Patient-reported outcome changes at the end of life in recurrent platinum-resistant ovarian cancer: An NRG oncology/GOG study.

OBJECTIVES: In a prospective study of platinum-resistant ovarian cancer patients, we examined whether the Disease-related Symptoms-Physical (DRS--P) scale of the NCCN/FACT-Ovarian Cancer Symptom Index-18 (NFOSI-18) is responsive to clinical change in patients estimated by their provider to survive at least six months. METHODS: The NFOSI-18, and other FACT measures, was collected at study entry and 3 and 6 months post-enrollment. Measures were compared for those who died or dropped off study prior to 3 months or prior to 6 months (assumed as health deterioration over time), or those who stayed on study through 6 months (presumed as stable disease over time). Statistical analyses included a fitted linear mixed model for estimating the group differences over time, Cox regression to assess the probability of survival with patient-reported outcomes, and effect size. RESULTS: DRS-P scores of patients who completed only one assessment were significantly lower compared to patients who were able to complete two assessments [5.9 points lower (2.0-9.8); p < 0.01], or three assessments [8.1 points lower (4.8-11.5); p < 0.01]. Measures of abdominal discomfort, functional well-being, emotional well-being, and quality of life were also significant, but treatment side effects were not. Further, in every scale except for neurotoxicity, higher (better) baseline scores were associated with a decreased likelihood of death, after adjusting for age, performance and disease status. CONCLUSION: The NFOSI-18 DRS-P scale is responsive to clinical change. It has potential as an indicator of changing health status with ovarian cancer disease progression, distinct from treatment side effects.

Randomized trial of exercise on depressive symptomatology and brain derived neurotrophic factor (BDNF) in ovarian cancer survivors: The Women's Activity and Lifestyle Study in Connecticut (WALC).

OBJECTIVES: Depression is one of the most prevalent mental disorders, and rates are higher among cancer survivors than the general population, and higher in ovarian cancer patients compared to cohorts of other cancer survivors. Physical activity has been associated with lower depressive symptoms in cancer survivors, yet no trial has examined this association in women with ovarian cancer. We examined the effect of exercise on depression symptomatology and serum brain derived neurotrophin factor (BDNF) which has been associated with depression, in women with ovarian cancer. METHODS: We conducted a 6-month home-based randomized trial of exercise vs. attention-control (AC) in 144 ovarian cancer survivors. Depressive symptomatology was measured via the Center for Epidemiologic Studies Depression Scale (CES-D). Serum total and free BDNF was measured at baseline and 6-months. Student's t-statistic and mixed-model repeated measures analysis was used to evaluate six-month change between arms in CES-D scores and BDNF. RESULTS: Women were 57.3 ±â€¯8.6 (mean ±â€¯SD) years old, 1.7 ±â€¯1.0 years post-diagnosis with a baseline CES-D score of 11.79 ±â€¯10.21. The majority (55%) were diagnosed with stage III/IV ovarian cancer. CES-D scores decreased in the exercise arm by 2.7 points (95% CI: -4.4, -0.9) or a 21% decrease compared to a 0.3 point decrease (-2.2, 1.5) (3% decrease) in the AC arm (P = 0.05). There was no difference in change in total or free BDNF between the exercise and AC arms. CONCLUSIONS: Ovarian cancer survivors are able to exercise at recommended levels, and exercise was associated with a significant reduction in depressive symptomatology.

Sexual harassment in the work place: Its impact on gynecologic oncology and women's health.

For the last few months, media and news outlets have exposed prominent professionals in many settings who have taken advantage of their status of power and influence to engage in sexual harassment and discrimination in the workplace. In medicine, harassment may include many types of health professionals including physicians, nurses, medical students, colleagues and even patients. Programs for sexual harassment prevention, education and training vary between industries, workplaces, medical schools and hospitals. It is imperative to engage men and women in awareness, education, empowerment of the bystander and movement for cultural change. A grass roots effort should be started by each of us to reach out to our academic institutions, health systems and private practices to review policy, education and codes of conduct. We have the ability to embrace improvement around gender and diversity in our words and actions.

