Non-endometrioid Endometrial Cancer Research Articles

The Results of Surgico-Pathologic Factors in Patients with Non-Endometrioid Type Endometrial Cancer: Is Tumor Type Important for Lymph Node Metastasis?

The Results of Surgico-Pathologic Factors in Patients with Non-Endometrioid Type Endometrial Cancer: Is Tumor Type Important for Lymph Node Metastasis?

The prognostic significance of aortic lymph node metastasis in endometrial cancer: Potential implications for selective aortic lymph node assessment

ObjectivesTo evaluate the prognostic impact of aortic vs. pelvic lymph node (LN) metastasis among women with endometrial cancer (EC). MethodsUsing data from the SEER 18 Registries we identified 3650 women with LN positive (stage IIIC) EC. We used Kaplan-Meier curves and log-rank tests to compare mortality between women with stage IIIC1 and IIIC2 disease. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between stage III sub-stage (IIIC1 vs. IIIC2) and survival. ResultsEndometrioid tumors were more common among women with stage IIIC1 than IIIC2 tumors (62.5% vs. 54.3%) while, non-endometrioid histologies were more common among stage IIIC2. In the multivariable model, stage IIIC2 was associated with higher all-cause (HR = 1.44, 95% CI = 1.22–1.69) and EC-specific mortality (HR = 1.49, 95% CI = 1.25–1.77) compared with IIIC1. Women with non-endometrioid EC had poor survival, in particular, women with carcinosarcomas had higher EC-specific mortality compared to women with endometrioid EC (HR = 3.32, 95% CI = 2.71–4.07). When stratifying women according to substage, older age and non-endometrioid histology were associated with higher EC-specific mortality. Compared to women with a pelvic-only LN dissection, women with pelvic and aortic dissections had lower all-cause (HR = 0.74, 95% CI = 0.63–0.88) and EC-specific (HR = 0.79, 95% CI = 0.66–0.95) mortality. ConclusionWomen with aortic LN positive EC are more likely to die from their disease. Older women and non-endometrioid histologies are more likely to have aortic LN involvement. Compared to women with a pelvic-only LN dissection, women with pelvic and aortic dissections had lower EC mortality.

Patterns of Failures and Clinical Outcome of Patients with Early-Stage, High-Risk, Node-Negative Endometrial Cancer Treated with Surgery Followed by Adjuvant Platinum-Based Chemotherapy and Vaginal Brachytherapy

Objective: To assess the clinical outcome of patients with high-risk early-stage endometrial cancer and negative pelvic nodes who received adjuvant platinum-based chemotherapy plus vaginal brachytherapy (VBT). Methods: This investigation assessed 80 patients who underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy for stage Ib-II, grade 2–3 endometrioid (n = 43) or stage Ia-II nonendometrioid (n = 37) endometrial cancer. Results: Five-year local control rate, 5-year disease-free survival, and 5-year overall survival were 97, 87, and 97%, respectively, for endometrioid carcinoma, and 66, 50, and 72%, respectively, for nonendometrioid carcinoma. Conclusions: This retrospective study appears to show that adjuvant platinum-based chemotherapy plus VBT achieve very good results in endometrioid carcinoma. This combined treatment seems to be less effective in nonendometrioid carcinoma.

Impact of gene-specific germline pathogenic variants on presentation of endometrial cancer in Lynch syndrome.

