Search

ObjectiveTo describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials.MethodsGynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data.Results2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p

Background: Despite physical and emotional distress in patients with gynecologic malignancies, palliative care (PC) is underutilized. Objectives: We characterize referral practices, symptom burden and functional status at the time of initial PC encounter for patients with gynecologic cancer. Design: Data were extracted from the standardized Quality Data Collection Tool for Palliative Care (QDACT-PC). We describe symptom burden and performance status. Results: At initial specialty PC encounter, patients with gynecologic cancers reported a mean of 3.3 moderate/severe symptoms. Outpatients experienced the most moderate/severe symptoms (mean 3.9) versus inpatient (mean 2.1) or home (mean 1.5). A total of 72.7% of patients had significantly impaired functional status (palliative performance scale [PPS] <70) at initial encounter. Inpatients had a more impaired functional status (mean PPS 48.8) than outpatients (mean PPS 67.0). Conclusions: The symptom burden for gynecologic cancer patients at initial PC encounter is high. Despite better functional status, patients referred in the outpatient setting had the highest symptom burden. [ABSTRACT FROM AUTHOR]

Simple Summary: NAD+ is a key cofactor that plays a role in various metabolic and signaling pathways. Understanding its ability to regulate cellular homeostasis also sheds light on its role in tumorigenesis and disease progression in gynecologic cancers. By reviewing the enzymes that consume NAD+ as well as the pathways and enzymes that synthesize NAD+, the vast influence NAD+ has on the survival of cancer cells becomes clear. With that information, advances have been made in the development of unique inhibitors to target NAD+ synthesizing and consuming enzymes. Nicotinamide adenine dinucleotide (NAD+) is an important cofactor for both metabolic and signaling pathways, with the dysregulation of NAD+ levels acting as a driver for diseases such as neurodegeneration, cancers, and metabolic diseases. NAD+ plays an essential role in regulating the growth and progression of cancers by controlling important cellular processes including metabolism, transcription, and translation. NAD+ regulates several metabolic pathways such as glycolysis, the citric acid (TCA) cycle, oxidative phosphorylation, and fatty acid oxidation by acting as a cofactor for redox reactions. Additionally, NAD+ acts as a cofactor for ADP-ribosyl transferases and sirtuins, as well as regulating cellular ADP-ribosylation and deacetylation levels, respectively. The cleavage of NAD+ by CD38—an NAD+ hydrolase expressed on immune cells—produces the immunosuppressive metabolite adenosine. As a result, metabolizing and maintaining NAD+ levels remain crucial for the function of various cells found in the tumor microenvironment, hence its critical role in tissue homeostasis. The NAD+ levels in cells are maintained by a balance between NAD+ biosynthesis and consumption, with synthesis being controlled by the Preiss–Handler, de novo, and NAD+ salvage pathways. The primary source of NAD+ synthesis in a variety of cell types is directed by the expression of the enzymes central to the three biosynthesis pathways. In this review, we describe the role of NAD+ metabolism and its synthesizing and consuming enzymes' control of cancer cell growth and immune responses in gynecologic cancers. Additionally, we review the ongoing efforts to therapeutically target the enzymes critical for NAD+ homeostasis in gynecologic cancers. [ABSTRACT FROM AUTHOR]

Despite its importance, there is no consensus definition of access to care, and several fundamental philosophical questions about access remain unanswered. Lack of clarity impedes interventional research designed to develop and test methods of correcting barriers to access. To help remedy this problem, we propose a conceptual framework to help guide empirical research about access to gynecologic cancer care. Relevant philosophical and empirical literature was reviewed and analyzed to highlight key elements needed to refine research on access to care. The DIMeS framework involves 1) choice and justification of a Definition of access to cancer care that will guide research; 2) Identification of essential gynecologic cancer care services for which access disparities are ethically unacceptable; 3) quantitative MEasurement of specific parameters that affect access to care; and 4) Selection of a target threshold on measured parameters above which access is acceptable. The DIMeS framework provides clarity and reproducibility for investigators seeking to develop and test interventions to improve cancer health equity. This framework should be considered for use in research on access to gynecologic cancer care. • There is no consensus definition of access to care, and fundamental philosophical questions about access remain unanswered. • A common, robust methodology is needed for interventional research to correct inequities in access to gynecologic cancer care. • The DIMeS framework provides a clear structure for the study of access to care and cancer health inequity. [ABSTRACT FROM AUTHOR]

