Changes in health-related quality of life in older women after diagnosis with gynecologic cancer.

PURPOSE: The impact of gynecologic cancer on health-related quality of life (HRQOL) is not fully understood. To our knowledge, this is the first longitudinal study to measure HRQOL changes from before to after gynecologic cancer diagnosis in older women. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results - Medicare Health Outcomes Survey database. Women aged 65 and older who were diagnosed with cervical, ovarian, or uterine cancer between baseline and follow-up surveys (n = 248; mean time from diagnosis = 12.54 ± 7.11 months) were propensity-matched to cancer-free controls (n = 1240). Logistic regression was used to assess risk of functional impairments and depressive symptoms at follow-up. Changes in HRQOL, as measured by the Medical Outcomes Study Short Form-36 and Veterans RAND 12-Item Survey, were estimated with mixed effects linear models. RESULTS: Women who were within 12 months of diagnosis and women diagnosed with regional/distant disease had significantly greater odds than controls of impairment at follow-up. HRQOL declines were greatest in those with advanced disease, with the most notable changes from baseline to follow-up observed for role limitations due to emotional problems (-8.60 vs. -3.42 in controls), general health (-7.76 vs 0.10), and physical functioning (-7.70 vs. -1.67). There were significant decreases in physical functioning and role limitations due to emotional problems for all cancer patients regardless of time since diagnosis. CONCLUSIONS: Gynecologic cancer has significant impacts on physical and mental aspects of HRQOL in older women. Interventions are needed to reduce pain, provide support, and prepare patients for changes in functioning and health.

Pre-diagnosis health-related quality of life and survival in older women with endometrial cancer.

PURPOSE: Health-related quality of life (HRQOL) is an important prognostic factor in cancer patients. To date, no other studies have assessed the association between HRQOL measured before diagnosis and survival in older women with endometrial cancer. METHODS: The Surveillance, Epidemiology, and End Results - Medicare Health Outcomes Survey linked database was used to identify 995 women who were at least 65 years old and completed a survey before diagnosis with endometrial cancer. We obtained scores for 10 HRQOL scales, as measured by Medical Outcomes Study Short Form-36 and Veterans RAND 12-Item Survey, and data on activities of daily living (ADLs) impairments and depressive symptoms. Fine and Gray competing risks regression and Cox proportional hazards were used to estimate the association of HRQOL with endometrial cancer-specific and overall survival, respectively. RESULTS: Women who died had worse pre-diagnosis HRQOL than women who were still alive at the end of the study period. For every five-point increase in HRQOL score, overall survival improved by 5-9%. The strongest associations were observed for vitality (HR = 0.91, 95% CI 0.86, 0.97, p = 0.0021) and physical functioning (HR = 0.92, 95% CI 0.87, 0.97, p = 0.0010). ADL impairments were generally not predictive of survival, though depressive symptoms were significantly associated with increased hazard of death from all causes (HR = 1.34, 95% CI 1.00, 1.79, p = 0.0466). CONCLUSION: HRQOL measured before diagnosis with endometrial cancer has prognostic value. Having measures of HRQOL available at diagnosis may facilitate timely supportive care to improve survival.

Contribution of age to clinical trial enrollment and tolerance with ovarian cancer.

