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.

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.

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.

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.

Randomized Trial of Exercise on Quality of Life in Women With Ovarian Cancer: Women's Activity and Lifestyle Study in Connecticut (WALC).

Background: Ovarian cancer survivors experience a wide range of treatment side effects that can negatively affect health-related quality of life (HRQOL). Physical activity has been shown to improve HRQOL and cancer-related fatigue (CRF) for other cancer survivors; however, no large randomized controlled trial (RCT) has been conducted for ovarian cancer. Methods: This study examined the impact of a six-month RCT of exercise vs attention control on change in HRQOL (Short Form Health Survey-36) and CRF (Functional Assessment of Cancer Therapy-Fatigue Scale) in ovarian cancer survivors. Women (n = 144) were randomly assigned to study arms between May 1, 2010, and March 20, 2014. All statistical tests were two-sided. Results: A total of 74 women were randomly assigned to exercise and 70 to attention control. A total of 113 (78.5%) of the participants completed the six-month assessment. Adherence to the exercise intervention was excellent (166.0±66.1 minutes/week in the exercise arm). At six months, women in the exercise arm had improved physical HRQOL (SF-36 Physical Component Summary Score) compared with the control arm, 1.8 (SD = 1.1) vs -2.0 (SD = 1.2) , respectively (group difference = 3.7, SD = 1.2, 95% confidence interval [CI] = 0.7 to 6.8, P = .02). No group differences were seen for change in mental HRQOL. There was a statistically significant improvement in the fatigue score (Functional Assessment of Cancer Therapy-Fatigue) for exercisers (4.0, SD = 1.1, 95% CI = 1.8 to 6.2, P < .001) but not for controls (1.2, SD = 1.2, 95% CI = -1.1 to 3.5, P = .31), with a between-group difference of 2.8 (SD = 1.5, 95% CI = -0.2 to 5.7, P = .06). Conclusions: We found a six-month home-based, telephone-delivered exercise intervention of primarily brisk walking to be associated with improved physical HRQOL in women with ovarian cancer. Given that higher HRQOL and exercise have both been associated with overall survival in women diagnosed with ovarian cancer, oncologists and primary care providers should recommend and refer women diagnosed with ovarian cancer to clinic- or community-based exercise programs.

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.

Development and implementation results of an interactive computerized surgical checklist for robotic-assisted gynecologic surgery.

To address surgical complications, the World Health Organization (WHO) developed the Safe Surgery Saves Lives Checklist. With the foundation of the WHO's checklist, a robotic-specific checklist (RORCC) was developed using standardized content and face validity methods. The RORCC was implemented in a high volume gynecological (GYN) specialty group using minimally invasive robotic-assisted surgery. Data were abstracted from patients undergoing GYN procedures from four GYN surgeons at an urban, community hospital during November 16, 2010 to May 15, 2011 (pre-RORCC) n = 89 and from the period May 16, 2011 to November 16 2011 (post-RORCC) n = 121. Thirty-day readmissions pre-checklist and post-checklist were 12 and 5, respectively, which is a significant (p = 0.02) reduction. The duration of surgery was not significantly affected (p = 0.40) with pre-RORCC surgery time at 110.1 (35.7) min versus post-RORCC surgery time at 112.9 (37.4) min. This study demonstrated the feasibility of integrating an electronic, interactive, and robotic-specific checklist for gynecologic robotic-assisted surgery which resulted in a significant reduction in readmissions at the 30-day without significantly impacting operating room times.

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.).

Breast and ovarian cancer in the older woman.

Nearly half of all women diagnosed with breast or ovarian cancer are age 65 years or older with the number of women diagnosed expected to increase as the population ages and life expectancy improves. Older women are less likely to be offered standard cancer treatments, are more likely to develop higher toxicity, and have higher mortality. Chronologic age should not be the only factor used for making treatment decisions. Functional dependence, organ function, comorbidity, polypharmacy, social support, cognitive and/or psychosocial factors, overall life expectancy, and patient's goals of care are equally vital and should be assessed before and during treatment. In this review, current evidence and treatment guidelines for older women with breast or ovarian cancer are outlined.

Recommended patient-reported core set of symptoms and quality-of-life domains to measure in ovarian cancer treatment trials.

There is no consensus as to what symptoms or quality-of-life (QOL) domains should be measured as patient-reported outcomes (PROs) in ovarian cancer clinical trials. A panel of experts convened by the National Cancer Institute reviewed studies published between January 2000 and August 2011. The results were included in and combined with an expert consensus-building process to identify the most salient PROs for ovarian cancer clinical trials. We identified a set of PROs specific to ovarian cancer: abdominal pain, bloating, cramping, fear of recurrence/disease progression, indigestion, sexual dysfunction, vomiting, weight gain, and weight loss. Additional PROs identified in parallel with a group charged with identifying the most important PROs across cancer types were anorexia, cognitive problems, constipation, diarrhea, dyspnea, fatigue, nausea, neuropathy, pain, and insomnia. Physical and emotional domains were considered to be the most salient domains of QOL. Findings of the review and consensus process provide good support for use of these ovarian cancer-specific PROs in ovarian cancer clinical trials.

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.

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.

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.

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.

Using the "Summa Set-up" in robotic assisted gynecologic surgery.

During challenging gynecologic (GYN) procedures, the conventional robotic set-up can limit a surgeon's ability to effectively and efficiently perform these procedures. We present a novel set-up using a parallel-docking approach of the da Vinci (®) Surgical System with only three robotic arms and incorporating two patient side assist ports to overcome the difficulties presented during challenging GYN procedures. The Summa Set-up (SS) uses 4 ports actively, 2 assist ports and 2 robotic ports, compared to the traditional set-up which uses 4 ports: 1 assist port and 3 robotic ports. With the SS format, the patient-side assistant stands at the head of the bed and can simultaneously retract the uterus and aide in surgical dissection along with the console surgeon. While there are many possibilities of da Vinci (®) docking, port placement and assistant placement during robotic-assisted GYN surgery, we believe the SS can be an alternative for many GYN surgeons, especially those in teaching hospitals, for increased mobility and efficiency during complex GYN procedures.