Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Combined High-Dose Radiotherapy with Sequential Gemcitabine-Cisplatin Based Chemotherapy Increase the Resectability and Survival in Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma: A Multi-institutional Cohort Study: Jung Ho Im, Jeong Il Yu, Tae Hyun Kim, Tae Gyu Kim, Jun Won Kim, Jinsil Seong; Cancer Res Treat. 2024;56(3):838-846. Published online January 2, 2024; DOI: https://doi.org/10.4143/crt.2023.886

Abstract PDF Supplementary Material PubReader ePub: Purpose
The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC.
Materials and Methods
Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model.
Results
The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05).
Conclusion
Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.

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Risk Stratification of Pancreatic Ductal Adenocarcinoma Patients Undergoing Curative-Intent Surgery after Neoadjuvant Therapy: Hyun Kyung Yang, Mi-Suk Park, Kyunghwa Han, Geonsik Eom, Yong Eun Chung, Jin-Young Choi, Seungmin Bang, Chang Moo Kang, Jinsil Seong, Myeong-Jin Kim; Cancer Res Treat. 2024;56(1):247-258. Published online August 22, 2023; DOI: https://doi.org/10.4143/crt.2023.586

Abstract PDF Supplementary Material PubReader ePub: Purpose
Clinical prognostic criteria using preoperative factors were not developed for post–neoadjuvant therapy (NAT) surgery of pancreatic ductal adenocarcinoma (PDAC). We aimed to identify preoperative factors associated with overall survival (OS) in PDAC patients who underwent post-NAT curative-intent surgery and develop risk stratification criteria.
Materials and Methods
Consecutive PDAC patients who underwent post-NAT curative-intent surgeries between 2007 and 2020 were retrospectively analyzed. Demographic, laboratory, surgical, and histopathologic variables were collected. Baseline, preoperative, and interval changes of computed tomography (CT) findings proposed by the Society of Abdominal Radiology and the American Pancreatic Association were analyzed. Cox proportional hazard analysis was used to select preoperative variables associated with OS. We developed risk stratification criteria composed of the significant preoperative variables, i.e., post-NAT response criteria. We compared the discrimination performance of post-NAT response criteria with that of post-NAT pathological (yp) American Joint Cancer Committee TNM staging system.
Results
One hundred forty-five PDAC patients were included. Stable or increased tumor size on CT (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.58 to 4.21; p < 0.001) and elevated preoperative carbohydrate antigen 19-9 (CA19-9) level (HR, 1.98; 95% CI, 1.11 to 3.55; p=0.021) were independent factors of OS. The OS of the patient groups stratified by post-NAT response criteria which combined changes in tumor size and CA19-9 showed significant difference (p < 0.001). Such stratification was comparable to ypTNM staging in discrimination performance (difference of C-index, 0.068; 95% CI, –0.012 to 0.142).
Conclusion
“Any degree of decrease in tumor size on CT” and CA19-9 normalization or staying normal were independent favorable factors of OS. The combination of the two factors discriminated OS comparably to ypTNM staging.

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Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814): Younghee Park, Tae Hyun Kim, Kyubo Kim, Jeong Il Yu, Wonguen Jung, Jinsil Seong, Woo Chul Kim, Jin Hwa Choi, Ah Ram Chang, Bae Kwon Jeong, Byoung Hyuck Kim, Tae Gyu Kim, Jin Hee Kim, Hae Jin Park, Hyun Soo Shin, Jung Ho Im, Eui Kyu Chie; Cancer Res Treat. 2024;56(1):272-279. Published online July 31, 2023; DOI: https://doi.org/10.4143/crt.2023.616

Abstract PDF PubReader ePub: Purpose
Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated.
Materials and Methods
Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated.
Results
After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors.
Conclusion
Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

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General

Role of Interleukin-7 in the Development of and Recovery from Radiation-Induced Lymphopenia: A Post-hoc Analysis of a Prospective Cohort: Hwa Kyung Byun, Seung Yeun Chung, Kyoung-Jin Kim, Jinsil Seong; Cancer Res Treat. 2021;53(4):962-972. Published online January 26, 2021; DOI: https://doi.org/10.4143/crt.2020.1053

