Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-analysis Based on Individual Patient-Level Data of Randomized Trials: Jaewon Hyung, Minsu Kang, Ilhwan Kim, Kyu-pyo Kim, Baek-Yeol Ryoo, Jaekyung Cheon, Hyewon Ryu, Ji Sung Lee, Ji-Won Kim, In Sil Choi, Jin Hyun Park, Ghassan K. Abou-Alfa, Jin Won Kim, Changhoon Yoo; Cancer Res Treat. 2025;57(2):519-527. Published online October 17, 2024; DOI: https://doi.org/10.4143/crt.2024.652

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Purpose
While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head.
Materials and Methods
We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens.
Results
A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy.
Conclusion
Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

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Liposomal irinotecan for previously treated patients with biliary tract cancer: A pooled analysis of NIFTY and NALIRICC trials
Changhoon Yoo, Anna Saborowski, Jaewon Hyung, Patrick Wenzel, Ilhwan Kim, Henning Wege, Kyu-pyo Kim, Gunnar Folprecht, Baek-Yeol Ryoo, Phillip Schütt, Jaekyung Cheon, Thorsten Götze, Hyewon Ryu, Ji Sung Lee, Arndt Vogel
Journal of Hepatology.2025;[Epub] CrossRef

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A Single-Arm Phase II Study of Nab-Paclitaxel Plus Gemcitabine and Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer: Ting Liu, Qing Li, Zhen Lin, Chunhua Liu, Wei Pu, Shasha Zeng, Jun Lai, Xuebin Cai, Lisha Zhang, Shuyang Wang, Miao Chen, Wei Cao, Hongfeng Gou, Qing Zhu; Cancer Res Treat. 2024;56(2):602-615. Published online October 12, 2023; DOI: https://doi.org/10.4143/crt.2023.726

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Purpose
Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients.
Materials and Methods
Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m² nab-paclitaxel, 800 mg/m² gemcitabine, and 25 mg/m² cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy.
Results
After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients.
Conclusion
In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

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Combined Chemotherapy-Immunotherapy for Advanced Biliary Tract Cancer (BTC): A Clinical, Genomic, and Biomarker Analysis
Yong Zhang, Miaomiao Gou
Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
Efficacy and biomarker analysis of second‐line nab‐paclitaxel plus sintilimab in patients with advanced biliary tract cancer
Xiaofen Li, Nan Zhou, Yu Yang, Zijian Lu, Hongfeng Gou
Cancer Science.2024; 115(7): 2371. CrossRef

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ARID1A Mutation from Targeted Next-Generation Sequencing Predicts Primary Resistance to Gemcitabine and Cisplatin Chemotherapy in Advanced Biliary Tract Cancer: Sung Hwan Lee, Jaekyung Cheon, Seoyoung Lee, Beodeul Kang, Chan Kim, Hyo Sup Shim, Young Nyun Park, Sanghoon Jung, Sung Hoon Choi, Hye Jin Choi, Choong-kun Lee, Hong Jae Chon; Cancer Res Treat. 2023;55(4):1291-1302. Published online May 3, 2023; DOI: https://doi.org/10.4143/crt.2022.1450

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Purpose
There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC.
Materials and Methods
Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines.
Results
193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells.
Conclusion
Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

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Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer
Sohyun Hwang, Seonjeong Woo, Beodeul Kang, Haeyoun Kang, Jung Sun Kim, Sung Hwan Lee, Chang Il Kwon, Dong Soo Kyung, Hwang-Phill Kim, Gwangil Kim, Chan Kim, Hong Jae Chon
Journal of Hepatology.2025; 82(4): 649. CrossRef
The role of ARID1A in malignant neoplasms of the female reproductive system: a modern view on diagnostic and therapeutic opportunities
A. I. Marzaganova, I. R. Martirosyan, A. S. Korchemkina, E. G. Avanesyan, D. A. Korkmazova, O. B. Grakhnova, V. V. Akimina, A. P. Dzhamalutdinova, D. A. Bolloev, A. M. Dugulbgova, Z. G. Bakhmudova, A. T. Salikhova, P. A. Dzigora
Obstetrics, Gynecology and Reproduction.2025; 19(2): 282. CrossRef
Establishment and genomic profiling of cholangiocarcinoma cells with functional characterization
Rattanaporn Jaidee, Apinya Jusakul, Piman Pocasap, Veerapol Kukongviriyapan, Laddawan Senggunprai, Auemduan Prawan, Watcharin Loilome, Attapol Titapun, Apiwat Jareanrat, Vasin Thanasukarn, Natcha Khuntikeo, Nisana Namwat, Yaovalux Chamgramol, Malinee Than
Scientific Reports.2025;[Epub] CrossRef
Epidemiology and genomic features of biliary tract cancer and its unique features in Korea
Seonjeong Woo, Youngun Kim, Sohyun Hwang, Hong Jae Chon
Journal of Liver Cancer.2025; 25(1): 41. CrossRef
ARID1A in Gynecologic Precancers and Cancers
Jaida E. Morgan, Nishah Jaferi, Zainab Shonibare, Gloria S. Huang
Reproductive Sciences.2024; 31(8): 2150. CrossRef
Genomic analysis of bladder urothelial carcinoma with osteoclast‑like giant cells: A case report
Koji Kameyama, Kosuke Mizutani, Tetsuya Yamada, Seiji Sugiyama, Shingo Kamei, Shigeaki Yokoi, Kengo Matsunaga, Koseki Hirade, Yasutaka Kato, Hiroshi Nishihara, Satoshi Ishihara, Takashi Deguchi
Molecular and Clinical Oncology.2024;[Epub] CrossRef
A mutational signature and ARID1A mutation associated with outcome in hepatocellular carcinoma
Wei Zhou, Hao Chi, Xiaohu Zhao, Guangrong Tao, Jianhe Gan
Clinical and Translational Oncology.2024; 27(3): 1166. CrossRef
Advances in the study of the role of high-frequency mutant subunits of the SWI/SNF complex in tumors
Jiumei Zhao, Jing Zhu, Yu Tang, Kepu Zheng, Ziwei Li
Frontiers in Oncology.2024;[Epub] CrossRef

