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Impact of Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel Blockers and Thiazide Diuretics on Survival of Ovarian Cancer Patients
Min Ae Cho, Soo Young Jeong, Insuk Sohn, Myeong-Seon Kim, Jun Hyeok Kang, E Sun Paik, Yoo-Young Lee, Chel Hun Choi
Cancer Res Treat. 2020;52(2):645-654.   Published online January 16, 2020
DOI: https://doi.org/10.4143/crt.2019.509
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We investigated the impact of four types of antihypertensive medications, angiotensin receptor blockers (ARBs), beta blockers (BBs; both selective and non-selective), calcium channel blockers (CCBs), and thiazide diuretics (TDs) on survival outcomes in epithelial ovarian cancer (EOC).
Materials and Methods
A single-institutional retrospective chart review of 878 patients with EOC was performed. Survival was compared according to use of the four antihypertensive medications during primary treatment. Propensity score matching (ratio 1:3) was performed to control possible associated covariates, such as age, International Federation of Gynecology and Obstetrics stage, residual status after primary debulking surgery, and co-morbidity.
Results
Among 878 patients, 56 patients (6.4%) were ARB users, 62 (7.1%) were BB users, 107 (12.2%) were CCBs users and 32 (3.6%) used TDs. Median progression-free survival (PFS) for ARB, BB, and CCB users was 37.8, 27.2, and 23.6 months compared with 33.6 months for non-users. ARB was associated with 35% decreased risk of disease progression (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.42 to 0.99; p=0.046) in multivariate analysis. After propensity score matching, median PFS for ARB users was 37.8 months and ARB use remained to be associated with lower recurrence rate in univariate (p=0.035) and multivariate analysis (HR, 0.60; 95% CI, 0.39 to 0.93; p=0.022).
Conclusion
In this study, ARBs use during primary treatment is associated with lower recurrence in EOC patients. However, CCBs, BBs, and TDs did not show beneficial impact.

