Cancer Research and Treatment

Original Articles

Elimusertib, a Novel ATR Inhibitor, Induces Anti-Tumor Effects through Replication Catastrophe in Breast Cancers: Mudong Kim, Ahrum Min, Sohyeon Kim, Seongyeong Kim, Yu-jin Kim, Sujin Ham, Miso Lee, Eunice Yoojin Lee, Jinyong Kim, Dae-Won Lee, Kyung-Hun Lee, Seock-Ah Im; Received November 19, 2024 Accepted March 31, 2025 Published online April 7, 2025; DOI: https://doi.org/10.4143/crt.2024.1105 [Accepted]

Abstract PDF: Purpose
Sustained cell proliferation and cell cycle acceleration in cancer cells inherently increase DNA damage, which interferes with homeostatic replication and transcription. Ataxia telangiectasia and Rad3-related (ATR) is crucial for initiation of the DNA damage response, and ATR inhibitors, such as elimusertib, induce increased replication stress and DNA damage. We investigated the anti-tumor effects of elimusertib and its mechanism of action in relation to replication stress.
Materials and Methods
Anti-tumor effects were evaluated by MTT assay and colony formation assay in breast cancer cell lines in vitro, in breast cancer cell xenografts in vivo, and in patient-derived xenograft models. Cell cycle was assessed by flow cytometry and BrdU assay was used to measure replicating cells and S-phase progression. Alkaline and neutral comet assay was used to measure single and double stranded DNA damages, respectively.
Results
Elimusertib delayed S-phase progression in MDA-MB-453 and MDA-MB-231 cells and induced caspase-7-dependent apoptosis. Furthermore, the increase in sub-G1 population in the FACS analysis and Annexin V assay also confirmed apoptotic cell death. In the BrdU assay, single stranded DNA (ssDNA) increased in sensitive cells and aberrant ssDNA induced DNA damage in S-phase and eventually caused replication catastrophe. Finally, these anti-tumor effects were proven in in vivo xenograft and patient-derived xenograft models.
Conclusion
Elimusertib had anti-tumor effects and induced replication catastrophe in breast cancer cells with a high replication rate. Moreover, cells under high DNA replication stress were sensitive to elimusertib. Further studies and treatment strategies with elimusertib are warranted for cancers with a high replication rate.

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Breast cancer

Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Cancer Res Treat. 2025;57(2):443-456. Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296

Abstract PDF Supplementary Material PubReader ePub: Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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Review Article

Recent Developments in the Therapeutic Landscape of Advanced or Metastatic Hormone Receptor–Positive Breast Cancer: Eunice Yoojin Lee, Dae-Won Lee, Kyung-Hun Lee, Seock-Ah Im; Cancer Res Treat. 2023;55(4):1065-1076. Published online October 5, 2023; DOI: https://doi.org/10.4143/crt.2023.846

Abstract PDF PubReader ePub

Hormone receptor–positive (HR+) disease is the most frequently diagnosed subtype of breast cancer. Among tumor subtypes, natural course of HR+ breast cancer is indolent with favorable prognosis compared to other subtypes such as human epidermal growth factor protein 2–positive disease and triple-negative disease. HR+ tumors are dependent on steroid hormone signaling and endocrine therapy is the main treatment option. Recently, the discovery of cyclin-dependent kinase 4/6 inhibitors and their synergistic effects with endocrine therapy has dramatically improved treatment outcome of advanced HR+ breast cancer. The demonstrated efficacy of additional nonhormonal agents, such as targeted therapy against mammalian target of rapamycin and phosphatidylinositol 3-kinase signaling, poly(ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immunotherapeutic agents have further expanded the available therapeutic options. This article reviews the latest advancements in the treatment of HR+ breast cancer, and in doing so discusses not only the development of currently available treatment regimens but also emerging therapies that invite future research opportunities in the field.

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Breast Cancer and Tumor Microenvironment: The Crucial Role of Immune Cells
Tânia Moura, Paula Laranjeira, Olga Caramelo, Ana M. Gil, Artur Paiva
Current Oncology.2025; 32(3): 143. CrossRef
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Marion T. van Mackelenbergh, Michael Friedrich, Nicolai Maass
Die Gynäkologie.2025;[Epub] CrossRef
Therapies for the Treatment of Advanced/Metastatic Estrogen Receptor-Positive Breast Cancer: Current Situation and Future Directions
Rohan Kalyan Rej, Joyeeta Roy, Srinivasa Rao Allu
Cancers.2024; 16(3): 552. CrossRef

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Original Articles

Breast cancer

A Phase II Trial of S-1 and Oxaliplatin in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane (KCSG-BR07-03): Dae-Won Lee, Bhumsuk Keam, Keun Seok Lee, Jin-Hee Ahn, Joohyuk Sohn, Jin Seok Ahn, Moon Hee Lee, Jee Hyun Kim, Kyung Eun Lee, Hyo Jung Kim, Si-Young Kim, Yeon Hee Park, Chan-Young Ock, Kyung-Hun Lee, Sae-Won Han, Sung-Bae Kim, Young Hyuck Im, Hyun Cheol Chung, Do-Youn Oh, Seock-Ah Im; Cancer Res Treat. 2023;55(2):523-530. Published online November 8, 2022; DOI: https://doi.org/10.4143/crt.2022.1360

Abstract PDF PubReader ePub

Purpose
This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer.
Materials and Methods
Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events.
Results
A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%).
Conclusion
This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

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Unraveling the immune landscape and therapeutic biomarker PMEPA1 for oxaliplatin resistance in colorectal cancer: A comprehensive approach
Zhengguang Zhang, Tianming Lu, Zhe Zhang, Zixian Liu, Ruoning Qian, Ruogu Qi, Fuqiong Zhou, Min Li
Biochemical Pharmacology.2024; 222: 116117. CrossRef
Efficacy and safety of utidelone plus capecitabine in advanced first-line therapy for metastatic breast cancer: A multicenter real-world study
Pingping Bi, Xi Wang, Rui Liu, Xiuqin Li, Shanrong Wei, Jiawen Zhao, Xin Tan, Fan Zhang, Qing Mao, Ying Zhang, Baoyan Tang, Xueqiong Xun, Rong Guo, Kai Zheng, Shaoqiang Zhou, Shicong Tang
Surgery Open Science.2023; 16: 171. CrossRef

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General

Radiation Response Prediction Model Based on Integrated Clinical and Genomic Data Analysis: Bum-Sup Jang, Ji-Hyun Chang, Seung Hyuck Jeon, Myung Geun Song, Kyung-Hun Lee, Seock-Ah Im, Jong-Il Kim, Tae-You Kim, Eui Kyu Chie; Cancer Res Treat. 2022;54(2):383-395. Published online August 24, 2021; DOI: https://doi.org/10.4143/crt.2021.759

Abstract PDF Supplementary Material PubReader ePub

Purpose
The value of the genomic profiling by targeted gene-sequencing on radiation therapy response prediction was evaluated through integrated analysis including clinical information. Radiation response prediction model was constructed based on the analyzed findings.
Materials and Methods
Patients who had the tumor sequenced using institutional cancer panel after informed consent and received radiotherapy for the measurable disease served as the target cohort. Patients with irradiated tumor locally controlled for more than 6 months after radiotherapy were defined as the durable local control (DLC) group, otherwise, non-durable local control (NDLC) group. Significant genomic factors and domain knowledge were used to develop the Bayesian Network model to predict radiotherapy response.
Results
Altogether, 88 patients were collected for analysis. Of those, 41 (43.6%) and 47 (54.4%) patients were classified as the NDLC and DLC group, respectively. Somatic mutations of NOTCH2 and BCL were enriched in the NDLC group, whereas, mutations of CHEK2, MSH2, and NOTCH1 were more frequently found in the DLC group. Altered DNA repair pathway was associated with better local failure–free survival (hazard ratio, 0.40; 95% confidence interval, 0.19 to 0.86; p=0.014). Smoking somatic signature was found more frequently in the DLC group. Area under the receiver operating characteristic curve of the Bayesian network model predicting probability of 6-month local control was 0.83.
Conclusion
Durable radiation response was associated with alterations of DNA repair pathway and smoking somatic signature. Bayesian network model could provide helpful insights for high precision radiotherapy. However, these findings should be verified in prospective cohort for further individualization.

