Endometrial Carcinoma Patients Research Articles

A case series on endometrial cancer in multipara and their prognostication based on IHC markers

Endometrial carcinoma is one of the leading gynecological malignancies across the globe. With advent of molecular analysis, establishing an accurate treatment plan and improving patient outcome has become eminent. In resource limited settings like India, surrogate IHC markers like hormonal receptor expression are congruous substitutes that aid to accurately predict patient prognosis. In this case series, expression of hormonal receptors in multiparous women and it’s association with patient outcome seen as disease free survival at a span of 2 years was compared. This study opines inclusion of hormonal receptors in evaluation of endometrial carcinoma patients to accurately comment on patient outcome.

Missing concurrent endometrial carcinoma in patients with endometrial intraepithelial neoplasia: Which is better, directed biopsy versus blinded?

Missing concurrent endometrial carcinoma in patients with endometrial intraepithelial neoplasia: Which is better, directed biopsy versus blinded?

Machine learning for prediction of concurrent endometrial carcinoma patients diagnosed with endometrial intraepithelial neoplasia

Machine learning for prediction of concurrent endometrial carcinoma patients diagnosed with endometrial intraepithelial neoplasia

RNF144A as a potential risk gene for endometrial carcinoma: Insights from Mendelian randomization, bulk RNA sequencing, single-cell RNA, and experimental analysis.

Endometrial carcinoma (EC) is a prevalent gynecological malignancy that poses a significant threat to women's health worldwide. However, its pathogenesis and underlying mechanisms remains unclear. In this study, expression quantitative trait loci data, Mendelian randomization analysis, and differential expression analysis were performed to identify potential targets. A prognostic risk signature was subsequently constructed for EC patients based on the expression of these genes. Four bioinformatics algorithms, including generalized linear model, extreme gradient boosting, support vector machine, and random forest, were used to identify hub genes in EC. The expression of ring finger protein 144A (RNF144A) was validated using quantitative real-time polymerase chain reaction. Cellular proliferation and migration ability were evaluated using CCK-8 and Transwell assays, respectively. The genes RNF144A, ketohexokinase, and Rab interacting lysosomal protein like 2 were identified as potential targets for EC. Their differential expression was observed in EC patients, and Mendelian randomization analysis revealed a negative correlation between these genes and the development of EC. Mechanistic analyses suggested a strong association between these genes and the tumor immune microenvironment. The constructed risk signature was significantly associated with the prognosis, age, cancer stage, and grade of EC patients. Furthermore, based on interacted model algorithms, RNF144A was identified as a hub gene in EC. It was found to be significantly downregulated in EC samples, and its expression was positively correlated with the stage and grade of EC patients. In vitro experiments showed that overexpression of RNF144A significantly promoted cell growth and migration in EC cells. In conclusion, this study provides insights into the molecular mechanisms underlying EC progression and identifies preliminary candidate biomarkers for the development of EC treatment strategies.

Evaluation of lymphovascular space invasion in endometrial carcinoma by APTw and mDixon-Quant.

Lymphovascular space invasion (LVSI) is a strong and independent risk factor that increases the probability of endometrial carcinoma (EC) recurrence and reduces the survival rate of patients. To investigate the value of amide proton transfer weighted (APTw) and mDixon-Quant techniques in evaluating EC lymphovascular space invasion (LVSI). Data of 50 EC patients (18 LVSI+ and 32 LVSI-) confirmed by surgery and pathology were retrospectively analyzed. Preoperative magnetic resonance imaging (MRI) scans included APTw and mDixon-Quant imaging. APT, transverse relaxation rate (R2*), and fat fraction (FF) plots were obtained by postprocessing. The APT, R2*, and FF values of the two groups of cases were measured by two observers. The agreement between the two observers was good. The mean APT, R2*, and FF values of LVSI+ EC were 2.947% ± 0.399%, 20.605 /s (range = 18.525-27.953), and 2.234% ± 1.047%, respectively, while the parameters of LVSI- EC were 2.628% ± 0.307%, 18.968 /s (range = 16.225-20.544), and 2.103% ± 1.070%, respectively. The APT and R2* values of LVSI+ EC were higher than those of LVSI- EC (P < 0.05). There was no significant difference in FF value between the two groups. The AUC values of APT, R2*, and APT + R2* for LVSI were 0.751, 0.713, and 0.781, respectively (all P > 0.05). APT value was moderately correlated with R2* value (r = 0.528, P < 0.001) and weakly correlated with FF value (r = 0.312, P = 0.027). APTw and mDixon-Quant techniques could evaluate the LVSI status of EC, and their combined application could improve diagnostic efficiency.