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Establishing Patient-Derived Cancer Cell Cultures and Xenografts in Biliary Tract Cancer: Jihoon Kang, Ji-Young Lee, Sunmin Lee, Danbee Kim, Jinyeong Lim, Ha Ra Jun, Seyeon Jeon, Young-Ae Kim, Hye Seon Park, Kyu-pyo Kim, Sung-Min Chun, Hee Jin Lee, Changhoon Yoo; Cancer Res Treat. 2023;55(1):219-230. Published online April 6, 2022; DOI: https://doi.org/10.4143/crt.2021.1166

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Purpose
Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC.
Materials and Methods
Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed.
Results
From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines.
Conclusion
We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.

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The importance of preclinical models for cholangiocarcinoma drug discovery
Felix J. Krendl, Florian Primavesi, Rupert Oberhuber, Daniel Neureiter, Matthias Ocker, Dino Bekric, Tobias Kiesslich, Christian Mayr
Expert Opinion on Drug Discovery.2025; 20(2): 205. CrossRef
Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience
Ruri Nishie, Tomohito Tanaka, Kensuke Hirosuna, Shunsuke Miyamoto, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Shoko Ueda, Natsuko Morita, Sousuke Hashida, Atsushi Daimon, Shinichi Terada, Hiroshi Maruoka, Hiromi Konishi, Yuhei Kogata, Kohei Tan
Journal of Clinical Medicine.2024; 13(9): 2718. CrossRef

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Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer: Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh; Cancer Res Treat. 2022;54(2):541-553. Published online August 6, 2021; DOI: https://doi.org/10.4143/crt.2021.473

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Purpose
Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC.
Materials and Methods
We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments.
Results
In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug.
Conclusion
This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.

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WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation
Anling Chen, Ke Yin, Yu Liu, Lei Hu, Qianwen Cui, Xiaofeng Wan, Wulin Yang
Current Cancer Drug Targets.2025; 25(4): 370. CrossRef
WEE1 inhibition in cancer therapy: Mechanisms, synergies, preclinical insights, and clinical trials
Krishnapriya Thangaretnam, Md Obaidul Islam, Jialun Lv, Ahmed El-Rifai, Ava Perloff, Houda L. Soutto, Dunfa Peng, Zheng Chen
Critical Reviews in Oncology/Hematology.2025; 211: 104710. CrossRef
Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma
Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller, Arne Kandulski
Cancers.2024; 16(9): 1690. CrossRef
Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
Frontiers in Oncology.2024;[Epub] CrossRef
Update on Combination Strategies of PARP Inhibitors
Zhuoqun Lin, Lingfang Wang, Ziyu Xing, Fenfen Wang, Xiaodong Cheng
Cancer Control.2024;[Epub] CrossRef
The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer
Deqian Xie, Bowen Jiang, Shijin Wang, Qifei Wang, Guangzhen Wu
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives
Öykü Gönül Geyik, Giulia Anichini, Engin Ulukaya, Fabio Marra, Chiara Raggi
Cells.2022; 11(9): 1463. CrossRef
Targeted Therapy of HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy between CDK4/6, PI3K and Sometimes FGFR Inhibitors, but Rarely between PARP and WEE1 Inhibitors
Ourania N. Kostopoulou, Mark Zupancic, Mariona Pont, Emma Papin, Monika Lukoseviciute, Borja Agirre Mikelarena, Stefan Holzhauser, Tina Dalianis
Viruses.2022; 14(7): 1372. CrossRef
Targeted Therapy with PI3K, PARP, and WEE1 Inhibitors and Radiotherapy in HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy while Effects with APR-246 Are Limited
Karin Byskata, Monika Lukoseviciute, Filippo Tuti, Mark Zupancic, Ourania N. Kostopoulou, Stefan Holzhauser, Tina Dalianis
Cancers.2022; 15(1): 93. CrossRef

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Comparison of the Prognostic Value of Platelet-Related Indices in Biliary Tract Cancer Undergoing Surgical Resection: Lejia Sun, Yuxi Wei, Yang Chen, Wenmo Hu, Xin Ji, Haifeng Xu, Shunda Du, Haitao Zhao, Xin Lu, Xinting Sang, Shouxian Zhong, Huayu Yang, Yilei Mao; Cancer Res Treat. 2021;53(2):528-540. Published online November 23, 2020; DOI: https://doi.org/10.4143/crt.2020.833

