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It has been postulated that the combination of intracavitary and interstitial brachytherapy (IC/IS) is effective and safe for large and irregularly shaped uterine cervical cancer patients. However, due to its invasiveness compared to conventional intracavitary brachytherapy (ICBT), it has to be said that the implementation speed of IC/IS is slow. Until now, there have been no guidelines for required equipment, human resources, and procedural guide focusing solely on IC/IS. The purpose of this guideline is to provide radiation oncologists and medical physicists who wish to start IC/IS with practical and comprehensive guidance for a safe IC/IS introduction and to help accelerate the spread of the utilization of IC/IS nationwide. This is the English translation of the Japanese IC/IS Guidelines, and it was created in an effort to share the Japanese approach to the management of locally advanced uterine cervical cancer worldwide.

It is well recognized that some patients with endometrioid gynecological cancers have tumors arising in multiple sites (ovary, endometrium, and endometriosis) at the time of diagnosis. Molecular analysis has helped discern whether these multisite cancers represent synchronous primary tumors or alternatively metastatic disease. We present a complex case of a patient with endometrioid carcinomas arising in multiple sites. We discuss the use of mutation profiling to discern clonality and highlight how this information may inform the clinical management of such cases.

PURPOSE To evaluate the impact of gas removal on bladder and rectal doses during intracavitary and interstitial high-dose-rate brachytherapy (HDRB) for gynecologic cancers. MATERIAL AND METHODS Fifteen patients treated with definitive external beam radiation followed by HDRB for gynecologic cancers for a total of 21 fractions, presented with a significant amount of rectal gas at initial CT imaging (CTGAS ) after implantation. The gas was removed via rectal tubing followed by subsequent scan acquisition (CTCLINICAL ), which was used for planning and treatment delivery. To assess the effect of gas removal on dosimetry, both bladder and rectum volumes were recontoured on CTGAS . In order to evaluate the clinical impact on the total Equivalent-Dose-in-2Gy-fraction (EQD2 ), each fraction was also replanned to maintain clinically delivered target coverage (HRCTV D90). EQD2 D2cm3 for bladder and rectum were compared between plans. The Wilcoxon signed rank test was performed to evaluate statistically significant differences for all comparisons (P

The incidence of cancer in reproductive-aged women is 7%, but, despite the increased number of cancer cases, advances in early diagnosis and treatment have raised the survival rate. Furthermore, in the last four decades, there has been a rising trend of delaying childbearing. There has been an increasing number of couples referred to Reproductive Medicine Centers for infertility problems after one partner has been treated for cancer. In these cases, the main cause of reduced fertility derives from treatments. In this review, we describe the effects and the risks of chemotherapy, radiotherapy, and surgery in women with cancer, and we will focus on available fertility preservation techniques and their efficacy in terms of success in pregnancy and live birth rates.

Background Delays in care and increased risk for mental health diagnoses put individuals identifying as a sexual minority with cancer at risk for decreased quality of life. Aim To assess psychosocial health among sexual minority gynecologic cancer survivors, we compared self‐reported quality of life and psychosocial measures between individuals diagnosed with gynecologic cancers identifying as lesbian/gay/bisexual (LGB) and heterosexual. Methods and Results English‐speaking adults with gynecologic cancers were invited to participate in an ongoing cohort survey study. Quality of life and psychosocial measures included the Functional Assessment of Cancer Therapy‐General, Distress Thermometer (distress), Patient Health Questionnaire‐8 (depression), General Anxiety Disorder‐7 (anxiety), and Post‐traumatic Stress Disorder Checklist for DSM‐5 (post‐traumatic stress disorder; PTSD). Measures were compared by self‐reported sexual orientation (heterosexual vs. LGB) using descriptive statistics (frequencies and means) and linear and logistic regression models, adjusting for college education. Of 814 patients invited, 457 enrolled (56.1%) and 401 (92.6%) completed the survey and provided information on their sexuality. All but one self‐identified as cisgender women and 22 (5.5%) as LGB. LGB participants were more likely to have completed college (68.2% vs. 40.1%, p = .009) but were otherwise similar across demographic and clinical characteristics. Quality of life and distress scores were similar between groups. LGB participants, compared to heterosexual, reported higher rates of depression (31.8% vs. 10.6%, adjusted odds ratio [OR] = 4.1 [95% confidence interval [CI]: 1.6–11.0], p = .004), anxiety (25.0% vs. 7.1%, adjusted OR = 5.4 [95% CI: 1.7–16.7], p= .004), and PTSD (13.6% vs. 3.5%, adjusted OR = 4.2 [95% CI: 1.1–16.3], p = .04). Conclusion LGB participants reported poorer emotional health following a gynecologic cancer diagnosis than heterosexual participants. Our data suggest this population may need additional resources and support during and after their cancer diagnosis. Future work is needed to identify additional risk factors and the underlying sources of these disparities in order to improve patient care and wellness in this population.

Purpose The International Federation of Gynecology and Obstetrics (FIGO) stage remains the standard staging system for the assessment of endometrial cancer (EC) prognosis. Thus, we aim to identify the significant genes or biomarkers associated with the stage of endometrial cancer, which may also help reveal the mechanism of EC progression and assess the prognosis of patients with EC. Materials and methods We compared the mRNA expression levels of EC patients with stages I and II as well as stages III and IV in the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) of EC patients at different stages were selected by volcano plot and Venn analysis. Gene Ontology (GO) and Pathways were applied to analyze the identified genes. Protein protein interaction (PPI) network was employed to identify the correlation. The survival analyses based on TCGA database were conducted for further screening. The Human Protein Atlas, quantitative PCR and immunohistochemistry were utilized to confirm the differences in expression of DEGs in endometrial cancer samples at different FIGO stages. Results CKMT1A was identified as a candidate gene. Through survival analyses, we found that CKMT1A may be a poor prognostic factor in the overall survival of endometrial cancer patients. GO and Pathways revealed that CKMT1A is closely associated with the metabolic process. More importantly, Human Protein Atlas and quantitative PCR confirmed the differences in expression of CKMT1A in endometrial cancer samples at different FIGO stages. Conclusion In summary, this study shows that CKMT1A is a newly identified essential tumor progression regulator of endometrial cancer, which may give rise to novel therapeutic strategies in the management of endometrial cancer patients to prolong its prognosis and prevent tumor progression.

Objective: To evaluate the accuracy, sensitivity, specificity, and predictive value of preoperative core needle biopsy (CNB) assessment of histological characteristics in primary cervical cancer. Setting: Retrospective cohort study. Population: Women older than 18 with primary cervical cancer enrolled in the prospective Leipzig School MMR study and had CNBs taken before their operation. Methods: We reviewed 318 cases of cervical carcinoma with available pathology reports from preoperative CNB assessment and from final postoperative evaluation of the hysterectomy specimen. Setting the postoperative comprehensive pathological evaluation as reference, we analysed CNB assessment of histological tumor characteristics. In addition, we performed multivariable logistic regression to identify factors influencing the accuracy in identifying lymphovascular space invasion (LVSI) and tumor grade. Main outcome measures: Accuracy, sensitivity, specificity, and predictive values of CNB assessment of histological tumor characteristics and the variables influencing these. Results: CNB was highly accurate in discriminating histological subtype. Sensitivity and specificity were 98.8% and 89% for squamous cell carcinoma (SCC), 92.9% and 96.6% for adenocarcinoma (AC), 33.3% and 100% in adenosquamous carcinoma respectively. Neuroendocrine carcinoma was always recognized correctly. The accuracy of the prediction of lymphovascular space invasion (LVSI) was 61.9% and was positively influenced by tumor size in preoperative MRI and negatively influenced by strong peritumoral inflammation. High tumor grade was diagnosed accurately in 73.9% of cases and was influenced by histological tumor type. Conclusions: CNB is an accurate sampling technique for histological classification of cervical cancer and represents a reasonable alternative to other biopsy techniques. Funding: “Stiftung gynäkologische Onkologie” (non-profit-organization).