Screening of prognostic factors and survival analysis based on histological type for perimenopausal endometrial carcinoma treated with hysterectomy

PurposeThis study aimed to explore the prognostic factors and survival patterns based on the histological type for the perimenopausal endometrial carcinoma (PIPEC) patients treated with hysterectomy.MethodsThe PIPEC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Methods of random survival forest (RSF) and Cox regression were used to identify the possible prognostic factors of PIPEC patients. Then overall survival (OS) and cancer-specific survival (CSS) of PIPEC data were analyzed by histological types with regional lymph nodes status and SEER-stage to investigate the survival patterns of the PIPEC patients.ResultsA total of 14,178 PIPEC patients were included in the study. We found tumor size, grade, histology, SEER-stage, AJCC-stage, AJCC-T stage, metastasis to distant organs and regional lymph nodes status had a significant survival outcome for PIPEC both for OS and CSS (all p < 0.05). Regardless of regional lymph nodes status and SEER-stage for OS and CSS, the low-grade endometrioid carcinoma had the best prognosis outcome, followed by the mix cell adenocarcinoma and high-grade endometrioid carcinoma, while the carcinosarcoma and undifferentiated carcinoma had relatively poor prognosis outcome. And the survival patterns of different histological types of PIPEC were diverse and changed along with the time.ConclusionWe identified the possible prognostic factors of PIPEC patients treated with hysterectomy. And survival analysis based on the regional lymph nodes status and SEER-stage revealed the different histological types of PIPEC had diverse survival patterns, which will be helpful for guiding clinical practice.

Analysis of characteristics of peripheral blood lymphocytes in endometrial carcinoma: a single-center study based on five-year clinical data

IntroductionThis study analyzed and discussed the characteristics of peripheral blood lymphocytes (PBLs) in patients with endometrial carcinoma (EC) to explore the PBLs’ clinical application value.MethodsThis single-center case‒control study analyzed the clinical data of patients with EC and uterine fibroids who underwent surgery at the First Affiliated Hospital of Chongqing Medical University between October 2018 and October 2023 retrospectively. The Center for Clinical Molecular Medical Detection of our hospital performed PBLs detection using flow cytometry, and recorded the detection results in the electronic medical records system. Between-group and subgroup comparisons of PBLs in patients with EC were analyzed using t-test or Mann–Whitney U test. The effect of surgery on PBLs in patients with EC was assessed using a paired t-test or the Wilcoxon signed rank test.ResultsThe immune function of patients with EC was significantly lower than that of healthy people (P < 0.05) and those with benign uterine diseases (P < 0.05) and was related to body mass index (BMI), hypertension, diabetes, and blood lipids (P < 0.05). In patients with EC, the PBLs counts decreased significantly after surgery (P < 0.05) and more kinds of lymphocytes were affected in the laparoscopic surgery group than in the open surgery group.ConclusionsWith the decrease of PBLs counts, the immune status of patients with EC is impaired. Metabolic syndrome (Mets), including obesity, hypertension, diabetes, and high blood lipids, also affects the immune function of patients with EC. And for EC patients, the effect of laparoscopic surgery is greater than that of open surgery. PBLs has the potential to be one of indicator during the diagnosis and treatment of EC.Trial registrationThis study was retrospectively registered by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (approval number K2023-578).

