Vivian E. von Gruenigen

Endometrial cancer and obesity: Epidemiology, biomarkers, prevention and survivorship

Endometrial cancer is the most common gynecologic malignancy in the Western world and is strongly associated with obesity. Despite the fact that most cases are diagnosed in early, more favorable stages, endometrial cancer incidence and mortality rates are on the rise. Morbidly obese women with endometrial cancer are more likely to die of their co-morbidities and also of their cancers when compared to their leaner cohorts. Given the increasing rates of morbid obesity in the United States, it is essential to develop appropriate screening tools and guidelines to reduce cancer morbidity and death amongst this group. Through an analysis of the existing literature, we present a review of the epidemiologic trends in obesity and endometrial cancer, discuss the promising role of screening biomarker studies, review prevention efforts and modifiable risk factors, and ways in which health outcomes and quality of life for endometrial cancer survivors may be optimized.

Treatment effects, disease recurrence, and survival in obese women with early endometrial carcinoma : a Gynecologic Oncology Group study.

The objective was to examine whether rates of disease recurrence, treatment‐related adverse effects, and survival differed between obese or morbidly obese and nonobese patients.

Feasibility and effectiveness of a lifestyle intervention program in obese endometrial cancer patients: A randomized trial

OBJECTIVE The majority of endometrial cancer survivors (ECS) are obese and at risk for premature death. The purpose of this study was to assess feasibility of a lifestyle intervention program for promoting weight loss, change in eating behaviors, and increased physical activity in obese ECS. STUDY DESIGN Early stage ECS (n=45) were randomized to a 6-month lifestyle intervention (LI; n=23) or usual care (UC; n=22). The LI group received group and individual counseling for 6 months. The primary endpoint was weight change. Secondary endpoints were physical activity, [Leisure score index (LSI)] and nutrient intake (3-day food records). Quantitative vitamin C and folate intake were used to assess fruit/vegetable intake. RESULTS Recruitment was 29%, adherence (LI group) was 73% and 84% of participants completed follow-up assessments. At 12 months, the intervention group lost 3.5 kg compared to a 1.4 kg gain in the control group [mean difference=-4.9 kg; 95% CI: -9.0 to -0.9 kg; p=.018] and had an increased LSI score of 16.4 versus -1.3 in the control group from baseline [mean group difference=17.8; 95% CI=7.1 to 28.4; p=.002]. There were no differences in vitamin C and folate intake. The LI group had lower intake of kilocalories, although differences were not significant. CONCLUSION(S) A lifestyle intervention program in obese ECS is feasible and can result in sustained behavior change and weight loss over a 1-year period.

Survivors of uterine cancer empowered by exercise and healthy diet (SUCCEED): A randomized controlled trial

OBJECTIVE The majority of endometrial cancer survivors (ECS) are obese and at risk for premature death. The purpose of this study was to evaluate an intervention for ECS to promote weight loss and a healthy lifestyle. METHODS Early stage overweight and obese (body mass index ≥ 25) ECS (N=75) were randomized to a 6-month lifestyle intervention (LI) or usual care (UC). The LI group received education and counseling for six months (10 weekly followed by 6 bi-weekly sessions). Weight change at 12 months was the primary endpoint. Secondary outcomes included fruit/vegetable servings/day and physical activity (PA). Multiple imputations were used for missing data and mixed models were used to analyze changes from baseline. RESULTS Adherence was 84% and follow-up data were available from 92% of participants at 6 months and 79% at 12 months. Mean [95% CI] difference in weight change between LI and UC groups at 6 months was -4.4 kg [-5.3, -3.5], p<0.001 and at 12 months was -4.6 kg [-5.8, -3.5], p<0.001. Mean [95% CI] difference in PA minutes between groups at 6 months was 100 [6, 194], p=0.038 and at 12 months was 89 [14, 163], p=0.020. Mean difference in kilocalories consumed was -217.8 (p<0.001) at 6 months and -187.2 (p<0.001) at 12 months. Mean [95% CI] difference in fruit and vegetable servings was 0.91 servings/day at 6 months and 0.92 at 12 months (p<0.001). CONCLUSIONS Behavior change and weight loss are achievable in overweight and obese ECS, however, the clinical implications of these changes are unknown and require a larger trial with longer follow-up.

