Management Of Endometrial Cancer Research Articles

Clinical Outcomes of Endometrial Cancer Patients By Microsatellite Instability Status

Endometrial cancer is the most common gynecological malignancy in the United States. Up to one third of all endometrial tumor types exhibit microsatellite instability (MSI). The influence of this genetic aberration on treatment outcomes remains unclear. We compared the clinical outcomes of patients whose tumors demonstrated MSI to those whose tumors were microsatellite stable. We conducted a retrospective chart review of 35 sequential patients with non-metastatic endometrial cancer who had been tested for MSI status who underwent curative surgery and radiation and/or chemotherapy January 2013 and December 2016 at a single institution. Information regarding demographics, clinical & pathologic tumor characteristics, treatment modalities, recurrence, and survival were recorded. Age, stage, histology, grade, and lymphovascular invasion (LVSI) were compared with Fisher’s Exact test. Survival and recurrence estimates were calculated using to Kaplan-Meier method and compared by the log–rank test. 19 tumors were reported microsatellite stable and 16 were microsatellite unstable. Median follow up for the whole cohort was 34.1 months. There were no significant differences between groups in age, histology, stage, grade, LVSI, or myometrial invasion (Table 1). Between patients with microsatellite stable and microsatellite unstable tumors, there was no difference in rates of local or distance recurrence between groups (10.5% vs. 25.0%, p=0.76 and 21.1% vs 6.3%, p=0.58, respectively). Survival was also not found to be significantly different between groups (median survival microsatellite stable 33.7 months vs 34.2 months microsatellite unstable, p=0.37). In patients undergoing definitive management of non-metastatic endometrial cancer, tumor microsatellite instability was not associated with significant differences in adverse pathologic features at presentation nor differences in recurrence rates or survival. Additional studies are warranted to confirm any prognostic and/or predictive value of tumor MSI status in the treatment of endometrial cancer.Abstract 2812; Table 1Clinical characteristics of endometrial cancer patients by MSI statusCharacteristicMSI stable n = 19MSI unstable n = 16p-valueCharacteristicMSI stable n = 19MSI unstable n = 16p-valueStage1A, 1B1490.479Grade1230.2382, 2A2328103, 3B, 3C243934B10Lymphovascular invasionPositive1090.830HistologyEndometrioid13150.101Negative86Serous30Myometrial invasionConfined200.625Mixed20<50%65Clear cell10>50%1111Other01Age in years, median (IQR)64 (57-71)68 (56-72.5)0.501 Open table in a new tab

Utilizing the Radiosensitivity Index (RSI) to Predict Pelvic Failure in Endometrial Cancer Treated with Adjuvant Radiotherapy

Various adjuvant approaches are utilized in the management of endometrial cancer based on surgical pathology and institutional preference. The radiosensitivity index (RSI) is a previously validated multi-gene expression index that estimates tumor radiosensitivity. In this study, we evaluate RSI as a genomic predictor for pelvic failure (PF) in patients treated with adjuvant radiotherapy. A total of 204 consecutively treated patients with endometrial cancer were identified from our IRB-approved institutional tissue biorepository. All patients underwent hysterectomy with bilateral salpingo-oophorectomy with the majority undergoing lymph node dissection (n=181; 88%) between 01/99 and 04/11 and followed until 01/19. Gene expression was from Affymetrix Hu-RSTA-2a520709 (Affymetrix; Santa Clara, CA). The RSI 10-gene signature was calculated for each sample using the previously published algorithm. Radiophenotype was determined by dichotomization of RSI at the previously identified cutpoint of 0.375; ≥0.375 = radioresistant (RR) and <0.375 = radiosensitive (RS). Time to event analysis was performed with Kaplan-Meier estimates and the log-rank test. Associations between radiophenotype and outcomes were explored with univariable (UVA) and multivariable (MVA) Cox regression. The threshold for statistical significance in all tests was set at p<0.05. Median follow-up was 38.5 months (range: 0.2-216). The median RSI was 0.42 (range: 0.11-0.70). There were no significant differences in RS and RR patients in age (p=0.99), serosa and/or adnexa involvement (p=0.37), vaginal and/or parametrial involvement (p=0.48), cervical stromal invasion (p=0.59), receipt of adjuvant chemotherapy (p=0.12), and node involvement (p=0.78). A total of 83 (41%) patients were treated with adjuvant radiotherapy with vaginal brachytherapy (n=19; 23%), pelvic radiotherapy (n=26; 31%), or both (n=38; 46%). In patients treated with radiation, RR patients were more likely to undergo PF (3 year pelvic control 84% vs 100%; p=0.02) with worse PF free survival (PFFS) (3 year PFFS 65% vs. 89%; p=0.04). However, since RSI is a radiation specific signature it did not predict PF (p=0.86) or PFFS (p=0.57) in patients not treated with radiation. Factors found to predict PF on UVA included grade 3/1-2 (HR 3.8; 95% CI 1.2-14.8, p=0.03), serosa and/or adnexa involvement (5.9; 95% CI 1.6-20.2, p=0.008), lymph node involvement (4.9; 95% CI 1.5-18.8, 0.009), and RR/RS (7.7; 95% CI 1.5-140.9, 0.01). On MVA, factors that continued to predict for PF included RR/RS (10.7; 95% CI 1.9-202.4, p=0.004), lymph node involvement (4.1; 95% CI 1.2-16.3, p=0.03), and serosa and/or adnexa involvement (4.3; 95% CI 1.2-16.4, p=0.03). RSI was found to be a significant predictor of PF in patients treated with adjuvant radiotherapy on MVA. We propose RSI may be a method to predict which patients are most likely to fail in the pelvis and candidates for treatment escalation in the adjuvant setting.

