scholarly journals Development and validation of Nomograms for predicting overall survival and Cancer-specific survival in patients with ovarian clear cell carcinoma

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Qian Chen ◽  
Shu Wang ◽  
Jing-He Lang
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Cox Regression ◽  
Validation Cohort ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Ovarian Clear Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Training Cohort ◽  
Organ Metastasis

Abstract Background Ovarian clear cell carcinoma (OCCC) is a rare histologic type of ovarian cancer. There is a lack of an efficient prognostic predictive tool for OCCC in clinical work. This study aimed to construct and validate nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with OCCC. Methods Data of patients with primary diagnosed OCCC in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016 was extracted. Prognostic factors were evaluated with LASSO Cox regression and multivariate Cox regression analysis, which were applied to construct nomograms. The performance of the nomogram models was assessed by the concordance index (C-index), calibration plots, decision curve analysis (DCA) and risk subgroup classification. The Kaplan-Meier curves were plotted to compare survival outcomes between subgroups. Results A total of 1541 patients from SEER registries were randomly divided into a training cohort (n = 1079) and a validation cohort (n = 462). Age, laterality, stage, lymph node (LN) dissected, organ metastasis and chemotherapy were independently and significantly associated with OS, while laterality, stage, LN dissected, organ metastasis and chemotherapy were independent risk factors for CSS. Nomograms were developed for the prediction of 3- and 5-year OS and CSS. The C-indexes for OS and CSS were 0.802[95% confidence interval (CI) 0.773–0.831] and 0.802 (0.769–0.835), respectively, in the training cohort, while 0.746 (0.691–0.801) and 0.770 (0.721–0.819), respectively, in the validation cohort. Calibration plots illustrated favorable consistency between the nomogram predicted and actual survival. C-index and DCA curves also indicated better performance of nomogram than the AJCC staging system. Significant differences were observed in the survival curves of different risk subgroups. Conclusions We have constructed predictive nomograms and a risk classification system to evaluate the OS and CSS of OCCC patients. They were validated to be of satisfactory predictive value, and could aid in future clinical practice.

scholarly journals Development and Validation of Nomograms for Predicting Overall Survival and Cancer-Specific Survival in Patients with Ovarian Clear Cell Carcinoma

2020 ◽  
Author(s):  
Qian Chen ◽  
Shu Wang ◽  
Jing-he Lang
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Cox Regression ◽  
Validation Cohort ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Ovarian Clear Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Training Cohort ◽  
Organ Metastasis

Abstract Background: Ovarian clear cell carcinoma (OCCC) is a rare histologic type of ovarian cancer. There is a lack of an efficient prognostic predictive tool for OCCC in clinical work. This study aimed to construct and validate nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with OCCC.Methods: Data of patients with primary diagnosed OCCC in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016 was extracted. Prognostic factors were evaluated with LASSO Cox regression and multivariate Cox regression analysis, which were applied to construct nomograms. The performance of the nomogram models was assessed by the concordance index (C-index), calibration plots, decision curve analysis (DCA) and risk subgroup classification. The Kaplan-Meier curves were plotted to compare survival outcomes between subgroups.Results: A total of 1541 patients from SEER registries were randomly divided into a training cohort (n=1079) and a validation cohort (n=462). Age, laterality, stage, lymph node (LN) dissected, organ metastasis and chemotherapy were independently and significantly associated with OS, while laterality, stage, LN dissected, organ metastasis and chemotherapy were independent risk factors for CSS. Nomograms were developed for the prediction of 3‐ and 5‐year OS and CSS. The C-indexes for OS and CSS were 0.802[95% confidence interval (CI) 0.773-0.831] and 0.802 (0.769-0.835), respectively, in the training cohort, while 0.746 (0.691-0.801) and 0.770 (0.721-0.819), respectively, in the validation cohort. Calibration plots illustrated favorable consistency between the nomogram predicted and actual survival. C-index and DCA curves also indicated better performance of nomogram than the AJCC staging system. Significant differences were observed in the survival curves of different risk subgroups.Conclusions: We have constructed predictive nomograms and a risk classification system to evaluate the OS and CSS of OCCC patients. They were validated to be of satisfactory predictive value, and could aid in future clinical practice.

scholarly journals Development and Validation of Nomograms for Predicting Overall Survival and Cancer-Specific Survival in Patients with Ovarian Clear Cell Carcinoma