Abstract Objectives The relationship between hepatitis B virus (HBV) infection and gynecologic cancers is controversial. We aimed to evaluate the risk of gynecologic cancers associated with HBV infection using a meta-analysis. Methods Two independent reviewers identified publications in the PubMed, Embase and Cochrane Library databases that reported an association between HBV and the risk of gynecologic malignancy from inception to December 31, 2022. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included articles. Pooled odds ratios (ORs) and 95% corresponding confidence intervals (CIs) were calculated using a fixed effects model or random effects model. Results We collected data from 7 studies that met the inclusion criteria, including 2 cohort studies and 5 case-control studies. HBV was significantly associated with the risk of cervical cancer in the general population (OR 1.22, 95% CI 1.09–1.38, P = 0.001), although the same trend was not found in endometrial cancer (OR 1.30, 95% CI 0.95–1.77, P = 0.105) and ovarian cancer (OR 1.03, 95% CI 0.79–1.35, P = 0.813). Subgroup analysis showed that HBV infection was positively associated with the risk of cervical cancer (OR 1.27, 95% CI 1.13–1.44, P = 0.000) in case-control studies. Asian women infected with HBV have a significantly increased risk of cervical cancer (OR 1.24, 95% CI 1.10–1.40, P = 0.001) and endometrial cancer (OR 1.46, 95% CI 1.07–1.99, P = 0.018). Hospital-based studies were found to be associated with an increased risk of cervical cancer (OR 1.30, 95% CI 1.14–1.47, P = 0.000) and endometrial cancer (OR 1.61, 95% CI 1.04–2.49, P = 0.032). The results of Begg’s and Egger’s tests showed no publication bias. Conclusions This meta-analysis shows a positive association between HBV infection and cervical cancer. HBV is positively correlated with the risk of cervical cancer and endometrial cancer in Asian women and hospital-based populations. More multicenter prospective studies are required to confirm the findings.

Objectives: The relationship between hepatitis B virus (HBV) infection and gynecologic cancers is controversial. We aimed to evaluate the risk of gynecologic cancers associated with HBV infection using a meta-analysis. Methods: Two independent reviewers identified publications in the PubMed, Embase and Cochrane Library databases that reported an association between HBV and the risk of gynecologic malignancy from inception to December 31, 2022. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included articles. Pooled odds ratios (ORs) and 95% corresponding confidence intervals (CIs) were calculated using a fixed effects model or random effects model. Results: We collected data from 7 studies that met the inclusion criteria, including 2 cohort studies and 5 case-control studies. HBV was significantly associated with the risk of cervical cancer in the general population (OR 1.22, 95% CI 1.09–1.38, P = 0.001), although the same trend was not found in endometrial cancer (OR 1.30, 95% CI 0.95–1.77, P = 0.105) and ovarian cancer (OR 1.03, 95% CI 0.79–1.35, P = 0.813). Subgroup analysis showed that HBV infection was positively associated with the risk of cervical cancer (OR 1.27, 95% CI 1.13–1.44, P = 0.000) in case-control studies. Asian women infected with HBV have a significantly increased risk of cervical cancer (OR 1.24, 95% CI 1.10–1.40, P = 0.001) and endometrial cancer (OR 1.46, 95% CI 1.07–1.99, P = 0.018). Hospital-based studies were found to be associated with an increased risk of cervical cancer (OR 1.30, 95% CI 1.14–1.47, P = 0.000) and endometrial cancer (OR 1.61, 95% CI 1.04–2.49, P = 0.032). The results of Begg's and Egger's tests showed no publication bias. Conclusions: This meta-analysis shows a positive association between HBV infection and cervical cancer. HBV is positively correlated with the risk of cervical cancer and endometrial cancer in Asian women and hospital-based populations. More multicenter prospective studies are required to confirm the findings. [ABSTRACT FROM AUTHOR]