Quality of life, symptoms and care needs in patients with persistent or recurrent platinum-resistant ovarian cancer: An NRG Oncology/Gynecologic Oncology Group study.

OBJECTIVES: The goals of treating recurrent platinum-resistant ovarian cancer are palliative, aimed at reducing symptoms and improving progression free survival. A prospective trial was conducted to determine the prevalence and severity of symptoms, and associated care needs. METHODS: Eligible women included those with persistent or recurrent platinum-resistant ovarian cancer with an estimated life expectancy of at least 6 months. The Needs at the End-of-Life Screening Tool (NEST), FACIT-Fatigue (FACIT-F), NCCN-FACT Ovarian Symptom Index [NFOSI-18]; Disease Related Symptoms (DRS), Treatment Side Effects (TSE), and Function/Well Being (F/WB) were collected at study entry, 3 and 6 months. RESULTS: We enrolled 102 evaluable patients. Initiation of Do Not Resuscitate (DNR) discussions increased over time from 28% at study entry to 37% at 6 months. At study entry, the most common disease-related symptoms were fatigue (92%), worry (89%), and trouble sleeping (76%); 73% reported being "bothered by treatment side effects", which included nausea (41%) and hair loss (51%) neither of which changed over time. The most common NEST unmet needs were in the symptom dimension. The social dimension was associated with F/WB (p = 0.002) and FACIT-F (p = 0.006); symptoms were associated with DRS (p = 0.04), TSE (p = 0.03), and FACIT-F (p = 0.04); existential was not associated with any of the patient-reported symptoms; therapeutic was associated with F/WB (p = 0.02). CONCLUSIONS: In patients nearing the end of life, there are significant associations between disease and treatment related symptoms and unmet patient needs, which do not change substantially over time. Careful exploration of specific end-of-life care needs can improve patient-centered care and QOL.

Chemotherapy completion in elderly women with ovarian, primary peritoneal or fallopian tube cancer - An NRG oncology/Gynecologic Oncology Group study.

PURPOSE: A simple measure to predict chemotherapy tolerance in elderly patients would be useful. We prospectively tested the association of baseline Instrumental Activities of Daily Living (IADL) score with ability to complete 4 cycles of first line chemotherapy without dose reductions or >7days delay in elderly ovarian cancer patients. PATIENTS AND METHODS: Patients' age ≥70 along with their physicians chose between two regimens: CP (Carboplatin AUC 5, Paclitaxel 135mg/m2) or C (Carboplatin AUC 5), both given every 3weeks either after primary surgery or as neoadjuvant chemotherapy (NACT) with IADL and quality of life assessments performed at baseline, pre-cycle 3, and post-cycle 4. RESULTS: Two-hundred-twelve women were enrolled, 152 selecting CP and 60 selecting C. Those who selected CP had higher baseline IADL scores (p<0.001). After adjusting for age and PS, baseline IADL was independently associated with the choice of regimen (p=0.035). The baseline IADL score was not found to be associated with completion of 4 cycles of chemotherapy without dose reduction or delays (p=0.21), but was associated with completion of 4 cycles of chemotherapy regardless of dose reduction and delay (p=0.008) and toxicity, with the odds ratio (OR) of grade 3+ toxicity decreasing 17% (OR: 0.83; 95%CI: 0.72-0.96; p=0.013) for each additional activity in which the patient was independent. After adjustment for chemotherapy regimen, IADL was also associated with overall survival (p=0.019) for patients receiving CP. CONCLUSION: Patients with a higher baseline IADL score (more independent) were more likely to complete 4 cycles of chemotherapy and less likely to experience grade 3 or higher toxicity.