Surgery in Endometrial Cancer: An Audit of Quality Across Centers in India

Surgical management is the cornerstone in the treatment of endometrial cancer. However, there are many controversies involved in the management starting from what constitutes adequate staging to the type of adjuvant treatment. In India, surgeons from several specialties operate on patients with endometrial cancer and there is a lack of guideline-based practice which necessitates an audit on the quality of care offered to women with endometrial cancer. The study was a questionnaire-based study conducted at various conference venues. The study participants included general surgeons, gynecologists, surgical oncologists and gynecologic oncologists who operate on endometrial cancer. There is an extensive variation in the management of endometrial cancer among practitioners and lack of consensus regarding lymphadenectomy and its extent during surgery. Also, the use of intraoperative frozen section and comprehensive staging is more commonly seen among oncosurgeons when compared to other specialties.

Management of high-risk endometrial cancer: are we there yet?

Management of high-risk endometrial cancer: are we there yet?

A systematic review and meta-analysis of prognostic factors for remission in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma.

Endometrial cancer and atypical hyperplasia are rare in young women but create a dilemma between desire for pregnancy and oncologic outcomes. To identify remission rates and associated prognostic factors in patients undergoing fertility-sparing management for endometrial cancer and atypical hyperplasia. MEDLINE was searched for studies published between January 1, 1950 and July 31, 2017 using various search terms. Studies evaluating fertility-sparing management in patients aged between 19 and 44years with atypical hyperplasia or stage I endometrial cancer. Use of PRISMA guidelines to conduct a meta-analysis of the proportion of patients in remission and meta-regression analysis to test the effect of possible prognostic factors for remission. A total of 3673 studies were screened; 65 studies including 1604 patients met the inclusion criteria. The remission rate was 0.75 (95% CI, 0.73-0.77). Operative hysteroscopy for endometrial sampling was associated with higher remission rates (OR 2.31; 95% CI, 1.10-4.84; P=0.03). Studies with higher ratios of infertile women were associated with higher remission rates (OR 4.21; 95% CI, 1.44-12.33; P<0.01). Operative hysteroscopy is the preferred endometrial sampling method for patients with atypical hyperplasia or endometrial cancer undergoing fertility-sparing management.