Multiparametric MRI-based radiomics combined with 3D deep transfer learning to predict cervical stromal invasion in patients with endometrial carcinoma.

To develop and compare various preoperative cervical stromal invasion (CSI) prediction models, including radiomics, three-dimensional (3D) deep transfer learning (DTL), and integrated models, using single-sequence and multiparametric MRI. Data from 466 early-stage endometrial carcinoma (EC) patients from three centers were collected. Radiomics models were constructed based on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) mapping, contrast-enhanced T1-weighted imaging (CE-T1WI), and four combined sequences as well as 3D DTL models. Two integrated models were created using ensemble and stacking algorithms based on optimal radiomics and DTL models. Model performance and clinical benefits were assessed using area under the curve (AUC), decision curve analysis (DCA), net reclassification index (NRI), integrated discrimination index (IDI), and the Delong test for model comparisons. Multiparametric MRI models were superior to single-sequence models for radiomics or DTL models. Ensemble and stacking integrated models displayed excellent performance. The stacking model had the highest average AUC (0.908) and accuracy (0.883) in external validation groups 1 and 2 (AUC = 0.965 and 0.851, respectively) and emerged as the best predictive model for CSI. All models significantly outperformed the radiologist (P < 0.05). In terms of net benefits, all models demonstrated favorable outcomes in DCA, NRI, and IDI, with the stacking model yielding the highest net benefit. Multiparametric MRI-based radiomics combined with 3D DTL can be used to noninvasively predict CSI in EC patients with greater diagnostic accuracy than the radiologist. Stacking integrated models showed significant potential utility in predicting CSI. Which helps to provide new treatment strategy for clinicians to treat early-stage EC patients.

GnRH-a-based fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients: a multicenter, open-label, randomized designed clinical trial protocol

BackgroundAround 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes.MethodsThis study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence.Ethics and disseminationThe protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association’s Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal.ConclusionsProspective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH.Trial registration numberChinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.

Prognostic Significance of Disseminated Tumor Cells in Bone Marrow for Endometrial Carcinoma Patients.

Background: Until now, limited clinical significance had been reported for disseminated tumor cells (DTCs) in gynecologic malignancies. DTCs were previously reported not to be associated with established risk factors, L1CAM immunoreactivity, and outcome in endometrial carcinoma (EC). This study's primary objective was to investigate potential correlations of DTCs in the bone marrow (BM) of EC patients with disease-related survival, and a secondary objective was to evaluate associations between molecular classification of EC and DTCs. Methods: Patients treated for primary EC at Tuebingen University women's hospital between 2003 and 2016 were identified. A total of 402 patients with a complete set of BM cytology, molecular, and clinical data were evaluable. Results: DTC occurrence was distributed equally among all four molecular groups (p = 0.651). DTC positivity was associated with a less favorable disease-free survival (HR: 1.86, 95% CI: 1.03-3.36, p = 0.036) and progression-free survival (HR: 1.86, 95% CI: 1.01-3.44, p = 0.045). Presence of DTCs was associated with a higher frequency of distant disease recurrence (p = 0.017). Conclusions: In line with our previous findings, tumor cell dissemination is not associated with molecular features in our large cohort of primary EC patients. Since DTCs seem to be associated with survival and location of disease recurrence, further studies are needed to decisively define their role in EC survival.

Comparative effects of different treatments based on the levonorgestrel intrauterine system in endometrial carcinoma and endometrial hyperplasia patients: a network meta-analysis.