2020 ◽  
Author(s):  
Qian Chen ◽  
Shu Wang ◽  
Jing-he Lang
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Cox Regression ◽  
Validation Cohort ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Ovarian Clear Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Training Cohort ◽  
Organ Metastasis

Abstract Background Ovarian clear cell carcinoma (OCCC) is a rare histologic type of ovarian cancer. There is a lack of useful prognostic predictive tool for OCCC in clinical work. This study aimed to construct and validate nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with OCCC. Methods Data of patients with primary diagnosed OCCC in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016 was extracted. Prognostic factors were evaluated with LASSO COX regression and multivariate Cox regression analysis, which were applied to construct nomograms. The performance of the nomogram models was assessed by concordance index (C-index), calibration plots, decision curve analysis (DCA) and risk subgroup classification. The Kaplan-Meier curves were plotted to compare survival outcomes between subgroups. Results A total of 1541 patients from SEER registries were randomly divided into a training cohort (n = 1079) and a validation cohort (n = 462). Age, laterality, stage, lymph node (LN) dissected, organ metastasis and chemotherapy were independently and significantly associated with OS, while laterality, stage, LN dissected, organ metastasis and chemotherapy were independent risk factors for CSS. Nomograms were developed for prediction of 3- and 5‐year OS and CSS. The C-indexes for OS and CSS were 0.802[95% confidence interval (CI) 0.773–0.831] and 0.802 (0.769–0.835), respectively, in the training cohort, while 0.746 (0.691–0.801) and 0.770 (0.721–0.819), respectively, in the validation cohort. Calibration plots illustrated favorable consistency between the nomogram predicted and actual survival. C-index and DCA curves also indicated better performance of nomogram than the AJCC staging system. Significant differences were observed in survival curves of different risk subgroups. Conclusions We constructed predictive nomograms and a risk classification system to evaluate the OS and CSS of OCCC patients. They were validated to be of satisfactory predictive value, and could aid in future clinical practice.

Fertility sparing surgery for patients with FIGO stage I clear cell ovarian carcinoma: a database analysis and systematic review of the literature

2020 ◽  
Vol 30 (9) ◽  
pp. 1372-1377 ◽  
Author(s):  
Dimitrios Nasioudis ◽  
Lakeisha Mulugeta-Gordon ◽  
Erin McMinn ◽  
Melissa K Frey ◽  
Eloise Chapman-Davis ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Radical Surgery ◽  
Clear Cell Carcinoma ◽  
Stage I ◽  
Ovarian Clear Cell Carcinoma ◽  
Fertility Sparing Surgery ◽  
Fertility Sparing

ObjectiveFertility sparing surgery for patients with early stage ovarian clear cell carcinoma is controversial. We aimed to investigate the impact of fertility sparing surgery on the oncologic outcomes of young patients with stage I ovarian clear cell carcinoma.MethodsThe National Cancer Database was accessed and patients with pathological stage IA or IC ovarian clear cell carcinoma, aged <45 years, were selected. Based on site specific surgery codes, patients who underwent fertility sparing or radical surgery were identified. Overall survival was evaluated following generation of Kaplan–Meier curves, and compared with the log rank test. Multivariate Cox analysis was performed to control for possible confounders. A systematic review of literature of the Pubmed, EMBASE and Web of Science databases was also performed to summarize all reported cases.ResultsA total of 57 (35.8%) and 102 (64.2%) patients underwent fertility sparing and radical surgery. There was no difference in overall survival between patients who had fertility sparing and radical surgery (p=0.92); 5 year overall survival rates were 89% and 87.9%, respectively. After controlling for the performance of lymphadenectomy and disease substage, fertility sparing surgery was not associated with worse survival (hazard ratio 0.83, 95% confidence interval 0.30 to 2.32). A systematic review of the literature identified 132 patients with stage I disease who underwent fertility sparing surgery; a total of 20 patients (15.2%) experienced a relapse at a median of 18 months from surgery.ConclusionsIn a large cohort of young patients with stage I ovarian clear cell carcinoma, fertility sparing surgery was not associated with worse survival.

scholarly journals High PON1 Expression Predicts Poor Prognosis In Kidney Renal Clear Cell Carcinoma

2021 ◽  
Author(s):  
Chenxia Jiang ◽  
Xinyu Zhang ◽  
Xiaoyan Li ◽  
Jia Li ◽  
Hua Huang
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Independent Prognostic Factor ◽  
Cox Regression Analysis