Abstract PDF Supplementary Material PubReader ePub

Purpose
Radiation-induced lymphopenia is associated with worse outcomes in solid tumors. We assessed the impact of interleukin-7 (IL-7), a key cytokine in lymphocyte homeostasis, on radiation-induced lymphopenia.
Materials and Methods
A post-hoc analysis was performed in a prospective cohort of 98 patients with hepatocellular carcinoma who were treated with radiotherapy in 2016-2018. Blood IL-7 levels were assayed before and at the end of radiotherapy. Acute severe lymphopenia (ASL) was defined as a total lymphocyte count of < 200/μL during radiotherapy. Cox and logistic regression analyses were performed to identify predictors of survival and ASL development, respectively.
Results
Patients with ASL (n=41) had significantly poorer overall survival than those without (12.0 months vs. 25.3 months, p=0.001). Patients with lymphocyte recovery showed significantly longer overall survival than those without (21.8 months vs. 10.3 months, p=0.042). ASL was an independent predictor of poor survival (hazard ratio, 2.07; p=0.015). Patients with ASL had significantly lower pre-radiotherapy IL-7 levels (2.07 pg/mL vs. 3.01 pg/mL, p=0.010). A high pre-radiotherapy IL-7 level was an independent predictor of a reduced risk of ASL development (hazard ratio, 0.40; p=0.004). IL-7 levels reflected a feedback response to ASL, with a higher ΔIL-7 in patients with ASL and a lower ΔIL-7 in those without ASL (0.48 pg/mL vs. –0.66 pg/mL, p < 0.001). Post-radiotherapy IL-7 levels were significantly positively correlated with the total lymphocyte counts at 2 months.
Conclusion
IL-7 is associated with the development of and recovery from ASL, which may impact survival. To overcome radiation-induced lymphopenia, a novel strategy using IL-7 may be considered.

Citations

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International Journal of Radiation Oncology*Biology*Physics.2024; 119(1): 42. CrossRef
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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.

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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
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Sunmin Park, Chai Hong Rim, Won Sup Yoon
Saudi Journal of Gastroenterology.2024;[Epub] 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
Journal of Cancer Research and Therapeutics.2023; 19(3): 639. CrossRef
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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Long-term characterization of MRI-morphologic alterations after active motion-compensated liver SBRT: a multi-institutional pooled analysis
Constantin Dreher, Gustavo R. Sarria, Georgia Miebach, Christel Weiss, Daniel Buergy, Paulina Wojtal, Anoshirwan A. Tavakoli, David Krug, Hans Oppitz, Frank A. Giordano, Marcus Both, Frank Lohr, Jürgen Dunst, Oliver Blanck, Judit Boda-Heggemann
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Bong Kyung Bae, Jeong Il Yu, Hee Chul Park, Myung Ji Goh, Yong-Han Paik
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Rui-Jun Zhang, Hong-Mei Zhou, Hai-Yan Lu, Hong-Ping Yu, Wei-Zhong Tang, Mo-Qin Qiu, Liu-Ying Yan, Mei-Ying Long, Ting-Shi Su, Bang-De Xiang, Mei-Ling He, Xiao-Ting Wang, Shi-Xiong Liang, Jian-Xu Li
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Japanese Journal of Clinical Oncology.2022; 52(6): 616. CrossRef
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Sunmin Park, Chai Hong Rim, Young Kul Jung, Won Sup Yoon, Alessandro Granito
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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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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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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
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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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Altered Biological Potential and Radioresponse of Murine Tumors in Different Microenvironments: Ik Jae Lee, Eun Jeong Lee, Hyojin Park, Wonwoo Kim, Sang-Jun Ha, You Keun Shin, Jinsil Seong; Cancer Res Treat. 2016;48(2):727-737. Published online July 28, 2015; DOI: https://doi.org/10.4143/crt.2014.350

