Endometrial Cancer Outcomes Research Articles

Genomic landscape of circulating tumor DNA and real-world outcomes in advanced endometrial cancer.

ctDNA is a novel technique extensively studied in solid tumors, although not currently well defined in endometrial cancer (EC). A de-identified retrospective analysis of 1988 patients with advanced/recurrent EC was performed. In addition, an analysis of a real-world evidence (RWE) cohort was completed (n=1266). Patients underwent ctDNA testing using Guardant360 during routine clinical care. The objective was to describe and assess molecular landscape using ctDNA. Among 1988 ctDNA samples, at least one somatic alteration was detected in 91.6% (n=1821). Most frequently altered genes were TP53 (64%), PIK3CA (29%), PTEN (25%), ARID1A (20%) and KRAS (14%). Overall, 18.5% had amplifications, with the majority identified in CCNE1 (40.9%), PIK3CA (22%) and EGFR (19.3%). From the RWE cohort, those with TP53 mutations had a worse overall survival (OS) vs those without TP53 mutations (p=0.02) and those with TP53 co-mutations had an inferior OS in comparison to TP53-mutated only (p=0.016). Amongst these, patients with a PIK3CA co-mutation (p=0.012) and CCNE1 amplification (p=0.01) had inferior OS compared to those with only TP53 mutations. 57 patients with newly diagnosed EC had at least 2 serial ctDNA samples showing evolution in detected variants compared to baseline samples, with TP53 being the most frequent change. This study is one of the largest cohorts of ctDNA currently reported in EC. The presence of TP53 mutation and other co-mutations detected by ctDNA have a negative effect on outcomes. This report suggests that ctDNA analysis is feasible and could become a useful biomarker for EC.

Association of glutaminase expression with immune-suppressive tumor microenvironment, clinicopathologic features, and clinical outcomes in endometrial cancer

ObjectiveIncreased glutamine metabolism by cancer cells via upregulation of the drug-targetable enzyme glutaminase may contribute to an immune-suppressive tumor microenvironment. Inhibiting glutamine metabolism can not only suppress tumor growth, but...

A 10-Year Retrospective Cohort Study of Endometrial Cancer Outcomes and Associations with Lymphovascular Invasion: A Single-Center Study from Germany.

This 10-year retrospective cohort study at a single-center clinic in Germany aimed to analyze the outcomes of endometrial cancer patients and explore the impact of lymphovascular invasion (LV) on patient outcomes and disease-free survival (DFS). Identifying correlations among demographic data, tumor characteristics, treatment modalities, and survival outcomes could enhance patient management and improve survival rates. The study encompassed patients diagnosed and treated for endometrial cancer from January 2010 to December 2020. Clinical and pathological data were extracted from medical records for 311 patients, focusing on variables such as age, histological type, tumor grade, type of surgical treatment, and adjuvant therapies. Survival analysis was conducted using the Kaplan-Meier method and multivariate Cox proportional hazard models to identify factors independently associated with survival. The study demonstrated that lymphovascular invasion significantly impacted survival outcomes on Kaplan-Meier analysis (log-rank p-value = 0.0058). Patients with LV showed a marked decrease in DFS compared to those without LV invasion, with a median DFS of 3.2 years and a hazard ratio of 2.18 (95% CI: 1.56-3.04, p < 0.001). Furthermore, high-grade tumors and p53 positivity were strongly associated with reduced DFS, with hazard ratios of 1.93 (p = 0.001) and 2.11 (p < 0.001), respectively. Patients with distant metastasis exhibited the most significant decline in survival, with a hazard ratio of 5.56 (95% CI: 2.45-10.18, p < 0.001). Despite comprehensive surgical and adjuvant therapies, these high-risk factors dictated poorer outcomes. The presence of lymphovascular invasion, high-grade tumors, and genetic markers like MSI and p53 are pivotal in predicting the course of endometrial cancer. This study underscores the necessity for aggressive management strategies in patients exhibiting these high-risk features to potentially improve prognosis and survival outcomes. The findings advocate for enhanced therapeutic strategies tailored to the biological behavior of the tumor, thereby aiming to elevate the overall survival rates for women diagnosed with endometrial cancer.