Body mass index and mortality in endometrial cancer: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between body mass index (BMI) and mortality in women with endometrial cancer. METHODS: A systematic review was performed utilizing a Medline search with Mesh keywords 'endometrial neoplasms' and ('body mass index' or 'obesity') and ('survival analysis' or 'mortality' or 'survivor' or 'survival') for studies published prior to June 2013. Inclusion criteria included studies that assessed associations between BMI and survival in endometrial cancer patients. Two investigators independently reviewed the title and abstract and full-text of articles for inclusion or exclusion decision; discordant decisions were adjudicated by a third reviewer. A random-effects model was constructed that was comparable to the standard random-effects models used in the meta-analysis of odds ratios. The model was fitted using SAS PROC NLMIXED. RESULTS: 1451 studies were identified and reviewed in duplicate, 18 met inclusion criteria. A random-effects meta-analysis demonstrated significantly higher odds of mortality with increasing BMI in endometrial cancer patients. Specifically the odds ratios were 1.01, 1.17, 1.26, and 1.66 for BMI categories of 25-29.9, 30-34.9, 35-39.9, and 40+, respectively. The odds ratio for all-cause mortality in endometrial cancer patients with a BMI≥40 compared to those with a BMI<25 was 1.66 (CI: 1.10-2.51, p=0.02). A single dose-response model indicated that a 10% increase in BMI resulted in a 9.2% increase in the odds of all-cause mortality (p=0.007). CONCLUSION: Increased BMI is significantly associated with increased all-cause mortality in women with endometrial cancer, with the highest risk for those with a BMI≥40.

Feasibility of a lifestyle intervention for overweight/obese endometrial and breast cancer survivors using an interactive mobile application.

OBJECTIVE: The study aimed to assess a one-month lifestyle intervention delivered via a web- and mobile-based weight-loss application (app) (LoseIt!) using a healthcare-provider interface. METHODS: Early-stage overweight/obese (body mass index [BMI]≥25kg/m(2)) cancer survivors (CS) diagnosed in the past three years, and without recurrent disease were enrolled and received exercise and nutrition counseling using the LoseIt! app. Entry and exit quality of life (FACT-G) and Weight Efficacy Lifestyle Questionnaire (WEL) measuring self-efficacy were measured along with anthropometrics, daily food intake, and physical activity (PA) using the app. RESULTS: Mean participant age was 58.4±10.3years (n=50). Significant reductions (p<0.0006) in anthropometrics were noted between pre- and post-intervention weight (105.0±21.8kg versus 98.6±22.5kg); BMI (34.9±8.7kg/m(2) versus 33.9±8.4kg/m(2)); and waist circumference (108.1±14.9cm versus 103.7±15.1cm). A significant improvement in pre- and post-intervention total WEL score was noted (99.38±41.8 versus 120.19±47.1, p=0.043). No significant differences were noted in FACT-G, macronutrient consumption, and PA patterns. CONCLUSION: These results indicate that a lifestyle intervention delivered via a web- and mobile-based weight-loss app is a feasible option by which to elicit short-term reductions in weight. Though these results parallel the recent survivors of uterine cancer empowered by exercise and healthy diet (SUCCEED) trial, it is notable that they were achieved without encumbering significant cost and barrier-access issues (i.e. time, transportation, weather, parking, etc.).

Randomized phase II trial of sorafenib alone or in combination with carboplatin/paclitaxel in women with recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer.

BACKGROUND/PURPOSE: This study was designed to evaluate the response and toxicity of sorafenib alone or when combined with carboplatin and paclitaxel in patients with platinum-sensitive, recurrent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (EOC). METHODS: Patients with recurrent platinum-sensitive EOC with no more than 2 prior courses of chemotherapy were randomized to single-agent sorafenib 400 mg twice daily or combination sorafenib 400 mg bid (days 2-19) with IV carboplatin (AUC 6) and IV paclitaxel 175 mg/m(2) (S+C/T) every 3 weeks. Single agent sorafenib could cross over to combination upon progression. RESULTS: Patients were initially randomized to either arm, however, due to poor accrual, sorafenib arm was prematurely closed. A total of 13 patients were evaluable for response to sorafenib and 23 patients were evaluable for response to S+C/T. Objective response rate (RR) was 15 % for patients on sorafenib vs. 61 % for patients on S+C/T (p = 0.014); stable disease was seen in 62 % and 35 %, respectively. Clinical benefit rate (CBR) at 4 months (mos.) was 69 % for S and 65 % for S+C/T. The median progression free survival was 5.6 months on sorafenib vs. 16.8 months on S+C/T (p = 0.012) and there was no significant difference of overall survival between two arms (p = 0.974) with median overall survival 25.6 months under sorafenib vs. 25.9 months on S+C/T. Patients remained on trial for a median of 7.8 cycles on sorafenib and 5.4 cycles on S+C/T. CONCLUSION: Sorafenib, alone or in combination with carboplatin and paclitaxel, has activity in patients with platinum-sensitive EOC. Sorafenib in combination with carboplatin and paclitaxel improved RR and PFS; however, there were increased grade and frequencies of toxicities.

