OBJECTIVE:: Endometrial cancer (EC) is increasing in incidence and mortality rates, possibly due to the rising rates of obesity in the United States. The type I/II EC classification system was first proposed by Bokhman in 1983 following 20 years of personal observations among 366 women and established obesity as a classical risk factor for low-grade EC with a good prognosis. However, more recent pooled analyses suggest that the 2 types share many etiologic risk factors, including obesity. Given the increase in mortality as a consequence of high-risk EC, the relationship between obesity and uterine cancer, as proposed by Bohkman, may be oversimplified. This study aimed to analyze the trend of type I/II EC in the United States as it relates to obesity using national statistics. STUDY DESIGN:: Data were obtained from the United States Cancer Statistics database and the Behavioral Risk Factors Surveillance System survey from 2001 to 2017. The incidence of uterine cancer, histologic type, obesity, and average annual percentage change (AAPC) were calculated using Joinpoint regression. Endometrial histology was classified according to traditional type I (endometrioid grade 1–3) and type II (serous, clear cell, carcinosarcoma) categories. RESULTS:: Over this 17-year study period, 778,891 patients were diagnosed with uterine cancer. Overall, the rate of new uterine cancer cases increased by 0.82% annually (P<.005), leading to an incidence of 24.07 per 100,000 in 2001 as compared with 27.04 per 100,000 women in 2017. The incidence of type I EC remained stable (AAPC, 0.40; P=.061) with a stable incidence of grade I EC (AAPC, −0.48; P=.125) and a decreasing incidence of grade 2 and grade 3 EC (AAPC, −2.61 and −2.63, respectively; P<.001). Alternatively, the incidence of type II EC increased by 3.12% annually (P<.001), leading to an increase of 63% since 2001. Serous carcinoma increased by 4.88% annually (P<.001). Clear cell and carcinosarcoma also increased significantly (AAPC, 1.02 and 1.51, respectively; P<.05). For illustrative purposes, we calculated the percentage increase in the incidence of cancer types over the last 17 years in comparison with the year 2001 (Figure). Overall, the proportion of women with obesity also increased significantly from 19.5% to 27.5% during this period (AAPC, 1.5; P<.001). CONCLUSION:: Utilizing 17 years of data from a national cancer registry, we demonstrated that the incidence of high-risk type II EC has increased, whereas the incidence of low-risk grade I EC has remained stable. In another survey study, we showed the rising incidence of obesity. These findings suggest that the traditional type I/II approach to classifying EC may be oversimplified, particularly as it relates to obesity. Recent studies utilizing The Cancer Genome Atlas classification for EC demonstrated an association between a mean body mass index (BMI) of ≥30 and each of the 4 clusters except for DNA polymerase epsilon gene ultramutated tumors. Furthermore, up-regulation of several genes known to play a role in EC pathogenesis were associated with BMI, suggesting that obesity may create a unique, proinflammatory microenvironment that affects tumor biology at a molecular level. Limitations of the current study include possible information reporting bias, lack of central pathology review, and limited ability to correlate data between multiple databases. Incidence rates are also not corrected for hysterectomy prevalence. However, these trends suggest a potential impact of obesity on the rising rates of type II EC that should be explored further.

Objective

To determine the role of miR-378 as a biomarker for anti-angiogenic therapy response in ovarian cancer.

Methods

Expression of miR-378 was analyzed in ovarian cancer cell lines and human tumors vs. normal ovarian epithelial cells by qRT-PCR. After miR-378 transfection in SKOV3 cells, dysregulated genes were identified using microarray. Data from The Cancer Genome Atlas (TCGA) was utilized to correlate miR-378 expression with progression-free survival (PFS) among patients treated with anti-angiogenic therapy by using Kaplan-Meier and Cox proportional hazards.

Results

MiR-378 was overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. Overexpressing miR-378 in ovarian cancer cells altered expression of genes associated with angiogenesis (ALCAM, EHD1, ELK3, TLN1), apoptosis (RPN2, HIPK3), and cell cycle regulation (SWAP-70, LSM14A, RDX). In the TCGA dataset, low vs. high miR-378 expression was associated with longer PFS in a subset of patients with recurrent ovarian cancer treated with bevacizumab (9.2 vs. 4.2months; p=0.04). On multivariate analysis, miR-378 expression was an independent predictor for PFS after anti-angiogenic treatment (HR=2.04, 95% CI: 1.12-3.72; p=0.02). Furthermore, expression levels of two miR-378 targets (ALCAM and EHD1) were associated with PFS in this subgroup of patients who received anti-angiogenic therapy (9.4 vs. 4.2months, p=0.04 for high vs. low ALCAM; 7.9 vs. 2.3months, p<0.01 for low vs. high EHD1).

Conclusions

Our data suggest that miR-378 is overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. MiR-378 and its downstream targets may serve as markers for response to anti-angiogenic therapy.

