Multiple genetic alterations to predict the clinical outcome for bevacizumab plus chemotherapy in advanced ovarian cancer: A retrospective study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17037-e17037
Author(s):  
Nan Du ◽  
Jie Gao ◽  
Fang Li ◽  
Zihao Liu ◽  
Huoming Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Target Therapy ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
P Value ◽  
Positive Trend ◽  
Wild Type

e17037 Background: Bevacizumab(BV) plus chemotherapy is widely used in patients with advanced ovarian cancer(OC). However, there was not predict biomakers to determined the use of BV-based treatment in OC currently.Therefore, exploring the predict biomarkers for BV is imperative. Methods: Tumor issues of advanced OC treated with BV plus chemotherapy were used for next generation sequencing (NGS) with a 150-gene targeted panel. The correlation between Progression-Free Survival (PFS) and genes or clinicopathology features was analyzed by Kaplan-Meier or Cox regression. For multivariate Cox regression, all factors with a p-value < 0.05 in univariate Cox regression were included. The potential predictive genes would be analyzed with VEGF-related signatures by using 374 OC mRNA data from The Cancer Genome Atlas (TCGA).Statistical analysis was performed using GraphPad Prism and SPSS. Results: 62 Chinese advanced OC patients treated with BV-base therapy were enrolled in this study from May 2015 to March 2018.The median PFS of these patients was 5.7 months , while ORR and DCR rate was 14.5% and 96.8%, repecitively.Patients with EGFR or HER2 alterations had poorer PFS compared with wild-type (EGFR,4.2 months vs. 7.4 months,p = 0.019;HER2,3.8 months vs. 7.3 months, p = 0.045), while MYC amplification patients got better PFS than MYC wild-type patients(17.4 months vs. 6.0 months,p = 0.049). However, in multivariate Cox regression anlysis, EGFR and HER2 were significantly correlated with PFS(P < 0.001 and p = 0.016,respectively),and MYC amplification seemed to have a positive trend(p = 0.052).Moreover,patients with HER2 alterations has a poorer OS(p = 0.008).The VEGF-related signatures analysis results indicated EGFR variants may upregulated VEGFA expression to induced resistant of BV,while downregulation of HIF was significantly correlated with MYC amplification,which was beneficial to efficacy of BV.HER2 alterations has not correlated with VEGF pathways,suggesting HER2 was a poor prognosis of OC instead of an negative predictor of BV. Conclusions: NGS is an effective method to reveal the potential predictor for BV plus chemotherapy in advanced ovarian cancer, and the patients with EGFR or HER2 alterations should consider alternative regimens such as anti-EGFR or anti-HER2 target therapy instead of BV-based regimens.

Double-loaded mature dendritic cell (DC) therapy for non-HLA-restricted patients with advanced ovarian cancer: Final results of a clinical phase I study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3052-3052 ◽  
Author(s):  
Marianne Imhof ◽  
Markus Lipovac ◽  
Lukas Angleitner-Boubenizek ◽  
Johannes Barta ◽  
Ivan Gomez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Responses ◽  
Immune Therapy ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Positive Trend ◽  
Clinical Phase ◽  
Dc Vaccine

