Cancer Research and Treatment

Original Articles

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 [Epub ahead of print]

Abstract PDF Supplementary Material: 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 59 consecutive patients with inoperable EHCC treated with PBT. The median prescribed dose of PBT was 50 GyE (range, 45 to 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 PFS 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 freedom from local progression (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 to 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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General

Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients: Wonyoung Choi, Yun-Hee Kim, Sang Myung Woo, Yebeen Yu, Mi Rim Lee, Woo Jin Lee, Jung Won Chun, Sung Hoon Sim, Heejung Chae, Hyoeun Shim, Keun Seok Lee, Sun-Young Kong; Cancer Res Treat. 2023;55(4):1077-1086. Published online June 12, 2023; DOI: https://doi.org/10.4143/crt.2022.1630

Abstract PDF Supplementary Material PubReader ePub

Purpose
Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions.
Materials and Methods
Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients.
Results
We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients.
Conclusion
Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

Citations

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The use of patient-derived xenografts and patient-derived organoids in the search for new therapeutic regimens for pancreatic carcinoma. A review
Emin Gayibov, Tomáš Sychra, Alžběta Spálenková, Pavel Souček, Martin Oliverius
Biomedicine & Pharmacotherapy.2025; 182: 117750. CrossRef
Precision Medicine for Peritoneal Carcinomatosis—Current Advances in Organoid Drug Testing and Clinical Applicability
Harleen Kaur, Josephine A. Wright, Daniel L. Worthley, Elizabeth Murphy, Susan L. Woods
Organoids.2025; 4(1): 2. CrossRef
Three-dimensional models: from cell culture to Patient-Derived Organoid and its application to future liposarcoma research
SAYUMI TAHARA, SYDNEY RENTSCH, FERNANDA COSTAS CASAL DE FARIA, PATRICIA SARCHET, ROMA KARNA, RAPHAEL E. POLLOCK, FEDERICA CALORE
Oncology Research.2025; 33(1): 1. CrossRef
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Cell Reports Medicine.2024; 5(3): 101461. CrossRef
Establishment and Advancement of Pancreatic Organoids
Dong Hyeon Lee
Keimyung Medical Journal.2024; 43(1): 3. CrossRef
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Xuekai Hu, Jiayun Wei, Pinyan Liu, Qiuxia Zheng, Yue Zhang, Qichen Zhang, Jia Yao, Jingman Ni
Cell & Bioscience.2024;[Epub] CrossRef
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Ling-Feng Zhou, Hui-Yan Liao, Yang Han, Yang Zhao
Journal of Translational Medicine.2024;[Epub] CrossRef
The pros and cons of mechanical dissociation and enzymatic digestion in patient-derived organoid cultures for solid tumor
Jing Ren, Mengli Liu, Mingjie Rong, Xuan Zhang, Gang Wang, Yihan Liu, Haijun Li, Shichao Duan
Cell Organoid.2024;[Epub] CrossRef
Organoid: Bridging the gap between basic research and clinical practice
Guihu Weng, Jinxin Tao, Yueze Liu, Jiangdong Qiu, Dan Su, Ruobing Wang, Wenhao Luo, Taiping Zhang
Cancer Letters.2023; 572: 216353. CrossRef

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Gastrointestinal cancer

Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma: Kum Hei Ryu, Sunhwa Park, Jung Won Chun, Eunhae Cho, Jongmun Choi, Dong-Eun Lee, Hyoeun Shim, Yun-Hee Kim, Sung-Sik Han, Sang-Jae Park, Sang Myung Woo, Sun-Young Kong; Cancer Res Treat. 2023;55(4):1303-1312. Published online April 3, 2023; DOI: https://doi.org/10.4143/crt.2023.291

Abstract PDF Supplementary Material PubReader ePub

Purpose
The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC.
Materials and Methods
Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed.
Results
PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035).
Conclusion
Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

Citations

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Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2025; 1871(3): 167673. CrossRef
Mutant KRAS and GATA6 Stratify Survival in Patients Treated with Chemotherapy for Pancreatic Adenocarcinoma: A Prospective Cohort Study
Jung Won Chun, Dong-eun Lee, Nayoung Han, SooBeen Heo, Hyeji Kim, Mi Rim Lee, Hyeong Min Park, Sung-Sik Han, Sang-Jae Park, Tae Hyun Kim, Woo Jin Lee, Yun-Hee Kim, Sun-Young Kong, Sang Myung Woo
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Laboratory Investigation.2024; 104(9): 102107. CrossRef
Clinical Significance of PALB2 Pathogenic Germline Variant
Min-Chae Kang, R.N., Jong Eun Park, Mi-Ae Jang, Dongju Won, Boyoung Park, Seeyoun Lee, Dong Ock Lee, Kum Hei Ryu, Yoon-Jung Chang, Sun-Young Kong
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Jong Eun Park, Min-Chae Kang, Taeheon Lee, Eun Hye Cho, Mi-Ae Jang, Dongju Won, Boyoung Park, Chang-Seok Ki, Sun-Young Kong
Cancers.2024; 16(19): 3318. CrossRef
Understanding the Genetic Landscape of Pancreatic Ductal Adenocarcinoma to Support Personalized Medicine: A Systematic Review
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