Incidence of Cancer and Cardiovascular Disease After Bariatric Surgery in Older Patients

Bariatric surgery is associated with decreased risk of obesity-related cancer and cardiovascular disease but is typically reserved for patients younger than 60 years. Whether these associations hold for patients who undergo surgery at older ages is uncertain. To determine whether bariatric surgery is associated with a decreased risk of obesity-related cancer and cardiovascular disease in patients who underwent surgery at age 60 years or older. Population-based cohort study of patients from Denmark, Finland, and Sweden who underwent bariatric surgery at age 60 years or older without previous malignant neoplasm or cardiovascular disease between 1989 and 2019. Each patient who underwent surgery was exactly matched to 5 patients with nonoperative treatment for obesity of the same country, sex, and age at the date of surgery. Data were analyzed in December 2023. Receiving treatment for obesity, including bariatric surgery and nonoperative treatments. The main outcome was obesity-related cancer, defined as a composite outcome of breast, endometrial, esophageal, colorectal, and kidney cancer, identified from the national cancer registries. The secondary outcome was cardiovascular disease, defined as a composite outcome of myocardial infarction, ischemic stroke, and cerebral hemorrhage, identified from the patient registries. Multivariable Cox regression provided hazard ratios (HR) with 95% CIs adjusted for diabetes, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, kidney disease, and frailty. In total, 15 300 patients (median [IQR] age, 63 [61-65] years; 10 152 female patients [66.4%]) were included, of which 2550 (16.7%) had bariatric surgery at age 60 or older and 12 750 (83.3%) had nonoperative treatment. During a median (IQR) of 5.8 (2.8-8.5) person-years of follow-up, 658 (4.3%) developed obesity-related cancer and 1436 (9.4%) developed cardiovascular disease. The risk of obesity-related cancer (HR, 0.81; 95% CI, 0.64-1.03) and cardiovascular disease (HR, 0.86; 95% CI, 0.74-1.01) were similar among who underwent surgery and those who did not. Gastric bypass (1930 patients) was associated with a decreased risk of obesity-related cancer (71 patients [3.7%]; HR, 0.74; 95% CI, 0.56-0.97) and cardiovascular disease (159 patients [8.2%]; HR, 0.82; 95% CI, 0.69-0.99) compared with matched controls (9650 patients; obesity-related cancer: 442 patients [4.6%]; cardiovascular disease: 859 patients [8.9%]). This cohort study found that bariatric surgery in older patients is not associated with lower rates of obesity-related cancer and cardiovascular events, but there was evidence that gastric bypass may be associated with lower risk of both outcomes.

Construction of an immune-related gene prognostic model for obese endometrial cancer patients based on bioinformatics analysis

BackgroundThe tumor microenvironment (TME) affected the prognosis of tumors. However, its effect on the outcomes of obese endometrial cancer (EC) patients had not been reported. MethodsThis research performed a retrospective analysis of the transcriptome profiles and medical data of 503 EC patients. Immune scores were assessed by estimation algorithms. Cox and LASSO regression analyses were utilized to pinpoint key genes linked to prognosis, and the RPS was created to forecast the outcomes of obese EC patients. The relationship among genetic mutations and RPS was examined using CNV and somatic mutation information. ssGSEA and GSVA were employed to detect immune infiltration and immune pathway enrichment associated with key genes. The TIDE algorithm and GDSC database were utilized to forecast patients’ responses of patients to immunotherapy and chemotherapy, respectively. Finally, we employed the 'rms' R software package to construct the nomogram. ResultsThe prognosis of obese EC patients was associated with immune scores. Three key genes (EYA4, MBOAT2 and SCGB2A1) were identified. The risk prognosis score (RPS) for obese EC patients was established by risk stratification and prognostic prediction using prognostic genes. The higher the RPS, the worse the prognosis, and the more malignant the genomic alterations. The high RPS group had a significantly reduced proportion of most immune cells in comparison to the low RPS group. The high RPS group was linked to G2M, MYC and E2F related pathways such as cell proliferation, cell cycle and cell death. Cisplatin, tamoxifen and topotecan had a greater effect on the low RPS group. Notably, the nomogram had a good predictive ability. ConclusionOur study designed a reliable RPS for obese EC patients to forecast their prognosis, immune aggressiveness, and responses to immunotherapy and drug treatments.

