Early-stage Endometrial Carcinoma Research Articles

VNOTES retroperitoneal sentinel lymph node dissection for endometrial cancer staging: First multicenter, prospective case series.

The current standard treatment for endometrial cancer is a laparoscopic hysterectomy with adnexectomies and bilateral sentinel node resection. A retroperitoneal vNOTES sentinel node resection has several theoretical potential advantages. These include being less invasive, leaving no visible scars, operating without Trendelenburg, and therefore offering the anesthetic advantage of easier ventilation in obese patients and following the natural lymph node trajectory from caudally to cranially and therefore a lower risk of missing the sentinel node. The aim of this study is to determine the feasibility of a retroperitoneal vNOTES approach to sentinel lymph node dissection for staging of endometrial cancer. A prospective multicenter case series was performed in four hospitals. A total of 64 women with early-stage endometrial carcinoma suitable for surgical staging with sentinel lymph node removal were operated via a transvaginal retroperitoneal vNOTES approach. The paravesical space was entered through a vaginal incision after injecting the cervix with indocyanine green. A vNOTES port was placed into this space and insufflation of the retroperitoneum was performed. Sentinel lymph nodes were identified bilaterally using near-infrared light followed by endoscopic removal of these nodes. A total of 64 women with early-stage endometrial cancer underwent sentinel lymph node removal by retroperitoneal vNOTES technique. All patients also underwent subsequent vNOTES hysterectomy and bilateral salpingo-oophorectomy. The median age was 69.5 years, median total operative time was 126 min and the median estimated blood loss was 80 mL. In 97% of the cases bilateral sentinel nodes could be identified. A total of 60 patients had negative sentinel nodes, three had isolated tumor cells and one had macroscopically positive sentinel nodes. No complications with sequel occurred. This prospective multicenter case series demonstrates the feasibility of the vNOTES approach for identifying and removing sentinel lymph nodes in women with endometrial carcinoma successfully and safely. vNOTES allows sole transvaginal access with exposure of the entire retroperitoneal space, following the natural lymph trajectory caudally to cranially, and without the need for a Trendelenburg position.

Abstract 7312: Construction of a gene panel for liquid biopsy-based diagnostics of gynecologic cancer

Abstract Background: Ovarian carcinoma (OC) is the leading cause of death from gynecologic cancers mainly due to late detection, where most patients are diagnosed at advanced stages (51% in stage III; 29% in stage IV). Despite an overall more favorable prognosis, endometrial carcinoma (EC) is the most common gynecologic cancer, with an increasing incidence and where some subtypes are associated with a poor prognosis. Identification of DNA mutations from precancerous lesions or early-stage OC and EC would allow for early intervention. Liquid biopsies through routine sampling such as endocervical sampling, or blood collection for isolation and analysis of ctDNA have previously been assessed for their use in detection of OC and EC. These studies have provided evidence that tumor-derived mutations can be detected in endocervical samples, supporting endocervical liquid biopsies as a potential source of ctDNA. Herein, we aimed to construct a diagnostic gene panel corresponding to common mutation profiles of OC and EC to detect early-stage malignancy through a non-invasive approach. Methods: Using the NGS-method, Simple multiplexed PCR-based barcoding of DNA for sensitive mutation detection using sequencing (SiMSen-Seq), a gene panel was constructed targeting hotspot mutations in known OC- and EC-associated genes. Hotspots were identified using the Catalogue of Somatic Mutations in Cancer (COSMIC) database or retrieved from the literature and assays were designed for amplification of short DNA fragments. Precise assay development was carried out including multiple steps of careful validation to ensure high specificity and efficient amplification. Individual assays were validated in multiple steps using qPCR and fragment analysis. Results: The gene panel was designed as two non-overlapping subunits for comprehensive diagnosis of OC and EC. The two constructed multiplexes, together composed of 125 single assays target genomic regions in 34 EC and OC-associated genes e.g., PTEN, TP53, PIK3CA and CTNNB1. Included assays had a median amplicon size of 92 bp (range 57-111 bp). Both multiplexes displayed good performance with distinguishable libraries at low DNA input (10 ng). Validation of individual assays showed high specificity and efficient amplification where >80% of assays displayed a sequencing coverage >500 UMI counts at a consensus depth of 3. Patient coverage calculations of COSMIC data suggested comparable coverage as similar published approaches. Conclusion: The results suggest that the constructed gene panel has great potential to detect mutations in liquid biopsies collected from the gynecologic tract, despite low tumor DNA levels. Validation of the two multiplexes by fragment analysis and sequencing showed high performance, hence, prospective for the approaching sequencing of liquid biopsies. Citation Format: Sara Schumacher, Therese Carlsson, Jacob Malchau Lauesgaard, Anna Linder, Amanda Olsson Widjaja, Karin Sundfeldt. Construction of a gene panel for liquid biopsy-based diagnostics of gynecologic cancer [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 7312.