Levonorgestrel intrauterine system (LNG-IUS) has been widely used in patients with endometrial carcinoma (EC), endometrial hyperplasia without atypical (EH), and atypical endometrial hyperplasia (AEH). The purpose of our Network meta-analysis (NMA) is to evaluate the efficacy of the treatments based on the LNG-IUS in patients with EC and EH with or without atypical. We examined PubMed, EMBASE, Web of Science and the Cochrane Library up to 22 April 2024 to determine studies reporting treatment outcomes in EC and EH patients receiving LNG-IUS therapy, LNG-IUS + metformin (MET), oral progestins (OP), etc. We used EndNote 9 to select studies, Jadad scale and NOS scale to assess quality, stata(16.0) and R (4.3.1) to analysis the data. Overall, 28 studies involving 3752 patients were included in our NMA. As for EH patients, LNG-IUS (RR 1.21; 95% CrI [1.11, 1.34]) and LNG-IUS + MET (RR 323.57; 95% CrI [1.61, 214,223,188.1])] significantly increased CR rate in comparison with OP. Based on SUCRA, LNG-IUS + OP was the best treatment to improve CR(SUCRA = 67.2%) in patients with EC, whereas LNG-IUS + MET was superior in increasing CR (SUCRA = 99.8%) than any other treatments for EH patients. Besides, the ranking based on SUCRA illustrated that LNG-IUS alone was the best choice to raise CR rates (SUCRA = 76.7%) for AEH patients. In head-to-head meta-analysis, OP has a higher progression rate (RR 4, 95% CI 1.89-8.46, p = 0.062; I2 = 71.3%), a higher nausea rate (RR 1.93, 95% CI 1.24-3.01, p = 0.187; I2 = 40.4%) than LNG-IUS in patients with EH. In contrast, LNG-IUS had a irregular vaginal bleeding rates (RR 0.76, 95% CI 0.64-0.90, p = 0.034; I2 = 77.7%) than OP in EH patients. In addition, as for AEH patients, OP has a higher persistence rate (RR 4.31, 95% CI 1.43-13.00, p = 0.93; I2 = 0.0%) than LNG-IUS. According to the NMA, LNG-IUS related studies are feasible for conservative therapy in patients with EC and EH with or without atypical. Therefore, concerning the curative effect, we recommend LNG-IUS-based treatments as the best conservative therapy for EC and EH patients. However, future studies require large sample sizes and more outcomes to further evaluate the differences of treatment selections based on LNG-IUS.

Construction of the prognostic nomogram and treatment recommendation in patients with mixed endometrial carcinoma treated with hysterectomy.

The study aimed to identify the independent prognostic factors of mixed endometrial carcinoma (MEC) patients treated with hysterectomy and to explore the optimal treatment modalities for overall survival (OS) and cancer-specific survival (CSS). Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 12,848 MEC patients treated with hysterectomy were screened out. Independent prognostic factors were identified by Cox regression analysis and used to construct the nomogram. The concordance index (C-index) of OS and CSS were 0.807 and 0.834 in the training set. Validation of the nomogram revealed that the receiver operating curve (ROC) maintained good discrimination, the decision curve analysis (DCA) had a high net benefit rate, and the calibration curves showed high consistency. Patients were grouped by the nomogram formula and the number of positive regional lymph nodes (NPR-Lymph node) to evaluate the therapeutic outcomes of chemotherapy, radiotherapy, neoadjuvant treatment and lymph node operation. Survival analysis revealed that chemotherapy could improve the prognosis for OS and CSS in the high-risk group and in the group with NPR-Lymph node counts above 1 (P < 0.05). Radiotherapy was associated with better OS and CSS in the intermediate-risk and high-risk groups, and in the group with NPR-Lymph node counts above 0 (P < 0.05). Lymphadenectomy was found to prolong OS and CSS in the high-risk group (P < 0.05), while neoadjuvant treatment did not prolong OS and CSS in any group. Thus, in this study, the nomogram for MEC patients treated with hysterectomy was successfully built and validated which could effectively predict the prognosis and identify at-risk population to guide clinical decision-making. The NPR-Lymph node was identified as a potentially strong prognostic indicator with good clinical value.

