γ-synuclein expression in ovarian cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5574-5574
Author(s):  
Kristina Mori ◽  
Stacey Akers ◽  
Wiam Bshara ◽  
Barbara Buttin ◽  
Peter J. Frederick ◽  
...  

5574 Background: γ-synuclein (SNCG) expression is associated with advanced disease and chemo-resistance in multiple solid tumors. Our goal was to determine if SNCG expression in ovarian cancer was correlated with clinicopathologic variables and patient outcomes. Methods: Tissue microarrays from primary tumors of 358 ovarian, fallopian tube, and primary peritoneal cancer patients, who underwent primary surgery at Roswell Park Cancer Institute between 1995 and 2007 were constructed and stained for SNCG. A blinded pathologist scored tumors as positive if ≥10% of the sample stained. Medical records were reviewed for clinicopathologic and demographic variables. Between the positive and negative groups, Wilcoxon rank-sum test was used to compare the median ages and Fisher’s exact test was used to compare groups in categorical variables. Cox proportional hazard models were used to determine associations between SNCG and overall (OS) and progression-free survival (PFS). Results: The median follow-up was 36 months, median OS was 39 months, and median PFS was 18 months. SNCG presence was significant in patients with serous histology, grade 3 disease, suboptimal debulking, ascites at surgery, FIGO stage III-IV cancer, or initial CA-125 level >485. There was no significant difference in OS (HR 1.06 95% CI 0.81-1.39 P 0.69) or PFS (HR 1.16 95% CI 0.89-1.50 P 0.28) for patients with SNCG expression. Conclusions: SNCG expression in ovarian cancer is more frequent in patients with high-risk features, but it does not correlate with chemotherapy response, OS, or PFS. [Table: see text]

2010 ◽  
Vol 28 (1) ◽  
pp. 154-159 ◽  
Author(s):  
Richard T. Penson ◽  
Don S. Dizon ◽  
Stephen A. Cannistra ◽  
Maria R. Roche ◽  
Carolyn N. Krasner ◽  
...  

Purpose New strategies are needed to improve outcomes for patients with advanced ovarian cancer. Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes vascular endothelial growth factor but is associated with GI perforations (GIPs) in patients with recurrent disease. Patients and Methods An open-label, phase II clinical trial was conducted in newly diagnosed patients with stage ≥ IC epithelial müllerian tumors. Patients received intravenous (IV) carboplatin (area under the curve = 5), paclitaxel (175 mg/m2 IV), and bevacizumab (15 mg/kg IV) for six to eight cycles on day 1 every 21 days. Bevacizumab was omitted in the first cycle and continued as a single agent for 1 year. Results Sixty-two women participated in this study. Fifty-one patients (82%) were optimally surgically cytoreduced before treatment. The median age was 58 years (range, 18 to 77 years). Forty-five women (73%) had ovarian cancer, 10 (16%) had peritoneal cancer, four (6%) had fallopian tube cancers, and three (5%) had uterine papillary serous tumors. The majority of patients (90%) had stage III or IV disease. A median of 17 maintenance cycles (range, 0 to 25+ cycles) of bevacizumab (556 cycles) were administered with mild toxicity. Treatment was associated with two pulmonary embolisms and two GIPs, all occurring during the chemotherapy phase of treatment (364 total cycles). No grade 4 toxicities were seen during maintenance bevacizumab treatment. Radiographic responses were documented in 21 (75%) of 28 women with measurable disease (11 complete responses and 10 partial responses), with CA-125 responses in 76% of patients (11 complete responses, 21%; and 35 partial responses, 55%). The progression-free survival rate at 36 months was 58%. Conclusion The regimen of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab is feasible, safe, and worthy of future study in advanced ovarian cancer.


2016 ◽  
Author(s):  
Neha Kumar ◽  
Amita Maheshwari ◽  
Sudeep Gupta ◽  
Jaya Ghosh ◽  
Jyoti Bajpai ◽  
...  