Molecular classification of endometrial carcinoma applied to endometrial biopsy specimens: Towards early personalized patient management

BackgroundThe current risk stratification systems used to guide management of endometrial cancer are based on irreproducible post surgical pathological information, hence the need for more reliable classification systems. Using microarray and sequencing technologies, TCGA recently identified four prognostically significant endometrial carcinoma subtypes, which subsequently proved reproducible using clinically applicable surrogate tests. Using these tests, we sought to determine the level of concordance between endometrial biopsies and subsequent hysterectomy specimens in assessing the molecular classification of endometrial carcinoma. Materials and methodsFifty biopsies with corresponding hysterectomy specimens for endometrial carcinomas were collected. Additionally, 10 cases of biopsy proven atypical hyperplasia/EIN who were found to have endometrial carcinoma on resection were included. IHC for mismatch repair (MMR) proteins (MLH1, PMS2, MSH2 and MSH6) and P53 was performed. Microsatellite instability analysis was performed by PCR and Sanger sequencing was performed to detect mutations in exons 9 and 13 of the POLE gene. The level of concordance for tumor grade, histologic subtype, immunohistochemical and molecular profile in both specimens was determined using Cohen's kappa estimates. ResultsA high level of concordance was achieved for MMR-loss, MSI-high, P53-wild and abnormal types. In contrast, grade and histologic subtype showed only moderate levels of agreement. POLE gene mutation was detected in two patients. For both cases, mutations were detected only in resection specimens. When comparing atypical hyperplasia/EIN with subsequent hysterectomy tumor, the profile was identical to that of endometrial carcinoma. ConclusionIn our cohort of endometrial carcinoma, a high level of concordance was achieved between biopsy and hysterectomy specimens for MMR-loss, MSI-high, P53-wild and abnormal types, superior to that of grade and histologic subtype, providing earlier and more reliable prognostic information to inform management. Similar concordance could not be achieved for POLE mutation, given the low frequency of this mutation in our study.

The Use of microRNAs in the Management of Endometrial Cancer: A Meta-Analysis.

Introduction: Endometrial cancer (EC) is the most important gynecological cancer in terms of incidence. microRNAs (miRs), which are post-transcriptional regulators implicated in a variety of cellular functions including carcinogenesis, are particularly attractive candidates as biomarkers. Indeed, several studies have shown that the miR expression pattern appears to be associated with prognostic factors in EC. Our objective is to review the current knowledge of the role of miRs in carcinogenesis and tumor progression and their association with the prognosis of endometrial cancer. Materials and Method: We performed a literature search for miR expression in EC using MEDLINE, PubMed (the Internet portal of the National Library of Medicine) and The Cochrane Library, Cochrane databases “Cochrane Reviews” and “Clinical Trials” using the following keywords: microRNA, endometrial cancer, prognosis, diagnosis, lymph node, survival, plasma, FFPE (formalin-fixed, paraffin-embedded). The miRs were classified and presented according to their expression levels in cancer tissue in relation to different prognostic factors. Results: Data were collected from 74 original articles and 8 literature reviews which described the expression levels of 261 miRs in ECs, including 133 onco-miRs, 110 miR onco-suppressors, and 18 miRs with discordant functions. The review identified 30 articles studying the expression pattern of miR in neoplastic endometrial tissue compared to benign and/or hyperplastic tissues, 12 articles detailing the expression profile of miRs as a function of lymph node status, and 14 articles that detailed the expression pattern of miRs in endometrial tumor tissue according to overall survival or in the absence of recurrence. Conclusions: The findings presented here suggest that miR analysis merits a role as a prognostic factor in the management of patients with endometrial cancer.

A multi-centre prospective study comparing costs between robotics, laparoscopy and laparotomy in management of endometrial cancer

Objective: To compare the immediate operating room), inpatient, and overall costs between three surgical modalities—laparotomy, laparoscopy, and robotics—among patients with endometrial cancer. The differences in costs between the three surgical modalities were also compared among patients with a BMI <40 and ≥40.

Pregnancy and oncologic outcomes after fertility-sparing management for early stage endometrioid endometrial cancer

Pregnancy and oncologic outcomes after fertility-sparing management for early stage endometrioid endometrial cancer

Factors influencing time interval between diagnosis and primary surgical management of endometrial cancer

Factors influencing time interval between diagnosis and primary surgical management of endometrial cancer

Impact of non-compliance with guidelines in early type 1 endometrial cancers management, study from FRANCOGYN group.