Insights into inflammation and implications for the pathogenesis and long-term outcomes of endometrial cancer: genome-wide surveys and a clinical cohort study

BackgroundDespite evidence showing a connection between inflammation and endometrial cancer (EC) risk, the surveys on genetic correlation and cohort studies investigating the impact on long-term outcomes have yet to be refined. We aimed to address the impact of inflammation factors on the pathogenesis, progression and consequences of EC.MethodsFor the genetic correlation analyses, a two-sample of Mendelian randomization (MR) study was applied to investigate inflammation-related single-nucleotide polymorphisms involved with endometrial cancer from GWAS databases. The observational retrospective study included consecutive patients diagnosed with EC (stage I to IV) with surgeries between January 2010 and October 2020 at the Cancer Hospital of Shantou University Medical College.ResultsThe 2-sample MR surveys indicated no causal relationship between inflammatory cytokines and endometrial cancer. 780 cases (median age, 55.0 years ) diagnosed with EC were included in the cohort and followed up for an average of 6.8 years. Increased inflammatory parameters at baseline were associated with a higher FIGO stage and invasive EC risk (odds ratios [OR] 1.01 to 4.20). Multivariate-cox regression suggested that multiple inflammatory indicators were significantly associated with overall survival (OS) and progression-free survival (PFS) (P < 0.05). Nomogram models based on inflammatory risk and clinical factors were developed for OS and PFS with C-index of 0.811 and 0.789, respectively. LASSO regression for the validation supported the predictive efficacy of inflammatory and clinical factors on the long-term outcomes of EC.ConclusionsDespite the fact that the genetic surveys did not show a detrimental impact of inflammatory cytokines on the endometrial cancer risk, our cohort study suggested that inflammatory level was associated with the progression and long-term outcomes of EC. This evidence may contribute to new strategies targeted at decreasing inflammation levels during EC therapy.

The impact of estrogen receptor and L1 cell adhesion molecule expression on endometrial cancer outcome correlates with clinicopathological risk group and molecular subgroup

ObjectiveTo assess the risk stratification of clinicopathologically and molecularly classified endometrial cancer based on estrogen receptor (ER) and L1 cell adhesion molecule (L1CAM) expression. MethodsThis was a retrospective study of patients who underwent primary treatment at a single tertiary center. Carcinomas were classified into 5 clinicopathological risk groups, as per European guidelines. Immunohistochemistry and polymerase-ϵ sequencing were conducted for molecular classification and determination of ER and L1CAM expression. ResultsData from 1044 patients were analyzed. The median follow-up was 67.5 months. In univariable analyses, ER expression correlated with improved disease-specific survival (DSS) in the “no specific molecular profile” (NSMP) (P < 0.001) and mismatch repair deficient (MMRd) (P = 0.002) subgroups. Negative L1CAM expression was associated with enhanced DSS in the NSMP subgroup alone (P < 0.001). ER (hazard ratio [HR] 0.18), but not L1CAM, exhibited prognostic significance within NSMP when controlling for parameters available at the time of diagnosis (tumor histotype, grade, age). ER and L1CAM were not independently associated with DSS within NSMP when controlling for parameters available after surgery (clinicopathological risk groups, age, adjuvant therapy). However, in high-risk–advanced-metastatic cases, both ER (HR 0.26) and L1CAM (HR 3.9) independently correlated with DSS. Similarly, within MMRd, ER was associated with improved DSS in high-risk–advanced-metastatic carcinomas (HR 0.42). ConclusionThe prognostic significance of ER and L1CAM varies across clinicopathological risk groups and molecular subgroups of endometrial cancer. Notably, risk assessment for high-risk–advanced-metastatic NSMP and MMRd subtype carcinomas can be refined by ER status.

Asparaginase-like protein 1 as a prognostic tissue biomarker in clinicopathologically and molecularly characterized endometrial cancer

