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Development of Web-Based Nomograms to Predict Treatment Response and Prognosis of Epithelial Ovarian Cancer
Se Ik Kim, Minsun Song, Suhyun Hwangbo, Sungyoung Lee, Untack Cho, Ju-Hyun Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Dae-Shik Suh, Taesung Park, Yong-Sang Song
Cancer Res Treat. 2019;51(3):1144-1155.   Published online November 20, 2018
DOI: https://doi.org/10.4143/crt.2018.508
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Discovery of models predicting the exact prognosis of epithelial ovarian cancer (EOC) is necessary as the first step of implementation of individualized treatment. This study aimed to develop nomograms predicting treatment response and prognosis in EOC.
Materials and Methods
We comprehensively reviewed medical records of 866 patients diagnosed with and treated for EOC at two tertiary institutional hospitals between 2007 and 2016. Patients’ clinico-pathologic characteristics, details of primary treatment, intra-operative surgical findings, and survival outcomes were collected. To construct predictive nomograms for platinum sensitivity, 3-year progression-free survival (PFS), and 5-year overall survival (OS), we performed stepwise variable selection by measuring the area under the receiver operating characteristic curve (AUC) with leave-one-out cross-validation. For model validation, 10-fold cross-validation was applied.
Results
The median length of observation was 42.4 months (interquartile range, 25.7 to 69.9 months), during which 441 patients (50.9%) experienced disease recurrence. The median value of PFS was 32.6 months and 3-year PFS rate was 47.8% while 5-year OS rate was 68.4%. The AUCs of the newly developed nomograms predicting platinum sensitivity, 3-year PFS, and 5-year OS were 0.758, 0.841, and 0.805, respectively. We also developed predictive nomograms confined to the patients who underwent primary debulking surgery. The AUCs for platinum sensitivity, 3-year PFS, and 5-year OS were 0.713, 0.839, and 0.803, respectively.
Conclusion
We successfully developed nomograms predicting treatment response and prognosis of patients with EOC. These nomograms are expected to be useful in clinical practice and designing clinical trials.