Endometrioid endometrial carcinomas (EECs) are the most common histological subtype of uterine cancer. Late-stage disease is an adverse prognosticator for EEC. The purpose of this study was to analyze EEC exome mutation data to identify late-stage-specific statistically significantly mutated genes (SMGs), which represent candidate driver genes potentially associated with disease progression. We exome sequenced 15 late-stage (stage III or IV) non-ultramutated EECs and paired non-tumor DNAs; somatic variants were called using Strelka, Shimmer, SomaticSniper and MuTect. Additionally, somatic mutation calls were extracted from The Cancer Genome Atlas (TCGA) data for 66 late-stage and 270 early-stage (stage I or II) non-ultramutated EECs. MutSigCV (v1.4) was used to annotate SMGs in the two late-stage cohorts and to derive p-values for all mutated genes in the early-stage cohort. To test whether late-stage SMGs are statistically significantly mutated in early-stage tumors, q-values for late-stage SMGs were re-calculated from the MutSigCV (v1.4) early-stage p-values, adjusting for the number of late-stage SMGs tested. We identified 14 SMGs in the combined late-stage EEC cohorts. When the 14 late-stage SMGs were examined in the TCGA early-stage data, only Krüppel-like factor 3 (KLF3) and Paired box 6 (PAX6) failed to reach significance as early-stage SMGs, despite the inclusion of enough early-stage cases to ensure adequate statistical power. Within TCGA, nonsynonymous mutations in KLF3 and PAX6 were, respectively, exclusive or nearly exclusive to the microsatellite instability (MSI)-hypermutated molecular subgroup and were dominated by insertions-deletions at homopolymer tracts. In conclusion, our findings are hypothesis-generating and suggest that KLF3 and PAX6, which encode transcription factors, are MSI target genes and late-stage-specific SMGs in EEC.

Purpose: The optimal surgical approach for para-aortic lymphadenectomy (PALND) in gynecologic cancers using minimally invasive surgery (laparoscopy or robotic-assisted) is controversial. This study summarizes the current evidence on the extraperitoneal (EP) approach and compares its perioperative, surgical outcomes, and complications to the transperitoneal (TP) approach in an updated meta-analysis.Methods: We performed a systematic search in PubMed, Embase, Web of Science, Cochrane Library database for randomized controlled trials (RCTs) and non-RCTs that compare EP to TP for PALND. The main outcomes included surgical, perioperative outcomes, and complications. The weighted mean difference (WMD) and odds ratio (OR) were applied for the comparison of continuous and dichotomous variables with 95% CIs. Three RCTs and 10 non-RCTs trials, including 2,354 patients were identified and enrolled in the meta-analysis.Results: A total of three RCTs and ten non-RCTs trials, including 2,354 patients were identified and enrolled in the meta-analysis. We reported similar results for EP and TP in terms of the hospital stay, estimated blood loss, blood transfusion, conversion to laparotomy, total operative time, and postoperative complications (Clavien grade ≥ 1 and Clavien grade ≥ 3). However, the PALND operative time (WMD −10.46 min, 95% CI −19.04, −1.88; p = 0.02) and intraoperative complications (OR 0.40, 95% CI 0.23, 0.69; p = 0.001) were less with EP. Also, more nodes were removed in EP compared with the TP (WMD 1.45, 95% CI 0.05, 2.86; p = 0.04).Conclusions: The EP approach did not show differences regarding surgical and perioperative parameters compared with the TP approach. However, the number of aortic nodes retrieved was higher. Furthermore, The PALND operative time and intraoperative complications were less in EP.

Objective: To investigate the prevalence and oncologic outcomes of patients with multiple primary malignant tumors (MPMT) with gynecologic cancer. Methods: This retrospective study included 1929 patients diagnosed with gynecologic cancer at a tertiary medical center between August 2005 and April 2021. The clinical data included cancer location, age at primary malignancy diagnosis, interval between primary and secondary cancer, stage of cancer, family history of cancer, genetic testing, dates of last follow-up, recurrence, and death. Results: The prevalence of MPMT with gynecologic cancer in patients was 8.6% and the mean diagnostic period between primary and secondary cancer was 60 months. Furthermore, 20 of the 165 patients with MPMT had multiple primary gynecologic cancers (MPGC), whereas 145 had gynecologic cancer coexisting with non-gynecologic cancer (GNC). Endometrial-ovarian cancer (60%) was the most common coexisting cancer in the MPGC group, whereas the most common non-gynecologic cancer in the GNC group was breast cancer (34.5%). There were 48 patients with synchronous cancer and 117 patients with metachronous cancer. The incidence of synchronous cancer was higher in the MPGC group than in the GNC group (p = 0.037). Significantly more patients had early-stage ovarian cancer in the MPGC group than in the GNC group (p = 0.031). The overall recurrence and mortality rates were 15.8% and 8.5%, respectively, in patients with MPMT. Conclusion: Synchronous cancer incidence was significantly higher in the MPGC than in the GNC group. Early-stage ovarian cancer was more highly diagnosed in patients with MPGC than in those with GNC. A systematic examination after primary cancer diagnosis could facilitate the early diagnosis of secondary primary malignancy, thereby improving patient prognosis.

Purpose To identify patient and hospital characteristics associated with extended surgical cytoreduction in the treatment of ovarian cancer. Methods A retrospective analysis using the National Inpatient Sample (NIS) database identified women hospitalized for surgery to remove an ovarian malignancy between 2013 and 2017. Extended cytoreduction (ECR) was defined as surgery involving the bowel, liver, diaphragm, bladder, stomach, or spleen. Chi-square and logistic regression were used to analyze patient and hospital demographics related to ECR, and trends were assessed using the Cochran-Armitage test. Results Of the estimated 79,400 patients undergoing ovarian cancer surgery, 22% received ECR. Decreased adjusted odds of ECR were found in patients with lower Elixhauser Comorbidity Index (ECI) scores (OR 0.61, p Conclusions Likelihood of ECR was associated with increased medical comorbidity complexity, higher income, and undergoing the procedure at high surgical volume hospitals. The proportion of ovarian cancer cases with ECR has decreased from 2013–17, with more cases performed at high surgical volume hospitals.

Background Cancer can cause physical changes and affect satisfaction with a persons’ physical appearance, which in turn can affect overall quality of life. Previous studies have primarily focused on women with breast cancer and few is known about body image in patients with other cancers and especially men. The present study compares satisfaction with body image of patients with different types of cancer with the general population and across sexes and identifies risk factors for diminished body image. Additionally, patients that were diagnosed within the last year and those living with cancer for longer are compared. Methods In this cross-sectional study, N = 531 cancer patients answered the German Self-Image Scale to assess body image. One sample t-tests are utilized to compare the body image of cancer patients with the general population. Stepwise regression analyses were used to identify factors associated with body image and ANOVAs with posthoc tests as well as t-tests were used to examine group differences. Results Cancer patients showed diminished body image compared to the general population. For men, higher relationship satisfaction and lower cancer-specific distress were associated with more positive body self-acceptance (SA), whereas younger age, higher relationship satisfaction, and lower cancer-specific distress resulted in better perceived partner-acceptance of one’s body (PA). In women, higher education, lower anxiety and cancer-specific distress were associated with more positive SA. Female cancer patients with breast/gynecological cancer reported better SA than those with visceral cancers. Higher relationship satisfaction and lower cancer-specific distress were found to be associated with more satisfactory PA in females. Time since diagnosis did not affect body image in this study. Conclusions Results indicate that cancer patients regardless of sex tend to have decreased body image satisfaction. Future research directions include examination of additional entities of cancer, deeper research in men and the role of time since diagnosis.

Objective: The aim of this study is to calculate hemoglobin (Hb) levels and find the prevalence of anemia in gynecological cancer patients undergoing cancer treatments including chemotherapy and radiotherapy attending Princess Noorah Oncology Center in King Abdul Aziz Medical City in Jeddah. Method: A cross-sectional chart review study was conducted in gynecological cancer patients receiving chemotherapy/radiotherapy to find the prevalence of anemia in the period between 2016 and 2018. All data were collected from the electronic medical records using a data collection sheet. Results: A total of 107 female patients who had gynecologic cancers and received chemotherapy/radiotherapy were included. Ninety percent (90.7%) of them developed anemia during the treatment course. Conclusion: The prevalence of anemia in patients with gynecological cancers during their active treatment was high. This is attributed to the chemotherapy and radiotherapy they were receiving that affected their Hb levels. Better monitoring and, in severe cases, blood transfusion could be beneficial.