ObjectivePrognostic stratification of endometrial cancer involves the assessment of stage, uterine risk factors, and molecular classification. This process can be further refined through annotation of prognostic biomarkers, notably L1 cell adhesion molecule (L1CAM) and hormonal receptors. Loss of asparaginase-like protein 1 (ASRGL1) has been shown to correlate with poor outcome in endometrial cancer. Our objective was to assess prognostication of endometrial cancer by ASRGL1 in conjunction with other available methodologies. Study DesignThis was a retrospective study of patients who underwent primary treatment at a single tertiary center. Tumors were molecularly classified by the Proactive Molecular Risk Classifier for Endometrial Cancer. Expression of ASRGL1, L1CAM, estrogen receptor, and progesterone receptor was determined by immunohistochemistry. ASRGL1 expression intensity was scored into four classes. ResultsIn a cohort of 775 patients, monitored for a median time of 81 months, ASRGL1 expression intensity was related to improved disease-specific survival in a dose-dependent manner (P < 0.001). Low expression levels were associated with stage II–IV disease and presence of uterine factors, i.e. high grade, lymphovascular space invasion, and deep myometrial invasion (P < 0.001 for all). Among the molecular subgroups, low expression was most prevalent in p53 abnormal carcinomas (P < 0.001). Low ASRGL1 was associated with positive L1CAM expression and negative estrogen and progesterone receptor expression (P < 0.001 for all). After adjustment for stage and uterine factors, strong ASRGL1 staining intensity was associated with a lower risk for cancer-related deaths (hazard ratio 0.56, 95 % confidence interval 0.32–0.97; P = 0.038). ASRGL1 was not associated with the outcome when adjusted for stage, molecular subgroups, L1CAM, and hormonal receptors. When analyzed separately within the different molecular subgroups, ASRGL1 showed an association with disease-specific survival specifically in “no specific molecular profile” subtype carcinomas (P < 0.001). However, this association became nonsignificant upon controlling for confounders. ConclusionsLow ASRGL1 expression intensity correlates with poor survival in endometrial cancer. ASRGL1 contributes to more accurate prognostication when controlled for stage and uterine factors. However, when adjusted for stage and other biomarkers, including molecular subgroups, ASRGL1 does not improve prognostic stratification.

Mismatch Repair (MMR) Gene Mutation Carriers Have Favorable Outcome in Colorectal and Endometrial Cancer: A Prospective Cohort Study.

Germline (Lynch syndrome, LS) and somatic deficiencies of mismatch repair proteins (MMRd) are linked to colorectal and endometrial cancer; however, their prognostic impact in Asian populations remains unclear. This prospective cohort study aimed to determine the prevalence and outcome of germline and somatic MMRd in cancer patients suspected of LS. Patients with colorectal or endometrial cancer suspected of LS were enrolled and underwent gene sequencing for germline MMRd (gMMRd) and immunohistochemistry staining of MMR proteins in a subset of the pathological samples (pMMRd). Among the 451 enrolled patients, 36 patients were gMMRd (+). Compared with gMMRd (-) patients, the 10-year relapse-free survival in gMMRd (+) patients was significantly higher (100% vs. 77.9%; p = 0.006), whereas the 10-year overall survival was similar (100% vs. 90.9%; p = 0.12). Among the 102 gMMRd (-) patients with available pMMR status, 13.7% were pMMRd (+). The 5-year relapse-free survival was 62.9% in gMMRd (-) pMMRd (+) patients and 35.0% in gMMRd (-) pMMRd (-) patients, both lower than gMMRd (+) patients (100%; p < 0.001). This study showed that having LS confers a favorable outcome in colorectal and endometrial cancer patients and highlights the importance of germline genetic testing following the detection of somatic MMRd.

Proficiency-based progression training in robot-assisted laparoscopy for endometrial cancer: peri-operative and survival outcomes from an observational cohort study.

Over the last decade there has been a transition from traditional laparoscopy to robotic surgery for the treatment of endometrial cancer. A number of gynecological oncology surgical fellowship programmes have adopted robot-assisted laparoscopy, but the effect of training on complications and survival has not been evaluated. Our aim was to assess the impact of a proficiency-based progression training curriculum in robot-assisted laparoscopy on peri-operative and survival outcomes for endometrial cancer. This is an observational cohort study performed in a tertiary referral and subspecialty training center. Women with primary endometrial cancer treated with robot-assisted laparoscopic surgery between 2015 and 2022 were included. Surgery would normally include a hysterectomy and salpingo-oophorectomy with some form of pelvic lymph node dissection (sentinel lymph nodes or lymphadenectomy). Training was provided according to a training curriculum which involves step-wise progression of the trainee based on proficiency to perform a certain surgical technique. Training cases were identified pre-operatively by consultant surgeons based on clinical factors. Case complexity matched the experience of the trainee. Main outcome measures were intra- and post-operative complications, blood transfusions, readmissions < 30 days, return to theater rates and 5-year disease-free and disease-specific survival for training versus non-training cases. Mann-Witney U, Pearson's chi-squared, multivariable regression, Kaplan-Meier and Cox proportional hazard analyses were performed to assess the effect of proficiency-based progression training on peri-operative and survival outcomes. Training cases had a lower BMI than non-training cases (30 versus 32 kg/m2, p = 0.013), but were comparable in age, performance status and comorbidities. Training had no influence on intra- and post-operative complications, blood transfusions, readmissions < 30 days, return to theater rates and median 5-year disease-free and disease-specific survival. Operating time was longer in training cases (161 versus 137 min, p = < 0.001). The range of estimated blood loss was smaller in training cases. Conversion rates, critical care unit-admissions and lymphoedema rates were comparable. Proficiency-based progression training can be used safely to teach robot-assisted laparoscopic surgery for women with endometrial cancer. Prospective trails are needed to further investigate the influence of distinct parts of robot-assisted laparoscopic surgery performed by a trainee on endometrial cancer outcomes.

