Journal of Liver Cancer

Articles in E-pub version are posted online ahead of regular printed publication.

Editorial

Congratulatory remarks: Kyung Sik Kim; Published online September 13, 2024; DOI: https://doi.org/10.17998/jlc.2024.09.10 [Epub ahead of print]

49 Views
4 Downloads

PDF

Review Article

Multidisciplinary approaches to downstaging hepatocellular carcinoma: present and future: Sang-Youn Hwang, Hyunwook Choi, Wan Jeon, Ryoung-Go Kim; Received July 15, 2024 Accepted August 30, 2024 Published online September 5, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.30 [Epub ahead of print]

75 Views
8 Downloads

Abstract 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.

Recommendation and Guideline

Local ablation for hepatocellular carcinoma: 2024 expert consensus-based practical recommendation of the Korean Liver Cancer Association: Seungchul Han, Pil Soo Sung, Soo Young Park, Jin Woong Kim, Hyun Pyo Hong, Jung-Hee Yoon, Dong Jin Chung, Joon Ho Kwon, Sanghyeok Lim, Jae Hyun Kim, Seung Kak Shin, Tae Hyung Kim, Dong Ho Lee, Jong Young Choi; Received August 2, 2024 Accepted August 4, 2024 Published online August 30, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.04 [Epub ahead of print]

237 Views
25 Downloads

Abstract PDF Supplementary Material: Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the firstline treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and posttreatment management of patients.

Editorial

The position of loco-regional therapy in the management of hepatocellular carcinoma with extrahepatic metastases: Beom Kyung Kim; Received August 23, 2024 Accepted August 26, 2024 Published online August 29, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.26 [Epub ahead of print]

147 Views
11 Downloads

PDF

Original Article

Evolving trends in treatment patterns for hepatocellular carcinoma in Korea from 2008 to 2022: a nationwide population-based study: Ji Won Han, Won Sohn, Gwang Hyeon Choi, Jeong Won Jang, Gi Hyeon Seo, Bo Hyun Kim, Jong Young Choi; Received July 24, 2024 Accepted August 13, 2024 Published online August 26, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.13 [Accepted]

185 Views
38 Downloads

Abstract PDF: Background/Aims
The treatment landscape for hepatocellular carcinoma (HCC) has significantly evolved over the past decade. We aimed to analyze trends in treatment patterns for HCC using a nationwide claims database from the Korean Health Insurance Review and Assessment Service.
Methods
This retrospective population-based cohort study analyzed 171,002 newly diagnosed HCC patients between 2008 and 2022. Etiologies and treatment modalities were categorized based on the ICD-10 codes and insurance data.
Results
The annual incidence decreased from 11,814 in 2008 to 10,443 in 2022. However, patients aged ≥ 70 increased noticeably, with those aged ≥ 80 rising from 3.8% in 2008 to 13.1% in 2022. From 2008 to 2022, the predominant cause of hepatitis B virus decreased from 68.9% to 59.7%, whereas nonalcoholic fatty liver disease increased from 8.9% to 15.8%. The initial treatment trends shifted: surgical resection and systemic therapy increased from 12.2% to 21.3% and from 0.2% to 9.6%, whereas transarterial therapy decreased from 49.9% to 36.6%. Best supportive care decreased from 31.7% to 21.3%. In the subgroup analysis, laparoscopic resection rate increased from 10.6% to 60.6% among the surgical resections. Sorafenib initially accounted for 100%, lenvatinib peaked at 36.5% in 2021, and atezolizumab–bevacizumab became the most widely used (63.1%) by 2022 among the systemic therapies.
Conclusions
This study demonstrates the temporal changes in the treatment patterns of Korean HCC patients. Surgical resection, particularly laparoscopic liver resection, and systemic therapy has increased significantly. These changes may have been influenced by reimbursement policies and advances in clinical research.

