Endometrium Cancer Research Articles

THE USE OF BEVACIZUMAB ALONE AND IN COMBINATION WITH CLASSICAL CHEMOTHEROPATHICS IN ISHIKAWA ENDOMETRIAL CANCER CELL CULTURE

Purpose: The aim of our study is to determine the effects of an antiangiogenic agent (bevacizumab) in combination with or without classic chemotherapeutics on the endometrium carcinoma and use these information in our clinic practice. Materials and Methods: In vitro tests were done to determine the cytotoxic and apoptotic effects of Cisplatin, Adriablastine and Bevacizumab. Cytotoxic effect was determined by the standard MTT assay (Tetrozolium Test) and apopthosis by DAPI staining, caspase-3 on human endometrium cancer cell culture (Ishikawa). Results: The MTT assay determined that 9.6 mg/ml dose of bevacizumab caused a higher rate of decrease in cell number on Ishikawa cells compared to the highest doses of Cisplatin and Adriablastine. Therewithal, when Bevacizumab, Cisplatin, and Adriablastine were applied together for 24 hours, the number of cells decreased with an increasing dose. With the use of the triple combination with DAPI staining, it is seen that the cell silhouettes are effaced and the findings indicating apoptosis become more apparent. When bevacizumab was applied alone, the caspase 3 activity it produced was ascertained to be higher than the other two drugs individually and in combination. Caspase-3 activity was ascertained to have increased significantly as a result of the collective usage of 40 µM Cisplatin + 20 µM Adriablastine + 9.6 µgram / ml Bevacizumab, and this was found to be the highest cytotoxic activity compared to other applications. Conclusion: Preclinical studies have shown that murine antihuman monoclonal antibody against Vascular Endothelial Growth Factor (VEGF) have promising activity in many gynecologic and non-gynecologic human tumors.

Transvaginal Real-Time Shear Wave Elastography in the Diagnosis of Endometrial Lesions.

BackgroundTo explore the value of transvaginal real-time shear wave elastography (SWE) in the diagnosis of endometrial lesions.MethodsA total of 140 female patients with endometrial lesions, confirmed by pathological results, were divided into three groups: 45 cases of endometrial polyps, 29 cases of endometrial hyperplasia and 66 cases of endometrial cancer. A total of 100 cases of normal endometrium were used as the control group, including 52 cases in the proliferative stage and 48 cases in the secretory stage. Transvaginal real-time shear wave elastography was performed in all four groups.ResultsEmean, Emax and Esd were expressed as the average standard deviation. Among the control group, the results were 26.24±9.74, 38.09±9.18, and 4.25±2.73 kPa, respectively, in the proliferative endometrium cases and 12.51±7.46, 27.22±11.32, 4.40±2.52 kPa, respectively, in the secretory endometrium cases. Among the experimental group, the result was 15.68±8.18, 27.28±10.28 and 3.62±1.81 kPa respectively in the endometrial polyps cases; 21.20 ± 12.57, 36.32 ± 15.04, and 5.09 ±3.93 kPa in the endometrial hyperplasia cases; 49.36±25.51, 86.66±42.27 and 14.86±10.63 kPa in the endometrial cancer cases. The difference was statistically significant (P <0.05). When the truncation values of Emean, Emax and Esd were 28.50, 52.45 and 9.05 kPa, respectively, to distinguish between normal endometrium and endometrial cancer, Emax has the highest diagnostic value.ConclusionReal-time SWE technology might be used as an auxiliary method in the diagnosis and differential diagnosis of endometrial cancer. More quantitative indicators are conducive to diagnosis.

Effects of Gallic Acid on Endometrial Cancer Cells in Two and Three Dimensional Cell Culture Models.