Safety culture in the gynecology robotics operating room.

STUDY OBJECTIVE: To measure the safety culture in the robotics surgery operating room before and after implementation of the Robotic Operating Room Computerized Checklist (RORCC). DESIGN: Prospective study. SUBJECTS: Gynecology surgical staff (n = 32). SETTING: An urban community hospital. INTERVENTIONS: The Safety Attitudes Questionnaire domains examined were teamwork, safety, job satisfaction, stress recognition, perceptions of management, and working conditions. Questions and domains were described using percent agreement and the Cronbach alpha. Paired t-tests were used to describe differences before and after implementation of the checklist. MEASUREMENTS AND MAIN RESULTS: Mean (SD) staff age was 46.7 (9.5) years, and most were women (78%) and worked full-time (97%). Twenty respondents (83% of nurses, 80% of surgeons, 66% of surgical technicians, and 33% of certified registered nurse anesthetists) completed the Safety Attitudes Questionnaire; 6 were excluded because of non-matching identifiers. Before RORCC implementation, the highest quality of communication and collaboration was reported by surgeons and surgical technicians (100%). Certified registered nurse anesthetists reported only adequate levels of communication and collaboration with other positions. Most staff reported positive responses for teamwork (48%; α = 0.81), safety (47%; α = 0.75), working conditions (37%; α = 0.55), stress recognition (26%; α = 0.71), and perceptions of management (32%; α = 0.52). No differences were observed after RORCC implementation. CONCLUSION: Quality of communication and collaboration in the gynecology robotics operating room is high between most positions; however, safety attitude responses are low overall. No differences after RORCC implementation and low response rates may highlight lack of staff support.

Health care and social media platforms in hospitals.

The objective of this article is to illustrate user characteristics of a hospital's social media structure using analytics and user surveys. A 1-year retrospective analysis was conducted along with an Internet survey of users of the hospital's Facebook, Twitter, and blog. Of the survey respondents (n = 163), 95.7% are female and 4.3% are male; most are ages 50-59 years (31.5%) and 40-49 years (27.8%); and 93.2% are Caucasian. However, the hospital system database revealed 55% female and 37% minority population, respectively. Of the survey respondents, 61.4% reported having a bachelor's degree or higher, whereas only 11.7% reported having a high school degree/equivalent or lower. However, within the hospital patient databases, 93% of patients have a high school degree/equivalent or lower and only 3% have a bachelor's degree or higher in our women's services population. Social media were used to seek personal health information 68.7% (n = 112), to learn about hospital programming 27.6% (n = 45), and to seek family health information 25.2% (n = 41). Respondents younger than 49 years of age were more likely to seek personal health information using social media compared to those 50 years of age and older (p = .02). Respondents with a bachelor's degree or higher education were statistically less likely to search for physician information compared to those less educated individuals (p = .04). We conclude that social media may play an important role in personal health information, especially for young female respondents; however, the survey provides strong evidence that further research is needed to ensure that social network sites provided by hospitals are reaching the full spectrum of health system patients.

Management of the late effects of treatments for gynecological cancer.

PURPOSE OF REVIEW: As the number of gynecologic cancer survivors grows, there is an increased awareness and need for effective therapy for late side-effects caused by cancer treatments. Several treatment modalities are used to treat gynecologic malignancies, including surgery, radiotherapy, and chemotherapy. Each modality can be responsible for causing late-term side-effects. RECENT FINDINGS: There has been an increased awareness of the late detrimental side-effects of cancer treatment, mostly by the use of patient-generated surveys. Effective ways to treat and ameliorate the late side-effects have lagged behind the ability to describe and categorize these effects on patient's quality of life. SUMMARY: This review will highlight the recent studies to help the clinician caring for gynecologic cancer survivors in recognizing and treating the late effects of cancer therapy.