Abstract PDF Supplementary Material PubReader ePub

Purpose
Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection.
Materials and Methods
Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model.
Results
MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power.
Conclusion
MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

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Predictive value of platelet count-related ratios for severity in biliary Escherichia coli and Klebsiella pneumonia bloodstream infections
Peng Zhou, Xiemin Wang, Linfang Deng, Shixiao Li
European Journal of Clinical Microbiology & Infectious Diseases.2025;[Epub] CrossRef
Mean platelet volume/platelet count ratio in combination with tumor markers in colorectal cancer: a retrospective clinical study
Huan Zhang, Fan Lin, Zhuocai Wang
BMC Cancer.2023;[Epub] CrossRef
Thrombocytopenia as an important determinant of poor prognosis in patients with pyogenic liver abscess: a retrospective case series
Sheng-zhong Li, Shao-hua Liu, Meng Hao, Tian Yu, Song Hu, Li Liu, Zhe-long Liu
Frontiers in Surgery.2023;[Epub] CrossRef
Prognostic value of platelet count-related ratios on admission in patients with pyogenic liver abscess
Shixiao Li, Sufei Yu, Jiajia Qin, Minfei Peng, Jiao Qian, Peng Zhou
BMC Infectious Diseases.2022;[Epub] CrossRef

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Targeting Hypoxia Using Evofosfamide and Companion Hypoxia Imaging of FMISO-PET in Advanced Biliary Tract Cancer: Jeesun Yoon, Seo Young Kang, Kyung-Hun Lee, Gi Jeong Cheon, Do-Youn Oh; Cancer Res Treat. 2021;53(2):471-479. Published online October 22, 2020; DOI: https://doi.org/10.4143/crt.2020.577

Abstract PDF Supplementary Material PubReader ePub

Purpose
Hypoxia is widely known as one of the mechanisms of chemoresistance and as an environmental condition which triggers invasion and metastasis of cancer. Evofosfamide is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard conjugated with 2-nitroimidazole. Biliary tract cancer (BTC) is known to contain large hypoxic area. This study evaluated the efficacy and safety of evofosfamide as a second-line treatment of advanced BTC.
Materials and Methods
Patients received evofosfamide at a dose of 340 mg/m² on days 1, 8, and 15 of every 28-day cycle. Primary end-point was progression-free survival (PFS) rate at 4-months (4m-PFSR). Secondary end-points included overall survival (OS), PFS, disease control rate (DCR), metabolic response by ¹⁸F-fluorodeoxyglucose positron emission tomography (PET), hypoxic parameters evaluated by ¹⁸F-fluoromisonidazole (FMISO) PET and toxicity.
Results
Twenty patients were treated with evofosfamide, with 16 response-evaluable patients. There was no objective response; stable disease was observed in nine patients, with a DCR of 56.25%. 4m-PFSR was 40.6%. Median PFS was 3.60 months (95% confidence interval [CI], 1.68 to 5.52). Median OS was 6.37 months (95% CI, 3.94 to 8.79). Reduction of tumor metabolic activity was observed in eight of 15 patients (53.3%). High baseline hypoxic parameters were associated with poor PFS. Change of hypoxic parameters between pretreatment and post-treatment reflected hypoxic-activated drug response. There was no treatment-related death.
Conclusion
Evofosfamide as second-line treatment of advanced BTC showed acceptable safety and comparable efficacy to other agents. Changes in volumetric parameters measured with FMISO PET, showing the degree of tumor hypoxia, reflected the response to evofosfamide based on the mode of action.

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Hypoxia and intrinsic radiosensitivity: Exploring mechanisms in radiation resistance of cancers and biomarkers for enhanced treatment strategies
Elham Khakshour, Mohammad Amin Shahram, Reza Chaman, Hamed Shoorei, Elham Samami, James S. Welsh, Gaurav Dhawan, Seyed Alireza Javadinia, Hosein Azimian
Journal of Radiation Research and Applied Sciences.2025; 18(2): 101450. CrossRef
Functional Imaging of Hypoxia: PET and MRI
Ryan C. Perez, DaeHee Kim, Aaron W. P. Maxwell, Juan C. Camacho
Cancers.2023; 15(13): 3336. CrossRef
Phase Ib dose-escalation study of the hypoxia-modifier Myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors
Marcel A. Schneider, Michael Linecker, Ralph Fritsch, Urs J. Muehlematter, Daniel Stocker, Bernhard Pestalozzi, Panagiotis Samaras, Alexander Jetter, Philipp Kron, Henrik Petrowsky, Claude Nicolau, Jean-Marie Lehn, Bostjan Humar, Rolf Graf, Pierre-Alain C
Nature Communications.2021;[Epub] CrossRef