The highest frequency of genetic alterations in the tumor suppressor ARID1A occurs in malignancies of the female reproductive tract. The prevalence of ARID1A alterations in gynecologic precancers and cancers is summarized from the literature, and the putative mechanisms of tumor suppressive action examined both in benign/precursor lesions including endometriosis and atypical hyperplasia and in malignancies of the ovary, uterus, cervix and vagina. ARID1A alterations in gynecologic cancers are usually loss-of-function mutations, resulting in diminished or absent protein expression. ARID1A deficiency results in pleiotropic downstream effects related not only to its role in transcriptional regulation as a SWI/SNF complex subunit, but also related to the functions of ARID1A in DNA replication and repair, immune modulation, cell cycle progression, endoplasmic reticulum (ER) stress and oxidative stress. The most promising actionable signaling pathway interactions and therapeutic vulnerabilities of ARID1A mutated cancers are presented with a critical review of the currently available experimental and clinical evidence. The role of ARID1A in response to chemotherapeutic agents, radiation therapy and immunotherapy is also addressed. In summary, the multi-faceted role of ARID1A mutation in precancer and cancer is examined through a clinical lens focused on development of novel preventive and therapeutic interventions for gynecological cancers. [ABSTRACT FROM AUTHOR]

This article delves into the intricate interplay between tumors, particularly gynecologic malignancies, and neutrophil extracellular traps (NETs). The relationship between tumors, specifically gynecologic malignancies, and NETs is a multifaceted and pivotal area of study. Neutrophils, pivotal components of the immune system, are tasked with combating foreign invaders. NETs, intricate structures released by neutrophils, play a vital role in combating systemic infections but also play a role in non-infectious conditions such as inflammation, autoimmune diseases, and cancer. Cancer cells have the ability to attract neutrophils, creating tumor-associated neutrophils, which then stimulate the release of NETs into the tumor microenvironment. The impact of NETs within the tumor microenvironment is profound and intricate. They play a significant role in influencing cancer development and metastasis, as well as modulating tumor immune responses. Through the release of proteases and pro-inflammatory cytokines, NETs directly alter the behavior of tumor cells, increasing invasiveness and metastatic potential. Additionally, NETs can trigger epithelial-mesenchymal transition in tumor cells, a process associated with increased invasion and metastasis. The interaction between tumors and NETs is particularly critical in gynecologic malignancies such as ovarian, cervical, and endometrial cancer. Understanding the mechanisms through which NETs operate in these tumors can offer valuable insights for the development of targeted therapeutic interventions. Researchers are actively working towards harnessing this interaction to impede tumor progression and metastasis, opening up new avenues for future treatment modalities. As our understanding of the interplay between tumors and NETs deepens, it is anticipated that novel treatment strategies will emerge, potentially leading to improved outcomes for patients with gynecologic malignancies. This article provides a comprehensive overview of the latest research findings on the interaction between NETs and cancer, particularly in gynecologic tumors, serving as a valuable resource for future exploration in this field.

ObjectiveThis study aims to evaluate the nutritional status of Chinese gynecologic cancer survivors with post-surgical lower limb lymphedema (LLL) by analyzing serum albumin levels and the prognostic nutritional index (PNI).MethodsA retrospective cross-sectional study was conducted at two Chinese medical centers. The cohort comprised 155 gynecologic cancer survivors who developed symptomatic unilateral LLL post-surgery, during the period from September 2021 to June 2024. Nutritional status was assessed by measuring serum albumin and PNI. Statistical analysis was performed using univariate and multivariate logistic regression models to identify factors associated with low serum albumin and PNI.ResultsThe mean age of the cohort was 55.47 ± 10.56 years, and the median total survival time was 72.0 months (36.5, 111.5 months). The prevalence of low serum albumin (< 40 g/L) was 40.0%, and low PNI (< 45) was 80.6%. Significant associations were found between low hemoglobin levels and both low serum albumin (OR = 1.05, 95% CI: 1.02–1.08, p < 0.001) and low PNI (OR = 1.09, 95% CI: 1.04–1.13, p < 0.001). Advanced International Society of Lymphology stage 3 was also associated with low albumin (OR = 0.18, 95% CI: 0.03–0.99, p < 0.05).ConclusionThe study highlights a significant prevalence of high risk of malnutrition among Chinese gynecologic cancer survivors with LLL, underscoring the need for regular nutritional assessments and interventions.