Background and Aim:Cell culture studies are an indispensable tools used to understand basic physiological, biophysical and biomolecular mechanisms. Although traditional two-dimensional (2D) cell culture models are more preferred in experimental studies, three-dimensional (3D) cell culture models, attract more attention due to several advantages including mimicking tumor physiology, biochemistry and biomechanics. We aimed to investigate the effects of Gallic Acid, an antimutagenic, antioxidant and anticarcinogenic agent, on both 2D and 3D cultured endometrial cancer cells for the first time. Methods:IC50 values were determined in 2D and 3D cultured endometrial cancer cells exposed to different doses of GA. In the 2D culture model exposed to GA, Caspase 3 expression levels were analyzed. In addition, the effect of GA on the migration of 2D cultured endometrium cancer cells was investigated. Results:IC50 value in the 3D model was found significantly higher than the 2D model. In 2D culture model, Caspase 3 expression and apoptosis was increased significantly in cells of GA exposed group compared to the control group. GA did not have a significant effect on the migration profile of cells. Conclusion:Gallic Acid is shown to induce apoptosis in Ishikawa cells via Caspase 3 activation. We demonstrated a significantly higher IC50 level in 3D model which provide evidence to prefer 3D models in drug-test trials. The data obtained in the current study will provide a basis for further experiments to analyze the effects of GA on endometrial cancer and to develop strategies for clinical treatment.

First-in-human dose-finding study of venadaparib (IDX-1197), a potent and selective PARP inhibitor, in patients with advanced solid tumors.

3107 Background: Poly ADP-ribose polymerase (PARP) is an enzyme that is central to the repair of DNA replication errors known as single-strand breaks (SSBs). PARP inhibitors are currently approved for ovary, breast, pancreatic and prostate cancers which harbor germline or somatic BRCA1/2 mutations (g/sBRCAmt) and/or homologous recombinant repair mutation (g/sHRRmt). In this phase 1 dose finding study of venadaparib, we determined the maximum tolerated dose for venadaparib monotherapy and explored the safety, tolerability, pharmacokinetics, pharmacodynamics and anticancer efficacy of venadaparib in patients with advanced solid tumor which progressed after an attempt of standard-of-care therapy and for which effective therapy does not exist. Methods: Subjects who satisfied all of the inclusion/exclusion criteria and provided written informed consent were enrolled in this study. The investigational product was administered orally once daily continuously in a 3 weekly cycle. Enrolled subjects were assessed for safety and evaluated on tumor response using RECIST 1.1. The study was carried out in a conventional 3+3 design, starting from 2 mg up to 240 mg. Dose limiting toxicities (DLTs) and pharmacokinetics were assessed during the first cycle. Results: As of 08 Feb 2021, enrollment is completed with 32 patients enrolled. Most common tumor types enrolled are breast cancer (16 patients) and ovarian cancer (11 patients). Other tumor types include cancers of endometrium, fallopian tube, uterus and prostate. No DLTs were observed up to the maximum tested dose of 240 mg. Frequently observed adverse drug reactions were as follows – Anemia (56%), nausea (38%) and neutropenia (25%). Overall objective response rate (ORR) was 16% and clinical benefit rate (CBR) was 47%. Partial response was observed starting from 40 mg and clinical benefit was observed from the lowest dose of 2 mg. From optional tumor tissue samples, venadaparib exhibited ≥ 90% PAR inhibitory effect in pharmacodynamic analysis from 10 mg. For patients with known germline or somatic BRCA status either from local lab results or examined at a central lab retrospectively, ORR and CBR was 22% and 44% respectively for BRCAm(+) (9) patients. Interestingly, clinical efficacy was observed in BRCAm(-) (18) patients also, with ORR and CBR of 17% and 50% respectively. Conclusions: Safety and tolerability of the venadaparib monotherapy was confirmed with preliminary efficacy signals observed, even in BRCAm(-) patients. Clinical benefit was observed from the lowest tested dose, suggesting the potential to combine with other chemotherapeutic agents. Further studies to explore efficacy and safety of venadaparib in other tumor types and combinations, as well as to explore adequate biomarkers are warranted. Clinical trial information: NCT03317743.

The role of neurological involvement in malignant tissues: architecture deterioration as a new medical hypothesis explaining cancer progression

In this study, we reported our previous observations and perceptions regarding the involvement of neurological components in the malignant tissues. We used to examine different tissues with malignancy, and we observed increased involvement of neurological components as peripheral nerves. At the beginning, no plausible explanation to such phenomenon. Later, we showed in diabetic rat model that white matter was involved in diabetic progression through the up-regulation of inducible nitric oxide synthase (iNOS) and the down-regulation of heat shock protein70 (HSP70). We extended our investigations in other organs in the same model including kidney, liver, testes, and prostate. We found the same phenomenon of the expression of iNOS and HSP70 in the tissues of these organs. We also observed that there was a deterioration of tissue architecture due to diabetic effects. We think that this deterioration may result from the neurological involvement in these tissues. However, because diabetes may result in initiation of some tumors such as endometrium cancer, deterioration of tissue architecture and neurological involvement are becoming more importantly. This study aimed to introduce our hypothesis in this issue “Architecture deterioration as a new medical hypothesis explaining cancer progression”. We also reviewed the relevant literature.