Objective: Diagnosis and treatment of gynecologic cancers can have a negative impact on sexuality. Identification of sexual problems and concerns is key to enable appropriate management. Therefore, there is a need for a valid and reliable instrument for evaluating the sexuality of patients. This study aimed to adapt the sexuality scale for women with gynecologic cancer for Turkish patients with gynecologic cancer. Methods: A cross-sectional study of 150 volunteer patients with gynecologic cancer was undertaken in Turkey. The patients completed a semi-structured demographic data form and the sexuality scale for women with gynecologic cancer. We assessed the reliability, language accuracy, and content and construct validities of the Turkish version of the scale. Results: Exploratory and confirmatory factor analyses showed that the scale had four factors. In the exploratory factor analysis, seven items were discarded from the scale because their load values were

Background With the growing understanding of the molecular and genetic profiles of cancers, targeted treatments are increasingly utilized in personalized cancer care. The objective of this study was to determine how these advances have translated into practice by examining how often molecular profiling of gynecological tumors led to treatment changes. Methods We identified women with gynecological cancers at our institution who had molecular tumor testing performed from November 2014 to June 2017. Clinicopathologic data were extracted from medical records. We determined (a) if molecular profiling identified actionable targets for which therapy is available, and (b) whether the patient's treatment course changed as a result of molecular profiling. Chi‐square, Wilcoxon rank‐sum, and Fisher's exact tests were used with a P

Background Endometriosis is associated with increased risk of clear cell ovarian cancer and has even suggested being an etiological factor for this cancer. Association between endometriosis and extraovarian clear cell cancers is unclear. This study aimed to assess the association between surgically diagnosed endometriosis and risk of extraovarian clear cell cancers according to the type of endometriosis (i.e., ovarian, peritoneal, and other endometriosis) and the site of clear cell cancer. Methods In this register-based historic cohort study we identified all women with surgically diagnosed endometriosis from the Finnish Hospital Discharge Registry 1987–2012. Data on extraovarian clear cell cancers of these women were obtained from the Finnish Cancer Registry. The follow-up started January 1st, 2007 or at endometriosis diagnosis (if later), and ended at emigration, death or on the December 31st, 2014. Standardized incidence ratios were calculated for each site of clear cell carcinoma (intestine, kidney, urinary tract, gynecological organs other than ovary), using the Finnish female population as reference. Results The endometriosis cohort consisted of 48,996 women, including 22,745 women with ovarian and 19,809 women with peritoneal endometriosis. Altogether 23 extraovarian clear cell cancers were observed during 367,386 person-years of follow-up. The risk of extraovarian clear cell cancer was not increased among all women with surgically diagnosed endometriosis (standardized incidence ratio 0.89, 95% confidence interval 0.56–1.33) nor in different types of endometriosis. The incidence of clear cell cancer in any specific site was not increased either. Conclusions The risk of extraovarian clear cell cancers in women with surgically diagnosed endometriosis is similar to that in the general population in Finland. publishedVersion

The purpose of the current study was to clarify differences in microRNA expression according to clinicopathological characteristics, and to investigate if miRNA profiles could predict cytoreductive outcome in patients with FIGO stage IIIC and IV ovarian cancer. Patients enrolled in the Pelvic Mass study between 2004 and 2010, diagnosed and surgically treated for epithelial ovarian cancer, were used for investigation. MicroRNA was profiled from tumour tissue with global microRNA microarray analysis. Differences in miRNA expression profiles were analysed according to histologic subtype, FIGO stage, tumour grade, type I or II tumours and result of primary cytoreductive surgery. One microRNA, miR-130a, which was found to be associated with serous histology and advanced FIGO stage, was also validated using data from external cohorts. Another seven microRNAs (miR-34a, miR-455-3p, miR-595, miR-1301, miR-146-5p, 193a-5p, miR-939) were found to be significantly associated with the clinicopathological characteristics (p ≤ 0.001), in our data, but mere not similarly significant when tested against external cohorts. Further validation in comparable cohorts, with microRNA profiled using newest and similar methods are warranted.

Purpose The purpose of this study is to examine the prevalence, associated factors and quality of life associated with depressive disorder in cervical cancer patients. Patients and methods This cross-sectional study was carried out in a gynecologic oncology clinic of a university hospital in Northern Thailand from October 2018 to August 2019. Two-hundred cervical cancer patients were screened for depressive disorder using the nine-item Patient Health Questionnaire (PHQ-9), and psychiatrists interviewed eligible patients to confirm diagnoses. We measured the quality of life using questionnaires from the European Organisation for the Research and Treatment of Cancer: Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Cervical Cancer Module 24 (EORTC QLQ-Cx24). Associated factors, including comorbidity, fatigue, and pain, were collected using the Charlson Comorbidity Index (CCI), the eleven-item Chalder Fatigue Scale (CFQ 11), and the visual analog scale (VAS) for pain, respectively. Results Twenty-seven (13.5%) cervical cancer patients were diagnosed with depressive disorder by psychiatrists according to the DSM-5. Depressive disorder was related to a worse quality of life in these patients. A binary logistic regression analysis revealed that depressive disorder among these patients was linked with these factors: high fatigue score (aOR: 1.35; CI: 1.18–1.53), high pain score (aOR: 1.25; CI: 1.02–1.54), no perception of social support, (aOR: 3.12; CI: 1.11–8.81), and no previous surgical treatment for cervical cancer (aOR: 2.99; CI: 1.08–8.29). Conclusion The depressive disorder prevalence was 13.5% in Northern Thai cervical cancer patients. In this demographic, cervical cancer patients—who reported high fatigue or pain scores, did not perceive social support, or had no previous cervical cancer surgery- were more likely to have depressive disorder.

Introduction There are no reliable blood biomarkers for monitoring endometrial cancer patients in the current clinical practice. Circulating tumor DNA (ctDNA) is emerging as a promising non-invasive method to measure tumor burden, define prognosis and monitor disease status in many solid cancers. In this pilot study, we investigated if unique tumor-specific DNA junctions can be used to detect ctDNA levels in patients with endometrial cancer. Methods Chromosomal rearrangements in primary tumors of eleven patients with high-grade or advanced stage endometrial cancer were determined by whole-genome Mate-Pair sequencing. Identified unique tumor-specific junctions were evaluated in pre- and six-week post-surgery patient plasma using individualized quantitative polymerase chain reaction (qPCR) assays. The relationship between clinicopathological features and detection of ctDNA was investigated. Results CtDNA was detected in 60% (6/10) of cases pre-surgery and in 27% (3/11) post-surgery. The detection of ctDNA pre-surgery was consistent with clinical indicators of aggressive disease such as advanced stage (80% - 4/5), lymphatic spread of disease (100% - 3/3), serous histology (80% - 4/5), deep myometrial invasion (100% - 3/3), lympho-vascular space invasion (75% - 3/4). All patients in which ctDNA was detected post-surgically had type II endometrial cancer. Discussion This pilot study demonstrates the feasibility of using personalized tumor-specific junction panels for detecting ctDNA in the plasma of endometrial cancer patients. Larger studies and longer follow-up are needed to validate the potential association between pre-surgical ctDNA detection and the presence of cancers with aggressive pathologic tumor characteristics or advanced stage observed in this study.

Background Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors. Methods Patients receiving checkpoint inhibitors between January 2013 and May 2020 at the University Medical Center Utrecht, the Netherlands, were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in serum creatinine of ≥1.5 times the baseline value, based on the Kidney Disease: Improving Global Outcomes criteria. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent renal dysfunction was diagnosed in AKI patients with a final serum creatinine measurement of >1.3 times the baseline value. Results Among 676 patients receiving checkpoint inhibitors, the overall incidence of AKI was 14.2%. Baseline variables independently associated with AKI were a gynecologic malignancy, monotherapy with ipilimumab, and the use of a diuretic, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, or proton pump inhibitor at baseline. AKI was checkpoint inhibitor-associated in one third of all patients with AKI. Checkpoint inhibitor-associated AKI was mostly low-grade, occurred a median of 15 weeks after checkpoint inhibitor initiation, and resulted in persistent renal dysfunction in approximately 40% of the patients. Patients with all-cause AKI had a twofold increased mortality risk, but checkpoint inhibitor-associated AKI was not associated with increased mortality. Conclusions In this study, patients receiving checkpoint inhibitors frequently developed AKI due to various etiologies. AKI directly related to the effect of checkpoint inhibitor toxicity did not increase mortality. However, AKI not related to the effect of checkpoint inhibitor toxicity was associated with increased mortality.