Lynch syndrome is a risk factor for developing endometrial carcinoma. Our aim was to evaluate the impact of gene-specific germline pathogenic variants on clinical features of patients affected by endometrial cancer. Patients with a diagnosis of endometrial cancer and with a germline pathogenic variant in mismatch repair genes were reviewed. Patients were classified on the basis of classes of risk according to the ESGO-ESGO-ESTRO (European Society of Medical Oncology/European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology) guidelines. One-way analysis of variance (ANOVA) and Kruskal-Wallis test were performed to compare three groups of continuous parametric and non-parametric variables, respectively. χ2 test was used to analyze proportions. Overall, 68 patients with endometrial cancer and Lynch syndrome were evaluated. Ten (14.7%) patients were excluded because of absence of information about the gene involved in Lynch syndrome, thus leaving 58 (85.3%) patients available for the final analysis. MLH1, MSH2, and MSH6 pathogenic variants were observed in 19 (32.7%), 33 (56.9%), and six (10.3%) patients, respectively. Mean±SD age at endometrial cancer diagnosis was 51±6.4, 43.5±7.4, and 60.3±8.8 years (p=0.0002). Prevalence of non-endometrioid endometrial cancer was 15.7%, 24.2%, and 0% in the MLH1, MSH2, and MSH6 groups, respectively (p=0.345). According to the ESMO-ESGO-ESTRO classification, low, intermediate, and high risk endometrial cancer accounted for 47.3%, 10.5%, and 42.1% of the MLH1 group, 57.6%, 3%, and 39.4% of the MSH2 group, and 50%, 50%m and 0% of the MSH6 group (p=0.009). Patients with MLH1 and MSH2 pathogenic variants are at a higher risk of early onset of endometrial cancer than patients with MSH6 pathogenic variants.

Vaginal Brachytherapy for Stage I-II Non-endometrioid Endometrial Cancer Using a Low-dose Scheme

To evaluate outcomes for women with FIGO stage I-II non-endometrioid endometrial adenocarcinoma treated with adjuvant vaginal brachytherapy (VB) using a low-dose scheme with or without adjuvant chemotherapy (CT). We retrospectively identified 122 women with FIGO stage I-II non-endometrioid endometrial cancer (serous carcinoma [SC], clear cell carcinoma [CC], mixed histology [MH, endometrioid and SC or CC components], carcinosarcoma [CS]) who received VB to 24 Gy in 6 fractions from 2005 – 2017. Dose was prescribed to the cylinder surface of the full vaginal length. CT imaging was performed prior to each fraction to confirm cylinder diameter and insertion depth. Women with < 6 months follow-up from VB completion were excluded (n = 16). Rates of vaginal relapse (VR), pelvic relapse (PR), distant metastasis including para-aortic relapse (DM), recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Univariate analyses (UVA) were performed using logrank test or Cox proportional hazards. Multivariable analyses (MVA) using Cox proportional hazards modeling with backwards selection was used to identify independent predictors of RFS. Characteristics of the 106 eligible patients are summarized in Table 1. At a median follow up of 49 months (r, 9 – 119) from surgery, 26 women developed recurrence at a median of 39 months (r, 12 – 119), and 14 died of disease. The 5-year rates of VR, PR, DM, RFS and OS were: 7%, 8%, 21%, 74% and 83%, respectively. On UVA, age, histology, lymphovascular invasion (LVI), stage and %MMI were associated with RFS (all p < 0.05). By histology, the 5-year RFS rates were 77%, 68%, 88% and 56% for SC, CC, MH and CS, respectively (p = 0.046). On MVA including stage, histology and LVI, only stage remained significantly associated with RFS (hazard ratio [HR] 2.8 [95%CI: 0.96 – 7.39] for IB vs IA; HR 4.9 for II vs IA [95%CI: 1.34 – 14.77]; p=0.018). 5-year PR was higher for women with CS compared to other high-risk histologies (20% vs 6%; p = 0.017), while VR and DM did not significantly differ. Clinical outcomes for patients with early-stage, non-endometrioid endometrial cancer varied significantly by histologic subtype. Women with CS had significantly higher rates of pelvic relapse after VB, compared to those with other high-risk histologies.Abstract TU_19_3509: Table 1Univariate PAge (med, range)66 yr (40-93)0.029BMI (med, range)28 (20-53)0.352FIGO 2009 Stage IA IB II80% (85) 14% (15) 6% (6)0.004Histology Serous carcinoma (SC) Clear cell carcinoma (CC) Mixed histology (endometrioid and SC/CC) Carcinosarcoma (CS)47% (50) 10% (11) 27% (29) 15% (16)0.046No. of pelvic LN (med, range)13 (0-44)0.560No. of para-aortic LN (med, range)0 (0-14)0.788%MMI (med, range)10% (0-99)0.044LVI13% (14)0.001Positive pelvic washings12% (13)0.100Adjuvant chemotherapy SC CC MH CS75% (79) 90% (45) 73% (8) 63% (10) 55% (16)0.197Patterns of failure Vaginal Pelvic Distant Combined local-regional & distant6% (6) 7% (7) 20% (21) 7% (7)NA Open table in a new tab