Comparison of Long-Term Outcomes in Early-Stage Endometrial Cancer: Robotic Single-Site vs. Multiport Laparoscopic Surgery.

The purpose of this study was to establish the noninferiority of robotic single-site (RSS) surgery compared with multiport laparoscopic (MPL) surgery in surgical outcomes and overall survival for early endometrial cancer. This study was conducted retrospectively in a single center and included 421 patients who underwent either RSS (n = 146) or MPL (n = 275) surgery between 2014 and 2022. In terms of perioperative outcomes, the RSS group had a longer operating time than the MPL surgery group (mean (standard deviation [SD]) RSS 97.55 [29.79] vs. MPL 85.56 [26.13], p < 0.001). However, no significant differences in estimated blood loss or perioperative complications were found between the groups (p = 0.196 and p = 0.080, respectively). The patients in the RSS group were discharged earlier than those in the MPL group (mean [SD]): 4.06 [3.24] vs. 9.39 [4.76], p < 0.001). Regarding oncologic outcomes, no significant differences in the type of therapy, disease stage, tumor grade, histopathological type, or lymphovascular invasion were found between the groups. No statistically significant differences were found in the disease-free (p = 0.27) and overall survival rates (p = 0.5) either. In conclusion, this study suggests that RSS and MPL surgery are both safe and effective options for staging operations in patients with early-stage endometrial cancer.

Tumor Stiffness Measurement at Multifrequency MR Elastography to Predict Lymphovascular Space Invasion in Endometrial Cancer.

Background Pathologic lymphovascular space invasion (LVSI) is associated with poor outcome in endometrial cancer. Its relationship with tumor stiffness, which can be measured with use of MR elastography, has not been extensively explored. Purpose To assess whether MR elastography-based mechanical characteristics can aid in the noninvasive prediction of LVSI in patients with endometrial cancer. Materials and Methods This prospective study included consecutive adult patients with a suspected uterine tumor who underwent MRI and MR elastography between October 2022 and July 2023. A region of interest delineated on T2-weighted magnitude images was duplicated on MR elastography images and used to calculate c (stiffness in meters per second) and φ (viscosity in radians) values. Pathologic assessment of hysterectomy specimens for LVSI served as the reference standard. Data were compared between LVSI-positive and -negative groups with use of the Mann-Whitney U test. Multivariable logistic regression was used to determine variables associated with LVSI positivity and develop diagnostic models for predicting LVSI. Model performance was assessed with use of area under the receiver operating characteristic curve (AUC) and compared using the DeLong test. Results A total of 101 participants were included, 72 who were LVSI-negative (median age, 53 years [IQR, 48-62 years]) and 29 who were LVSI-positive (median age, 54 years [IQR, 49-60 years]). The tumor stiffness in the LVSI-positive group was higher than in the LVSI-negative group (median, 4.1 m/sec [IQR, 3.2-4.6 m/sec] vs 2.2 m/sec [IQR, 2.0-2.8 m/sec]; P < .001). Tumor volume, cancer antigen 125 level, and tumor stiffness were associated with LVSI positivity (adjusted odds ratio range, 1.01-9.06; P range, <.001-.04). The combined model (AUC, 0.93) showed better performance for predicting LVSI compared with clinical-radiologic model (AUC, 0.77; P = .003) and similar performance to the MR elastography-based model (AUC, 0.89; P = .06). Conclusion The addition of tumor stiffness as measured at MR elastography into a clinical-radiologic model improved prediction of LVSI in patients with endometrial cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ehman in this issue.

Racial/ethnic inequities in care for patients with advanced endometrial cancer: What’s structural racism and social determinants of health got to do with it?