Pattern of care and clinical outcome of patients with carcinoma endometrium and the impact of central histopathological review on management: A tertiary cancer centre experience.

Endometrial carcinoma (EC) is the third most common gynecological malignancy in India. Recent PORTEC-3 analysis emphasized the role of central histopathological review. We aimed to retrospectively analyze the demographic and histopathological characteristics of EC patients treated at our institute and assess the impact of the central histopathological review on management and also analyze clinical outcomes in this cohort of patients. Data of 75 EC patients treated at our center between 2013 and 2022 were retrieved from our departmental archives. Patients were analyzed for demographic details, histopathological findings, details of surgery and histopathology (HPE), results of a review of HPE, adjuvant treatment details, and clinical outcomes. All patients with HPE outside of our institute were reviewed at our center prior to initiation of treatment. In cases of discordance, patients were discussed in the multidisciplinary tumor board for the final treatment decisions. Patients were staged as per International Federation of Gynaecology and Obstetrics 2018. The median age was 57 years (range: 37-74 years). Twenty-seven patients with HPE reported from the outside center were reviewed at our institute and changes were observed in 26 patients (96.3%). HPE review changes were observed in terms of histological grade, histological type, myometrial invasion, and lymph node involvement in five (18.5%), three (11.1%), seven (25.9%), and three (42.8%), respectively. HPE review leads to changes in the management of 19/26 patients. Stage distribution was I: II: III in 48 (64%): 9 (13.3%): 18 (24%) patients, respectively. The median external beam radiotherapy dose was 50 Gray (range: 45-50.4 Gray at 1.8-2 Gray per fraction). The median brachytherapy dose for patients treated with brachytherapy alone was 7 Gray each for three sessions and in combination with EBRT was 6 Gray each in two sessions. At a median follow-up of 51 months (range: 6-116 months), seven (9.3%) patients developed distant metastasis, two (2.7%) patients had local plus distant metastasis, and two (2.7%) patients had local recurrence. The overall survival and disease-free survival rates at 3 years were 93.5% and 86.7%, respectively. EC patients treated at our center have excellent local control rates with a combination of external beam radiotherapy and brachytherapy. The central histopathological review may result in changes impacting patient management and should be routinely done prior to initiation of treatment in EC.

Signature identification based on immunogenic cell death-related lncRNAs to predict the prognosis and immune activity of patients with endometrial carcinoma.

Endometrial carcinoma (EC) is one of the most prevalent gynecologic malignancies and requires further classification for treatment and prognosis. Long non-coding RNAs (lncRNAs) and immunogenic cell death (ICD) play a critical role in tumor progression. Nevertheless, the role of lncRNAs in ICD in EC remains unclear. This study aimed to explore the role of ICD related-lncRNAs in EC via bioinformatics and establish a prognostic risk model based on the ICD-related lncRNAs. We also explored immune infiltration and immune cell function across prognostic groups and made treatment recommendations. A total of 552 EC samples and clinical data of 548 EC patients were extracted from The Cancer Genome Atlas (TCGA) database and University of California Santa Cruz (UCSC) Xena, respectively. A prognostic-related feature and risk model was developed using the least absolute shrinkage and selection operator (LASSO). Subtypes were classified with consensus cluster analysis and validated with t-Distributed Stochastic Neighbor Embedding (tSNE). Kaplan-Meier analysis was conducted to assess differences in survival. Infiltration by immune cells was estimated by single sample gene set enrichment analysis (ssGSEA), Tumor IMmune Estimation Resource (TIMER) algorithm. Quantitative polymerase chain reaction (qPCR) was used to detect lncRNAs expression in clinical samples and cell lines. A series of studies was conducted in vitro and in vivo to examine the effects of knockdown or overexpression of lncRNAs on ICD. In total, 16 ICD-related lncRNAs with prognostic values were identified. Using SCARNA9, FAM198B-AS1, FKBP14-AS1, FBXO30-DT, LINC01943, and AL161431.1 as risk model, their predictive accuracy and discrimination were assessed. We divided EC patients into high-risk and low-risk groups. The analysis showed that the risk model was an independent prognostic factor. The prognosis of the high- and low-risk groups was different, and the overall survival (OS) of the high-risk group was lower. The low-risk group had higher immune cell infiltration and immune scores. Consensus clustering analysis divided the samples into four subtypes, of which cluster 4 had higher immune cell infiltration and immune scores. A prognostic signature composed of six ICD related-lncRNAs in EC was established, and a risk model based on this signature can be used to predict the prognosis of patients with EC.