Editorials

Exploring the role of liver resection as a first-line treatment option for multinodular BCLC-A hepatocellular carcinoma: Joo Hyun Oh, Dong Hyun Sinn; Received August 7, 2024 Accepted August 8, 2024 Published online August 16, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.08 [Epub ahead of print]

172 Views
13 Downloads

PDF

Inter-reader agreement for LR-M imaging features: a premise for better imaging-based diagnosis in liver imaging: Jaeseung Shin; Received August 5, 2024 Accepted August 6, 2024 Published online August 13, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.06 [Epub ahead of print]

194 Views
9 Downloads

PDF

Review Articles

New systemic treatment options for advanced cholangiocarcinoma: Valentina Zanuso, Giulia Tesini, Elena Valenzi, Lorenza Rimassa; Received June 19, 2024 Accepted August 7, 2024 Published online August 8, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.07 [Epub ahead of print]

483 Views
59 Downloads

Abstract 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.

Disease modifiers and novel markers in hepatitis B virus-related hepatocellular carcinoma: Lung-Yi Mak; Received June 23, 2024 Accepted August 3, 2024 Published online August 5, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.03 [Epub ahead of print]

690 Views
51 Downloads

Abstract PDF: Chronic hepatitis B (CHB) infection is responsible for 40% of the global burden of hepatocellular carcinoma (HCC) with a high case fatality rate. The risk of HCC differs among CHB subjects owing to differences in host and viral factors. Modifiable risk factors include viral load, use of antiviral therapy, co-infection with other hepatotropic viruses, concomitant metabolic dysfunctionassociated steatotic liver disease or diabetes mellitus, environmental exposure, and medication use. Detecting HCC at early stage improves survival, and current practice recommends HCC surveillance among individuals with cirrhosis, family history of HCC, or above an age cut-off. Ultrasonography with or without serum alpha feto-protein (AFP) every 6 months is widely accepted strategy for HCC surveillance. Novel tumor-specific markers, when combined with AFP, improve diagnostic accuracy than AFP alone to detect HCC at an early stage. To predict the risk of HCC, a number of clinical risk scores have been developed but none of them are clinically implemented nor endorsed by clinical practice guidelines. Biomarkers that reflect viral transcriptional activity and degree of liver fibrosis can potentially stratify the risk of HCC, especially among subjects who are already on antiviral therapy. Ongoing exploration of these novel biomarkers is required to confirm their performance characteristics, replicability and practicability.

Original Articles

Recent update of proton beam therapy for hepatocellular carcinoma: A systematic review and meta-analysis: Sun Hyun Bae, Won Il Jang, Hanna Rahbek Mortensen, Britta Weber, Mi Sook Kim, Morten Høyer; Received May 16, 2024 Accepted June 26, 2024 Published online July 4, 2024; DOI: https://doi.org/10.17998/jlc.2024.06.26 [Accepted]

801 Views
45 Downloads

Abstract PDF: Backgrounds/Aims
Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and meta-analysis to investigate the updated evidence of PBT for HCC.
Methods
The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024.
Results
A total of 1858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range: 41–100%), and the median tumor size was 3.6 cm (range: 1.2–9 cm). The median total dose ranged from 55 GyE to 76 GyE (median, 69 GyE). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85–91%) and 86% (95% CI, 82–90%), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54–66%) and 46% (95% CI, 38–54%), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiation-induced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively.
Conclusions
The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.

Assessment of real-time US-CT/MR-guided percutaneous gold fiducial marker implementation in malignant hepatic tumors for stereotactic body radiation therapy: Sungjun Hwang, Seok-Joo Chun, Eui Kyu Chie, Jeong Min Lee; Received March 20, 2024 Accepted June 2, 2024 Published online June 10, 2024; DOI: https://doi.org/10.17998/jlc.2024.06.03 [Epub ahead of print]