3052 Background: Prognosis of ovarian cancer remains poor after initial responsiveness to surgery and chemotherapy followed by high recurrence and mortality rates and new experimental approaches are warranted. Our goal was to evaluate a novel DC-based vaccine, which exploits a unique dual loading strategy to amplify specific anti-tumor short- and long-term immune responses to delay or even prevent recurrent and metastatic disease. Methods: Monocytes were collected via apheresis, matured into DCs and pulsed with two universal tumor associated antigens (uTAA) in our GMP facility. DCs were loaded with TERT and Survivin via two different pathways (mRNA and peptide) to elicit CD8+ and CD4+T cells directly. Endpoints of the study were tolerability and safety, immunological and clinical responses. T cell responses against the IMP and loaded antigens were evaluated by cytokine bead array (CBA) and intracellular staining assays. Results: 15 non HLA-restricted patients with advanced ovarian cancer were enrolled 8 weeks after standard treatment (surgery and chemotherapy). Each patient was vaccinated intradermally on a weekly or fortnightly basis with a maximum of 8 doses of 13*106 double loaded DCs. The majority of treatment related side effects were grade 1 fever and erythema. Overall the therapy was well tolerated. Immune response data is available for 14/15 patients, 1 was withdrawn after the first administration. The IMP leads to strong immune responses with high frequency (>90%), which is proven for both uTAAs in CD8+ as well as CD4+ T cells. A clear positive trend in progression free survival is demonstrated compared to matched historical control. Conclusions: Therapy with our unique double loaded DC vaccine was feasible, safe and well-tolerated by patients. The vaccine was highly immune stimulatory and elicited both, long-term and short-term anti-tumor immune responses, establishing a promising platform for immune therapy for ovarian cancer and all solid tumors in general. The first two authors contributed equally. Clinical trial information: NCT01456065.

Pretreatment CA-125 and Risk of Relapse in Advanced Ovarian Cancer

2006 ◽  
Vol 24 (9) ◽  
pp. 1454-1458 ◽  
Author(s):  
Maurie Markman ◽  
P.Y. Liu ◽  
Mace L. Rothenberg ◽  
Bradley J. Monk ◽  
Mark Brady ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Interaction Analysis ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Continuous Variable ◽  
Ca 125 ◽  
Maintenance Chemotherapy ◽  
Risk Of Relapse

Purpose A previous report suggested the nadir serum CA-125 level within the group of patients with ovarian cancer who achieved normalization of CA-125 accurately defined the risk of relapse. Using similar CA-125 subgroups, we sought to determine if the baseline CA-125 level before initiation of maintenance chemotherapy in women achieving a clinically-defined complete response to primary chemotherapy would be of prognostic value. Patients and Methods Patients included in this retrospective analysis had been treated on one of two previously reported trials of maintenance chemotherapy (three v 12-monthly cycles of paclitaxel; oral altretamine), with a baseline CA-125 level of ≤ 35 u/mL. Progression-free survival (PFS) from study entry was analyzed by the Cox regression model. Results The distribution of premaintenance baseline CA-125 levels for the 384 patients was 58%, 34%, and 8% for values of (A) ≤ 10 u/mL, (B) 11 to 20 u/mL, and (C) 21 to 35 u/mL, respectively. The baseline CA-125 was highly statistically significant, either as a categoric variable (P < .001) or as a continuous variable (P < .0001). Median PFS was 24 months, 17 months, and 7 months for groups (A), (B), and (C), respectively. There was no evidence the CA-125 effect differed by trial or treatment in an interaction analysis (P = .70). Conclusion The baseline CA-125 level before initiation of maintenance chemotherapy strongly predicts the risk of subsequent relapse. Patients with premaintenance baseline CA-125 values ≤ 10 u/mL have a superior PFS compared with higher levels in the normal CA-125 range.

ATL

2014 ◽  
Vol 24 (8) ◽  
pp. 1395-1400 ◽  
Author(s):  
Vilius Rudaitis ◽  
Tadas Zvirblis ◽  
Daiva Kanopiene ◽  
Dovile Janulynaite ◽  
Laimonas Griskevicius ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Significant Risk ◽  
Advanced Ovarian Cancer ◽  
Advanced Stage ◽  
Wild Type ◽  
Debulking Surgery ◽  
Cox Regression Analysis ◽  
Platinum Based Chemotherapy

