Cancer Research and Treatment

Original Articles

Safety and Efficacy of Combining Metastasis-Directed Stereotactic Ablative Radiation Therapy with Tyrosine Kinase Inhibitors Versus Immune Checkpoint Inhibitors in Metastatic Hepatocellular Carcinoma: Eunyeong Yang, Jeong Il Yu, Hee Chul Park, Myung Ji Goh, Byeong Geun Song, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Moon Seok Choi, Jung Yong Hong, Minsuk Kwon, Nalee Kim; Received September 5, 2025 Accepted February 1, 2026 Published online February 3, 2026; DOI: https://doi.org/10.4143/crt.2025.966 [Accepted]

Abstract PDF: Purpose
Immune checkpoint inhibitors (ICIs) have become a standard therapy for metastatic hepatocellular carcinoma (HCC), often as an alternative to tyrosine kinase inhibitors (TKIs). However, safety data combining ICIs with stereotactic ablative radiotherapy (SABR) remain limited. We compared the safety and efficacy of SABR combined with ICIs versus TKIs in patients with extrahepatic metastatic HCC.
Materials and methods
This single-center retrospective study included patients with HCC who received SABR for extrahepatic metastases combined with either TKIs or ICIs within 30 days of SABR between January 2010 and June 2024. Adverse events (AEs; CTCAE v5.0) and oncologic outcomes were evaluated using logistic regression and Cox models.
Results
Among 103 patients with 128 SABR-treated lesions, 72 patients (90 lesions) received SABR+TKI and 31 patients (38 lesions) received SABR+ICI. Acute AEs occurred only in the SABR+TKI group (8.9%), predominantly grade 1. Grade 3 late AEs were rare, occurring in one case in each group, while late AEs of lower grades were more frequent with SABR+ICI (any-grade: 57.9% vs. 25.6%, p<0.001; grade ≥2: 23.7% vs. 8.9%, p=0.024). Multivariable analysis showed borderline increased risk of grade ≥2 late AEs with SABR+ICI (p=0.052). One-year local control, progression-free survival, and overall survival were 76.6%, 35.3%, and 72.3% respectively, with no significant differences between groups.
Conclusion
Metastasis-directed SABR combined with either TKIs or ICIs was generally well tolerated in patients with extrahepatic metastatic HCC, with rare grade 3 late AEs; grade ≥2 late AEs were more frequent with SABR plus ICIs, warranting prospective evaluation.

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Effectiveness of Radiotherapy for Hepatocellular Carcinoma with Lymph Node Metastasis: A Meta-Analysis: Sooyoung Hwang, Seoon Hur, Won Sup Yoon, Sunmin Park, Chai Hong Rim; Received May 2, 2025 Accepted August 11, 2025 Published online August 12, 2025; DOI: https://doi.org/10.4143/crt.2025.475 [Accepted]

Abstract PDF: Purpose
Lymph node metastasis (LNM) of hepatocellular carcinoma (HCC) carries a poor prognosis; however, no standard treatment has been established. Radiotherapy (RT) has demonstrated favorable tumor response, with the advantage of being less affected by anatomical hindrances.
Materials and Methods
Databases were searched up to April 2024. The inclusion criteria were: (1) ≥5 patients with HCC LNM, (2) studies that performed external RT, and (3) reporting survival or response rate (RR). The main effect measures are pooled 1- and 2-year overall survival (OS) rates, response rate (RR) and grade ≥3 complications.
Results
Twelve studies involving 825 patients were included. The pooled 1-year OS rate and 2-year OS rate were 49.3% (95% confidence interval [CI]: 39.2%-59.4%) and 24.5% (95% CI: 17.0%-34.0%), respectively. The median OS ranged from 5.8 to 29.7 months, with a median value of 9.7 months. In one study, 14.7% of patients were prescribed an immunoagent. In other studies, some patients received sorafenib, but no specific systemic therapy was performed for the majority. The pooled RR was 75.1% (95% CI: 66.9%-81.8%). The pooled RR of high dose and low dose groups was 83.8% (95% CI: 76.3-89.3) vs. 55.6% (95% CI: 44.4-66.3), respectively (p<0.001). The pooled rate of grade ≥3 gastrointestinal toxicity was 3.7% (95% CI: 2.1%-6.6%).
Conclusion
RT is an effective and feasible palliative option for HCC LNM. Further researches of combined treatment with novel systemic agents are necessary.

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Gastrointestinal cancer

Combined Transarterial Chemoembolization and External Beam Radiotherapy for Identifying Surgical Candidates for Hepatocellular Carcinoma with Macroscopic Vascular Invasion: A Propensity Score–Weighted Analysis: Sumin Lee, Jinhong Jung, Jonggi Choi, So Yeon Kim, Jin Hyoung Kim, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Gi-Won Song, Jin-hong Park, Sang Min Yoon; Cancer Res Treat. 2026;58(1):275-283. Published online May 22, 2025; DOI: https://doi.org/10.4143/crt.2025.076

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI).
Materials and Methods
We retrospectively reviewed the patients treated with combined TACE and RT for HCC with MVI between 2010 and 2015. Some of the patients with objective responses underwent hepatic resection or liver transplantation; to investigate the impact of surgery, patients with objective responses who did not undergo surgery were selected as the control group. Survival outcomes were compared using a propensity score–based stabilized inverse probability of treatment weighting method.
Results
Out of the 170 patients with objective responses after combined TACE and RT, 41 patients underwent surgery, including eight liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumors and unilateral vascular involvement. After adjustment, the 3-year overall survival (OS) rates were 61.0% and 28.6% in the surgery and non-surgery groups, respectively. The most important prognostic factor for OS was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17 to 0.46; p < 0.001). Complete response after TACE and RT (vs. partial response) was also a significant prognostic factor for OS (adjusted HR, 0.41; 95% CI, 0.27 to 0.61; p < 0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery due to bleeding or graft failure.
Conclusion
Hepatic resection was significantly associated with improved OS in patients who showed objective responses after receiving combined TACE and RT for HCC with MVI.

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Multimodal deep learning model for predicting prognosis following radiotherapy-based combination therapy in unresectable hepatocellular carcinoma
Haoming Xia, Qizhen Huang, Ziyue Huang, Ziqi Zhou, Yongyi Zeng, Jingguang Ma, Xiangyu Fan, Yechong Huang, Yuexi Dong, Haitao Zhao, Gong Li, Jitao Wang, Shizhong Yang, Jiahong Dong
Cancer Letters.2026; 636: 218122. CrossRef

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Malignant Hepatocellular Neoplasm, Not Otherwise Specified, Displays Poorer Chemoresponsiveness and Postoperative Prognosis Than Hepatoblastoma: In Hye Song, Sujin Gang, Hee Mang Yoon, Pyeong Hwa Kim, Bokyung Ahn, Jihun Kim, Deok Hoon Kim, Jung-Man Namgoong, Kyung-Nam Koh; Received February 1, 2025 Accepted May 9, 2025 Published online May 12, 2025; DOI: https://doi.org/10.4143/crt.2025.117 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Malignant hepatocellular neoplasm, not otherwise specified (HCN-NOS) is a provisional diagnostic entity, characterised by intermediate or a combination of hepatoblastoma and pediatric hepatocellular carcinoma (p-HCC) features. We compared the characteristics of HCN-NOS with hepatoblastoma and p-HCC.
Materials and Methods
The records of 148 pediatric patients diagnosed with hepatocellular malignancy after resection were retrieved from the institutional database. Clinical parameters and histopathology slides were reviewed to re-establish each patient’s diagnosis. Molecular analyses were conducted in 37 patients.
Results
Patients were profiled as 21 (14.2%) with HCN-NOS, 109 (73.6%) with hepatoblastoma, and 18 (12.2%) with p-HCC. The median age was 8.6 years in HCN-NOS, 1.2 years in hepatoblastoma, and 7.9 years in p-HCC. Background liver disease was frequently observed in p-HCC (11/18, 61%) but infrequent in HCN-NOS (4/21, 19%) and hepatoblastoma (4/109, 3.7%). HCN-NOS presented with a more advanced PRETEXT stage (p=0.012), metastasis (p < 0.001), and lymphovascular invasion (p < 0.001) than hepatoblastoma and p-HCC. Patients with HCN-NOS received longer cycles of preoperative chemotherapy; however, they reported a lower decrease in serum alpha-fetoprotein and tumor size than hepatoblastoma (p=0.043, p=0.004, and p=0.044, respectively). HCN-NOS was an independent poor prognostic factor for event-free survival (hazard ratio, 4.968; 95% confidence interval, 2.004 to 12.32; p < 0.001).
Conclusion
The possibility of HCN-NOS should be considered in pediatric patients with liver cancer, especially those ≥ 5 years old with no background liver disease. Because HCN-NOS exhibits poor chemoresponsiveness and unfavourable postoperative prognosis, liver transplantation should be strongly considered.

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Gastrointestinal cancer

Evaluation of Nomenclature of Fatty Liver Disease in Association with Hepatocellular Carcinoma: A 14.5-Year Cohort Study in Korea: Tung Hoang, Jeonghee Lee, Bo Hyun Kim, Yuri Cho, Jeongseon Kim; Cancer Res Treat. 2025;57(4):1144-1155. Published online February 11, 2025; DOI: https://doi.org/10.4143/crt.2024.876

Abstract PDF Supplementary Material PubReader ePub

Purpose
New nomenclature has incorporated metabolic traits and/or alcohol intake history to replace nonalcoholic fatty liver disease (NAFLD). Concerning the performance of different terminologies in Asian population, this study aimed to investigate the risk of developing hepatocellular carcinoma (HCC) in persons meeting the criteria for subclasses of fatty liver disease.
Materials and Methods
Between 2002 and 2021, 28,749 participants from the cancer registry linkage, who had no prior history of HCC, were prospectively included. Fatty liver disease was defined using abdominal sonography and fatty liver index. Participants were classified as having NAFLD, metabolic dysfunction–associated fatty liver disease (MAFLD), metabolic dysfunction–associated steatotic liver disease (MASLD), steatotic liver disease with increased alcohol intake (MetALD), or alcohol-related liver disease (ALD) and their association with HCC risk was investigated using Cox regression models.
Results
During a median follow-up of 14.5 years, 143 HCC cases were newly diagnosed. The prevalences of NAFLD and MASLD were 19.7% and 18.7%, respectively, whereas MAFLD was observed in 32.3% of the study population. Given the low proportion of excessive alcohol consumption, we identified 3.3% MetALD and 3.5% ALD cases. Overall, MAFLD was suggestively associated with HCC risk (hazard ratio, 1.40; 95% confidence interval, 0.99 to 1.98). In contrast, the results for other nomenclature were not significant.
Conclusion
Our results suggest the importance of both fatty liver and the presence of metabolic dysfunction in relation to HCC risk and the need to reconsider alcohol intake thresholds in the diagnostic criteria for NAFLD and MASLD within the Korean population.