Impact of the COVID-19 pandemic on pathology and cytology practice in University Hospital Centre Rijeka

Aim: To determine the impact of the COVID-19 pandemic on the overall practice of the histopathological and cytological laboratory at the University Hospital Centre Rijeka, and on the diagnosis of the most common cancers. Methods: The numbers of histopathological and cytological reports, newly diagnosed cancers of breast, lung, colon, endometrium, and prostate, molecular tests for EGFR mutations and HPV were extracted. Two periods, from March 1 to September 30 in 2019 and 2020 were analysed and compared, as the periods before and during the COVID-19 pandemic. Results: The total number of reports was statistically significantly lower during the COVID-19 pandemic in 2020, compared to the same period in 2019 (p<0.000), histopathology by 24%, non-gynecological cytology by 20%, gynecological cytology by 13%, and Pap tests by 11%. During COVID-19 compared to the same period in 2019 the number of newly diagnosed malignant tumors was significantly reduced for colon cancers (–25%, p <0.0001). The decrease in the new cases of breast (–3%) and prostate cancer (–4%) was less pronounced while the increase was recorded for lung (+ 2%) and endometrial cancer (+ 53%). The number of HPV tests dropped significantly during the COVID-19 pandemic, by 40% (p <0.0001). Conclusions: This study confirmed the expected significant reduction in workload during the first wave of the COVID-19 pandemic in 2020, from 11% to 40%, although the number of patients with newly diagnosed cancers, except for colon, did not fall significantly. It would be important to form a joint national registry that would collect diagnostic and also therapeutic procedures, especially for oncology patients, in order to gain a more objective insight into the problems of the health system during pandemics. These data can be used to consider measures and strategies for the most adequate care, not only for COVID-19 but also for all other patients. © 2021 Hrvatski Lijecnicki Zbor. All rights reserved.

Effects of irradiation doses

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Bone marrow is one of the organs at risk of complications during irradiation due to its radiosensitivity. Hematopoietic toxicity remains one of the main toxicities during irradiation of pelvis. Modern radiotherapy techniques, such as intensity modulation and three-dimensional conformal radiotherapy, allow for better dose compliance in target volumes while optimally sparing organs at risk. There is a lack of prospective studies and comparative trials specifying the dose constraints according to the presence or absence of chemotherapy and correlating with the patient’s bone marrow potential.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This monocentric and prospective study conducted by the Strasbourg Europe Cancerology Institute aims to evaluate the hematological toxicity in patients treated with pelvic irradiation for prostate, rectum, anal canal, endometrium, or cervix cancer. One hundred patients will be included. The primary objective is to quantify the relationship between acute hematological toxicity and delivered doses and irradiated volumes in pelvic bone marrow for pelvic cancers. The prescribed dose to the pelvis depends on the tumor location, from 25 Gy in 5 fractions for rectal cancer to 78 Gy in 39 fractions for low-risk prostate cancer. Hematological toxicity will be measured by weekly blood count during radiotherapy and at one month and three months after the end of radiotherapy.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The aim of this study is to improve and optimize radiotherapy if a dose limit or volume constraint is imposed by the results of the study. To our knowledge, this is the first study including several types of pelvic cancers and involving patients treated exclusively with radiotherapy, chemoradiotherapy or radiohormonotherapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial Registration:&lt;/strong&gt; Trial registration number is NCT04626466.&lt;/p&gt;

Incidence and Risk Factors for Venous Thromboembolism Following 2462 Major Abdomino-Pelvic Surgeries in Tertiary Hospital.