Introduction: Both primary (PDS) and interval debulking surgery (IDS) have reported similar progression free survival (PFS) and overall survival (OS) rates in various studies. Complete resection of all macroscopic disease is the strongest independent variable in predicting survival in both groups. Objective: To evaluate the demographics, surgical outcomes and survival in women with advanced ovarian cancer undergoing IDS. Methods: All women with Stage IIIC or Stage IV epithelial ovarian or primary peritoneal cancer, registered at our institution from January 2010 to December 2010, who were treated with NACT followed by IDS, were included in the study. Demographic data, CA-125 levels (baseline and presurgery), chemotherapy and surgical details were collected. Progression free survival (PFS) and overall survival (OS) were calculated and Cox regression and Kaplan-Meier survival analysis were used to evaluate factors associated with survival. Results: One hundred fifty women with Stage IIIC or Stage IV epithelial ovarian or primary peritoneal cancer were included in the analysis. The mean age was 51.08 years (27 to 73 years) and 97.3% had serous histology. Eighty percent (n = 120) had Stage IIIC and 20% (n = 30) had Stage IV disease. Ninety five percent women received Carboplatin and Paclitaxel or single agent Carboplatin as NACT and the median number of NACT cycles was 3. The median baseline CA-125 was 1649.3 U/ml (Range 16.4–235,100 U/ml) and the median CA-125 post NACT was 42.75 U/ml (Range 4.4–5151 U/ml). Seventy four percent women (n = 111) underwent an optimal cytoreduction – 62.7% (n = 94) had R0 and 11.3% (n = 17) had R1 resection. Twenty six percent women (n = 39) had R2 resection. The median CA-125 post NACT was 27.3 U/ml, 36 U/ml and 99 U/ml in women with R0, R1 and R2 resection respectively and the difference was statistically significant (p < 0.0005). The CA125 response was respectively, 97.6%, 95.7% and 93.8% in R0, R1 and R2 resection (p < 0.0005). The median follow up was 42.48 months (Range 1.48–70.93 months). The median PFS was 12.06 months (95% CI 10.02-14.1) – 12.98 months (95% CI 9.7–16.2) in R0, 9.56 months (95% CI 1.7–17.4) in R1 and 6.64 months (95% CI 4.9–8.3) in women with R2 resection (p = 0.158). The median OS was 38.9 months (95% CI 31.7–46.1) – 43.3 months (95% CI 33–53.5) in R0, 46.1 months (95% CI 26.6–65.5) in R1 and 28 months (95% CI 25–30.9) in R2 resection (p = 0.121). The median PFS and OS in women undergoing optimal cytoreduction (R0 and R1) was 12.98 months (95% CI 9.86–16.1) and 43.7 months (95% CI 34.7–52.7) respectively as compared to 6.64 months (95% CI 4.95–8.32) and 28 months (95% CI 25–30.9) respectively in women with R2 resection (PFS p = 0.064, OS p = 0.04). Multivariate analysis discussing the factors affecting the probability of optimal cytoreduction and the survival will be discussed. Conclusion: In women with advanced ovarian cancer undergoing NACT followed by IDS, a high rate of optimal cytoreduction is achieved. Residual disease is a primary factor affecting the survival of these women.


2021 ◽  
Vol 52 (3) ◽  
pp. 205-210
Author(s):  
Miroslav Popović ◽  
Tanja Milić-Radić ◽  
Arnela Cerić-Banićević

Introduction: Ovarian cancer has the highest mortality rate of all gynaecologic malignancies. The aim of this study was the evaluation of the clinical pathological characteristics and survival analysis of primarily operated patients with advanced stages of malignant epithelial ovarian tumour. Methods: The research was conducted as a cohort study with 59 patients with FIGO stage III and IV, which were primarily operated between 1 January 2008 and 31 December 2010 (three years). Age, comorbidities, BMI, presence of ascites, the level of the marker CA-125, histopathology and FIGO stage were analysed. The survival rate was estimated at the level of 1, 3 and 5 years. Results: The median age was 53 years (range 29-86). The most common histopathological type was serous (66.1 %) and the most common FIGO stage was 3a (49.2 %). Optimal cytoreduction was performed in 35.5 % of patients, 84.7 % of patients survived for one year, 44.1 % three years and 37.3 % for five years. The median survival was 26.25 months (range 0-91). Chi-square test showed significant difference between the number of months of survival and: the value of CA125 (t = 2.004, p = 0.050), cytoreduction (p < 0.001) and FIGO stage (p < 0.01). Conclusion: According to the results of this study, optimal cytoreduction and FIGO stage significantly influence survival (p < 0.001). Optimal cytoreduction (< 2 cm of residual disease) had the highest prognostic value for survival. A total five-year survival in this study was 37.3 %.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15040-15040
Author(s):  
F. Abushahin ◽  
E. C. Grendys ◽  
J. R. Lurain ◽  
D. K. Singh ◽  
A. W. Rademaker ◽  
...  