ObjectiveThe aim of this study was to explore BRCA mutation frequency and to evaluate its impact on prognosis of advanced-stage ovarian cancer patients treated with debulking surgery and platinum-based chemotherapy.MethodsPatients with advanced-stage epithelial ovarian cancer were enrolled in a prospective, single-center study from September 2008 to December 2011. All cases were screened for BRCA1 and BRCA2 gene mutations. Progression-free survival (PFS) was assessed between BRCA1/2 mutation carriers and BRCA1/2 wild-type patients.ResultsOne hundred seven patients were enrolled and screened for BRCA1 and BRCA2 mutations; 51.4% patients were positive for BRCA1/2 gene mutation, 63.6% of which carried a single Baltic mutation, and 98.2% of them had serous histology. Older age (hazard ratio [HR], 1.032; 95% confidence interval [CI], 1.010–1.055; P = 0.0047), nonoptimal cytoreduction (HR, 3.170; 95% CI, 1.986–5.060; P < 0.0001), and BRCA1/2 wild type (HR, 1.625 [1.003–2.632]; P = 0.0486) were significantly associated with shorter PFS in multivariate Cox regression analysis. Only the nonoptimal cytoreduction was a statistically significant risk factor for shorter overall survival (HR, 2.684; 95% CI, 1.264–5.701; P= 0.0102).ConclusionsAdvanced ovarian cancer patients harboring BRCA1/2 mutation treated with debulking surgery and platinum-based adjuvant chemotherapy have a longer PFS.

The impact of interval cytoreduction and age in advanced-stage ovarian cancer: A GOG ancillary study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5056-5056
Author(s):  
Stuart M. Lichtman ◽  
James Java ◽  
John L. Lovecchio ◽  
Dennis Chi ◽  
William P. Tew ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Residual Disease ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Ancillary Study ◽  
Primary Surgery ◽  
The Impact

5056 Background: To determine if an age group exists for which interval cytoreductive surgery (ICS) in patients with suboptimal residual disease at primary surgery influences progression free survival (PFS) and overall survival (OS) among women with advanced ovarian cancer treated on GOG 182. Methods: GOG 182 was a prospective, randomized trial of first-line chemotherapy in patients with advanced ovarian cancer. Patients with both optimal and suboptimal residual disease were included, and those with suboptimal residual were considered for ICS, with intent registered and stratified prior to randomization. Patients were randomized to one of five chemotherapy arms, employing combinations of either two or three agents delivered intravenously, with a control arm of paclitaxel and carboplatin. A retrospective analysis was approved by the GOG Ancillary Study Committee to investigate the influence of age on treatment and outcomes. In that analysis, Cox regression was used to identify independent prognostic factors and estimate their covariate effects on the adjusted PFS and OS of patients with suboptimal residual disease. Statistical significance was set at p<0.05. Results: Among the entire eligible study population, 28% (n=1,042) were registered with suboptimal residual disease (> 1 cm) and 109 of these patients elected to undergo ICS. Hazard ratios (HR) were determined for patients undergoing ICS with reference to patients with suboptimal disease not undergoing ICS. Based on the most current follow-up data, the HR for progression or death was not statistically different between the groups, but the HR of death alone was significant at 0.72 (95% CI: 0.57–0.92, p=0.008). There was no significant association of age with ICS in either the PFS or the OS model. Conclusions: In this trial, a patient’s age did not influence the effect of ICS on PFS or OS. There is no demonstrable benefit in PFS associated with ICS, but there was a statistically significant improvement in OS. To elucidate this finding, further study is warranted, likely in the form of a meta-analysis incorporating data from other prospective trials.

scholarly journals Evaluating the Association between Clinical Characteristics with Progression-Free Survival and 3-Year Survival in Patients with Epithelial Ovarian Cancer

2021 ◽  
Vol 15 (4) ◽  
pp. 162
Author(s):  
Brahmana Askandar Tjokroprawiro ◽  
Sonny Fadli ◽  
Budiono Budiono
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Disease Recurrence ◽  
P Value ◽  
Free Survival ◽  
Hazard Ratios

