu Lee, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon; J Liver Cancer. 2022;22(1):30-39. Published online March 21, 2022; DOI: https://doi.org/10.17998/jlc.2022.02.25

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Abstract PDF Supplementary Material: Background
/Aim: Hepatocellular carcinoma (HCC) is associated with poor prognosis, largely due to late detection. Highly accurate biomarkers are urgently needed to detect early-stage HCC. Our study aims to explore the diagnostic performance of serum exosomal microRNA (miR)-720 in HCC.
Methods
Exosomal miRNA was measured via quantitative real-time PCR. A correlation analysis of exosomal miR-720 and tumor or clinico-demographic data of patients with HCC was performed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of serum exosomal miR-720 for HCC, in comparison with α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II).
Results
MiR-720 was chosen as a potential HCC marker via miR microarray based on significant differential expression between tumor and non-tumor samples. Serum exosomal miR-720 was significantly upregulated in patients with HCC (n=114) versus other liver diseases (control, n=30), with a higher area under the ROC curve (AUC=0.931) than the other markers. Particularly, serum exosomal miR-720 showed superior performance in diagnosing small HCC (< 5 cm; AUC=0.930) compared with AFP (AUC=0.802) or PIVKA-II (AUC=0.718). Exosomal miR-720 levels showed marginal correlation with tumor size. The proportion of elevated miR-720 also increased with intrahepatic tumor stage progression. Unlike AFP or PIVKA-II showing a significant correlation with aminotransferase levels, the exosomal miR-720 level was not affected by aminotransferase levels.
Conclusions
Serum exosomal miR-720 is an excellent biomarker for the diagnosis of HCC, with better performance than AFP or PIVKA-II. Its diagnostic utility is maintained even in small HCC and is unaffected by aminotransferase levels.

Case Report

Multidisciplinary treatment with immune checkpoint inhibitors for advanced stage hepatocellular carcinoma: Ahlim Lee, Jaejun Lee, Hyun Yang, Soo-Yoon Sung, Chang Ho Jeon, Su Ho Kim, Moon Hyung Choi, Young Joon Lee, Ho Jong Chun, Si Hyun Bae; J Liver Cancer. 2022;22(1):75-83. Published online March 18, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.04

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Abstract PDF

Hepatocellular carcinoma (HCC) is a cytotoxic chemotherapy-resistant tumor and most HCCs arise in a background of liver cirrhosis of various causes. Although the IMBrave150 trial showed remarkable advancements in the treatment of unresectable HCC with atezolizumab plus bevacizumab (AteBeva), therapeutic outcomes were unsatisfactory in more than half of the patients. Accordingly, many ongoing trials combine conventional modalities with new drugs such as immune checkpoint inhibitors for better treatment outcomes, and they are expected to benefit patients with limited responses to conventional treatment. Here, two patients with advanced stage HCC with preserved liver function and good performance status showed partial response after treatment with combination or sequential therapy of AteBeva, hepatic arterial infusion chemotherapy, radiation therapy, and transarterial chemoembolization. These findings indicate the efficacy of multidisciplinary treatment against advanced HCC. Additional studies are required to establish optimal treatment strategies.

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Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
Won Hyeok Choe
Journal of Liver Cancer.2022; 22(1): 1. CrossRef

Review Article

Radioembolization for hepatocellular carcinoma: what clinicians need to know: Jin Woo Choi, Hyo-Cheol Kim; J Liver Cancer. 2022;22(1):4-13. Published online February 23, 2022; DOI: https://doi.org/10.17998/jlc.2022.01.16

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Abstract PDF

Transarterial radioembolization (TARE) with yttrium 90 (⁹⁰Y) has been used in the management of hepatocellular carcinoma (HCC) for more than 10 years in Korea. There are two types of ⁹⁰Y radioactive microspheres available, namely, glass and resin microspheres, with comparable clinical outcomes. In general, TARE outperforms transarterial chemoembolization regarding post-embolization syndrome, time to progression, tumor downsizing for liver transplantation, and hospitalization stay. Although TARE is commonly recommended for patients with unresectable large HCCs, it can be an alternative to or performed in combination with ablation, surgical resection, and systemic treatment. This review aimed to address ⁹⁰Y radioactive microspheres, patient selection, clinical outcomes, simulation tests, radioembolization procedures, follow-up imaging, and complications.

