Uterine Corpus Cancer Research Articles

内膜ポリープ様隆起を呈した早期子宮体癌症例の診断に子宮鏡下手術が有用であった1例

内膜ポリープ様隆起を呈した早期子宮体癌症例の診断に子宮鏡下手術が有用であった1例

Major clinical research advances in gynecologic cancer in 2016: 10-year special edition.

In 2016, 13 topics were selected as major research advances in gynecologic oncology. For ovarian cancer, study results supporting previous ones regarding surgical preventive strategies were reported. There were several targeted agents that showed comparable responses in phase III trials, including niraparib, cediranib, and nintedanib. On the contrary to our expectations, dose-dense weekly chemotherapy regimen failed to prove superior survival outcomes compared with conventional triweekly regimen. Single-agent non-platinum treatment to prolong platinum-free-interval in patients with recurrent, partially platinum-sensitive ovarian cancer did not improve and even worsened overall survival (OS). For cervical cancer, we reviewed robust evidences of larger-scaled population-based study and cost-effectiveness of nonavalent vaccine for expanding human papillomavirus (HPV) vaccine coverage. Standard of care treatment of locally advanced cervical cancer (LACC) was briefly reviewed. For uterine corpus cancer, new findings about appropriate surgical wait time from diagnosis to surgery were reported. Advantages of minimally invasive surgery over conventional laparotomy were reconfirmed. There were 5 new gene regions that increase the risk of developing endometrial cancer. Regarding radiation therapy, Post-Operative Radiation Therapy in Endometrial Cancer (PORTEC)-3 quality of life (QOL) data were released and higher local control rate of image-guided adaptive brachytherapy was reported in LACC. In addition, 4 general oncology topics followed: chemotherapy at the end-of-life, immunotherapy with reengineering T-cells, actualization of precision medicine, and artificial intelligence (AI) to make personalized cancer therapy real. For breast cancer, adaptively randomized trials, extending aromatase inhibitor therapy, and ribociclib and palbociclib were introduced.

High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers.

Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients.

Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement.

Clinical practice guidelines for gynecologic cancers have been developed by many organizations. Although these guidelines have much in common in terms of the practice of standard of care for uterine corpus cancer, practice guidelines that reflect the characteristics of patients and healthcare and insurance systems are needed for each country. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to produce the third edition of the guidelines as an advanced form based on evidence-based medicine, considering up-to-date clinical trials and abundant qualified Korean data. These guidelines cover screening, surgery, adjuvant treatment, and advanced and recurrent disease with respect to endometrial carcinoma and uterine sarcoma. The committee members and many gynecologic oncologists derived key questions from the discussion, and a number of relevant scientific literatures were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, together with other details. The objective of these practice guidelines is to establish standard policies on issues in clinical areas related to the management of uterine corpus cancer based on the findings in published papers to date and the consensus of experts as a KSGO Consensus Statement.

A prediction model of survival for patients with bone metastasis from uterine corpus cancer

The aim of the study was to establish a predictive model of survival period after bone metastasis from endometrial cancer. A total of 28 patients with bone metastasis from uterine corpus cancer were included in the study. Data at the time of bone metastasis diagnosis, which included presence of extraskeletal metastasis, performance status, history of any previous radiation/chemotherapy and the number of bone metastases, were collected. Survival data were analyzed using Kaplan-Meier methods and Cox proportional hazard models. The most common site of bone metastasis was the pelvis (50.0%), followed by lumbar spine (32.1%), thoracic spine (25.0%) and rib bone (17.9%). The median survival period after bone metastasis was 25 weeks. The overall rate of survival after bone metastasis of the entire cohort was 75.0% at 13 weeks, 46.4% at 26 weeks and 42.9% at 52 weeks. Performance status of 3-4 was confirmed as an independent prognostic factor (Hazard ratio, 3.5; 95% confidence interval, 1.41-8.70) and multiple bone metastases tended to be associated with poor prognosis (Hazard ratio, 2.4; 95% confidence interval, 0.95-5.97). A prognostic score was calculated by adding up the number of these two factors. The 26-week survival rates after bone metastasis were 88.9% for those with a score of 0, 45.5% for those with a score of 1 and 0% for those with a score of 2 (P = 0.0006). This scoring system can be used to determine the optimal treatment for patients with bone metastasis from endometrial cancer.