Citations

Citations to this article as recorded by

Dual etiology vs. MetALD: how MAFLD and MASLD address liver diseases coexistence
Shadi Zerehpooshnesfchi, Amedeo Lonardo, Jian-Gao Fan, Reda Elwakil, Tawesak Tanwandee, Munira Y. Altarrah, Necati Örmeci, Mohammed Eslam
Metabolism and Target Organ Damage.2025;[Epub] CrossRef
Comment on " posttreatment FIB-4 score change predicts hepatocellular carcinoma in chronic hepatitis C patients: Findings from the Taiwan hepatitis C registry program"
Junwei Guo, Dongsheng Huang
Journal of the Formosan Medical Association.2025;[Epub] CrossRef
MAFLD vs. MASLD: a year in review
Mingqian Jiang, Amna Subhan Butt, Ian Homer Cua, Ziyan Pan, Said A Al-Busafi, Nahum Méndez-Sánchez, Mohammed Eslam
Expert Review of Endocrinology & Metabolism.2025; 20(4): 267. CrossRef
Risk of hepatic and extrahepatic outcomes associated with metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction and alcohol-associated steatotic liver disease: a systematic review and meta-analysis
Ciro Celsa, Grazia Pennisi, Adele Tulone, Giacinta Ciancimino, Marco Vaccaro, Fabiana Pecorella, Gabriele Di Maria, Marco Enea, Federico Midiri, Alessandro Mantovani, Giovanni Targher, Aleksander Krag, Mary E Rinella, Calogero Cammà, Salvatore Petta
The Lancet Gastroenterology & Hepatology.2025; 10(11): 998. CrossRef

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Distinct Characteristics and Changes in Liver Function of Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab for More Than 1 Year: Youngun Kim, Jung Sun Kim, Beodeul Kang, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Yun Beom Sang, Sanghoon Jung, Chansik An, Chan Kim, Hong Jae Chon; Cancer Res Treat. 2024;56(4):1231-1239. Published online May 27, 2024; DOI: https://doi.org/10.4143/crt.2024.237

Abstract PDF Supplementary Material PubReader ePub

Purpose
Since 2020, atezolizumab plus bevacizumab (Ate/Bev) has been the standard first-line therapy for unresectable hepatocellular carcinoma (HCC), but long-term treatment studies are limited. This study evaluated the clinical characteristics and effects of Ate/Bev for over 1 year.
Materials and Methods
This study included patients with unresectable HCC treated with first-line Ate/Bev between May 2020 and April 2022. Those receiving Ate/Bev for 1 year or more were classified as the long-term treatment group.
Results
Of 246 patients, 69 (28.0%) were in the long-term treatment group, which comprised more proportions of intrahepatic tumor burden < 25%, Eastern Cooperative Oncology Group 0, and a lower proportion of portal vein tumor thrombosis than the short-term treatment group. The long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (31.9% vs. 10.7%, p < 0.001; median time to onset [mTTO], 2.8 months), dermatologic toxicity (29.0% vs. 14.7%, p=0.017; mTTO, 3.3 months), bevacizumab-related hypertension (44.9% vs. 22.0%, p=0.001; mTTO, 4.2 months), and proteinuria (69.6% vs. 38.4%, p < 0.001; mTTO, 6.8 months), compared to the short-term treatment group. Regarding liver function in the long-term treatment group, patients initially classified as Child-Pugh class A decreased from 87.0% to 75.4%, and albumin-bilirubin grade 1 decreased from 68.1% to 50.7% after 1 year of treatment.
Conclusion
The Ate/Bev long-term treatment group had a lower intrahepatic tumor burden, less portal vein tumor thrombosis, and better performance status and liver function at baseline. Atezolizumab-related immunological adverse events emerged relatively early in treatment compared to the bevacizumab-related. Additionally, some patients demonstrated liver function deterioration during long-term Ate/Bev treatment.

Citations

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Outcomes of Nivolumab Plus Ipilimumab After Atezolizumab Plus Bevacizumab in Advanced HCC: An International Multicentre Study
Jung Sun Kim, Jeffrey Wong, San‐Chi Chen, David Tai, Hannah Yang, Youngun Kim, Beodeul Kang, Ilhwan Kim, Hyeyeong Kim, Chansik An, Su Jin Jang, Masatoshi Kudo, Ho Yeong Lim, Chan Kim, Thomas Yau, Hong Jae Chon
Liver International.2026;[Epub] CrossRef
Integrative multi-omics profiling identifies infiltrative hepatocellular carcinoma as an immunotherapy-resistant subtype with distinct molecular features
Won Suk Lee, Seonjeong Woo, Sung Hwan Lee, Gae Hoon Jo, Ilhwan Kim, Hyeyeong Kim, Chansik An, Sanghoon Jung, Gwangil Kim, Haeyoun Kang, Beodeul Kang, Jung Sun Kim, Ho Yeong Lim, Incheon Kang, Hannah Yang, So Jung Kong, Dahyeon Son, Dong Jun Shin, Woo Youn
Clinical and Molecular Hepatology.2026; 32(1): 258. CrossRef
A case of long-term therapy of hepatocellular carcinoma with atezolizumab and bevacizumab combination
K. V. Menshikov, A. V. Sultanbaev, Sh. H. Musin, V. A. Valishin, I. A. Men′shikova, V. S. Chalov, N. I. Sultanbaeva, Sh. N. Galimov
Meditsinskiy sovet = Medical Council.2025; (10): 49. CrossRef
Current Insights into the Long-Term Management of HCC with Immunotherapy-Based Regimens
Sukbae Kim
Convergence Hepatology.2025; 1(1): 14. CrossRef
The Low Platelet Count at the Start of Atezolizumab Plus Bevacizumab Therapy for Unresectable Hepatocellular Carcinoma Predicts Deteriorated Liver Function at the Time of Disease Progression Thereafter: A Multicenter Analysis
Ryo Sato, Takanori Suzuki, Kentaro Matsuura, Daisuke Kato, Katsumi Hayashi, Kohei Okayama, Fumihiro Okumura, Satoshi Sobue, Atsunori Kusakabe, Izumi Hasegawa, Kiyoto Narita, Tsutomu Mizoshita, Yoshihide Kimura, Hiromu Kondo, Hisayo Kojima, Kazuki Hayashi,
Hepatology Research.2025;[Epub] CrossRef
Clinical Feasibility of Circulating Tumor DNA in Patients with Advanced Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab
Sohyun Hwang, Dong Jun Shin, Beodeul Kang, Haeyoun Kang, Sung Hwan Lee, Jung Sun Kim, Je-Gun Joung, Suyog Jain, Steven Olsen, Lars Becker, Richard S. Finn, Josep M. Llovet, Gwangil Kim, Chan Kim, Hong Jae Chon
Liver Cancer.2025; : 1. CrossRef
Current perspectives and future strategies for the systemic treatment of hepatocellular carcinoma: a narrative review
Hong Jae Chon
Journal of the Korean Medical Association.2025; 68(12): 809. CrossRef

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Clinical and Radiologic Predictors of Response to Atezolizumab-Bevacizumab in Advanced Hepatocellular Carcinoma: Se Jin Choi, Sung Won Chung, Jonggi Choi, Kang Mo Kim, Hyung-Don Kim, Changhoon Yoo, Baek-Yeol Ryoo, Seung Soo Lee, Won-Mook Choi, Sang Hyun Choi; Cancer Res Treat. 2024;56(4):1219-1230. Published online May 7, 2024; DOI: https://doi.org/10.4143/crt.2024.283

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to identify clinical and radiologic characteristics that could predict response to atezolizumab-bevacizumab combination therapy in patients with advanced hepatocellular carcinoma (HCC).
Materials and Methods
This single-center retrospective study included 108 advanced HCC patients with intrahepatic lesions who were treated with atezolizumab-bevacizumab. Two radiologists independently analyzed imaging characteristics of the index tumor on pretreatment computed tomography. Predictive factors associated with progressive disease (PD) at the best response based on Response Evaluation Criteria in Solid Tumors, ver. 1.1 were evaluated using logistic regression analysis. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared with the log-rank test.
Results
Of 108 patients with a median PFS of 15 weeks, 40 (37.0%) had PD during treatment. Factors associated with PD included the presence of extrahepatic metastases (adjusted odds ratio [aOR], 4.13; 95% confidence interval [CI], 1.19 to 14.35; p=0.03), the infiltrative appearance of the tumor (aOR, 3.07; 95% CI, 1.05 to 8.93; p=0.04), and the absence of arterial-phase hyperenhancement (APHE) (aOR, 6.34; 95% CI, 2.18 to 18.47; p < 0.001). Patients with two or more of these factors had a PD of 66.7% and a median PFS of 8 weeks, indicating a significantly worse outcome compared to the patients with one or no of these factors.
Conclusion
In patients with advanced HCC treated with atezolizumab-bevacizumab treatment, the absence of APHE, infiltrative appearance of the intrahepatic tumor, and presence of extrahepatic metastases were associated with poor response and survival. Evaluation of early response may be necessary in patients with these factors.

Citations

Citations to this article as recorded by

Integrative multi-omics profiling identifies infiltrative hepatocellular carcinoma as an immunotherapy-resistant subtype with distinct molecular features
Won Suk Lee, Seonjeong Woo, Sung Hwan Lee, Gae Hoon Jo, Ilhwan Kim, Hyeyeong Kim, Chansik An, Sanghoon Jung, Gwangil Kim, Haeyoun Kang, Beodeul Kang, Jung Sun Kim, Ho Yeong Lim, Incheon Kang, Hannah Yang, So Jung Kong, Dahyeon Son, Dong Jun Shin, Woo Youn
Clinical and Molecular Hepatology.2026; 32(1): 258. CrossRef
Transarterial chemoembolization combined with immune checkpoint inhibitors and anti-VEGF agents for intermediate HCC: a multicenter study
Wei-Yi Jiang, Jin-Kai Feng, Bin Zhou, Si-Si Ren, Yu-Chao Hou, Fang-Fang Zhang, Yan-Jun Xiang, Zong-Han Liu, Rong-Chen Chen, Yun-Feng Shan, Chao Liang, Hong-Kun Zhou, Lin Gong, Shu-Qun Cheng
European Journal of Surgical Oncology.2026; 52(3): 111407. CrossRef
Application of imaging modalities in predicting and evaluating response to anti-vascular endothelial growth factor agents and immune checkpoint inhibitors in patients with hepatocellular carcinoma
Li-Ping Zhou, Wei Yang
World Chinese Journal of Digestology.2025; 33(6): 441. CrossRef
Clinical Significance of Intratumoral Contrast Pooling on Contrast-Enhanced CT After Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma
Kiyoyuki Minamiguchi, Mariko Irizato, Ryota Nakano, Hideki Kunichika, Tetsuya Tachiiri, Ryosuke Taiji, Yuki Tsuji, Satoshi Yasuda, Hitoshi Yoshiji, Masayuki Sho, Toshihiro Tanaka
Current Oncology.2025; 32(12): 694. CrossRef
Liver Transplantation for Hepatocarcinoma: Results over Two Decades of a Transplantation Programme and Analysis of Factors Associated with Recurrence
María Martínez Burgos, Rocío González Grande, Susana López Ortega, Inmaculada Santaella Leiva, Jesús de la Cruz Lombardo, Julio Santoyo Santoyo, Miguel Jiménez Pérez
Biomedicines.2024; 12(6): 1302. CrossRef