Background: This study was conducted to determine the association between clinical characteristics, progression-free survival (PFS), and 3-year survival in patients with epithelial ovarian cancer who underwent surgery in 2016-2017 at RSUD Dr. Soetomo. This study was carried out with the hope of contributing to services for patients with epithelial ovarian cancer to improve outcomes at RSUD Dr. Soetomo. Methods: This retrospective analytic study used medical record data. Survival analysis was done employing Kaplan-Meier and log-rank tests, while Cox regression was utilized to analyze characteristics, recurrence, and mortality. Results: In 2016-2017, 56 patients with epithelial ovarian cancer met the inclusion criteria. Clinical characteristics of residue, stage had significant associations with PFS (P-value of 0.007 and P-value of 0.005, respectively). Residue, stage, histopathology, and the number of chemotherapy cycles had significant associations with 3-year survival (P-value of 0.001, P-value of < 0.001, P-value of < 0.001, P-value of 0.031, respectively). Recurrence and stage had a significant association with the following hazard ratios: stage I HR: 1 (CI 95%, P-value 0.145), stage II HR: 6.5 (CI 95% 0.6–74.7, P-value 0.134), stage III HR: 12.2 (CI 95% 1.4–105.4, P-value 0.061), and stage IV HR: 10.4 (CI 95% 0.8–120.8, P-value 0.061). Mortality had significant associations with stage, histopathology, and the number of chemotherapy cycles, with hazard ratios as follows: stage IV HR: 43.6 (CI 95% 4.5–417.9, P-value 0.001), seromucinous histopathology HR: 20.1 (CI 95% 0.9–408.6, P-value 0.026), chemotherapy cycles < 3 HR: 3.6 (CI 95% 1.2–11.5, P-value 0.459), and > 3 HR: 1 (CI 95%, P-value 0.028).Conclusions: Residue and stage had statistically significant associations with PFS and can be predictors for disease recurrence. Residue, stage, histopathology, number of chemotherapy cycles had significant associations with 3-year survival, but only the latter three characteristics can be predictors for mortality

Wnt Signaling and Survival of Women With High-Grade Serous Ovarian Cancer: A Brief Report

2016 ◽  
Vol 26 (6) ◽  
pp. 1078-1080 ◽  
Author(s):  
Brandon-Luke L. Seagle ◽  
Monica Dandapani ◽  
Judy Y. Yeh ◽  
Shohreh Shahabi
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Wnt Signaling ◽  
Cancer Survival ◽  
Cox Regression ◽  
Case Fatality ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Chemotherapy Response ◽  
Free Survival

ObjectiveOvarian cancer is the gynecologic malignancy with the highest case-fatality rate due to the development of chemotherapy resistance. Predictors of chemotherapy response are needed to guide chemotherapy selection and improve survival for patients with ovarian cancer. Wnt signaling may impact chemoresistance in ovarian cancer.MethodsWe studied The Cancer Genome Atlas patients with ovarian cancer treated with intraperitoneal or intravenous-only adjuvant chemotherapy. Cox regression tested associations of expression of 26 Wnt pathway genes with progression-free survival and overall survival. Permutation tests compared survival between chemotherapy groups stratified by expression.Pvalues are two-tailed.ResultsIncreasedFZD3was associated with increased survival (intraperitoneal group, overall survival: hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.11–0.72,P= 0.009; progression-free survival: HR, 0.58; 95% CI, 0.37–0.92,P= 0.020) (intravenous-only group, overall survival: HR, 0.85; 95% CI, 0.72–0.99,P= 0.039; progression-free survival: HR, 0.83; 95% CI, 0.73–0.95,P= 0.006). LowFZD3predicted decreased overall survival after intraperitoneal versus intravenous-only chemotherapy (21.7 vs 33.3 months,P< 0.0001). IncreasedAPC2was associated with decreased overall survival (HR, 1.22; 95% CI, 1.05–1.42;P= 0.009) and progression-free survival (HR, 1.28; 95% CI, 1.12–1.45;P= 0.0002).ConclusionsUp-regulated tumor Wnt signaling predicts increased ovarian cancer survival.FZD3may predict benefit from intraperitoneal chemotherapy.