Citations

Citations to this article as recorded by  
  • Evaluation of antihypertensive medications use and survival in patients with ovarian cancer: a population-based retrospective cohort study
    Rūta Everatt, Irena Kuzmickienė, Birutė Brasiūnienė, Ieva Vincerževskienė, Birutė Intaitė, Saulius Cicėnas, Ingrida Lisauskienė
    BMC Women's Health.2024;[Epub]     CrossRef
  • Advanced progress of the relationship between renin–angiotensin–aldosterone system inhibitors and cancers
    Ruixing Zhang, Hongtao Yin, Mengdi Yang, Jinjin Liu, Donghu Zhen, Zheng Zhang
    Journal of Hypertension.2024; 42(11): 1862.     CrossRef
  • Impact of ACEI/ARB use on the survival of hypertensive patients with cancer: A meta‑analysis
    Yao Xiao, Xinlong Chen, Wancheng Li, Xin Li, Wence Zhou
    Oncology Letters.2024;[Epub]     CrossRef
  • Renin-Angiotensin-Aldosterone System Inhibitors and Development of Gynecologic Cancers: A 23 Million Individual Population-Based Study
    Nhi Thi Hong Nguyen, Phung-Anh Nguyen, Chih-Wei Huang, Ching-Huan Wang, Ming-Chin Lin, Min-Huei Hsu, Hoang Bui Bao, Shuo-Chen Chien, Hsuan-Chia Yang
    International Journal of Molecular Sciences.2023; 24(4): 3814.     CrossRef
  • Association of Hypertension and Breast Cancer: Antihypertensive Drugs as an Effective Adjunctive in Breast Cancer Therapy
    Yuanyuan Fan, Nazeer Hussain Khan, Muhammad Farhan Ali Khan, MD Faysal Ahammad, Tayyaba Zulfiqar, Razia Virk, Enshe Jiang
    Cancer Management and Research.2022; Volume 14: 1323.     CrossRef
  • The effect of angiotensin receptor blockers and angiotensin-converting enzyme inhibitors on progression of gastric cancer: systematic review and meta-analysis
    Seyed Ali Mehrdad, Farshad Mirzavi, Seyed Mohammad Reza Seyedi, Ahmad Asoodeh
    Anti-Cancer Drugs.2022; 33(10): 983.     CrossRef
  • Repurposing approved drugs for cancer therapy
    Catherine H Schein
    British Medical Bulletin.2021; 137(1): 13.     CrossRef
  • Norepinephrine inhibits migration and invasion of human glioblastoma cell cultures possibly via MMP-11 inhibition
    Jing Zhong, Weiran Shan, Zhiyi Zuo
    Brain Research.2021; 1756: 147280.     CrossRef
  • Antihypertensive Drug Use and the Risk of Ovarian Cancer Death among Finnish Ovarian Cancer Patients—A Nationwide Cohort Study
    Eerik E. E. Santala, Miia Artama, Eero Pukkala, Kala Visvanathan, Synnöve Staff, Teemu J. Murtola
    Cancers.2021; 13(9): 2087.     CrossRef
  • The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer
    José A. Carlos-Escalante, Marcela de Jesús-Sánchez, Alejandro Rivas-Castro, Pavel S. Pichardo-Rojas, Claudia Arce, Talia Wegman-Ostrosky
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Post-Diagnostic Beta Blocker Use and Prognosis of Ovarian Cancer: A Systematic Review and Meta-Analysis of 11 Cohort Studies With 20,274 Patients
    Zhao-Yan Wen, Song Gao, Ting-Ting Gong, Yu-Ting Jiang, Jia-Yu Zhang, Yu-Hong Zhao, Qi-Jun Wu
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Stress Hormones: Emerging Targets in Gynecological Cancers
    Guoqiang Chen, Lei Qiu, Jinghai Gao, Jing Wang, Jianhong Dang, Lingling Li, Zhijun Jin, Xiaojun Liu
    Frontiers in Cell and Developmental Biology.2021;[Epub]     CrossRef
  • The Effect of Local Renin Angiotensin System in the Common Types of Cancer
    Moudhi Almutlaq, Abir Abdullah Alamro, Hassan S. Alamri, Amani Ahmed Alghamdi, Tlili Barhoumi
    Frontiers in Endocrinology.2021;[Epub]     CrossRef
  • Does sympathetic nervous system modulate tumor progression? A narrative review of the literature
    Ioannis Stavropoulos, Angelos Sarantopoulos, Anastasios Liverezas
    Journal of Drug Assessment.2020; 9(1): 106.     CrossRef
  • 14,233 View
  • 163 Download
  • 18 Web of Science
  • 14 Crossref
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Pretreatment Lymph Node Metastasis as a Prognostic Significance in Cervical Cancer: Comparison between Disease Status
Soo Young Jeong, Hyea Park, Myeong Seon Kim, Jun Hyeok Kang, E Sun Paik, Yoo-Young Lee, Tae Joong Kim, Jeong Won Lee, Byoung-Gie Kim, Duk Soo Bae, Chel Hun Choi
Cancer Res Treat. 2020;52(2):516-523.   Published online October 29, 2019
DOI: https://doi.org/10.4143/crt.2019.328
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Lymph node metastasis (LNM) is the most significant prognostic factor in cervical cancer that was recently incorporated into the International Federation of Gynecology and Obstetrics (FIGO) staging system. This study was performed to evaluate whether the prognostic significance of LNM differs according to disease status.
Materials and Methods
Patients with FIGO stage IB or higher cervical cancer who had pretreatment computed tomography and/or magnetic resonance imaging studies as well as long-term follow-up were enrolled in this retrospective study. The hazard ratio (HR) of Cox regression was used to determine the prognostic significance of LNM. The HRs were compared between the different tumor groups (based on stage, histology, tumor size, primary treatment, age, parametrium involvement, and lymphovascular space invasion).
Results
A total of 970 patients treated between January 1999 and December 2007 were included. The pretreatment LNM had prognostic significance in patients with stage IB1/IIA (HR for progression-free survival 2.10, p=0.001; HR for overall survival 1.99, p=0.005). However, the significance gradually decreased or disappeared with advancing stages. Similarly, the prognostic significance of the pretreatment LNM decreased with advancing disease status, including old age, parametrial involvement or lymphovascular space involvement. In contrast, the tumor size was associated with the prognostic significance of LNM with advancing status. The significance of the clinical LNM did not reflect the significance of the clinical stage. In contrast, the tumor size, parametrial involvement, and significance of the pathologic LNM reflected the clinical stage.
Conclusion
In patients with cervical cancer, pretreatment LNM on imaging has different clinical significance depending on the tumor status.