Early-stage endometrial carcinoma; risk factors for recurrence

Background: Endometrial carcinoma (EC) is the most common gynecological malignancy in developed countries. The overall prognosis is excellent, as most cases are diagnosed at an early stage with low-grade histology, but once the recurrence occurs, the median survival decreases severely. Aims and Objectives: The aim of this study was to identify the risk factors associated with recurrence in early-stage EC and explore their impact on overall survival (OS) after recurrence. Materials and Methods: Records from patients diagnosed with EC were retrospectively reviewed. 220 patients were identified as early-stage, low-risk EC who underwent primary surgical treatment between January 2010 and December 2022, and their baseline characteristics were analyzed. Cox regression analysis was used to identify various factors for tumor recurrence. Survival analysis was done using the Kaplan-Meier method. Results: In a cohort of 220 patients, we observed tumor recurrence in 44 (20%) patients and 34 (15.45%) deaths over a median follow-up of 72 months (range, 12–144 months). Multivariate analysis confirmed two risk factors: myometrial invasion (MMI) of any depth and lymphovascular invasion (LVI) as independent predictors of recurrence. The prognosis was worse for patients with recurrence than for those without. The OS for the recurrent group was 38.6%, compared to 96.0% in the non-recurrent group. In our study, the median time to recurrence was 19 months (confidence interval 18–30) months. Conclusion: The presence of MMI and LVI are important predictors for recurrence in early-stage low-risk EC.

Associations between modifiable lifestyle factors and health-related quality of life among endometrial carcinoma survivors - A cross-sectional study

ObjectiveTo explore possible associations between modifiable lifestyle factors and health-related quality of life (HRQoL) in endometrial carcinoma survivors by assessing differences in HRQoL between survivors meeting and not meeting the World Health Organization's (WHO) recommendations regarding physical activity, BMI, and smoking. MethodsThis was a cross-sectional population-based study in women having undergone surgery for assumed early-stage endometrial carcinoma. Thresholds for clinical importance based on the EORTC QoL working group were used to interpret scores. Effect size (ES) was interpreted as small (d = 0.2–0.49), medium (d = 0.5–0.8), and large (d > 0.8). ResultsIn total, 1200 evaluable women were included. Meeting physical activity recommendations and BMI <25 kg/m2 was associated with significantly better global health status, (ES) = 0.18 and ES = −0.11, respectively. On multivariate analysis, women meeting physical activity recommendations had significantly higher scores on physical- (ES = 0.31), role- (ES = 0.15), and social functioning (ES = 0.15), and lower levels of fatigue (ES = −0.16), pain (ES = −0.10), and appetite loss (ES = −0.15) (all p < 0.05) compared to non-meeting survivors. Participants with BMI ≥25 kg/m2 had lower scores for social functioning (ES = −0.10), and higher levels of pain (ES = 0.13) and dyspnea (ES = 0.12) (all p < 0.05) compared to those with BMI <25 kg/m2. Smokers had lower scores for emotional functioning (ES = −0.09) and higher levels of diarrhea (ES = 0.10) (all p < 0.05) compared to non-smokers. ConclusionMeeting WHO recommendations for modifiable life-style factors is associated with better HRQoL among endometrial carcinoma survivors: Being sufficiently physical active and having a BMI <25 kg/m2 are significantly associated with better self-reported global health status. All modifiable factors are associated with better functioning, and reduced symptom-burden.