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Transarterial chemoembolization as an alternative to radioembolization is associated with earlier tumor recurrence than in radioembolization-eligible patients
Sung Won Chung, Heejin Cho, Hyunjae Shin, Jeayeon Park, Ju Yeon Kim, Ji Hoon Hong, Moon Haeng Hur, Min Kyung Park, Yun Bin Lee, Su Jong Yu, Myungsu Lee, Yoon Jun Kim, Jin Chul Paeng, Jung-Hwan Yoon, Jin Wook Chung, Jeong-Hoon Lee, Hyo-Cheol Kim
Frontiers in Oncology.2023;[Epub] CrossRef

Case Reports

Sorafenib combined with radiation therapy for advanced hepatocellular carcinoma with portal and hepatic vein invasion extending to the inferior vena cava: a complete response case according to modified RECIST criteria: Yuri Cho, Bo Hyun Kim, Tae Hyun Kim, Young Hwan Koh, Joong-Won Park; J Liver Cancer. 2022;22(1):63-68. Published online February 14, 2022; DOI: https://doi.org/10.17998/jlc.2022.01.18

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Abstract PDF

The prognosis of patients with advanced hepatocellular carcinoma (HCC) with tumor thrombus extending to the inferior vena cava (IVC) is extremely poor. Herein, we present a rare case of advanced HCC that was treated with sorafenib and radiotherapy, leading to complete remission. This patient had a 9 cm infiltrative HCC occupying almost the entire left lobe with a tumor thrombus extending through the hepatic vein, IVC, and left portal vein. The patient received 400 mg sorafenib twice daily. One year after the start of sorafenib, intensity-modulated radiation therapy for viable HCC and tumor thrombus was performed with a dose of 5,500 cGy. Twenty-seven months after the starting date of sorafenib, there was no intratumoral arterial enhancement, which suggested a complete response according to the modified RECIST criteria. This case suggests that the combination of sorafenib and radiotherapy might provide clinical benefits in patients with advanced HCC with IVC tumor thrombus.

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Citations to this article as recorded by

Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
Won Hyeok Choe
Journal of Liver Cancer.2022; 22(1): 1. CrossRef

Complete response to local therapy for advanced hepatocellular carcinoma with lung metastasis: a case report: Daeun Kim, Seiyeon Park, Won Sohn, Hyun Pyo Hong, Byung Ik Kim; J Liver Cancer. 2022;22(1):51-56. Published online January 27, 2022; DOI: https://doi.org/10.17998/jlc.2021.12.28

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Abstract PDF: The concept of oligometastasis is widely accepted for various types of solid tumors; accordingly, better outcomes can be anticipated with aggressive local interventions. The treatment of advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis is systemic therapy. However, treatment responses to systemic therapy are poor. Recently, a small number of metastatic cancers (oligometastasis) have been controlled by local therapy rather than systemic therapy. Our study reports a case of a 66-year-old male patient with advanced HCC with lung metastasis, which was treated with local therapy. There were less than four metastases in the lungs, which were treated with wedge resection, radiofrequency, and radiation therapy. He repeatedly underwent local therapy for lung oligometastasis and locoregional therapy for intrahepatic HCC rather than systemic therapy; control by local therapy was possible as his liver function was preserved with Child-Turcotte-Pugh class A.

A case report of advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy and sorafenib combination therapy followed by metastasectomy of lung and muscle metastases: Sang Yi Moon, Sang Young Han, Yang-Hyun Baek; J Liver Cancer. 2022;22(1):57-62. Published online January 6, 2022; DOI: https://doi.org/10.17998/jlc.2021.12.20

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Abstract PDF: Currently, various tyrosine kinase inhibitors and immune checkpoint inhibitors have been suggested in the treatment guidelines for advanced hepatocellular carcinoma (HCC). However, sorafenib was the only systemic drug approved 10 years ago. In 2010, a woman diagnosed with HCC rupture and multiple lung metastases visited our hospital. At the time of visiting our hospital, she had undergone transarterial chemoembolization at another hospital to control bleeding due to HCC rupture. We treated her with hepatic arterial infusion chemotherapy and sorafenib combination therapy to increase the control of intrahepatic tumors in consideration of the modest efficacy of sorafenib. The intrahepatic tumor was almost controlled. Metastasectomy was performed to control lung oligometastasis. Subsequently, additional muscle metastasis was confirmed, and metastasectomy was performed. Although this is a very rare case, it shows that a multidisciplinary approach can improve the prognosis of patients with HCC.

Review Article

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

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79 Downloads

Abstract 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.

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