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Purpose
This study was conducted to evaluate the biological features of murine hepatocarcinoma according to different tumor microenvironmental models and to determine the change in molecular and immunologic responses after radiation.
Materials and Methods
Tumor models were established in the liver (orthotopic) and thigh (heterotopic) of male C3H/HeN mice. Tumor growth and lung metastasis were assessed in these models. To evaluate the radiation effect, the tumors were irradiated with 10 Gy. Factors associated with tumor microenvironment including vascular endothelial growth factor (VEGF), cyclooxygenase- 2 (COX-2), transforming growth factor beta1 (TGF-β1), CD31, and serum interleukin- 6 (IL-6) were evaluated. Tumor-infiltrating regulatory immune cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) were also analyzed.
Results
A higher number of lung metastases were observed in the orthotopic tumor model than in the heterotopic tumor model. VEGF, CD31, COX-2, and TGF-β1 expression was more prominent in the orthotopic tumor model than in the heterotopic tumor model. Expression of the angiogenic factor VEGF and key regulatory molecules (TGF-β1 and COX-2) decreased following radiation in the orthotopic tumor model, while the serum IL-6 level increased after radiation. In the orthotopic tumor model, the number of both Tregs and MDSCs in the tumor burden decreased after radiation.
Conclusion
The orthotopic tumor model showed higher metastatic potential and more aggressive molecular features than the heterotopic tumor model. These findings suggest that the orthotopic tumor mouse model may be more reflective of the tumor microenvironment and suitable for use in the translational research of radiation treatment.

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The Effect of Radiation Treatment of Solid Tumors on Neutrophil Infiltration and Function: A Systematic Review
Léon Raymakers, Thijs J. Demmers, Gert J. Meijer, I. Quintus Molenaar, Hjalmar C. van Santvoort, Martijn P.W. Intven, Jeanette H.W. Leusen, Patricia A. Olofsen, Lois A. Daamen
International Journal of Radiation Oncology*Biology*Physics.2024; 120(3): 845. CrossRef
Polymorphonuclear-MDSCs Facilitate Tumor Regrowth After Radiation by Suppressing CD8+ T Cells
Jieying Zhang, MD, Liling Zhang, MD, Yuhui Yang, MD, Qing Liu, MD, Hong Ma, MD, Ai Huang, MD, Yanxia Zhao, MD, Zihan Xia, MD, Tao Liu, MD, Gang Wu, MD
International Journal of Radiation Oncology*Biology*Physics.2021; 109(5): 1533. CrossRef
Preclinical Quantification of Prostate Cancer-Associated Vascular Alterations in the Bone Microenvironment in vivo
Malte Schroeder, Lennart Viezens, Jördis Sündermann, Svenja Hettenhausen, Gerrit Hauenherm, Jasmin Wellbrock, Haider Mussawy, Kai Kossow, Christian Schaefer
European Surgical Research.2020; 61(6): 188. CrossRef
The bone microenvironment promotes tumor growth and tissue perfusion compared with striated muscle in a preclinical model of prostate cancer in vivo
Haider Mussawy, Lennart Viezens, Malte Schroeder, Svenja Hettenhausen, Jördis Sündermann, Jasmin Wellbrock, Kai Kossow, Christian Schaefer
BMC Cancer.2018;[Epub] CrossRef

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Surgery Alone Versus Surgery Followed by Chemotherapy and Radiotherapy in Resected Extrahepatic Bile Duct Cancer: Treatment Outcome Analysis of 336 Patients: Jung Ho Im, Jinsil Seong, Ik Jae Lee, Joon Seong Park, Dong Sup Yoon, Kyung Sik Kim, Woo Jung Lee, Kyung Ran Park; Cancer Res Treat. 2016;48(2):583-595. Published online July 22, 2015; DOI: https://doi.org/10.4143/crt.2015.091