A randomized trial of a lifestyle intervention in obese endometrial cancer survivors: quality of life outcomes and mediators of behavior change

BackgroundTo examine the effects of a 6 month lifestyle intervention on quality of life, depression, self-efficacy and eating behavior changes in overweight and obese endometrial cancer survivors.MethodsEarly stage endometrial cancer survivors were randomized to intervention (n = 23) or usual care (n = 22) groups. Chi-square, Students t-test and repeated measures analysis of variance were used in intent-to-treat analyses. Outcomes were also examined according to weight loss.ResultsMorbidly obese patients had significantly lower self-efficacy, specifically when feeling physical discomfort. There was a significant improvement for self-efficacy related to social pressure (p = .03) and restraint (p = .02) in the LI group. There was a significant difference for emotional well-being quality of life (p = .02), self-efficacy related to negative emotions (p < .01), food availability (p = .03), and physical discomfort (p = .01) in women who lost weight as compared to women who gained weight. Improvement in restraint was also reported in women who lost weight (p < .01).ConclusionThis pilot lifestyle intervention had no effect on quality of life or depression but did improve self-efficacy and some eating behaviors.Trial Registrationhttp://www.clinicaltrials.gov; NCT00420979

Lifestyle challenges in endometrial cancer survivorship.

OBJECTIVE: To examine lifestyle behaviors that may contribute to endometrial cancer survivor morbidity and to identify associations with quality of life. METHODS: Patients with early-stage (I or II) endometrial cancer with a body mass index of at least 25 kg/m2 completed questionnaires on smoking, physical activity, fruit and vegetable intake, and the Functional Assessment of Cancer Therapy (FACT) and Short-Form medical outcomes (SF-36) quality-of-life surveys. Behaviors were compared with American Cancer Society 2006 guidelines for cancer survivors (150 min/wk of moderate-to-vigorous physical activity; five servings fruit and vegetables per day; no smoking). Effect size (d) was calculated for the difference in means between meeting and not meeting guidelines (d=0.5 moderate effect). RESULTS: A total of 120 participants were enrolled. Of those, 43% had hypertension, 35% osteoarthritis, 33% metabolic syndrome, 21% type 2 diabetes mellitus, and 93% abdominal obesity. Only 12% of participants were meeting physical activity guidelines. Fifteen percent reported five or more servings of fruit and vegetables per day; mean intake was 2.6 servings per day. Seventy-four percent of participants were nonsmokers. Only 1% of participants met all three American Cancer Society guidelines; 22% met none of the recommendations. The emotional well-being (mean 17.4 [±4.1] compared with 20.1 [±4.1]; d=0.66) and fatigue scores (mean 34.6 [±9.5] compared with 40.5 [±9.6]; d=0.62) indicate that those who do not meet the guidelines had lower emotional well-being and increased fatigue. CONCLUSION: Endometrial cancer survivors have unhealthy lifestyles that put them at risk for morbidity. This survivor group should be offered multi-behavioral lifestyle interventions after diagnosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT 00420979 and NCT00732173. LEVEL OF EVIDENCE: II

Indwelling Catheters for the Management of Refractory Malignant Ascites: A Systematic Literature Overview and Retrospective Chart Review