1602 Background: Structural racism and social determinants of health (SDOH) have been linked to inequities in cancer care and outcomes. However, little is known about the contribution of such factors to care inequities among patients with endometrial cancer, where Black women experience a nearly two-fold increased risk of death relative to their White counterparts. We examined the role of structural racism and SDOH in explaining racial/ethnic inequities in care for patients with advanced endometrial cancer (aEC). Methods: This retrospective study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database, focusing on patients diagnosed with aEC from January 2013 to September 2023 (follow-up through December 2023). Outcomes included time-to-treatment initiation, use of immunotherapy or targeted therapy, biomarker testing, and clinical trial participation. We estimated a series of multivariable Cox proportional hazards models assessing racial/ethnic inequities in outcomes, sequentially adjusting for clinical factors (e.g., age, stage at diagnosis) followed by structural racism (residential segregation) and SDOH factors (e.g., insurance, practice setting, area-level vehicle ownership). Results: The cohort included 5,496 patients (2.2% Asian, 14.8% Black, 5.2% Latinx, 61.4% White, and 16.0% Other/Unknown). Although diagnosed with more aggressive disease (37% vs. 21% serous carcinoma), Black patients were less likely than White patients to initiate treatment during follow-up (hazard ratio [HR]=0.91 [95% CI: 0.83-0.99]), participate in a clinical trial (HR=0.56 [95% CI: 0.38-0.84]), and receive biomarker testing (HR=0.88 [95% CI: 0.81-0.97]). Compared with their White counterparts, Latinx patients were less likely to participate in a clinical trial (HR=0.41 [95% CI: 0.19-0.87]). Black-White (HR=0.80 [95% CI: 0.47-1.38]) and Latinx-White (HR=0.71 [95% CI: 0.31-1.60]) inequities in clinical trial participation were partly explained by structural racism and SDOH factors, while Black-White inequities in treatment and biomarker testing remained largely unchanged following structural and social determinants adjustment. We saw no racial/ethnic differences in use of immunotherapy or targeted therapy. Conclusions: We observed racial/ethnic inequities in treatment initiation, biomarker testing, and clinical trial participation among patients with aEC, with structural racism and SDOH substantially accounting for inequities in trial participation. Thus, findings from this study suggest that efforts aimed at improving diversity in endometrial cancer trials, and overall equity in endometrial cancer outcomes, should prioritize mitigating the structural and social barriers to clinical trial participation.

Patient Surveillance Adherence After Treatment for Endometrial Cancer

BACKGROUND: To assess factors that may affect patients' adherence to recommended surveillance after treatment for endometrial cancer. METHODS: We performed a retrospective study of all patients undergoing primary treatment for endometrial cancer from January 1, 2010, to December 30, 2017, at a tertiary referral center. Patients were included for analysis if there was sufficient information in the electronic medical records. Patient demographic information, cancer characteristics, and surveillance adherence data were collected. The median inflation-adjusted income was calculated from the patients' ZIP codes and U.S. Census data. The primary outcome assessed was adherence to surveillance, defined as two or more visits per 12 months in individuals at low risk and four or more visits per 12 months in individuals at high risk, consistent with recommended guidelines. RESULTS: During the study period, 870 patients were included for analysis. The mean age at diagnosis and body mass index (BMI) of the entire cohort were 63.4 years and 35.8, respectively. Overall, 761 patients (87.5%) were adherent to the recommended surveillance guidelines. Patients who were not adherent to recommended surveillance lived significantly farther from the cancer center (39.2 miles vs 20.7 miles, P=.026) and had a significantly lower median inflation-adjusted income ($74,015 vs $80,435, P=.027). CONCLUSION: Increased distance to a tertiary care center and lower median income were significantly associated with decreased adherence to recommended surveillance guidelines. This is consistent with current literature on increased distance traveled as a proxy for worse survival in gynecologic malignancies, as well as worse endometrial cancer outcomes in patients of lower socioeconomic status. This highlights an area of disparity that needs improvement and warrants further investigation.

Metabolic Syndrome and Survival Outcomes in Endometrial Cancer.