Fertility-sparing re-treatment for endometrial cancer and atypical endometrial hyperplasia patients with progestin-resistance: a retrospective analysis of 61 cases

ObjectiveThis study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) women who desire to maintain their fertility.MethodsOur study included 61 progestin-resistant EC/AEH patients. These patients underwent treatment with gonadotropin-releasing hormone agonist (GnRHa) solely or a combination of GnRHa with levonorgestrel-releasing intrauterine system (LNG-IUD) or aromatase inhibitor (AI). Histological evaluations were performed every 3–4 months. Upon achieving complete remission (CR), we recommended maintenance treatments including LNG-IUD, cyclical oral contraceptives, or low-dose cyclic progestin until they began attempting conception. Regular follow-up was conducted for all patients. The chi-square method was utilized to compare oncological and fertility outcomes, while the Cox proportional hazards regression analysis helped identify risk factors for CR, recurrence, and pregnancy.ResultsOverall, 55 (90.2%) patients achieved CR, including 90.9% of AEH patients and 89.7% of EC patients. The median re-treatment time was 6 months (ranging from 3 to 12 months). The CR rate for GnRHa alone, GnRHa + LNG-IUD and GnRHa + AI were 80.0%, 91.7% and 93.3%, respectively. After a median follow-up period of 36 months (ranging from 3 to 96 months), 19 women (34.5%) experienced recurrence, 40.0% in AEH and 31.4% in EC patients, with the median recurrence time of 23 months (ranging from 6 to 77 months). Among the patients who achieved CR, 39 expressed a desire to conceive, 20 (51.3%) became pregnant, 11 (28.2%) had successfully deliveries, 1 (5.1%) was still pregnant, while 8 (20.5%) suffered miscarriages.ConclusionGnRHa-based fertility-sparing treatment exhibited promising oncological and reproductive outcomes for progestin-resistant patients. Future larger multi-institutional studies are necessary to confirm these findings.

Prognostic significance of adjuvant chemotherapy in stage I-II endometrial carcinoma patients who underwent lymphadenectomy.

Endometrial carcinoma, the most common gynecologic carcinoma, has an excellent prognosis post-surgery when diagnosed early. The role of postoperative adjuvant chemotherapy in stages I-II endometrial carcinoma remains controversial. This study assesses the efficacy of adjuvant chemotherapy in improving prognosis for these patients. A retrospective analysis was conducted on 1223 stage I-II endometrial carcinoma patients who underwent surgical treatment including total hysterectomy, bilateral salpingo-oophorectomy, and lymph-node biopsy or dissection across four Jikei University School of Medicine-affiliated facilities between 2001 and 2018. Patients were divided into low intermediate risk (LIR) and high intermediate risk (HIR) groups based on recurrence risk. Propensity score matching adjusted for various covariates was used to compare progression-free survival (PFS) and overall survival (OS) between patients who received adjuvant chemotherapy and those who did not. The study included 443 eligible patients, with 288 in the LIR group and 155 in the HIR group. Post propensity score matching, no significant difference in PFS or OS was observed between the observation and adjuvant chemotherapy groups within both risk categories. Notably, the 5-year OS for LIR was 97.6% in the observation group and 96.7% in the chemotherapy group; for HIR, the 5-year OS was similarly high with no significant difference. The findings suggest that postoperative adjuvant chemotherapy does not significantly contribute to the improvement of recurrence or prognosis in patients with stage I-II endometrial carcinoma who are categorized outside the low-risk group and have no lymph-node metastasis.