1445P - Efficacy of rikkunshito, a Japanese herbal medicine, on nausea, vomiting and anorexia in patients with uterine cervical or corpus cancer treated with cisplatin and paclitaxel –A randomized phase II study

1445P - Efficacy of rikkunshito, a Japanese herbal medicine, on nausea, vomiting and anorexia in patients with uterine cervical or corpus cancer treated with cisplatin and paclitaxel –A randomized phase II study

Conditional Cancer Survival of the Corpus Uterine in the USA

Purpose To identify relative survival probabilities for corpus uterine cancer patients accounting for time already survived, as well as age, race, ethnicity, marital status, tumor stage, and tumor grade at diagnosis. Methods Analyses are based on 78,147 women diagnosed with corpus uterine cancer during 2000-2008 and followed through 2013, using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program. Results Age, race, marital status, tumor stage, and tumor grade, but not ethnicity, significantly impacted relative cancer survival rates of the corpus uterine. Improvement in 5-year relative survival, when conditioned on 1-5 years already survived, occurs in each stage category, more so in later staged cases. The effect of age, race, marital status, and tumor grade on 5-year relative survival, after conditioning on years ( 1 - 2 - 3 - 4 - 5 ) already survived, varied by stage at diagnosis. For example, poorer prognosis with older age was only observed for regional and distant staged cases, but being married had a greater beneficial impact in regional and distant staged cases. The difference in 5-year relative survival rates diminished for age, race, marital status, tumor stage and grade when conditioned on years ( 1 - 2 - 3 - 4 - 5 ) already survived. The greatest improvement in 5-year conditional relative survival was in patients 70 years or older, Blacks, singles, later staged tumors, and higher grade tumors. Conclusions Reporting cancer survival estimates according to time already survived and demographic subgroups provide health-care providers and patients with more instructive prognostic information.

Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations

The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial. To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy. This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression. Incidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database. Among the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1-56.9; P < .001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2-35.5; P = .15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors. Although the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women.

Lymphovascular space invasion in uterine corpus cancer: What is its prognostic significance in the absence of lymph node metastases?

ObjectiveLymphovascular space invasion (LVSI) is a poor prognostic indicator in uterine cancer, primarily due to its association with lymph node metastases. We sought to determine if LVSI provides any prognostic information for uterine cancer subjects in the absence of nodal disease. MethodsA retrospective review was performed using a database of women treated for uterine cancer at MUSC from 2005 to 2012. Subjects with negative nodes after complete staging were identified. Multiple regression modeling was used to adjust for demographic and histopathologic covariates. The C-index was calculated for models of survival that included LVSI and those that did not. Competing risks analysis was conducted to examine factors associated with time to recurrence. ResultsTwo hundred and five subjects were completely staged and had negative nodes, 24 with LVSI and 181 without. Factors significantly associated with survival included age, race, stage, grade, histology, and LVSI. Regression models for recurrence-free survival (RFS) and overall survival (OS) had similar C-indices regardless of whether LVSI was included. Competing risks analysis confirmed no significant difference in time to recurrence for subjects with LVSI compared to those without, after adjusting for other prognostic factors (P=0.53). ConclusionsLVSI is associated with shorter recurrence-free and overall survival in uterine cancer subjects with negative lymph nodes. However, after adjusting for other prognostic factors, LVSI status does not provide additional prognostic information. This finding suggests that recurrence-free and overall survival for uterine cancer patients with negative lymph nodes can be estimated without factoring in LVSI.

