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Item Adult Comorbidity Evaluation 27 score as a predictor of survival in endometrial cancer patients(Elsevier, 2016-12) BINDER, Pratibha S; PEIPERT, Jeffrey F; KALLOGJERI, D; BROOKS, Rebecca A; MASSAD, Leslie S; MUTCH, David G; POWELL, Matthew A; THAKER, Premal H; McCOURT, Carolyn K; Obstetrics and Gynecology, School of MedicineBACKGROUND The incidence of endometrial cancer increases with age and is associated with medical comorbidities such as obesity and diabetes. While a few cohort studies of less than 500 patients showed an association between comorbidity and survival in endometrial cancer patients, the degree of association needs to be better described. The Adult Comorbidity Evaluation 27 (ACE-27) is a validated comorbidity instrument that provides a score (0–3) based on the number and severity of medical comorbidities. OBJECTIVE This study was performed to explore the association between medical comorbidities and survival of endometrial cancer patients. STUDY DESIGN Patients diagnosed with endometrial cancer from 2000–2012 were identified from the prospectively maintained Siteman Cancer Center tumor registry. Patients undergoing primary surgical treatment for endometrioid, serous and clear cell endometrial carcinoma were included. Patients primarily treated with radiation, chemotherapy or hormone therapy were excluded. Patients with uterine sarcomas or neuroendocrine tumors were excluded. Patients with missing ACE-27 scores were also excluded from analysis. Information including patient demographics, ACE-27 score, tumor characteristics, adjuvant treatment and survival data were extracted from the database. The association of ACE-27 and overall as well as recurrence-free survival was explored in a multivariable Cox regression analysis after controlling for variables found to be significantly associated with survival in univariable analysis. RESULTS A total of 2073 patients with a median age of 61 years (range 20–94) at diagnosis were identified. ACE-27 score was 0, 1, 2 and 3 in 22%, 38%, 28% and 12% of patients, respectively. Stage distribution was I (73%), II (5%), III (15%) and IV (7%) and grade distribution was 1 (52%), 2 (23%) and 3 (25%). Most patients had endometrioid histology (87%) followed by serous (11%) and clear cell (3%). The median OS for the entire cohort was 54 months [95% confidence interval (CI) 3, 154 months] and median PFS was 50 months [95% CI 2, 154 months]., On univariable analysis, age, race, marital status, stage, grade, histology and treatment type were significantly associated with overall survival and recurrence-free survival. After adjusting for these covariates, patients with ACE-27 score of 2 had a 52% higher risk of death [95% CI 1.16, 2.00] and patients with ACE-27 score of 3 had a 2.35-fold increased risk of death [95% CI 1.73, 3.21] compared to patients with an ACE-27 score of 0. Similarly, patients with ACE-27 score of 2 had a 38% higher risk of recurrence [95% CI 1.07, 1.78] and patients with ACE-27 score of 3 had a 2.05-fold increased risk of recurrence [95% CI 1.53, 2.75] compared to patients with an ACE-27 score of 0. We found no interaction between ACE-27 score and age, stage or treatment type. CONCLUSIONS Our findings demonstrate the importance of comorbidities in estimating the prognosis of endometrial cancer patients, even after adjusting for age and known tumor-specific prognostic factors like stage, grade, histology and adjuvant treatment.Item Association between intrauterine device use and endometrial, cervical, and ovarian cancer: an expert review(Elsevier, 2023-08) Minalt, Nicole; Caldwell, Amy; Yedlicka, Grace M.; Joseph, Sophia; Robertson, Sharon E.; Landrum, Lisa M.; Peipert, Jeffrey F.; Obstetrics and Gynecology, School of MedicineThe intrauterine device is one of the most effective forms of contraception. Use of the intrauterine device has increased in the United States over the last 2 decades. Two formulations are commercially available in the United States: the levonorgestrel-releasing intrauterine device and the copper intrauterine device. The levonorgestrel intrauterine device releases progestin, causing endometrial suppression and cervical mucus thickening, whereas the primary mechanism of action of the copper intrauterine device is to create a local inflammatory response to prevent fertilization. Whereas the protective effects of combined hormonal contraception against ovarian and endometrial cancer, and of tubal sterilization against ovarian cancer are generally accepted, less is known about the effects of modern intrauterine devices on the development of gynecologic malignancies. The best evidence for a protective effect of intrauterine device use against cancer incidence pertains to levonorgestrel intrauterine devices and endometrial cancer, although studies suggest that both copper intrauterine devices and levonorgestrel intrauterine devices reduce endometrial cancer risk. This is supported by the proposed dual mechanisms of action including both endometrial suppression and a local inflammatory response. Studies on the relationship between intrauterine device use and ovarian cancer risk show conflicting results, although most data suggest reduced risk of ovarian cancer in intrauterine device users. The proposed biological mechanisms of ovarian cancer reduction (foreign-body inflammatory response, increased pH, antiestrogenic effect, ovulation suppression) vary by type of intrauterine device. Whereas it has been well established that use of copper intrauterine devices confers a lower risk of cervical intraepithelial neoplasms, the effect of levonorgestrel intrauterine device use on cervical cancer remains unclear. Older studies have linked its use to a higher incidence of cervical dysplasia, but more recent literature has found a decrease in cervical cancer with intrauterine device use. Various mechanisms of protection are postulated, including device-related inflammatory response in the endocervical canal and prostaglandin-mediated immunosurveillance. Overall, the available evidence suggests that both levonorgestrel intrauterine devices and copper intrauterine devices reduce gynecologic cancer risk. Whereas there is support for the reduction of endometrial cancer risk with hormonal and copper intrauterine device use, and reduction of cervical cancer risk with copper intrauterine device use, evidence in support of risk reduction with levonorgestrel intrauterine device use for cervical and ovarian cancers is less consistent.