INTRODUCTION: Increasing age has been correlated with shorter survival in ovarian cancer patients, a finding attributed to diminished tolerance of standard therapy. Elderly patients, however, are less likely to enroll on clinical trials; thus, limited data exists to evaluate their response to front line treatment. This study describes how elderly patients on trial fared, with respect to toxicity and response, compared to younger women. METHODS: A retrospective cohort study was performed of ovarian cancer patients enrolled in front line chemotherapy trials at our institution between 2000 and 2013. Patients were dichotomized by age: <70 and ≥70years. Clinical, pathologic, and treatment characteristics were recorded and analyzed using SAS version 9.3. RESULTS: 336 patients were enrolled. Of these, 79 (23.5%) were ≥70yrs. Demographics were similar between the two groups. Compared to patients <70, those ≥70 completed a comparable number of chemotherapy cycles (p=0.16) and had similar numbers of dose modifications (p=0.40) and delays (p=0.26). Both hematologic and non-hematologic toxicities occurred at similar rates as well. Age≥70 (HR 1.8, 95% CI 1.27-2.54, p=0.0009), stage III/IV (HR 3.44, 95% CI 1.08-10.95, p=0.036), and residual disease (HR 2.63, 95% CI 1.82-3.78, p<0.0001) were independently predictive of shorter overall survival. CONCLUSION: Our data continues to support reports of shorter survival for older women with ovarian cancer. With physician bias removed and similar chemotherapy tolerance noted, our study suggests that inherent tumor biology may be a significant contributor. Further research is needed to identify the mechanisms which contribute to the inequality that age imposes on outcomes.

Post-intensive care unit syndrome in gynecologic oncology patients.

PURPOSE: The purposes of the present study are to describe the demographic and treatment characteristics of women on the gynecologic oncology service who required intensive care and assess prevalence of risk factors for post-intensive care syndrome (PICS). METHODS: A retrospective chart review was performed encompassing patients requiring admission to the intensive care unit (ICU) on the gynecology oncology service between 1/2008 and 12/2012. Descriptive statistics were computed using SAS version 9.3. RESULTS: One hundred eleven patients met study criteria. Most were Caucasian (85 %), were married (50 %), and had stage III/IV disease (82 %). Risk factors for PICS were as follows: 9 % had baseline anxiety, 20 % had baseline depression, 21 % were taking an SSRI prior to admission, and 18 % took other psychiatric medications. Most ICU admissions (47 %) were for planned post-operative management. Thirty-seven percent required mechanical ventilation for a median of 1 day (range, 1-24). Twenty percent required new scheduled psychiatric medications while in the ICU, and 8.1 % of patients were discharged with a newly prescribed antidepressant. Of patients, 15.3 % had consultations with psychiatry or social work. Six percent of patients expired, and 18 % had a nontraditional discharge disposition. Overall, 60 % of the patients had at least one recognized risk factor for PICS. CONCLUSIONS: Given the preponderance of psychiatric disorders and mechanical ventilation during post-operative ICU care in patients with gynecologic cancer, prospective evaluation of risk factors and utility of risk-reducing interventions for PICS is warranted. Long-term cognitive or physical disability is known to hasten mortality; thus, preventative strategies may increase the survival and quality of life for this patient population.

Improvement in symptom burden within one day after palliative care consultation in a cohort of gynecologic oncology inpatients.

OBJECTIVE: The aim of this study is to evaluate the magnitude and time course of change in symptom burden after palliative care (PC) consultation in a cohort of gynecologic oncology inpatients. METHODS: Women with a gynecologic malignancy and PC consultation for symptom management between 3/1/12 and 2/28/13 were identified. Charts were reviewed for demographic and disease characteristics. Symptom scores on a modified Edmonton Symptom Assessment System (ESAS) scale were abstracted for pain, anorexia, fatigue, depression, anxiety, nausea and dyspnea. Prevalence of moderate-to-severe symptom intensity was compared between the day of PC consultation (D1), the day after PC consultation (D2) and the last recorded symptoms before discharge (DLast). RESULTS: PC was consulted for symptom management during 129 admissions of 95 unique patients. Median age was 59, 84% were white and 67% had stage III/IV disease, with ovarian the most common site (52%). Symptom prevalence on D1 for at least mild intensity ranged 14% (dyspnea) to 80% (pain) and for at least moderate intensity from 3% (dyspnea) to 50% (pain). Statistically significant decreases in prevalence of moderate to severe symptom intensity between D1 and DLast occurred for pain, anorexia, fatigue and nausea (magnitude 58-66%) and between D1 and D2 for pain, fatigue and nausea (magnitude 50-55%). The majority of the improvement that occurred between D1 and DLast happened by D2. CONCLUSIONS: PC consultation is associated with improvement in symptom burden, the majority of which occurs within one day of consultation. PC may be an effective tool for symptom management in patients with moderate to severe symptom intensity even during short hospitalizations and should be considered early in the hospitalization to effect timely symptom relief.