Abstract LB-127: Enrichment of chromosome 1 and 6p21 genes associated with worse progression-free and overall survival in endometrial cancer patients

Abstract Endometrial cancers are generally considered to have favorable outcomes. However, recurrent, and/or non-endometrioid types and some high-grade endometrioid lesions often have very poor survival with limited treatment options. The genes specifically associated with these poor outcomes are not well described. The integrated genomic characterization of endometrial cancers was published in 2013 and the associated RNA-Seq data of these uterine corpus cancers are publicly available at The Cancer Genome Atlas [Nature 497 (7447):67-73]. However, studies on the association of gene expression with the overall survival and recurrence of these endometrial cancers are not yet reported. In this work, we identify those genes associated with survival and recurrence endpoints. RSEM Normalized RNA-Seq (UNC Illumina HiSeq RNASeq V2, level 3) data was downloaded from the TCGA website and survival data extracted from this resource. Cox regression analysis was performed using the survival package in R-environment. The cohort of the patients used in this study cover a large proportion of endometrioid type, while the remaining are serous and mixed histologic types. The proportion of grades 1 to 3 is 84:101:168 and stages I &amp; II (low) to III &amp; IV (high) is 263:87. The ratio of microsatellite unstable to stable cases is about 1:2 approximately both in living and diseased. The tissues were not micro-dissected leaving tumor infiltrates, stroma and other debris. This analysis identified 160 genes significant at p ≤ 0.001 for either overall survival and recurrence free survival or both. In the overall survival analysis, 82 genes were at hazard ratio (HR) ≥ 1 and 48 were at HR ≤ 1. We noted that chromosome 1 was over-represented among gene locations from these gene transcripts. In addition to enrichment of chromosome 1 genes we noted a cluster of genes located on 6p21 with elevated hazard ratios associated with poor clinical outcome. Ontology analysis of the survival associated genes was assessed by EASE software which pointed out the immune response genes have hazard ratios under 1 suggesting that it is a predominant mechanism associated with positive clinical outcome. The finding of immune response genes association with positive clinical outcome (HR ≤ 1) is provocative that prompts further investigation in the assessment and therapy of endometrial cancer. The enrichment of genes on chromosomes 1 and 6 offer further clues to the mechanisms underlying those endometrial cancers with poor clinical outcome. Citation Format: Rusheeswar Challa, GVR Chandramouli, Alyssa Fedorko, Thomas P. Conrads, John I. Risinger. Enrichment of chromosome 1 and 6p21 genes associated with worse progression-free and overall survival in endometrial cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-127. doi:10.1158/1538-7445.AM2015-LB-127

Lymph-vascular space invasion in uterine corpus cancer: What is its prognostic significance in the absence of lymph node metastases?

Lymph-vascular space invasion in uterine corpus cancer: What is its prognostic significance in the absence of lymph node metastases?

Hypertension and subsequent genitourinary and gynecologic cancers risk: a population-based cohort study.

Although a relationship between hypertension and the development of renal cancer and other types of cancer have been proposed for decades, the results of epidemiologic studies remain inconclusive. This study was conducted to evaluate the association between hypertension and genitourinary and gynecologic cancers in Taiwan.In this study, we conducted a populated-based retrospective cohort study by using data from the Taiwanese National Health Insurance program. The study period was from 2000 to 2011, and the cohort comprised 111,704 insurants: 57,961 patients with hypertension and 53,743 patients without hypertension. A Cox proportional hazard regression analysis was performed to estimate the effects of hypertension on genitourinary and gynecologic cancers risk.Among the patients with hypertension, the risks of developing renal and uterine corpus cancers were significantly higher in the hypertension group than they were in the nonhypertension group. Further stratified analyses by sex, age, and hypertension duration revealed distinct cancer-specific patterns. Higher cancer risk appears to be more obvious among younger hypertensive patients with longer follow-up time.The results of this study indicate that Taiwanese patients with hypertension have higher risks for some types of cancer, and cancer-specific patterns vary by sex, age, and hypertension duration.

Epidemiologic characteristics of uterine corpus cancer in Korean women

Epidemiologic characteristics of uterine corpus cancer in Korean women

National age standardized rate (ASR) of uterine corpus cancer (CC) correlates with Human Development Index (HDI), analysis of data from 154 countries

Objectives: To describe the associations between national CC incidence, HDI, and mean body mass index (BMI).