The financial performance of labor and delivery units.

Hospitals and health care systems are already seeing the effect of health care reform with declining dollars. Hospital services, which had narrow financial margins in the past, will have further challenges. This article will review definitions, challenges, and potential financial solutions for labor and delivery units. Improving quality, efficiency, and cost requires substantial physician cooperation in the changing paradigm from physician-centric care to the transparent safety of teams. The financial contribution margin should increase the net revenue, but significant volumes are also needed. The challenge of this model for obstetrics is the slowing birth rate with the ultimate limitation for growth. Therefore, cost containment is imperative for sustainability. Standardization of hospital policies and procedures can improve quality and cost-savings with new incentive models. Examples include decreasing expensive pharmaceuticals, minimizing elective inductions of labor, and encouraging breast-feeding. As providers of health care to women, we all must engage in the triple aim of (1) improving the experience of care, (2) improving the health of populations, and (3) reducing per capita costs of health care. Although accountable care organizations presently are focused on Medicare populations for cost containment, all health care providers and institutions must be vigilant on both quality cost-effective care for sustainability, especially in obstetrics.

Does enhanced "bundling" criteria improve outcomes? A comparative study of elective inductions.

OBJECTIVE: To assess outcomes and costs of dyads achieving elective induction bundle criteria with a favorable Bishop score. STUDY DESIGN: In a historical automated records-based cohort study, 180 dyads undergoing elective induction bundling at a single institution from 2009 to 2010 were compared to a pre-introduction of bundling cohort. The bundled cohort was then compared by Bishop score. RESULTS: The bundled cohort (n = 180) had a lower cesarean delivery rate (12% vs. 21%, p = 0.01), but neonatal special or intensive care admissions were not statistically significant compared to the pre-introduction of bundling cohort (n = 473). Ninety-six percent (n = 173) of the bundled cohort achieved bundle criteria. Those with a Bishop score > 6 (52%, n = 90) had fewer cesarean deliveries (4% vs. 19%, p = 0.003), fewer neonatal special or intensive care admissions (1% vs. 10%, p = 0.015), shorter induction time to vaginal delivery (8.8 vs. 17 hrs, p < 0.001), fewer cesareans for dystocia (75% vs. 94%, p = 0.002) or fetal heart rate abnormalities (25% vs. 50%, p = 0.015), and had one-sixth the average net income lost ($423 vs. $2,600, p < 0.001) compared to bundle achievers with a Bishop score of < or = 6. CONCLUSION: The elective induction bundle does not guarantee quality and should require favorable cervix instead of documented Bishop score to proceed with induction.

Robotic-assisted hysterectomy for the management of severe endometriosis: a retrospective review of short-term surgical outcomes.

OBJECTIVES: The primary objective was to examine the safety and feasibility of robotic-assisted laparoscopy in a cohort of women treated surgically for stage III and IV endometriosis. The secondary objective was to explore whether the stage of endometriosis affected surgical outcome. METHODS: In this cohort study, 43 women with severe endometriosis were treated with robot-assisted laparoscopic hysterectomy with unilateral or bilateral salpingooophorectomy for stage III (n = 19) or stage IV (n = 24) disease. RESULTS: Histopathologic evaluation confirmed endometriosis in all patients, and fibroids were also shown in 12 patients. The median actual operative time was 145 min (range, 67-325 min), and the median blood loss was 100 mL (range, 20 - 400 mL). All but one of the procedures were completed successfully robotically. The length of hospital stay was 1 d for 95% of patients (41 of 43), and 2 patients had prolonged stays of 4 d and 5 d, respectively. One patient was readmitted for a vaginal cuff abscess; this represented the only complication identified in this series. CONCLUSIONS: Robot-assisted laparoscopic surgery appears to be a reasonably safe and feasible method for the definitive surgical management of women with severe endometriosis.