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Estimating the risk and benefit of radiation therapy in (y)pN1 stage breast cancer patients: A Bayesian network model incorporating expert knowledge (KROG 22–13)
Bum-Sup Jang, Seok-Joo Chun, Hyeon Seok Choi, Ji Hyun Chang, Kyung Hwan Shin
Computer Methods and Programs in Biomedicine.2024; 245: 108049. CrossRef
Prediction of Overall Disease Burden in (y)pN1 Breast Cancer Using Knowledge-Based Machine Learning Model
Seok-Joo Chun, Bum-Sup Jang, Hyeon Seok Choi, Ji Hyun Chang, Kyung Hwan Shin
Cancers.2024; 16(8): 1494. CrossRef
Selection of patients with pancreatic adenocarcinoma who may benefit from radiotherapy
I-Shiow Jan, Hui Ju Ch’ang
Radiation Oncology.2023;[Epub] CrossRef
Characterization of the gene signature correlated with favorable response to chemoradiotherapy in rectal cancer: A hypothesis‐generating study
Seung Hyuck Jeon, Eui Kyu Chie
Cancer Medicine.2023; 12(7): 8981. CrossRef
Krüppel-like Factor 10 as a Prognostic and Predictive Biomarker of Radiotherapy in Pancreatic Adenocarcinoma
Yi-Chih Tsai, Min-Chieh Hsin, Rui-Jun Liu, Ting-Wei Li, Hui-Ju Ch’ang
Cancers.2023; 15(21): 5212. CrossRef

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Breast cancer

A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer: Jung Sun Kim, Koung Jin Suh, Dae-Won Lee, Go-un Woo, Miso Kim, Se Hyun Kim, Han Suk Ryu, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, So Yeon Park, In Ae Park, Jee Hyun Kim, Seock-Ah Im; Cancer Res Treat. 2022;54(2):488-496. Published online August 13, 2021; DOI: https://doi.org/10.4143/crt.2021.394

Abstract PDF PubReader ePub

Purpose
We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.
Materials and Methods
This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled.
Results
A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m² on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m² every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction.
Conclusion
This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.

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Long-term outcomes of a randomized, open-label, phase II study comparing cabazitaxel versus paclitaxel as neoadjuvant treatment in patients with triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE)
P. Meyer-Wilmes, J. Huober, M. Untch, J.-U. Blohmer, W. Janni, C. Denkert, P. Klare, T. Link, K. Rhiem, C. Bayer, M. Reinisch, V. Bjelic-Radisic, D.M. Zahm, C. Hanusch, C. Solbach, G. Heinrich, A.D. Hartkopf, A. Schneeweiss, P. Fasching, N. Filmann, V. Ne
ESMO Open.2024; 9(5): 103009. CrossRef
Real-world study on the effect of nab-paclitaxel treatment on clinical outcomes and laboratory parameters in patients across metastatic tumor sites
Vikas Talreja, Sangeeta Khetwani, Ethirajan Nanadagopal, Nilesh Eknath Borkar, Kunal Khobragade
International Journal of Molecular and Immuno Oncology.2024; 9: 46. CrossRef
Safety and efficacy of generic nab-paclitaxel-based therapy in Chinese patients with malignant tumors in a real-world setting: a multicenter prospective observational study
Fei He, Yancai Sun, Wenzhou Zhang, Qiongshi Wu, Donghang Xu, Zaixian Bai, Zhiying Hao, Weiyi Feng, Kanghuai Zhang, Jiang Liu, Mei Dong, Guangxuan Liu, Guohui Li
Discover Oncology.2024;[Epub] CrossRef
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Zhichao Tian, Shuping Dong, Yang Yang, Shilei Gao, Yonghao Yang, Jinpo Yang, Peng Zhang, Xin Wang, Weitao Yao
BMC Cancer.2022;[Epub] CrossRef
Paclitaxel

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Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity
Ľuboš Nižnanský, Denisa Osinová, Roman Kuruc, Alexandra Hengerics Szabó, Andrea Szórádová, Marián Masár, Žofia Nižnanská
International Journal of Molecular Sciences.2022; 23(24): 15619. CrossRef
A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma
Hua Yang, Mu-Zi-he Zhang, Hui-wei Sun, Yan-tao Chai, Xiaojuan Li, Qiyu Jiang, Jun Hou
Frontiers in Oncology.2021;[Epub] CrossRef

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Breast Cancer

Talazoparib Versus Chemotherapy in Patients with HER2-negative Advanced Breast Cancer and a Germline BRCA1/2 Mutation Enrolled in Asian Countries: Exploratory Subgroup Analysis of the Phase III EMBRACA Trial: Kyung-Hun Lee, Joohyuk Sohn, Annabel Goodwin, Tiziana Usari, Silvana Lanzalone, Seock-Ah Im, Sung-Bae Kim; Cancer Res Treat. 2021;53(4):1084-1095. Published online March 24, 2021; DOI: https://doi.org/10.4143/crt.2020.1381

Abstract PDF Supplementary Material PubReader ePub

Purpose
We evaluated study outcomes in patients enrolled in Asian regions in the phase III EMBRACA trial of talazoparib vs. chemotherapy.
Materials and Methods
Patients with human epidermal growth factor receptor 2–negative germline BRCA1/2-mutated advanced breast cancer who received prior chemotherapy were randomized 2:1 to talazoparib 1 mg/day or chemotherapy (physician’s choice). Primary endpoint was progression-free survival (PFS) per independent central review in the intent-to-treat (ITT) population. This post-hoc analysis evaluated efficacy/safety endpoints in the ITT population of patients enrolled in Asian regions.
Results
Thirty-three patients were enrolled at Asian sites (talazoparib, n=23; chemotherapy, n=10). Baseline characteristics were generally comparable with the overall EMBRACA population. In Asian patients, median PFS was 9.0 months (95% confidence interval [CI] 3.0, 15.2) for talazoparib and 7.1 months (95% CI, 1.2, not reached) for chemotherapy (hazard ratio [HR] 0.74 [95% CI, 0.22, 2.44]). Objective response rate was numerically higher for talazoparib vs. chemotherapy (62.5% [95% CI, 35.4, 84.8] vs. 25.0% [95% CI, 3.2, 65.1]). Median overall survival was 20.7 months (95% CI, 9.4, 40.1) versus 21.2 months (95% CI, 2.7, 35.0) months (HR, 1.41 [95% CI, 0.49, 4.05]). In Asian patients, fewer grade 3/4 adverse events (AEs), serious AEs (SAEs), grade 3/4 SAEs, and AEs resulting in dose reduction/discontinuation occurred with talazoparib than chemotherapy; for talazoparib, the frequency of these events was lower in Asian patients versus overall EMBRACA population.
Conclusion
In this subgroup analysis, talazoparib numerically improved efficacy versus chemotherapy and was generally well tolerated in Asian patients, with fewer grade 3/4 TEAEs, SAEs, and TEAEs leading to dose modification vs. the overall EMBRACA population.

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Pu-Chun Li, Yi-Fan Zhu, Jia-Ni Pan, Qiao-Yan Zhu, Yu-Yang Liao, Xiao-Wen Ding, Lin-Feng Zheng, Wen-Ming Cao
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Detection and analysis of the safety profile of talazoparib based on FAERS database
Mufei Tang, Peiyan Liu, Linzhe Du, Yuanyuan Li, Jinjin Chen, Yang Li
Expert Opinion on Drug Safety.2024; : 1. CrossRef
Facing inevitable PARPis resistance: Mechanisms and therapeutic strategies for breast cancer treatment
Haixia Liu, Xiaohui Chen, Yimin Jia, Hengyi Chen, Xiaohui Wang, Guoxiang Liu, Yang Luo
Interdisciplinary Medicine.2023;[Epub] CrossRef
Sustained delivery of PARP inhibitor Talazoparib for the treatment of BRCA-deficient ovarian cancer
Shicheng Yang, Allen Green, Needa Brown, Alexis Robinson, Merline Senat, Bryanna Testino, Daniela M. Dinulescu, Srinivas Sridhar
Frontiers in Oncology.2023;[Epub] CrossRef
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer
S.-A. Im, A. Gennari, Y.H. Park, J.H. Kim, Z.-F. Jiang, S. Gupta, T.H. Fadjari, K. Tamura, M.Y. Mastura, M.L.T. Abesamis-Tiambeng, E.H. Lim, C.-H. Lin, A. Sookprasert, N. Parinyanitikul, L.-M. Tseng, S.-C. Lee, P. Caguioa, M. Singh, Y. Naito, R.A. Hukom,
ESMO Open.2023; 8(3): 101541. CrossRef
Molecular Biology Mechanisms and Emerging Therapeutics of Triple-Negative Breast Cancer
Zhiying Zhang, Rui Zhang, Donghai Li
Biologics: Targets and Therapy.2023; Volume 17: 113. CrossRef
Development of the PARP inhibitor talazoparib for the treatment of advanced BRCA1 and BRCA2 mutated breast cancer
Evthokia A. Hobbs, Jennifer K. Litton, Timothy A. Yap
Expert Opinion on Pharmacotherapy.2021; : 1. CrossRef