Survival Outcomes of Stage IIIC Endometrioid and Non-Endometrioid Endometrial Cancer Treated with Combined Modality Adjuvant Therapy

The optimal adjuvant treatment for stage IIIC endometrial cancer remains controversial with the recent report of GOG 258 and PORTEC-3 leading to potentially conflicting conclusions about the benefit of combined modality treatment. These randomized trials included endometrioid and non-endometrioid subsets although they are known to have different patterns of recurrence. We aimed to identify the adjuvant treatment regimen associated with the best survival outcomes for histologic subsets. Patients with clinical or pathological stage IIIC who underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymph node sampling between 2/1985 – 9/2015 were identified. Median follow-up time from the time of surgery for these 282 patients was 56 months (range, 2-325 months). The Kaplan-Meier method was used to calculate overall survival (OS), disease specific survival (DSS), and pelvic disease control from the time of surgery. Comparisons between patient and treatment characteristics were assessed using log-rank tests. Univariate and multivariable analyses were calculated using Cox proportional hazards modeling. Among patients with endometrioid histology (n=177), 87% received external beam radiation therapy (EBRT); the most common regimen was concurrent chemoradiation followed by adjuvant chemotherapy (34%). The majority of patients with non-endometrioid (serous, clear cell, carcinosarcoma, adenosquamous; n=105) and grade 3 (n=143) histologies received chemotherapy with or without EBRT at rates of 84% and 80%, respectively; adjuvant chemotherapy alone was utilized in 44% and 37% of patients, respectively. OS, DSS, and pelvic disease control for all patients at 5 years was 63%, 65%, and 77%. Among the grade 1/2 endometrioid subset, 5-year DSS was 80% for EBRT alone and 84% for chemoradiation (p=0.8); grade 3 endometrioid patients had rates of 58% and 66%, respectively (p=0.6). For non-endometrioid patients, 5-year DSS improved with chemoradiation (72%) as compared to chemotherapy alone (42%; p<0.02). Age >60 (HR 2.39 [95% CI 1.57-3.63], p<0.001), non-endometrioid histology (HR 2.27 [95% CI 1.22-4.23], p=0.01), grade 3 (HR 2.62 [95% CI 1.65-4.14], p<0.001), adnexal involvement (HR 1.65 [95% CI 1.08-2.50], p=0.02), and >50% myometrial invasion (HR 2.47 [95% CI 1.55-3.91], p<0.001) were independently associated with lower DSS. Pelvic failure was associated with death (HR 1.68 [95% CI 1.08-2.60], p=0.02). Patients with gross disease who received EBRT with a boost experienced a similar high rate of pelvic disease control as patients without gross disease treated with EBRT without a boost (92% vs. 90%, p=0.8). Patients with endometrioid cancer had similar outcomes if treated with EBRT with or without chemotherapy. Combined modality treatment resulted in higher rates of DSS and pelvic disease control in patients with non-endometrioid high-risk histology as compared to patients who received chemotherapy alone.

Antidiabetic Medication, Statins and the Risk and Prognosis of Non-endometrioid Endometrial Cancer in Women with Type 2 Diabetes.