Menopause, through attributable estrogen level decline and the corresponding increase in circulating androgens, significantly elevates a woman's risk for cardiometabolic diseases, including metabolic syndrome (MetS), type 2 diabetes, and cardiovascular disease. Metabolic syndrome itself is a cluster of interconnected risk factors, and among them, central obesity is a well-established factor for the development of endometrial cancer (EC), the most common gynecologic malignancy. This research investigates the impact of metabolic syndrome on survival rates among patients with endometrial cancer. The goal is to assess whether having metabolic syndrome or its individual components influences disease-free survival (DFS), overall survival (OS), cancer-specific survival, and recurrence rates. Understanding this link is crucial for determining risk levels and could help tailor treatment approaches for better long-term outcomes in endometrial cancer care.

Development and Potential Implementation of Endometrial Cancer Screening in a Poor-Prognosis Endemic Cancer Community [ID 2683642

INTRODUCTION: Endometrial cancer incidence and mortality both are increasing in the United States. Certain patient populations are disproportionately affected by this disease. Currently, there is no recommendation from any professional society to screen high-risk patients for premalignancy or cancer. Our patient population is composed of predominantly Black women, a group that experiences worse endometrial cancer outcomes than other demographics. A risk assessment nomogram may be able to be developed using data from this unique patient population that can identify women at high risk of developing endometrial disease. METHODS: Endometrial pathology specimens collected at a large safety-net hospital between the years of 2013 and 2022 were analyzed. A retrospective chart review was performed on this data, looking for the patient characteristics of race, age, body mass index (BMI), parity, hemoglobin A1C level, and tamoxifen use history at the time of specimen collection. Odds ratios were calculated for those variables individually as well as collectively to determine whether they could be used to predict risk of endometrial disease in a woman with some of all those characteristics. RESULTS: The odds ratios for age, BMI, and parity were statistically significant between benign and abnormal pathologic specimens. The area under the receiver operating characteristic curve was 0.76 when combining age, BMI, and parity. CONCLUSION: Our data suggest that at-risk patients can be reliably identified using simple characteristics. Strengths of our study include a unique patient population and large database. Future directions include refinement of the model and prospective application in the clinical setting.

Real world outcomes of patients with endometrial cancer from a South African radiation oncology unit

Background: Endometrial cancer adds significantly to the burden placed on the South African health care system with GLOBOCON 2020 cancer statistics ranking it as the 5th most frequently diagnosed cancer in South African women.Aim: A retrospective audit to assess real-world clinical outcomes in women with endometrial carcinoma that received radiation as a treatment modality.Setting: A radiation oncology unit at a public tertiary hospital in the Johannesburg area, Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in South Africa.Methods: Medical records between 2010 and 2020 were evaluated for patients who received either combination external beam (EBRT) and vaginal brachytherapy (VBT) or VBT alone. Overall survival rates (OS) and progression-free survival (PFS) were assessed.Results: One hundred and two patients were analysed. Demographic profiles were 76,5% black people, 18.6% white people, 3.9% asian people and 1% mixed race. Median age was 66 years (range: 64 years—67 years).Type 1 histology in 70%.OS at 5-year was 61.75% and at 10-year was 40% with stage and histological type being significant contributors. Statisical significance in survival occurred with a combination of LVSI with greater than 50 % myometrial invasion(P=0.038) and a combination of greater than 50% myometrial invasion with positive margins (P=0.032).Radiation treatment was completed in 102 (100%) of the patients.Conclusion: Real world outcomes of overall survival rates of endometrial carcinoma are lower than projected in our developing country, although contributory high risk factors play a role in keeping with international literature and historic landmark trials.Contribution: This study contributes to the growing body of research on endometrial cancer outcomes in low- and middle-income countries (LMICs).

Upregulation of ESPL1 is associated with poor prognostic outcomes in endometrial cancer

Background Extra spindle pole bodies-like 1 (ESPL1) is known to play a crucial role in the segregation of sister chromatids during mitosis. Overexpression of ESPL1 is considered to have oncogenic effects in various human cancers. However, the specific biological function of ESPL1 in endometrial cancer (EC) remains unclear. Methods The TCGA and GEO databases were utilized to assess the expression of ESPL1 in EC. Immunohistochemistry was utilized to detect separase expression in EC samples. Kaplan-Meier survival analysis and Cox regression analysis were performed to evaluate the diagnostic and prognostic significance of ESPL1 in EC. Gene Set Enrichment Analysis (GSEA) was employed to explore the potential signaling pathway of ESPL1 in EC. Cell proliferation and colony formation ability were analyzed using CCK-8 and colony formation assay. Results Our analysis revealed that ESPL1 is significantly upregulated in EC, and its overexpression is associated with advanced clinical characteristics and unfavourable prognostic outcomes. Suppression of ESPL1 attenuated proliferation of EC cell line. Conclusion The upregulation of ESPL1 is associated with advanced disease and poor prognosis in EC patients. These findings suggest that ESPL1 has the potential to serve as a diagnostic and prognostic biomarker in EC, highlighting its significance in the management of EC patients.