Multiparameter MRI-based radiomics analysis for preoperative prediction of type II endometrial cancer

ObjectivesThis study aimed to develop and validate a radiomics nomogram based on multiparameter MRI for preoperative differentiation of type II and type I endometrial carcinoma (EC). MethodsA total of 403 EC patients from two centers were retrospectively recruited (training cohort, 70 %; validation cohort, 30 %). Radiomics features were extracted from T2-weighted imaging, dynamic contrast-enhanced T1-weighted imaging at delayed phase(DCE4), and apparent diffusion coefficient (ADC) maps. Following dimensionality reduction, radiomics models were developed by logistic regression (LR), random forest (RF), bootstrap aggregating (Bagging), support vector machine (SVM), artificial neural network (ANN), and naive bayes (NB) algorithms. The diagnostic performance of each radiomics model was evaluated using the ROC curve. A nomogram was constructed by incorporating the optimal radiomics signatures with significant clinical-radiological features and immunohistochemistry (IHC) markers obtained from preoperative curettage specimens. The diagnostic performance and clinical value of the nomogram were evaluated using ROC curves, calibration curves, and decision curve analysis (DCA). ResultsAmong the radiomics models, the NB model, developed from 12 radiomics features derived from ADC and DCE4 sequences, exhibited strong performance in both training and validation sets, with the AUC values of 0.927 and 0.869, respectively. The nomogram, incorporating the radiomics model with significant clinical-radiological features and IHC markers, demonstrated superior performance in both the training (AUC = 0.951) and the validation sets (AUC = 0.915). Additionally, it exhibited excellent calibration and clinical utility. ConclusionsThe radiomics nomogram has great potential to differentiate type II from type I EC, which may be an effective tool to guide clinical decision-making for EC patients.

Impact of cachexia on disease recurrence and survival outcomes in endometrial cancer patients

ObjectiveCancer cachexia is progressive weight loss due to muscle/adipose tissue wasting and inadequate intake that occurs in response to malignancy. It is an independent predictor of disease recurrence and reduced survival in several cancers. However, cachexia’s relationship with gynecologic malignancy outcomes has only been examined in small studies with limited follow-up and inconsistent definitions of cachexia. This study investigated the impact of cachexia on disease recurrence and overall survival in high-risk endometrial carcinoma patients. MethodsThis retrospective cohort study examined data from patients with high-risk non-metastatic primary endometrial carcinoma treated at a single institution from 2015 to 2020. Treatment for all subjects included total hysterectomy, surgical staging, pelvic external beam radiotherapy with or without adjuvant chemotherapy. Radiation planning CT datasets were used to measure skeletal musculature at the L3 vertebral level. Skeletal muscle index (SMI) was defined as total L3 skeletal muscle cross sectional area (cm2)/height2 (m2), and cachexia was defined based on SMI. Results55 patients were eligible for analysis. Several SMI thresholds were used to define cachexia, and analysis was performed for each definition. Kaplan-Meier and Cox-proportional hazards regression analysis yielded no significant reduction in overall survival (OS) or progression-free survival (PFS) in patients with cachexia, regardless of threshold chosen. However, 4 of 13 definitions of cachexia showed significantly improved OS in patients without cachexia, relative to those with cachexia. There were no significant differences in disease recurrence. ConclusionsCachexia as defined in this study was not associated with poor outcomes in endometrial carcinoma patients based on OS, PFS, or disease recurrence.

The Expression and Amplification of HER2 Has a Significant Impact on the Prognosis of Endometrial Carcinoma in Korean Patients.