To determine the incidence and prognosis of non-endometrioid endometrial cancer (EC) in relation to the use of metformin, other antidiabetic medication (ADM) and statins in patients with type 2 diabetes (T2D). In order to analyze the incidence and prognosis of non-endometrioid EC, two cohorts were obtained from a nationwide diabetes database (FinDM); 57 non-endometrioid ECs were observed in a cohort of 92,366 women with newly-diagnosed T2D during the follow-up (1996 to 2011) to assess the incidence, and a retrospective cohort of 105 women with T2D diagnosed with non-endometrioid EC (1998 to 2011) was used to estimate cumulative mortality from EC and other causes of death. Hazard ratios (HRs) with 95% confidence intervals (CIs) for EC incidence were estimated in the full-cohort analysis and in the nested case-control analysis, matched for age and duration of T2D. Cumulative mortality was estimated by using the Aalen-Johansen estimator. Cause-specific mortality rates were analyzed by using Cox models regarding the pre-diagnostic use of different forms of ADM and statins. In the nested case-control analysis, the use of metformin was not associated with the risk of non-endometrioid EC (HR=1.09, 95% CI=0.59-2.00), whereas statin use was associated with a lower risk (HR=0.47, 95% CI=0.26-0.84). The results from the full-cohort analysis supported these findings. Mortality from non-endometrioid EC was not different between users of metformin and other types of oral ADM (HR=1.56, 95% CI=0.40-6.07) but was observed to be lower in statin users (HR=0.41, 95% CI=0.20-0.82). Our findings were inconclusive regarding the association of metformin with the risk and prognosis of non-endometrioid EC. However, statin use was associated with a lower incidence and mortality from this disease.

Lower uterine segment involvement in non-endometrioid endometrial cancer is correlated with a lack of driver mutations and unfavorable outcome

Lower uterine segment involvement in non-endometrioid endometrial cancer is correlated with a lack of driver mutations and unfavorable outcome

Association of obesity with survival in patients with non-endometrioid endometrial cancer

Objective: Obesity confers an overall increased risk for development of endometrial cancer. However, there are conflicting reports regarding the effect of obesity on patients’ overall and disease-specific survival. The purpose of this study was to evaluate the effect of obesity on survival in women with endometrial cancer.

LONG-TERM RESULTS OF TREATMENT OF ENDOMETRIAL CANCER OF HIGH-RISK STAGE I DEPENDING ON THE MORPHOLOGICAL TUMOR TYPE

The work is devoted to the study of the long-term results of treatment and the effect of adjuvant chemotherapy on the survival of patients with endometrial cancer (EC) of high-risk stage I, depending on the histological tumor type. The study included 225 patients with endometrial cancers of the IBG1 stage and nonendometrioid stage I cancer (serous, clear cell, undifferentiated carcinoma, carcinosarcomama) who received treatment in Belarus in 2006–2010. The overall (OS), cancerspecific (CSS) and disease-free (DFS) 5-year survival in high-risk EC was 66.7 ± 3.2, 77.4 ± 2.9 and 77.0 ± 2.9 % 10-year-old – 53.7 ± 4.5, 69.7 ± 4.2 and 69.3 ± 4.2 % respectively. There were no statistically significant differences in the survival, depending on the morphological tumor type, but the endometrioid carcinoma of the IBG3 stage is defined as the most favorable form of the high-risk EC, and the undifferentiated carcinoma and carcinosarcoma are the most unfavorable forms. There were no statistically significant differences in OS, CSS and DFS between the endometriod carcinoma of the IBG3 stage and the nonendometrioid forms of the EC stage I and the difference in the 5-year survival was about 10 % in favor of endometrioid carcinoma. Adjunctive chemotherapy did not improve the long-term outcome of treatment in general, as well as separately in the IBG3 stage of the endometrioid carcinoma stage and the nonendometrioid EC stage I. In the both groups, the difference in the 5-year OS was about 10 % in favor of the subgroups with chemotherapy. Thus, the question of the role of chemotherapy in treatment with high-risk EC is not resolved and requires further research.