Palliative care improves quality-of-life and extends survival, however, is underutilized among gynecological cancer patients in the United States (U.S.). Our objective was to evaluate associations between healthcare access (HCA) measures and palliative care utilization among U.S. gynecological cancer patients overall and by race/ethnicity. We used 2004–2016 data from the U.S. National Cancer Database and included patients with metastatic (stage III–IV at-diagnosis) ovarian, cervical, and uterine cancer (n = 176,899). Palliative care was defined as non-curative treatment and could include surgery, radiation, chemotherapy, and pain management, or any combination. HCA measures included insurance type, area-level socioeconomic measures, distance-to-care, and cancer treatment facility type. We evaluated associations of HCA measures with palliative care use overall and by race/ethnicity using multivariable logistic regression. Our population was mostly non-Hispanic White (72%), had ovarian cancer (72%), and 24% survived &lt, 6 months. Five percent of metastatic gynecological cancer patients utilized palliative care. Compared to those with private insurance, uninsured patients with ovarian (aOR: 1.80,95% CI: 1.53–2.12), and cervical (aOR: 1.45,95% CI: 1.26–1.67) cancer were more likely to use palliative care. Patients with ovarian (aOR: 0.58,95% CI: 0.48–0.70) or cervical cancer (aOR: 0.74,95% CI: 0.60–0.88) who reside &gt, 45 miles from their provider were less likely to utilize palliative care than those within &lt, 2 miles. Ovarian cancer patients treated at academic/research programs were less likely to utilize palliative care compared to those treated at community cancer programs (aOR: 0.70, 95%CI: 0.58–0.84). Associations between HCA measures and palliative care utilization were largely consistent across U.S. racial-ethnic groups. Insurance type, cancer treatment facility type, and distance-to-care may influence palliative care use among metastatic gynecological cancer patients in the U.S.

Ovarian cancer is the fifth most common cause of cancer deaths among American women. Platinum and taxane combination chemotherapy represents the first-line approach for ovarian cancer, but treatment success is often limited by chemoresistance. Therefore, it is necessary to find new drugs to sensitize ovarian cancer cells to chemotherapy. Persistent activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling plays an important role in oncogenesis. Using a novel approach called advanced multiple ligand simultaneous docking (AMLSD), we developed a novel nonpeptide small molecule, LLL12B, which targets the STAT3 pathway. In this study, LLL12B inhibited STAT3 phosphorylation (tyrosine 705) and the expression of its downstream targets, which are associated with cancer cell proliferation and survival. We showed that LLL12B also inhibits cell viability, migration, and proliferation in human ovarian cancer cells. LLL12B combined with either paclitaxel or with cisplatin demonstrated synergistic inhibitory effects relative to monotherapy in inhibiting cell viability and LLL12B-paclitaxel or LLL12B-cisplatin combination exhibited greater inhibitory effects than cisplatin-paclitaxel combination in ovarian cancer cells. Furthermore, LLL12B-paclitaxel or LLL12B-cisplatin combination showed more significant in inhibiting cell migration and growth than monotherapy in ovarian cancer cells. In summary, our results support the novel small molecule LLL12B as a potent STAT3 inhibitor in human ovarian cancer cells and suggest that LLL12B in combination with the current front-line chemotherapeutic drugs cisplatin and paclitaxel may represent a promising approach for ovarian cancer therapy.

EXCLI Journal; 20:Doc194; ISSN 1611-2156

There are currently no reliable, established serum biomarkers to predict the prognosis of radiotherapy for advanced cervical cancer. We aimed to identify serum biomarkers for survival after radiotherapy for cervical cancer. In this multicenter prospective cohort study, the usefulness of pre- and posttreatment serum protein levels of potential biomarkers, including squamous cell carcinoma antigen (SCC-Ag), apolipoprotein C-II (ApoC-II), matrix metalloproteinase (MMP)1, and MMP2, were evaluated together with clinical factors in 145 cervical cancer patients in order to determine their suitability to predict survival. Progression-free survival (PFS) was the primary endpoint, and overall survival (OS), pelvic PFS (PPFS), and distant metastasis-free survival (DMFS) were the secondary endpoints. Blood samples were collected before and 1 month after radiotherapy to measure serum biomarker levels. ApoC-II was measured using a monoclonal antibody-based enzyme-linked immunosorbent assay, which was developed for this purpose. Kaplan-Meier method, log-rank test, and univariate and multivariate Cox proportional hazards models were used for statistical analyses. In multivariate analysis, larger tumor size was independently associated with shorter PFS, OS, PPFS, and DMFS, while longer overall treatment time was independently associated with shorter PPFS. Higher pretreatment SCC-Ag (P < 0.001) was associated with shorter DMFS. Higher posttreatment SCC-Ag (P = 0.017) was also associated with shorter DMFS. Pretreatment ApoC-II was associated with PPFS in univariate analysis (P = 0.048), but not in multivariate analysis. Patients with pretreatment ApoC-II levels ≤ 25.8 μg/ml had shorter PPFS than those with pretreatment ApoC-II levels > 25.8 μg/ml (P = 0.023, log-rank test). Pre- and posttreatment serum SCC-Ag and pretreatment serum ApoC-II levels may be important biomarkers to predict survival outcomes of patients with cervical cancer after radiotherapy. Pre- and posttreatment SCC-Ag and pretreatment ApoC-II might be useful in clinical settings for screening patients to improve treatment strategies in cervical cancer.

The objectives of this study were to identify the associated factors with cancerous and precancerous lesions of cervix. In Africa, the incidence of uterine cervical neoplasms varies from one region to another, where most women with uterine cervical neoplasms are seen at an advanced stage. For this reason, uterine cervical neoplasms mass screening reduces the incidence and mortality due to this disease, similar to what is being done in Europe. A cross-sectional analytical study was conducted. Socio-demographic characteristics, gynaecological-obstetrical history, risk factors, data from visual inspection with acetic acid and visual inspection with Lugol, colposcopy impressions and results of cytological analysis were performed. A simple and multiple regression were performed to establish a statistically significant difference between certain factors and the presence of precancerous or cancerous lesions of uterine cervical. In this study, of 63 women diagnosed histologically, 43 had precancerous lesions and 20 had cancerous lesions. we found that being older than 35, having the first intercourse before 18, having an antecedent of STI, being a widow and using of tobacco were risk factors associated with precancerous lesions (p = 0.013 with OR = 3.44 (1.22–9.73), p = 0.009 with OR = 4.07 (1.69–13.08), p < 0.001 with OR = 3.80 (1.94–7.47), p < 0.001 with OR = 9.77 (3.87–24.70) and p < 0.001 with OR = 5.47 (2.60–11.52)) respectively. Only being older than 45, being a widow and using tobacco were risk factors associated with cancerous lesions (p = 0.021 with OR = 2.01 (1.58–3.56), p = 0.02 with OR = 2.96 (2.10–3.87), p = 0.041 with OR = 1.98 (1.46–2.44)) respectively. Among participants diagnosed with uterine cervical neoplasms, there was a significant association with the STI, marital status and smoking. Despite the integration of the detection of precancerous uterine cervical neoplasms lesions into health facilities in Gabon, uterine cervical neoplasms ranks second among women’s cancers in terms of incidence and first in terms of mortality.

Advanced ovarian cancer is one of the most lethal gynecological tumor, mainly due to late diagnoses and acquired drug resistance. MicroRNAs (miRNAs) are small-non coding RNA acting as tumor suppressor/oncogenes differentially expressed in normal and epithelial ovarian cancer and has been recognized as a new class of tumor early detection biomarkers as they are released in blood fluids since tumor initiation process. Here, we evaluated by droplet digital PCR (ddPCR) circulating miRNAs in serum samples from healthy (N = 105) and untreated ovarian cancer patients (stages I to IV) (N = 72), grouped into a discovery/training and clinical validation set with the goal to identify the best classifier allowing the discrimination between earlier ovarian tumors from health controls women. The selection of 45 candidate miRNAs to be evaluated in the discovery set was based on miRNAs represented in ovarian cancer explorative commercial panels. We found six miRNAs showing increased levels in the blood of early or late-stage ovarian cancer groups compared to healthy controls. The serum levels of miR-320b and miR-141-3p were considered independent markers of malignancy in a multivariate logistic regression analysis. These markers were used to train diagnostic classifiers comprising miRNAs (miR-320b and miR-141-3p) and miRNAs combined with well-established ovarian cancer protein markers (miR-320b, miR-141-3p, CA-125 and HE4). The miRNA-based classifier was able to accurately discriminate early-stage ovarian cancer patients from health-controls in an independent sample set (Sensitivity = 80.0%, Specificity = 70.3%, AUC = 0.789). In addition, the integration of the serum proteins in the model markedly improved the performance (Sensitivity = 88.9%, Specificity = 100%, AUC = 1.000). A cross-study validation was carried out using four data series obtained from Gene Expression Omnibus (GEO), corroborating the performance of the miRNA-based classifier (AUCs ranging from 0.637 to 0.979). The clinical utility of the miRNA model should be validated in a prospective cohort in order to investigate their feasibility as an ovarian cancer early detection tool.

