Cancer Research and Treatment

Original Articles

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; Received September 7, 2024 Accepted February 10, 2025 Published online February 11, 2025; DOI: https://doi.org/10.4143/crt.2024.876 [Accepted]

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, 166 HCC cases were newly diagnosed. The prevalences of NAFLD and MASLD were 19.7% and 18.7%, respectively, whereas MAFLD was observed in 35.2% 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 0.99-1.98). 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

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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; : 1. CrossRef

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Role and Effectiveness of Hypofractionated Proton Beam Therapy and Combinations with Systemic Chemotherapy in Inoperable Extrahepatic Cholangiocarcinoma: Sung Uk Lee, Tae Hyun Kim, Sang Myung Woo, Jung Won Chun, Hyunjae Shin, Yu Ri Cho, Bo Hyun Kim, Young-Hwan Koh, Sang Soo Kim, Yang-Gu Suh, Sung Ho Moon, Woo Jin Lee; Received August 19, 2024 Accepted December 16, 2024 Published online December 17, 2024; DOI: https://doi.org/10.4143/crt.2024.805 [Accepted]

Abstract PDF: Purpose
This study aims to assess the clinical outcomes of hypofractionated proton beam therapy (PBT) for extrahepatic cholangiocarcinoma (EHCC) and to investigate the optimal sequencing for combining PBT with chemotherapy.
Materials and Methods
We retrospectively analyzed fifty-nine consecutive patients with inoperable EHCC treated with PBT. The median prescribed dose of PBT was 50 GyE (range, 45–66 GyE) in 10 fractions. The combination sequences of PBT and chemotherapy were categorized as ‘Pre-PBT chemo’ (chemotherapy before PBT), ‘Post-PBT chemo’ (chemotherapy after PBT), and ‘No pre-/post-PBT chemo’ (no chemotherapy before or after PBT). Overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS) were estimated using the Kaplan-Meier method.
Results
All patients completed the planned treatments without any interruptions, and ≥grade 3 acute adverse events were noted in 1.6% of the cases. The 1-year and 2-year FFLP rates were 86.1% and 66.4%, respectively, with a median time of FFLP of 30.9 months. The 1- and 2-year OS rates were 74.5% and 25.3%, respectively, with a median survival time of 16.7 months. For prognostic factor analysis, pre- or post-PBT chemo was associated with a significantly reduced hazard ratio of 0.473 (95% confidence interval 0.233-0.959, p=0.038) in the multivariate analysis. The median OS times for the groups receiving no pre-/post-PBT chemo, pre-PBT chemo, and post-PBT chemo were 14.6, 18.2, and 21.8 months, respectively (p<0.05 for each).
Conclusion
Hypofractionated PBT for inoperable EHCC has demonstrated promising FFLP and OS rates with a safe toxicity profile. The combination of PBT with chemotherapy shows potential to improve clinical outcomes.

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Special Article

Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea: Jii Bum Lee, Minkyu Jung, June Hyuk Kim, Bo Hyun Kim, Yeol Kim, Young Seok Kim, Byung Chang Kim, Jin Kim, Sung Ho Moon, Keon-Uk Park, Meerim Park, Hyeon Jin Park, Sung Hoon Sim, Hong Man Yoon, Soo Jung Lee, Eunyoung Lee, June Young Chun, Youn Kyung Chung, So-Youn Jung, Jinsoo Chung, Eun Sook Lee, Hyun Cheol Chung, Tak Yun, Sun Young Rha; Cancer Res Treat. 2021;53(2):323-329. Published online March 15, 2021; DOI: https://doi.org/10.4143/crt.2020.1256

Abstract PDF PubReader ePub

At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.

