Nicole S. Nevadunsky

Metformin use and endometrial cancer survival

OBJECTIVE Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancers using metformin has been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). METHODS We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. RESULTS Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio=0.54, 95% CI: 0.30-0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and the presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. CONCLUSION Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC.

Obesity and age at diagnosis of endometrial cancer.

OBJECTIVE: Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity–endometrial cancer association might also accelerate tumorigenesis. METHODS: A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test. RESULTS: A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (±11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (±10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89–1.86x, R2=0.049, P<.001). This association persisted after multivariable adjustment (R2=0.181, P<.02). A linear association between BMI and age of nonendometrioid cancers was not found (P=.12). There were no differences in overall survival by BMI category. CONCLUSIONS: Obesity is associated with earlier age at diagnosis of endometrioid-type endometrial cancers. Similar associations were not, however, observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis. LEVEL OF EVIDENCE: II

Association Between Statin Use and Endometrial Cancer Survival.

OBJECTIVE: To evaluate the association of 3 hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) use and concordant polypharmacy with disease-specific survival from endometrial cancer. METHODS: A retrospective cohort study was conducted of 985 endometrial cancer cases treated from January 1999 through December 2009 at a single institution. Disease-specific survival was estimated by Kaplan-Meier analyses. A Cox proportional hazards model was used to study factors associated with survival. All statistical tests were two-sided and performed using Stata. RESULTS: At the time of analysis, 230 patients (22% of evaluable patients) died of disease and median follow-up was 3.28 years. Disease-specific survival was greater (179/220 [81%]) for women with endometrial cancer taking statin therapy at the time of diagnosis and staging compared with women not using statins (423/570 [74%]) (log rank test, P=.03). This association persisted for the subgroup of patients with nonendometrioid endometrial tumors who were statin users (59/87 [68%]) compared with nonusers (93/193 [43%]) (log rank test, P=.02). The relationship remained significant (hazard ratio 0.63, 95% confidence interval [CI] 0.40–0.99) after adjusting for age, clinical stage, radiation, and other factors. Further evaluation of polypharmacy showed an association between concurrent statin and aspirin use with an especially low disease-specific mortality (hazard ratio 0.25, 95% CI 0.09–0.70) relative to those who used neither. CONCLUSION: Statin and aspirin use was associated with improved survival from nonendometrioid endometrial cancer.

End-of-life care of women with gynecologic malignancies: a pilot study.

Objective There are limited data regarding the end-of-life care for women with gynecologic malignancies. We set out to generate pilot data describing the care that women with gynecologic malignancies received in the last 6 months of life. Patient demographics, patterns of care, and utilization of palliative medicine consultation services were evaluated. Methods One hundred patients who died of gynecologic malignancies were identified in our institutional database. Only patients who had received treatment with a gynecologic oncologist within 1 year of death were included. Medical records were reviewed for relevant information. Data were abstracted from the electronic medical record, and analyses were made using Student t test and Mann-Whitney U test with SPSS software. Results The mean age of patients was 60 years (range, 30–94 years). Racial/ethnic distribution was as follows: 38%, white; 34%, black; and 15%, Hispanic. Seventy-five percent of patients received chemotherapy within the last 6 months of life, and 30% received chemotherapy within the last 6 weeks of life. The median number of days hospitalized during the last 6 months of life was 24 (range, 0–183 days). During the last 6 months of life, 19% were admitted to the intensive care unit, 17% were intubated, 5% had terminal extubation, and 13% had cardiopulmonary resuscitative efforts. Sixty-four percent had a family meeting, 50% utilized hospice care, and 49% had palliative medicine consultations. There was a significant difference in hospice utilization when comparison was made between patients who had 14 days or more from consultation until death versus patients who had 14 days or less or no consultation, 21 (72%) versus 29 (41%), P = 0.004. Patients who were single were less likely to have a palliative medicine consultation, P = 0.005. Conclusions End-of-life care for patients with gynecologic malignancies often includes futile, aggressive treatments and invasive procedures. It is unknown whether these measures contribute to longevity or quality of life. These pilot data suggest that factors for implementation of timely hospice referral, family support, and legacy building should include specialists trained in palliative medicine.

Abstract 5026: Utilization of palliative medicine in a racially and ethnically diverse population of women with gynecologic malignancies