Predictors of high symptom burden in gynecologic oncology outpatients: who should be referred to outpatient palliative care?

OBJECTIVE: To characterize symptom prevalence in gynecologic oncology outpatients and identify predictors of high symptom burden. METHODS: We performed a retrospective analysis of a convenience sample of symptom surveys from gynecologic oncology patients at a single cancer center over a 20-month period. The survey was based on the Edmonton Symptom Assessment System (ESAS), and assessed pain, depression, anxiety, fatigue and well-being. Information on demographics, disease, treatment and history of chronic pain, depression or anxiety was abstracted from medical records. Data was analyzed with descriptive and t-test statistics. RESULTS: We analyzed 305 surveys from unique patients. Symptom prevalence (severity score>0/10) ranged from 60.1% (pain) to 79.7% (fatigue). Prevalence of moderate to severe symptoms (score≥4/10) ranged from 32% (pain) to 47% (fatigue). There were no differences in symptom burden by site or stage of cancer. Patients with no active disease (38%) were less symptomatic. There was a trend toward higher symptom burden in patients younger than 50years. There was higher symptom burden in patients receiving cancer treatment or with a pre-existing history of pain, anxiety or depression. Patients who expressed an interest in being seen by a symptom management service also had higher symptom burden. CONCLUSIONS: Gynecologic oncology outpatients have a high symptom burden regardless of stage and site of cancer. Patients who are young, on treatment or have a history of chronic pain, depression or anxiety have a higher symptom burden. Consideration should be given to targeting these patients for outpatient palliative care services.

Management of ruptured ovarian teratoma mimicking advanced ovarian cancer.

•Chronic chemical peritonitis caused by spontaneous rupture of a mature cystic teratoma may result in prolonged hospitalization and respiratory decline and can mimic a gynecologic malignancy.•Earlier surgical intervention for mature teratoma may prevent morbidity.•Inclusion of a gynecologic oncologist is advised for management discussions and/or surgical back-up.•Complex benign gynecologic surgeries may have some benefit for gynecologic oncologic trainees, which can be used for later oncologic cases.

Predictors of intensive care unit utilization in gynecologic oncology surgery.

OBJECTIVES: The objectives of the study were to examine factors predicting intensive care unit (ICU) admission after surgery for gynecologic cancer and to determine the impact of ICU admission on survival. METHODS: This was a retrospective study of women undergoing laparotomy for staging and debulking of gynecologic cancer at an academic hospital with tertiary ICU facilities from July 2000 through June 2003. Data on clinicopathologic factors, comorbidities, operative outcomes, and survival were obtained from medical records and institutional cancer registry. The χ analysis, Kaplan-Meier analysis, and Cox regression methods were used for analyses. RESULTS: Two hundred fifty-five patients met our inclusion criteria, 43 of whom had a postoperative admission to the ICU. Factors predicting ICU admission on univariate analysis included age 60 years or older, hematocrit of 30% or less, albumin of 3.5 g/dL or less, and Charlson Comorbidity Index (CCI) score greater than 8; after multivariate analysis, CCI score of greater than 8 (hazard ratio, 2.5; confidence interval, 1.11-5.69) and albumin of 3.5 or less (hazard ratio, 3.8; confidence interval, 1.66-8.85) were associated with an increased risk of ICU admission. After adjusting for albumin and CCI score, ICU admission did not have a significant effect on survival. CONCLUSIONS: The ability to predict ICU admission helps in appropriate counseling of patients and identification of institutional resource utilization.

Recommendations for intrauterine contraception: a randomized trial of the effects of patients' race/ethnicity and socioeconomic status.