Citations

Citations to this article as recorded by  
  • Development of cervical intraepithelial neoplasia and invasive cervical cancer due to oxidative stress
    Amir Asotić, Memić Asotić, Muhamed Memić, Kerim Asotić, Amra Asotić
    Sanamed.2024; 19(1): 39.     CrossRef
  • Investigating and Analyzing Prognostic Factors and Their Impact on Recurrent Cervical Cancers
    Ashish Uke, Shweta B Dahake, Anurag Luharia, Monika Luharia, Gaurav V Mishra, Chanrashekhar Mahakalkar
    Cureus.2024;[Epub]     CrossRef
  • Based on 3D-PDU and clinical characteristics nomogram for prediction of lymph node metastasis and lymph-vascular space invasion of early cervical cancer preoperatively
    Shuang Dong, Yan-Qing Peng, Ya-Nan Feng, Xiao-Ying Li, Li-Ping Gong, Shuang Zhang, Xiao-Shan Du, Li-Tao Sun
    BMC Women's Health.2024;[Epub]     CrossRef
  • Recent Advances in Cervical Cancer Management: A Review on Novel Prognostic Factors in Primary and Recurrent Tumors
    Angela Santoro, Frediano Inzani, Giuseppe Angelico, Damiano Arciuolo, Emma Bragantini, Antonio Travaglino, Michele Valente, Nicoletta D’Alessandris, Giulia Scaglione, Stefania Sfregola, Alessia Piermattei, Federica Cianfrini, Paola Roberti, Gian Franco Za
    Cancers.2023; 15(4): 1137.     CrossRef
  • Identification of lymph node metastasis in pre‐operation cervical cancer patients by weakly supervised deep learning from histopathological whole‐slide biopsy images
    Qingqing Liu, Nan Jiang, Yiping Hao, Chunyan Hao, Wei Wang, Tingting Bian, Xiaohong Wang, Hua Li, Yan zhang, Yanjun Kang, Fengxiang Xie, Yawen Li, XuJi Jiang, Yuan Feng, Zhonghao Mao, Qi Wang, Qun Gao, Wenjing Zhang, Baoxia Cui, Taotao Dong
    Cancer Medicine.2023; 12(17): 17952.     CrossRef
  • Roles of DWI and T2-weighted MRI volumetry in the evaluation of lymph node metastasis and lymphovascular invasion of stage IB–IIA cervical cancer
    Y. Wang, X. Chen, H. Pu, Y. Yuan, S. Li, G. Chen, Y. Liu, H. Li
    Clinical Radiology.2022; 77(3): 224.     CrossRef
  • Risk Factor Assessment of Lymph Node Metastasis in Patients With FIGO Stage IB1 Cervical Cancer
    Mu Xu, Xiaoyan Xie, Liangzhi Cai, Yongjin Xie, Qiao Gao, Pengming Sun
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Intravoxel Incoherent Motion (IVIM) MR Quantification in Locally Advanced Cervical Cancer (LACC): Preliminary Study on Assessment of Tumor Aggressiveness and Response to Neoadjuvant Chemotherapy
    Miriam Dolciami, Silvia Capuani, Veronica Celli, Alessandra Maiuro, Angelina Pernazza, Innocenza Palaia, Violante Di Donato, Giusi Santangelo, Stefania Maria Rita Rizzo, Paolo Ricci, Carlo Della Rocca, Carlo Catalano, Lucia Manganaro
    Journal of Personalized Medicine.2022; 12(4): 638.     CrossRef
  • The prognostic significance of pretreatment squamous cell carcinoma antigen levels in cervical cancer patients treated by concurrent chemoradiation therapy and a comparison of dosimetric outcomes and clinical toxicities between tomotherapy and volumetric
    Yuan-Kai Cheng, Shih-Hsun Kuo, Heng-Hsuan Yen, Jing-Hu Wu, Yu-Chieh Chen, Ming-Yii Huang
    Radiation Oncology.2022;[Epub]     CrossRef