Detection of Somatic Alterations in Peritoneal Lavages of Early-Stage Endometrial Carcinoma Patients

Detection of Somatic Alterations in Peritoneal Lavages of Early-Stage Endometrial Carcinoma Patients

Laparoscopic Sentinel Lymph Node Mapping Using NIR Fluorescence with ICG in Early Endometrial Cancer: Experience at a Tertiary Care Oncology Centre

Objective: To determine the detection rates and location of sentinel nodes as well as to determine intraoperative and postoperative surgico-pathological outcomes in endometrial cancer patients who underwent laparoscopic staging with sentinel node biopsy using ICG dye. Materials and Methods: This retrospective study was conducted in a tertiary care oncology centre, Amrita Institute of medical sciences, Kochi from April 2021 to March 2023. All cases of biopsy proven early stage endometrial carcinoma that underwent laparoscopic staging with SLN mapping using the ICG dye were included. All histological types were included, as long as the disease was confined to the uterus, clinically and on MRI. Results: A total of 80 patients were found eligible for the study. Only the patients with apparent uterine confined disease on preoperative MRI were selected for sentinel mapping, 80 % of whom had IA disease on MRI, and 20 % had IB, 13.5 % were high grade histology.The overall SLN detection rate was 93.75%, and bilateral detection rate was 92.5 %. Most common location was external iliac in 40.8% cases. Only 1 patient was found to harbour nodal micro metastasis on ultrastaging. Final histopathology identified stage IA in 63 (78.75%) patients, IB in 14 (17.5%), Stage II in 2 (2.5%) and Stage IIIC1 in 1 (1.25%) patient. Conclusion: Laparoscopic staging with SLNB using ICG is a practicable approach for uterine limited disease on preoperative evaluation. It extends the benefits of minimally invasive surgery to these patients, while overcoming the limitations of prohibitive cost or availability of expensive robotic equipment.

Timing of Postoperative Radiation Therapy for Early-Stage Endometrial Carcinoma: A 20-Year Single-Center Retrospective Cohort Experience in China

To investigate the appropriate timing of radiotherapy (RT) after hysterectomy for women with early-stage endometrial carcinoma (EC). Between 1999 and 2020, 1080 patients with I and II endometrial cancer received postoperative RT at our hospital. All patients underwent hysterectomy followed by RT. The optimal cut-off values for the surgery-RT interval (SRI) based on overall survival (OS) were determined using the R software. The disease-free survival (DFS), OS, locoregional recurrence free survival (LRFS), and distant metastasis free survival (DMFS) rates were estimated using the Kaplan-Meier method. Multivariate analyses were performed using Cox proportional hazards regression. Median follow-up time was 52 months. Median SRI were 46 days. The optimal cut-off value for the surgery-RT interval (SRI) based on overall survival (OS) is 40 days. The group initiated RT within 40 days following surgery has higher OS (P = 0.004), higher LRFS (P = 0.002) and higher DMFS (P = 0.039). An SRI of ≤ 40 days was independently associated with higher OS (HR 0.454, 95% CI:0.261-0.788), higher LRFS (HR 0.487, 95% CI:0.304-0.779), and higher DMFS (HR 0.643, 95% CI:0.421-0.982) than SRI of >40 days. However, SRI had no significant effect on DFS. The surgery-RT interval affects the patients' survival endpoints. Based on this analysis, the timing of the initiation of RT after hysterectomy is crucial for patients with early-stage endometrial carcinoma (EC). The postoperative radiation therapy for endometrial cancer should be initiated within 40 days following surgery.

Mismatch Repair Status is an Effective Prognostic Factor for Early-Stage Endometrial Carcinoma