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Gastrointestinal Cancer

Phase II Trial of Postoperative Adjuvant Gemcitabine and Cisplatin Chemotherapy Followed by Chemoradiotherapy with Gemcitabine in Patients with Resected Pancreatic Cancer: Kyung-Hun Lee, Eui Kyu Chie, Seock-Ah Im, Jee Hyun Kim, Jihyun Kwon, Sae-Won Han, Do-Youn Oh, Jin-Young Jang, Jae-Sung Kim, Tae-You Kim, Yung-Jue Bang, Sun Whe Kim, Sung W. Ha; Cancer Res Treat. 2021;53(4):1096-1103. Published online December 30, 2020; DOI: https://doi.org/10.4143/crt.2020.928

Abstract PDF PubReader ePub

Purpose
Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed.
Materials and Methods
Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m² on days 1 and 8 and cisplatin 60 mg/m² on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m²/wk), and then gemcitabine 1,000 mg/m² on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety.
Results
Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia.
Conclusion
Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

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NUDT21 interacts with NDUFS2 to activate the PI3K/AKT pathway and promotes pancreatic cancer pathogenesis
Xiao-Dong Huang, Yong-Wei Chen, Lv Tian, Li Du, Xiao-Chen Cheng, Yu-Xin Lu, Dong-Dong Lin, Feng-Jun Xiao
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
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Obaid Ur Rehman, Eeshal Fatima, Zain Ali Nadeem, Arish Azeem, Jatin Motwani, Habiba Imran, Hadia Mehboob, Alishba Khan, Omer Usman
Journal of Gastrointestinal Cancer.2024; 55(2): 559. CrossRef
OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death
Xiao-Dong Huang, Li Du, Xiao-Chen Cheng, Yu-Xin Lu, Qiao-Wei Liu, Yi-Wu Wang, Ya-Jin Liao, Dong-Dong Lin, Feng-Jun Xiao
Cell Death Discovery.2024;[Epub] CrossRef
Impact of obesity on pathological complete remission in early stage breast cancer patients after neoadjuvant chemotherapy: a retrospective study from a German University breast center
Johannes Felix Englisch, Alexander Englisch, Dominik Dannehl, Kenneth Eissler, Christian Martin Tegeler, Sabine Matovina, Léa Louise Volmer, Diethelm Wallwiener, Sara Y. Brucker, Andreas Hartkopf, Tobias Engler
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Chunhong Sui, Yijia Luo, Xiao Xiao, Jiaxue Liu, Xiaotong Shao, Yingxue Xue, Cheng Wang, Wenliang Li
ChemistrySelect.2023;[Epub] CrossRef
Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
Da Eun Lee, Hyeon Woong Kang, So Yi Kim, Myeong Jin Kim, Jae Woong Jeong, Woosol Chris Hong, Sungsoon Fang, Hyung Sun Kim, Yun Sun Lee, Hyo Jung Kim, Joon Seong Park
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Effects of Radiotherapy and Chemotherapy on Postoperative Prognosis of Patients Undergoing Radical Surgery for Pancreatic Cancer—Based on SEER Database Analysis
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Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
Peng Chen, Zhiwei He, Jie Wang, Jian Xu, Xueyi Jiang, Yankun Chen, Xinyuan Liu, Jianxin Jiang
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef

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153 Download
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Gastrointestinal cancer

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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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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Breast cancer

Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients: Mihong Choi, Jiyeon Han, Bo Ram Yang, Myoung-jin Jang, Miso Kim, Dae-Won Lee, Tae-Yong Kim, Seock-Ah Im, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh, Kyung-Hun Lee; Cancer Res Treat. 2021;53(1):65-76. Published online September 23, 2020; DOI: https://doi.org/10.4143/crt.2020.430

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer.
Materials and Methods
We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer.
Results
Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05).
Conclusion
Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

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

Abstract PDF Supplementary Material PubReader ePub

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

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Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells: Miso Lee, Kyung-Hun Lee, Ahrum Min, Jeongeun Kim, Seongyeong Kim, Hyemin Jang, Jee Min Lim, So Hyeon Kim, Dong-Hyeon Ha, Won Jae Jeong, Koung Jin Suh, Yae-Won Yang, Tae Yong Kim, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2019;51(2):451-463. Published online June 6, 2018; DOI: https://doi.org/10.4143/crt.2017.341

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells.
Materials and Methods
The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis.
Results
AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines.
Conclusion
Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.

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Ping Lin, Lingyan He, Nan Tian, Xuchen Qi
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Toxic effects of AZD1208 on mouse oocytes and its possible mechanisms
Feng‐Ze Yan, Ying‐Chun Ouyang, Tie‐Gang Meng, Hong‐Yong Zhang, Wei Yue, Xin‐Ran Zhang, Yue Xue, Zhen‐Bo Wang, Qing‐Yuan Sun
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Aanchal Rathi, Dhiraj Kumar, Gulam Mustafa Hasan, Mohammad Mahfuzul Haque, Md Imtaiyaz Hassan
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TDP1 and TOP1 Modulation in Olaparib-Resistant Cancer Determines the Efficacy of Subsequent Chemotherapy
Jin Won Kim, Ahrum Min, Seock-Ah Im, Hyemin Jang, Yu Jin Kim, Hee-Jun Kim, Kyung-Hun Lee, Tae-Yong Kim, Keun Wook Lee, Do-Youn Oh, Jee-Hyun Kim, Yung-Jue Bang
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PIM1 (Moloney Murine Leukemia Provirus Integration Site) Inhibition Decreases the Nonhomologous End-Joining DNA Damage Repair Signaling Pathway in Pulmonary Hypertension
Marie-Claude Lampron, Géraldine Vitry, Valérie Nadeau, Yann Grobs, Renée Paradis, Nolwenn Samson, Ève Tremblay, Olivier Boucherat, Jolyane Meloche, Sébastien Bonnet, Steeve Provencher, François Potus, Roxane Paulin
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Inhibition of PIM1 attenuates the stem cell–like traits of breast cancer cells by promoting RUNX3 nuclear retention
Hui Liu, Cheng Chen, Dongshen Ma, Yubing Li, Qianqian Yin, Qing Li, Chenxi Xiang
Journal of Cellular and Molecular Medicine.2020; 24(11): 6308. CrossRef
Antitumor effect of a WEE1 inhibitor and potentiation of olaparib sensitivity by DNA damage response modulation in triple-negative breast cancer
Dong-Hyeon Ha, Ahrum Min, Seongyeong Kim, Hyemin Jang, So Hyeon Kim, Hee-Jun Kim, Han Suk Ryu, Ja-Lok Ku, Kyung-Hun Lee, Seock-Ah Im
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Soraya Alnabulsi, Enas A. Al-Hurani
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Maiara Bernardes Marques, Michael González-Durruthy, Bruna Félix da Silva Nornberg, Bruno Rodrigues Oliveira, Daniela Volcan Almeida, Ana Paula de Souza Votto, Luis Fernando Marins
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Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01): In Hae Park, Seock-Ah Im, Kyung Hae Jung, Joo Hyuk Sohn, Yeon Hee Park, Keun Seok Lee, Sung Hoon Sim, Kyong-Hwa Park, Jee Hyun Kim, Byung Ho Nam, Hee-Jun Kim, Tae-Yong Kim, Kyung-Hun Lee, Sung-Bae Kim, Jin-Hee Ahn, Suee Lee, Jungsil Ro; Cancer Res Treat. 2019;51(1):43-52. Published online February 14, 2018; DOI: https://doi.org/10.4143/crt.2017.562

Abstract PDF PubReader ePub

Purpose
We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC).
Materials and Methods
A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS.
Results
There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea.
Conclusion
Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.

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The Impact of Skin Problems on the Quality of Life in Patients Treated with Anticancer Agents: A Cross-Sectional Study: Jaewon Lee, Jin Lim, Jong Seo Park, Miso Kim, Tae-Yong Kim, Tae Min Kim, Kyung-Hun Lee, Bhumsuk Keam, Sae-Won Han, Je-Ho Mun, Kwang Hyun Cho, Seong Jin Jo; Cancer Res Treat. 2018;50(4):1186-1193. Published online December 14, 2017; DOI: https://doi.org/10.4143/crt.2017.435

Abstract PDF Supplementary Material PubReader ePub

Purpose
Patients treated with anticancer agents often experience a variety of treatment-related skin problems, which can impair their quality of life.
Materials and Methods
In this cross-sectional study, Dermatology Life Quality Index (DLQI) and clinical information were evaluated in patients under active anticancer treatment using a questionnaire survey and their medical records review.
Results
Of 375 evaluated subjects with anticancer therapy, 136 (36.27%) and 114 (30.40%) were treated for breast cancer and colorectal cancer, respectively. We found that women, breast cancer, targeted agent use, and longer duration of anticancer therapy were associated with higher dermatology-specific quality of life distraction. In addition, itching, dry skin, easy bruising, pigmentation, papulopustules on face, periungual inflammation, nail changes, and palmoplantar lesions were associated with significantly higher DLQI scores. Periungual inflammation and palmoplantar lesions scored the highest DLQI.
Conclusion
We believe our findings can be helpful to clinicians in counseling and managing the patients undergoing anticancer therapy.