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Efficacy of Lenvatinib Combined with Anti–PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study: Xiangye Ou, Junyi Wu, Jiayi Wu, Yangkai Fu, Zhenxin Zeng, Shuqun Li, Yinan Li, Deyi Liu, Han Li, Bin Li, Jianyin Zhou, Shaowu Zhuang, Shuqun Cheng, Zhibo Zhang, Kai Wang, Shuang Qu, Maolin Yan; Cancer Res Treat. 2024;56(4):1207-1218. Published online April 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1165

Abstract PDF Supplementary Material PubReader ePub

Purpose
The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT.
Materials and Methods
This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles.
Results
During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively.
Conclusion
Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

Citations

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Real-world outcomes of stereotactic body radiotherapy plus sintilimab and bevacizumab for hepatocellular carcinoma with portal vein tumor thrombus
Bin Zhou, Zihui Ma, Lei Wang, Yue Lu, Xi Cheng, Yabo Jiang, Xubiao Wei, Chongde Lu, Shuqun Cheng, Xingsheng Lu
The Oncologist.2026;[Epub] CrossRef
A real-world study of the efficacy of second-line treatment of unresectable hepatocellular carcinoma with esophagogastric varices after progression on first-line lenvatinib combined with PD-1 inhibitor
Saifeng Li, Qin Wen, Wenwu Huang, Zeyu Qiu, Long Feng, Fengming Yi
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Personalized prognosis in unresectable hepatocellular carcinoma: Development and validation of a model for transcatheter arterial chemoembolization plus lenvatinib
Jia-Hui Yu, Jun Yu, Jin-Xin Yu, Lin-Feng Yang, Duan Yan, Yi Liu, Ju-Rui Xian, Peng-Sheng Yi
World Journal of Gastrointestinal Oncology.2025;[Epub] CrossRef
Safety and efficacy of salvage surgery for unresectable hepatocellular carcinoma after conversion with triple therapy: a systematic review and meta-analysis of data from Chinese patients
Qingqing Pang, Xingling Mo, Zhihong Tang, Meng Wei, Danxi Liu, Zenghua Zhou, Baishan Huang, Tao Bai, Xiaobo Wang, Feixiang Wu
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Locoregional therapy combined with targeted therapy and immunotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a systematic review and meta-analysis
Mengjie Jiang, Chao Chen, Yujie Hu, Gang Lin, Huafeng Li
Scientific Reports.2025;[Epub] CrossRef
The effectiveness and safety of immune checkpoint inhibitors in conversion or neoadjuvant therapy for hepatocellular carcinoma: a meta-analysis and systematic review
Lingbo Hu, Yongfu Xu, Yingli Qiao, Aidong Wang, Caidi He, Rongrong Wang
BMC Cancer.2025;[Epub] CrossRef

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Intraindividual Comparison of MRIs with Extracellular and Hepatobiliary Contrast Agents for the Noninvasive Diagnosis of Hepatocellular Carcinoma Using the Korean Liver Cancer Association–National Cancer Center 2022 Criteria: Ja Kyung Yoon, Dai Hoon Han, Sunyoung Lee, Jin-Young Choi, Gi Hong Choi, Do Young Kim, Myeong-Jin Kim; Cancer Res Treat. 2023;55(3):939-947. Published online February 10, 2023; DOI: https://doi.org/10.4143/crt.2022.1645

Abstract PDF Supplementary Material PubReader ePub

Purpose
The aim of the present study was to evaluate the per-lesion sensitivity and specificity of the Korean Liver Cancer Association–National Cancer Center (KLCA-NCC) 2022 criteria for the noninvasive diagnosis of hepatocellular carcinoma (HCC), with intraindividual comparison of the diagnostic performance of magnetic resonance imaging with extracellular agents (ECA-MRI) and hepatobiliary agents (HBA-MRI).
Materials and Methods
Patients at high risk for HCC who were referred to a tertiary academic institution for hepatic lesions with size ≥ 10 mm between July 2019 and June 2022 were enrolled. A total of 91 patients (mean age, 58.1 years; 76 men and 15 women) with 118 lesions who underwent both ECA-MRI and HBA-MRI were eligible for final analysis. The per-lesion sensitivities and specificities of the KLCA-NCC 2022 criteria using ECA-MRI and HBA-MRI were compared using McNemar’s test.
Results
The 118 lesions were 93 HCCs, 4 non-HCC malignancies, and 21 benign lesions. On HBA-MRI, the “definite” HCC category showed significantly higher sensitivity than ECA-MRI (78.5% vs. 58.1%, p < 0.001), with identical specificity (92.0% vs. 92.0%, p > 0.999). For “probable” or “definite” HCC categories, there were no differences in the sensitivity (84.9% vs. 84.9%, p > 0.999) and specificity (84.0% vs. 84.0%, p > 0.999) between ECA-MRI and HBA-MRI.
Conclusion
The “definite” HCC category of the KLCA-NCC 2022 criteria showed higher sensitivity in diagnosing HCC on HBA-MRI compared with ECA-MRI, without compromising specificity. There were no significant differences in the sensitivity and specificity of “probable” or “definite” HCC categories according to ECA-MRI and HBA-MRI.

Citations

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Diagnosing HCC with conventional and late portal venous phase MRI: intraindividual comparison of MRI with extracellular contrast agent
Boryeong Jeong, Dai Hoon Han, Sunyoung Lee, Ja Kyung Yoon, Jin-Young Choi, Gi Hong Choi, Do Young Kim, Myeong-Jin Kim
European Radiology.2025;[Epub] CrossRef
Intraindividual comparison of prognostic imaging features of HCCs between MRIs with extracellular and hepatobiliary contrast agents
Ja Kyung Yoon, Dai Hoon Han, Sunyoung Lee, Jin‐Young Choi, Gi Hong Choi, Do Young Kim, Myeong‐Jin Kim
Liver International.2024; 44(10): 2847. CrossRef

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Hepatitis B Virus Core Protein Mediates the Upregulation of C5α Receptor 1 via NF-κB Pathway to Facilitate the Growth and Migration of Hepatoma Cells: Fanyun Kong, Yukai Tao, Dongchen Yuan, Ning Zhang, Qi Li, Tong Yu, Xiaoying Yang, Delong Kong, Xiaohui Ding, Xiangye Liu, Hongjuan You, Kuiyang Zheng, Renxian Tang; Cancer Res Treat. 2021;53(2):506-527. Published online November 16, 2020; DOI: https://doi.org/10.4143/crt.2020.397

Abstract PDF PubReader ePub

Purpose
C5α receptor 1 (C5ΑR1) is associated with the development of various human cancers. However, whether it is involved in the development of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) is poorly understood. We explored the expression, biological role, and associated mechanisms of C5AR1 in HBV-related hepatoma cells.
Materials and Methods
The expression of C5ΑR1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor кB (NF-κB) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5ΑR1 in the activation of intracellular signal pathways, the upregulation of inflammatory cytokines, and the growth and migration of hepatoma cells mediated by HBc, were investigated. The effect of C5α in the development of HCC mediated by C5AR1 was also measured.
Results
C5ΑR1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5ΑR1 at the mRNA and protein levels. Besides, HBc could promote C5ΑR1 expression via the NF-κB pathway. Based on the C5ΑR1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Furthermore, C5ΑR1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5α could promote the malignant development of HBc-positive HCC via C5AR1.
Conclusion
We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5ΑR1 has a significant role in the functional abnormality of hepatoma cells mediated by HBc, and might be utilized as a potential therapeutic target for HBV-related HCC.

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Case Report

Hyperammonemic Encephalopathy Mimicking Ornithine Transcarbamylase Deficiency in Fibrolamellar Hepatocellular Carcinoma: Successful Treatment with Continuous Venovenous Hemofiltration and Ammonia Scavengers: Jeong-Seon Lee, Hye Young Jin, Jung Min Ko, Seoung Hoon Kim, Nayoung Han, Byung Kiu Park, Meerim Park, Hyeon Jin Park, Jun Ah Lee; Cancer Res Treat. 2021;53(1):283-288. Published online September 7, 2020; DOI: https://doi.org/10.4143/crt.2020.575

Abstract PDF PubReader ePub

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver cancer affecting adolescents and young adults without any pre existing liver disease. Hyperammonemic encephalopathy (HAE) is a serious paraneoplastic syndrome, and several cases of HAE have been reported in patients with FLHCC. This condition is rare; hence, there are currently no management guidelines for cancer-related HAE. Herein, we report a case of an 18-year-old man with advanced FLHCC who developed HAE during the first course of chemotherapy consisting of cisplatin, doxorubicin, 5-fluorouracil, and interferon-α. He was successfully treated with continuous venovenous hemofiltration, sodium benzoate, sodium phenylbutyrate, and amino acid supplementation for HAE. After the second course of chemotherapy, he underwent surgery, and thereafter, his ammonia levels were normal without any ammonia scavenger therapy. Treatments for HAE described here will be helpful for this rare, but serious metabolic complication of FLHCC and could partially applied to HAE related to any malignancies.

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Original Articles

Gastrointestinal cancer

Evaluation of the American Joint Committee on Cancer (AJCC) 8th Edition Staging System for Hepatocellular Carcinoma in 1,008 Patients with Curative Resection: Sujin Park, Sangjoon Choi, Yoon Ah Cho, Dong Hyun Sinn, Jong Man Kim, Cheol-Keun Park, Sang Yun Ha; Cancer Res Treat. 2020;52(4):1145-1152. Published online April 28, 2020; DOI: https://doi.org/10.4143/crt.2020.208

Abstract PDF Supplementary Material PubReader ePub

Purpose
Recently, the 8th edition staging system of the American Joint Committee on Cancer (AJCC) for hepatocellular carcinoma (HCC) was released, including a change in T category. We aimed to validate the new AJCC system.
Materials and Methods
The predictive value of the new AJCC was validated in comparison to the previous edition, in a total 1,008 patients who underwent curative resection for HCC as initial treatment.
Results
The 2-year area under the curve values for recurrence-free survival (RFS) and overall survival (OS) were comparable in the 7th and 8th editions. Stage migration was observed in 63 patients (6.3%); from T2 to T1a for 44 patients and from T3 to T4 for 19 patients. The RFS and OS were not different between T1a and T1b in the 8th edition. For solitary tumors ≤ 2 cm, those with microvascular invasion had lower RFS and OS values than those without although they were all classified as T1a in the 8th edition. Tumors involving a major branch of the portal or hepatic vein (T4 by the 8th edition and T3b by the 7th edition) had shorter RFS and OS than multifocal tumors, at least one of which was > 5 cm (T3 by the 8th edition and T3a by the 7th edition).
Conclusion
The AJCC 8th edition staging system for HCC showed comparable predictive performance to the 7th edition. It is desirable in a future revision to consider sub-stratification of solitary tumors ≤ 2 cm (T1a) depending on the presence of vascular invasion, which is not included in the 8th edition.