15040 Background: Topotecan is currently used to treat recurrent ovarian cancer after failure of platinum-based therapy. The FDA-recommended regimen (1.5 mg/m2 for 5 consecutive days of a 21-day cycle) is associated with a high incidence of grade 3/4 myelosuppression. Alternate dosing and scheduling may increase patient convenience and reduce toxicity. The objective of this study is to evaluate toxicity, response and progression free survival of weekly topotecan therapy in women with primary and secondary platinum resistant ovarian cancer after failure of 1 or more regimens. Methods: A retrospective analysis of 59 patients that received weekly topotecan with a median dose of 3.75 on days 1, 8, and 15 of a 28-day cycle treated between November 2002 and May 2005. All patients had recurrent epithelial ovarian cancer with primary or secondary resistance to platinum. Disease response was evaluated by CA-125 levels, physical exam, and when appropriate by imaging studies. Toxicity was evaluated using the NCI Common Toxicity Criteria. Results: Response to therapy was noted in (22%) 13 of 59 patients (complete 6.75%, partial 15.25%). Stable disease was noted in 19 patients (32.2%) and progression in 25 patients (42.4%). Two patients (3.4%) had significant side effects that warranted the discontinuation of therapy. There was no significant difference in response to therapy between patients with primary and secondary platinum resistance. A total of 204 cycles were given with a median of 3 (1–12) cycles per patient. Grade 3 and 4 myelosuppression were rare with 1 cycle (0.5%) with grade 3 leukopenia, 15 cycles (6.4%) with grade 3 or 4 neutropenia, 1 cycle (0.5%) with grade 3 anemia, and 1 cycle (0.5%) with grade 3 thrombocytopenia. No patients were admitted with neutropenic fever. The Median Progression-free-survival for responders was 195 days (56–471). Conclusions: Weekly topotecan is a well tolerated and effective regimen for platinum resistant ovarian cancer with considerable less hematological toxicity when compared with historical data for the 5-day regimen. [Table: see text]


2007 ◽  
Vol 25 (19) ◽  
pp. 2811-2818 ◽  
Author(s):  
David G. Mutch ◽  
Mauro Orlando ◽  
Tiana Goss ◽  
Michael G. Teneriello ◽  
Alan N. Gordon ◽  
...  

Purpose Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients. Patients and Methods Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life. Results In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia. Conclusion Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.


2021 ◽  
Author(s):  
Shahan Mamoor

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding SLIT and NTRK-like family member 3, SLITRK3, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. SLITRK3 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. SLITRK3 expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of SLITRK3 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. SLITRK3 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.


2021 ◽  
Author(s):  
Shahan Mamoor

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding sarcospan, SSPN, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. SSPN expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. SSPN expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of SSPN is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. SSPN may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.


2021 ◽  
Author(s):  
Shahan Mamoor

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding phosphodiesterase 5A, PDE5A, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. PDE5A expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. PDE5A expression correlated with progression-free survival in patients with p53 mutant ovarian cancer. These data indicate that expression of PDE5A is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. PDE5A may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.


2020 ◽  
Author(s):  
Jiani Yang ◽  
Jun Ma ◽  
Yue Jin ◽  
Shanshan Cheng ◽  
Shan Huang ◽  
...  

Abstract We aimed to determine prognosis value of circulating tumor cells(CTCs) undergoing epithelial–mesenchymal transition(EMT) in epithelial ovarian cancer(EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan–Meier analysis among training group(n=114) and validation group(n=38). By regression screening, both CTC counts(HR 1.187; 95%CI 1.098-1.752; p=0.012) and M-CTC(HR 1.098; 95%CI 1.047-1.320; p=0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites and CA-125 were also collected(p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive value for nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts(p=0.0241), M-CTC(p=0.0107) and the nomogram(p=0.0021) were drawn with significant difference. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration: Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016


1999 ◽  
Vol 17 (2) ◽  
pp. 501-501 ◽  
Author(s):  
John A. Bridgewater ◽  
Ann E. Nelstrop ◽  
Gordon J.S. Rustin ◽  
Martin E. Gore ◽  
William P. McGuire ◽  
...  

PURPOSE: To assess CA-125 as a measure of response in patients treated with paclitaxel. PATIENTS AND METHODS: One hundred forty-four patients treated with paclitaxel derived from four different trials and 625 patients treated with platinum from two trials were analyzed using precisely defined 50% and 75% reductions in CA-125. The standard and CA-125 response rates to paclitaxel and platinum were compared. In addition, we analyzed individual patient groups in which there was a difference in response according to the two response criteria. RESULTS: Patients with stable disease as determined by standard criteria who were treated with platinum and responded according to CA-125 criteria have an improved median progression-free survival compared with patients with stable disease who did not respond according to CA-125 criteria (10.6 v 4.8 months; P < .001). Standard and CA-125 response rates for patients treated with platinum (58.93% v 61.31%, respectively) and paclitaxel (30.65% v 31.67%, respectively) were very similar, as were rates of false-positive prediction of response by CA-125 (platinum 2.2% and paclitaxel 2.9%). Responders to paclitaxel had a significantly improved progression-free survival compared with nonresponders by both standard criteria (median progression-free survival, 6.8 v 2.5 months; P < .001) and CA-125 criteria (median progression-free survival, 6.8 v 3.4 months; P < .001). CONCLUSION: For assessing activity of therapy for ovarian cancer, these data show that precise 50% or 75% CA-125 response criteria are as sensitive as standard response criteria. We propose that they may be used as a measure of response in lieu of or in addition to standard response criteria in clinical trials involving epithelial ovarian cancer. Sensitivity is maintained whether patients are treated with platinum or paclitaxel.


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