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Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3^- CD4⁺ T Cells in Biliary Tract Cancer: Hyung-Don Kim, Jwa Hoon Kim, Yeon-Mi Ryu, Danbee Kim, Sunmin Lee, Jaehoon Shin, Seung-Mo Hong, Ki-Hun Kim, Dong‐Hwan Jung, Gi‐Won Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Baek-Yeol Ryoo, Jae Ho Jeong, Kyu-pyo Kim, Sang-Yeob Kim, Changhoon Yoo; Cancer Res Treat. 2021;53(1):162-171. Published online August 31, 2020; DOI: https://doi.org/10.4143/crt.2020.704

Abstract PDF Supplementary Material PubReader ePub

Purpose
The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated.
Materials and Methods
A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core.
Results
The density of CD8⁺ T cells, FoxP3^- CD4⁺ helper T cells, and FoxP3⁺ CD4⁺ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8⁺ T cell and FoxP3^- CD4⁺ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3^-CD4⁺ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3^- CD4⁺ helper T cells in the tumor margin was independently associated with favorable PFS and OS.
Conclusion
The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3^-CD4⁺ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

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Infiltrating T lymphocytes and tumor microenvironment within cholangiocarcinoma: immune heterogeneity, intercellular communication, immune checkpoints
Yunyan Dai, Chenyang Dong, Zhiming Wang, Yunpeng Zhou, Yi Wang, Yi Hao, Pinggui Chen, Chaojie Liang, Gaopeng Li
Frontiers in Immunology.2025;[Epub] CrossRef
Advancing biliary tract malignancy treatment: emerging frontiers in cell-based therapies
Jianyang Ao, Mingtai Hu, Jinghan Wang, Xiaoqing Jiang
Frontiers in Immunology.2025;[Epub] CrossRef
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Zhiming Wang, Yunyan Dai, Yunpeng Zhou, Yi Wang, Pinggui Chen, Yaoxuan Li, Yunfei Zhang, Xiaocui Wang, Ying Hu, Haonan Li, Gaopeng Li, Yukai Jing
Frontiers in Immunology.2025;[Epub] CrossRef
Mapping of the T-cell Landscape of Biliary Tract Cancer Unravels Anatomic Subtype-Specific Heterogeneity
Jianhua Nie, Shuyuan Zhang, Ying Guo, Caiqi Liu, Jiaqi Shi, Haotian Wu, Ruisi Na, Yingjian Liang, Shan Yu, Fei Quan, Kun Liu, Mingwei Li, Meng Zhou, Ying Zhao, Xuehan Li, Shengnan Luo, Qian Zhang, Guangyu Wang, Yanqiao Zhang, Yuanfei Yao, Yun Xiao, Sheng
Cancer Research.2025; 85(4): 704. CrossRef
Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond
Zhaokai Zhou, Jiahui Wang, Jiaojiao Wang, Shuai Yang, Ruizhi Wang, Ge Zhang, Zhengrui Li, Run Shi, Zhan Wang, Qiong Lu
Molecular Cancer.2024;[Epub] CrossRef
Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma
Sijia Hua, Xinyi Gu, Hangbin Jin, Xiaofeng Zhang, Qiang Liu, Jianfeng Yang
Biomedicine & Pharmacotherapy.2024; 177: 117080. CrossRef
Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer
Luohang Ni, Jianing Xu, Quanpeng Li, Xianxiu Ge, Fei Wang, Xueting Deng, Lin Miao
Cancer Management and Research.2024; Volume 16: 941. CrossRef
Artificial Intelligence-Powered Spatial Analysis of Tumor-Infiltrating Lymphocytes as a Potential Biomarker for Immune Checkpoint Inhibitors in Patients with Biliary Tract Cancer
Yeong Hak Bang, Choong-kun Lee, Kyunghye Bang, Hyung-Don Kim, Kyu-pyo Kim, Jae Ho Jeong, Inkeun Park, Baek-Yeol Ryoo, Dong Ki Lee, Hye Jin Choi, Taek Chung, Seung Hyuck Jeon, Eui-Cheol Shin, Chiyoon Oum, Seulki Kim, Yoojoo Lim, Gahee Park, Chang Ho Ahn, T
Clinical Cancer Research.2024; 30(20): 4635. CrossRef
Prognostic value of tumor-infiltrating lymphocytes in distal extrahepatic bile duct carcinoma
S.-Y. Jun, S. An, S.-M. Hong, J.-Y. Kim, K.-P. Kim
ESMO Open.2024; 9(11): 103969. CrossRef
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Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer: Ah-Rong Nam, Mei-Hua Jin, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Do-Youn Oh, Yung-Jue Bang; Cancer Res Treat. 2020;52(3):945-956. Published online April 17, 2020; DOI: https://doi.org/10.4143/crt.2020.080

Abstract PDF Supplementary Material PubReader ePub

Purpose
Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC.
Materials and Methods
In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models.
Results
AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy.
Conclusion
Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