Ovarian cancer (OC), the eighth-leading cause of cancer-related death among females worldwide, is mainly represented by epithelial OC (EOC) that can be further subdivided into four subtypes: serous (75%), endometrioid (10%), clear cell (10%), and mucinous (3%). Major reasons for high mortality are the poor biological understanding of the OC mechanisms and a lack of reliable markers defining each EOC subtype. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression primarily by targeting messenger RNA (mRNA) transcripts. Their aberrant expression patterns have been associated with cancer development, including OC. However, the role of miRNAs in tumorigenesis is still to be determined, mainly due to the lack of consensus regarding optimal methodologies for identification and validation of miRNAs and their targets. Several tools for computational target prediction exist, but false interpretations remain a problem. The experimental validation of every potential miRNA-mRNA pair is not feasible, as it is laborious and expensive. In this study, we analyzed the correlation between global miRNA and mRNA expression patterns derived from microarray profiling of 197 EOC patients to identify the signatures of miRNA-mRNA interactions associated with overall survival (OS). The aim was to investigate whether these miRNA-mRNA signatures might have a prognostic value for OS in different subtypes of EOC. The content of our cohort (162 serous carcinomas, 15 endometrioid carcinomas, 11 mucinous carcinomas, and 9 clear cell carcinomas) reflects a real-world scenario of EOC. Several interaction pairs between 6 miRNAs (hsa-miR-126-3p, hsa-miR-223-3p, hsa-miR-23a-5p, hsa-miR-27a-5p, hsa-miR-486-5p, and hsa-miR-506-3p) and 8 mRNAs (ATF3, CH25H, EMP1, HBB, HBEGF, NAMPT, POSTN, and PROCR) were identified and the findings appear to be well supported by the literature. This indicates that our study has a potential to reveal miRNA-mRNA signatures relevant for EOC. Thus, the evaluation on independent cohorts will further evaluate the performance of such findings.

Objective To characterize the microbiota of postmenopausal women undergoing hysterectomy for endometrioid (EAC) or uterine serous cancers (USC) compared to controls with non-malignant conditions. Methods Endometrial, cervicovaginal and anorectal microbial swabs were obtained from 35 postmenopausal women (10 controls, 14 EAC and 11 USC) undergoing hysterectomy. Extracted DNA was PCR amplified using barcoded 16S rRNA gene V4 primers. Sequenced libraries were processed using QIIME2. Phyloseq was used to calculate α- and β- diversity measures. Biomarkers associated with case status were identified using ANCOM after adjustment for patient age, race and BMI. PICRUSt was used to identify microbial pathways associated with case status. Results Beta-diversity of microbial communities across each niche was significantly different (R2 = 0.25, p < 0.001). Alpha-diversity of the uterine microbiome was reduced in USC (Chao1, p = 0.004 and Fisher, p = 0.007) compared to EAC. Biomarkers from the three anatomical sites allowed samples to be clustered into two distinct clades that distinguished controls from USC cases (p = 0.042). The USC group was defined by 13 bacterial taxa across the three sites (W-stat>10, FDRLactobacillus and elevation of uterine Pseudomonas. PICRUSTt analysis revealed highly significant differences between the USC-associated clades within the cervicovaginal and uterine microbiota. Conclusions The microbial diversity of anatomic niches in postmenopausal women with EAC and USC is different compared to controls. Multiple bacteria are associated with USC case status including elevated levels of cervicovaginal Lactobacillus, depletion of uterine Pseudomonas, and substantially different functional potentials identified within cervicovaginal and uterine niches.

Background A diverse and abundant gut microbiome can improve cancer patients’ treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT. Materials and methods Rectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. 42 of these patients received antibiotics during the study period. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size. Results Gut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; all P Conclusion After CRT, the diversity of the gut microbiomes in this population tended to return to baseline levels by the 12 week follow-up period, but structure and composition remained significantly altered. These changes should be considered when designing studies to analyze the gut microbiome in patients who receive pelvic CRT for gynecologic cancers.

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse reaction in cancer patients treated with several cytotoxic anticancer agents including paclitaxel. Duloxetine, an antidepressant known as a serotonin-noradrenalin reuptake inhibitor, is the only agent that has moderate evidence for the use to treat painful CIPN. The present retrospective cohort study aimed to analyze risk factors for paclitaxel-induced peripheral neuropathy (PIPN), and investigate ongoing prescription drug use for PIPN in Japan. Female breast and gynecologic cancer patients who underwent paclitaxel-based chemotherapy at a single center in Japan between January 2016 and December 2019 were enrolled in this study. Patients’ information obtained from electronic medical records were statistically analyzed to test possible risk factors on PIPN diagnosis. Patients’ age, total paclitaxel dose, the history of female hormone-related diseases, hypertension and body mass index (BMI), but not additional platinum agents, were significantly associated with increased PIPN diagnosis. Drugs prescribed for PIPN included duloxetine, pregabalin, mecobalamin and Goshajinkigan, a polyherbal medicine, regardless of poor evidence for their effectiveness against CIPN, and were greatly different between breast and gynecologic cancer patients diagnosed with PIPN at the departments of Surgery and Gynecology, respectively. Thus, older age, greater total paclitaxel dose, the history of estrogen-related diseases, hypertension and BMI are considered risk factors for PIPN in paclitaxel-based chemotherapy of female cancer patients. It appears an urgent need to establish a guideline of evidence-based pharmacotherapy for PIPN.

Introduction Our institution implemented a preoperative protocol to identify high-risk cases for which power morcellation should be avoided. Material and methods In this retrospective cohort study, an institutional protocol requiring preoperative Magnetic Resonance Imaging with diffusion-weighted imaging and serum Lactate Dehydrogenase levels was implemented. Chart review was performed including all women who underwent intra-abdominal surgery for symptomatic fibroids from 4/23/2013 to 4/23/2015. Results A total of 1,085 women were included, 479 before and 606 after implementation of the Magnetic Resonance Imaging / Lactate Dehydrogenase protocol. The pre-protocol group had more post-menopausal women (4% vs. 2%, p = 0.022) and women using tamoxifen (2% vs. 0%, p = 0.022) than those in the post-protocol group, but baseline patient characteristics were otherwise similar between groups. Incidence of malignant pathological diagnoses did not change significantly over the time period in relation to protocol implementation. The rate of open surgery for both hysterectomy and myomectomy remained the same in the year preceding and the year following initiation of the protocol (open hysterectomy rate was 19% vs. 16% in pre- and post-protocol groups, respectively, P = 0.463, and open myomectomy rate was 10% vs. 9% rates in pre- and post-protocol groups, respectively, P = 0.776). There was a significant decrease in the use of power morcellation (66% in pre- and 50% in post-protocol cohorts, p Conclusions Rates of MIS procedures were decreased for women with abnormal preoperative Magnetic Resonance Imaging results. False positive results appear to be one of the main drivers for the use of an open surgical route.

Purpose Although current clinical guidelines recommend surgery or radiotherapy for non-bulky IB-IIA cervical cancer, clinical data supporting the curative role of radiotherapy in the early-stage disease are insufficient. We evaluated the prognostic implications of definitive radiotherapy and determined its optimal use in clinical practice. Methods Patients with non-bulky ( Results Among the 9,391 initially identified patients, 1,762, 1,244, and 750 patients were classified into cohorts A, B, and C, respectively, after propensity score matching. In cohort A, DSS after primary radiotherapy was inferior to that after hysterectomy (P = 0.001). In cohort B, a trend toward differential survival in favor of hysterectomy was observed with marginal significance (P = 0.061). However, in cohort C, DSS after primary radiotherapy was not significantly different to that after hysterectomy (P = 0.127). According to hazard rate function plots, patients receiving external beam radiation alone had an increased short-term risk of disease-specific mortality, whereas patients without evidence of chemotherapy had a distinct late risk surge at approximately 15 years of follow-up. Conclusion Optimizing radiotherapy methods with brachytherapy and the use of chemotherapy should be considered for the long-term curative efficacy of primary radiotherapy for non-bulky IB-IIA cervical cancer. Further studies are warranted to corroborate our results.