Abstract Background: Relevant study had demonstrated that Paraoxonase-1 (PON1) had relationship with occurrence and development of tumors which suggested that PON1 was a key gene in promoting tumor progression. However, the relationship between PON1 and Kidney renal clear cell carcinoma (KIRC) is still unclear so far. Methods: We downloaded relevant data about KIRC from TCGA dataset and compared it with normal renal tissues. Immunohistochemistry (IHC) was applied to analyze the expression of PON1. Univariate cox regression analysis and multivariate cox regression analysis were also utilized to analyze independent factors associated with prognosis. Gene set enrichment analysis was conducted to find the signaling pathways of PON1 in KIRC. Finally, we also investigated whether PON1 had relationship with immunity. Results: As shown in results, PON1 expression was decreased in KIRC compared with adjacent paracancer tissues. Immunohistochemistry (IHC) was utilized to find the expression of PON1. After survival analysis, the high expression of PON1 was significantly related to overall survival (P<0.001). Univariate/Multivariate cox regression analysis both revealed that PON1 could serve as an independent prognostic factor. To analyze overall survival (OS) of patients with KIRC, nomogram was developed. GSEA revealed that PON1 was correlated with homologous recombination. Besides, PON1 had few relationships with immunity. Conclusions: Our results revealed that PON1 could serve as an independent prognostic factor for KIRC, providing a novel target for KIRC future treatments.

HERV-K Hypomethylation in Ovarian Clear Cell Carcinoma Is Associated With a Poor Prognosis and Platinum Resistance

2011 ◽  
Vol 21 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Kanokwan Iramaneerat ◽  
Prakasit Rattanatunyong ◽  
Nipon Khemapech ◽  
Surang Triratanachat ◽  
Apiwat Mutirangura
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Treatment Response ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Platinum Resistance ◽  
Ovarian Clear Cell Carcinoma ◽  
Platinum Based Chemotherapy

Introduction:In general, ovarian clear cell carcinoma (OCCC) has a history of poor response to standard platinum-based chemotherapy regimens, and advanced cases have short survival periods. Therefore, the discovery of a biomarker for the pretreatment prediction of OCCC is crucial. Loss of methylation of a retrotransposable sequence, such as long interspersed repetitive sequence 1 (LINE-1), frequently occurs in cancers, including ovarian cancer, and it has been proven to be associated with poor survival. The expressions of human endogenous retrovirus (HERV) K and E were found to be increased in tissues from patients with OCCC. Here, we propose that methylation levels of HERV are associated with treatment response and prognosis of OCCC.Methods:Twenty-nine patients with OCCC were enrolled. Methylation levels of HERV-K, HERV-E, and LINE-1 were measured from microdissected cancer and normal ovarian tissues. The methylation levels were correlated with stage, treatment response, and prognosis.Results:Methylation levels of HERV-K, HERV-E, and LINE-1 were decreased in tissues from patients with advanced stage cancer (P= 0.0179,P= 0.0021, andP= 0.0307, respectively). Human endogenous retrovirus K demonstrated significantly lower methylation levels in the platinum-resistant group (P= 0.0004). Patients with lower levels of methylated (hypomethylated) HERV-K had a shorter mean overall survival (P= 0.006). In advanced OCCC cases, patients with hypomethylated HERV-K had shorter mean progression-free survival (P= 0.018) and mean overall survival (P= 0.018) than did patients with higher methylation levels of HERV-K.Conclusions:Methylation levels of HERV-K, HERV-E, and LINE-1 are decreased during OCCC multistep carcinogenesis. Moreover, HERV-K hypomethylation is a promising biomarker for predicting OCCC treatment response and prognosis.

scholarly journals Mismatch Repair Status as a Predictor of Benefit From Platinum-Based Adjuvant Therapy in Ovarian Clear Cell Carcinoma

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 217s-217s
Author(s):  
J. Zhu ◽  
X. Wu ◽  
X. Ju
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Mismatch Repair ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Progression Free Survival ◽  
Ovarian Clear Cell Carcinoma ◽  
Free Survival ◽  
Pathologic Features