Citations

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Combination of S-1 and the oral ATR inhibitor ceralasertib is effective against pancreatic cancer cells
Yoshihito Morimoto, Kimihiko Takada, Ami Nakano, Osamu Takeuchi, Kazuhiro Watanabe, Masayoshi Hirohara, Yutaka Masuda
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ATR inhibitor AZD6738 increases the sensitivity of colorectal cancer cells to 5‑fluorouracil by inhibiting repair of DNA damage
Takuya Suzuki, Takahisa Hirokawa, Anri Maeda, Shinnosuke Harata, Kaori Watanabe, Takeshi Yanagita, Hajime Ushigome, Nozomi Nakai, Yuzo Maeda, Kazuyoshi Shiga, Ryo Ogawa, Akira Mitsui, Masahiro Kimura, Yoichi Matsuo, Hiroki Takahashi, Shuji Takiguchi
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Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer
Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
Cancer Research and Treatment.2022; 54(2): 541. CrossRef
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Targeting P53 as a Future Strategy to Overcome Gemcitabine Resistance in Biliary Tract Cancers
Chiao-En Wu, Yi-Ru Pan, Chun-Nan Yeh, John Lunec
Biomolecules.2020; 10(11): 1474. CrossRef

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Therapeutic Targeting of the DNA Damage Response Using an ATR Inhibitor in Biliary Tract Cancer: Ah-Rong Nam, Mei Hua Jin, Ji Eun Park, Ju-Hee Bang, Do-Youn Oh, Yung-Jue Bang; Cancer Res Treat. 2019;51(3):1167-1179. Published online December 3, 2018; DOI: https://doi.org/10.4143/crt.2018.526

Abstract PDF PubReader ePub

Purpose
The DNA damage response (DDR) is a multi-complex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints, and apoptosis. In the case of biliary tract cancer (BTC), the strategy of DDR targeting has not been evaluated, even though many patients have DNA repair pathway alterations. The purpose of this study was to test the DDR-targeting strategy in BTC using an ataxia-telangiectasia and Rad3-related (ATR) inhibitor.
Materials and Methods
A total of nine human BTC cell lines were used for evaluating anti-tumor effect of AZD6738 (ATR inhibitor) alone or combination with cytotoxic chemotherapeutic agents through MTT assay, colony-forming assays, cell cycle analyses, and comet assays. We established SNU478-mouse model for in vivo experiments to confirm our findings.
Results
Among nine human BTC cell lines, SNU478 and SNU869 were the most sensitive to AZD6738, and showed low expression of both ataxia-telangiectasia mutated (ATM) and p53. AZD6738 blocked p-Chk1 and p-glycoprotein and increased γH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis, G2/M arrest and p21, and decreased CDC2. Combinations of AZD6738 and cytotoxic chemotherapeutic agents exerted synergistic effects in colony-forming assays, cell cycle analyses, and comet assays. In our mouse models, AZD6738 monotherapy decreased tumor growth and the combination with cisplatin showed more potent effects on growth inhibition, decreased Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling than monotherapy with each drug.
Conclusion
In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC.

Citations

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Wenjun Wang, Yu Liu, Dong Chen, Jiajia Pang, Chunyu Lai, Mingbao Gu, Meilun Zhai, Qian Yu, Yang Wang, Xuanwen Bao, Yangyang Li, Xiaomeng Dai, Dong Chen, Peng Zhao, Jinghong Xu, Rui Lei
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DNA damage response mutations enhance the antitumor efficacy of ATR and PARP inhibitors in cholangiocarcinoma cell lines
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Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
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AZD6738 promotes the tumor suppressive effects of trifluridine in colorectal cancer cells
Shinnosuke Harata, Takuya Suzuki, Hiroki Takahashi, Takahisa Hirokawa, Akira Kato, Kaori Watanabe, Takeshi Yanagita, Hajime Ushigome, Kazuyoshi Shiga, Ryo Ogawa, Akira Mitsui, Masahiro Kimura, Yoichi Matsuo, Shuji Takiguchi
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Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer
Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
Cancer Research and Treatment.2022; 54(2): 541. CrossRef
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Öykü Gönül Geyik, Giulia Anichini, Engin Ulukaya, Fabio Marra, Chiara Raggi
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ATR inhibition amplifies antitumor effects of olaparib in biliary tract cancer
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Sofia Genta, Federica Martorana, Anastasios Stathis, Ilaria Colombo
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Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer
Ah-Rong Nam, Mei-Hua Jin, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Do-Youn Oh, Yung-Jue Bang
Cancer Research and Treatment.2020; 52(3): 945. CrossRef
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Targeting P53 as a Future Strategy to Overcome Gemcitabine Resistance in Biliary Tract Cancers
Chiao-En Wu, Yi-Ru Pan, Chun-Nan Yeh, John Lunec
Biomolecules.2020; 10(11): 1474. CrossRef
ATM Inhibitor Suppresses Gemcitabine-Resistant BTC Growth in a Polymerase θ Deficiency-Dependent Manner
Yi-Ru Pan, Chiao-En Wu, Chun-Nan Yeh
Biomolecules.2020; 10(11): 1529. CrossRef
The Cancer Stem Cell Inhibitor Napabucasin (BBI608) Shows General Cytotoxicity in Biliary Tract Cancer Cells and Reduces Cancer Stem Cell Characteristics
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Biochemical Pharmacology.2019; 164: 273. CrossRef

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Clinical Benefit of Maintenance Therapy for Advanced Biliary Tract Cancer Patients Showing No Progression after First-Line Gemcitabine Plus Cisplatin: Jaewon Hyung, Bumjun Kim, Changhoon Yoo, Kyo-pyo Kim, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo; Cancer Res Treat. 2019;51(3):901-909. Published online October 4, 2018; DOI: https://doi.org/10.4143/crt.2018.326