Is Omentectomy Necessary for Non-Endometrioid Endometrial Cancer

Background: In subtypes of non-endometrioid endometrium cancers (non-ECC), it is not clear whether the omentectomy is a part of debulking if visual assessment is normal. Recently, the ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group in their report titled “Endometrial Cancer: diagnosis, treatment and follow-up” recommended that omentectomy be performed in the serous subtype, but not in carcinosarcoma, undifferentiated endometrial carcinoma or clear cell. In this study, the question is whether omentectomy should be a part of a staging procedure in patients with non-ECC. Besides, the sensitivity and specificity of the visual assessment of omentum were analyzed. Methods: Patients diagnosed with non-ECC in 2 gynecological oncology clinics between 2005 and 2015 were retrospectively reviewed. Occult (absence of visible lesions) and gross (presence of visible lesions) omental metastasis rates of histological subtypes were analyzed. Results: We identified 218 patients with non-ECC. Thirty-four of them (15.1%) had omental metastases and 44.1% of these metastases (n = 15) were occult metastases. The sensitivity of the surgeon's visual assessment of an omentum (positive or negative) was 0.55. The highest rate of omental metastasis was found in carcinosarcoma followed by serous, mixed subtypes, and clear-cell (20.4, 17.3, 16.6, 10.0%, respectively). Adnexal metastasis was the only factor associated with occult omental metastasis (p = 0.003). Conclusion: Omental metastases occur too often to omit omentectomy during surgical procedures for non-ECC regardless of histological subtypes, and visual assessment is insufficient in recognizing the often occult metastases. Omentectomy should be a part of the staging surgery in patients with non-ECC.

Population-based cohort study of the effect of endometrial cancer classification and treatment criteria on long-term survival.

To evaluate if increased individualization in endometrial cancer classification/treatment affected relative survival. The present retrospective register-based population study included data from all women in the western Swedish healthcare region who were treated for endometrial cancer between January 1, 1995, and December 31, 2011. Outcomes and prognostic data were retrieved from the western Swedish healthcare region's cancer and clinical endometrial cancer registries. Patients were stratified based on two different treatment programs (cohort 1 January 1, 1995, to September 10, 2006, and cohort 2 September 11, 2006, to December 31, 2011) and relative survival was compared. Data from 4338 patients were included; 2936 in cohort 1 and 1402 in cohort 2. Among endometrioid endometrial carcinomas, the 5-year relative survival rate for did not differ significantly between the groups (P=0.751); radiotherapy was used more frequently in cohort 1 (P<0.001). Among non-endometrioid endometrial carcinomas, relative survival was lower in cohort 1 (P=0.006); radiotherapy use was more frequent in cohort 1 and chemotherapy use was more frequent in cohort 2 (P=0.001). Increased individualization in endometrioid endometrial cancer management did not improve relative survival. Improved relative survival was observed for non-endometrioid endometrial cancer; possibly due to increased adjuvant chemotherapy use. This article is protected by copyright. All rights reserved.

Expression of PD-1, PD-L1 and PD-L2 is associated with differentiation status and histological type of endometrial cancer.

Endometrial cancer (EC) is the most frequent gynecological malignancy and a major cause of morbidity and mortality for women worldwide. Programmed cell death protein 1 (PD-1) and its ligands programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) have been well studied in lung cancer, melanoma and renal-cell cancer. However, few studies have been performed in EC. The purpose of the present study was to assess the expression of PD-1, PD-L1 and PD-L2 in 35 human normal endometrial tissue samples and 75 human EC tissue samples using immunohistochemical staining. It was found that 61.3% of ECs were positive for PD-1 staining, which was almost exclusively found in the tumor-infiltrating immune cells. By contrast, PD-1 was not expressed in the tumor cells or normal endometrial tissues. It was also found that 14.3% of normal endometria and 17.3% of EC tissues were positive for PD-L1 expression, while 20.0% of normal endometrium and 37.3% of EC tissues were positive for PD-L2 expression; however, there was no statistically significant difference between the normal endometrium and EC tissues. PD-1 expression in the tumor-infiltrating immune cells was more frequently found in the moderately and poorly-differentiated ECs and non-endometrioid (type II) ECs than in the well-differentiated ECs and endometrioid (type I) ECs. Similarly, PD-L1 and PD-L2 expression in the tumor-infiltrating immune cells was more frequently found in the moderately and poorly-differentiated ECs and type II ECs than in the type I ECs. The present findings indicate a possible better outcome for future treatment with anti-PD-1 or anti-PD-L1 antibody-based therapies against these subgroups of endometrial cancers with frequent expression of the PD-1/PD-L1/PD-L2 axis.