Abstract PDF PubReader ePub

Purpose
This study analyzed the outcomes of patients with resected extrahepatic bile duct cancer (EHBDC) in order to clarify the role of adjuvant treatments in these patients.
Materials and Methods
A total of 336 patients with EHBDC who underwent curative resection between 2001 and 2010 were analyzed retrospectively. The treatment types were as follows: surgery alone (n=168), surgery with chemotherapy (CTx, n=90), surgery with radiotherapy (RT) alone (n=29), and surgery with chemoradiotherapy (CRT, n=49).
Results
The median follow-up period was 63 months. The 5-year rates of locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) for all patients were 56.5%, 59.7%, 36.6%, and 42.0%, respectively. In multivariate analysis, surgery with RT and CRT was a significant prognostic factor for LRFFS, and surgery with CTx was a significant prognostic factor for DMFS, and surgery with CTx, RT, and CRT was a significant prognostic factor for PFS (p < 0.05). Surgery with CTx and CRT showed association with superior OS (p < 0.05), and surgery with RT had marginal significance (p=0.078). In multivariate analysis of the R1 resection patients, surgery with CRT showed significant association with OS (p < 0.05).
Conclusion
Adjuvant RT and CTx may be helpful in improving clinical outcomes of patients with resected EHBDC who have a high risk of disease recurrence, particularly R1 resection patients. Conduct of additional prospective, larger-scale studies will be required in order to confirm the benefit of adjuvant RT and CTx in these patients.

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Clinical Benefit of Hepatic Arterial Infusion Concurrent Chemoradiotherapy in Locally Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis: Hong In Yoon, Ki Jun Song, Ik Jae Lee, Do Young Kim, Kwang-Hyub Han, Jinsil Seong; Cancer Res Treat. 2016;48(1):190-197. Published online March 5, 2015; DOI: https://doi.org/10.4143/crt.2014.276

Abstract PDF PubReader ePub

Purpose
The aim of this study was to evaluate whether hepatic arterial infusion concurrent chemoradiotherapy (CCRT) could improve overall survival (OS) in patients with locally advanced hepatocellular carcinoma (LAHCC). Materials and Methods Two databases were reviewed from Yonsei Cancer Center (YCC) and Korean Liver Cancer Study Group (KLCSG) nationwide multi-center hepatocellular carcinoma (HCC) cohort. The CCRT group included 106 patients, with stage III-IV, Child-Pugh classification A, Eastern Cooperative Oncology Group performance status 0 or 1, who underwent definitive CCRT as the initial treatment at YCC. We used propensity score matching to adjust for seven clinical factors, including age, tumor size, TNM stage by the Liver Cancer Study Group of Japan, T stage, Barcelona Clinic Liver Cancer (BCLC) staging system, etiology of HCC, and portal vein invasion, which all differed significantly in the two databases. From the KLCSG cohort enrolled at 32 institutions, 106 patients for the non-CCRT group were defined. Results After propensity score matching, all patient characteristics were balanced between the two groups. The CCRT group had better OS (median, 11.4) than the non-CCRT group (6.6 months; p=0.02). In multivariate analyses for all patients, CCRT (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.11 to 1.97; p=0.007), tumor size (HR, 1.08; 95% CI, 1.04 to 1.12; p < 0.001), and BCLC stage (HR, 0.54; 95% CI, 0.36 to 0.8; p=0.003) were independent prognostic factors for OS. Conclusion CCRT showed better OS for LAHCC patients. In LAHCC patients with a good performance and normal liver function, CCRT could be a feasible treatment option. All of these findings need to be validated in prospective clinical trials.