Abstract PDF Supplementary Material PubReader ePub

Purpose
Gemcitabine plus cisplatin (GemCis) is the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC). In ABC-02 study, the BTC patients received up to 6-8 cycles of 3-weekly GemCis; however, those without progression often receive more than 6-8 cycles. The clinical benefit of maintenance treatment in patients without progression is uncertain.
Materials and Methods
Advanced BTC patients treated with GemCis between April 2010 and February 2015 at Asan Medical Center, Seoul, Korea, were retrospectively analysed. The patients without progression after 6-8 cycles were stratified according to further treatment i.e., with or without further cycles of GemCis (maintenance vs. observation groups). The primary endpoint was overall survival (OS) and progression-free survival (PFS).
Results
Among the 740 BTC patients in the initial screen, 231 cases (31.2%) were eligible for analysis (111 in the observation group, 120 in the maintenance group). The median OS from the GemCis initiation was 20.5 months (95% confidence interval [CI], 15.4 to 25.6) and 22.4 months (95% CI, 17.0 to 27.8) in the observation and maintenance groups, respectively (p=0.162). The median PFS was 10.4 months (95% CI, 7.0 to 13.8) and 13.2 months (95% CI, 11.3 to 15.2), respectively (p=0.320).
Conclusions
GemCis maintenance is not associated with an improved survival outcome.

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Jab1 Silencing Inhibits Proliferation and Sensitizes to Cisplatin in Biliary Tract Cancer: Ah-Rong Nam, Ji-Won Kim, Ji Eun Park, Ju-Hee Bang, Mei Hua Jin, Do-Youn Oh, Yung-Jue Bang; Cancer Res Treat. 2019;51(3):886-900. Published online October 1, 2018; DOI: https://doi.org/10.4143/crt.2018.375

Abstract PDF Supplementary Material PubReader ePub

Purpose
Jab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied.
Materials and Methods
We performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC.
Results
Among 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and p27 expression.
Conclusion
Jab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.

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COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma
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Chunjue Yuan, Dong Wang, Guohong Liu, Yunbao Pan
International Journal of Clinical Oncology.2021; 26(7): 1159. CrossRef

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Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer: Changhoon Yoo, Boram Han, Hyeong Su Kim, Kyu-pyo Kim, Deokhoon Kim, Jae Ho Jeong, Jae-Lyun Lee, Tae Won Kim, Jung Han Kim, Dae Ro Choi, Hong Il Ha, Jinwon Seo, Heung-Moon Chang, Baek-Yeol Ryoo, Dae Young Zang; Cancer Res Treat. 2018;50(4):1324-1330. Published online January 8, 2018; DOI: https://doi.org/10.4143/crt.2017.526

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC.
Materials and Methods
Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m² oxaliplatin (day 1), 135 mg/m² irinotecan (day 1), and 40 mg/m² S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue.
Results
In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07).
Conclusion
OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.

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Chemotherapy versus Best Supportive Care in Advanced Biliary Tract Carcinoma: A Multi-institutional Propensity Score Matching Analysis: Jun Ho Ji, Young Saing Kim, Inkeun Park, Soon Il Lee, Rock Bum Kim, Joon Oh Park, Sung Yong Oh, In Gyu Hwang, Joung-Soon Jang, Haa-Na Song, Jung-Hun Kang; Cancer Res Treat. 2018;50(3):791-800. Published online August 23, 2017; DOI: https://doi.org/10.4143/crt.2017.044

Abstract PDF PubReader ePub

Purpose
Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients.
Materials and Methods
Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis.
Results
In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052).
Conclusion
Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.

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Observational Study of Best Supportive Care With or Without Oral Capecitabine in Patients With Metastatic Gallbladder Carcinoma at a Tertiary Center in India
Abhinav Srivastava, Shagun Misra, Neeraj Rastogi, Vishwas Kapoor, Shaleen Kumar
JCO Global Oncology.2025;[Epub] CrossRef
National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma
Faisal Saud Dar, Zaigham Abbas, Irfan Ahmed, Muhammad Atique, Usman Iqbal Aujla, Muhammad Azeemuddin, Zeba Aziz, Abu Bakar Hafeez Bhatti, Tariq Ali Bangash, Amna Subhan Butt, Osama Tariq Butt, Abdul Wahab Dogar, Javed Iqbal Farooqi, Faisal Hanif, Jahanzai
World Journal of Gastroenterology.2024; 30(9): 1018. CrossRef
Treatment patterns and survival in older adults with unresected nonmetastatic biliary tract cancers
Ali Belkouz, Elise de Savornin Lohman, Jyothi R. Thumma, Bas Groot Koerkamp, Philip R. de Reuver, Martijn G.H. van Oijen, Cornelis J.A. Punt, Hari Nathan, Heinz-Josef Klümpen
Journal of Geriatric Oncology.2023; 14(3): 101447. CrossRef
Main causes of death in advanced biliary tract cancer
Kana Kimura‐Seto, Yasushi Kojima, Shiori Komori, Yuya Hisada, Yuki Otake, Yuka Yanai, Akiko Saito, Naoki Akazawa, Yasuo Tanaka, Chizu Yokoi, Mikio Yanase, Junichi Akiyama, Natsuyo Yamamoto, Kazuhiko Yamada
Cancer Medicine.2023; 12(9): 10889. CrossRef
A Systematised Literature Review of Real-World Treatment Patterns and Outcomes in Unresectable Advanced or Metastatic Biliary Tract Cancer
Vivian Peirce, Michael Paskow, Lei Qin, Ruby Dadzie, Maria Rapoport, Samantha Prince, Sukhvinder Johal
Targeted Oncology.2023; 18(6): 837. CrossRef
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Clinical Epidemiology.2023; Volume 15: 1069. CrossRef