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Objective: There is limited information regarding the role of a palliative care consultation for ethnically and racially diverse women with gynecologic malignancies. The purpose of this study was to determine the characteristics, clinical findings and outcomes of patients with gynecologic malignancies who were referred for hospital inpatient palliative medicine consultation. Methods: Patients with gynecologic malignancies were identified who requested a Palliative Medicine consultation from January 1, 2007 to June 1, 2010. Their medical records were reviewed for information including demographics, disease status, reasons for the consultation, clinical findings, interventions, and outcomes. Results: 84 evaluable patients were identified. Forty-five percent (n=38) of patients were referred by their primary Gynecologic Oncologist. The average age was 63 years (range 22-96). The disease site was: uterus/endometrium (n=37, 44%), ovary (n=24, 29%), cervix (n=15, 18%), and vulva (n=5, 6%). Racial distribution included, African American (n=3, 39%), Caucasian (n=33, 28%), and Hispanic (n=13, 16%). Reasons for consultation were pain (n = 41; 45%), future goals of care (n=42; 46%) nausea/vomiting (n = 1; 1%), bowel obstruction (n=3, 3.3%) and dyspnea (n=4, 4%). Seventy-five percent of patients had medical co-morbidities, 27% had psychiatric co-morbidities and six patients were identified to have altered mental status at the time of interview. Eighty percent of patients were on narcotic medications at the time of consultation; however pain was adequately controlled in only 45% of patients. In 81% of the consultations, pharmacologic interventions were advised. The median number of days from consultation to death was 31. Hospice referral was recommended for 19 patients and thirty-eight patients were transitioned to “do not resuscitate” (DNR) status after consultation. The median number of days from DNR status to death was 19, and the median number of days from consult to DNR was 8. Sixteen patients (19%) died in the hospital setting. Conclusion: This patient population represents a unique perspective of racial diversity and predominantly advanced or recurrent gynecologic cancers. Pharmacologic interventions were advised in the majority of consults, however end-of-life decision making was a common reason for consultation. The consultation team proved effective in transitioning patients to DNR status, however there may be barriers to early palliative intervention and symptom control as the median time of intervention to death was only one month. Pain and symptom control remain a significant challenge that earlier intervention may alleviate. This diverse, minority and low socio-economic status population may be resistant and/or unable to seek palliative care outside the hospital or their home. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5026. doi:10.1158/1538-7445.AM2011-5026

Saddle pulmonary embolus resulting in cardiovascular collapse requiring extracorporeal membrane oxygenation in a postoperative patient with endometrial cancer

Background Venous thromboembolism after open gynecologic surgery is not uncommon, especially in the presence of other risk factors such as obesity, prolonged surgical time or gynecologic malignancy. Case We present the case of a 62 y.o. patient who underwent open hysterectomy and surgical staging for uterine serous carcinoma. She was readmitted with lower extremity edema. During her workup, she underwent cardiovascular arrest secondary to saddle pulmonary embolus requiring cardiopulmonary resuscitation and extracorporeal membrane oxygenation. After systemic and catheter directed thrombolysis, and a long hospitalization, she was discharged home in stable condition. Conclusion Saddle pulmonary embolus is a potentially catastrophic and fatal postoperative complication. This case demonstrates a successful implementation of directed thrombolysis, veno-arterial extracorporeal membrane oxygenation and multidisciplinary management in a case of postoperative saddle pulmonary embolus. Précis We report a case of an endometrial cancer patient who sustained a massive postoperative pulmonary embolus and was successfully resuscitated using extracorporeal membrane oxygenation.

Inpatient Palliative Care Consultation for Women with Gynecologic Malignancies

Objective: Recommendations to improve end-of-life cancer care include integration of palliative care into standard cancer care. There is limited information regarding palliative care for ethnic and racial minority women with gynecologic malignancies. The purpose of this study was to determine the impact of clinical, socio-demographic, and provider factors on palliative medicineconsultation. Methods: After IRB approval, patients with gynecologic malignancies who received a palliative medicine consultation from January 1, 2008 until June 1, 2010 were identified. Abstracted data included demographics, reason/s for consultation, and outcomes. Results were described and comparison made using Fisher’s Exact Test, Student’s T analysis, and Kaplan-Meier time to event analysis with SPSS software. Results: 84 patients were referred for palliative medicine consultation. Ethnic/racial distribution was Black (37%), White (39%), and Hispanic (16%). The reason/s for consultation included pain (45%), goals of care (46%), and bowel obstruction (4%), dyspnea (4%). Median number of days from the initial consultation until death by Kaplan-Meier time to event analysis, which is a proxy metric for timely consultation was 35 days [Range 0-1005 days].Younger patients (<60) were less likely to be DNR (p=0.03, 60% verses 79.5%) or referred to hospice (p=0.02, 9% versus 33%). “Goals of care” was the consultation reason in 61% of patients of medical sub-specialists vs. 26% of Gynecologic Oncologists (p=0.003). 28% of patients from medical sub-specialists died in the hospital verses 8% of gynecologic oncologist referred patients (p=0.02). Conclusions: These data suggest that there may be barriers to the implementation of palliative medicine for women with gynecologic malignancies. Providers may be influenced by patient age as well as their own specialty background. Reasons for the barriers to access in these women need to be further explored.

Abstract 3587: Effect of race on outcome in women with uterine cancers

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background: Incidence rates for malignant tumors of the uterine corpus have been reported to be lower among women of color than among whites, whereas mortality rates have been reported to be higher among African-American women and women of Latina origin. Reasons for the higher level of mortality among women of color are currently unknown. Methods: After Institutional Review Board approval, we accessed the prospective clinical databases in the Division of Gynecologic Oncology at our institution. We abstracted socio-demographic and survival data from all women who were diagnosed with endometrial cancer from January 1990-January 2010. Pathology records were reviewed and the final pathology confirmed. Results: Nine hundred and ninety patients were identified. Racial distribution was 381 (38%) white, 310 (31%) black, 231 (23%) Hispanic, 21 (2%) other, and 72 (3%) unknown or unclassified. Five hundred and ninety-six (60%) patients had Type I endometriod histological subtype. At time of censor, 269 (27%) were confirmed deceased. The hazard ratio for black verses white women was 1.91 (p<0.001) when all histological subtypes were included. However, when patients were divided into Type I and Type II histological subtypes there was no significant difference in survival by race. Conclusion: Our data show no difference in survival among women of Asian, African-American/Caribbean, and Caucasian races with uterine cancer after control for histological subtype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3587. doi:1538-7445.AM2012-3587