OBJECTIVE: Recommendations by health care providers have been found to vary by patient race/ethnicity and socioeconomic status and may contribute to health disparities. This study investigated the effect of these factors on recommendations for contraception. STUDY DESIGN: One of 18 videos depicting patients of varying sociodemographic characteristics was shown to each of 524 health care providers. Providers indicated whether they would recommend levonorgestrel intrauterine contraception to the patient shown in the video. RESULTS: Low socioeconomic status whites were less likely to have intrauterine contraception recommended than high socioeconomic status whites (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.06-0.69); whereas, socioeconomic status had no significant effect among Latinas and blacks. By race/ethnicity, low socioeconomic status Latinas and blacks were more likely to have intrauterine contraception recommended than low socioeconomic status whites (OR, 3.4; and 95% CI, 1.1-10.2 and OR, 3.1; 95% CI, 1.0-9.6, respectively), with no effect of race/ethnicity for high socioeconomic status patients. CONCLUSION: Providers may have biases about intrauterine contraception or make assumptions about its use based on patient race/ethnicity and socioeconomic status.

Depressive symptoms and health-related quality of life in older women with gynecologic Cancers.

OBJECTIVES: This study aims to assess factors associated with depressive symptoms in older women with gynecologic cancers and to examine the association of depression with health-related quality of life (HRQOL). MATERIALS AND METHODS: Women aged 65 and older previously diagnosed with cervical, ovarian, or uterine cancer (n=1977) were identified from the Surveillance, Epidemiology, and End Results - Medicare Health Outcomes Survey database and compared to propensity-matched cancer-free controls (n=9885). Women with and without depressive symptoms were compared by cancer status. Logistic regression was used to identify factors associated with depressive symptoms, and linear regression was used to determine the association of depressive symptoms with HRQOL measures. RESULTS: The prevalence of depressive symptoms was higher among older women with gynecologic cancer (31.9%, 32.2%, and 25.3% for cervical, ovarian, and uterine cancer, respectively) than cancer-free older women (24.9%) (p=0.05). Adjusting for demographic and clinical factors, older women with ovarian cancer were significantly more likely to have depressive symptoms than controls (Prevalence Odds Ratio = 1.74, 95% CI: 1.31, 2.32, p < 0.01). Among older women with gynecologic cancer, comorbid conditions and functional limitations were strongly associated with depressive symptoms. Women with depressive symptoms showed significant decrements in both physical and mental measures of HRQOL. CONCLUSION: This study gives insight into correlates of depressive symptoms that may be used to better identify women with gynecologic cancers who are at risk of depression. The relatively high prevalence of depressive symptoms and significant deficits in HRQOL underscore the need for effective screening and treatment of depression in older women with gynecologic cancers.

A Non-invasive Liquid Biopsy Screening of Urine-Derived Exosomes for miRNAs as Biomarkers in Endometrial Cancer Patients.

Exosomes have great potential to serve as a source of diagnostic and prognostic biomarkers for endometrial cancer (EC). Urine-derived exosomes from patients with EC and patients with symptoms of EC, but without established EC, were used to evaluate a unique miRNA expression profile. Of the 84 miRNA studied, 57 were amplified in qPCR, suggesting the differential packaging of miRNA in exosomes. Further, hsa-miR-200c-3p was identified to be enriched the most. Various bioinformatics and in silico tools were used to evaluate the biological significance of hsa-miR-200c-3p in EC. We conclude that differential miRNA in exosomes can be utilized for discovery of biomarker signatures and EC diagnosis; hsa-miR-200c-3p is one such candidate. Urine-derived exosomes pave the way for the development of non-invasive biomarkers.

Exploitation of Exosomes as Nanocarriers for Gene-, Chemo-, and Immune-Therapy of Cancer.

The bottleneck in current vector-based cancer therapy is the targeted and controlled release of therapeutics in tumors. Exosomes are submicron-sized vesicles that are secreted by all cell types and are involved in communication and transportation of materials between cells. Analogous in size and function to synthetic nanoparticles, exosomes offer many advantages, rendering them the most promising candidates for targeted drug or gene delivery vehicles. Patient-specific customized therapeutic strategies can be engineered using exosomes derived from the patient's own healthy cells. Therefore, exosome-based cancer therapy has the potential to become an important part of personalized medicine. Interest in exosomes as carrier organelles is relatively recent. Knowledge about exosomal biology and its applications remains limited. The present review is an attempt to describe the current status of the application of exosomes to cancer therapy and the potential challenges associated with their use.