  • What MRI-based tumor size measurement is best for predicting long-term survival in uterine cervical cancer?
    Njål Lura, Kari S. Wagner-Larsen, David Forsse, Jone Trovik, Mari K. Halle, Bjørn I. Bertelsen, Øyvind Salvesen, Kathrine Woie, Camilla Krakstad, Ingfrid S. Haldorsen
    Insights into Imaging.2022;[Epub]     CrossRef
  • Clinical value of MRI, serum SCCA, and CA125 levels in the diagnosis of lymph node metastasis and para-uterine infiltration in cervical cancer
    Chao Ran, Jian Sun, Yunhui Qu, Na Long
    World Journal of Surgical Oncology.2021;[Epub]     CrossRef
  • A Novel Four-Gene Prognostic Signature as a Risk Biomarker in Cervical Cancer
    Jun Wang, Hua Zheng, Yatian Han, Geng Wang, Yanbin Li, Cuida Meng
    International Journal of Genomics.2020; 2020: 1.     CrossRef
  • 10,363 View
  • 223 Download
  • 14 Web of Science
  • 12 Crossref
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Prognostic Model for Survival and Recurrence in Patients with Early-Stage Cervical Cancer: A Korean Gynecologic Oncology Group Study (KGOG 1028)
E Sun Paik, Myong Cheol Lim, Moon-Hong Kim, Yun Hwan Kim, Eun Seop Song, Seok Ju Seong, Dong Hoon Suh, Jong-Min Lee, Chulmin Lee, Chel Hun Choi
Cancer Res Treat. 2020;52(1):320-333.   Published online August 5, 2019
DOI: https://doi.org/10.4143/crt.2019.124
AbstractAbstract PDFPubReaderePub
Purpose
We aimed to develop and validate individual prognostic models in a large cohort of cervical cancer patients that were primarily treated with radical hysterectomy.
Materials and Methods
We analyzed 1,441 patients with early-stage cervical cancer treated between 2000 and 2008 from the Korean Gynecologic Oncology Group multi-institutional cohort: a train cohort (n=788) and a test cohort (n=653). Models predicting the risk for overall survival (OS), disease- free survival (DFS), lymphatic recurrence and hematogenous recurrence were developed using Cox analysis and stepwise backward selection and best-model options. The prognostic performance of each model was assessed in an independent patient cohort. Model-classified risk groups were compared to groups based on traditional risk factors.
Results
Independent risk factors for OS, DFS, lymphatic recurrence, and hematogenous recurrence were identified for prediction model development. Different combinations of risk factors were shown for each outcome with best predictive value. In train cohort, area under the curve (AUC) at 2 and 5 years were 0.842/0.836 for recurrence, and 0.939/0.882 for OS. When applied to a test cohort, the model also showed accurate prediction result (AUC at 2 and 5 years were 0.799/0.723 for recurrence, and 0.844/0.806 for OS, respectively). The Kaplan-Meier plot by proposed model-classified risk groups showed more distinctive survival differences between each risk group.
Conclusion
We developed prognostic models for OS, DFS, lymphatic and hematogenous recurrence in patients with early-stage cervical cancer. Combining weighted clinicopathologic factors, the proposed model can give more individualized predictions in clinical practice.