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Liver-Directed Concurrent Chemoradiotherapy versus Sorafenib in Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis
Jina Kim, Hwa Kyung Byun, Tae Hyung Kim, Sun Il Kim, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Jinsil Seong
Cancers.2022; 14(10): 2396. CrossRef
Selection Strategy of Chemoradiotherapy in Patients with Unoperated Hepatocellular Carcinoma
华温
Advances in Clinical Medicine.2022; 12(08): 7520. CrossRef
Progress in Transformation Therapy of Hepatocellular Carcinoma with Portal Vein Cancer Thrombus
雍博周
Advances in Clinical Medicine.2022; 12(12): 11521. CrossRef
Efficacy and Safety of Liver-Directed Concurrent Chemoradiotherapy and Sequential Sorafenib for Advanced Hepatocellular Carcinoma: A Prospective Phase 2 Trial
Beom Kyung Kim, Do Young Kim, Hwa Kyung Byun, Hye Jin Choi, Seung-Hoon Beom, Hye Won Lee, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Jinsil Seong, Kwang-Hyub Han
International Journal of Radiation Oncology*Biology*Physics.2020; 107(1): 106. CrossRef
Successful palliative radiation therapy for hemobilia and obstructive jaundice due to bile duct invasion of hepatocellular carcinoma: a case report
Shinya Endo, Shinya Kawaguchi, Kazuhisa Asahara, Ryosuke Itai, Shuzo Terada, Naofumi Shirane, Kengo Kuriyama
Kanzo.2020; 61(9): 447. CrossRef
Dose escalation by intensity modulated radiotherapy in liver-directed concurrent chemoradiotherapy for locally advanced BCLC stage C hepatocellular carcinoma
Hwa Kyung Byun, Hyun Ju Kim, Yoo Ri Im, Do Young Kim, Kwang-Hyub Han, Jinsil Seong
Radiotherapy and Oncology.2019; 133: 1. CrossRef
Strategic application of radiotherapy for hepatocellular carcinoma
Seo Hee Choi, Jinsil Seong
Clinical and Molecular Hepatology.2018; 24(2): 114. CrossRef
Factors affecting survival after concurrent chemoradiation therapy for advanced hepatocellular carcinoma: a retrospective study
Ja Kyung Kim, Jun Won Kim, Ik Jae Lee, Seung-Moon Joo, Kwang-Hun Lee, Eun-Suk Cho, Jeong-Sik Yu, Tae Joo Jeon, Yonsoo Kim, Jung Il Lee, Kwan Sik Lee
Radiation Oncology.2017;[Epub] CrossRef
Transarterial Radioembolization Versus Concurrent Chemoradiation Therapy for Locally Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis
Jeong Eun Song, Kyu Sik Jung, Do Young Kim, Kijun Song, Jong Yun Won, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Jinsil Seong, Kwang-Hyub Han
International Journal of Radiation Oncology*Biology*Physics.2017; 99(2): 396. CrossRef
Conditional survival estimate in patients with Barcelona Clinic Liver Cancer stage B/C hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy with/without concurrent radiotherapy
In Rae Cho, Hye Won Lee, Ki Jun Song, Beom Kyung Kim, Seung Up Kim, Do Young Kim, Sang Hoon Ahn, Jinsil Seong, Kwang-Hyub Han, Jun Yong Park
Oncotarget.2017; 8(45): 79914. CrossRef
Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis
Jeong Il Yu, Hee Chul Park
World Journal of Gastroenterology.2016; 22(30): 6851. CrossRef
The effect of radiotherapy in liver-confined but non-resectable Barcelona Clinic Liver Cancer stage C large hepatocellular carcinoma
Hong In Yoon, Inkyung Jung, Kwang-Hyub Han, Jinsil Seong
Oncotarget.2016; 7(38): 62715. CrossRef
Prognostic Significance of18F-FDG Uptake in Hepatocellular Carcinoma Treated with Transarterial Chemoembolization or Concurrent Chemoradiotherapy: A Multicenter Retrospective Cohort Study
Jeong Won Lee, Jin Kyoung Oh, Yong An Chung, Sae Jung Na, Seung Hyup Hyun, Il Ki Hong, Jae Seon Eo, Bong-Il Song, Tae-sung Kim, Do Young Kim, Seung Up Kim, Dae Hyuk Moon, Jong Doo Lee, Mijin Yun
Journal of Nuclear Medicine.2016; 57(4): 509. CrossRef

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Multicenter Validation Study of a Prognostic Index for Portal Vein Tumor Thrombosis in Hepatocellular Carcinoma: Jeong Il Yu, Sang Min Yoon, Hee Chul Park, Jong Hoon Kim, Tae Hyun Kim, Joong-Won Park, Jinsil Seong, Ik Jae Lee, Hong Seok Jang, Chul Seung Kay, Chul Yong Kim, Eui Kyu Chie, Jin Hee Kim, Mi-Sook Kim, Young Min Choi; Cancer Res Treat. 2014;46(4):348-357. Published online July 16, 2014; DOI: https://doi.org/10.4143/crt.2013.142