Citations

Citations to this article as recorded by  
  • Comprehensive analyses of mitophagy-related genes and mitophagy-related lncRNAs for patients with ovarian cancer
    Jianfeng Zheng, Shan Jiang, Xuefen Lin, Huihui Wang, Li Liu, Xintong Cai, Yang Sun
    BMC Women's Health.2024;[Epub]     CrossRef
  • Peripheral and tumor‐infiltrating immune cells are correlated with patient outcomes in ovarian cancer
    Weiwei Zhang, Yawen Ling, Zhidong Li, Xingchen Peng, Yazhou Ren
    Cancer Medicine.2023; 12(8): 10045.     CrossRef
  • Nonalcoholic fatty liver disease and early prediction of gestational diabetes mellitus using machine learning methods
    Seung Mi Lee, Suhyun Hwangbo, Errol R. Norwitz, Ja Nam Koo, Ig Hwan Oh, Eun Saem Choi, Young Mi Jung, Sun Min Kim, Byoung Jae Kim, Sang Youn Kim, Gyoung Min Kim, Won Kim, Sae Kyung Joo, Sue Shin, Chan-Wook Park, Taesung Park, Joong Shin Park
    Clinical and Molecular Hepatology.2022; 28(1): 105.     CrossRef
  • Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer Part 2: Medical Perspectives
    Stanislas Quesada, Michel Fabbro, Jérôme Solassol
    Cancers.2022; 14(4): 1098.     CrossRef
  • Construction and validation of a transcription factors-based prognostic signature for ovarian cancer
    Qingyuan Cheng, Liman Li, Mingxia Yu
    Journal of Ovarian Research.2022;[Epub]     CrossRef
  • Predicting preterm birth through vaginal microbiota, cervical length, and WBC using a machine learning model
    Sunwha Park, Jeongsup Moon, Nayeon Kang, Young-Han Kim, Young-Ah You, Eunjin Kwon, AbuZar Ansari, Young Min Hur, Taesung Park, Young Ju Kim
    Frontiers in Microbiology.2022;[Epub]     CrossRef
  • Prognostic nomogram that predicts progression-free survival and overall survival of patients with ovarian clear cell carcinoma
    Jiayi Li, Dongyan Cao
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Recent Advances and Future Directions of Diagnostic and Prognostic Prediction Models in Ovarian Cancer
    Judan Zeng, Wenjiao Cao, Lihua Wang
    Journal of Shanghai Jiaotong University (Science).2021; 26(1): 10.     CrossRef
  • Sphingolipids as multifaceted mediators in ovarian cancer
    MelissaR Pitman, Martin K. Oehler, Stuart M. Pitson
    Cellular Signalling.2021; 81: 109949.     CrossRef
  • Development and validation for prognostic nomogram of epithelial ovarian cancer recurrence based on circulating tumor cells and epithelial–mesenchymal transition
    Jiani Yang, Jun Ma, Yue Jin, Shanshan Cheng, Shan Huang, Nan Zhang, Yu Wang
    Scientific Reports.2021;[Epub]     CrossRef
  • Prediction Models for the Clinical Severity of Patients With COVID-19 in Korea: Retrospective Multicenter Cohort Study
    Bumjo Oh, Suhyun Hwangbo, Taeyeong Jung, Kyungha Min, Chanhee Lee, Catherine Apio, Hyejin Lee, Seungyeoun Lee, Min Kyong Moon, Shin-Woo Kim, Taesung Park
    Journal of Medical Internet Research.2021; 23(4): e25852.     CrossRef
  • Development of Machine Learning Models to Predict Platinum Sensitivity of High-Grade Serous Ovarian Carcinoma
    Suhyun Hwangbo, Se Ik Kim, Ju-Hyun Kim, Kyung Jin Eoh, Chanhee Lee, Young Tae Kim, Dae-Shik Suh, Taesung Park, Yong Sang Song
    Cancers.2021; 13(8): 1875.     CrossRef
  • M2 Macrophage-Based Prognostic Nomogram for Gastric Cancer After Surgical Resection
    Jianwen Hu, Yongchen Ma, Ju Ma, Yanpeng Yang, Yingze Ning, Jing Zhu, Pengyuan Wang, Guowei Chen, Yucun Liu
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Prognosis for intrahepatic cholangiocarcinoma patients treated with postoperative adjuvant transcatheter hepatic artery chemoembolization
    Ji-Bin Liu, Kai-Jian Chu, Chang-Chun Ling, Ting-Miao Wu, Hui-Min Wang, Yi Shi, Zhi-Zhen Li, Jing-Han Wang, Zhi-Jun Wu, Xiao-Qing Jiang, Gao-Ren Wang, Yu-Shui Ma, Da Fu
    Current Problems in Cancer.2020; 44(6): 100612.     CrossRef
  • Can we predict who lives long with ovarian cancer?
    Michael A. Bookman
    Cancer.2019; 125(S24): 4578.     CrossRef
  • 10,447 View
  • 268 Download
  • 16 Web of Science
  • 15 Crossref
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Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2
Kyung Jin Eoh, Ji Eun Kim, Hyung Seok Park, Seung-Tae Lee, Ji Soo Park, Jung Woo Han, Jung-Yun Lee, Sunghoon Kim, Sang Wun Kim, Jae Hoon Kim, Young Tae Kim, Eun Ji Nam
Cancer Res Treat. 2018;50(3):917-925.   Published online September 27, 2017
DOI: https://doi.org/10.4143/crt.2017.220
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS.
Materials and Methods
Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 toDecember 2016.GermlineDNAwas sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing.
Results
Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance.
Conclusion
Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.

Citations

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  • 16,958 View
  • 810 Download
  • 37 Web of Science
  • 35 Crossref
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Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies
Eun Jin Heo, Young Jae Cho, William Chi Cho, Ji Eun Hong, Hye-Kyung Jeon, Doo-Yi Oh, Yoon-La Choi, Sang Yong Song, Jung-Joo Choi, Duk-Soo Bae, Yoo-Young Lee, Chel Hun Choi, Tae-Joong Kim, Woong-Yang Park, Byoung-Gie Kim, Jeong-Won Lee
Cancer Res Treat. 2017;49(4):915-926.   Published online January 4, 2017
DOI: https://doi.org/10.4143/crt.2016.322
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research.
Materials and Methods
We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues.
Results
Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor–overexpressing PDX with clear cell histology (p=0.023).
Conclusion
PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.