Loss of stromal caveolin-1 (Cav-1) is a biomarker of a cancer-associated fibroblast (CAF) phenotype and is related to progression, metastasis, and poor outcomes in several cancers. The objective of this study was to evaluate the clinical significance of Cav-1 expression in invasive epithelial ovarian cancer (OvCa). Epithelial and stromal Cav-1 expression were quantified in serous OvCa and benign ovarian tissue in two, independent cohorts–one quantified expression using immunohistochemistry (IHC) and the other using multiplex immunofluorescence (IF) with digital image analysis designed to target CAF-specific expression. Cav-1 expression was significantly downregulated in OvCa stroma compared to non-neoplastic stroma using both the IHC (p = 0.002) and IF (p = 1.8x10-13) assays. OvCa stroma showed Cav-1 downregulation compared to tumor epithelium with IHC (p = 1.2x10-24). Conversely, Cav-1 expression was higher in OvCa stroma compared to tumor epithelium with IF (p = 0.002). There was moderate correlation between IHC and IF methods for stromal Cav-1 expression (r2 = 0.69, p = 0.006) whereas there was no correlation for epithelial expression (r2 = 0.006, p = 0.98). Irrespective of the staining assay, neither response to therapy or overall survival correlated with the expression level of Cav-1 in the stroma or tumor epithelium. Our findings demonstrate a loss of stromal Cav-1 expression in ovarian serous carcinomas. Studies are needed to replicate these findings and explore therapeutic implications, particularly for immunotherapy response.

The National Comprehensive Cancer Network recommends palliative care should be integrated in to cancer care starting from cancer diagnosis. However, traditionally palliative care is prioritized for cancer patients at the end-of-life. In our main article titled “Racial and Ethnic Disparities in Palliative Care Utilization Among Gynecological Cancer Patients” we present data describing racial/ethnic disparities among metastatic gynecological cancer patients who were deceased at last follow-up. Here, we expand our population to evaluate racial disparities in palliative care utilization among (1) all metastatic gynecologic cancer patients, regardless of vital status (alive or deceased) (n = 176,899) and (2) among only patients who were alive at last follow-up (n = 66,781). We used data from the 2016 National Cancer Database (NCDB) and included patients between ages 18–90 years with metastatic (stage III-IV) gynecologic cancers including, ovarian, cervical and uterine cancer. Palliative care was defined by NCDB as non-curative treatment, and could include surgery, radiation, chemotherapy, and pain management or any combination. We used multivariable logistic regression to evaluate racial disparities in palliative care use among our two populations of interest. Overall, the mean age of gynecologic cancer patients utilizing palliative care was 66 years. Five percent of all metastatic gynecologic oncology patients utilized palliative care overall; and by cancer site palliative care use was as follows: 4% among ovarian, 9% among cervical, and 11% among uterine cancer patients. Among patients who utilized palliative care, 62% utilized surgery, radiation or chemotherapy only and 12% utilized pain management as a form of palliative care. Among ovarian cancer patients, Hispanic ovarian cancer patients were less likely to utilize palliative care compared to their NH-White counterparts (aOR: 0.79, 95% CI: 0.68–0.91). Among cervical cancer patients, we observed that Hispanic (aOR: 0.65, 95% CI: 0.56–0.75) and Asian (aOR: 0.74, 95% CI: 0.59–0.93) were less likely to utilize palliative care than NH-White cervical cancer patients. We observed no racial disparities in palliative care utilization among uterine cancer patients. When we focused on patients who were alive at last follow-up we found that only 3% of patients utilized palliative care. We also conducted multivariable analyses of racial/ethnic disparities among ovarian and cervical cancer patients who were alive at last follow-up. We were unable to conduct multivariable analyses of uterine cancer patients who were alive at last follow-up due to limited sample size of those who utilized palliative care. We observed no racial/ethnic disparities among this patient population of metastatic gynecologic patients.

Background Clinical factors may influence endometrial cancer survival outcomes. We examined the prognostic significance of age, body mass index (BMI), and type 2 diabetes among molecular subgroups of endometrial cancer. Methods This was a single institution retrospective study of patients who underwent surgery for endometrial carcinoma between January 2007 and December 2012. Tumors were classified into four molecular subgroups by immunohistochemistry of mismatch repair (MMR) proteins and p53, and sequencing of polymerase-ϵ (POLE). Overall, cancer-related, and non-cancer-related mortality were estimated using univariable and multivariable survival analyses. Results Age >65 years was associated with increased mortality rates in the whole cohort (n = 515) and in the “no specific molecular profile” (NSMP) (n = 218) and MMR deficient (MMR-D) (n = 191) subgroups during a median follow-up time of 81 months (range 1‒136). However, hazard ratios for cancer-related mortality were non-significant for NSMP and MMR-D. Diabetes was associated with increased overall and non-cancer-related mortality in the whole cohort and MMR-D subgroup. Overweight/obesity had no effect on outcomes in the whole cohort, but was associated with decreased overall and cancer-related mortality in the NSMP subgroup, and increased overall and non-cancer-related mortality in the MMR-D subgroup. Overweight/obesity effect on cancer-related mortality in the NSMP subgroup remained unchanged after controlling for confounders. High-risk uterine factors were more common, and estrogen and progesterone receptor expression less common in NSMP subtype cancers of normal-weight patients compared with overweight/obese patients. No clinical factors were associated with outcomes in p53 aberrant (n = 69) and POLE mutant (n = 37) subgroups. No cancer-related deaths occurred in the POLE mutant subgroup. Conclusions The prognostic effects of age, BMI, and type 2 diabetes do not appear to be uniform for the molecular subgroups of endometrial cancer. Our data support further evaluation of BMI combined with genomics-based risk-assessment.

Amacımız, yaş ve aile hikayesinden bağımsız olarak merkezimizde over (OC) ve endometriyum kanseri (EC) tanısı ile cerrahisi ve ardından genetik mutasyon analizi uygulanan hastalarımızın mutasyon sıklığını ve sekanslarını araştırmaktır. Son yıllarda önleyici stratejilerin gelişimi dışında tedavi seçeneklerindeki fırsatlar ve genetik çalışmaların artışı herediter kanserlere ilgiyi arttırmıştır. En sık görülen herediter jinekolojik kanserler; herediter meme over kanseri (HBOC) ve Lynch Sendromu (LS) dur. Hastalığın düşük prevalansı, test pahalılığı ve etik sebepler popülasyon bazlı taramayı kullanışsız hale getirmektedir. Birimimizde 01.04.2018-01.10.2019 tarihleri arasında genetik araştırması yapılan 37 EC ve 15 OC tanısı almış hastamız çalışmaya dahil edilmiştir. BRCA1/2 ve LS genlerini de içeren (MLH1, MSH2, MSH6, PMS 2) 25 genden oluşan geniş ailevi panel testi uygulanmıştır. Ailevi gen paneli testi yapılan 27 EC hastamızda, 1 MLH1 ve 1 ATM geninde patolojik mutasyon saptandı (%3.7 LS,%3.7 non LS). 11 hastada önemi belirsiz varyant mutasyon (VUS) görüldü (%40.7). BRCA mutasyon araştırması yapılan 20 EC’li hastamızda patolojik mutasyon saptanmadı. BRCA mutasyonu araştırılan 14 OC’lu hastamızda 3 patolojik varyant identifiye edildi ve hepsi BRCA1 genindeydi (HBOC %21,4). Ailevi kanser paneli değerlendirilen 4 OC’lu hastada 1 MSH6 ve 1 ATM geninde patolojik mutasyonlar izlendi. Over ve endometriyum kanserlerinde ailevi geniş mutasyon verilerinin çoğalması ve literatürde paylaşımı VUS oranlarını azaltacak, BRCA ve LS dışındaki genlerin jinekolojik kanserlerdeki rolünü ortaya çıkartacak ve yeni tarama algoritmalarını oluşturacaktır. Our objective is to investigate the mutation frequency and sequences of our patients, who underwent surgery with a diagnosis of ovarian (OC) and endometrial cancer (EC) and subsequently underwent genetic mutation analysis, regardless of age and family history. In recent years, apart from the development of preventive strategies, opportunities in treatment options and increase in genetic studies have increased the interest in hereditary cancers. The most common hereditary gynecological cancers are hereditary breast ovarian cancer (HBOC) and Lynch Syndrome (LS). The low prevalence of the disease, cost of testing, and ethical reasons make population-based screening impractical. 37 patients diagnosed with endometrial cancer and 15 patients diagnosed with ovarian cancer were included in the study, and their genetic research was conducted in our department between 01.04.2018 and 01.10.2019. A large familial panel test consisting of 25 genes including BRCA1/2 and LS genes (MLH1, MSH2, MSH6, PMS 2) was performed. Pathological mutation was found in 1 MLH1 and 1 ATM genes in 27 patients with endometrial cancer who underwent familial gene panel test (3.7% LS, 3.7% non LS). Eleven patients had a variant mutation of uncertain significance (VUS) (40.7%). No pathological mutation was found in our 20 patients with endometrial cancer who were investigated for BRCA mutation. In our 14 patients with ovarian cancer whose BRCA mutation was investigated, 3 pathological variants were identified, and all of them were in BRCA1 gene (HBOC 21.4%). Pathological mutations in 1 MSH6 and 1 ATM genes were observed in 4 patients with ovarian cancer whose familial cancer panel was evaluated. The proliferation of comprehensive familial mutation data in ovarian and endometrial cancers and their sharing in the literature will reduce VUS rates, reveal the role of genes other than BRCA and LS in gynecological cancers, and create new screening algorithms.