Background: Previous studies have indicated that patients with colorectal cancer who demonstrate defective DNA mismatch repair (dMMR) have clinical and pathologic features that distinguish them from patients who have proficient mismatch repair (pMMR) tumors. However, the influence of mismatch repair (MMR) status in ovarian clear cell carcinoma (OCCC) is still unknown. Aim: To evaluate the MMR statuses in OCCC and its correlation with clinicopathological and prognostic characteristics. Methods: MMR statuses were measured by tissue microarray–based immunohistochemistry from 120 OCCC patients. The associations of clinicopathologic features with progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed by Cox regression model. Results: Overall, 120 OCCC patients met the entry criteria and their MMR status were detected, consisting of 24 patients with dMMR and 96 patients with pMMR. Tumors with dMMR were strongly associated with platinum-sensitive disease ( P = 0.008) and large tumor volume ( P = 0.028). Among all the patients who have received surgery, tumors with dMMR had a better progression-free survival and overall survival (OS) than those with pMMR (hazard ratio [HR] for recurrence, 0.459 [95% confidence interval (95% CI), 0.224-0.940]; P = 0.029; HR for death, 0.381 [95% CI, 0.170-0.853]; P = 0.015). In subgroup analysis, dMMR patients experienced a better PFS (HR, 0.242; P = 0.055) and OS (HR, 0.141; P = 0.039) than pMMR cases among early stages (I-II), but this difference was not observed in advanced stage (III-IV) patients. Meanwhile, pMMR was associated with more favorable prognosis than dMMR in platinum-resistant patients (PFS, HR: 0.317, P = 0.052; OS, HR: 0.370, P = 0.046). Multivariate analysis revealed that only advanced stages (III-IV) were adverse independent prognosticators for both PFS (HR, 5.938; [95% CI, 2.804-12.574], P < 0.001) and OS (HR, 6.209; [95% CI, 2.724-14.156], P < 0.001). Conclusion: MMR status in ovarian clear cell carcinoma is not only a prognostic indicator, but also appears to be a possible predictor for the use of platinum-based adjuvant chemotherapy.

scholarly journals Clinical Characteristics and Prognosis of Ovarian Clear Cell Carcinoma: a Retrospective Study of 112 Patients in Beijing

2020 ◽  
Author(s):  
Huimei Zhou ◽  
Qian Liu ◽  
Xiaohua Shi ◽  
Jiaxin Yang ◽  
Dongyan Cao ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Cell Carcinoma ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Stage I ◽  
Stage Iii ◽  
Ca 125 ◽  
Ovarian Clear Cell Carcinoma

Abstract ObjectivesThis retrospective study aimed to evaluate the clinical characteristics and prognosis of ovarian clear cell carcinoma (OCCC) and to further explore the monitoring value of cancer antigen 125 (CA-125).MethodsThe medical records of 112 OCCC patients who were treated in Peking Union Medical College Hospital (PUMCH) between 2014 and 2019 were collected and reviewed, and data such as age, Federation of Gynecology and Obstetrics (FIGO) stage, CA-125 level, treatment, recurrence, and death were extracted.OutcomesThe median patient age was 50 (45, 57) years. Sixty (53.57%) patients were in stage I, 13 (11.61%) patients were in stage II, 22 (28.57%) patients were in stage III, and 7 (6.25%) patients were in stage IV. In total, 109 (97.32%) patients received adjuvant chemotherapy. The median chemotherapy cycles of CA-125 normalization was 2 (0, 3). The 1-year and 3-year progression-free survival (PFS) rates were 87.85% and 72.90%, respectively. The median PFS1 duration was 19 (11, 35) months, and the median overall survival (OS) duration was 24 (13, 40) months. Recurrence occurred in 32 patients, of whom 7 (21.88%) developed platinum-resistant recurrence. Fifty percent of relapsed patients had a CA-125 level<35 IU/ml at the time of relapse. Nine (28.13%) patients experienced a second recurrence. In the multivariate Cox regression analysis, the Chemotherapy cycles of CA-125 normalization remained nonsignificant for stage I (P=0.003, HR 4.287, 95% CI=1.632–11.258) and stage III (P=0.003, HR 4.287, 95% CI=1.632–11.258) disease. Multivariate Cox regression showed that platinum resistance was an independent factor for PFS2 (P=0.008, HR 11.562, 95% CI=1.873–71.353).ConclusionsFIGO stage and chemotherapy resistance are independent risk factors for prognosis. CA-125 levels following treatment are a valid indicator for treatment monitoring. Regardless of chemosensitivity to CA-125, CA-125 normalization before chemotherapy cycle 2 may not be a distinct inflection point for PFS and OS.