PurposeTo determine the incidence and risk factor of postoperative venous thromboembolism (VTE) in Thai populations and to evaluate morbidity, mortality, bleeding complications and the benefit of thromboprophylaxis in real-world practice.Patients and MethodsWe performed a retrospective, single-center, cohort study of patients from all age groups who underwent elective open or laparoscopic major abdomino-pelvic surgery between January 2008 and December 2018 at Chulabhorn Hospital, Bangkok, Thailand. We collected general medical information and specific data based on items from the Caprini risk scoring system.ResultsA total of 2462 major abdomino-pelvic surgeries were included. The study population consisted of 742 males (30.1%) and 1720 females (69.9%) aged 54.59 ± 13.27 years. The incidence of VTE in Thai patients that underwent major abdominal surgery was 0.48%. The most frequent influencing factor for VTE was a history of pulmonary embolism, which increased the risk of VTE 98.28-fold, whereas a history of deep vein thrombosis increased the risk of VTE by 12.34-fold. Other factors influencing VTE development were obesity, anticoagulant use, postoperative chemotherapy, preoperative chemotherapy, endometrium cancer, tumor-node-metastasis (TNM) stage 4 and American College of Chest Physicians (ACCP) class 4. Protective factors included no history of VTE, laparoscopic surgery, TNM stage 0 and benign disease and BMI<30. VTE significantly increased mortality whereas following ACCP guideline reduced mortality.ConclusionPost-operative VTE incidence in Thai patients undergoing major abdomino-pelvic surgery was lower compared with Western patients. Factors influencing for VTE were history of VTE, anticoagulant use, postoperative chemotherapy, preoperative chemotherapy, endometrium cancer, TNM stage 4 and ACCP class 4. Following ACCP guideline reduced the incidence of mortality.

Dietary glycemic index, glycemic load, insulin index, insulin load and risk of diabetes-related cancers: A systematic review of cohort studies

It is believed that diets high in glycemic index (GI), glycemic load (GL), Insulin index (II), and Insulin load (IL) are associated with the increased risks of certain cancers through increasing serum glucose or insulin levels. We conducted this systematic review of cohort studies to evaluate the possible relation between GI, GL, II, and IL with diabetes-related cancers, including colorectal, bladder, breast, endometrium, liver, pancreas, and prostate cancers. Two separate investigators conducted a literature search through PubMed/Medline, Scopus, and Web of Science databases up to February 2020, plus reference lists of relevant articles. Fifty-three cohort studies with a total of 100098 cancer cases were included in this systematic review. Fifteen out of eighteen studies among breast cancer cases reported no significant association between GI/GL and cancer risk. These numbers were 4 out of 13 for colorectal cancer, 7 out of 9 for endometrial cancer, 2 out of 3 for liver cancer, 8 out of 10 for pancreatic cancer, and 3 out of 3 for prostate cancer. Only one cohort investigated this association in terms of bladder cancer and reported a significant association. Also, five studies reported this relation in terms of II/IL, and only one cohort among endometrial cancer patients observed a significant positive association between the risk of cancer and IL. We concluded a weak association between dietary GI/GL and no association between II/IL with diabetes-related cancer risk. More cohort studies are required to be performed regarding II/IL and the risk of cancer.

Accuracy of intra-operative frozen section in guiding surgical staging of endometrial cancer.

Surgery consists the main treatment of endometrial cancer; however, decision of lypmhadenectomy is controversial. Intra-operative frozen section (FS) is commonly used in guiding surgical staging; nevertheless, there are different reports regarding its adequacy and reliability. Aim of this study is to assess accuracy of FS in predicting paraffin section (PS) results in patients with endometrium cancer. Data of 223 cases, who were operated for endometrial cancer at a tertiary hospital in 2012-2019, were analyzed retrospectively. Histological type, grade, tumor diameter, depth of myometrial invasion, and cervical and adnexal involvement in frozen and paraffin section were evaluated. Positive and negative predictive values and accuracy of frozen results in predicting paraffin results for each parameter was assessed. Statistical significance was taken as 0.05 in all tests. Accuracy of FS in predicting PS results were 76.23% for histology, 75.45% for grade, 85.31% for depth of myometrial invasion, and 95.45% for tumor diameter. Surgery, based on FS results, caused undertreatment in 4 patients, while metastatic lymph node ratios were found in only 35.3-50.0% of cases who had high risk parameters at FS. Our FS results have reasonable accuracy rates in predicting PS results, in comparison with the previous literature. However, even if the high risk parameters detected in FS predict PS accurately, absence of lymph node involvement in all cases with high risk parameters indicates that FS-based triage cannot prevent unnecessary lymphadenectomies.

