Heidi Frasure

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.

An updated clinicopathologic study of early-stage uterine papillary serous carcinoma (UPSC)

OBJECTIVES Stage I-II uterine papillary serous carcinoma (UPSC) patients have a significant risk for extrapelvic recurrence. However, clinicopathologic risk factors for recurrence are not well understood. This study was undertaken to define the prognostic factors for recurrence and survival in patients with early-stage UPSC. METHODS A retrospective, multi-institution analysis of surgically staged I-II UPSC patients was performed. Patients were treated by various adjuvant modalities. Age, race, sub-stage, percentage UPSC histology, lymphvascular space invasion (LVSI), tumor size and adjuvant treatment modality were evaluated for their effect on recurrence and survival outcomes. RESULTS We identified 206 patients. Forty patients (19.4%) had 5-49% UPSC, 55 (26.7%) had 50-99% and 111 patients (53.9%) had 100% UPSC in their respective uterine specimens. Twenty one percent of patients experienced a primary recurrence. On univariate analysis, age, increasing %UPSC, LVSI, and tumor size were not significantly associated with recurrence or progression-free survival (PFS). However, substage (p=0.005) and treatment with platinum/taxane-based chemotherapy (p=0.001) were associated with recurrence/PFS. On multivariate analysis, only chemotherapy (p=0.01) was a significant factor affecting PFS, whereas age (p=0.05), substage (p=0.05), and chemotherapy (p=0.02) were associated with overall survival. CONCLUSIONS Traditional risk factors for recurrence and survival in patients with early-stage endometrial cancer may not be relevant in patients with UPSC. Patients with any percentage UPSC in their uterine specimens are at a significant risk for recurrence and poor survival outcomes. Given that current clinicopathologic data does not accurately identify women most likely to benefit from adjuvant therapy, alternative prognostic markers based on novel techniques should be explored.

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.

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

Self-efficacy, quality of life, and weight loss in overweight/obese endometrial cancer survivors (SUCCEED): A randomized controlled trial

OBJECTIVE More patient-centered programming is essential for endometrial cancer (EC) survivors needing to lose weight to reduce cardiovascular disease risk (CVD). The purpose of this study was to improve self-efficacy (SE) and quality of life (QOL) using a lifestyle intervention program designed for weight loss. METHODS Overweight and obese early-stage EC survivors, n = 75, were randomized into two groups: 1) Survivors of Uterine Cancer Empowered by Exercise and Healthy Diet (SUCCEED), a six-month lifestyle intervention or 2) a usual care group (UC). Participants completed the Weight Efficacy Lifestyle Questionnaire (WEL) to assess SE and the Functional Assessment of Cancer Therapy-General (FACT-G) to measure QOL, and their body mass index (BMI) was calculated at baseline, 3, 6, and 12 months. Mixed, repeated-measures ANCOVA models with baseline covariates were employed using SPSS 20.0. RESULTS Positive effects in every WEL domain, including the total score, were statistically significant in the SUCCEED group versus the UC group. A linear regression model demonstrated that, if BMI decreased by 1 unit, the total WEL score increased by 4.49 points. Significant negative correlations were found in the total WEL score and a change in BMI of R = -0.356 (p = 0.006). Between-group differences in the FACT-G were significant from baseline in the fatigue domain at three months (p = .008) and in the physical domain at six months (p = .048). No other significant differences were found. CONCLUSION Overall, this study shows promise for targeted interventions to help improve SE, thus improving BMI.

Minimally invasive surgery versus laparotomy in women with high grade endometrial cancer: A multi-site study performed at high volume cancer centers

OBJECTIVE The study aim was to compare outcomes in women with high-grade endometrial cancer (EC) who underwent surgical staging via minimally invasive surgery (MIS) versus laparotomy. METHODS This is a retrospective, multi-institutional cohort study of patients with high-grade EC who were comprehensively surgically staged by either MIS or laparotomy. Demographic, surgical variables, complications, and survival were analyzed. RESULTS Three hundred and eighty-three patients met criteria: 191 underwent laparotomy and 192 MIS (65% robotic, 35% laparoscopy). Subgroups were well matched by age (mean 66 years), stage, body mass index, histology and adjuvant therapies. Median operative time was longer in the MIS group (191 vs. 135 min; p<.001). However, the MIS cohort had a higher mean lymph node count (39.0 vs. 34.0; p=.03), shorter hospital stay (1 vs. 4 days) and significantly fewer complications (8.4% vs. 31.3%; p<.001). There was no significant difference in lymph node count with laparoscopic versus robotic staging. With a median follow-up time of 44 months, progression-free (PFS) and overall survival were not significantly different between the surgical cohorts. On multivariable analysis, stage, treatment were associated with PFS. CONCLUSIONS Women with high grade endometrial cancers staged by minimally invasive techniques experienced fewer complications and similar survival outcomes compared to those staged by laparotomy. As this population is elderly and most will receive adjuvant therapies, minimization of surgical morbidity is of interest. When managed by expert laparoscopists or robotic surgeons, a high-risk histologic subtype is not a contraindication to minimally invasive surgery in women with apparent early-stage disease.

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.

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.

Quality of Life in Endometrial Cancer Survivors: What Does Obesity Have to Do with It?

Objective. Most women with type I endometrial cancer (EC) are obese, increasing the risk of morbidity and mortality in this population. The study objective was to evaluate the impact of obesity on quality of life (QOL) and general health status in EC survivors with early-stage disease. Methods. A prospective ancillary analysis of stage I/II EC survivors. The association of BMI with QOL questionnaire variables measured with the functional assessment of cancer therapy (subscales: physical (PWB), functional (FWB), social, and emotional well-being) and the physical (PCS) and mental component summary subscales of the short-form medical outcomes survey was determined. Results. 152 women completed both questionnaires; 81% were obese. After multiple linear regression, BMI was inversely associated with PWB (P = .001), FWB (P = 0.048), and PCS (P = .001). Conclusions. Despite the good prognosis associated with early-stage EC, QOL, and physical health are not optimized in obese survivors. This paper highlights the importance of incorporating health-related QOL assessments and obesity interventions during the survivorship period.