Genitofemoral neuropathy after pelvic lymphadenectomy in patients with uterine corpus cancer.

The aim of this study was to estimate the incidence, etiology, and outcomes of genitofemoral neuropathy after pelvic lymphadenectomy (PLD) for uterine corpus cancer. The medical records of women who underwent PLD for uterine corpus cancer between June 2001 and June 2013 were reviewed. Information regarding neuropathy was directly reported by each subject. Thirty-two of 300 patients undergoing PLD during the defined period experienced postoperative neuropathy due to genitofemoral nerve injury, for an incidence of 10.7%. The patients treated with PLD with para-aortic lymphadenectomy (PALD) exhibited a lower rate of genitofemoral neuropathy than those treated without PALD (4.3% vs 13.5%, P = 0.01). The laparoscopy group displayed a higher rate of genitofemoral neuropathy than the laparotomy group (19.1% vs 9.1%, P = 0.04). A total of 81.3% of the patients experienced a full recovery, with a medium time to resolution of 6 months (3-12 months). The administration of adjuvant chemotherapy, including paclitaxel, did not extend the time to recovery. Neuropathy resulting from genitofemoral nerve injury is not infrequent; however, most of the patients recover completely. In this study, the use of laparoscopic procedures increased the incidence of genitofemoral neuropathy, whereas that of PALD did not.

Gynecologic Cancer InterGroup (GCIG) consensus review for clear cell carcinoma of the uterine corpus and cervix.

Clear cell carcinomas of the uterine corpus and cervix are rare gynecological cancers with limited information regarding the pathogenesis and biology. At present, the approach to management is the same as for patients with the more common histological subtypes of endometrioid endometrial cancer and adenocarcinoma of the cervix. Surgical resection is the standard treatment for patients with early-stage disease, but there is no evidence-based approach to direct the management of patients with more advanced-stage disease at presentation or with recurrent disease. We review the epidemiology, pathology, and what is known about both uterine corpus and cervical clear cell cancers and make management recommendations.

Synthesis and characterization of tributyltin derivatives from 4‐oxo‐4‐(arylamino)butanoic acids and their in vitrobiological activity against cervical cancer cell lines

Uterine (cervix and corpus) cancer is one of the major causes of mortality in women in Mexico. Organotin carboxylated derivatives have shown high cytotoxic activity against various cell lines of human origin. We describe the synthesis of three new tri‐n‐butyltin derivatives from 4‐oxo‐4‐(arylamino)butanoic acids; their structures were confirmed using spectral data (1H NMR, 13C NMR, 119Sn NMR and infrared), elemental analyses, mass spectrometry and X‐ray diffraction. All the tri‐n‐butyltin carboxylates exhibit 1 J (119/117Sn–13C) coupling satellites in solution and lie in the range 357 to 339 Hz, suggesting a tetrahedral geometry around the tin atom. The polymeric structures of two of the derivatives and the monomeric structure of another were confirmed using X‐ray crystallography. Using succinic anhydride as raw material, five N‐substituted succinamic acid compounds were synthesized by the acylation reaction with aniline, 4‐nitroaniline, 4‐nitro‐3‐(trifluoromethyl)aniline, 2‐amino‐5‐nitrothiazole and 4‐aminoantipyrine. From these compounds, five tin derivatives were prepared and their in vitro anti‐proliferative effect on HeLa, CaSki and ViBo cell lines was screened. All of the compounds showed potency against all three strains and null or low cytotoxic activity (necrotic) as well. The most potent of our derivatives as an anti‐proliferative agent against the three cell lines was tributylstannyl 4‐oxo‐4‐[(3‐trifluoromethyl‐4‐nitrophen‐1‐yl)amino]butanoate, exhibiting an IC50 value of 0.43 μM against the HeLa cell line. Copyright © 2014 John Wiley &amp; Sons, Ltd.