P63 expression in human tumors and normal tissues: a tissue microarray study on 10,200 tumors

BackgroundTumor protein 63 (p63) is a transcription factor of the p53 gene family involved in differentiation of several tissues including squamous epithelium. p63 immunohistochemistry is broadly used for tumor classification but published data on its expression in cancer is conflicting.MethodsTo comprehensively catalogue p63 expression, tissue microarrays (TMAs) containing 12,620 tissue samples from 115 tumor entities and 76 normal tissue types were analyzed.Resultsp63 expression was seen in various normal tissues including squamous epithelium and urothelium. At least occasional weak p63 positivity could be detected in 61 (53%) of 115 different tumor types. The frequencies of p63 positivity was highest in squamous cell carcinomas irrespective of their origin (96–100%), thymic tumors (100%), urothelial carcinomas (81–100%), basal type tumors such as basal cell carcinomas (100%), and various salivary gland neoplasias (81–100%). As a rule, p63 was mostly expressed in cancers derived from p63 positive normal tissues and mostly not detectable in tumors derived from p63 negative cancers. However, exceptions from this rule occurred. A positive p63 immunostaining in cancers derived from p63 negative tissues was unrelated to aggressive phenotype in 422 pancreatic cancers, 160 endometrium cancers and 374 ovarian cancers and might be caused by aberrant squamous differentiation or represent stem cell properties. In 355 gastric cancers, aberrant p63 expression occurred in 4% and was linked to lymph node metastasis (p = 0.0208). Loss of p63 in urothelial carcinomas - derived from p63 positive urothelium - was significantly linked to advanced stage, high grade (p < 0.0001 each) and poor survival (p < 0.0001) and might reflect clinically relevant tumor dedifferentiation.ConclusionThe high prevalence of p63 expression in specific tumor types makes p63 immunohistochemistry a suitable diagnostic tool. Loss of p63 expression might constitute a feature of aggressive cancers.

Natural Compounds in Sex Hormone-Dependent Cancers: The Role of Triterpenes as Therapeutic Agents.

Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.

Early Predictors of the Endometrium Cancer Recurrence in Our Environment

Objective: to find out the predictors in the recurrence of the illness in patients suffering from endometrium cancer at the differet stages of it. Material and Method: Retrospective study of 170 patients who were diagnosed with endometrium cancer between 2013-2017 at “Juan Ramon Jimenez” Hospital in Huelva. Variables such us age, degree of tumour differentation, miometrial invasion (MI), post surgical staging and lympho-vascular space infiltration (LVSI) were analysed in all those patients that had recurrences during the period of the study. The study was sone by using SPSS 23rd V. Once the analysis of Kolmorov-Smirnov concluded in an unusual result; the Chi-Squared test was used in order to obtain parametric categorical data; whereas the U (by Mann Whitney) test was used for the non-parametric data. P<0.01 was accepted as significant from a statistic point of view. results: During the study, 9 patients were diagnosed with tumoral affects recurrence. This means 5.3 % out of the whole sample. The statistic analysis concluded that there is no relation of dependence among the recurrence varible and the Miometrial Invasion variable (χ2=4.780,p=0.092) recurrence and Tumor grade (χ2=7.765, p=0.051) and recurrence and post surgical (χ2=10.200, p=0.070). On the contrary, it is stated that there is a relation of dependence among lymph-node damage variable and LSVI+(χ2=9.954, Cc=0.235, p<.01). The existence of LSVI was evaluated in all the patients. lVSI was negative in 141 cases and 4 of these cases had recurrence of the illness 55.5 % of the patients in which the illness recurred had positive LVSI (5 out of 9). Conclusions: our results proved that more than a half of the patients with recurrence of the illness have Lympho-vascular infiltration and also; if the LVSI is negative, there is a risk of 2.8% of having recurrence. Although it would be neccessary to carry out prospective multi-center studies, this preliminary study determines an obvious relation between LVSI and the recurrence in a short or long term period. Again, The variable that stablishes the LVSI can be a relevant datum when dealing with the staging process of the endometrium cancer, apart from being very useful in the prediction of the illness recurrence.

Dostarlimab for the treatment of endometrium cancer and other solid tumors.