A study of physician recommendations for reversible contraceptive methods using standardized patients.

CONTEXT: Health care providers may influence patients' choice of contraceptive method, yet little is known about the recommendations they make to their patients. METHODS: In 2007-2008, a total of 468 physicians at four family medicine and obstetrics and gynecology meetings were randomly assigned to view one of 18 videos of a patient seeking contraceptive advice; the patients were standardized for most relevant behaviors and characteristics, but differed by race and ethnicity, socioeconomic status and gynecologic history. Participants provided their demographic and practice characteristics and completed a survey about their contraceptive recommendations for the patient. Multivariate logistic regression analyses were conducted to identify associations between physician characteristics and recommendations for specific contraceptive methods. RESULTS: The most frequently recommended methods were the pill (89%) and ring (80%), followed by the levonor-gestrel IUD (64%), patch (56%), injectable (49%) and copper IUD (45%). Oral contraceptives were more likely to be recommended by private practice physicians than by academic physicians (odds ratio, 2.9). Recommendations for the ring were less common among family physicians and those 56 or older than among obstetrician-gynecologists and those 35 or younger (0.6 and 0.3, respectively), and more common among physicians in private practice than among those in academia (2.4). The patch and injectable were more commonly recommended by family physicians than by obstetrician-gynecologists (2.6 and 2.5, respectively). Both IUD types were recommended less often by physicians 36 or older than by younger ones (0.2-0.5). DISCUSSION: The advice women receive about contraception may vary according to the characteristics of their provider. Research on the reasons for these differences is needed.

Health care providers' knowledge about contraceptive evidence: a barrier to quality family planning care?

BACKGROUND: The underuse of effective contraceptive methods by women at risk for unintended pregnancy is a major factor contributing to the high rate of unintended pregnancy in the United States. As health care providers are important contributors to women's contraceptive use, this study was conducted to assess provider knowledge about contraception. STUDY DESIGN: Bivariate and multivariate analyses were performed using data collected from a convenience sample of health care providers (physicians, nurse practitioners and physician assistants) at meetings of the professional societies of family medicine and obstetrics and gynecology. RESULTS: Younger providers were more knowledgeable, as were obstetrician/gynecologists, female providers and providers who provide intrauterine contraception in their practice. CONCLUSIONS: The lack of consistent and accurate knowledge about contraception among providers has the potential to dramatically affect providers' ability to provide quality contraceptive care for their patients, which could have an impact on their ability to prevent unintended pregnancies.

The effect of patient gynecologic history on clinician contraceptive counseling.

BACKGROUND: Contraceptive providers have an important influence on women's selection of contraception. Previous studies suggest that clinicians inappropriately limit use of intrauterine contraception (IUC). This study investigated the influence of patients' gynecologic histories on recommendations for IUC and other methods of contraception. STUDY DESIGN: Videos of standardized patients varying by history of pelvic inflammatory disease (PID) and parity were shown to clinicians at meetings of national medical societies. Participants indicated their contraceptive recommendations for the patient and whether they would have concerns were the patient to use IUC. RESULTS: Five hundred twenty-four providers viewed one video of a standardized patient and completed the survey. Gynecologic history was significantly associated with recommendations for the contraceptive ring, contraceptive patch, and copper IUC. Many clinicians indicated that they had concerns about the use of IUC with respect to risks such as PID, infertility and ectopic pregnancy. Concerns about infertility and pain with use of IUC were related to gynecologic history. CONCLUSIONS: Patient gynecologic characteristics affect recommendations for some reversible contraceptive methods. Clinicians continue to have concerns about IUC use despite evidence supporting its safety.