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Prognostic Factors and Scoring Model for Survival in Metastatic Biliary Tract Cancer: Hyung Soon Park, Ji Soo Park, You Jin Chun, Yun Ho Roh, Jieun Moon, Hong Jae Chon, Hye Jin Choi, Joon Seong Park, Dong Ki Lee, Se-Joon Lee, Dong Sup Yoon, Hei-Cheul Jeung; Cancer Res Treat. 2017;49(4):1127-1139. Published online February 6, 2017; DOI: https://doi.org/10.4143/crt.2016.538

Abstract PDF Supplementary Material PubReader ePub

Purpose
Metastatic biliary tract cancer (mBTC) has a dismal prognosis. In this study, an independent dataset of patients with mBTC was used to implement and validate a routine clinico-laboratory parameter-based scoring model for risk group identification.
Materials and Methods
From September 2006 to February 2015, 482 patients with mBTC were assigned randomly (ratio, 7:3) into investigational (n=340) and validation datasets (n=142). The continuous variables were dichotomized using a normal range or the best cutoff values determined using the Contal and O'Quigley statistical methods. Following a Cox’s proportional hazard model, the scoring model was derived by summing the rounded chi-square scores for the factors identified by multivariate analysis.
Results
The performance status (Eastern Cooperative Oncology Group 3-4), hypoalbuminemia (< 3.4 mg/dL), carcinoembryonic antigen (≥ 9 ng/mL), neutrophil-to-lymphocyte ratio (≥ 3.0), and carbohydrate antigen 19-9 (≥ 120 U/mL) were identified as independent prognosticators (Harrell’s C index, 0.682; integrated area under the curve, 0.653). Survival was clearly correlated with the risk groups (low, intermediate, and high, 14.0, 7.3, and 2.3 months, respectively; p < 0.001). The prognosis was also discriminative in the validation data set (median survival, 16.7, 7.5, and 1.9 months, respectively; p < 0.001). Chemotherapy did not offer any survival benefits for high-risk patients.
Conclusion
These proposed prognostic criteria for mBTC can facilitate accurate patient risk stratification and treatment-related decision-making.

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Ting Liu, Qing Li, Zhen Lin, Chunhua Liu, Wei Pu, Shasha Zeng, Jun Lai, Xuebin Cai, Lisha Zhang, Shuyang Wang, Miao Chen, Wei Cao, Hongfeng Gou, Qing Zhu
Cancer Research and Treatment.2024; 56(2): 602. CrossRef
Novel Prognostic Model Construction of Tongue Squamous Cell Carcinoma Based on Apigenin-Associated Genes
Jianfei Lai, Chen Fang, Guohua Zhang, Chao Shi, Feng Yu, Weiguo Gu, Jianxiong Deng, Jingbiao Xu, Chaoxing Liu, Feng Qiu
Frontiers in Bioscience-Landmark.2024;[Epub] CrossRef
Survival Analysis of 1140 Patients with Biliary Cancer and Benefit from Concurrent Renin-Angiotensin Antagonists, Statins, or Aspirin with Systemic Therapy
Valerie Gunchick, Rachel L McDevitt, Elizabeth Choi, Katherine Winslow, Mark M Zalupski, Vaibhav Sahai
The Oncologist.2023; 28(6): 531. CrossRef
Development of a nomogram to predict survival in advanced biliary tract cancer
Hiroshi Imaoka, Masafumi Ikeda, Shogo Nomura, Chigusa Morizane, Takuji Okusaka, Masato Ozaka, Satoshi Shimizu, Kentaro Yamazaki, Naohiro Okano, Kazuya Sugimori, Hirofumi Shirakawa, Nobumasa Mizuno, Sohei Satoi, Hironori Yamaguchi, Rie Sugimoto, Kunihito G
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Giulia Rovesti, Francesco Leone, Giovanni Brandi, Lorenzo Fornaro, Mario Scartozzi, Monica Niger, Changhoon Yoo, Francesco Caputo, Roberto Filippi, Mariaelena Casagrande, Nicola Silvestris, Daniele Santini, Luca Faloppi, Andrea Palloni, Massimo Aglietta,
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Clinical insights and prognostic factors from an advanced biliary tract cancer case series: a real-world analysis
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Clinical epidemiology of gallbladder cancer in North-Central India and association of immunological markers, NLR, MLR and PLR in the diagnostic/prognostic prediction of GBC
Jyotsna Singh, Durgesh Shukla, Sanjiv Gupta, Braj Raj Shrivastav, Pramod Kumar Tiwari
Cancer Treatment and Research Communications.2021; 28: 100431. CrossRef
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Sri Harsha Tella, Anuhya Kommalapati, Mitesh J Borad, Amit Mahipal
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Byung min Lee, Yeona Cho, Jun Won Kim, Hei Cheul Jeung, Ik Jae Lee
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Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef
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Yuko Suzuki, Motoyasu Kan, Gen Kimura, Kumiko Umemoto, Kazuo Watanabe, Mitsuhito Sasaki, Hideaki Takahashi, Yusuke Hashimoto, Hiroshi Imaoka, Izumi Ohno, Shuichi Mitsunaga, Masafumi Ikeda
Journal of Gastroenterology.2019; 54(3): 281. CrossRef
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CA19-9 or CEA Decline after the First Cycle of Treatment Predicts Survival in Advanced Biliary Tract Cancer Patients Treated with S-1 and Cisplatin Chemotherapy: Dae-Won Lee, Seock-Ah Im, Yu Jung Kim, Yaewon Yang, Jiyoung Rhee, Im Il Na, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, Yung-Jue Bang; Cancer Res Treat. 2017;49(3):807-815. Published online January 18, 2017; DOI: https://doi.org/10.4143/crt.2016.326