Targeted Agents in Gynecologic Cancers

Citation: Ozgu E (2014) Targeted Agents in Gynecologic Cancers. Obstet Gynecol Int J 1(1): 00006. DOI: 10.15406/ogij.2014.01.00006 Submit Manuscript | http://medcraveonline.com In 21st century, cancer has become one of the leading causes of death especially in developed countries. On the other hand, gynecologic malignancies take an important part in women cancers that uterine corpus and ovarian cancers are in the ten leading cancer types for both new cases and deaths. While endometrial cancer is the most common gynecologic malignancy, ovarian cancer has the greatest mortality rate among them. Additionally cervical cancer is tremendously increasing especially in low socioeconomic regions [1]. Although using surgery for primary treatment is still essential for especially gynecologic cancers, investigations are aimed for developing new treatment modalities for decreasing the mortality and morbidity due to malignancies.

Mass spectrometry is a new approach to diagnosing adenomyosis and cancer of the corpus uteri

Sera from 60 apparently healthy women (mean age 40 years; a control group), 40 patients with a verified diagnosis of adenomyosis (mean age 41 years) and 42 patients with uterine corpus cancer (UCC) (mean age 58 years) were fractionated on magnetic beads with weak cation exchange surface, followed by an examination of the obtained fractions by time-of-flight mass spectroscopy (MS) with ma- trix-activated laser desorption/ionization. MS data analysis using classification algorithms, such as a genetic algorithm and a learning neural network, made it possible to construct mathematical models that were able to differentiate MS profiles of the above sample groups with a high specificity and a high sensitivity. The best values of the specificity and sensitivity of the classification models adenomyosis- control and UCC-control were 86.2, 93.8, 90.5, and 90.5%, respectively. Analysis of the statistical diagrams of these peak areas between different sample groups could identify 3 MS profile peaks for adenomyosis and 3 peaks for UCC.

A prospective study of gynecological cancer risk in relation to adiposity factors: cumulative incidence and association with plasma adipokine levels.

BackgroundAssociations of obesity and obesity-related metabolic factors (adiposity factors) with uterine corpus cancer (UCC) and ovarian cancer (OVC) risk have been described. Still, a cause-effect relationship and the underlying mediators remain unclear, particularly for low-incidence populations. We aimed to prospectively determine whether adiposity factors could predict the development of UCC and OVC in Taiwanese women. To explore the biological mediators linking adiposity factors to cancer risk, we examined the association of two adipokines, leptin and adiponectin, with the gynecological cancers.MethodsTotally, 11,258 women, aged 30–65, were recruited into the Community-Based Cancer Screening Program (CBCSP) study during 1991–1993, and were followed for UCC and OVC cases until December 31, 2011. Cox proportional hazard models were used to estimate hazard ratios (HRs). Adiposity factors and risk covariates were assessed at recruitment. Newly-developed cancer cases were determined from data in the government’s National Cancer Registry and Death Certification System. For adipokienes study, a nested case-control study was conducted within the cohort. Baseline plasma samples of 40 incident gynecological cancer cases and 240 age-menopause-matched controls were assayed for adipokines levels.FindingsThere were 38 and 30 incident cases of UCC and OVC, respectively, diagnosed during a median 19.9 years of follow-up. Multivariate analysis showed that alcohol intake (HR = 16.00, 95% = 4.83–53.00), high triglyceride levels (HR = 2.58, 95% = 1.28–5.17), and years of endogenous estrogen exposure per 5-year increment (HR = 1.91, 95% = 1.08–3.38) were associated with increased UCC risk. High body mass index (BMI≥27 kg/m2, HR = 2.90, 95% = 1.30–6.46) was associated with increased OVC risk. Analysis further showed an independent effect of adipokines on UCC and OVC risk after adjustment of the risk covariates.ConclusionWe provided evidence that alcohol intake, high triglyceride levels and long endogenous estrogen exposure increase UCC risk, whereas obesity positively predicts OVC risk. Circulating adipokines may mediate the link of adiposity factors to gynecological cancer risk.