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Prognostic Value of TP53 Mutation for Transcatheter Arterial Chemoembolization Failure/Refractoriness in HBV-Related Advanced Hepatocellular Carcinoma: Miao Xue, Yanqin Wu, Wenzhe Fan, Jian Guo, Jialiang Wei, Hongyu Wang, Jizhou Tan, Yu Wang, Wang Yao, Yue Zhao, Jiaping Li; Cancer Res Treat. 2020;52(3):925-937. Published online March 30, 2020; DOI: https://doi.org/10.4143/crt.2019.533

Abstract PDF PubReader ePub

Purpose
This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE).
Materials and Methods
From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA).
Results
Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness.
Conclusion
Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.

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Soluble Axl Is a Novel Diagnostic Biomarker of Hepatocellular Carcinoma in Chinese Patients with Chronic Hepatitis B Virus Infection: Xiaoting Song, Ailu Wu, Zhixiao Ding, Shixiong Liang, Chunyan Zhang; Cancer Res Treat. 2020;52(3):789-797. Published online March 5, 2020; DOI: https://doi.org/10.4143/crt.2019.749

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to evaluate the diagnostic value of soluble Axl (sAxl) in hepatocellular carcinoma (HCC) in comparison with serum α-fetoprotein (AFP).
Materials and Methods
Eighty HCC patients, 80 liver cirrhosis patients (LC), 80 patients with hepatitis B virus (HBV) infection, and 80 healthy controls (HC) were enrolled. sAxl levels were measured by an enzyme-linked immunosorbent assay, serum AFP levelswere measured by an electrochemiluminescence immunoassay. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic performances.
Results
The results show that levels of sAxl were high expression in patients with HCC (p < 0.05), varied with disease state as follows: HCC > LC > HC > HBV. Logistic regression and ROC curve analysis identified the optimal cut-off for sAxl in differentiating all HCC and non-HCC patients was 1,202 pg/mL (area under the receiver operating characteristic [AUC], 0.888; 95% confidence interval [CI], 0.852 to 0.924) with sensitivity 95.0%, specificity 73.3%. Furthermore, differential diagnosis of early HCC with non-HCC patients for sAxl showed the optimal cut-off was 1,202 pg/mL (AUC, 0.881; 95% CI, 0.831 to 0.931; sensitivity, 94.1%; specificity, 73.3%). Among AFP-negative HCC patients with non-HCC patients, the cut-off was 1,301 pg/mL (AUC, 0.898; 95% CI, 0.854 to 0.942) with a sensitivity of 84.6%, a specificity of 76.3%. The optimal cut-off for sAxl in differentiating all HCC and chronic liver disease patients was 1,243 pg/mL (AUC, 0.840; 95% CI, 0.791 to 0.888) with sensitivity 93.8%, specificity 61.9%. The combination of AFP and sAxl increased diagnostic value for HCC.
Conclusion
sAxl outperforms AFP in detecting HCC, especially in early HCC and in AFP-negative HCC. Combination sAxl with AFP improved the specificity for early HCC diagnosis. In summary, sAxl is a candidate serum marker for diagnosing HCC.

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Activation of Tyrosine Metabolism in CD13⁺ Cancer Stem Cells Drives Relapse in Hepatocellular Carcinoma: Li Sun, Lin Zhang, Jun Chen, Chaoqun Li, Hongqin Sun, Jiangrong Wang, Hong Xiao; Cancer Res Treat. 2020;52(2):604-621. Published online December 27, 2019; DOI: https://doi.org/10.4143/crt.2019.444

Abstract PDF Supplementary Material PubReader ePub

Purpose
Cancer stem cells (CSCs) are naturally resistant to chemotherapy, explaining why tumor relapse frequently occurs after initial regression upon administration of chemotherapeutic agents in most cases. A CSC population characterized by CD13 expression has been identified in hepatocellular carcinoma (HCC). In the current study, we aimed to clarify the molecular mechanism by which it escapes conventional therapies. Materials and Methods Here, we used flow cytometry to examine the percentage of CD13⁺ CSCs in HepG2 and HuH7 cells after chemotherapy. Using in vitro isotope labeling technique, we compared metabolic pathways between CD13⁺ and CD13^– subpopulations. Using co-immunoprecipitation and western blotting, we determined the target expressions in protein levels under different conditions. We also performed immunohistochemistry to detect the target proteins under different conditions. Animal models were constructed to verify the potential role of tyrosine metabolism in post-chemotherapeutic relapse in vivo.
Results
We observed that quiescent CD13⁺ CSCs are enriched after chemotherapy in HCCs, and serve as a reservoir for recurrence. Mechanistically, CD13⁺ CSCs were dependent on aerobic metabolism of tyrosine rather than glucose as energy source. Tyrosine metabolism also generated nuclear acetyl-CoA to acetylate and stabilize Foxd3, thereby allowing CD13⁺ CSCs cells to sustain quiescence and resistance to chemotherapeutic agents.
Conclusion
These findings encourage further exploration of eliminating CD13⁺ cells by targeting specific metabolic pathways to prevent recurrence in HCCs.

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Cathepsin C Interacts with TNF-α/p38 MAPK Signaling Pathway to Promote Proliferation and Metastasis in Hepatocellular Carcinoma: Guo-Pei Zhang, Xiao Yue, Shao-Qiang Li; Cancer Res Treat. 2020;52(1):10-23. Published online April 26, 2019; DOI: https://doi.org/10.4143/crt.2019.145

Abstract PDF PubReader ePub

Purpose
Although cathepsin C (CTSC) has been reported to maintain malignant biological properties in various cancers, its functions in hepatocellular carcinoma (HCC) remain obscure. We aimed to investigate the potential role of CTSC in HCC.
Materials and Methods
HCC tissue microarrays (n=122) were employed to analyze the correlation between CTSC expression and clinicopathological characteristics through immunohistochemistry staining. Quantitative real-time polymerase chain reaction, western blot assay, Cell Counting Kit-8 assay, colony formation, cell migration, and invasion assays, xenograft mice model were adopted to validate what had been indicated by the bioinformatic web tools.
Results
By bioinformatic tools and tissue microarrays, CTSC was found upregulated in HCC compared with normal liver tissues, and its higher expression was correlated with poor prognosis of HCC patients (hazard ratio, 2.402; 95% confidence interval, 1.493 to 3.865; p < 0.001). By gain/loss-of-function assays, we implicated that CTSC functioned as an oncogene to promote the proliferation and metastasis of HCC cells. Mechanistically, we revealed that CTSC was involved in several cancer-related signaling pathways by Gene Set Enrichment Analysis, among which tumor necrosis factor α (TNF-α)/p38 pathway was verified to be activated by CTSC. Furthermore, we found that TNF-α could activate CTSC expression in a concentration- dependent manner. Ralimetinib, an oral p38 mitogen-activated protein kinase (MAPK) inhibitor could inhibit CTSC expression. These indicated a potential positive feedback loop between CTSC and TNF-α/MAPK (p38) signaling.
Conclusion
Taken together, CTSC plays an important role in the growth and metastasis of HCC and may be a promising therapeutic target upon HCC.

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Treatment Outcome after Fractionated Conformal Radiotherapy for Hepatocellular Carcinoma in Patients with Child-Pugh Classification B in Korea (KROG 16-05): Sun Hyun Bae, Hee Chul Park, Won Sup Yoon, Sang Min Yoon, In-Hye Jung, Ik Jae Lee, Jun Won Kim, Jinsil Seong, Tae Hyun Kim, Taek-Keun Nam, Youngmin Choi, Sun Young Lee, Hong Seok Jang, Dong Soo Lee, Jin Hee Kim; Cancer Res Treat. 2019;51(4):1589-1599. Published online April 10, 2019; DOI: https://doi.org/10.4143/crt.2018.687

Abstract PDF Supplementary Material PubReader ePub

Purpose
There is limited data on radiotherapy (RT) for hepatocellular carcinoma (HCC) in patients with Child-Pugh classification B (CP-B). This study aimed to evaluate the treatment outcomes of fractionated conformal RT in HCC patients with CP-B.
Materials and Methods
We retrospectively reviewed the data of HCC patients with CP-B treated with RT between 2009 and 2014 at 13 institutions in Korea. HCC was diagnosed by the Korea guideline of 2009, and modern RT techniques were applied. Fraction size was ≤ 5 Gy and the biologically effective dose (BED) ≥ 40 Gy10 (α/β = 10 Gy). A total of 184 patients were included in this study.
Results
Initial CP score was seven in 62.0% of patients, eight in 31.0%, and nine in 7.0%. Portal vein tumor thrombosis was present in 66.3% of patients. The BED ranged from 40.4 to 89.6 Gy10 (median, 56.0 Gy10). After RT completion, 48.4% of patients underwent additional treatment. The median overall survival (OS) was 9.4 months. The local progression-free survival and OS rates at 1 year were 58.9% and 39.8%, respectively. In the multivariate analysis, non-classic radiation-induced liver disease (RILD) (p < 0.001) and additional treatment (p < 0.001) were the most significant prognostic factors of OS. Among 132 evaluable patients without progressive disease, 19.7% experienced non-classic RILD. Normal liver volume was the most predictive dosimetric parameter of non-classic RILD.
Conclusion
Fractionated conformal RT showed favorable OS with a moderate risk non-classic RILD. The individual radiotherapy for CP-B could be cautiously applied weighing the survival benefits and the RILD risks.