The use of monoclonal antibodies directed against programmed cell death protein 1 (PD-1) and its ligand, programmed cell death 1 ligand 1 (PD-L1), widely extends to a large number of tumors such as melanoma, non-small cell lung, renal or lymphomas, among others. Some of them are already approved as first- or second-line treatment, as pembrolizumab, nivolumab or cemiplimab. Dostarlimab is an investigational humanized anti-PD-1 that is being developed both in monotherapy and as combination therapy, for gynecological tumors but also for lung cancer or melanoma. The preliminary results, particularly in endometrial cancer, show a high affinity against PD-1 with encouraging clinical activity. Here we summarize the development of this compound as well as the current preclinical and clinical data and potential future development.

Incidence of omental metastasis in uterine serous carcinoma: study protocol for a systematic review and meta-analysis

IntroductionUterine serous carcinoma accounts for only about 10% of all endometrial cancers but this subtype is the most common amongst non-endometrioid endometrium cancers and contributes to more than half of...

Impact of diabetes on gastrointestinal and urinary toxicity after radiotherapy for gynecologic malignancy.

Objective:Although diabetes is a common co-morbidity in patients with gynecologic cancer, information about its impact on radiation toxicity in patients with gynecologic cancer treated with external pelvic irradiation is scarce. We aimed to investigate the relation of diabetes with acute toxicity in patients with gynecologic tumors who underwent pelvic +/- paraaortic radiotherapy.Materials and Methods:One hundred twenty-nine patients with endometrium or cervix carcinoma were enrolled in the study. Demographic features, presence of diabetes, incidence and severity of upper gastrointestinal (UGIS), lower gastrointestinal (LGIS), and urinary symptoms were recorded from files. Correlation and logistic regression analysis was used to determine the impact of diabetes, age, chemotherapy, paraaortic irradiation on toxicities, and a prediction model was developed.Results:The median age of 77 patients with endometrium cancer and 52 cervix cancer was 61 (range, 25-92) years, and 28 (21.7%) of them had diabetes. The median pelvic and tumor/tumor bed dose was 5040+247.65 cGy and 5040+222.91 cGy, respectively. Age and Gr 0 UGIS toxicity were significantly related (p=0.047). LGIS Gr 0 toxicity was found to be significantly higher in patients with diabetes (p=0.045). Gr 0 and 2 UGIS toxicities were both found to be significantly correlated with paraaortic irradiation (both p<0.001). Diabetes is also an important determinant on UGIS toxicity in patients who underwent paraaortic irradiation.Conclusion:The correlation we found between toxicity and diabetes, concurrent chemotherapy or paraaortic radiation necessitates special care and risk stratification for patients with diabetes. Further prospective studies with long follow-up and larger patient groups are warranted.

Nulliparity and postmenopausal status are independent factors of malignancy potential of endometrial intraepithelial neoplasia in polyps.

To estimate the risk of concurrent endometrial cancer in endometrium when endometrial intraepithelial neoplasia (EIN) is found within an endometrial polyp and to identify the possible predictive factors for concurrent endometrial cancer. Histopathologic data of women who underwent hysteroscopy for resection of endometrial polyps at Ankara Baskent University Hospital, between 2011 and 2019 were screened. Patients whose polypectomy report was EIN in a polyp, and who had a final report of the hysterectomy specimen were included. Patients were divided into two groups according to the presence of concurrent cancer in the hysterectomy material: group 1, concurrent cancer present and group 2, concurrent cancer absent. Statistical analyses were performed using SPSS. A total of 4125 women underwent hysteroscopy for the resection of endometrial polyps. Of those women, 161 (3.9%) were diagnosed as having EIN and 115 met the criteria. The rate of concurrent endometrial cancer was 28.6% (33/115). According to multivariate analysis, nulliparity (odds ratio [OR] 0.38; 95% confidence interval [CI] 1.04-3.67; p=0.036) and postmenopausal status (OR 0.64; 95% CI 0.42-0.98; p=0.042) were found to be independent factors significantly associated with concurrent endometrial cancer. The incidence of concurrent cancer is higher in postmenopausal or nulliparous women when EIN is detected in a polyp.