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Korean Cancer Patients’ Awareness of Clinical Trials, Perceptions on the Benefit and Willingness to Participate: Yoojoo Lim, Jee Min Lim, Won Jae Jeong, Kyung-Hun Lee, Bhumsuk Keam, Tae-Yong Kim, Tae Min Kim, Sae-Won Han, Do Youn Oh, Dong-Wan Kim, Tae-You Kim, Dae Seog Heo, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2017;49(4):1033-1043. Published online April 7, 2017; DOI: https://doi.org/10.4143/crt.2016.413

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to assess current levels of awareness of clinical trials (CTs), perceptions regarding their benefits and willingness to participate to CTs among Korean cancer patients.
Materials and Methods
From December 2012 to August 2015, we distributed questionnaires to cancer patients receiving systemic anti-cancer therapy at Seoul National University Hospital, Seoul, Korea.
Results
A total of 397 out of 520 requested patients (76.3%) responded to the survey. Among the 397 patients, 62.5% were female and the median age was 52 years. Overall, 97.4% (387/397) answered that they have at least heard of CTs. When asked about their level of awareness, 23.8% (92/387) answered that they could more than roughly explain about CTs. The average visual analogue scale score of CT benefit in all patients was 6.43 (standard deviation, 2.20). Patients who were only familiar with the term without detailed knowledge of the contents had the least expectation of benefit from CTs (p=0.015). When asked about their willingness to participate in CTs, 56.7% (225/397) answered positively. Patients with higher levels of awareness of CTs showed higher willingness to participate (p < 0.001). Heavily treated patients and patients with previous experience regarding CTs also showed a higher willingness to participate (p < 0.001). The perceived benefit of CTs was higher in the group willing to participate (p=0.026).
Conclusion
The patient’s level of awareness regarding CTs was positively related to the positive perception and willingness to participate. Although the general awareness of CTs was high, a relatively large proportion of patients did not have accurate knowledge; therefore, proper and accurate patient education is necessary.

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Ji Hyun Park, Ji Sung Lee, HaYeong Koo, Jeong Eun Kim, Jin-Hee Ahn, Min-Hee Ryu, Sook-ryun Park, Shin-kyo Yoon, Jae Cheol Lee, Yong-Sang Hong, Sun Young Kim, Kyo-Pyo Kim, Chang-Hoon Yoo, Jung Yong Hong, Jae Lyun Lee, Kyung Hae Jung, Baek-Yeol Rhyoo, Tae W
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Colorectal cancer survivors’ willingness to participate in a hypothetical clinical trial of Korean medicine: A cross-sectional study
Yown Hwangbo, Gyung Mo Son, Kyung Hee Kim, Myeong Sook Kwon, Kun Hyung Kim
European Journal of Integrative Medicine.2020; 33: 101033. CrossRef
Perception and Satisfaction of Anticancer Drug Clinical Trials in Cancer Patients
Ju Kyung Jeon, Jeong Hye Kim
Asian Oncology Nursing.2019; 19(1): 18. CrossRef
Challenges in informed consent decision-making in Korean clinical research: A participant perspective
Im-Soon Choi, Eun Young Choi, Iyn-Hyang Lee, Dermot Cox
PLOS ONE.2019; 14(5): e0216889. CrossRef
Clinical Trials: What, Where, When?
Olga S. Kobyakova, Ivan A. Deev, Evgeny S. Kulikov, Roman I. Shtykh, Igor D. Pimenov, Olga I. Zvonareva, Igor V. Mareev
Annals of the Russian academy of medical sciences.2018; 73(5): 314. CrossRef

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S-1–Induced Lacrimal Drainage Obstruction and Its Association with Ingredients/Metabolites of S-1 in Tears and Plasma: A Prospective Multi-institutional Study: Namju Kim, Jin Won Kim, Je-Hyun Baek, Jin-Soo Kim, Ho-Kyung Choung, Tae-Yong Kim, Kyung-Hun Lee, Yung-Jue Bang, Sang In Khwarg, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Jae-Yong Chung, Soyeon Ahn, Keun-Wook Lee; Cancer Res Treat. 2018;50(1):30-39. Published online February 27, 2017; DOI: https://doi.org/10.4143/crt.2016.569

Abstract PDF Supplementary Material PubReader ePub

Purpose
This prospective study was conducted to determine the incidence of lacrimal drainage obstruction (LDO) during S-1 chemotherapy and evaluate the association between the development of LDO and the concentrations of ingredients/metabolites of S-1 in tears and plasma.
Materials and Methods
A total of 145 patients with gastric cancer who received adjuvant S-1 therapy were enrolled. Ophthalmologic examinations were performed regularly during S-1 chemotherapy. Concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and 5-fluorouracil at steady-state trough level were measured in both tears and plasma.
Results
Fifty-three patients (37%) developed LDO. The median time to the onset of LDO was 10.9 weeks, and LDO developed most frequently in the nasolacrimal duct. Univariable analyses revealed that an older age (≥ 70 years), creatinine clearance rate (Ccr) < 80 mL/min, 5-fluorouracil concentration in plasma ≥ 22.3 ng/mL (median), CDHP concentration in plasma ≥ 42.0 ng/mL (median), and tegafur concentration in tears ≥ 479.2 ng/mL (median) were related to increased development of LDO. Multivariable analysis indicated that a high plasma 5-fluorouracil concentration was predictive of increased development of LDO (hazard ratio, 2.02; p=0.040), along with older age and decreased Ccr. Patients with LDO also developed S-1–related non-hematologic toxicity more frequently than those without LDO (p=0.016).
Conclusion
LDO is a frequent adverse event during S-1 chemotherapy. An older age, decreased Ccr, and high plasma 5-fluorouracil concentration were found to be independent risk factors for LDO. The high incidence of LDO warrants regular ophthalmologic examination and early intervention in patients receiving S-1 therapy.

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Ocular complication induced by anticancer drug S-1: association with drug concentrations in tears
Masakazu Yamada, Tomoyuki Kamao, Atsushi Shiraishi, Jo Sakai, Yuichi Ohashi, Masashi Mimura, Yoshitsugu Inoue, Kazuyoshi Ohtomo, Tai-ichiro Chikama, Chika Miyazaki, Yuka Hosotani
Japanese Journal of Ophthalmology.2025;[Epub] CrossRef
Influenza A Virus Utilizes the Nasolacrimal System to Establish Respiratory Infection after Ocular Exposure in the Swine Model
Shubin Li, Xuebin Peng, MinJie Wang, Wenqian Wang, Yuye Liu, Qian Yang, Makoto Ozawa
Transboundary and Emerging Diseases.2024;[Epub] CrossRef
Nasolacrimal Duct Obstruction in the Patients Receiving Treatment for Cancer
Vasily D. Yartsev, Eugenia L. Atkova
International Ophthalmology Clinics.2023; 63(3): 137. CrossRef
Obstrução lacrimal pós-tratamento oncológico: revisão de literatura
Camilla Duarte Silva, Fabricio Lopes da Fonseca, Juliana Mika Kato, Suzana Matayoshi
Revista Brasileira de Oftalmologia.2022;[Epub] CrossRef
A Case of Nasolacrimal Duct Obstruction During S-1 Treatment For Breast Cancer
Hisataka Ominato, Michihisa Kono, Hidekiyo Yamaki, Takumi Kumai, Miki Takahara, Akihiro Katada, Tatsuya Hayashi
Practica Oto-Rhino-Laryngologica.2022; 115(6): 503. CrossRef
Corneal nerve changes following treatment with neurotoxic anticancer drugs
Jeremy Chung Bo Chiang, David Goldstein, Susanna B. Park, Arun V. Krishnan, Maria Markoulli
The Ocular Surface.2021; 21: 221. CrossRef
The impact of anticancer drugs on the ocular surface
Jeremy Chung Bo Chiang, Ilyanoon Zahari, Maria Markoulli, Arun V. Krishnan, Susanna B. Park, Annalese Semmler, David Goldstein, Katie Edwards
The Ocular Surface.2020; 18(3): 403. CrossRef
Pharmacokinetics of S-1 monotherapy in plasma and in tears for gastric cancer patients
Hirofumi Yasui, Takeshi Kawakami, Hiroya Kashiwagi, Keita Mori, Katsuhiro Omae, Jun Kasai, Kunihiro Yoshisue, Masahiro Kawahira, Takahiro Tsushima, Nozomu Machida, Akira Fukutomi, Ken Yamaguchi
International Journal of Clinical Oncology.2019; 24(6): 660. CrossRef