The association between quality of life domains and overall survival in ovarian cancer patients during adjuvant chemotherapy: a Gynecologic Oncology Group Study.

PURPOSE: To explore the association between baseline quality of life (QOL) scores and overall survival (OS) in ovarian cancer patients receiving adjuvant chemotherapy. METHODS: Patients with stage III ovarian cancer on Gynecologic Oncology Group protocol #172 completed the Functional Assessment of Cancer Therapy-General (FACT-G) and were then randomly assigned to either intravenous (IV) or intraperitoneal (IP) chemotherapy. The FACT scale includes physical, functional, social, and emotional well-being domains (PWB, FWB, SWB, EWB). The PWB item, lack of energy, was used to assess the presence of fatigue. RESULTS: After adjusting for patient age, treatment assignment, and the presence of gross disease, PWB was associated with OS. Patients who reported baseline PWB scores in the lowest 25% (PWB score<15 points) relative to those who scored in the highest 25% (PWB score>24 points) had decreased OS (HR: 1.81; 95% CI: 1.2-2.72; p=0.005). Patients experienced death rates 20% lower for every mean item point increase in PWB (Hazard Ratio [HR]: 0.80; 95% CI: 0.68-0.93; p=0.005). Patients complaining of fatigue did not have an increased risk of death compared with those not feeling fatigued (HR: 1.21; 95% CI: 0.91-1.61; p=0.19). CONCLUSIONS: Poor physical well-being reported at baseline is associated with risk of death in patients undergoing adjuvant chemotherapy for advanced ovarian cancer. Identifying modifiable characteristics that are associated with survival offers the potential for providing support that may improve outcomes.

Toxicity of weekly oral topotecan in relation to dosage for gynecologic malignancies: a phase I study.

The aim of this study was to determine the dose of weekly oral topotecan that allows safe administration and to evaluate the pharmacokinetics of this dose in patients with recurrent gynecologic malignancies. The first cohort of patients received oral topotecan 6 mg/week administered orally on days 1, 8, and 15 of a 28-day regimen. A standard 3+3 dose-escalating phase design was used for dose levels II-V (8, 10, 12 and 14 mg/week). Toxicity was scored according to the Common Terminology Criteria for Adverse Events. Cumulative toxicity was summarized in the 6-12 mg/week combined cohort and 14 mg/week cohort separately. Pharmacokinetic samples were obtained for day 1, cycle 1 only in the expansion cohort (dose level V). Twenty-five patients received a total of 88 cycles of therapy. Hematologic toxicities of grade 3 (6-12 mg dose) were neutropenia (25%) and anemia (8.3%). Gastrointestinal toxicities of grade 3 were diarrhea (16.7%) and obstruction (8.3%, disease-related). Grade 3 or 4 (14 mg/week) hematologic toxicities consisted of neutropenia (38.5%), platelets (15.4%), anemia (15.4%), infection with neutropenia (7.7%), and thrombosis (7.7%). Gastrointestinal toxicities of grade 3 were diarrhea (7.7%), obstruction (7.7%), and vomiting (7.7%). One patient died secondary to neutropenic sepsis. One patient (4%; 95% confidence interval: 2.1, 22.3) showed a partial response and five patients (20%; 95% confidence interval: 7.6, 41.3) had stable disease. An oral topotecan dose of 14 mg/week for 3 consecutive weeks out of 4 is mostly associated with acceptable toxicities and may be considered for use in future single-agent phase II trials.

Palliative and end-of-life care for patients with ovarian cancer.

Palliative care improves the quality of life of patients and their families through the prevention and treatment of distressing symptoms while addressing the psychological, social, and spiritual aspects of patient care. Emerging paradigms of delivery promote early involvement in the disease trajectory and specialty approaches to care. Interdisciplinary assessment and shared decision making are important components. Throughout the disease course, aggressive symptom management can improve patients' quality of life and their ability to tolerate and continue treatment. End-of-life care focuses on comfort, control, meaning, and support that become particularly intense when death is imminent.