Abstract PDF PubReader ePub

Purpose
We previously reported on a staging system and prognostic index (PITH) for portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) patients treated with radiotherapy (RT) at a single institution. The aim of this study is to validate the PITH staging system using data from patients at other institutions and to compare it with other published staging systems. Materials and Methods A total of 994 HCC patients with PVTT who were treated with RT between 1998 and 2011 by the Korean Radiation Oncology Group were analyzed retrospectively. All patients were staged using the Cancer of the Liver Italian Program (CLIP), Japanese Integrated Staging (JIS), Okuda, and PITH staging systems, and survival data were analyzed. The likelihood ratio, Akaike information criteria (AIC), time-dependent receiver operating characteristics, and prediction error curve analysis were used to determine discriminatory ability for comparison of staging systems. Results The median survival was 9.2 months. Compared with the other staging systems, the PITH score gave the highest values for likelihood ratio and lowest AIC values, demonstrating that PITH may be a better prognostic model. Although the values were not significant and differences were not exceptional, the PITH score showed slightly better performance with respect to time-dependent area under curve and integrated Brier score of prediction error curve. Conclusion The PITH staging system was validated in this multicenter retrospective study and showed better stratification ability in HCC patients with PVTT than other systems.

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Efficacy and safety of radiotherapy combined with atezolizumab plus bevacizumab in treating hepatocellular carcinoma with portal vein tumour thrombus: a study protocol
Kang Wang, Hong-Ming Yu, Yan-Jun Xiang, Yu-Qiang Cheng, Qian-Zhi Ni, Wei-Xing Guo, Jie Shi, Shuang Feng, Jian Zhai, Shu-Qun Cheng
BMJ Open.2022; 12(12): e064688. CrossRef
Comparison of Transcatheter Arterial Chemoembolization-Radiofrequency Ablation and Transcatheter Arterial Chemoembolization Alone for Advanced Hepatocellular Carcinoma with Macrovascular Invasion Using Propensity Score Analysis: A Retrospective Cohort Stu
Yao Liu, Yuxin Li, Fangyuan Gao, Qun Zhang, Xue Yang, Bingbing Zhu, Shuaishuai Niu, Yunyi Huang, Ying Hu, Wei Li, Xianbo Wang
Journal of Oncology.2020; 2020: 1. 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
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Korean Journal of Radiology.2019; 20(7): 1042. CrossRef
Outcome of transarterial chemoembolization in Egyptian patients with hepatocellular carcinoma and branch portal vein thrombosis
H. Abdella, M. K. Shaker, Iman Fawzy Montasser, M. Sobhi, H. Aly, A. Sayed, S. Saleh, A. El Dorry
Indian Journal of Gastroenterology.2018; 37(2): 127. CrossRef
Strategic application of radiotherapy for hepatocellular carcinoma
Seo Hee Choi, Jinsil Seong
Clinical and Molecular Hepatology.2018; 24(2): 114. CrossRef
Proton therapy for hepatocellular carcinoma: Current knowledges and future perspectives
Gyu Sang Yoo, Jeong Il Yu, Hee Chul Park
World Journal of Gastroenterology.2018; 24(28): 3090. CrossRef
Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis
Jeong Il Yu, Hee Chul Park
World Journal of Gastroenterology.2016; 22(30): 6851. CrossRef
Radiotherapy for liver tumors
Florence K Keane, Shyam K Tanguturi, Andrew X Zhu, Laura A Dawson, Theodore S Hong
Hepatic Oncology.2015; 2(2): 133. CrossRef
New perspectives on the management of hepatocellular carcinoma with portal vein thrombosis
Hyun Young Woo, Jeong Heo
Clinical and Molecular Hepatology.2015; 21(2): 115. CrossRef
Current management of hepatocellular carcinoma: An Eastern perspective
Hyung Joon Yim
World Journal of Gastroenterology.2015; 21(13): 3826. CrossRef
Portal vein thrombosis: What is new?
María del Carmen Manzano-Robleda, Beatriz Barranco-Fragoso, Misael Uribe, Nahum Méndez-Sánchez
Annals of Hepatology.2015; 14(1): 20. CrossRef