This study is to evaluate the impact of mismatch repair (MMR) status on prognosis among patients with stage I to II (FIGO 2009) endometrial carcinoma (EC) treated with hysterectomy and adjuvant RT. Between Oct. 2017 and Dec. 2020, patients with stage I to II (FIGO 2009) EC who had undergone hysterectomy followed by adjuvant RT in our institution were retrospectively reviewed. Clinical characteristics were compared between patients with proficient and deficient mismatch repair (pMMR and dMMR) using Pearson Chi-Square test for categorical variables. Kaplan-Meier method and log-rank test were used to compared overall survival (OS), disease-free survival (DFS), local-regional recurrence free survival (LRFS) and distant metastasis free survival (DMFS). Statistically significant difference was set as p<0.05. Totally 276 stage I to II EC patients with known MMR status were included in this study. Among them, 211 patients were classified as pMMR while 65 patients were classified as dMMR. When compared to pMMR, patients with dMMR were more likely to have grade 3 and non-endometrioid type(37.8% vs. 20.8%, p = 0.014), lympho-vascular invasion (36.7% vs. 16.3%, p = 0.000), young age (<60) (28.6% vs. 17.2%, p = 0.027), HIR to HR classification(30.9% vs. 16.1%, p = 0.004). Of all the 276 patients, the median follow-up time was 31 months. Two-year DMFS was superior for pMMR compared to dMMR patients (96.3% vs. 95.0%, p = 0.048). Two-year DFS tended to be better for pMMR than dMMR patients with survival curves not crossed over each other (93.0% vs. 86.8%, p = 0.074). Two-year OS (98.9% vs. 98.4%, p = 0.716) and LRFS (96.3% vs. 95.0%, p = 0.815) were not different between pMMR/dMMR patients. For HIR to HR group, we reached the similar conclusion while for LR to IR group, survival statistics were not different between pMMR/dMMR patients. As to failure pattern, dMMR were more likely to have distant failure while local and regional failure were not different between the two groups. For stage I to II EC, patients with dMMR have poorer DMFS and DFS compared to pMMR patients especially in HIR to HR risk classification. The combination of MMR status and other clinical and pathological factors may establish a new prognostic model and form a new risk stratification system.

Comparison of Methods for Testing Mismatch Repair Status in Endometrial Cancer.

Approximately 20-30% of endometrial carcinomas (EC) are characterized by mismatch repair (MMR) deficiency (dMMR) or microsatellite instability (MSI), and their testing has become part of the routine diagnosis. The aim of this study was to establish and compare the MMR status using various approaches. Immunohistochemistry (IHC), PCR-based MSI, and the detection of defects in the four key MMR genes (MLH1, PMS2, MSH2, and MSH6) via methylation-specific multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) were performed. MSH3 expression was also evaluated. A set of 126 early-stage EC samples were analyzed, 53.2% of which were dMMR and 46.8% of which were proficient MMR (pMMR) as determined using IHC, whereas 69.3% were classified as microsatellite stable, while 8.8% and 21.9% were classified MSI-low (MSI-L) and MSI-high (MSI-H), respectively. In total, 44.3% of the samples showed genetic or epigenetic alterations in one or more genes; MLH1 promoter methylation was the most common event. Although acceptable concordance was observed, there were overall discrepancies between the three testing approaches, mainly associated with the dMMR group. IHC had a better correlation with MMR genomic status than the MSI status determined using PCR. Further studies are needed to establish solid conclusions regarding the best MMR assessment technique for EC.

Does sentinel node mapping impact morbidity and quality of life in endometrial cancer?

ObjectivesTo evaluate the prevalence of post-operative complications and quality of life (QoL) related to sentinel lymph node (SLN) biopsy vs systematic lymphadenectomy in endometrial cancer.MethodsA prospective cohort included women with...

Non-operative management of clinical early-stage endometrioid endometrial carcinoma: Hormonal or radiation therapy? (1290)

Non-operative management of clinical early-stage endometrioid endometrial carcinoma: Hormonal or radiation therapy? (1290)

Practice patterns of adjuvant radiotherapy in women with stage I to II endometrial carcinoma: a real-world multi-institutional analysis in China

BackgroundThis study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers.MethodsWe included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014).ResultsA total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients.There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3–5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy.ConclusionWe report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China.Trial registrationThe clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139).

Superiority of indocyanine green-enhanced near-infrared fluorescence-guided imaging for laparoscopic lymph node dissection in patients with early-stage endometrial cancer: A retrospective cohort study