The safety and efficacy of indwelling intraperitoneal (IP) catheters for the management of refractory malignant ascites is unclear. A systematic literature overview and retrospective chart review of patients with malignant refractory ascites who underwent indwelling IP catheter placement was performed. Standardized literature abstraction and chart review templates were used to ensure that consistent information was collected. Fifteen publications met literature search criteria, representing 221 patients. Tenckhoff (Quinton Instrument Company, Seattle, WA, USA), Pleurex (Denver Biomedical Inc., Golden, CO, USA), and peritoneal catheters were used, along with IP ports. A median 5.9% of cases (range: 2.5%-34%) had documented peritonitis. In the literature, untunneled catheters were most commonly associated with infections. Our chart review added 19 cases from two academic institutions to this literature (median age: 60 years [range: 31-85]; females: 17 [89%]; gynecological malignancies: 14 [73%]). Palliative management before catheter placement included diuretics (n=4 [21%]) and multiple paracenteses (n=11 [58%] had two or more taps [range: 2-8]). Median time from diagnosis to catheter placement was 25 months (range: 1-77). Interventions were: French pigtail catheters (n=16 [84%]), Tenckhoff catheter (n=1 [5%]), and Port-A-Caths (Smith Medical MD, St. Paul, MN, USA) (n=2; 11%). Four (21%) catheters were tunneled. Prophylactic antibiotics were prescribed in six cases (32%). Two cases (11%) had documented infections, seven catheters (37%) became occluded, and two leaked (11%). The median time from catheter until death was 36 days (range: 4-660). Nine patients (47%) were admitted to hospice. In these retrospective studies, indwelling IP catheters appear to be a safe and effective palliative strategy to manage refractory malignant ascites, without overwhelming infection rates.

Assessment of factors that contribute to decreased quality of life in gynecologic oncology group ovarian cancer trials

The objective of this study was to assess which quality‐of‐life (QOL) line items on the Functional Assessment of Cancer Therapy‐Ovarian (FACT‐O) were associated with low QOL in women who were receiving chemotherapy for ovarian cancer.

A review of issues surrounding quality of life among women with ovarian cancer

OBJECTIVES Progress has been made towards prolonging survival of ovarian cancer patients. This trend has placed increasing attention upon the quality of life (QoL). The aim of this study was to review the existing literature on QoL, including measurement tools, and to explore opportunities to optimize well-being. METHODS A comprehensive computer literature search of English language studies was performed in MEDLINE databases up to February 2010. RESULTS Validated tools have been used in multiple studies to provide a mechanism to asses information about QoL in ovarian cancer. Ovarian cancer and its treatment have significant effects on QoL including fatigue and the physical and functional domains. Studies indicate that ovarian cancer patients needs and QoL change during the trajectory of the disease. CONCLUSIONS As new treatment strategies for ovarian cancer are developed, research efforts should identify how therapeutics will affect QoL and include interventions to prevent or minimize the detrimental effects.

A phase I/II study of extended field radiation therapy with concomitant paclitaxel and cisplatin chemotherapy in patients with cervical carcinoma metastatic to the para-aortic lymph nodes: A gynecologic oncology group study

OBJECTIVES To determine the maximum tolerated dose (MTD) of weekly paclitaxel and cisplatin chemotherapy concurrent with extended field irradiation in women with cervical cancer metastatic to the para-aortic nodes. METHODS Patients with carcinoma of the cervix and histologically documented para-aortic node metastases were eligible for this phase I/II trial. Chemotherapy agents were administered weekly concurrent with extended field radiation with escalating doses of paclitaxel from 30-50 mg/m(2) in each of three cohorts of three patients each. A phase II cohort was then evaluated at the selected maximum tolerated dose (MTD). RESULTS The MTD was determined to be cisplatin 40 mg/m(2) (maximum dose of 70 mg) and paclitaxel 40 mg/m(2) administered weekly for six cycles concurrent with extended field radiation therapy. There were 19 evaluable patients for the phase II analysis of toxicity and efficacy. Grade three and four gastrointestinal toxicity was seen in 6 and neutropenia in 7. Radiation therapy was successfully completed in 36.8% of patients at eight weeks and in 68.4% of patients at nine weeks, with a median time to completion was 56 days. A total of 27 evaluable patients were enrolled, twelve are dead (mean survival of those deceased is 25 months), and 15 (56%) are alive, and have been followed for a mean of 48 months (range 25-68; median of 46 months). CONCLUSIONS Paclitaxel and cisplatin combination chemotherapy concurrent with extended field pelvic para-aortic irradiation can be administered at the described MTD and shows a higher than previously reported disease-free survival in relation to historical data. The 56% survival to date, and 50% estimated 48 month survival, warrants validation in a larger prospective cohort. Central radiation dose reduction is being considered in the next trial to decrease late toxicity of regimen.