We used data from the US Cancer Statistics database to determine trends in cancer incidence, stratified by age, race, and ethnicity, among women aged 20 years or older during an 18-year study period (2001-2018). We limited analysis to cancers associated with 5 modifiable risk factors: tobacco use, excess body fat, alcohol consumption, insufficient physical activity, and human papillomavirus infection. The incidence of cancers associated with obesity have risen, particularly among women aged 20 to 49 years (vs ≥50 y) and among Hispanic women. Strategies that address obesity rates in these populations may help decrease cancer risk.

Objectives

To determine the association between timing of adjuvant therapy initiation and survival of early stage ovarian cancer patients.

Methods

Data were obtained from women who underwent primary surgical staging followed by adjuvant therapy from two Gynecologic Oncology Group trials (protocols # 95 and 157). Kaplan-Meier estimates and Cox proportional hazards model adjusted for covariates were used for analyses.

Results

Of 497 stage I-II epithelial ovarian cancer patients, the median time between surgery and initiation of adjuvant therapy was 23days (25th-75th%: 12-33days). The time interval from surgery to initiation of adjuvant therapy was categorized into three groups: <2weeks, 2-4weeks, and >4weeks. The corresponding 5-year recurrence-free survival rates were 72.8%, 73.9%, and 79.5% (p=0.62). The 5-year overall survival rates were 79.4%, 81.9%, and 82.8%, respectively (p=0.51; p=0.33 - global test). As compared to <2weeks, the hazard ratio for recurrence-free survival was 0.90 (95%CI=0.59-1.37) for 2-4weeks and 0.72 (95%CI=0.46-1.13) for >4weeks. Age, stage, grade, and cytology were important prognostic factors.

Conclusions

Timing of adjuvant therapy initiation was not associated with survival in early stage epithelial ovarian cancer patients.

Older patients and those who require interpreters are least likely to use telehealth for gynecologic oncology care, showing disparities which continued after statewide vaccinations.

Objective

To assess the presentation, characteristics, and prognostic significance of symptoms in patients with high-risk early-stage epithelial ovarian cancer.

Methods

A retrospective chart review was performed on all patients enrolled in a phase III clinical trial (GOG 157). All patients had surgically staged, high-risk early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II). Chi-square and Kaplan-Meier estimates and Cox proportional hazards models were used for statistical analyses.

Results

Of 419 patients evaluated for symptoms, 301 (72%) presented with one or more symptoms, and 118 (28%) were asymptomatic but had a mass found on examination. Forty percent had only one symptom, and 32% had more than one symptom. Among those with at least one symptom, the most common were abdominal and pelvic pain (31%), and increased girth or fullness (26%). Overall, 23% of patients with tumors 10 cm or smaller, 27% of patients with tumors larger than 10 cm to 15 cm, and 46% of patients with tumors larger than 15 cm had multiple symptoms (P<.001). There was no significant difference in presentation of symptoms based on age, stage, or histologic subtype. Symptoms at diagnosis were not associated with recurrence or survival.

Conclusion

More than 70% of patients with high-risk early-stage, epithelial ovarian cancer present with one or more symptoms, with the most common being abdominal or pelvic pain. The proportion of women with symptoms and the number of symptoms increase with enlarging tumor size.

Purpose

To compare patient/tumor characteristics and outcomes of Asians to Caucasian patients with epithelial ovarian cancer.

Methods

Ancillary data were pooled and analyzed from ten prospective randomized front-line Gynecologic Oncology Group clinical trials from 1996 to 2011. Demographic, clinicopathologic features, disease-specific and all-cause survival were analyzed.

Results

Of 7914 patients, 7641 were Caucasian and 273 Asian. When compared to Caucasians, Asians were younger at trial enrollment, had a better performance status, earlier-stage cancers (17.2% vs. 8.1% with stage I; p < 0.001), and were more likely to be of clear cell (15.8% vs. 6.2%, p < 0.001) and mucinous (3.3% vs. 1.9%, p < 0.001) histology. Asians had an improved 5-year disease-specific survival of 54.1% compared to 46.1% for Caucasians, p = 0.001. In multivariate analysis, the Asian race remained a significant prognostic factor for all-cause survival (HR: 0.84; 95% CI: 0.72-0.99; p = 0.04). Other factors predictive of improved survival included younger age, better performance status, optimal cytoreduction, earlier stage, non-clear cell histology, and lower grade tumors.

Conclusion

Asians enrolled into phase III ovarian cancer clinical trials were younger, with better performance status, earlier-stage of disease, and have a greater number of clear cell and mucinous tumors. After adjusting for these prognostic factors, Asians have a better survival compared to Caucasians.

Objective

To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials.

Methods

Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data.

Results

2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p < 0.0001).

Conclusion

Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials.

Purpose

We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities.

Methods

Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC).

Results

This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively).

Conclusions

Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.