ObjectiveLaparoscopic pelvic lymph node dissection (LPND), which is an effective therapy for endometrial cancer, is challenging because of the complexity of the procedure and the occurrence of postoperative complications. This study aimed to explore whether indocyanine green (ICG)-enhanced near-infrared (NIR) fluorescence-guided LPND is superior to LPND in the context of early-stage endometrial carcinoma. MethodsIn this retrospective study, we included the medical records of 190 patients with early-stage endometrioid adenocarcinoma who underwent LPND at the Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine between January 2019 and January 2021. Depending on whether ICG-enhanced NIR fluorescence guidance was used, the patients were assigned to the ICG group or non-ICG group. Patients were followed-up for one year after surgery. Data on demographic characteristics, pathological results, operative outcomes, and complications were collected and analyzed. ResultsThe baseline characteristics were comparable between the ICG group and non-ICG group, including age, BMI, pregnancy history, and preoperative hemoglobin. For surgical outcomes, the patients in ICG group had significantly lower intraoperative blood loss (50 mL vs. 120 mL, p < 0.001), less postoperative pelvic drainage time (4.14 ± 1.44 d vs. 5.70 ± 1.89 d, p = 0.001), shorter duration of hospital stay (5.26 ± 1.41 d vs. 7.37 ± 1.85 d, p = 0.003), higher number of positive pelvic lymph nodes (PLNs) (1 vs. 0, p = 0.003), and more PLN-positive cases (16.0% vs. 3.6%, p = 0.003) than the patients in non-ICG group. However, no significant differences were noted in blood transfusion requirement, operative time, hemoglobin level decreases, number of PLNs harvested, or the presence of lymphocysts between the two groups. ConclusionOur study showed that ICG-enhanced NIR fluorescence-guided operation may improve the accuracy and safety of LPND.

CTNNB1 p.D32A (c.95A > C) somatic mutation in stage I grade 1 endometrioid endometrial carcinoma with lung metastasis: a case report

BackgroundMost endometrial cancers are of low histological grade and uterine-confined, with a high 5-year survival rate. However, a small subset of women with low-grade and early-stage endometrioid endometrial cancer experience recurrence and death; thus, a more precise risk-stratification is needed.Case presentationA 29-year-old woman presented with abnormal vaginal bleeding and was diagnosed with FIGO grade 1 endometrioid endometrial carcinoma by curettage. Comprehensive cancer staging including pelvic and para-aortic lymphadenectomy was then performed. Postoperative pathological findings suggested an FIGO grade 1 endometrioid endometrial carcinoma infiltrating the superficial muscle layer. The patient did not receive adjuvant therapy. After 4 years of follow-up, the patient returned to our institution with lung metastasis. She underwent thoracoscopic resection of the affected lobes, followed by six cycles of combined chemotherapy of paclitaxel and carboplatin. Next-generation sequencing showed that the primary and lung metastatic tumors shared 4 mutations: PTEN (p.P248Lfs*8), CTNNB1 (p.D32A), BCOR (p.N1425S) and CBL (p.S439N). Immunohistochemistry revealed nuclear location of β–catenin in the primary and lung metastatic tumor samples, indicating abnormal activation of β–catenin.ConclusionCTNNB1p.D32A (c.95A > C) mutation may be related to lung metastasis in this patient with low-grade early-stage endometrioid endometrial carcinoma.

Comparison of oncological outcomes between sentinel lymph node biopsy and complete lymphadenectomy for endometrial cancer.

Sentinel lymph node (SLN) mapping allows node-negative patients to be spared from the surgical comorbidities associated with total lymphadenectomy. This study aimed to evaluate the oncological outcomes of SLN biopsy versus complete lymph node dissection in patients with early-stage endometrial carcinoma. Retrospective analyses were performed in patients with pathologically confirmed endometrioid endometrial carcinoma, who underwent minimally invasive surgical staging with SLN biopsy or complete lymph node dissection at Yonsei Cancer Center between 2015 and 2019. A total of 301 patients were included in this study. Eighty-two patients underwent SLN biopsy, while 219 underwent complete lymph node dissection. There were no significant differences in patient characteristics between the two groups. In terms of operative characteristics, the SLN biopsy-only group had a significantly shorter surgical duration (p < 0.001) than the lymphadenectomy group. The mean follow-up period was 41.4 months. There were no differences in progression-free survival (PFS) and overall survival (OS) between the two groups (SLN biopsy vs. complete lymph node dissection; p = 0.798 and 0.301, respectively). Multivariate analysis revealed that SLN biopsy was not an independent prognostic factor for PFS or OS. Our results showed that SLN biopsy provided oncological outcomes similar to those of lymphadenectomy.

Quantitative dynamic contrast-enhanced parameters and intravoxel incoherent motion facilitate the prediction of TP53 status and risk stratification of early-stage endometrial carcinoma.