Factors Affecting “Organs at Risk” Doses in 3 Dimensional Brachytherapy (3D BRT) of Cervical and Endometrium Cancers

In brachytherapy, both the tumor and organ at risk may have intrafractional and interfractional anatomical differences. In this study, we aimed to investigate the factors affecting Organs at Risk (OAR) doses in adaptive 3D BRT applications. A total of 55 patients that underwent intracavitary brachytherapy with the diagnosis of a gynecological tumor between September 2012 and December 2013 were evaluated retrospectively. The effect of the surgery, applicator type, bladder, rectum and sigmoid on D2cc, D1cc, D0.1cc values were investigated. The median age was 55 years. While there was no statistically significant difference between 1st and 2nd fractions measurements, the sigmoid D1cc values between the 1st and 3rd fractions were found to be statistically significant (p = 0.004). When the effect of the interfractional change of bladder filling on OAR doses in the first three fractions was examined, it was not statistically significant however, its effect on bladder, sigmoid and rectum D2cc, D1cc, D0.1cc values were observed in some fractions. The bladder point dose was found to be statistically significant in operated patients (p= 0.005). When the comparison was made according to the application type, the bladder dose was found to be statistically significant in roller applications than the other two applicator treatments (p= 0.001). 3D BRT provides maximum protection of healthy tissues while giving a high dose to the target as a result of adaptive planning by performing computed tomography in each fraction. The sigmoid is the OAR that makes the most distinctive interfraction. To obtain higher treatment accuracy in each fraction, routine preparation and tomographic imaging followed by adaptive planning should be done.

Radiation Treatment of Synchronous Gynaecologic Cancer: a Clinical Case

Introduction. Recent years have witnessed an increased incidence of multiple neoplasms. In multiple combined cancer, the choice of treatment strategy remains challenging, as two or more tumours require treatment in the shortest perspective. However, an intense treatment may induce many and severe complications with co-located organs and systems. No universal protocol or treatment standard for managing multiple primary cancers is accepted in Russia or worldwide.Materials and methods. The clinical case describes radiation treatment of a female patient with synchronous gynaecologic cancer of vagina and endometrium at the “TOOD” medical facility’s radiotherapy unit. Our treatment was designed to maximise the dosage targeting at a minimal off-coverage of healthy tissues. The treatment was conducted in two steps on an Elekta Synergy Platform S instrument, with the total duration of 62 days.Results and discussion. After radiotherapy, the patient had an oncologic and gynaecologic observation for one year. A complete tumour regression in two localities was confirmed visually, cytologically and instrumentally.Conclusion. A treatment strategy in multiple primary cancers should be personalised. With unfeasible “standard therapy”, alternative approaches for the patient’s treatment are to be explored. We report a successful therapy in a woman with synchronous gynaecologic cancer by applying remote conformal radiation in regional uterine cancers with simultaneous integrated boost to the vaginal tumour during the first radiation step. Brachytherapy at the second step was replaced with stereotactic radiation due to vaginal constriction, pain syndrome and unfeasible applicator installation.

A review on age-related cancer risks in PTEN hamartoma tumor syndrome.

Patients with PTEN hamartoma tumor syndrome (PHTS, comprising Cowden, Bannayan‐Riley‐Ruvalcaba, and Proteus‐like syndromes) are at increased risk of developing cancer due to pathogenic PTEN germline variants. This review summarizes age‐, sex‐, and type‐specific malignant cancer risks for PHTS patients, which is urgently needed for clinical management. A PubMed literature search for Standardized Incidence Ratios or Cumulative Lifetime cancer risks (CLTRs) resulted in nine cohort studies comprising four independent PHTS cohorts, including mainly index cases and prevalent cancer cases. The median age at diagnosis was 36 years. Reported CLTRs for any cancer varied from 81% to 90%. The tumor spectrum included female breast cancer (CLTRs including sex‐specific estimates at age 60‐70: 67% to 85%), endometrium cancer (19% to 28%), thyroid cancer (6% to 38%), renal cancer (2% to 24%), colorectal cancer (9% to 32%), and melanoma (0% to 6%). Although these estimates provide guidance for clinical care, discrepancies between studies, sample sizes, retrospective designs, strongly ascertained cases, and lack of pediatric research emphasizes that data should be interpreted with great caution. Therefore, more accurate and more personalized age‐, sex‐, and cancer‐specific risk estimates are needed to enable counseling of all PHTS patients irrespective of ascertainment, and improvement of cancer surveillance guidelines.