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Original Articles

A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer: Soo Jeong Nam, Hyun Yang Yeo, Hee Jin Chang, Bo Hyun Kim, Eun Kyung Hong, Joong-Won Park; Cancer Res Treat. 2016;48(4):1229-1242. Published online March 30, 2016; DOI: https://doi.org/10.4143/crt.2015.500

Abstract PDF PubReader ePub

Purpose
We developed a new method of detecting circulating tumor cells (CTCs) in liver cancer patients by constructing cell blocks from peripheral blood cells, including CTCs, followed by multiple immunohistochemical analysis.
Materials and Methods
Cell blockswere constructed from the nucleated cell pellets of peripheral blood afterremoval of red blood cells. The blood cell blocks were obtained from 29 patients with liver cancer, and from healthy donor blood spikedwith seven cell lines. The cell blocks and corresponding tumor tissues were immunostained with antibodies to seven markers: cytokeratin (CK), epithelial cell adhesion molecule (EpCAM), epithelial membrane antigen (EMA), CK18, α-fetoprotein (AFP), Glypican 3, and HepPar1.
Results
The average recovery rate of spiked SW620 cells from blood cell blocks was 91%. CTCs were detected in 14 out of 29 patients (48.3%); 11/23 hepatocellular carcinomas (HCC), 1/2 cholangiocarcinomas (CC), 1/1 combined HCC-CC, and 1/3 metastatic cancers. CTCs from 14 patients were positive for EpCAM (57.1%), EMA (42.9%), AFP (21.4%), CK18 (14.3%), Gypican3 and CK (7.1%, each), and HepPar1 (0%). Patients with HCC expressed EpCAM, EMA, CK18, and AFP in tissue and/or CTCs, whereas CK, HepPar1, and Glypican3 were expressed only in tissue. Only EMA was significantly associated with the expressions in CTC and tissue. CTC detection was associated with higher T stage and portal vein invasion in HCC patients.
Conclusion
This cell block method allows cytologic detection and multiple immunohistochemical analysis of CTCs. Our results show that tissue biomarkers of HCC may not be useful for the detection of CTC. EpCAM could be a candidate marker for CTCs in patients with HCC.

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Phase I Dose-Escalation Study of Proton Beam Therapy for Inoperable Hepatocellular Carcinoma: Tae Hyun Kim, Joong-Won Park, Yeon-Joo Kim, Bo Hyun Kim, Sang Myung Woo, Sung Ho Moon, Sang Soo Kim, Young-Hwan Koh, Woo Jin Lee, Sang Jae Park, Joo-Young Kim, Dae Yong Kim, Chang-Min Kim; Cancer Res Treat. 2015;47(1):34-45. Published online September 11, 2014; DOI: https://doi.org/10.4143/crt.2013.218

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to determine the optimal dose of proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients.
Materials and Methods
Inoperable HCC patients who had naïve, recurrent, or residual tumor to treatment were considered eligible for PBT. Patients received PBT with 60 GyE in 20 fractions (dose level 1; equivalent dose in 2 Gy fractions [EQD2], 65 GyE10); 66 GyE in 22 fractions (dose level 2; EQD2, 71.5 GyE10); or 72 GyE in 24 fractions (dose level 3; EQD2, 78 GyE10). Dose-limiting toxicity was determined by grade ≥ 3 acute toxicity.
Results
Twenty-seven patients were enrolled; eight, seven, and 12 patients were treated with dose levels 1, 2, and 3, respectively. Overall, treatment was well tolerated, with no dose-limiting toxicities. The complete response (CR) rates of primary tumors after PBT for dose levels 1, 2, and 3 were 62.5% (5/8), 57.1% (4/7), and 100% (12/12), respectively (p=0.039). The 3- and 5-year local progression-free survival (LPFS) rates among 26 patients, excluding one patient who underwent liver transplantation after PBT due to its probable significant effect on disease control, were 79.9% and 63.9%, respectively, and the 3- and 5-year overall survival rates were 56.4% and 42.3%, respectively. The 3-year LPFS rate was significantly higher in patients who achieved CR than in those who did not (90% vs. 40%, p=0.003).
Conclusion
PBT is safe and effective and an EQD2 ≥ 78 GyE10 should be delivered for achievement of local tumor control.

Citations

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