5587 Background: To standardize surgical practices, ESMO-ESGO-ESTRO consensus conference published in 2016 new guidelines on the management of endometrial cancer. The main objective of this study was to evaluate the impact of non-compliance with current surgical guidelines on disease-free survival and overall survival. Methods: 852 patients with presumptive stage I and II type 1 endometrial cancer were included in a multicenter retrospective study, conducted between January 2000 and November 2015. The main objective of this study was to evaluate the impact of non-compliance with current surgical recommendations on overall survival and disease-free survival. Results: Our study shows that 34.3% of patients (n = 292) did not benefit from optimal surgical treatment. These patients did not have a lombo-aortic lymphadenectomy (LAL) and were at high risk of recurrence. There is a significant difference in disease-free survival in favor of patients undergoing surgery according to the recommendations, (Hazard Ratio (HR): 0.37 (Confidence interval (95% CI): 0.26-0.54), p &lt; 0.001). In multivariate analysis, optimal surgical procedure performance is an independent factor for disease-free survival with HR at 2.04 (95% CI: 1.14-3.68), p = 0.01. There is a significant difference in overall survival in favor of patients undergoing surgery according to the recommendations, (HR: 0.31 (95% CI): 0.19-0.49), p &lt; 0.001. In multivariate analysis, there is a trend toward significance with HR: 2.24 (95% CI: 1-5.05), p = 0.05. Older patients, patients with a larger BMI, patients with no indication of LAL at the preoperative ESMO classification, and no node involvement in are factors contributing to the decision of not to perform a LAL: p &lt; 0.001, p = 0.03, p &lt; 0.001 and p &lt; 0.001 respectively. Conclusions: This study shows that patients with early type 1 endometrial cancer have improved recurrence-free survival and a statistical trend for an increased overall survival when recommended surgery is performed. Despite the current context of therapeutic de-escalation, we must strive to achieve the recommended optimal surgery, even if it requires secondary surgical revision, to avoid underestimation of patients with a poorer prognosis. To improve endometrial cancers management, amelioration of the preoperative assessment by increasing the sensitivity of emboli detection should be considered.

Lymph node dissection in endometrial cancer and clinical outcome: A population-based study in 5546 patients

BackgroundAccording to current treatment guidelines, comprehensive surgical staging procedures in endometrial cancer confined to the uterus depend on uterine risk factors: a systematic lymph node dissection (LND) is recommended in high risk patients and should be omitted in low risk patients. Its role in intermediate and high intermediate risk patients is inconclusive. The aim of this analysis was to review the implementation of this risk-adopted strategy. Materials and methodsData were provided by the population-based Munich Cancer Registry. Patients with endometrial cancer diagnosed between 1998 and 2016 were included. ResultsOf 5446 eligible patients, 58.5%, 30.1% and 11.4% belonged to the low risk, intermediate/high-intermediate and high risk group, respectively. Lymph node dissection was performed in 20.2%, 53.0% and 63.7% within these groups. Lymph node involvement was diagnosed in 1.7%, 9.6% and 19.3%, respectively. Within these risk groups, there was no significant difference in the time to local recurrence, lymph node recurrence or distant metastases between patients with and without LND. After adjusting for age and comorbidity-status, no significant difference in overall survival was found. ConclusionsThe application of a risk-adopted management of LND in early endometrial cancer in real-life is associated with a high rate of surgical under- and overtreatment. Corresponding survival data do not show a significant benefit of a systematic lymph node dissection. In order to improve the management and outcome of early endometrial cancer in the future, prospective trials, new surgical concepts and prognostic markers will be primary and necessary.