737 Views
33 Downloads

Abstract PDF: Backgrounds/Aims
This study explored the initial institutional experience of using gold fiducial markers for stereotactic body radiotherapy (SBRT) in treating malignant hepatic tumors using real-time ultrasound-computed tomography (CT)/magnetic resonance (MR) imaging fusion-guided percutaneous placement.
Methods
From May 2021 to August 2023, 19 patients with 25 liver tumors that were invisible on pre-contrast CT received fiducial markers following these guidelines. Postprocedural scans were used to confirm their placement. We assessed technical and clinical success rates and monitored complications. The implantation of fiducial markers facilitating adequate treatment prior to SBRT, which was achieved in 96% of the cases (24 of 25 tumors), was considered technical success. Clinical success was the successful completion of SBRT without evidence of marker displacement and was achieved in 88% of cases (22 of 25 tumors). Complications included one major subcapsular hematoma and marker migration into the right atrium in two cases, which prevented SBRT.
Results
Among the treated tumors, 20 of 24 (83.3%) showed a complete response, three of 24 (12.5%) remained stable, and one of 24 (4.2%) progressed during an average 11.7-month follow-up (range, 2-32 months).
Conclusions
This study confirms that percutaneous gold fiducial marker placement using real-time CT/MR guidance is effective and safe for SBRT in hepatic tumors, but warns of marker migration risks, especially near the hepatic veins and in subcapsular locations. Using fewer markers than traditionally recommended-typically two per patient, the outcomes were still satisfactory, particularly given the increased risk of migration when markers were placed near major hepatic veins.

Heavy smoking increases early mortality risk in patients with hepatocellular carcinoma after curative treatment: Jaejun Lee, Jong Young Choi, Soon Kyu Lee; Received April 24, 2024 Accepted June 2, 2024 Published online June 7, 2024; DOI: https://doi.org/10.17998/jlc.2024.06.02 [Epub ahead of print]

799 Views
46 Downloads
1 Citation

Abstract PDF Supplementary Material

Backgrounds/Aims
Although cigarette smoking has been associated with an increased risk of hepatocellular carcinoma (HCC), its association with HCC mortality remains underexplored. We aimed to evaluate the effect of smoking on early mortality in HCC patients following curative treatment.
Methods
Data from the Korean Primary Liver Cancer Registry were examined for HCC patients who underwent liver resection or radiofrequency ablation between 2015 and 2018. Smoking cumulative dose was assessed in pack-years. The primary outcome was the 3-year overall survival (OS).
Results
Among 1,924 patients, 161 were classified as heavy smokers (≥40 pack-years). Heavy smokers exhibited a lower 3-year survival rate (77.1%) than nonsmokers (83.3%), with a significant difference observed in the 3-year OS (P=0.016). The assessment of smoking pack-years in relation to 3-year OS revealed a dose-dependent pattern, with the hazard ratio exceeding 1.0 at 20 pack-years and continuing to rise until 40 pack-years, reaching peak at 1.21 (95% confidence interval, 1.01-1.45). Multivariate Cox-regression analysis revealed heavy smoking, age ≥60 years, underlying cirrhosis, tumor size >3 cm, vascular invasion, and Child-Pugh class B/C as risk factors for 3-year OS. Subgroup analyses of patients with a tumor size <3 cm, absence of vascular invasion, and meeting the Milan criteria also showed inferior outcomes for heavy smokers in all three subgroups.
Conclusions
Heavy smoking, defined as a history of >40 pack-years, was linked to poorer 3-year survival outcomes in HCC patients undergoing curative treatments, underscoring the importance of smoking cessation in this population.

Citations

Citations to this article as recorded by

Impacts of smoking on alcoholic liver disease: a nationwide cohort study
Jeong-Ju Yoo, Dong Hyeon Lee, Sang Gyune Kim, Jae Young Jang, Young Seok Kim, Log Young Kim
Frontiers in Public Health.2024;[Epub] CrossRef

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; Received March 5, 2024 Accepted May 26, 2024 Published online June 3, 2024; DOI: https://doi.org/10.17998/jlc.2024.05.26 [Epub ahead of print]