ObjectiveThis study aims to analyze the association between the weight-adjusted waist index (WWI) and the risk of gynecologic cancers, using data collected from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016.MethodsWe employed multiple logistic regression analysis to investigate the relationship between WWI and risk of gynecologic cancers. Subsequent subgroup analyses were performed on specific populations of interest. A restricted cubic spline model was used to explore potential non-linear relationships. Additionally, the effectiveness of WWI in predicting sarcopenia was assessed through Receiver Operating Characteristic (ROC) curve analysis. K-fold cross-validation was applied for model assessment.ResultsAmong the 4,144 participants, 98 self-reported having gynecologic cancers. In the fully adjusted model, WWI was significantly associated with the prevalence of gynecologic cancers (OR = 1.38, 95% CI: 1.02–1.88, p = 0.0344). Our findings indicate a linear positive association between WWI and the risk of gynecologic cancers. Subgroup analysis revealed that WWI had the strongest association with cervical cancer (OR = 1.46, 95% CI: 0.97–2.18, p = 0.0354) and endometrial cancer (OR = 1.39, 95% CI: 0.81–2.39, p = 0.0142). No significant association was found between WWI and the risk of ovarian cancer (OR = 1.16, 95% CI: 0.48–2.72, p = 0.5359). Restricted cubic spline analysis confirmed a linear relationship between WWI and the risk of cervical, endometrial, and ovarian cancers. ROC curve analysis demonstrated that WWI had superior predictive capability for gynecologic cancers.ConclusionElevated levels of WWI were significantly associated with an increased risk of gynecologic cancers in American women, displaying a stronger association than other obesity markers. Therefore, WWI may serve as a distinct and valuable biomarker for assessing the risk of gynecologic cancers, particularly cervical and endometrial cancers.

Background: The risk factors for acute care utilization in gynecologic oncology patients are poorly understood. This study aimed to evaluate risk factors for the utilization of our centre’s acute care radiation nursing clinic (RNC) by gynecologic oncology patients receiving radiotherapy (RT). Methods: This was a retrospective cohort study of gynecological cancer patients treated with RT at an academic cancer centre between 1 August 2021 and 31 January 2022. Data on socio-demographics, clinical and treatment characteristics, and RNC visits were collected and summarized by descriptive statistics. The Wilcoxon rank sum test and chi-squared test/Fisher’s exact test were used for comparisons of continuous and categorical variables, respectively. Results: RT was delivered to 180 patients, of whom 42 (23%) received concurrent chemoradiation (CCR). Compared to those receiving RT alone, patients receiving CCR had higher rates of RNC utilization (55% vs. 19%, p < 0.001). Within the CCR cohort, patients who presented to the RNC were more likely to be unpartnered (43% vs. 11%, p = 0.04), receive a referral to Psychosocial Oncology (39% vs. 5.3%, p = 0.01), and experience treatment interruptions (52% vs. 16%, p = 0.02). There were no associations between RNC visits and age, disease site, or distance from the cancer centre. Conclusions: The receipt of CCR and specific psychosocial risk factors were associated with increased RNC utilization. Targeted strategies and early intervention to better meet the supportive care and psychosocial needs of this vulnerable population are needed.

Participation in therapeutic clinical trials does not reflect the diversity of gynecologic cancer patients, limiting access to novel therapeutics and generalizability of results. Reasons for inequities in participation among historically underrepresented populations remain undertheorized, as studies have shown equal willingness to participate among groups. We sought to apply a precarity framework to conceptualize the factors that impact patients' desire to enroll, to improve equity in gynecologic oncology clinical trial participation. Gynecologic cancer patients at a single tertiary care facility in the Southwestern United States who discussed participation in therapeutic clinical trial with their oncology provider from 2020 to 2021 were identified. Enrolled participants completed surveys and qualitative interviews regarding treatment experiences and decision-making. Oncology providers completed parallel surveys at the time of their patient's enrollment. Descriptive statistics and thematic coding were used to analyze data. 30 patients were enrolled and participated in surveys and interviews. No differences were found in quantitative data assessing shared decision-making and patient-centered communication between those who enrolled and those who did not. Qualitative data demonstrated that patients who declined trial enrollment expressed concerns regarding uncertainty and loss of control, independence in decision-making, and significant resource challenges and financial toxicity of cancer treatment. We identified a constellation of factors that contribute to desire to enroll in clinical trials, that we describe using the framework of precarity. Through identification of precarious patients and mitigation of burdens, we anticipate improved enrollment and retention in therapeutic clinical trials among diverse gynecologic oncology patients. • Precarity describes intersections of marginalized identities with social and economic structures to define patient burden. • Precarious patients are unlikely to participate in cancer clinical trials due to uncertainty that enrollment entails. • Identifying and addressing precarity at initiation of treatment may encourage patient participation in clinical trials. • Decreasing clinical trial inequities requires community collaborations to address factors impacting marginalized patients. [ABSTRACT FROM AUTHOR]

