Objectives The CD47 “don’t eat me” signal allows tumor immune evasion. We tested the association of CD47 expression with outcomes in EOC. Methods CD47 expression was examined within the TCGA database for ovarian carcinoma. For validation, IHC was performed on a TMA consisting of specimens from 265 patients with EOC. The medical records of the patients were also retrospectively reviewed to correlate demographic and survival data. Results CD47 was amplified in 15/316 (5%) ovarian serous cancers in TCGA. In the validation cohort, the majority of patients had stage III/IV disease (208/265, 78.4%). CD47 expression was seen in 210/265 (79.2%). Patients were categorized into CD47hi (129/265; 48.7%) versus CD47lo (136/265; 51.3%). Patients with CD47lo tumors were more likely to have a complete response to adjuvant therapy than CD47hi (65% vs 50%, p= 0.026). Although there was a trend towards an increase in median OS (37.64 vs 45.26 mos, p=0.92) in the CD47lo group compared with CD47hi, the difference was not significant. Conclusions CD47 is expressed at high frequency in EOC. Patients with CD47lo EOC had a better treatment response to standard therapy, and trended towards improved OS. This demonstrates that while CD47 may be an immunologic shield that may be considered for targeted therapies, it is likely that it operates in concert with other mechanisms of immune evasion. Future studies to evaluate CD47 expression with other known mechanisms of immune escape in the tumor microenvironment may help further define its role.
Objectives Prognostic risk factors influencing survival in patients with epithelial ovarian cancer (EOC) include tumor stage, grade, histologic subtype, debulking, and platinum status. Little is known about the impact of hormonal milieu and reproductive factors before cancer diagnosis on clinical outcome. We sought to evaluate whether oral contraceptive (OC) use carries any prognostic significance on overall survival (OS) in patients with EOC. Methods Newly diagnosed patients with EOC, fallopian tube, and primary peritoneal cancers between 1982 and 1998 were prospectively evaluated with a comprehensive epidemiologic questionnaire. A retrospective chart review was performed to abstract clinicopathologic data, including OS. A Kaplan-Meier analysis was performed to compare survival across various exposures. A Cox regression model was used to compute adjusted hazards ratios (aHRs) and 95% confidence intervals (CIs). Results We identified 387 newly diagnosed cancers with evaluable information in this cohort. Decreased risk of death was observed in women who reported prior use of OC (aHR, 0.79; 95% CI, 0.58–1.09), previous pregnancy (aHR, 0.77; 95% CI, 0.57–1.04), or a live birth (aHR, 0.81; 95% CI, 0.60–1.08) after adjusting for age at diagnosis, stage, and histologic subtype. Oral contraceptive use was associated with a crude reduced risk of death (HR, 0.55; 95% CI, 0.42–0.72), with reported median OS of 81 months in OC users versus 46 months in nonusers. Patients who reported a single live birth experienced the largest potential survival advantage (aHR, 0.61; 95% CI, 0.39–0.94). Oral contraceptive use and prior pregnancy were associated with improved survival across all strata. Conclusions Oral contraceptive use may have lasting effects on epithelial ovarian tumor characteristics conferring favorable prognosis. Putative mechanisms that affect tumor biology include complex interactions between ovarian cells, host immune cells, and hormonal microenvironment during carcinogenesis. Future efforts should be directed to determine the role of reproductive factors in antitumor immunity.