scholarly journals Development and Validation of a Radiomic Nomogram for Predicting the Prognosis of Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ruizhi Gao ◽  
Hui Qin ◽  
Peng Lin ◽  
Chenjun Ma ◽  
Chengyang Li ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Cell Carcinoma ◽  
Validation Cohort ◽  
Clear Cell ◽  
Risk Group ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Clinicopathological Parameters ◽  
Training Cohort ◽  
Cox Analysis

PurposeThe present study aims to comprehensively investigate the prognostic value of a radiomic nomogram that integrates contrast-enhanced computed tomography (CECT) radiomic signature and clinicopathological parameters in kidney renal clear cell carcinoma (KIRC).MethodsA total of 136 and 78 KIRC patients from the training and validation cohorts were included in the retrospective study. The intraclass correlation coefficient (ICC) was used to assess reproducibility of radiomic feature extraction. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) as well as multivariate Cox analysis were utilized to construct radiomic signature and clinical signature in the training cohort. A prognostic nomogram was established containing a radiomic signature and clinicopathological parameters by using a multivariate Cox analysis. The predictive ability of the nomogram [relative operating characteristic curve (ROC), concordance index (C-index), Hosmer–Lemeshow test, and calibration curve] was evaluated in the training cohort and validated in the validation cohort. Patients were split into high- and low-risk groups, and the Kaplan–Meier (KM) method was conducted to identify the forecasting ability of the established models. In addition, genes related with the radiomic risk score were determined by weighted correlation network analysis (WGCNA) and were used to conduct functional analysis.ResultsA total of 2,944 radiomic features were acquired from the tumor volumes of interest (VOIs) of CECT images. The radiomic signature, including ten selected features, and the clinical signature, including three selected clinical variables, showed good performance in the training and validation cohorts [area under the curve (AUC), 0.897 and 0.712 for the radiomic signature; 0.827 and 0.822 for the clinical signature, respectively]. The radiomic prognostic nomogram showed favorable performance and calibration in the training cohort (AUC, 0.896, C-index, 0.846), which was verified in the validation cohort (AUC, 0.768). KM curves indicated that the progression-free interval (PFI) time was dramatically shorter in the high-risk group than in the low-risk group. The functional analysis indicated that radiomic signature was significantly associated with T cell activation.ConclusionsThe nomogram combined with CECT radiomic and clinicopathological signatures exhibits excellent power in predicting the PFI of KIRC patients, which may aid in clinical management and prognostic evaluation of cancer patients.

scholarly journals Identification and Validation of PIK3CA as a Marker Associated with Prognosis and Immune Infiltration in Renal Clear Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Ya Li ◽  
Chong Wang ◽  
Yang Gao ◽  
Liang Zhou
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Disease Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Potential Biomarker

Background. Kidney renal clear cell carcinoma (KIRC) is the most prevalent renal malignancy. The therapeutic strategies for advanced KIRC are very few, with only sunitinib being widely approved. Mutations in the PIK3CA gene can affect tumor cell proliferation, metastasis, and patients’ survival. Methods. Bioinformatics analysis was performed to explore the expression and clinical significance of PIK3CA in KIRC. Moreover, qRT-PCR was conducted to verify the result. Results. Subgroup analyses of KIRC tissue based on gender, tumor grade, and cancer stage indicated downregulation of PIK3CA mRNA expression. The KIRC patients with high PIK3CA expression indicated a better overall survival, progression-free survival, and disease-free survival. A predictive nomogram was constructed and demonstrated that the calibration plots for the 3-year and 5-year OS rates were predicted relatively well compared with an ideal model in the TCGA KIRC cohort. The validation study revealed that downregulation of PIK3CA in KIRC tissues and low PIK3CA expression had a poor overall survival with an AUC of 0.775 in the ROC curve. Moreover, Cox regression analysis revealed that PIK3CA expression and clinical stage were independent factors affecting the prognosis of KIRC patients. PIK3CA expression was found to be significantly associated with the abundance of immune cells and immune biomarker sets. PIK3CA and associated genes were found to be mainly associated with immune response and the JAK-STAT signaling pathway. Conclusion. We identified PIK3CA as a potential biomarker for prognosis correlated with immune infiltrates in KIRC. Further studies should focus on the functions of PIK3CA in KIRC carcinogenesis.

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