Abstract 559: Investigating DDX3X as a target to improve outcomes in Black and Native American endometrial cancer patients

Abstract Introduction: The goal of this project was to identify and test a new molecular target that will help reduce the worse outcomes of endometrial cancer, especially in Black and Native American patients. Endometrial cancer is rapidly on the rise in the developed world. It has overtaken many other types of cancer in both incidence and mortality. Black populations are disproportionately impacted by endometrial cancer, both in Oklahoma and across the United States. In Oklahoma specifically, Native Americans are the most heavily impacted group. Methods: Machine learning techniques were used to analyze comprehensive metabolic panel (CMP) data from electronic medical record of patients in the University of Oklahoma (OU) network of hospitals and clinics. This data was broken down by endometrial cancer status, race, and age. Plasma samples of endometrial cancer patients were collected from the OU Health Sciences Center Biobank. These samples were analyzed by mass spectrometry. Endometrial cancer cell lines Ishikawa (low-grade) and ARK-1 and ARK-4 (high grade) were cultured in EMEM. For treating the cells, we used RK-33, a small molecule inhibitor of DDX3X. MTT assays were performed in 96-well plates at increasing concentrations of RK-33 for 48 hours. Western blots were used to determine effect of the drug on cellular DDX3X and yH2AX protein levels. Results: Machine learning analysis EMR data revealed a difference between races in albumin levels of women with endometrial cancer. Black and Native American patients had lower albumin, which is known to correlate to worse outcomes. IPA analysis of plasma proteomics revealed several proteins that were differentially expressed between races. Among these was DDX3X, the X-linked form of DDX3, a DEAD-box RNA helicase which is involved in DNA damage repair. Patient data indicated that patients with high DDX3X expression tended to have lower survival rates. MTT analysis determined that Ishikawa has a lower IC50 than the high-grade cell lines, but all responded. Western blotting confirmed that treatment with RK-33 reduced the amount of DDX3X in the cells and increased y-H2AX, indicating more DNA damage. Conclusions: This study demonstrates that DDX3X is a valid molecular target in endometrial cancer. The differential expression across race groups indicates that Black and Native Americans may stand to benefit the most from a novel drug targeting this difference. Because DDX3X is involved in DNA damage repair, combining the treatment with a DNA-damaging drug may increase response to the drug as well. Citation Format: James D. Lausen, Doris M. Benbrook. Investigating DDX3X as a target to improve outcomes in Black and Native American endometrial cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 559.

Clinicopathological Features and Outcomes of Endometrial Cancer: A single institution experience.

This study aimed to report the demographic features, clinical presentation, pathological types and long-term outcomes of patients diagnosed with endometrial cancer (EC) in Oman. EC is the sixth most common cancer in women worldwide and the fifth most common cancer in women in Oman. Survival outcomes of EC have not been reported previously from Oman. This retrospective study was carried out on consecutive patients treated at the Sultan Qaboos University Hospital, Muscat, Oman, between 2008 and 2020. Survival was estimated using the Kaplan and Meier method. A total of 50 patients with EC were included. The median age was 61 years (range: 31-86 years), and 72% of the patients had type I histology. Most patients were diagnosed with stage IA and IB EC (49% and 20%, respectively), and the majority had grade 1 or 2 tumours (40% and 34%, respectively). Overall, the 5-year survival and 10-year survival rates were estimated to be 70% and 56%, respectively. Weight (>75 kg) and body mass index (>30 kg/m2) were significantly associated with better survival. Tumour histology (type I versus type II or carcinosarcoma), grade (1 versus 2 versus 3) and stage (IA or IB versus II-IV) were associated with better overall survival (P = 0.007, P <0.0001 and P <0.0003, respectively). Patients diagnosed with EC with co-morbidities, other than obesity, had inferior survival compared to those without co-morbidities. Median age at presentation, histological sub-type, clinical stage and outcomes are comparable to the published literature. Almost two-thirds of the patients were obese. These data could be used as a benchmark for outcomes of EC in the region.