Objectives To evaluate the impact of operative start time (OST) on surgical outcomes in patients with advanced ovarian cancer. Methods All stage IIIB–IV serous ovarian cancer patients who underwent primary surgery at our institution from 1/01–1/10 were identified. Fourteen factors were evaluated for an association with surgical outcomes including OST and OR tumor index (1 point each for carcinomatosis and/or bulky (≥1cm) upper abdominal disease). Univariate logistic regression considering within-surgeon clustering was performed for cytoreduction to ≤1cm versus >1cm residual disease. In patients with ≤1cm residual disease, univariate logistic regression considering within-surgeon clustering was performed for 1–10mm residual disease versus complete gross resection (CGR, 0mm residual). A multivariate logistic model was developed based on univariate analysis results in the ≤1cm residual disease cohort. Results Of 422 patients, residual disease was: 0mm, 144 (34.1%); 1 10mm, 175 (41.5%); >10mm, 103 (23.3%). OST was not associated with cytoreduction to ≤1cm residual disease on univariate analysis. In the ≤1cm residual disease cohort, albumin, CA-125, ascites, ASA score, stage, OR tumor index, and OST were associated with CGR on univariate analysis. Earlier OSTs were associated with increased rates of CGR. On multivariate analysis, CA-125 was independently associated with CGR. OST was associated with CGR in patients with an OR tumor index of 2 but not an OR tumor index <2. Conclusions OST was not associated with cytoreduction to ≤1cm residual disease in patients with advanced serous ovarian cancer. In the cohort of patients with ≤1cm residual disease, later OSTs were associated with reduced rates of CGR in patients with greater tumor burden.
Background: Low-density lipoproteins levels are significant predictors of clinical outcomes in ovarian cancer (OvCa) patients. Despite American Diabetes Association (ADA) guidelines, suboptimal hyperlipidemia management is reported in women diagnosed with both OvCa and diabetes mellitus (DM). This study evaluated the impact of cholesterol drugs utilization and importance of following ADA guidelines on OvCa recurrence and survival. Methods: All DM patients newly diagnosed with OvCa between 2003 and 2010 at Roswell Park Cancer Institute were retrospectively reviewed (n=482). A total of 60 newly diagnosed OvCa patients having a form of diabetes at the time of cancer diagnosis were identified. Out of these, 14 patients were excluded due to presence of type 1 diabetes (n=6) or prior cancer history (n=8). The remaining 46 patients were included in the final analyses. Tumor pathology, outcomes, baseline co-morbidities and self-reported drug therapy were documented. Follow-up began at cancer diagnosis and ended with first confirmed recurrence and/or death. Cases lost to follow-up were censored at the date of last contact. To analyze categorical outcomes across different treatment groups, Fisher's exact test was used. All multivariate analyses were done using Cox proportional hazards models while accounting for age, weight, stage, histology, and cumulative comorbidity. A nominal significance level of 0.05 was used in all testing. Results: Average age at diagnosis and body mass index in this data set was 70±10 years and 34.76±7.07 kg/m2, respectively. Over three quarters of this population was diagnosed with advanced stage OvCa and 96% had a tumor grade of 2 or higher. Roughly two thirds of the tumors evaluated had a serous histology. Out of the cases reviewed, 52% did not receive any form of cholesterol management and 46% received a statin alone or in combination. After a median follow-up of 26.9 months, patients receiving statin monotherapy for cholesterol management were found to have improved recurrence (HR=0.17, 95% CI: 0.04 to 0.73, P=0.02); however, no impact on overall mortality was noted as compared to patients not receiving any cholesterol management medication. Conclusions: This study explored for the first time the association between statin utilization and prognosis in OvCa patients with DM. Given the identified benefit, reinforcing compliance with DM guidelines for hyperlipidemia management in OvCa patients deserves further attention. Our findings seed the beginning of a novel approach in personalized OvCa care. Citation Format: Michelle E. Amsler, Kristina A. Chmiel, Olesya Yaremko, Clare Carroll, Jingjing Yin, Terry Mashtare, Anthony Miliotto, Rachel Brightwell, Kunle Odunsi, Alice C. Ceacareanu. Statins use prevents ovarian cancer recurrence in women with diabetes mellitus. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-18. doi:10.1158/1538-7445.AM2013-LB-18
HighlightsTreatment of sex-cord stromal tumors with carboplatin and taxane is both feasible and safe.FOXL2 mutations account for approximately 50% of these tumors.Carboplatin and taxane may afford a favorable outcome.
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