1,036 Views
50 Downloads

Abstract PDF Supplementary Material: Backgrounds/Aims
Systemic therapy is the current standard treatment for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, some patients with HCC and EHM undergo transarterial chemoembolization (TACE) to manage intrahepatic tumors. Herein, we aimed to explore the appropriateness of TACE in patients with HCC and EHM in an era of advanced systemic therapy.
Methods
This study analyzed 248 consecutive patients with HCC and EHM (median age, 58.5 years; male, 83.5%; Child-Pugh A, 88.7%) who received TACE or systemic therapy (83 sorafenib, 49 lenvatinib, 28 immunotherapy-based) between January 2018 and January 2021.
Results
Among the patients, 196 deaths were recorded during a median follow-up of 8.9 months. Patients who received systemic therapy had a higher albumin-bilirubin grade, elevated tumor markers, an increased number of intrahepatic tumors, larger-sized tumors, and more frequent portal vein invasion than those who underwent TACE. TACE was associated with longer median overall survival (OS) than sorafenib (15.1 vs. 4.7 months; 95% confidence interval [CI], 11.1-22.2 vs. 3.7-7.3; hazard ratio [HR], 1.97; P<0.001). After adjustment for potential confounders, TACE was associated with statistically similar survival outcomes to those of lenvatinib (median OS, 8.0 months; 95% CI, 6.5-11.0; HR, 1.21; P=0.411) and immunotherapies (median OS, 14.3 months; 95% CI, 9.5-27.0; HR, 1.01; P=0.973), demonstrating survival benefits equivalent to these treatments.
Conclusions
In patients with HCC and EHM, TACE can provide a survival benefit comparable to that of newer systemic therapies. Accordingly, TACE remains a valuable option in this era of new systemic therapies.

Cure can be achieved by conversion to microwave ablation following atezolizumab-bevacizumab therapy in unresectable hepatocellular carcinoma: Rene John D. Febro, Engelbert Simon S. Perillo, Akemi A. Kimura, Stephen N. Wong; Received February 19, 2024 Accepted May 23, 2024 Published online June 3, 2024; DOI: https://doi.org/10.17998/jlc.2024.05.23 [Epub ahead of print]

2,748 Views
89 Downloads

Abstract PDF: Backgrounds/Aims
Atezolizumab/bevacizumab is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC) and may facilitate curative conversion through resection and locoregional therapies. However, there have been very few reports on curative conversion using microwave ablation (MWA). This study aimed to determine the curative conversion rate with MWA using atezolizumab-bevacizumab as the first-line treatment in patients with uHCC, and to compare the characteristics and survival of patients with and without curative conversion.
Methods
Consecutive patients with uHCC who were started on atezolizumab-bevacizumab from May 2021 to December 2023 in a single tertiary center were included. Objective response rate (ORR) and disease control rate (DCR) were based on the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria.
Results
Twenty consecutive patients with uHCC (60% advanced-stage) were included, 90% exceeding the up-to-7 criteria. The ORR and DCR were 35% and 60%, 35% and 55% using RECIST and mRECIST, respectively. Five patients (25%) underwent successful curative conversion with MWA (four advanced and one intermediate stage) despite a median HCC size of 6.1 cm (range, 2.4-7.3). Two of these patients were tumor and drug-free 132-133 weeks from the 1st atezolizumab-bevacizumab dose. Patients who underwent curative conversion had significantly longer survival than those who did not (P=0.024). Other factors associated with survival were male sex, Child-Pugh class A, and an objective response.
Conclusions
Despite the relatively large tumor size, successful curative conversion with MWA was achieved with first-line atezolizumab-bevacizumab in uHCC. However, data from prospective multicenter trials are required to determine whether this strategy is universally applicable.

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; Received April 3, 2024 Accepted May 12, 2024 Published online May 27, 2024; DOI: https://doi.org/10.17998/jlc.2024.05.12 [Epub ahead of print]

1,395 Views
172 Downloads
1 Citation

Abstract PDF Supplementary 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

First
Prev
Page of 2
Next
Last

Ahead-of-print articles