Citations

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Lijun Chen, Min Liu, Shenshen Chen, Yi Wu, Shichun Guan, Jianxu Li, Shixiong Liang
ImmunoTargets and Therapy.2025; Volume 14: 1015. CrossRef
Development and validation of a nomogram for radiation-induced hepatic toxicity after intensity modulated radiotherapy for hepatocellular carcinoma: a retrospective study
Qiaoyuan Wu, Yudan Wang, Yuxin Wei, Zhengqiang Yang, Kai Chen, Jianxu Li, Liqing Li, Tingshi Su, Shixiong Liang
Japanese Journal of Clinical Oncology.2024; 54(6): 699. CrossRef
Managing hepatocellular carcinoma across the stages: efficacy and outcomes of stereotactic body radiotherapy
Ahmed Allam Mohamed, Marie-Luise Berres, Philipp Bruners, Sven Arke Lang, Christian Trautwein, Georg Wiltberger, Alexandra Barabasch, Michael Eble
Strahlentherapie und Onkologie.2024; 200(8): 715. CrossRef
Clinical outcomes and safety of external beam radiotherapy with extensive intrahepatic targets for advanced hepatocellular carcinoma: A single institutional clinical experience
Sunmin Park, Chai Hong Rim, Won Sup Yoon
Saudi Journal of Gastroenterology.2024; 30(6): 399. CrossRef
Role of rapid arc-image-guided radiotherapy in hepatocellular carcinoma with portal vein tumor thrombosis: A study from tertiary care center in Punjab, India
Manjinder Singh Sidhu, Ramandeep, Sandhya Sood, Ritu Aggarwal, Kulbir Singh, Divyanshi Sood
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Non-classic radiation-induced liver disease after intensity-modulated radiotherapy for Child–Pugh grade B patients with locally advanced hepatocellular carcinoma
Jian-Xu Li, Rui-Jun Zhang, Mo-Qin Qiu, Liu-Ying Yan, Mei-Ling He, Mei-Ying Long, Jian-Hong Zhong, Hai-Yan Lu, Hong-Mei Zhou, Bang-De Xiang, Shi-Xiong Liang
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Acta Oncologica.2023; 62(3): 281. CrossRef
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Bong Kyung Bae, Jeong Il Yu, Hee Chul Park, Myung Ji Goh, Yong-Han Paik
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In Young Jo, Hee Chul Park, Eun Seog Kim, Seung-Gu Yeo, Myungsoo Kim, Jinsil Seong, Jun Won Kim, Tae Hyun Kim, Won Sup Yoon, Bae Kwon Jeong, Sung Hwan Kim, Jong Hoon Lee
Japanese Journal of Clinical Oncology.2022; 52(6): 616. CrossRef
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Chai Hong Rim, Hye Yoon Lee, Jung Sun Kim, Hakyoung Kim
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Sunmin Park, Chai Hong Rim, Young Kul Jung, Won Sup Yoon, Alessandro Granito
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Han Lee, Sunmin Park, Yeon Seo, Won Yoon, Chai Rim
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Novel Prognostic Nomograms Based on Inflammation-Related Markers for Patients with Hepatocellular Carcinoma Underwent Hepatectomy: Yifei Wang, Kaiyu Sun, Jingxian Shen, Bin Li, Ming Kuang, Qinghua Cao, Sui Peng; Cancer Res Treat. 2019;51(4):1464-1478. Published online March 11, 2019; DOI: https://doi.org/10.4143/crt.2018.657

Abstract PDF Supplementary Material PubReader ePub

Purpose
Hepatocellular carcinoma (HCC) is an aggressive disease with high recurrence rate. However, current staging systems were lack of predictive capacity for HCC recurrence. We aimed to develop prognostic nomograms based on inflammation-related markers for HCC patients underwent hepatectomy.
Materials and Methods
We recruited 889 surgically treated patients from two medical centers. Independent prognostic factors were identified by cox regression analyses. Nomograms for recurrence-free survival (RFS) and overall survival (OS) were established, and validated internally and externally. The performance, discrimination, and calibration of nomograms were assessed, and compared with existed staging systems.
Results
Neutrophil to lymphocyte ratio (NLR) and gamma-glutamyl transpeptidase to platelet ratio (GPR) were the two inflammation-related factor that independently correlated with survival. NLR, GPR, international normalized ratio (INR), microvascular invasion, satellite lesions, tumour number, tumour diameter, and macrovascular invasion were used to construct nomogram for RFS while GPR, total bilirubin, INR, α-fetoprotein, microvascular invasion, satellite lesions, tumour diameter, and macrovascular invasion were for OS. In the training cohort, the C-index of nomogram was 0.701 (95% confidence interval [CI], 0.669 to 0.732) for RFS and 0.761 (95% CI, 0.728 to 0.795) for OS. These results received both internal and external validation with C-index of 0.701 (95% CI, 0.647 to 0.755) and 0.707 (95% CI, 0.657 to 0.756) for RFS, and 0.706 (95% CI, 0.640 to 0.772) and 0.708 (95% CI, 0.646 to 0.771) for OS, respectively. The nomograms showed superior accuracy to conventional staging systems (p<0.001).
Conclusion
The nomograms based on inflammation-related markers are of high efficacy in predicting survival of HCC patients after hepatectomy, which will be valuable in guiding postoperative interventions and follow-ups.

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Surveillance Rate and its Impact on Survival of Hepatocellular Carcinoma Patients in South Korea: A Cohort Study: Sanghyuk Im, Eun Sun Jang, Ju Hyun Lee, Chung Seop Lee, Beom Hee Kim, Jung Wha Chung, Jin-Wook Kim, Sook-Hyang Jeong; Cancer Res Treat. 2019;51(4):1357-1369. Published online February 12, 2019; DOI: https://doi.org/10.4143/crt.2018.430

Abstract PDF Supplementary Material PubReader ePub

Purpose
Though regular surveillance of hepatocellular carcinoma (HCC) for high-risk patients is widely recommended, its rate and effectiveness are not clear. The aim of this study is to investigate the actual rate of HCC surveillance and its related factors and to clarify its impact on survival in a Korean HCC cohort.
Materials and Methods
From 2012 to 2015, 319 newly diagnosed HCC patients were prospectively enrolled at a tertiary hospital. Patient interviews based on a structured questionnaire survey were conducted. Surveillance was defined as liver imaging test ≥ 2 times with at least 3-month interval within 2 years prior to HCC diagnosis.
Results
Surveillance rate was 39.8%. Of the HCC patients with high-risk factors, only 182 (57.1%) had knowledge for the need for regular surveillance, and 141 (44.2%) had the accurate information about the method (ultrasound-based study). Surveillance group showed a higher proportion of early HCC (p < 0.001) and a longer overall survival (p < 0.001) compared to non-surveillance group. The multivariable Cox regression analysis indicated Child-Pugh class A, history of anti-viral therapy, low serum α-fetoprotein level, non-advanced Barcelona Clinic Liver Cancer stage as independent predictors of overall survival, while regular surveillance was not (p=0.436).
Conclusion
Less than half of the newly diagnosed Korean HCC patients were under surveillance and the accurate perception for the need of HCC surveillance was insufficient. Of those under surveillance, most patients were diagnosed with early stage HCC, which led to the improved survival. Comprehensive efforts to optimize the surveillance program for the target population are warranted.

Citations

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Dedicated Automatic Recall Hepatocellular Cancer Surveillance Programme Demonstrates High Retention: A Population‐Based Cohort Study
Mayur Brahmania, Stephen Congly, Yashasavi Sachar, Kelly W. Burak, Brendan Lethebe, Jessie Hart Szostakiwskyj, David Lautner, Alexandra Medellin, Deepak Bhayana, Jason Wong, Henry Nguyen, Matthew D. Sadler, Meredith Borman, Alexander I. Aspinall, Carla S.
Liver International.2025;[Epub] CrossRef
Optimal surveillance intervals for hepatocellular carcinoma screening in cirrhotic patients with hepatitis C infection: a Taiwanese national cohort study
Shen-Shong Chang, Yu-Chin Chen, Hsiao-Yun Hu, Yung-Feng Yen, Nicole Huang
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Kalyani Narra, Madison Hull, Kari J. Teigen, Vedaamrutha Reddy, Jolonda C. Bullock, Riyaz Basha, Nadia Alawi-Kakomanolis, David E. Gerber, Timothy J. Brown
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Benefits and harms of screening for hepatocellular carcinoma in high-risk populations: systematic review and meta-analysis
Jichun Yang, Zhirong Yang, Xueyang Zeng, Shuqing Yu, Le Gao, Yu Jiang, Feng Sun
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Frontiers in Oncology.2023;[Epub] CrossRef
Prognosis of hepatocellular carcinoma patients diagnosed under regular surveillance: potential implications for surveillance goal
Joo Hye Song, Myung Ji Goh, Yewan Park, Joo Hyun Oh, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik
Scandinavian Journal of Gastroenterology.2021; 56(3): 274. CrossRef
Prior antiviral treatment and mortality among patients with hepatitis C virus-related hepatocellular carcinoma: A national cohort study
Dong Hyun Sinn, Danbee Kang, Yun Soo Hong, Kwang Cheol Koh, Eliseo Guallar, Juhee Cho, Geum-Youn Gwak, Luca Rinaldi
PLOS ONE.2021; 16(8): e0255624. CrossRef

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Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma: Changhoon Yoo, Jihoon Kang, Ho Yeong Lim, Jee Hyun Kim, Myung-Ah Lee, Kyung-Hun Lee, Tae-You Kim, Baek-Yeol Ryoo; Cancer Res Treat. 2019;51(2):510-518. Published online June 13, 2018; DOI: https://doi.org/10.4143/crt.2018.226

Abstract PDF Supplementary Material PubReader ePub

Purpose
The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC).
Materials and Methods
This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints.
Results
A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8).
Conclusion
OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.

Citations

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Hepatic Resection Provides Survival Benefit for Selected Intermediate-Stage (BCLC-B) Hepatocellular Carcinoma Patients: Zhang Zhaohui, Shen Shunli, Chen Bin, Li Shaoqiang, Hua Yunpeng, Kuang Ming, Liang Lijian, Peng Bao Gang; Cancer Res Treat. 2019;51(1):65-72. Published online February 26, 2018; DOI: https://doi.org/10.4143/crt.2018.038

Abstract PDF PubReader ePub

Purpose
The intermediate stage of hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] B) comprises a highly heterogeneous population, and the treatment strategy is still controversial. Because of the heterogeneity, a subclassification of intermediate-stage HCCs was put forward by Bolondi according to the ‘beyond Milan and within up-to-7’ criteria and Child-Pugh score. In this study, we aim to analyze the prognosis of BCLC-B stage HCC patients who received hepatic resection according to the Bolondi’s subclassification.
Materials and Methods
One thousand and one hundred three patients diagnosedwith HCC and treatedwith hepatic resectionwere enrolled in our hospital between 2006 and 2012. According to Bolondi’s subclassification, the BCLC-B patients were divided into four groups. Recurrence-free survival (RFS) and overall survival (OS) were analyzed.
Results
According to Bolondi’s subclassification, the BCLC-B patients were divided into four groups: B1 (n=41, 18.7%), B2 (n=160, 73.1%), B3 (n=11, 5.0%), and B4 (n=7, 3.2%). Significant difference was observed between B1 and other groups (B1 vs. B2, p=0.022; B1 vs. B3, p < 0.001; B1 vs. B4, p < 0.001), but no difference for B2 vs. B4 (p=0.542) and B3 vs. B4 (p=0.542). In addition, no significant differences were observed between BCLC-A and BCLC-B1 group for both RFS (p=0.087) and OS (p=0.643). In multivariate analysis, BCLC-B subclassification was not a risk factor for both OS (p=0.263) and RFS (p=0.892).
Conclusion
In our study, HCC patients at B1 stagewere benefited from hepatic resection and had similar survival to BCLC-A stage patients. Our study provided rationality of hepatic resection for selected BCLC-B stage HCC patients instead of routine transarterial chemoembolization.