Bone recurrence rarely seen in endometrial cancer and review of the literature

To evaluate the clinical findings and treatment results of patients with endometrial cancer (EC) who experienced initial recurrence or progression in bones. Ten EC patients experiencing initial recurrence or disease progression in bones were included in the study. Disease recurrences located in a single bone and in more than one bone were defined as single localization bone recurrence (BR) and multiple localization BR, respectively. Time from initial surgery to BR was determined as disease-free interval (DFI) and time from BR to death or last contact with a patient was described as post-recurrence survival (PRS). Seven of 10 patients were asymptomatic. The median DFI was 13 months (range: 2-68). While eight patients had isolated BR, two patients also had concurrent extraosseous recurrences. Five patients had single and four patients had multiple localization BR. The most common sites for BR were the femur (55.5%) and vertebra (44.4%). Two-year PRS was 37.5% in all patients and 50% in patients with endometrioid EC. None of the patients with non-endometrioid type EC survived. In patients with multiple localization BR and with recurrence only occurred in the bones, two-year PRS was 75% and 50%, respectively. None of the patients with BR with extraosseous involvement survived beyond two years. Two-year PRS was 50% in patients without extraosseous dissemination, independent from localization. The BR rate was remarkable in asymptomatic EC survivors. A single bone was frequently involved. Little is known of the optimal treatment for metastatic bone disease in EC, thus, management should be individualized and patients should be encouraged to participate in clinical trials.

Adjuvant concurrent chemoradiation followed by chemotherapy for high-risk endometrial cancer

ObjectiveThe adjuvant treatment of high-risk endometrial cancer (HREC) remains controversial. This prospective phase-II clinical trial was conducted to evaluate the adjuvant concurrent chemoradiotherapy followed by chemotherapy in patients with HREC. MethodsAltogether 122 patients were enrolled between January 2007 and January 2013, in which 112 were analyzable. The inclusion criteria included endometrioid endometrial cancer of histological grade 3 and with greater than 50% myometrial invasion, cervical stromal invasion, pelvic and/or para-aortic lymph node metastases; non-endometrioid endometrial cancer; no residual disease and distant metastases. Pelvic radiation was administered with cisplatin on days 1 and 28. Para-aortic radiation was administered with confirmed para-aortic lymph node metastases, and vaginal afterloading brachytherapy with cervical stromal invasion after total hysterectomy. Four courses of paclitaxel and carboplatin (PC) or cisplatin, cyclophosphamide and epirubicin (CEP) were administered at three-week interval after radiation. ResultsNinety-six patients (85.7%) completed the planned treatment. Treatment discontinuation was the result of toxicity (5/112, 4.5%), disease progression (8/112, 7.1%), and patients refusal (3/112, 2.7%). There was no life-threatening toxicity. Twenty-five (22.3%) patients recurred, in which 4 cases recurred in the field of radiation, and 13 (11.6%) patients died of endometrial cancer during follow-up. The estimated five-year progression-free survival and overall survival were 73% and 84%, respectively. Adverse effects were less common in patients who received PC than CEP (p=0.001). ConclusionsThis regimen demonstrated acceptable toxicity and good survival outcomes despite a preponderance (62.5%) of late stage disease. PC showed less adverse effects than CEP. A well designed randomized trial is under development. Clinical trial IDhttps://clinicaltrials.gov/: 070148-7.