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Bilateral Salpingo-oophorectomy Compared to Gonadotropin-Releasing Hormone Agonists in Premenopausal Hormone Receptor–Positive Metastatic Breast Cancer Patients Treated with Aromatase Inhibitors: Koung Jin Suh, Se Hyun Kim, Kyung-Hun Lee, Tae-Yong Kim, Yu Jung Kim, Sae-Won Han, Eunyoung Kang, Eun-Kyu Kim, Kidong Kim, Jae Hong No, Wonshik Han, Dong-Young Noh, Maria Lee, Hee Seung Kim, Seock-Ah Im, Jee Hyun Kim; Cancer Res Treat. 2017;49(4):1153-1163. Published online February 27, 2017; DOI: https://doi.org/10.4143/crt.2016.463

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although combining aromatase inhibitors (AI) with gonadotropin-releasing hormone agonists (GnRHa) is becoming more common, it is still not clear if GnRHa is as effective as bilateral salpingo-oophorectomy (BSO).
Materials and Methods
We retrospectively analyzed data of 66 premenopausal patients with hormone receptor– positive, human epidermal growth factor receptor 2–negative recurrent and metastatic breast cancer who had been treated with AIs in combination with GnRHa or BSO between 2002 and 2015.
Results
The median patient age was 44 years. Overall, 24 (36%) received BSO and 42 (64%) received GnRHa. The clinical benefit rate was higher in the BSO group than in the GnRHa group (88% vs. 69%, p=0.092). Median progression-free survival (PFS) was longer in the BSO group, although statistical significance was not reached (17.2 months vs. 13.3 months, p=0.245). When propensity score matching was performed, the median PFS was 17.2 months for the BSO group and 8.2 months for the GnRHa group (p=0.137). Multivariate analyses revealed that the luminal B subtype (hazard ratio, 1.67; 95% confidence interval [CI], 1.08 to 2.60; p=0.022) and later-line treatment (≥ third line vs. first line; hazard ratio, 3.24; 95% CI, 1.59 to 6.59; p=0.001) were independent predictive factors for a shorter PFS. Incomplete ovarian suppression was observed in a subset of GnRHa-treated patients whose disease showed progression, with E2 levels higher than 21 pg/mL.
Conclusion
Both BSO and GnRHa were found to be effective in our AI-treated premenopausal metastatic breast cancer patient cohort. However, further studies in larger populations are needed to determine if BSO is superior to GnRHa.

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Incomplete ovarian function suppression in premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonists
Jinna Lin, Shuqi Zheng, Qiang Liu
Cancer Treatment Reviews.2025; 133: 102879. CrossRef
Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study
Yifei Chen, Ruyan Zhang, Ying Yan, Huiping Li, Guohong Song
Breast Cancer Research and Treatment.2024; 206(3): 543. CrossRef
Oophorectomy in Premenopausal Patients with Estrogen Receptor-Positive Breast Cancer: New Insights into Long-Term Effects
Fatima Khan, Kristin Rojas, Matthew Schlumbrecht, Patricia Jeudin
Current Oncology.2023; 30(2): 1794. CrossRef
Comparison of outcomes in patients with luminal type breast cancer treated with a gonadotropin-releasing hormone analog or bilateral salpingo-oophorectomy: A cohort retrospective study
Dwi Ris Andriyanto, Prihantono, Salman Ardi Syamsu, Muhammad Ihwan Kusuma, Joko Hendarto, Indra, Nilam Smaradania, Elridho Sampepajung, Asrul Mappiwali, Muhammad Faruk
Annals of Medicine & Surgery.2022;[Epub] CrossRef
Awareness of the Causes Leading to Surgical Ablation of Ovarian Function in Premenopausal Breast Cancer—A Single-Center Analysis
Joana Correia Oliveira, Filipa Costa Sousa, Inês Gante, Margarida Figueiredo Dias
Medicina.2021; 57(4): 385. CrossRef
Long-term effect of repeated deslorelin acetate treatment in bitches for reproduction control
Brändli SP, Palm J, Kowalewski MP, Reichler IM
Theriogenology.2021; 173: 73. CrossRef
Prognostic Factors in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2–) Advanced Breast Cancer: A Systematic Literature Review
Gebra Cuyún Carter, Maitreyee Mohanty, Keri Stenger, Claudia Morato Guimaraes, Shivaprasad Singuru, Pradeep Basa, Sheena Singh, Vanita Tongbram, Sherko Kuemmel, Valentina Guarneri, Sara M Tolaney
Cancer Management and Research.2021; Volume 13: 6537. CrossRef
Oophorectomy as a Hormonal Ablation Therapy in Metastatic and Recurrent Breast Cancer: Current Indications and Results
Islam H. Metwally, Omar Hamdy, Saleh S. Elbalka, Mohamed Elbadrawy, Dina M. Elsaid
Indian Journal of Surgical Oncology.2019; 10(3): 542. CrossRef
Targeted Therapy for Premenopausal Women with HR+, HER2− Advanced Breast Cancer: Focus on Special Considerations and Latest Advances
Aditya Bardia, Sara Hurvitz
Clinical Cancer Research.2018; 24(21): 5206. 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
Cancer Treatment and Research Communications.2021; 28: 100431. CrossRef
Neoadjuvant Intraperitoneal Chemotherapy in Patients with Pseudomyxoma Peritonei—A Novel Treatment Approach
Aruna Prabhu, Andreas Brandl, Satoshi Wakama, Shouzou Sako, Haruaki Ishibashi, Akiyoshi Mizumoto, Nobuyuki Takao, Kousuke Noguchi, Shunsuke Motoi, Masumi Ichinose, Yang Liu, Yutaka Yonemura
Cancers.2020; 12(8): 2212. CrossRef
Clinical and Translational Research Challenges in Biliary Tract Cancers
Angela Lamarca, Melissa Frizziero, Mairéad G. McNamara, Juan W. Valle
Current Medicinal Chemistry.2020; 27(29): 4756. CrossRef
Therapeutic outcomes and prognostic factors in unresectable gallbladder cancer treated with gemcitabine plus cisplatin
Min su You, Ji Kon Ryu, Young Hoon Choi, Jin Ho Choi, Gunn Huh, Woo Hyun Paik, Sang Hyub Lee, Yong-Tae Kim
BMC Cancer.2019;[Epub] CrossRef
Efficacy of interventional therapy and effect on inflammatory factors in patients with gastric cancer after chemotherapy
Puzhao Wu, Jing Wang
Oncology Letters.2019;[Epub] CrossRef
CA19-9 kinetics during systemic chemotherapy in patients with advanced or recurrent biliary tract cancer
Naminatsu Takahara, Yousuke Nakai, Hiroyuki Isayama, Takashi Sasaki, Kei Saito, Kensaku Noguchi, Tatsunori Suzuki, Tomoka Nakamura, Tatsuya Sato, Kazunaga Ishigaki, Ryunosuke Hakuta, Tsuyoshi Takeda, Rie Uchino, Suguru Mizuno, Hirofumi Kogure, Minoru Tada
Cancer Chemotherapy and Pharmacology.2017; 80(6): 1105. CrossRef

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Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis: Seongyeong Kim, Ahrum Min, Kyung-Hun Lee, Yaewon Yang, Tae-Yong Kim, Jee Min Lim, So Jung Park, Hyun-Jin Nam, Jung Eun Kim, Sang-Hyun Song, Sae-Won Han, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, David Hangauer, Johnson Yiu-Nam Lau, Kyongok Im, Dong Soon Lee, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2017;49(3):643-655. Published online October 6, 2016; DOI: https://doi.org/10.4143/crt.2016.168

Abstract PDF Supplementary Material PubReader ePub

Purpose
KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo.
Materials and Methods
The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects.
Results
KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho- Src and proliferative-signaling molecules were down-regulated in KX-01–sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01– induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01–sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model.
Conclusion
KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.