Citations

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Sorafenib with or without co-interventions for hepatocellular carcinoma
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TAC score better predicts survival than the BCLC following resection of hepatocellular carcinoma
Henrique A. Lima, Yutaka Endo, Zorays Moazzam, Laura Alaimo, Chanza Shaikh, Muhammad M. Munir, Vivian Resende, Alfredo Guglielmi, Hugo P. Marques, François Cauchy, Vincent Lam, George A. Poultsides, Irinel Popescu, Sorin Alexandrescu, Guillaume Martel, It
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Everolimus Plus Ku0063794 Regimen Promotes Anticancer Effects against Hepatocellular Carcinoma Cells through the Paradoxical Inhibition of Autophagy: Sang Chul Lee, Kee-Hwan Kim, Ok-Hee Kim, Sang Kuon Lee, Ha-Eun Hong, Byung Jo Choi, Wonjun Jeong, Say-June Kim; Cancer Res Treat. 2018;50(3):1023-1038. Published online November 9, 2017; DOI: https://doi.org/10.4143/crt.2017.085

Abstract PDF PubReader ePub

Purpose
Everolimus only inhibits mammalian target of rapamycin complex 1 (mTORC1), whereas Ku0063794 inhibits both mTORC1 and mTORC2. Although they have similar anticancer effects, their combination has a synergistic effect against hepatocellular carcinoma (HCC) cells. We aimed to determine the mechanism underlying the synergistic effects of everolimus and Ku0063794 associated with autophagy in HCC cells.
Materials and Methods
We compared the effects of everolimus and Ku0063794, individually or in combination, on both the in vitro and in vivo models of HCCs.
Results
HepG2 cells treated with both agents had significantly lower rates of cell proliferation and higher apoptosis than the individual monotherapies (p < 0.05). Autophagic studies consistently indicated that, unlike the monotherapies, the combination therapy significantly reduced autophagy (p < 0.05). Autophagic blockage directly promoted the pro-apoptotic effects of combination therapy, suggesting autophagy as the survival mechanism of HCC cells. Unlike the monotherapies, combination therapy showed the potential to inhibit sirtuin 1 (SIRT1), the positive regulator of autophagy. SIRT1 overexpression abrogated the autophagy-inhibiting and pro-apoptotic effects of combination therapy. In a nude mouse xenograft model, the shrinkage of tumors was more prominent in mice treated with combination therapy than in mice treated with the respective monotherapies (p < 0.05). The immunohistochemical and immunofluorescence stains of the tumor obtained from the xenograft model showed that combination therapy had the potential of reducing autophagy and promoting apoptosis.
Conclusion
The combination of everolimus and Ku0063794 potentiates anticancer effects on HCCs through a decrease in autophagy, which is prompted by SIRT1 downregulation.

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Sarcopenia Predicts Prognosis in Patients with Newly Diagnosed Hepatocellular Carcinoma, Independent of Tumor Stage and Liver Function: Yeonjung Ha, Daejung Kim, Seungbong Han, Young Eun Chon, Yun Bin Lee, Mi Na Kim, Joo Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang; Cancer Res Treat. 2018;50(3):843-851. Published online September 4, 2017; DOI: https://doi.org/10.4143/crt.2017.232

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to demonstrate the prognostic significance of changes in body composition in patients with newly diagnosed hepatocellular carcinoma (HCC).
Materials and Methods
Patients (n=178) newly diagnosed with HCC participated in the study between 2007 and 2012. Areas of skeletal muscle and abdominal fat were directly measured using a three-dimensional workstation. Cox proportional-hazards modes were used to estimate the effect of baseline variables on overall survival. The inverse probability of treatmentweighting (IPTW) method was used to minimize confounding bias.
Results
Cutoff values for sarcopenia, obtained from receiver-operating characteristic curves, were defined as skeletal muscle index at the third lumbar vertebra of ≤ 45.8 cm/m² for males and ≤ 43.0 cm/m² for females. Sarcopenia patients were older, more likely to be female, and had lower body mass index. Univariable analysis showed that the presence of sarcopenia and visceral to subcutaneous fat area ratio (VSR) were significantly associatedwith prognosis. The multivariable analyses revealed that VSR was predictive of overall survival. However, in the multivariable Cox model adjusted by IPTW, sarcopenia, not VSR, were associated with overall survival.
Conclusion
The presence of sarcopenia at HCC diagnosis is independently associated with survival.

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Inter-alpha Inhibitor H4 as a Potential Biomarker Predicting the Treatment Outcomes in Patients with Hepatocellular Carcinoma: Eun-Jung Lee, Seung-Hyun Yang, Kyoung-Jin Kim, Hyejung Cha, Seo Jin Lee, Ji-Hye Kim, Junkyu Song, Kyung-Hee Chun, Jinsil Seong; Cancer Res Treat. 2018;50(3):646-657. Published online July 17, 2017; DOI: https://doi.org/10.4143/crt.2016.550

Abstract PDF Supplementary Material PubReader ePub

Purpose
Early prediction of treatment outcomes represents an essential step towards increased treatment efficacy and survival in patients with hepatocellular carcinoma (HCC). In this study, we performed two-dimensional electrophoresis (2-DE) followed by protein profiling to identify biomarkers predictive of therapeutic outcomes in patients with HCC who received liver-directed therapy (LDTx) involving local radiotherapy (RT), and studied the underlying mechanisms of the identified proteins.
Materials and Methods
2-DE analysis was conducted by pooling sera from patients with a good or poor prognosis; serum proteomic profiles of the two groups were compared and analyzed using matrixassisted laser desorption/ionization time-of-flight mass spectrometry. Identified proteins were confirmed via enzyme-linked immunosorbent assay. An invasion assay was performed after overexpression and knockdown of target protein in Huh7 cells.
Results
Levels of inter-alpha inhibitor H4 (ITIH4), fibrinogen gamma chain, keratin 9/1 complex, carbonic anhydrase I, and carbonmonoxyhemoglobin S were changed by more than 4-fold in response to LDTx. In particular, pre-LDTx ITIH4 expression was more than 5-fold higher in patients with a good prognosis, compared to patients with a poor prognosis. The migration ability of Huh7 cells was significantly suppressed and enhanced by ITIH4 overexpression and knockdown, respectively. The tumors of patients with HCC and a good prognosis expressed high levels of ITIH4, compared to those of patients with a poor prognosis.
Conclusion
Taken together, ITIH4 may be a potential therapeutic target that could inhibit cancer metastasis, as well as a prognostic marker for patients with HCC who are receiving LDTx.

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Body Composition Predicts Survival in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization: Neehar D. Parikh, Peng Zhang, Amit G. Singal, Brian A. Derstine, Venkat Krishnamurthy, Pranab Barman, Akbar K. Waljee, Grace L. Su; Cancer Res Treat. 2018;50(2):530-537. Published online June 1, 2017; DOI: https://doi.org/10.4143/crt.2017.156

Abstract PDF Supplementary Material PubReader ePub

Purpose
The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is often uncertain. We aimed to utilize analytic morphomics, a high-throughput imaging analysis, to assess if body composition is predictive of post-TACE survival.
Materials and Methods
We included patients from a single center (Ann Arbor VA)who had TACE as the primary treatment forHCC and had a pre-treatment computed tomography scans. Univariate analysis and multivariate conditional inference tree analysis were utilized to identify the morphomic characteristics predictive of 1-year survival. Resultswere validated in an external cohort(University of MichiganHealth System) ofHCC patientswho underwent TACE as their primary treatment.
Results
In the 75 patients in the derivation cohort, median survival was 439 (interquartile range, 377 to 685) days from receipt of TACE, with 1-year survival of 61%. Visceral fat density (VFD) was the only morphomic factor predictive of overall and 1-year survival (p < 0.001). Patients with VFD above the 56th percentile had a 1-year survival of 39% versus 78% for those below the 56th percentile. VFD also correlated with 1-year survival in the external validation cohort (44% vs. 72%, p < 0.001). In a secondary analysis, patients with higher VFD were significantly more likely to experience hepatic decompensation after TACE (p < 0.001).
Conclusion
VFD served as an objective predictor of mortality in patients undergoing TACE, possibly through its ability to predict hepatic decompensation. VFD may serve as a radiographic biomarker in predicting TACE outcomes.

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Sub-classification of Advanced-Stage Hepatocellular Carcinoma: A Cohort Study Including 612 Patients Treated with Sorafenib: Jeong-Ju Yoo, Goh Eun Chung, Jeong-Hoon Lee, Joon Yeul Nam, Young Chang, Jeong Min Lee, Dong Ho Lee, Hwi Young Kim, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Seoul Liver Group; Cancer Res Treat. 2018;50(2):366-373. Published online May 15, 2017; DOI: https://doi.org/10.4143/crt.2017.126

Abstract PDF PubReader ePub

Purpose
Advanced hepatocellular carcinoma (HCC) is associated with various clinical conditions including major vessel invasion, metastasis, and poor performance status. The aim of this study was to establish a prognostic scoring system and to propose a sub-classification of the Barcelona-Clinic Liver Cancer (BCLC) stage C.
Materials and Methods
This retrospective study included consecutive patientswho received sorafenib for BCLC stage C HCC at a single tertiary hospital in Korea. A Cox proportional hazard model was used to develop a scoring system, and internal validationwas performed by a 5-fold cross-validation. The performance of the model in predicting risk was assessed by the area under the curve and the Hosmer-Lemeshow test.
Results
A total of 612 BCLC stage C HCC patients were sub- classified into strata depending on their performance status. Five independent prognostic factors (Child-Pugh score, α-fetoprotein, tumor type, extrahepatic metastasis, and portal vein invasion) were identified and used in the prognostic scoring system. This scoring system showed good discrimination (area under the receiver operating characteristic curve, 0.734 to 0.818) and calibration functions (both p < 0.05 by the Hosmer-Lemeshow test at 1 month and 12 months, respectively). The differences in survival among the different risk groups classified by the total score were significant (p < 0.001 by the log-rank test in both the Eastern Cooperative Oncology Group 0 and 1 strata).
Conclusion
The heterogeneity of patientswith BCLC stage C HCC requires sub-classification of advanced HCC. A prognostic scoring system with five independent factors is useful in predicting the survival of patients with BCLC stage C HCC.