Sentinel lymph node mapping in non-endometrioid endometrial cancer

Sentinel lymph node mapping in non-endometrioid endometrial cancer

927P - Adjuvant Sequential Radiotherapy and Chemotherapy in High-Risk Endometrial Cancer: Preliminary Analysis of a Phase Ii Clinical Trial in One Institution

ABSTRACT Aim: The management of high-risk endometrial cancer (HREC) and the sequence of chemotherapy and radiotherapy remain controversial. A prospective phase-II clinical trial was conducted to evaluate the sequence and toxicity of adjuvant chemoradiotherapy and chemotherapy in patients with HREC. Methods: Eligibility included endometrioid endometrial cancer with histologic grade 3 and greater than 50% myometrial invasion, or stromal invasion of the cervix, or pelvic lymph node metastases, or para-aortic lymph node metastases, or extrauterine disease confined to the pelvis; non-endometrioid endometrial cancer regardless of stage; with no gross residual disease and distant metastases. This study was designed to administer pelvic radiation (45 Gy/ 25 fractions), along with cisplatin (50 mg/m2) on Days 1 and 28. Vaginal afterloading brachytherapy (5 Gy/d, 6 fractions) was given for patients with stromal cervical invasion. External para-aortic intensity-modulated radiation was allowed for patients with confirmed para-aortic lymph nodes metastases. Four courses of paclitaxel (135 mg/m2) and carboplatin (AUC = 5), or cisplatin (50 mg/m2) and cyclophosphamide (600 mg/m2) and epirubicin (60 mg/m2) were allowed at 3-week intervals after RT completion. Results: Number of Events Estimated 3-year rate (%) Estimated 5-year rate (%) Recurrence in the field of radiation 4 5 5 Local-regional failure 7 10 13 Distant metastases failure 17 20 20 Progression-free survival 24 74 72 Overall survival 12 87 83 One hundred and three patients were enrolled between January 2007 and January 2011. Eighty-eight patients (85.4%) completed the planned treatment. Treatment discontinuation was the result of toxicity (4/103, 3.9%), disease progression (4/103, 3.9%), and patients refusal (3/103, 2.9%). Four patients died before completing therapy. There were no treatment-related deaths. Median follow-up was 35 months (range 3-80 months). Twenty-four (23.3%) patients recurred, in which 4 cases recurred in the field of radiation, and 12 cases died of endometrial cancer. The estimated 3-year and 5-year progression-free survival and overall survival were listed in table1. Conclusions: This treatment protocol demonstrated an excellent treatment completion rate and expected toxicity. Subsequent phase-III trials are warranted. Disclosure: All authors have declared no conflicts of interest.

Anti-diabetic doses of metformin decrease proliferation markers in tumors of patients with endometrial cancer

BackgroundMetformin has been associated with reduced cancer risk. The mechanisms underlying this cancer protective effect remain unknown. Methods“Window of opportunity” study of metformin in women with operable endometrial cancer (EC). Eleven newly diagnosed, untreated, non-diabetic patients with EC received metformin 500mg tid from diagnostic biopsy to surgery. Fasting plasma insulin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 1 (IGFBP-1) and insulin-like growth factor binding protein 7 (IGFBP-7) measurements were taken before and after metformin treatment. Ki-67, pAMPK, and pS6 immunohistochemistry staining was performed on the endometrial cancer before and after metformin treatment and was compared to a control group of 10 women with EC who did not receive metformin. ResultsMetformin was administered for a mean of 36.6days. None of the patients suffered side effects requiring withdrawal from the study. The study group comprised 8 patients with endometrioid EC, and 3 non-endometrioid EC, with a mean follow-up time of 57months. Mean plasma insulin (p=0.0005), IGF-1 (p=0.001), and IGFBP-7 (p=0.0098) were significantly reduced after metformin treatment. A clear reduction in ki-67 and pS6 expression was observed by both conventional light microscope analysis and digital image analysis with a significant mean reduction in percentage of cells staining for ki-67 (9.7%, P=0.02) and pS6 (31%, P=0.03). In the non-treated control group expression was similar between the biopsy and the surgical specimens. ConclusionsThis pilot trial presents biological evidence consistent with anti-proliferative effects of metformin in women with EC in the clinical setting.