Background: The risk factors for acute care utilization in gynecologic oncology patients are poorly understood. This study aimed to evaluate risk factors for the utilization of our centre's acute care radiation nursing clinic (RNC) by gynecologic oncology patients receiving radiotherapy (RT). Methods: This was a retrospective cohort study of gynecological cancer patients treated with RT at an academic cancer centre between 1 August 2021 and 31 January 2022. Data on socio-demographics, clinical and treatment characteristics, and RNC visits were collected and summarized by descriptive statistics. The Wilcoxon rank sum test and chi-squared test/Fisher's exact test were used for comparisons of continuous and categorical variables, respectively. Results: RT was delivered to 180 patients, of whom 42 (23%) received concurrent chemoradiation (CCR). Compared to those receiving RT alone, patients receiving CCR had higher rates of RNC utilization (55% vs. 19%, p < 0.001). Within the CCR cohort, patients who presented to the RNC were more likely to be unpartnered (43% vs. 11%, p = 0.04), receive a referral to Psychosocial Oncology (39% vs. 5.3%, p = 0.01), and experience treatment interruptions (52% vs. 16%, p = 0.02). There were no associations between RNC visits and age, disease site, or distance from the cancer centre. Conclusions: The receipt of CCR and specific psychosocial risk factors were associated with increased RNC utilization. Targeted strategies and early intervention to better meet the supportive care and psychosocial needs of this vulnerable population are needed. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the association between race/ethnicity and all-cause mortality among women with advanced-stage ovarian cancer who received systemic therapy. Methods: We analyzed data from the National Cancer Database on women diagnosed with advanced-stage ovarian cancer from 2004 to 2015 who received systemic therapy. Race/ethnicity was categorized as Non-Hispanic (NH) White, NH-Black, Hispanic, NH-Asian/Pacific Islander, and Other. Income and education were combined to form a composite measure of socioeconomic status (SES) and categorized into low-, mid-, and high-SES. Multivariable Cox proportional hazards models were used to assess whether race/ethnicity was associated with the risk of death after adjusting for sociodemographic, clinical, and treatment factors. Additionally, subgroup analyses were conducted by SES, age, and surgery receipt. Results: The study population comprised 53,367 women (52.4% ages ≥ 65 years, 82% NH-White, 8.7% NH-Black, 5.7% Hispanic, and 2.7% NH-Asian/Pacific Islander) in the analysis. After adjusting for covariates, the NH-Black race was associated with a higher risk of death versus NH-White race (aHR: 1.12; 95% CI: 1.07,1.18), while Hispanic ethnicity was associated with a lower risk of death compared to NH-White women (aHR: 0.87; 95% CI: 0.80, 0.95). Furthermore, NH-Black women versus NH-White women had an increased risk of mortality among those with low-SES characteristics (aHR:1.12; 95% CI:1.03–1.22) and mid-SES groups (aHR: 1.13; 95% CI:1.05–1.21). Conclusions: Among women with advanced-stage ovarian cancer who received systemic therapy, NH-Black women experienced poorer survival compared to NH-White women. Future studies should be directed to identify drivers of ovarian cancer disparities, particularly racial differences in treatment response and surveillance. [ABSTRACT FROM AUTHOR]

As more premenopausal patients undergo fertility preserving cancer treatments, there is an increased need for fertility counseling and ovarian sparing strategies. Many patients receive gonadotoxic chemotherapeutic agents which can put them at risk of primary ovarian insufficiency or profoundly diminished ovarian reserve. Traditionally, estradiol and follicle stimulating hormone (FSH) values have been used to evaluate ovarian function but more recently, reproductive endocrinologists have been proponents of anti-mullerian hormone (AMH) as a validated measure of ovarian potential. While the gold standard for fertility preservation remains oocyte cryopreservation, data suggest there may be additional interventions that can mitigate the gonadotoxic effects of chemotherapeutic agents. The main objectives of this focused review were to quantify the risk of primary ovarian failure associated with the most common chemotherapies used in treatment of gynecologic cancers and to evaluate and recommend potential interventions to mitigate toxic effects on ovarian function. Chemotherapeutic agents can cause direct loss of oocytes and primordial follicles as well as stromal and vascular atrophy and the extent is dependent upon mechanism of action and age of the patient. The risk of ovarian failure is the highest with alkylating agents (42.2 %), anthracyclines (