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Tumor burden affects the progression pattern on the prognosis in patients treated with sorafenib
Jun Sun, Dongdong Xia, Wei Bai, Xiaomei Li, Enxing Wang, ZhanXin Yin, Guohong Han
Frontiers in Oncology.2024;[Epub] CrossRef
A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma
Ji W. Han, Soon K. Lee, Jung H. Kwon, Soon W. Nam, Hyun Yang, Si H. Bae, Ji H. Kim, Heechul Nam, Chang W. Kim, Hae L. Lee, Hee Y. Kim, Sung W. Lee, Ahlim Lee, U I. Chang, Do S. Song, Seok-Hwan Kim, Myeong J. Song, Pil S. Sung, Jong Y. Choi, Seung K. Yoon,
Clinical Cancer Research.2024; 30(13): 2812. CrossRef
Subclassification of advanced-stage hepatocellular carcinoma with macrovascular invasion: combined transarterial chemoembolization and radiotherapy as an alternative first-line treatment
Sujin Jin, Won-Mook Choi, Ju Hyun Shim, Danbi Lee, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Jinhong Jung, Sang Min Yoon, Jonggi Choi
Journal of Liver Cancer.2023; 23(1): 177. CrossRef
Development and validation of web‐based prognostic nomograms for massive hepatocellular carcinoma (≥10 cm): A retrospective study based on the SEER database
Guizhong Huang, Qiaohong Lin, Pengfei Yin, Kai Mao, Jianlong Zhang
Cancer Medicine.2023; 12(12): 13167. CrossRef
Development of a Multivariate Prognostic Model for Lenvatinib Treatment in Hepatocellular Carcinoma
Xiaomi Li, Xiaoyan Ding, Mei Liu, Jingyan Wang, Wei Li, Jinglong Chen
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Prognostic models for outcome prediction in patients with advanced hepatocellular carcinoma treated by systemic therapy: a systematic review and critical appraisal
Li Li, Xiaomi Li, Wendong Li, Xiaoyan Ding, Yongchao Zhang, Jinglong Chen, Wei Li
BMC Cancer.2022;[Epub] CrossRef
Identification and validation of a prognostic model of necroptosis-related lncRNAs in hepatocellular carcinoma
Min Chen, Guang-Bo Wu, Shan Hua, Zhi-Feng Zhao, Hong-Jie Li, Meng Luo
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Prognostic value of a nomogram based on peripheral blood immune parameters in unresectable hepatocellular carcinoma after intensity-modulated radiotherapy
Jian-Xu Li, Mei-Ling He, Mo-Qin Qiu, Liu-Ying Yan, Mei-Ying Long, Jian-Hong Zhong, Rui-Jun Zhang, Chun-Feng Liang, Ya-Dan Pang, Jun-Kun He, Qian-Qian Chen, Jin-Xia Weng, Shi-Xiong Liang, Bang-De Xiang
BMC Gastroenterology.2022;[Epub] CrossRef
A Nomogram-Based Prognostic Model for Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib: A Multicenter Study
Giovanni Marasco, Francesco Poggioli, Antonio Colecchia, Giuseppe Cabibbo, Filippo Pelizzaro, Edoardo Giannini, Sara Marinelli, Gian Rapaccini, Eugenio Caturelli, Mariella Di Marco, Elisabetta Biasini, Fabio Marra, Filomena Morisco, Francesco Foschi, Marc
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Clinical Characteristics of Long-Term Survivors After Sorafenib Treatment for Unresectable Hepatocellular Carcinoma: A Korean National Multicenter Retrospective Cohort Study
Young Youn Cho, Su Jong Yu, Hye Won Lee, Do Young Kim, Wonseok Kang, Yong-Han Paik, Pil Soo Sung, Si Hyun Bae, Su Cheol Park, Young Seok Doh, Kang Mo Kim, Eun Sun Jang, In Hee Kim, Won Kim, Yoon Jun Kim
Journal of Hepatocellular Carcinoma.2021; Volume 8: 613. CrossRef
Identification and Validation of a Prognostic Prediction Model of m6A Regulator-Related LncRNAs in Hepatocellular Carcinoma
Chen Jin, Rui Li, Tuo Deng, Jialiang Li, Yan Yang, Haoqi Li, Kaiyu Chen, Huihua Xiong, Gang Chen, Yi Wang
Frontiers in Molecular Biosciences.2021;[Epub] CrossRef
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Peng Zhu, Qianqian Ren, Nan He, Cheng Zhou, Qianna Jin, Zhao Gong
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Tingting Zhang, Zhe Liu, Xiangqian Zhao, Zhiyuan Mao, Li Bai
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Combined transarterial chemoembolization and radiotherapy as a first-line treatment for hepatocellular carcinoma with macroscopic vascular invasion: Necessity to subclassify Barcelona Clinic Liver Cancer stage C
Yeon Joo Kim, Jinhong Jung, Ji Hyeon Joo, So Yeon Kim, Jin Hyoung Kim, Young-Suk Lim, Han Chu Lee, Jong Hoon Kim, Sang Min Yoon
Radiotherapy and Oncology.2019; 141: 95. CrossRef
Sorafenib for Recurrent Hepatocellular Carcinoma after Liver Transplantation
Bo Hyun Kim, Joong-Won Park
Journal of Korean Medical Science.2018;[Epub] CrossRef

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309 Download
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Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma: Hae Il Jung, Dongjun Jeong, Sanghee Ji, Tae Sung Ahn, Sang Ho Bae, Susie Chin, Jun Chul Chung, Hyung Chul Kim, Moon Soo Lee, Moo-Jun Baek; Cancer Res Treat. 2017;49(1):246-254. Published online July 7, 2016; DOI: https://doi.org/10.4143/crt.2016.066

Abstract PDF PubReader ePub

Purpose
Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC.
Materials and Methods
Formalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis.
Results
The proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034).
Conclusion
The overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted.

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Journal of Hematology & Oncology.2018;[Epub] CrossRef
Immunotherapy for pulmonary squamous cell carcinoma and colon carcinoma with pembrolizumab
Yoshihiro Nozawa, Yuka Oka, Jun Oosugi, Shinichi Takemura
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Ioannis Zerdes, Alexios Matikas, Jonas Bergh, George Z. Rassidakis, Theodoros Foukakis
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MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity
Alisa B. Lee-Sherick, Kristen M. Jacobsen, Curtis J. Henry, Madeline G. Huey, Rebecca E. Parker, Lauren S. Page, Amanda A. Hill, Xiaodong Wang, Stephen V. Frye, H. Shelton Earp, Craig T. Jordan, Deborah DeRyckere, Douglas K. Graham
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Jaafar Jaafar, Eugenio Fernandez, Heba Alwan, Jacques Philippe
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Xiao Xiang, Peng-Cheng Yu, Di Long, Xiao-Li Liao, Sen Zhang, Xue-Mei You, Jian-Hong Zhong, Le-Qun Li
Oncotarget.2018; 9(4): 5058. CrossRef
CXCL12 expression and PD-L1 expression serve as prognostic biomarkers in HCC and are induced by hypoxia
Alexander Semaan, Dimo Dietrich, Dominik Bergheim, Jörn Dietrich, Jörg C. Kalff, Vittorio Branchi, Hanno Matthaei, Glen Kristiansen, Hans-Peter Fischer, Diane Goltz
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Cheng-Piao Luo, Han-Yue Mo, Ling-Ling Wu, Yun Ma, Ning-Fu Peng
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Immune checkpoints and their inhibition in cancer and infectious diseases
Lydia Dyck, Kingston H.G. Mills
European Journal of Immunology.2017; 47(5): 765. CrossRef
Expression and prognostic significance of programmed death protein 1 and programmed death ligand‐1, and cytotoxic T lymphocyte‐associated molecule‐4 in hepatocellular carcinoma
Hyeyoon Chang, Wonkyung Jung, Aeree Kim, Han Kyeom Kim, Wan Bae Kim, Ji Hoon Kim, Baek‐hui Kim
APMIS.2017; 125(8): 690. CrossRef
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Junyu Long, Jianzhen Lin, Anqiang Wang, Liangcai Wu, Yongchang Zheng, Xiaobo Yang, Xueshuai Wan, Haifeng Xu, Shuguang Chen, Haitao Zhao
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PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer
Dagmar Kollmann, Thomas Schweiger, Stefan Schwarz, Desislava Ignatova, Yun-Tsan Chang, Gerrit Lewik, Sebastian F. Schoppmann, Wolfram Hoetzenecker, Walter Klepetko, Emmanuella Guenova, Konrad Hoetzenecker
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PD-1 and PD-L1 co-expression predicts favorable prognosis in gastric cancer
Yanhua Wu, Donghui Cao, Limei Qu, Xueyuan Cao, Zhifang Jia, Tiancheng Zhao, Quan Wang, Jing Jiang
Oncotarget.2017; 8(38): 64066. CrossRef

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Studying the Effect of Downregulating Autophagy-Related Gene LC3 on TLR3 Apoptotic Pathway Mediated by dsRNA in Hepatocellular Carcinoma Cells: Guilan Wang, Maona Zhang, Yunlong Li, Jiaming Zhou, Li Chen; Cancer Res Treat. 2017;49(1):230-245. Published online June 13, 2016; DOI: https://doi.org/10.4143/crt.2015.506

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to examine the role of the double-stranded RNA (dsRNA) activated Toll–interleukin-1 receptor domain-containing adaptor inducing interferon β (TRIF) signal pathway in triggering apoptosis in hepatocellular carcinoma (HCC) cells.
Materials and Methods
First, siRNA targeted autophagy–related gene LC3 (pU6H1-LC3 siRNA and siLC3) and a dsRNA used as a Toll-like receptor 3 (TLR3) ligand was constructed and synthesized, respectively. Then, a human HCC cell line was transfected with dsRNA, siLC3, and cotransfected with siLC3 and dsRNA (siLC3+dsRNA), respectively. Finally, quantification real-time polymerase chain reaction, western blotting, and immunofluorescence staining were used in the HCC line (SMMC7721), and MTT assay, flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling, and transmission electron microscopy were used in an HCC xenograft model of nude mice. Human umbilical vein endothelial cell tube forming assay, color Doppler ultrasonographic flow image examination, and CD34-positive microvessel density were used in vitro and in vivo.
Results
Compared with untreated cells, the protein and mRNA expression of TLR3 and TRIF was up-regulated, in order, siLC3+dsRNA, dsRNA, and siLC3. Expression of LC3 was obviously down-regulated and the autophagosomes were significantly decreased in siLC3+dsRNA and siLC3, whereas in dsRNA (p < 0.05). LC3 and TRIF colocation was observed in HepG2 cells. Decreased cell viability, increased apoptosis, decrease in xenograft tumor volume, and angiogenesis potential were also observed in order (p < 0.05).
Conclusion
Suppression of intracellular autophagy resulted in decreased degradation of TRIF protein, which can promote triggering of apoptosis by the TLR3-TRIF pathway. dsRNA and siLC3 could play anticancer roles in coordination.