Peritoneal cytology: A risk factor of recurrence for non-endometrioid endometrial cancer

ObjectiveWe compared the impact of positive peritoneal cytology on prognosis between patients with endometrioid and non-endometrioid endometrial carcinoma. MethodsWe retrospectively reviewed the medical records of 490 patients diagnosed with endometrial cancer between 2000 and 2012. These patients were divided into two groups: endometrioid and non-endometrioid histologies. We compared the patients' baseline characteristics, tumor recurrence patterns, and survival to determine the prognostic factors and how they differed between the two groups. ResultsOf the included patients, 448 had endometrioid histology and 42 had non-endometrioid histology. A total of 27 patients experienced tumor recurrence: 17 with endometrioid histology (4.0%) and 10 with non-endometrioid histology (23.8%). Compared to endometrioid type, non-endometrioid type exhibited higher rates of recurrence (p<0.01). Recurrence sites of the non-endometrioid group were mainly peritoneal seeding (p<0.01) and distant organ metastasis (p=0.02). Risk factors for tumor recurrence included patient age, stage of disease, and adjuvant treatment for endometrioid type. On the other hand, in cases of non-endometrioid endometrial cancer, positive peritoneal cytology was an independent prognostic factor regardless of tumor stage (HR, 15.34; 95% CI, 3.55–66.25; p<0.01). Among cases with non-endometrioid histology, median recurrence-free survival significantly differed between the negative peritoneal cytology group and the positive peritoneal cytology group (120months versus 22months, respectively; p<0.01). ConclusionsPositive peritoneal cytology is an independent prognostic factor for patients with non-endometrioid endometrial cancer.

Risk-scoring models for individualized prediction of overall survival in low-grade and high-grade endometrial cancer

ObjectiveOverall survival (OS) in endometrial cancer (EC) is dependent on patient-, disease-, and treatment-specific risk factors. Comprehensive risk-scoring models were developed to estimate OS in low-grade and high-grade EC. MethodsPatients undergoing primary surgery for EC from 1999 through 2008 were stratified histologically according to the International Federation of Gynecology and Obstetrics (FIGO) as either (i) low grade: grades 1 and 2 endometrioid EC or (ii) high grade: grade 3, including non-endometrioid EC. Associations between patient-, pathological-, and treatment-specific risk factors and OS starting on postoperative day 30 were assessed using multivariable Cox regression models. Factors independently associated with OS were used to construct nomograms and risk-scoring models. ResultsEligible patients (N=1281) included 925 low-grade and 356 high-grade patients; estimated 5-year OSs were 87.0% and 51.5%, respectively. Among patients alive at last follow-up, median follow-up was 5.0 (low grade) and 4.6years (high grade), respectively. In low-grade patients, independent factors predictive of compromised OS included age, cardiovascular disease, pulmonary dysfunction, stage, tumor diameter, pelvic lymph node status, and grade 2 or higher 30-day postoperative complications. Among high-grade patients, age, American Society of Anesthesiologists score, stage, lymphovascular space invasion, adjuvant therapy, para-aortic nodal status, and cervical stromal invasion were independent predictors of compromised OS. The two risk-scoring models/nomograms had excellent calibration and discrimination (unbiased c-indices=0.803 and 0.759). ConclusionPatients with low-grade and high-grade EC can be counseled regarding their predicted OS using the proposed risk-scoring models. This may facilitate institution of personalized treatment algorithms, surveillance strategies, and lifestyle interventions.