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Annabel Shen, Rebecca A. Simonette, Peter L. Rady, Stephen K. Tyring
Archives of Dermatological Research.2025;[Epub] CrossRef
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Yingjie Cui, Jing Zhang, Guifang Zhang
Current Medicinal Chemistry.2024; 31(14): 1874. CrossRef
Efficacy and tolerability of tirbanibulin 1% ointment in the treatment of cancerization field: a real‐life Italian multicenter observational study of 250 patients
Gianluca Nazzaro, Andrea Carugno, Paolo Bortoluzzi, Stefano Buffon, Chiara Astrua, Elena Zappia, Emanuele Trovato, Stefano Caccavale, Vincenzo Pellegrino, Giovanni Paolino, Riccardo Balestri, Rossella Lacava, Giulia Ciccarese, Alice Verdelli, Stefania Bar
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Dickkopf-1 (DKK1) drives growth and metastases in castration-resistant prostate cancer
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Anti-tumor effects of tirbanibulin in squamous cell carcinoma cells are mediated via disruption of tubulin-polymerization
Viola K. DeTemple, Antje Walter, Sabine Bredemeier, Ralf Gutzmer, Katrin Schaper-Gerhardt
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Stephen Moore, Veda Kulkarni, Angela Moore, Jennifer R. Landes, Rebecca Simonette, Qin He, Peter L. Rady, Stephen K. Tyring
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Angela Moore, Kara Hurley, Stephen A. Moore, Luke Moore
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Maan T. Khayat, Abdelsattar M. Omar, Farid Ahmed, Mohammad I. Khan, Sara M. Ibrahim, Yosra A. Muhammad, Azizah M. Malebari, Thikryat Neamatallah, Moustafa E. El-Araby
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Efficacy of Letrozole as First-Line Treatment of Postmenopausal Women with Hormone Receptor–Positive Metastatic Breast Cancer in Korea: Seung Hoon Beom, Jisu Oh, Tae-Yong Kim, Kyung-Hun Lee, Yaewon Yang, Koung Jin Suh, Hyeong-Gon Moon, Sae-Won Han, Do-Youn Oh, Wonshik Han, Tae-You Kim, Dong-Young Noh, Seock-Ah Im; Cancer Res Treat. 2017;49(2):454-463. Published online August 23, 2016; DOI: https://doi.org/10.4143/crt.2016.259

Abstract PDF PubReader ePub

Purpose
Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)–positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients.
Materials and Methods
This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment historywere extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity.
Results
The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated.
Conclusion
Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.

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Is hormonal therapy effective in advanced endometrial cancer? A systematic review and meta-analysis
Josee-Lyne Ethier, Danielle N. Desautels, Eitan Amir, Helen MacKay
Gynecologic Oncology.2017; 147(1): 158. CrossRef

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Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX: Mi-Jung Kim, Sae-Won Han, Dae-Won Lee, Yongjun Cha, Kyung-Hun Lee, Tae-Yong Kim, Do-Youn Oh, Se Hyung Kim, Seock-Ah Im, Yung-Jue Bang, Tae-You Kim; Cancer Res Treat. 2016;48(3):990-997. Published online January 14, 2016; DOI: https://doi.org/10.4143/crt.2015.296

Abstract PDF Supplementary Material PubReader ePub

Purpose
Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients.
Materials and Methods
Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells.
Results
Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, –42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly.
Conclusion
Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.

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Concurrent Chemoradiotherapy Versus Chemotherapy Alone for Unresectable Locally Advanced Pancreatic Cancer: A Retrospective Cohort Study: Younak Choi, Do-Youn Oh, Kyubo Kim, Eui Kyu Chie, Tae-Yong Kim, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Sung Whan Ha, Yung-Jue Bang; Cancer Res Treat. 2016;48(3):1045-1055. Published online October 16, 2015; DOI: https://doi.org/10.4143/crt.2015.226

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Purpose
The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), particularly the role of concurrent chemoradiotherapy (CCRT), remains debatable. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with unresectable LAPC. Materials and Methods Patients with LAPC who were consecutively treated between 2003 and 2010 were included. Resectability was evaluated according to National Comprehensive Cancer Network ver. 1.2012. The clinical outcomes for each treatment group (CCRT vs. CA) were evaluated retrospectively.
Results
Sixty-three patients (58.9%) and 44 patients (41.1%) were treated with CCRT and CA, respectively. The CCRT cohort included patients who were treated with CCRT with or without chemotherapy backbone (CCRT alone, induction chemotherapy-CCRT, CCRT-maintenance chemotherapy, and induction-CCRT-maintenance chemotherapy). Median progression-free survival (PFS) and overall survival (OS) of all patients were 7.2 months and 13.1 months. PFS of the CCRT and CA groups was 9.0 months and 4.4 months, respectively (p=0.020). OS of the CCRT and CA groups was 15.4 months and 9.3 months, respectively (p=0.011). In multivariate analysis, the adjusted hazard ratio of CCRT was 0.536 (p=0.003) for OS and 0.667 (p=0.078) for PFS. Although the pattern of failure was similar in the CCRT and CA groups, the times to both local and distant failure were significantly longer in the CCRT group. Conclusion In patients with unresectable LAPC, those who underwent CCRT during their entire treatment courses had longer OS than patients treated with chemotherapy alone.

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Dose-Escalated SBRT for Borderline and Locally Advanced Pancreatic Cancer: Resectability Rate and Pathological Results of a Multicenter Prospective Study
Barbara Salas-Salas, Laura Ferrera-Alayon, Alberto Espinosa-Lopez, Maria Luisa Perez-Rodriguez, Antonio Alayón Afonso, Andres Vera-Rosas, Gabriel Garcia-Plaza, Rodolfo Chicas-Sett, Maria Soledad Martinez-Martin, Elisa Salcedo, Andrea Kannemann, Marta Llor
Cancers.2025; 17(2): 191. CrossRef
Dose-escalated SBRT for borderline and locally advanced pancreatic cancer. Feasibility, safety and preliminary clinical results of a multicenter study
B. Salas, L. Ferrera-Alayón, A. Espinosa-López, A. Vera-Rosas, E. Salcedo, A. Kannemann, A. Alayon, R. Chicas-Sett, M. LLoret, P.C. Lara
Clinical and Translational Radiation Oncology.2024; 45: 100753. CrossRef
Survival benefits of radiotherapy in locally advanced unresectable and metastatic pancreatic cancer: a single-institution cohort and SEER database analysis
Bi-Yang Cao, Le-Tian Zhang, Chen-Chen Wu, Jing Wang, Lin Yang
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Comparing concurrent chemoradiotherapy, 125I seed implantation combined with chemotherapy, and chemotherapy alone efficacy in treating unresectable locally advanced pancreatic cancer
Yanfen Zheng, Rui Huang, Wenxue Zou, Chao Liu, Hongxin Niu, Jinbo Yue
Precision Radiation Oncology.2022; 6(2): 144. CrossRef
Concurrent Nab-paclitaxel and Radiotherapy
William T. Arscott, Kevin T. Nead, Adham Bear, Sriram Venigalla, Jacob Shabason, John N. Lukens, John P. Plastaras, Andrzej Wojcieszynski, James Metz, Mark O’Hara, Kim A. Reiss, Ursina Teitelbaum, Arturo Loaiza-Bonilla, Jeffrey Drebin, Major K. Lee, Stuti
American Journal of Clinical Oncology.2021; 44(9): 469. CrossRef
Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer
Mei Hua Jin, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh
Cancer Research and Treatment.2020; 52(1): 149. CrossRef
Current trends and issues of conversion surgery for patients with locally advanced unresectable pancreatic cancer
Toshimichi ASANO, Satoshi HIRANO, Toru NAKAMURA, Takehiro NOJI, Keisuke OKAMURA, Takahiro TSUCHIKAWA, Yuma EBIHARA, Toshiaki SHICHINOHE
Suizo.2018; 33(1): 48. CrossRef
Survival benefit of conversion surgery for patients with initially unresectable pancreatic cancer who responded favorably to nonsurgical treatment
Toshimichi Asano, Satoshi Hirano, Toru Nakamura, Keisuke Okamura, Takahiro Tsuchikawa, Takehiro Noji, Yoshitsugu Nakanishi, Kimitaka Tanaka, Toshiaki Shichinohe
Journal of Hepato-Biliary-Pancreatic Sciences.2018; 25(7): 342. CrossRef
Which patients with locally advanced pancreatic cancer treated with induction chemotherapy are most likely to benefit from post-induction chemoradiotherapy?
Sophie Otter, Irene Chong, Ria Kalaitzaki, Diana Tait
International Journal of Hepatobiliary and Pancreatic Diseases.2018; 8(1): 1. CrossRef
Change in carbohydrate antigen 19-9 level as a prognostic marker of overall survival in locally advanced pancreatic cancer treated with concurrent chemoradiotherapy
Yi-Jun Kim, Hyeon Kang Koh, Eui Kyu Chie, Do-Youn Oh, Yung-Jue Bang, Eun Mi Nam, Kyubo Kim
International Journal of Clinical Oncology.2017; 22(6): 1069. CrossRef
Risk factors of liver metastasis from advanced pancreatic adenocarcinoma: a large multicenter cohort study
Dong S., Wang L., Guo Y. B., Ying H. F., Shen X. H., Meng Z. Q., Chen Hao, Chen Q. W., Li Z. S.
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Risk factors for latent distant organ metastasis detected by staging laparoscopy in patients with radiologically defined locally advanced pancreatic ductal adenocarcinoma
Ilhan Karabicak, Sohei Satoi, Hiroaki Yanagimoto, Tomohisa Yamamoto, Satoshi Hirooka, So Yamaki, Hisashi Kosaka, Kentaro Inoue, Yoichi Matsui, Masanori Kon
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Effect of Time Interval between Breast-Conserving Surgery and Radiation Therapy on Outcomes of Node-Positive Breast Cancer Patients Treated with Adjuvant Doxorubicin/Cyclophosphamide Followed by Taxane: Hyeon Kang Koh, Kyung Hwan Shin, Kyubo Kim, Eun Sook Lee, In Hae Park, Keun Seok Lee, Jungsil Ro, So-Youn Jung, Seeyoun Lee, Seok Won Kim, Han-Sung Kang, Eui Kyu Chie, Wonshik Han, Dong-Young Noh, Kyung-Hun Lee, Seock-Ah Im, Sung Whan Ha; Cancer Res Treat. 2016;48(2):483-490. Published online June 5, 2015; DOI: https://doi.org/10.4143/crt.2015.111

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Purpose
This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. Materials and Methods From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome.
Results
The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. Conclusion RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.