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A Multi-Omics Analysis of a Mitophagy-Related Signature in Pan-Cancer
Nora Agir, Ilias Georgakopoulos-Soares, Apostolos Zaravinos
International Journal of Molecular Sciences.2025; 26(2): 448. CrossRef
The Functional Mechanisms of Toll-Like Receptor 3 and Its Implications in Digestive System Tumors
Bin Han, Chao Zhang, Xiaoxiao Wang, Huangqin Song, Lei Zhang, Tao Li, Jiefeng He, Haoliang Zhao
Frontiers in Bioscience-Landmark.2023;[Epub] CrossRef
The Role of Autophagy in Liver Cancer: Crosstalk in Signaling Pathways and Potential Therapeutic Targets
Jianzhou Cui, Han-Ming Shen, Lina Hsiu Kim Lim
Pharmaceuticals.2020; 13(12): 432. CrossRef
MiR-219a-5p enhances cisplatin sensitivity of human non-small cell lung cancer by targeting FGF9
Chuangzhou Rao, Xiaobo Miao, Guofang Zhao, Chen Zhang, Haibo Shen, Caijun Dong, Minglei Yang
Biomedicine & Pharmacotherapy.2019; 114: 108662. CrossRef
Up-regulation of miR-146a increases the sensitivity of non-small cell lung cancer to DDP by downregulating cyclin J
Lin Shi, Zhaozhong Xu, Gang Wu, Xiaoting Chen, Yuanyuan Huang, Yanjing Wang, Weiqiang Jiang, Bin Ke
BMC Cancer.2017;[Epub] CrossRef

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Clinical Practice Patterns of Radiotherapy in Patients with Hepatocellular Carcinoma: A Korean Radiation Oncology Group Study (KROG 14-07): Hyejung Cha, Hee Chul Park, Jeong Il Yu, Tae Hyun Kim, Taek-Keun Nam, Sang Min Yoon, Won Sup Yoon, Jun Won Kim, Mi Sook Kim, Hong Seok Jang, Youngmin Choi, Jin Hee Kim, Chul Seung Kay, Inkyung Jung, Jinsil Seong; Cancer Res Treat. 2017;49(1):61-69. Published online June 13, 2016; DOI: https://doi.org/10.4143/crt.2016.097

Abstract PDF PubReader ePub

Purpose
The aim of this study was to examine patterns of radiotherapy (RT) in Korean patients with hepatocellular carcinoma (HCC) according to the evolving guideline for HCC established by the Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC).
Materials and Methods
We reviewed 765 patients with HCC who were treated with RT between January 2011 and December 2012 in 12 institutions.
Results
The median follow-up period was 13.3 months (range, 0.2 to 51.7 months). Compared with previous data between 2004 and 2005, the use of RT as a first treatment has increased (9.0% vs. 40.8%). Increased application of intensity-modulated RT resulted in an increase in radiation dose (fractional dose, 1.8 Gy vs. 2.5 Gy; biologically effective dose, 53.1 Gy₁₀ vs. 56.3 Gy₁₀). Median overall survival was 16.2 months, which is longer than that reported in previous data (12 months). In subgroup analysis, treatments were significantly different according to stage (p < 0.001). Stereotactic body RT was used in patients with early HCC, and most patients with advanced stage were treated with three-dimensional conformal RT.
Conclusion
Based on the evolving KLCSG-NCC practice guideline for HCC, clinical practice patterns of RT have changed. Although RT is still used mainly in advanced HCC, the number of patients with good performance status who were treated with RT as a first treatment has increased. This change in practice patterns could result in improvement in overall survival.

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Complications After Exosome Treatment for Aesthetic Skin Rejuvenation
William J. Nahm, Sukruthi Thunga, Jane Yoo
Dermatological Reviews.2024;[Epub] CrossRef
2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma

Journal of Liver Cancer.2023; 23(1): 1. CrossRef
2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma

Clinical and Molecular Hepatology.2022; 28(4): 583. CrossRef
2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma

Korean Journal of Radiology.2022; 23(12): 1126. CrossRef
Multi-Institutional Retrospective Study of Radiotherapy for Hepatocellular Carcinoma in the Caudate Lobe
Sung Uk Lee, Sang Min Yoon, Jason Chia-Hsien Cheng, Tae Hyun Kim, Bo Hyun Kim, Jin-hong Park, Jinhong Jung, Chiao-Ling Tsai, Yun Chiang, Joong-Won Park
Frontiers in Oncology.2021;[Epub] CrossRef
Patterns of definitive radiotherapy practice for cervical cancer in South Korea: a survey endorsed by the Korean Radiation Oncology Group (KROG 20-06)
Nalee Kim, Won Park
Journal of Gynecologic Oncology.2021;[Epub] CrossRef
Indications of external radiotherapy for hepatocellular carcinoma from updated clinical guidelines: Diverse global viewpoints
Sunmin Park, Won Sup Yoon, Chai Hong Rim
World Journal of Gastroenterology.2020; 26(4): 393. CrossRef
Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma
Changhoon Choi, Gyu Sang Yoo, Won Kyung Cho, Hee Chul Park
World Journal of Gastroenterology.2019; 25(20): 2416. CrossRef
2018 Korean Liver Cancer Association–National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma
KLCA Korean Liver Cancer Association, NCC National Cancer Center
Gut and Liver.2019; 13(3): 227. CrossRef
2018 Korean Liver Cancer Association–National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma

Korean Journal of Radiology.2019; 20(7): 1042. CrossRef
Treatment Outcome after Fractionated Conformal Radiotherapy for Hepatocellular Carcinoma in Patients with Child-Pugh Classification B in Korea (KROG 16-05)
Sun Hyun Bae, Hee Chul Park, Won Sup Yoon, Sang Min Yoon, In-Hye Jung, Ik Jae Lee, Jun Won Kim, Jinsil Seong, Tae Hyun Kim, Taek-Keun Nam, Youngmin Choi, Sun Young Lee, Hong Seok Jang, Dong Soo Lee, Jin Hee Kim
Cancer Research and Treatment.2019; 51(4): 1589. CrossRef
EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma
Peter R. Galle, Alejandro Forner, Josep M. Llovet, Vincenzo Mazzaferro, Fabio Piscaglia, Jean-Luc Raoul, Peter Schirmacher, Valérie Vilgrain
Journal of Hepatology.2018; 69(1): 182. CrossRef

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Estimation of the Incidence of Hepatocellular Carcinoma and Cholangiocarcinoma in Songkhla, Thailand, 1989-2013, Using Multiple Imputation Method: Seesai Yeesoonsang, Surichai Bilheem, Edward McNeil, Sophon Iamsirithaworn, Chuleeporn Jiraphongsa, Hutcha Sriplung; Cancer Res Treat. 2017;49(1):54-60. Published online May 18, 2016; DOI: https://doi.org/10.4143/crt.2016.045

Abstract PDF PubReader ePub

Purpose
Histological specimens are not required for diagnosis of liver and bile duct (LBD) cancer, resulting in a high percentage of unknown histologies. We compared estimates of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) incidences by imputing these unknown histologies.
Materials and Methods
A retrospective study was conducted using data from the Songkhla Cancer Registry, southern Thailand, from 1989 to 2013. Multivariate imputation by chained equations (mice) was used in re-classification of the unknown histologies. Age-standardized rates (ASR) of HCC and CCA by sex were calculated and the trends were compared. Results Of 2,387 LBD cases, 61% had unknown histology. After imputation, the ASR of HCC in males during 1989 to 2007 increased from 4 to 10 per 100,000 and then decreased after 2007. The ASR of CCA increased from 2 to 5.5 per 100,000, and the ASR of HCC in females decreased from 1.5 in 2009 to 1.3 in 2013 and that of CCA increased from less than 1 to 1.9 per 100,000 by 2013.
Results
of complete case analysis showed somewhat similar, although less dramatic, trends.
Conclusion
In Songkhla, the incidence of CCA appears to be stable after increasing for 20 years whereas the incidence of HCC is now declining. The decline in incidence of HCC among males since 2007 is probably due to implementation of the hepatitis B virus vaccine in the 1990s. The rise in incidence of CCA is a concern and highlights the need for case control studies to elucidate the risk factors.

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Comparison of Cholangiocarcinoma and Hepatocellular Carcinoma Incidence Trends from 1993 to 2012 in Lampang, Thailand
Pianpian Cao, Laura S. Rozek, Donsuk Pongnikorn, Hutcha Sriplung, Rafael Meza
International Journal of Environmental Research and Public Health.2022; 19(15): 9551. CrossRef
Mitochondrial Dysfunction and Induction of Apoptosis in Hepatocellular Carcinoma and Cholangiocarcinoma Cell Lines by Thymoquinone
Reem J. Abdualmjid, Consolato M. Sergi
International Journal of Molecular Sciences.2022; 23(23): 14669. CrossRef
Hepatocellular carcinoma incidence at national and provincial levels in Iran from 2000 to 2016: A meta-regression analysis
Nima Fattahi, Negar Rezaei, Mohsen Asadi-Lari, Moein Yousefi, Zahra Madadi, Kimiya Gohari, Ali Sheidaei, Esmaeil Mohammadi, Nazila Rezaei, Mahboubeh Parsaeian, Farzad Kompani, Farshad Farzadfar, Amir Radfar
PLOS ONE.2021; 16(1): e0245468. CrossRef
Trends in Incidence of Two Major Subtypes of Liver and Bile Duct Cancer: Hepatocellular Carcinoma and Cholangiocarcinoma in Songkhla, Southern Thailand, 1989-2030
Seesai Yeesoonsang, Edward McNeil, Shama Virani, Surichai Bilheem, Chakrarat Pittayawonganon, Chuleeporn Jiraphongsa, Hutcha Sriplung
Journal of Cancer Epidemiology.2018; 2018: 1. CrossRef
National and Subnational Population-Based Incidence of Cancer in Thailand: Assessing Cancers with the Highest Burdens
Shama Virani, Surichai Bilheem, Wasan Chansaard, Imjai Chitapanarux, Karnchana Daoprasert, Somsak Khuanchana, Atit Leklob, Donsuk Pongnikorn, Laura Rozek, Surattaya Siriarechakul, Krittika Suwanrungruang, Sukit Tassanasunthornwong, Patravoot Vatanasapt, H
Cancers.2017; 9(8): 108. CrossRef

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