Citations

Citations to this article as recorded by  
  • External validation of the annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer
    Luigi A. De Vitis, Gabriella Schivardi, Aurora Gaeta, Giuseppe Caruso, Marina Rosanu, Lucia Ribero, Diletta Fumagalli, Jvan Casarin, Ilaria Betella, Giorgio Bogani, Carrie L. Langstraat, Giovanni D. Aletti, Nicoletta Colombo, Vanna Zanagnolo, Sara Gandini
    International Journal of Gynecological Cancer.2025; : 101756.     CrossRef
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    Chun Gao, Qian Zhou, Liting Liu, Hong Liu, Yifan Yang, Shen Qu, Qing He, Yafei Huang, Ximiao He, Hui Wang
    Phenomics.2025;[Epub]     CrossRef
  • Which factors predict the effectiveness of adjuvant treatment in patients with non-high-risk early-stage cervical cancer? Ancillary analysis of KGOG-1028
    Junhwan Kim, Jieun Jang, Myong Cheol Lim, Moon-Hong Kim, Yun Hwan Kim, Eun Seop Song, Seok Ju Seong, Dong Hoon Suh, Jong-Min Lee, Chulmin Lee, Chel Hun Choi, Sokbom Kang
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    David Cibula, Lukáš Dostálek, Jiri Jarkovsky, Constantijne H. Mom, Aldo Lopez, Henrik Falconer, Anna Fagotti, Ali Ayhan, Sarah H. Kim, David Isla Ortiz, Jaroslav Klat, Andreas Obermair, Fabio Landoni, Juliana Rodriguez, Ranjit Manchanda, Jan Kosťun, Ricar
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  • 9,461 View
  • 297 Download
  • 24 Web of Science
  • 25 Crossref
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Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer
E Sun Paik, Hyun Jin Choi, Tae-Joong Kim, Jeong-Won Lee, Byoung-Gie Kim, Duk-Soo Bae, Chel Hun Choi
Cancer Res Treat. 2018;50(2):461-473.   Published online May 22, 2017
DOI: https://doi.org/10.4143/crt.2017.104
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients.
Materials and Methods
We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation,we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database.
Results
We identified 21 mRNAs, and seven methylated DNAs from primary EOC tissues that predicted lymphatic invasion and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (p < 0.001 and p=0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (log-rank p-value=0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients’ survival.
Conclusion
Molecular signature model predicting lymphatic invasion was well performed and also associated with survival of EOC patients.

Citations

Citations to this article as recorded by  
  • Identifying Stage II Colorectal Cancer Recurrence Associated Genes by Microarray Meta-Analysis and Building Predictive Models with Machine Learning Algorithms
    Wei Lu, Xiang Pan, Siqi Dai, Dongliang Fu, Maxwell Hwang, Yingshuang Zhu, Lina Zhang, Jingsun Wei, Xiangxing Kong, Jun Li, Qian Xiao, Kefeng Ding, Quan Cheng
    Journal of Oncology.2021; 2021: 1.     CrossRef
  • 10,220 View
  • 249 Download
  • 5 Web of Science
  • 1 Crossref
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Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer
E Sun Paik, Insuk Sohn, Sun-Young Baek, Minhee Shim, Hyun Jin Choi, Tae-Joong Kim, Chel Hun Choi, Jeong-Won Lee, Byoung-Gie Kim, Yoo-Young Lee, Duk-Soo Bae
Cancer Res Treat. 2017;49(3):635-642.   Published online September 27, 2016
DOI: https://doi.org/10.4143/crt.2016.282
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS).
Materials and Methods
We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV).
Results
In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively.
Conclusion
Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes.

Citations

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  • The Gustave Roussy immune score as a novel scoring system for predicting platinum resistance in advanced high-grade serous ovarian cancer
    Xianglin Nie, Ting Xu, Lin Zhang, Wenjun Cheng
    European Journal of Obstetrics & Gynecology and Reproductive Biology.2024; 294: 97.     CrossRef
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    Qingyi Wang, Zhuo Chang, Xiaofang Liu, Yunrui Wang, Chuwen Feng, Yunlu Ping, Xiaoling Feng
    Journal of Medical Internet Research.2024; 26: e48527.     CrossRef
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    Maowei Ni, Danying Wan, Junzhou Wu, Wangang Gong, Junjian Wang, Zhiguo Zheng
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