scholarly journals The Prognostic and Predictive Role of Somatic BRCA Mutations in Ovarian Cancer: Results from a Multicenter Cohort Study

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 565
Author(s):  
Angela Toss ◽  
Claudia Piombino ◽  
Elena Tenedini ◽  
Alessandra Bologna ◽  
Elisa Gasparini ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Positive Impact ◽  
Progression Free Survival ◽  
Molecular Testing ◽  
Wild Type ◽  
Brca Mutations ◽  
Multicenter Cohort Study ◽  
Advanced Stages ◽  
Predictive Role

Previous research involving epithelial ovarian cancer patients showed that, compared to germline BRCA (gBRCA) mutations, somatic BRCA (sBRCA) mutations present a similar positive impact with regard to overall survival (OS) and platinum and PARP (poly (ADP-ribose) polymerase) inhibitor sensitivity. Nevertheless, molecular testing in these studies did not include copy number variation (CNV) analyses of BRCA genes. The aim of this study was to explore the prognostic and predictive role of sBRCA mutations as compared to gBRCA mutations in patients who were also tested for CNVs. Among the 158 patients included in the study, 17.09% of patients carried a pathogenic or likely pathogenic gBRCA variant and 15.19% of patients presented pathogenetic or likely pathogenic sBRCA variants and/or CNVs. Overall, 81.6% of the patients included in this study were diagnosed with a serous histotype, and 77.2% were in advanced stages. Among women diagnosed in advanced stages, gBRCA patients showed better progression-free survival and OS as compared to sBRCA and wild-type patients, whereas sBRCA patients did not show any advantage in outcome as compared to wild-type patients. In this study, the introduction of CNV analyses increased the detection rate of sBRCA mutations, and the resulting classification among gBRCA, sBRCA and wild-type patients was able to properly stratify the prognosis of OC patients. Particularly, sBRCA mutation patients failed to show any outcome advantage as compared to wild-type patients.

scholarly journals Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

2016 ◽  
Vol 397 (12) ◽  
pp. 1265-1276 ◽  
Author(s):  
Nancy Ahmed ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Enken Drecoll ◽  
Matthias Kotzsch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Residual Tumor ◽  
Mrna Levels ◽  
Serous Ovarian Cancer ◽  
Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

scholarly journals High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Min Li ◽  
Xue Cheng ◽  
Rong Rong ◽  
Yan Gao ◽  
Xiuwu Tang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Paraffin Section ◽  
Progression Free Survival ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Systematic Analysis ◽  
Cox Regression Analysis ◽  
Genes Expression ◽  
High Level

Abstract Background High-grade serous ovarian cancer (HGSOC) is a fatal form of ovarian cancer. Previous studies indicated some potential biomarkers for clinical evaluation of HGSOC prognosis. However, there is a lack of systematic analysis of different expression genes (DEGs) to screen and detect significant biomarkers of HGSOC. Methods TCGA database was conducted to analyze relevant genes expression in HGSOC. Outcomes of candidate genes expression, including overall survival (OS) and progression-free survival (PFS), were calculated by Cox regression analysis for hazard rates (HR). Histopathological investigation of the identified genes was carried out in 151 Chinese HGSOC patients to validate gene expression in different stages of HGSOC. Results Of all 57,331 genes that were analyzed, FAP was identified as the only novel gene that significantly contributed to both OS and PFS of HGSOC. In addition, FAP had a consistent expression profile between carcinoma-paracarcinoma and early-advanced stages of HGSOC. Immunological tests in paraffin section also confirmed that up-regulation of FAP was present in advanced stage HGSOC patients. Prediction of FAP network association suggested that FN1 could be a potential downstream gene which further influenced HGSOC survival. Conclusions High-level expression of FAP was associated with poor prognosis of HGSOC via FN1 pathway.

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