Background The serum biomarker cancer antigen 125 (CA125) is widely used as an investigation for possible ovarian cancer in symptomatic women presenting to primary care. However, its diagnostic performance in this setting is unknown. We evaluated the performance of CA125 in primary care for the detection of ovarian and non-ovarian cancers. Methods and findings We studied women in the United Kingdom Clinical Practice Research Datalink with a CA125 test performed between 1 May 2011–31 December 2014. Ovarian and non-ovarian cancers diagnosed in the year following CA125 testing were identified from the cancer registry. Women were categorized by age, Garth Funston and colleagues assess the diagnostic efficacy of CA125 for ovarian cancer detection, Author summary Why was this study done? CA125 is widely used as a test for ovarian cancer in women presenting with relevant symptoms, both in the UK and internationally. CA125 has been extensively evaluated in the specialist care setting and in screening studies but little was known about its diagnostic performance in primary care, where most patients with ovarian cancer first present. What did the researchers do and find? We evaluated the diagnostic performance of CA125 in 50,780 women undergoing testing in English general practice. Of women with CA125 levels above the current abnormal cut-off, 10.1% were diagnosed with ovarian cancer and a further 12.3% with another form of cancer. Cancer was more common in women with abnormal CA125 levels if they were ≥50 years of age. We developed models to estimate the probability of ovarian cancer and all cancer based on a woman’s age and CA125 level. What do these findings mean? Clinicians should consider the possibility of non-ovarian cancer, in addition to ovarian cancer, in women with high CA125 levels. Our models will enable patients and clinicians to determine the estimated probability of cancer based on an individual’s age and CA125 level. This information can be used to help make decisions about the need for further investigation or urgent referral to a specialist. The findings should also help inform guidelines, as they will allow recommendations for further testing to be made on the basis cancer probability rather than a single CA125 cutoff.

Objectives The aim of this study was to estimate the prevalence of anemia among patients newly diagnosed with solid malignancies at King Faisal Hospital in Taif Province, Kingdom of Saudi Arabia. Methods A descriptive, cross-sectional, hospital-based study was conducted from December 2017 to March 2020. A total of 320 patients newly diagnosed with solid malignancy were examined to assess anemia prevalence. Results Of 320 patients with solid cancers, 245 (76.6%) were female and 75 (23.4%) were male. The median (interquartile range) age of 57 (45 ─ 66) years, range between 16 and 108 years. The types of cancer included were breast (29.1%), female genital tract (20.0%), colorectal (25.3%), head and neck (10.3%), urinary bladder (4.7%), prostate (5.0%), lung (2.5%), liver (2.2%) and lymphoma (0.9%). The prevalence of anemia at diagnosis of cancer was 44.1% across all cancer types. A higher anemia prevalence was noted in colorectal (n = 46/81, 56.8%) (p = 0.047). Conclusion Patients with colorectal or female genital tract cancers had a higher anemia prevalence (56.8% and 43.8%, respectively) than did patients with other cancers.

Morocco and the rest of the world are experiencing a pandemic of a new coronavirus known as COVID-19 or SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). On August 24, 2020, the spread of the virus in Morocco had caused more than 52,000 cases and 880 deaths. Cancer patients are more susceptible to develop an infection than people without cancer because of their immunosuppression caused by the disease and treatments (surgery and chemotherapy). Therefore, these patients are at higher risk of infection with COVID-19 and a much higher risk of developing more serious forms. Given this epidemiological context, the establishment of guidelines for patients with gynecological cancers, requiring multidisciplinary management during the global COVID-19 pandemic, is crucial to limit their infection while maintaining their chances for a cure. In this paper, we summarize the international COVID-19 recommendations on the prioritization of surgical cases, the perioperative protective measures, the precautions to be taken in the brachytherapy unit, the COVID-19 screening, and finally the therapeutic indications of gynecological cancers by tumor location.

Molecular biomarkers that can predict survival and therapeutic outcome are still lacking for cervical cancer. Here we measured a panel of 19 serum proteins in sera from 565 patients with stage II or III cervical cancer and identified 10 proteins that have an impact on disease specific survival (DSS) (Hazzard&rsquo, s ratio, HR = 1.51&ndash, 2.1). Surprisingly, all ten proteins are implicated in senescence-associated secreted phenotype (SASP), a hallmark of cellular senescence. Machine learning using Ridge regression of these SASP proteins can robustly stratify patients with high SASP, which is associated with poor survival, and patients with low SASP associated with good survival (HR = 3.09&ndash, 4.52). Furthermore, brachytherapy, an effective therapy for cervical cancer, greatly improves survival in SASP-high patients (HR = 3.3, p &lt, 5 &times, 10&minus, 5) but has little impact on survival of SASP-low patients (HR = 1.5, p = 0.31). These results demonstrate that cellular senescence is a major determining factor for survival and therapeutic response in cervical cancer and suggest that senescence reduction therapy may be an efficacious strategy to improve the therapeutic outcome of cervical cancer.

Gynecologic cancers account for approximately 11% of the newly diagnosed cancers in women in the United States and for 18% globally. The presence of tumor-infiltrating lymphocytes (TILs) influences the clinical outcome of cancer patients and immune checkpoint inhibitors (ICIs), including anti programmed cell death protein-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), and anticytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), which have been approved for treating different types of malignancies. Antibodies targeting the PD-1/PD-L1 checkpoint have shown dynamic and durable tumor regressions, suggesting a rebalancing of the host–tumor interaction. There are several the US food and drug administration (FDA)-approved ICIs targeting PD-1, including pembrolizumab and nivolumab, as well as those targeting PD-L1, including avelumab, atezolizumab, and durvalumab for melanoma, renal cell cancer, colorectal cancer, head and neck cancer, cervix cancer, urothelial cancer, and lung cancer. Current pre-clinical and clinical studies assessing PD-1/PD-L1 inhibitors in several gynecologic cancers have reported significant antitumor activity. In this review, we investigate pre-clinical and clinical studies that describe the safety and efficacy of anti-PD-1/PD-L1 antibodies, with a particular focus on ongoing clinical trials, analyzing the oncological outcome and adverse effects of ICIs in gynecologic cancers.

BackgroundA cancer disease can affect the satisfaction with the physical appearance, so that the standardized assessment of the body image is important in cancer patients. The German version of the Self-Image Scale is a self-report measure that uses two subscales to assess appearance satisfaction (self-acceptance) and perceptions of partners' acceptance of their appearance (partner-acceptance). The present study aimed to validate the Self-Image Scale's two-factor structure in a sample of cancer patients with a variety of different diagnoses to further increase its utility.MethodsConfirmatory factor analysis methods were used to examine the two-factor model in a sample of cancer patients (N = 278). Scale reliability and validity were then assessed through internal consistency measures and correlations with external criteria such as depressiveness, anxiety, distress, and relationship satisfaction.ResultsThe proposed factor structure was supported by the results and the internal consistencies were good with α = .83 for the self-acceptance scale and α = .88 for the partner-acceptance scale while additional correlations with external criteria were observed as expected.ConclusionsThe results support the use of the German version of the Self-Image Scale in cancer patients in general. Future research directions include validation across further entities of cancer, the in-depth investigation of sex differences, and research in other diseases that might impact body image.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cell death in various types of cancer cells but has little or no effects on normal cells. Unfortunately, not all cancer cells respond to TRAIL; therefore, TRAIL sensitizing agents are currently being explored. Here, we reported that 6-(4-N,N-dimethylaminophenyltelluro)-6-deoxy-β-cyclodextrin (DTCD), a cyclodextrin-derived diorganyl telluride which has been identified as an excellent inhibitor of thioredoxin reductase (TrxR), could sensitize TRAIL resistant human ovarian cancer cells to undergo apoptosis. In vitro, DTCD enhanced TRAIL-induced cytotoxicity in human ovarian cancer cells through up-regulation of DR5. Luciferase analysis and CHIP assays showed that DTCD increased DR5 promoter activity via Sp1 activation. Additionally, DTCD stimulated extracellular signal-regulated kinase (ERK) activation, while the ERK inhibitor PD98059 blocked DTCD-induced DR5 expression and suppressed binding of Sp1 to the DR5 promoter. We further demonstrated that DTCD could induce the release of ASK1 from its complex with Trx-1, and recovered its kinase activity. Meanwhile, suppression of ASK1 by RNA interference led to decreased ERK phosphorylation induced by DTCD. The underlying mechanisms reveal that Trx-1 is heavily oxidized in response to DTCD treatment, in accordance with the fact that DTCD could inhibit the activity of TrxR that reduces oxidized Trx-1. Moreover, using an A2780 xenograft model, DTCD plus TRAIL significantly inhibited the growth of tumor in vivo. Our results suggest that Trx/TrxR system inhibition may play a critical role in apoptosis by combined treatment with DTCD and TRAIL, and raise the possibility that their combination may be a promising strategy for ovarian carcinoma treatment.