MON-310 Oncogenic Roles of Tripartite Motif 25 in Endometrial Cancer

The tripartite motif (TRIM) family proteins are known for their structure typically composed of integrated three components of RING, B-box and coiled-coil domains. Some of the TRIM proteins have been paid attention as they contribute to the development and progression of cancers. We previously identified that TRIM25/Efp promotes breast cancer proliferation by exerting its E3 ubiquitin ligase function to degrade a cell cycle checkpoint 14-3-3σ. TRIM25 also plays a critical role in antiviral immunity and interferon production by interacting with the DExD/H box RNA helicase family proteins. During the antiviral signaling, TRIM25 is involved in the activation of transcription factors such as nuclear factor κB (NF-κB). In the present study, we investigated whether TRIM25 contributes to the pathophysiology of endometrial cancer, one of the major gynecological tumors with an increasing incidence especially among postmenopausal women. In both estrogen receptor (ER)-positive and -negative endometrial cancer cells, the knockdown of TRIM25 substantially repressed the cell proliferation and migration. As expected, TRIM25 knockdown in endometrial cancer cells increased 14-3-3σ protein levels and decreased the cell population at proliferative stage. Moreover, TRIM25-specific siRNAs could successfully suppress the in vivo tumor growth of endometrial cancer cells in both subcutaneous and orthotopic xenograft models. Microarray analysis showed that genes involved in NF-κB-dependent pathway were particularly downregulated in endometrial cancer treated with TRIM25-specific siRNAs. Stable expression of TRIM25 substantially promoted the proliferation of endometrial cancer cells. Taken together, TRIM25 plays an oncogenic role in endometrial cancer by modulating 14-3-3σ protein degradation and NF-κB pathway. TRIM25 and its interacting factors would be potential diagnostic and therapeutic targets for clinical management of endometrial cancer.

SP-0122 Integration of molecular prognostic factors in the management of endometrial cancer

SP-0122 Integration of molecular prognostic factors in the management of endometrial cancer

Evaluation of the French medical practices in endometrial cancer management by using quality indicators

Study objectiveTo evaluate the French quality of care of endometrial cancer using published relevant quality indicators and researche explanatory factors influencing its management. Study designWe used databases from the “Echantillon Généraliste de Bénéficiaires”, sample of the French population, to identify cases operated on between 2005–2014. Quality indicators evaluated were: three years survival rate, time between surgery and adjuvant treatment, use of IRMT and 3DCRT for radiotherapy, rate of minimally invasive surgery. Multilevel analysis was performed to identify explanatory factors. Results405 women were included. 323 had a follow-up of more three years, and 250 were alive at three years (77.0%). 70 (17.3%) underwent minimally invasive surgery. 73 women of the 153 who received adjuvant treatment (47.8%) started it within 60 days after surgery. Among the 60 patients who received adjuvant radiotherapy, 50 (83.3%) underwent the IRMT or 3DCRT technique. In multilevel analysis, diabetes (OR = 1.24: 95% CI [1.08; 1.41]), and age under 65 (OR = 1.15: 95% CI [1.01; 1.35]) were associated with an increase of the three years survival rate.Lymphadenectomy (OR = 1.12: 95% CI [1.03; 1.22]), and management in an university institution (OR = 1.13: 95% CI [1.01; 1.25]) were associated with adequate technique for the adjuvant radiotherapy. Laparoscopic surgery increased after 2010 (OR = 1.18: 95% CI [1,10; 1,25]). ConclusionImprovements should be made to increase the rate of laparoscopy and reduce the delay before adjuvant treatment for the management of endometrial cancer in France, specifically in non-university centers.

Possible role of Thiazolidinedione in the management of Type-II Endometrial Cancer

Type-II Endometrial Cancer (EMC) is one of the most common types of gynaecological cancer affecting more than 2.7 million people worldwide. Clinical evidence shows that adipokines levels are abnormally altered in Type-II EMC and reported to be one of the major responsible factor for uncontrolled proliferation and metastasis in Type-II EMC. Reversing the altered adipokine levels, therefore, help to control Type-II EMC proliferation and metastasis. In the present hypothesis we focus on the possible role of Thiazolidinediones in favourably altering the adipokine levels to benefit in the management of Type-II EMC.

Fertility Preservation in Gynecologic Cancer.

To review current conservative fertility-sparing options for patients undergoing surgical and medical management of cervical, endometrial, and ovarian cancers. Standard and investigational fertility preservation alternatives using assisted reproductive technologies are described. A review of articles dated 2006-2018 from PubMed. While a frequently reported concern among female cancer survivors of childbearing potential, fertility preservation education and procedures continue to be an unmet need for this population. Knowledge of current fertility-sparing options is imperative for nurses to ensure fertility preservation is introduced early, and often, into education for patients from diagnosis, through treatment, and in survivorship.