The aim of the study was to investigate the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion (IVIM) in differentiating TP53-mutant from wild type, low-risk from non-low-risk early-stage endometrial carcinoma (EC). A total of 74 EC patients underwent pelvic MRI. Parameters volume transfer constant (Ktrans), rate transfer constant (Kep), the volume of extravascular extracellular space per unit volume of tissue (Ve), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and microvascular volume fraction (f) were compared. The combination of parameters was investigated by logistic regression and evaluated by bootstrap (1000 samples), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). In the TP53-mutant group, Ktrans and Kep were higher and D was lower than in the TP53-wild group; Ktrans, Ve, f, and D were lower in the non-low-risk group than in the low-risk group (all P < 0.05). In the identification of TP53-mutant and TP53-wild early-stage EC, Ktrans and D were independent predictors, and the combination of them had an optimal diagnostic efficacy (AUC, 0.867; sensitivity, 92.00%; specificity, 80.95%), which was significantly better than D (Z = 2.169, P = 0.030) and Ktrans (Z = 2.572, P = 0.010). In the identification of low-risk and non-low-risk early-stage EC, Ktrans, Ve, and f were independent predictors, and the combination of them had an optimal diagnostic efficacy (AUC, 0.947; sensitivity, 83.33%; specificity, 93.18%), which was significantly better than D (Z = 3.113, P = 0.002), f (Z = 4.317, P < 0.001), Ktrans (Z = 2.713, P = 0.007), and Ve (Z = 3.175, P = 0.002). The calibration curves showed that the above two combinations of independent predictors, both have good consistency, and DCA showed that these combinations were reliable clinical prediction tools. Both DCE-MRI and IVIM facilitate the prediction of TP53 status and risk stratification in early-stage EC. Compare with each single parameter, the combination of independent predictors provided better predictive power and may serve as a superior imaging marker.

Integration of clinical sequencing and immunohistochemistry for the molecular classification of endometrial carcinoma

PurposeUsing next generation sequencing (NGS), The Cancer Genome Atlas (TCGA) found that endometrial carcinomas (ECs) fall under one of four molecular subtypes, and a POLE mutation status, mismatch repair (MMR) and p53 immunohistochemistry (IHC)-based surrogate has been developed. We sought to retrospectively classify and characterize a large series of unselected ECs that were prospectively subjected to clinical sequencing by utilizing clinical molecular and IHC data. Experimental designAll patients with EC with clinical tumor-normal MSK-IMPACT NGS from 2014 to 2020 (n = 2115) were classified by integrating molecular data (i.e., POLE mutation, TP53 mutation, MSIsensor score) and MMR and p53 IHC results. Survival analysis was performed for primary EC patients with upfront surgery at our institution. ResultsUtilizing our integrated approach, significantly more ECs were molecularly classified (1834/2115, 87%) as compared to the surrogate (1387/2115, 66%, p < 0.001), with an almost perfect agreement for classifiable cases (Kappa 0.962, 95% CI 0.949–0.975). Discrepancies were primarily due to TP53 mutations in p53-IHC-normal ECs. Of the 1834 ECs, most were of copy number (CN)-high molecular subtype (40%), followed by CN-low (32%), MSI-high (23%) and POLE (5%). Histologic and genomic variability was present amongst all molecular subtypes. Molecular classification was prognostic in early- and advanced-stage disease, including early-stage endometrioid EC. ConclusionsThe integration of clinical NGS and IHC data allows for an algorithmic approach to molecularly classifying newly diagnosed EC, while overcoming issues of IHC-based genetic alteration detection. Such integrated approach will be important moving forward given the prognostic and potentially predictive information afforded by this classification.

The effect of impaired glucose metabolism on IVF-ET pregnancy outcome with endometrial hyperplasia and early-stage endometrial cancer