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Effect of Oral Supplementation with Branched-chain Amino Acid (BCAA) during Radiotherapy in Patients with Hepatocellular Carcinoma: A Double-Blind Randomized Study: Ik Jae Lee, Jinsil Seong, Jung Im Bae, Sei Hwan You, Yumie Rhee, Jong Ho Lee; Cancer Res Treat. 2011;43(1):24-31. Published online March 31, 2011; DOI: https://doi.org/10.4143/crt.2011.43.1.24

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PURPOSE
The present study evaluated whether oral supplementation with a branched-chain amino acid (BCAA) improves the biochemical and amino acid profiles of liver tumor patients undergoing radiotherapy.
MATERIALS AND METHODS
Patients were randomly assigned to one of 2 groups: a group given oral supplementation with BCAA granules (LIVACT granules; Samil Pharm Co., Korea, each granule containing L-isoleucine 952 mg, L-leucine 1,904 mg, and L-valine 1,144 mg) during radiotherapy, or a placebo group. Physical and biochemical examinations and measurements, including subjective symptoms, Child-Pugh class, body mass index, plasma albumin concentration, and plasma amino acid profiles were monitored.
RESULTS
Fifty were enrolled between November 2005 and November 2006. We also analyzed data from 37 hepatocellular carcinoma (HCC) patients in order to evaluate a more homogenous group. The two groups of patients were comparable in terms of age, gender, Child-Pugh score, and underlying hepatitis virus type. Serum albumin, total protein, liver enzymes, and cholesterol showed a tendency to increase in the BCAA group. In this group, the percentage of cases that reverted to normal serum albumin levels between 3 and 10 weeks after administration of BCAA was significantly higher (41.18%) than in the placebo group (p=0.043).
CONCLUSION
Oral supplementation with a BCAA preparation seems to help HCC patients undergoing radiotherapy by increasing the BCAA concentration.

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Clinical Significance of Apoptosis and p53 Protein Expression in Stage IIB Squamous Cell Carcinoma of the Cervix Treated with Radiotherapy Alone: Eun Ji Chung, Gwi Eon Kim, Jinsil Seong, Woo Ick Yang, Young Tae Kim, Chang Ok Suh; J Korean Cancer Assoc. 2000;32(3):638-646.

Abstract PDF: PURPOSE
The purpose was to investigate the spontaneous apoptotic index (SAI) and p53 protein expression and to identify the role of SAI and p53 protein positivity.
MATERIALS AND METHODS
Forty six patients with squamous cell carcinoma of the cervix, FIGO stage IIB, treated with curative radiotherapy alone between 1990 and 1993 were included in this study. Definitive radiotherapy including external beam and high-dose-rate brachytherapy was given. Pretreatment paraffin-embedded biopsy specimens of those patients were scored for apoptosis and p53 protein expression using mouse mondegrees Clonal antibody (DO-7) by immuno staining. Clinicopathologic characteristics were also studied in relation to SAI and p53 protein expression, and as prognostic factors for clinical outcome.
RESULTS
SAI and p53 were not related to any clinical characteristics. The range of the SAI was 0.2~4.7% (median 1.1%, mean 1.5%). The rate of p53 protein expression was 65.2% (30/46). Patients whose tumors had high SAI and low p53 protein positivity had better treatment outcome than those with lower SAI. There was also a significant correlation between the SAI and p53 protein expression.
CONCLUSION
The pretreatment SAI and p53 oncoprotein expression are clinically useful in predicting the clinical outcome of FIGO stage IIB squamous cell carcinoma of the uterine cervix patients treated with definitive radiotherapy.

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Efficacy of Local Radiotherapy as a Salvage Modality for Hepatocellular Carcinoma Which is Refractory to TACE ( Transcatheter Arterial Chemoembolization ): Hee Chul Park, Jinsil Seong, John Jihoon Lim, Gwi Eon Kim, Kwang Hyub Han, Chae Yoon Chon, Young Myoung Moon, Do Yun Lee, Jong Tae Lee, Chang Ok Suh; J Korean Cancer Assoc. 2000;32(1):220-228.