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MiR-210 regulates lung adenocarcinoma by targeting HIF-1α
Guolei Cao, Peiwen Fan, Ronghui Ma, Qinghe Wang, Lili He, Haiwen Niu, Qin Luo
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Timing of postmastectomy radiotherapy following adjuvant chemotherapy for high-risk breast cancer: A post hoc analysis of a randomised controlled clinical trial
Si-Ye Chen, Guang-Yi Sun, Yu Tang, Hao Jing, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Xu-Ran Zhao, Yu-Chun Song, Bo Chen, Shu-Nan Qi, Yuan Tang, Ning-Ning Lu, Ning Li, Hui Fang, Ye-Xiong Li, Shu-Lian Wang
European Journal of Cancer.2022; 174: 153. CrossRef
Timing of Postmastectomy Radiotherapy Following Adjuvant Chemotherapy for High-Risk Breast Cancer: A Post-Hoc Analysis of a Randomised Controlled Clinical Trial
Si-Ye Chen, Guang-Yi Sun, Yu Tang, Hao Jing, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Xu-Ran Zhao, Yu-Chun Song, Bo Chen, Shu-Nan Qi, Yuan Tang, Ning-Ning Lu, Ning Li, Hui Fang, Ye-Xiong Li, Shu-Lian Wang
SSRN Electronic Journal .2022;[Epub] CrossRef
Social Determinants of Racial Disparities in Breast Cancer Mortality Among Black and White Women
Oluwole Adeyemi Babatunde, Jan M. Eberth, Tisha Felder, Robert Moran, Samantha Truman, James R. Hebert, Jiajia Zhang, Swann Arp Adams
Journal of Racial and Ethnic Health Disparities.2021; 8(1): 147. CrossRef
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Lu Cao, Cheng Xu, Gang Cai, Wei-Xiang Qi, Rong Cai, Shu-Bei Wang, Dan Ou, Min Li, Kun-Wei Shen, Jia-Yi Chen
Annals of Surgical Oncology.2021; 28(4): 2155. CrossRef
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Mohammad Esmaeil Akbari, Maryam Khayamzadeh, Hamid Reza Mirzaei, Afshin Moradi, Atieh Akbari, Farid Moradian, Neda Khalili
International Journal of Surgical Oncology.2020; 2020: 1. CrossRef
Timing of Chemotherapy and Radiotherapy Following Breast-Conserving Surgery for Early-Stage Breast Cancer: A Retrospective Analysis
Si-Ye Chen, Yu Tang, Shu-Lian Wang, Yong-Wen Song, Hui Fang, Jian-Yang Wang, Hao Jing, Jiang-Hu Zhang, Guang-Yi Sun, Xu-Ran Zhao, Jing Jin, Yue-Ping Liu, Bo Chen, Shu-Nan Qi, Ning Li, Yuan Tang, Ning-Ning Lu, Hua Ren, Zi-Hao Yu, Ye-Xiong Li
Frontiers in Oncology.2020;[Epub] CrossRef
Evaluation of tissue computed tomography number changes and dosimetric shifts after conventional whole-breast irradiation in patients undergoing breast-conserving surgery
Joo Hwan Lee, Dong Soo Lee, So Hyun Park, Young Kyu Lee, Jeong Soo Kim, Yong Seok Kim
Tumor Biology.2018; 40(8): 101042831879188. CrossRef
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Marissa C van Maaren, Reini W Bretveld, Jan J Jobsen, Renske K Veenstra, Catharina GM Groothuis-Oudshoorn, Hendrik Struikmans, John H Maduro, Luc JA Strobbe, Philip MP Poortmans, Sabine Siesling
British Journal of Cancer.2017; 117(2): 179. CrossRef

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Case Report

Dermatomyositis in a Patient with Cholangiocarcinoma Detected by an [¹⁸F]-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography Scan: Koung Jin Suh, Jin Kyun Park, Seongcheol Cho, Hyunkyung Park, Hae Woon Baek, Kyoungbun Lee, Dong Soo Lee, Kyung-Hun Lee; Cancer Res Treat. 2016;48(2):848-852. Published online March 18, 2015; DOI: https://doi.org/10.4143/crt.2014.310

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Cholangiocarcinoma with paraneoplastic dermatomyositis (DM) is extremely rare, and the whole body positron emission tomography–computed tomography (PET-CT) finding of paraneoplastic DM is rarely reported. We report a 66-year-old woman with metastatic cholangiocarcinoma, initially presented with bilateral proximal muscle uptake on PET-CT without clinical muscle symptoms. The initial interpretation of the high muscle uptake was metastasis to the muscles. However, while awaiting for chemotherapy, muscle weakness evolved and rapidly progressed. The level of creatine phosphokinase was significantly elevated. Electromyography revealed moderate myopathy, and a muscle biopsy showed degenerating myofibers with variable sizes. The diagnosis of paraneoplastic dermatomyositis was made. This case highlights that, although rare, paraneoplastic dermatomyositis can be present with cholangiocarcinoma. Also, muscle inflammation can precede the clinical muscle symptoms, and paraneoplastic DM should be considered as a possible differential diagnosis in the assessment of cancer patients who present with abnormal muscle tracer uptake in PET-CT scans.

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The Constellation of Risk Factors and Paraneoplastic Syndromes in Cholangiocarcinoma: Integrating the Endocrine Panel Amid Tumour-Related Biology (A Narrative Review)
Mihai-Lucian Ciobica, Bianca-Andreea Sandulescu, Liana-Maria Chicea, Mihaela Iordache, Maria-Laura Groseanu, Mara Carsote, Claudiu Nistor, Ana-Maria Radu
Biology.2024; 13(9): 662. CrossRef
Dermatomyositis with intrahepatic cholangiocarcinoma: a case report and data mining based on machine learning
Xusheng Zhang, Bendong Chen
Frontiers in Oncology.2023;[Epub] CrossRef
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Andy Y. Wu, Diana Samberg, Thomas R. Radomski
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Junhao Wu, Lin Qiu, Yingwei Wang, Chunyin Zhang
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Stephanie Yung, Michael Arendse, Frank Weilert, Bong Suk Ko
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Saad Ur Rahman, Muhammad Khawar Sana, Zabreen Tahir, Aamir Ali, Pir Ahmad Shah
World Journal of Hepatology.2020; 12(11): 897. CrossRef
Paraneoplastic fibrillary glomerulonephritis associated with intrahepatic cholangiocarcinoma: When diagnosis of a rare kidney disease leads to successful hepatic cancer treatment
Gabrielle Normand, Anne Jolivot, Maud Rabeyrin, Valérie Hervieu, Pierre-Jean Valette, Jean-Yves Scoazec, Jean-Michel Gougon, Laurent Juillard, Jérôme Dumortier
Clinics and Research in Hepatology and Gastroenterology.2017; 41(1): e8. CrossRef

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Original Articles

The Impact of Diabetes Mellitus and Metformin Treatment on Survival of Patients with Advanced Pancreatic Cancer Undergoing Chemotherapy: Younak Choi, Tae-Yong Kim, Do-Youn Oh, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang; Cancer Res Treat. 2016;48(1):171-179. Published online March 13, 2015; DOI: https://doi.org/10.4143/crt.2014.292