Objective: The purpose of this study was to analyze the protein overexpression and gene amplification of HER2 in endometrial carcinoma (EC) and to evaluate its role as a prognostic factor in Korean women. Methods: A tissue microarray (TMA) was constructed from samples from 191 patients with diverse histologic types of EC. HER2 protein expression and gene amplification status were analyzed using immunohistochemistry (IHC) and silver in situ hybridization (SISH), respectively. All patients were treated and followed up at a single tertiary medical center in Seoul, Korea, between July 2009 and October 2020. Results: In terms of histological type, among the 191 EC patients, 157 had endometrioid carcinoma, nine had uterine serous papillary carcinoma (USPC), one had clear cell carcinoma, one had squamous cell carcinoma, eight had mixed carcinoma, and 15 had uterine carcinosarcoma (UC). HER2 protein overexpression was observed in eight of the 191 (4.2%) EC patients; of these patients, five had IHC scores of 2+, and three had IHC scores of 3+. The HER2 overexpression rates of USPC, UC, and endometrioid carcinomas were 33.3%, 26.6%, and 0.6%, respectively. HER2 protein overexpression was significant in USPC and UC tissues (p < 0.000) and was associated with poor overall survival (OS) (p < 0.001). HER2 gene amplification was confirmed in seven of 184 patients (3.8%), including three patients with USPC and four patients with UC. OS was significantly shorter in patients who had HER2 amplification (p < 0.001). On multivariate analysis, HER2 expression and HER2 amplification were statistically significantly associated with worse OS (p = 0.006). However, HER2 expression without amplification was not statistically associated with OS (p = 0.993). Conclusions: HER2 protein overexpression and gene amplification are significantly correlated with shorter OS in Korean women. HER2 can be considered an important predictor of survival outcomes in EC patients.

Abstract 6204: Differential gut microbiome alpha diversity in endometrial and ovarian carcinoma patients

Abstract Background: Emerging research underscores the gut microbiome's critical role in cancer development, progression, and response to treatment. As a part of the “ASAP” study, which focuses on the implementation of comprehensive molecular profiling and deep clinical annotation of electronic health records in participants diagnosed with or at risk of developing cancer, we have established a microbiome-associated biobank and corresponding clinical dataset to systematically explore the dynamics of the gut microbiome as patients progress through cancer treatment. We describe a pilot project where we explore the baseline microbiome samples collected from ASAP participants, particularly from those with endometrial and ovarian carcinomas. Methods: Stool samples from patients were collected at the time of enrollment in the ASAP study and sampling is repeated every three months to align with the additional biosampling procedures. Microbial DNA was extracted from the baseline stool samples and subjected to sequencing of the V4 region of the 16S rRNA gene. After generating species level operational taxonomic units (OTUs), alpha diversity measures were generated in the form of the inverse Simpson index. In order to determine whether there was a difference in alpha diversity between individuals with ovarian (N = 37) and endometrial (N = 35) carcinomas, we employed a t-test with 100,000 permutations to derive an empirical p-value. Results: We present sequencing results from the initial n=297 samples. Our comparison of the alpha diversity between ASAP study participants with ovarian and endometrial carcinomas showed a significant difference between the two groups, with the ovarian cancer patients having a lower alpha diversity (empirical p-value = 0.03915). Due to the uniform sampling, biobanking, and analytical procedures, our study allows the ability to explore microbiome features amongst various cancer diagnoses while minimizing laboratory and analytical differences that plague microbiome reproducibility. Conclusions: We observed a significant difference in alpha diversity between patients with endometrial and ovarian carcinomas. Although the current results are preliminary, the wealth of information available in the ASAP protocol will allow us to continue exploring the association of the gut microbiome with cancer and the associated treatment. Citation Format: Casey T. Finnicum, Tobias Meissner, Christel Davis, Sarah Viet, Jason L. Petersen, McKenna Deaton, Benjamin Solomon, William Spanos, David Starks, Rachel Elsey, Erik A. Ehli, Casey Williams. Differential gut microbiome alpha diversity in endometrial and ovarian carcinoma 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 6204.