Abstract: PURPOSE
Transcatheter arterial chemoembolization (TACE) has been actively performed for the treatment of unresectable or inoperable hepatocellular carcinoma. However, for the patients with treatment failure after TACE, few options are available for salvage. The purpose of this study was to investigate the efficacy of local radiotherapy as a salvage moda- lity for treatment failure after TACE.
MATERIALS AND METHODS
From January 1993 to December 1997, 27 patients were included in this study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Childs class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Mean tumor size was 7.2+/- 2.9 cm. Liver cirrhosis was associated in 10 patients. Portal vein thrombosis was presented in 5 patients. Serum alpha-fetoprotein was positive in 8 patients. According to VICC staging, the number of patients in III and IVA were 17 and 10, respectively. Treatment failure to TACE was evaluated by CT scan and angiography. Radiotherapy was given to the field including tumor with generous margin using 10-MV X-ray. Mean tumor dose was 51.8+-7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on CT scans 4~6 weeks following completion of treatment.
RESULTS
An objective response was observed in 16 of 24 patients who were possible to be evaluated, giving a response rate of 66.7%. Survival rates after salvage radiotherapy at 1, 2, 3 years were 55.9%, 35.7%, and 21.4%, respectively. The median survival was 14 months. Six patients among responders are surviving at present. Acute toxicity included G1 elevation of AST/ALT in 4 patients, G2 thrombocytopenia in 2, G2 hyperbilirubinemia in 5, and G2 hypoalbuminemia in 3. During follow-up, 4 patients developed ascites. At 6 months after treatment, gastric ulcers and duodenal ulcer were developed in 2 and 1 patient, respectively.
CONCLUSION
Local radiotherapy for treatment failure after TACE in hepatocellular carci- noma appears to be a feasible and effective salvage modality. It gives a 66.7% response rate with a median survival of 14 months. Acute toxicity was self-limiting and manageable. Gastric and duodenal ulcer were significant toxicities after treatment. Further studies are required to find optimal methods of radiotherapy to minimize toxicity.

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Strain - Specific Differences in Radiation - Induced Apoptosis in Murine Tissues: Jinsil Seong, Sung Hee Kim, Won Jae Lee, Chang Ok Suh, Jin Sik Min; J Korean Cancer Assoc. 1998;30(6):1259-1268.

Abstract PDF: PURPOSE
To characterize strain-specific differences in radiation response in murine tissues with different radiosensitivity.
MATERIALS AND METHODS
Six-week old male mice of 2 strains, C57Bl/6J and C3H/HeJ, were given whole body gamma-radiation with a single dose of 10 or 25 Gy. At different times after irradiation, mice were killed and tissues with different radiosensitivity, thymus and liver, were collected. Each tissue sample was stained with hematoxylin and eosin and apoptotic cells were scored. Expression of p53, Bcl-2, Bcl-x, and Bax was analysed by western blotting and densitometry.
RESULTS
Radiation induced massive apoptosis in thymus with a peak level at 8 h after radiation. With 10 Gy irradiation, apoptotic indices in C57Bl/6J and C3H/HeJ were 81.0 2.5% and 59.4 4.0%, respectively (p<0.05). Radiation upregulated the expression of p53, Bcl-x, and Bax, but not Bcl-2; p53 with a peak level of 2.5 fold (C57Bl/6J) and 1.4 fold (C3H/HeJ) at 4 h, Bax with a peak level of 2.6 fold (C57Bl/6J) and 1.3 fold (C3H/HeJ) at 8 h, and Bcl-x with a peak level of 11.1 fold (C57Bl/6J) and 8.2 fold (C3H/HeJ) at 8 h after radiation. In liver, however, radiation-induced apoptosis was minimal (peak apoptotic index of 2.1% in C57Bl/6J and 1.7% in C3H/HeJ). None of p53, Bcl-2, Bcl-x, and Bax was significantly increased.
CONCLUSIONS
Induction of apoptosis and regulation of related genes by radiation were tissue specific. Strain difference of radiation-induced apoptosis was well coupled with theinduction of related genes in thymus, a radiosensitive tissue. This study shows that quantitative difference of radiation induced apoptosis by strain is regulated at the gene level with the involvement of multiple genes.

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