ObjectiveImpaired glucose metabolism, including insulin resistance, diabetes, and obesity, is a high-risk factor for the development of endometrial cancer (EC). Most previous studies evaluated the safety and effectiveness of fertility preservation (FP) for endometrial hyperplasia (EH) and EC patients were from the perspective of oncology or case reports. The study aims to evaluate the effect of glucose metabolic status on clinical pregnancy outcome of in vitro fertilization and embryo transfer (IVF-ET) in infertile patients with endometrial hyperplasia and early-stage endometrial cancer. MethodsThis retrospectively analysis included the data from patients who underwent IVF-ET after fertility preservation (FP) with endometrial hyperplasia and early-stage endometrial carcinoma, and primary infertile patients with normal endometrium (NE) but the fallopian tubal factors or pelvic adhesions who underwent IVF-ET during the same period as control group. All the patients were further divided into the following four subgroups: A: FP+ impaired glucose metabolism (IGM) (N = 20); B: FP+ normal glucose tolerance (NGT) (N = 29); C: NE+ IGM (N = 130); and D: NE+ NGT (N = 98). The main research outcome measure was the live birth rate (LBR) per embryo transfer (ET) cycle. Student's t-test or analysis of variance (ANOVA) was used for intergroup comparisons. The least significant difference (LSD) test was used for pairwise comparison between multiple groups. ResultsThe differences in anti-Mullerian hormones (AMH) and body mass index (BMI) between the four groups were significant. As BMI increased, the total dose of gonadotropin (Gn) during the controlled ovarian stimulation in the IGM group was significantly higher than that in the NGT group. The LBR was 16.7%, 26.3%, 41.6%, and 45.3% in the four subgroups (p = 0.033), respectively. By multivariate Logistic analysis, it was found that in FP group, IGM (OR = 1.501, 95% CI: 1.045–2.154, p = 0.028) was an independent risk factor for IVF-ET. ConclusionIGM was negatively affected by the LBR after endometrial complete response (CR) from early-stage endometrial cancer and endometrial hyperplasia. It was essential for the early detection and control of insulin resistance with metformin.

Prognostic Impact of Pathologic Features in Molecular Subgroups of Endometrial Carcinoma.

The molecular characterization of endometrial carcinoma (EC) has recently been included in the ESGO/ESTRO/ESP guidelines. The study aims to evaluate the impact of integrated molecular and pathologic risk stratification in the clinical practice and the relevance of pathologic parameters in predicting prognosis in each EC molecular subgroup. ECs were classified using immunohistochemistry and next-generation sequencing into the four molecular classes: POLE mutant (POLE), mismatch repair deficient (MMRd), p53 mutant (p53abn), and no specific molecular profile (NSMP). According to the WHO algorithm, 219 ECs were subdivided into the following molecular subgroups: 7.8% POLE, 31% MMRd, 21% p53abn, 40.2% NSMP. Molecular classes as well as ESGO/ESTRO/ESP 2020 risk groups were statistically correlated with disease-free survival. Considering the impact of histopathologic features in each molecular class, stage was found to be the strongest prognostic factor in MMRd ECs, whereas in the p53abn subgroup, only lymph node status was associated with recurrent disease. Interestingly, in the NSMP tumor, several histopathologic features were correlated with recurrence: histotype, grade, stage, tumor necrosis, and substantial lymphovascular space invasion. Considering early-stage NSMP ECs, substantial lymphovascular space invasion was the only independent prognostic factor. Our study supports the prognostic importance of EC molecular classification and demonstrated the essential role of histopathologic assessment in patients' management.

Prospective analysis of the impact of adjuvant treatment with external beam radiation therapy and vaginal brachytherapy on health-related quality of life in patients with early-stage endometrioid endometrial carcinoma.

Our study evaluates the impact of adjuvant treatment with external beam radiotherapy (EBRT) combined with vaginal high dose rate brachytherapy (HDR BT) on health related quality of life (HRQL) in patients with early stage endometrioid endometrial carcinoma. From March 2019 to February 2021, 60 patients were enrolled with early stage endometrioid endometrial carcinoma, and qualified to adjuvant treatment after hysterectomy. HRQL was assessed using the EORTC QLQ-C30 questionnaire, with the endometrial cancer-specific HRQL module EORTC QLQ-EN24. Questionnaires were completed in four timepoints during adjuvant radiotherapy. A significant decrease in mean global health status / quality of life (p < 0.001) and role functioning (p = 0.028) was noted, as assessed in EORTC QLQ-C30 scale. Among the EORTC QLQ-C30 symptoms scales, significant differences were noted in the fatigue scale (p = 0.003), pain scale (p = 0.001), constipation scale (p < 0.001) and diarrhea scale (p < 0.001) over time. The EORTC QRQ-EN24 analysis showed significant deterioration in the urological symptoms scale (p < 0.001), gastrointestinal symptoms scale (p < 0.001) and in the mean pain in back and pelvis scale (p = 0.003). Adjuvant radiotherapy in patients with early-stage endometrioid endometrial cancer after hysterectomy is associated with worse quality of life, especially due to the toxicity of the treatment in relation to the gastrointestinal tract and urinary system.