Evolving trends in the management of high-intermediate risk endometrial cancer in the United States

ObjectiveGynecologic oncology group protocol 249 (GOG 249) is the contemporary US study that aimed to define the standard of care adjuvant therapy for patients with high-intermediate risk (HIR) endometrial cancer; patients were randomized to pelvic radiation therapy (RT) or vaginal brachytherapy (VBT) with chemotherapy (VBT-C). The preliminary results of GOG 249 were recently presented, yet the management of patients represented in this trial remains controversial. We set out to review US patterns of care for patients meeting eligibility criteria for GOG 249. MethodsThe National Cancer Database (NCDB) was used to identify patients meeting GOG 249 eligibility criteria between 2010 and 2015. The Man-Kendall trend test was used to assess for significant trends over time. ResultsWe identified 23,015 patients that met study inclusion criteria. Between 2010 and 2015, there was a decline in the use of pelvic RT from 9.8% to 7.5%, although not meeting statistical significance (p = 0.136), and an increase in the use of VBT-C from 4.6% to 7.7% (p = 0.017). Most patients did not receive treatment per either arm of GOG 249, with observation being the most common approach throughout this era, although the percentage of patients observed decreased from 58.1% to 45.8% between 2010 and 2015 (p = 0.003). Further, 21.5% of patients received VBT alone in 2010, increasing to 30.3% by 2015 (p = 0.003). ConclusionsNational practice trends in HIR endometrial cancer reveal that a large number of patients are observed in lieu of receiving adjuvant therapy. Further, the utilization of pelvic RT has declined below utilization of VBT-C, despite a lack of data supporting either improved disease outcomes or toxicity with this experimental regimen on GOG 249.

Impact of treatment duration in fertility-preserving management of endometrial cancer or atypical endometrial hyperplasia

Fertility preservation is an option for selected patients with endometrial hyperplasia or cancer. This study aimed to evaluate whether duration of treatment impacts the oncologic and reproductive outcomes. We retrospectively reviewed patients diagnosed with endometrial cancer/atypical endometrial hyperplasia who underwent fertility-sparing treatment from January 2012 to December 2016. As the duration of treatment required by the patients was different, the patients who achieved a complete response were grouped according to the treatment duration as groups A (≤6 months), B (6-9 months), and C (>9 months). With the prolongation of treatment duration from 6 months to 9 months to >9 months, the accumulative complete response rates for 67 patients were 58%, 76%, and 95.5%, respectively. Among groups A, B, and C there was no significant difference in the relapse rates (21.1%, 25%, and 36.4%, respectively, p=0.60) or the median time interval to relapse (14, 13, and 13.5 months, respectively, p=0.90). Maintenance treatment was an independent protective factor for recurrence (p=0.001), while the complication of diabetes was an independent risk factor for recurrence (p=0.03). Fertility rates (31%, 18.2%, and 62.5%, respectively, p=0.12) and the time interval to pregnancy (14, 13, and 8 months, respectively, p=0.67) were not significantly different among the three groups. Assisted reproductive technology was positively associated with a higher pregnancy rate (p=0.02) and a body mass index ≥25 kg/m2 was negatively associated with the pregnancy rate (p=0.047). Longer treatment duration was associated with higher rates of complete response. Longer treatment duration (>9 months) was not associated with a decrease in success rates of pregnancy.

Para-aortic Lymph Node Invasion in High-risk Endometrial Cancer: Performance of 18FDG PET-CT.

18F-Fluorodeoxyglucose positron-emission tomography integrated with computed tomography (18FDG PET-CT) is a non-invasive examination that could be helpful for the management of endometrial cancer. This study investigated the performance of 18FDG PET-CT in assessing para-aortic (PA) lymph-node involvement in high-risk endometrial cancer. This was a retrospective, single-center study carried out between 2009 and 2018. The inclusion criteria were high-risk and locally advanced type 1 or 2 endometrial cancer with 18FDG PET-CT before PA lymphadenectomy. During the study period, among 142 patients with high-risk endometrial cancer, 35 patients (24.6%) underwent 18FDG PET-CT followed by PA lymphadenectomy. In 25% of cases, PA lymphadenectomy was not performed due to the discovery of metastasis. 18FDG PET-CT had a sensitivity of 50%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 75%, accuracy of 80% and an area under the curve of 0.75 for the evaluation of PA involvement. According to its high specificity in PA lymph-node evaluation, a positive PET scan might allow PA lymphadenectomy to be avoided.