Abstract PDF Supplementary Material PubReader ePub

Purpose
A causal relationship between diabetes mellitus (DM) and pancreatic cancer is well established. However, in patients with advanced pancreatic cancer (APC) who receive palliative chemotherapy, the impact of DM on the prognosis of APC is unclear. Materials and Methods We retrospectively enrolled APC patients who received palliative chemotherapy between 2003 and 2010. The patients were stratified according to the status of DM, in accordance with 2010 DM criteria (American Heart Association/American Diabetes Association). DM at least 2 years’ duration prior to diagnosis of APC was defined as remote-onset DM (vs. recent-onset).
Results
Of the 349 APC patients, 183 (52.4%) had DM. Among the patients with DM, 160 patients had DM at the time of diagnosis of APC (remote-onset, 87; recent-onset, 73) and the remaining 23 patients developed DM during treatment of APC. Ultimately, 73.2% of patients (134/183) with DM received antidiabetic medication, including metformin (56 patients, 41.8%), sulfonylurea (62, 45.5%), and insulin (43, 32.1%). In multivariate analysis, cancer extent (hazard ratio [HR], 1.792; 95% confidence interval [CI], 1.313 to 2.445; p < 0.001) showed association with decreased overall survival (OS), whereas a diagnosis of DM (HR, 0.788; 95% CI, 0.615 to 1.009; p=0.059) conferred positive tendency on the OS. Metformin treatment itself conferred better OS in comparison within DM patients (HR 0.693; 95% CI, 0.492 to 0.977; p=0.036) and even in all APC patients (adjusted HR, 0.697; 95% CI, 0.491 to 1.990; p=0.044). Conclusion For APC patients receiving palliative chemotherapy, metformin treatment is associated with longer OS. Patients with DM tend to survive longer than those without DM.

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Nomogram for Predicting Breast Conservation after Neoadjuvant Chemotherapy: Min Kyoon Kim, Wonshik Han, Hyeong-Gon Moon, Soo Kyung Ahn, Jisun Kim, Jun Woo Lee, Ju-Yeon Kim, Taeryung Kim, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Seock-Ah Im, Tae-You Kim, In Ae Park, Dong-Young Noh; Cancer Res Treat. 2015;47(2):197-207. Published online September 4, 2014; DOI: https://doi.org/10.4143/crt.2013.247

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Purpose
The ability to accurately predict the likelihood of achieving breast conservation surgery (BCS) after neoadjuvant chemotherapy (NCT) is important in deciding whether NCT or surgery should be the first-line treatment in patients with operable breast cancers. Materials and Methods We reviewed the data of 513 women, who had stage II or III breast cancer and received NCT and surgery from a single institution. The ability of various clinicopathologic factors to predict the achievement of BCS and tumor size reduction to ≤ 3 cm was assessed. Nomograms were built and validated in an independent cohort. Results BCS was performed in 50.1% of patients, with 42.2% of tumors reduced to ≤ 3 cm after NCT. A multivariate logistic regression analysis showed that smaller initial tumor size, longer distance between the lesion and the nipple, absence of suspicious calcifications on mammography, and a single tumor were associated with BCS rather than mastectomy (p < 0.05). Negative estrogen receptor, smaller initial tumor size, higher Ki-67 level, and absence of in situ component were associated with residual tumor size ≤ 3 cm (p < 0.05). Two nomograms were developed using these factors. The areas under the receiver operating characteristic curves for nomograms predicting BCS and residual tumor ≤ 3 cm were 0.800 and 0.777, respectively. The calibration plots showed good agreement between the predicted and actual probabilities. Conclusion We have established a model with novel factors that predicts BCS and residual tumor size after NCT. This model can help in making treatment decisions for patients who are candidates for NCT.

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Risk scoring system for predicting breast conservation after neoadjuvant chemotherapy
Lobna Ouldamer, Sofiane Bendifallah, Joseph Pilloy, Flavie Arbion, Gilles Body, Caroline Brisson, Vincent Lavoué, Jean Lévêque, Emile Daraï
The Breast Journal.2019; 25(4): 696. CrossRef
Score for the Survival Probability in Metastasis Breast Cancer: A Nomogram-Based Risk Assessment Model
Zhenchong Xiong, Guangzheng Deng, Xinjian Huang, Xing Li, Xinhua Xie, Jin Wang, Zeyu Shuang, Xi Wang
Cancer Research and Treatment.2018; 50(4): 1260. CrossRef
Development of Nomogram to Predict the Best Military Category Using Physical Fitness Variables: A Model Development in Navy Trainees
Milad Nazarzadeh, Ali Reza Khoshdel, Abolfazl Goodarzi, Alireza Mosavi Jarrahi
Journal of Archives in Military Medicine.2018;[Epub] CrossRef
Predicting Successful Conservative Surgery after Neoadjuvant Chemotherapy in Hormone Receptor-Positive, HER2-Negative Breast Cancer
Chang Seok Ko, Kyu Min Kim, Jong Won Lee, Han Shin Lee, Sae Byul Lee, Guiyun Sohn, Jisun Kim, Hee Jeong Kim, Il Yong Chung, Beom Seok Ko, Byung Ho Son, Seung Do Ahn, Sung-Bae Kim, Hak Hee Kim, Sei Hyun Ahn
Journal of Breast Disease.2018; 6(2): 52. CrossRef
External validation of a published nomogram for prediction of brain metastasis in patients with extra-cerebral metastatic breast cancer and risk regression analysis
Ludivine Genre, Henri Roché, Léonel Varela, Dorra Kanoun, Monia Ouali, Thomas Filleron, Florence Dalenc
European Journal of Cancer.2017; 72: 200. CrossRef
Facteurs prédictifs de traitement conservateur après chimiothérapie néo-adjuvante dans le cancer du sein
J. Pilloy, C. Fleurier, M. Chas, L. Bédouet, M.L. Jourdan, F. Arbion, G. Body, L. Ouldamer
Gynécologie Obstétrique Fertilité & Sénologie .2017; 45(9): 466. CrossRef
Actual Conversion Rate from Total Mastectomy to Breast Conservation after Neoadjuvant Chemotherapy for Stages II–III Breast Cancer Patients
Hyejin Mo, Yumi Kim, Jiyoung Rhu, Kyung-Hun Lee, Tae-Yong Kim, Seock-Ah Im, Eun-Shin Lee, Han-Byoel Lee, Hyeong-Gon Moon, Dong-Young Noh, Wonshik Han
Journal of Breast Disease.2017; 5(2): 51. CrossRef

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A New Isolated Mediastinal Lymph Node or Small Pulmonary Nodule Arising during Breast Cancer Surveillance Following Curative Surgery: Clinical Factors That Differentiate Malignant from Benign Lesions: Tae-Yong Kim, Kyung-Hun Lee, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Wonshik Han, Kyubo Kim, Eui Kyu Chie, In-Ae Park, Young Tae Kim, Dong-Young Noh, Sung Whan Ha, Yung-Jue Bang; Cancer Res Treat. 2014;46(3):280-287. Published online July 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.3.280

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Purpose
A newly isolated mediastinal lymph node (LN) or a small pulmonary nodule, which appears during breast cancer surveillance, may pose a diagnostic dilemma with regard to malignancy. We conducted this study to determine which clinical factors were useful for the differentiation of malignant lesions from benign lesions under these circumstances. Materials and Methods We enrolled breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule that arose during surveillance, and whose lesions were pathologically confirmed. Tissue diagnosis was made by mediastinoscopy, video-assisted thoracic surgery or thoracotomy. Results A total of 43 patients were enrolled (mediastinal LN, 13 patients; pulmonary nodule, 30 patients). Eighteen patients (41.9%) were pathologically confirmed to have a benign lesion (benign group), and 25 patients (58.1%) were confirmed to have malignant lesion (malignant group). Between the two groups, the initial tumor size (p=0.096) and N stage (p=0.749) were similar. Hormone receptor negativity was more prevalent in the malignant group (59.1% vs. 40.9%, p=0.048). The mean lesion size was larger in the malignant group than in the benign group (20.8 mm vs. 14.4 mm, p=0.024). Metastatic lesions had a significantly higher value of maximal standardized uptake (mSUV) than that of benign lesions (6.4 vs. 3.4, p=0.021). Conclusion Hormone receptor status, lesion size, and mSUV on positron emission tomography are helpful in the differentiation of malignant lesions from benign lesions in breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule during surveillance.

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Unusual metastases of breast cancer: a single-center retrospective study
Pınar ÖZDEMİR AKDUR, Nazan ÇİLEDAĞ
The European Research Journal.2023; 9(6): 1444. CrossRef
18Fluorodeoxyglucose‐positron emission tomography/computed tomography features of suspected solitary pulmonary lesions in breast cancer patients following previous curative treatment
Lei Zhu, Haiman Bian, Lieming Yang, Jianjing Liu, Wei Chen, Xiaofeng Li, Jian Wang, Xiuyu Song, Dong Dai, Zhaoxiang Ye, Wengui Xu, Xiaozhou Yu
Thoracic Cancer.2019; 10(5): 1086. CrossRef

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