Abstract PDF PubReader ePub

Purpose
While tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) can aid in the diagnosis of biliary tract cancer, their prognostic role has not been clearly elucidated. Therefore, this study was conducted to evaluate the prognostic role of tumor markers and tumor marker change in patients with advanced biliary tract cancer.
Materials and Methods
Patients with pathologically proven metastatic or relapsed biliary tract cancer who were treated in a phase II trial of first-line S-1 and cisplatin chemotherapy were enrolled. Serum tumor markers were measured at baseline and after the first cycle of chemotherapy.
Results
Among a total of 104 patients, 80 (77%) had elevated baseline tumor markers (69 with CA 19-9 elevation and 40 with CEA). A decline ≥ 30% of the elevated tumor marker level after the first cycle of chemotherapy conferred an improved time to progression (TTP), overall survival (OS), and better chemotherapy response. Multivariate analysis revealed tumor marker decline as an independent positive prognostic factor of TTP (adjusted hazard ratio [HR], 0.44; p=0.003) and OS (adjusted HR, 0.37; p < 0.001). Subgroup analysis revealed similar results in each group of patients with CA 19-9 elevation and CEA elevation. In addition, elevated baseline CEA was associated with poor survival in both univariate and multivariate analysis.
Conclusion
Tumor marker decline was associated with improved survival in biliary tract cancer. Measuring tumor marker after the first cycle of chemotherapy can be used as an early assessment of treatment outcome.

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Clinical epidemiology of gallbladder cancer in North-Central India and association of immunological markers, NLR, MLR and PLR in the diagnostic/prognostic prediction of GBC
Jyotsna Singh, Durgesh Shukla, Sanjiv Gupta, Braj Raj Shrivastav, Pramod Kumar Tiwari
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Comparison of the Efficacy between Gemcitabine-Cisplatin and Capecitabine-Cisplatin Combination Chemotherapy for Advanced Biliary Tract Cancer: Jieun Lee, Tae Ho Hong, In Seok Lee, Young Kyoung You, Myung Ah Lee; Cancer Res Treat. 2015;47(2):259-265. Published online September 12, 2014; DOI: https://doi.org/10.4143/crt.2013.230

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Purpose
Gemcitabine-cisplatin combination chemotherapy has been regarded as standard regimen for advanced or metastatic biliary tract cancer (BTC), based on the ABC-02 trial. To date, however, no studies have compared the efficacies of gemcitabine-platinum and fluoropyrimidine- platinum combination chemotherapy, even though fluoropyrimidine has been widely used as a backbone agent for gastrointestinal cancer. This study compared the efficacy and toxicities of gemcitabine-cisplatin (GP) and capecitabine-cisplatin (XP) combination chemotherapy for treatment of advanced BTC. Materials and Methods We examined 49 patients treated with GP and 44 patients treated with XP from October 2009 to July 2012. All patients had unresectable BTC. The GP regimen comprised gemcitabine (1,000 mg/m2, intravenously [IV], days 1 and 8) and cisplatin (75 mg/m2, IV, day 1). The XP regimen comprised capecitabine (1,250 mg/m2 twice a day, peroral, days 1-14) and cisplatin (60 mg/m2, IV, day 1, every three weeks). We analyzed the response rate (RR), time to progression (TTP), overall survival (OS), and toxicity. Results The RRs were 27.3% and 6.1% in the XP and GP arms, respectively. XP resulted in longer TTP (5.2 months vs. 3.6 months, p=0.016), but OS was not statistically different (10.7 months vs. 8.6 months, p=0.365). Both regimens resulted in grade 3-4 hematologic toxicities, but febrile neutropenia was not noted. Grade 3-4 asthenia, stomatitis, and hand-foot syndrome occurred more frequently in the XP arm. Conclusion XP resulted in a superior TTP and RR compared to GP for treatment of advanced BTC, with comparable toxicity. Conduct of prospective large, randomized trials to evaluate the possibility of XP as another standard therapy is warranted.

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