Introduction CC-002 is a prospective cooperative group study conducted by NRG Oncology to evaluate whether a pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment (GA) is associated with major post-operative complications in elderly women with suspected ovarian, fallopian tube, primary peritoneal or advanced stage papillary serous uterine (GYN) carcinoma undergoing primary open cytoreductive surgery. Methods Patients 70 years or older with suspected advanced gynecologic cancers undergoing evaluation for surgery were eligible. A GA-GYN score was derived from a model utilizing the GA as a pre-operative tool. Patients were followed for six weeks post-operatively or until start of chemotherapy. Post-operative events were recorded either directly as binary occurrence (yes or no) using CTCAE version 4.0. Results There were 189 eligible patients, 117 patients with primary surgical intervention and 37 patients undergoing interval cytoreduction surgery. The association between higher GA-GYN score and major postoperative complications in patients undergoing primary surgery was not significant (p = 0.1341). In a subgroup analysis of patients with advanced staged malignant disease who underwent primary cytoreductive surgery, there was a trend towards an association with the GA-GYN score and post-operative complications. Conclusion The pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment was not predictive of major post-operative complications in elderly patients undergoing primary open cytoreductive surgery. However, there was an association between GA-GYN score and post-operative complications in a subgroup of patients with advanced staged malignant disease.

Background A large proportion of gynecological cancer survivors suffer from pain during sexual intercourse, also known as dyspareunia. Following a multimodal pelvic floor physical therapy (PFPT) treatment, a reduction in pain and improvement in psychosexual outcomes were found in the short term, but no study thus far has examined whether these changes are sustained over time. Purpose To examine the improvements in pain, sexual functioning, sexual distress, body image concerns, pain anxiety, pain catastrophizing, painful intercourse self-efficacy, depressive symptoms and pelvic floor disorder symptoms in gynecological cancer survivors with dyspareunia after PFPT, and to explore women’s perceptions of treatment effects at one-year follow-up. Methods This mixed-method study included 31 gynecological cancer survivors affected by dyspareunia. The women completed a 12-week PFPT treatment comprising education, manual therapy and pelvic floor muscle exercises. Quantitative data were collected using validated questionnaires at baseline, post-treatment and one-year follow-up. As for qualitative data, semi-structured interviews were conducted at one-year follow-up to better understand women’s perception and experience of treatment effects. Results Significant improvements were found from baseline to one-year follow-up on all quantitative outcomes (P ≤ 0.028). Moreover, no changes were found from post-treatment to one-year follow-up, supporting that the improvements were sustained at follow-up. Qualitative data highlighted that reduction in pain, improvement in sexual functioning and reduction in urinary symptoms were the most meaningful effects perceived by participants. Women expressed that these effects resulted from positive biological, psychological and social changes attributable to multimodal PFPT. Adherence was also perceived to influence treatment outcomes. Conclusions Findings suggest that the short-term improvements following multimodal PFPT are sustained and meaningful for gynecological cancer survivors with dyspareunia one year after treatment.

Purpose Evaluation of symptoms and signs for the management of neuropathic cancer pain (NCP) is challenging. This study aimed to identify clinical predictors of NCP and symptoms and signs most relevant of those in Korean patients. Methods This nationwide, descriptive, cross-sectional, multicenter, observational study included 2,003 cancer patients aged ≥20 years who reported a visual analog scale (VAS) score ≥1 for pain and provided informed consent for participation. The Douleur Neuropathic (DN4) questionnaire (score ≥4) was used to determine symptoms and signs as well as the presence of NCP. Results The prevalence of NCP was associated with age 6 months (OR, 1.57; 95% CI, 1.232–2.012), stage IV cancer (OR, 0.75; 95% CI, 0.593–0.955), history of chemotherapy (OR, 1.74; 95% CI, 1.225–2.472), and moderate-to-severe cancer pain (OR, 2.05; 95% CI, 1.671–2.524) after multivariate analysis. The most common descriptive symptoms of NCP were tingling, electric shock, and pins and needles. For NCP patients in the presence or absence of the clinical predictors, pins and needles (p = 0.001) and painful cold (p Conclusion Age 6 months, stage IV cancer, history of chemotherapy, and moderate-to-severe cancer pain, were identified as predictors of NCP. Some symptoms and signs of NCP were associated with these predictors. Further studies are warranted on the pathogenesis and management of NCP with respect to the symptoms and signs, and factors associated with pain severity in Korean patients.

A sperm-driven micromotor is presented as a targeted drug delivery system, which is appealing to potentially treat diseases in the female reproductive tract. This system is demonstrated to be an efficient drug delivery vehicle by first loading a motile sperm cell with an anticancer drug (doxorubicin hydrochloride), guiding it magnetically, to an in vitro cultured tumor spheroid, and finally freeing the sperm cell to deliver the drug locally. The sperm release mechanism is designed to liberate the sperm when the biohybrid micromotor hits the tumor walls, allowing it to swim into the tumor and deliver the drug through the sperm-cancer cell membrane fusion. In our experiments, the sperm cells exhibited a high drug encapsulation capability and drug carrying stability, conveniently minimizing toxic side effects and unwanted drug accumulation in healthy tissues. Overall, sperm cells are excellent candidates to operate in physiological environments, as they neither express pathogenic proteins nor proliferate to form undesirable colonies, unlike other cells or microorganisms. This sperm-hybrid micromotor is a biocompatible platform with potential application in gynecological healthcare, treating or detecting cancer or other diseases in the female reproductive system.

Gynecologic cancers are among the most common cancers in humans and animals. Treatment success depends on several factors including stage at diagnosis, tumor type, origin and metastasis. Currently, surgery, chemotherapy, and radiotherapy are preferred in the treatment of these cancers. However, many anticarcinogenic drugs can cause severe adverse effects and also the expected response to treatment may not be obtained. In recent studies, the importance of the relationship between cancer and inflammation has been emphasized. Therefore, several phytochemicals that exhibit beneficial bioactive effects towards inflammatory pathways were proven to have anticarcinogenic potential for gynecologic cancer therapy. This review summarizes the role of inflammatory pathways in gynecologic cancers and effective secondary metabolites for cancer therapy.

ObjectiveThe aim of the study was to compare the characteristics of procedures for gynecologic cancers conducted with conventional laparoscopy (CL) or robotically assisted laparoscopy (RAL) in the context of an enhanced recovery program (ERP).MethodsThis is a secondary analysis of prospectively collected data from a cohort study conducted between 2016 (when the ERP was first implemented at the Institut Paoli-Calmettes, a comprehensive cancer center in France) and 2018. We included patients who had undergone minimally invasive surgery for gynecological cancers and followed our ERP. The endpoints were the analysis of postoperative complications, the length of postoperative hospitalization (LPO), and the proportion of combined procedures depending on the approach (RAL or CL). Combined procedures were defined by the association of at least two of the following operative items: hysterectomy, pelvic lymphadenectomy, and para-aortic lymphadenectomy.ResultsA total of 362 women underwent either CL (n = 187) or RAL (n = 175) for gynecologic cancers and followed our ERP. The proportion of combined procedures performed by RAL was significantly higher (85/175 [48.6%]) than that performed by CL (23/187 [12.3%]; p < 0.001). The proportions of postoperative complications were similar between the two groups (19.4% versus 17.1%; p = 0.59). Logistic regression analysis revealed a statistically insignificant trend in the association of RAL with a reduced likelihood of an LPO > 3 days after adjusting for predictors of prolonged hospitalization (adjusted OR = 0.573 [0.236-1.388]; p = 0.217).ConclusionExperts from our cancer center preferentially choose RAL to perform gynecologic oncological procedures that present elements of complexity. More studies are needed to determine whether this strategy is efficient in managing complex procedures in the framework of an ERP.