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Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients
Kyung Jin Eoh, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Jeongwoo Han, Jung-Yun Lee, Sang Wun Kim, Sunghoon Kim, Young Tae Kim, Eun Ji Nam
Cancer Res Treat. 2017;49(2):408-415.   Published online July 27, 2016
DOI: https://doi.org/10.4143/crt.2016.135
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to investigate the clinical features of epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status (mutation, variant of uncertain significance [VUS], or wild type).
Materials and Methods
We analyzed 116 patients whose BRCA1/2 genetic test results were available for mutation type and clinical features, including progression-free survival (PFS), overall survival (OS), and response rate. These characteristics were compared according to BRCA1/2 mutation status.
Results
Thirty-seven (37/116, 31.9%) BRCA1/2 mutations were identified (BRCA1, 30; BRCA2, 7). Mutation of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients (5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal histories of breast cancer were observed in 48.6% of patients with BRCA1/2 mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively).
Conclusion
Patientswith BRCA1/2 mutation had longer OS than thosewith BRCA1/2wild type. Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.

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Safety of Fertility-Sparing Surgery in Primary Mucinous Carcinoma of the Ovary
Jung-Yun Lee, Yu Ri Jo, Tae Hun Kim, Hee Seung Kim, Min A Kim, Jae Weon Kim, Noh Hyun Park, Yong-Sang Song
Cancer Res Treat. 2015;47(2):290-305.   Published online August 29, 2014
DOI: https://doi.org/10.4143/crt.2014.004
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study is to evaluate the safety of fertility-sparing surgery as the treatment for patients with primary mucinous epithelial ovarian cancer.
Materials and Methods
A retrospective study of patients with mucinous ovarian cancer between 1991 and 2010 was performed. The demographics and survival outcomes were compared between patients who underwent fertility-sparing surgery and those who underwent radical surgery.
Results
A total of 110 patients underwent primary surgery. At the time of surgery, tumors appeared to be grossly confined to the ovaries in 90 patients, and evidence of metastasis was definite in 20 patients. Of the 90 patients with tumors that appeared to be grossly confined to the ovaries at surgical exploration, 35 (38.9%) underwent fertility-sparing surgery. The Kaplan- Meier curve and the log rank test showed no difference in either recurrence-free survival (p=0.792) or disease-specific survival (p=0.706) between the two groups. Furthermore, there was no significant difference in recurrence-free survival (p=0.126) or disease-specific survival (p=0.377) between the two groups, even when the analysis was limited to women below the age of 40. In a multivariate Cox model, fertility-sparing surgery had no effect on either recurrence-free survival (recurrence hazard ratio [HR], 1.20; 95% confidence interval [CI], 0.25 to 5.71) or disease-specific survival (death HR, 0.88; 95% CI, 0.17 to 4.60).
Conclusion
Fertility-sparing surgery in primary mucinous cancer grossly confined to the ovaries may be a safe option and one not associated with an increase in recurrence or mortality.

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Case Report
Fatal Ifosfamide-Induced Metabolic Encephalopathy in Patients with Recurrent Epithelial Ovarian Cancer: Report of Two Cases
You-Jung Shin, Ji-Young Kim, Jei-Won Moon, Rae-Mi You, Jeong-Yeol Park, Joo-Hyun Nam
Cancer Res Treat. 2011;43(4):260-263.   Published online December 27, 2011
DOI: https://doi.org/10.4143/crt.2011.43.4.260
AbstractAbstract PDFPubReaderePub
Central nervous system (CNS) toxicity has been reported in approximately 10-30% of patients receiving intravenous infusions of ifosfamide. Encephalopathy is a rare but serious CNS adverse reaction in these patients, and although usually transient and reversible, may cause persistent neurological dysfunction or death. Clinical features range from fatigue and confusion to coma and death. Although methylene blue can be used to treat ifosfamide-induced neurotoxicity, including encephalopathy, its mechanism of action remains poorly defined. We describe here two patients with recurrent epithelial ovarian cancer who experienced fatal encephalopathy following ifosfamide/mesna treatment.

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