To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data. 2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013–2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years – REMGs made up 19.6% of trial participants in 2007–2009 compared to 38.1% in 2016–2018 (p < 0.0001). Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials. • REMGs are understudied and under-enrolled in gynecologic oncology clinical trials. • Ovarian cancer trials enroll fewer REMGs compared to other cancer trials. • The recruitment of REMGs is modestly increasing in recent years. • Further efforts to increase REMG enrollment to achieve health equity are needed. [ABSTRACT FROM AUTHOR]

A Lifestyle Medicine approach to compliment cancer care is less commonly researched or implemented for women with gynecologic cancers as compared to better funded malignancies such as breast, prostate, and colorectal. Yet, several gynecologic malignancies are linked to obesity, estrogen/metabolic signaling pathways, and altered tumor microenvironment which could benefit greatly from a lifestyle medicine program. Lifestyle medicine, an evidenced-based branch of science, has expanded to the prevention and treatment of disorders caused by lifestyle factors (including cancer). Modifiable lifestyle factors such as obesity, lack of physical activity/nutrient density, microbial dysbiosis, sleep disturbance, and chronic stressors contribute greatly to cancer morbidity and mortality worldwide. This overarching area of research is evolving with some subtopics in their infancy requiring further investigation. Modern tools have allowed for better understanding of mechanisms by which adiposity and inactivity affect tumor promoting signaling pathways as well as the local tumor environment. Through the evolving use of these sophisticated techniques, novel prognostic biomarkers have emerged to explore efficacy of pharmacologic and lifestyle interventions in cancer. This state-of-the-art review article appraises recent evidence for a lifestyle medicine approach, beyond diet and exercise, to optimize survivorship and quality of life for patients with gynecologic cancers and introduces the 8-week web-based comprehensive HEAL-GYN program. [ABSTRACT FROM AUTHOR]

Purpose: The present study aimed to evaluate the associations between the gut microbiome and psychoneurological symptoms (PNS) cluster in women with gynecologic cancers over time. Methods: In this secondary data analysis, 19 women with cervical and endometrial cancers treated with radiotherapy were followed at pre-treatment, 6–8 weeks, and 6 months post-treatment. To measure symptoms, Functional Assessment of Cancer Therapy-General (FACT-G) and Patient Health Questionnaire-9 (PHQ-9) were used. An average Z score of at least three out of five symptoms was computed as the PNS cluster total score. Rectal swabs were also collected at the same time points and sequenced using 16S rRNA V4 regions. The Kruskal–Wallis and permutational multivariable analysis of variance tests were used to compare α- and β-diversity between patients with high and low PNS cluster. The linear discriminant analysis effect size (LEfSe) tested taxa differences between study groups. Also, the linear mixed-effect model was used to evaluate the association of the gut microbiome and the PNS cluster over cancer treatment. Results: The patients’ mean age was 58 years, 47% Black, 52% single/divorced, and 66% had college or above education. Among the participants, 63% had endometrial cancer with stage I disease. There was a different taxonomy profile between patients with high and low PNS. Patients with high PNS had a lower α-diversity than those with low PNS (Shannon, p = 0.03, evenness, p = 0.03). The mixed effects model results showed that low α-diversity and abundance of Fusicatenibacter and Ruminococcus were associated with high PNS cluster over cancer treatment. Conclusion: The association between the gut microbiome and PNS cluster suggest that the gut microbiota plays a role in developing the PNS cluster. Future larger studies are required to shed light on the gut microbiota role in symptom development in gynecologic cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: To probe the differences of dosimetry and acute radiation enteritis between prone and supine position in gynecological cancer patients treated with intensity‐modulate radiotherapy (IMRT). Methods: Gynecologic tumor patients who received IMRT from January 2020 to July 2021 were analyzed. 60 patients were enrolled and divided into the supine or prone position group according to different radiotherapy positions, including 34 patients in prone position and 26 patients in supine position. The dose‐volume histogram of organs at risk (OARs) and the incidence of acute radiation enteritis were compared between the two groups. Multivariate logistic regression analysis was conducted to show the clinical characteristics and dose volume metrics to the association of acute radiation enteritis. Results: The percentage of volume receiving 5 Gy, 10 Gy, 15 Gy, 20 Gy, 30 Gy, 40 Gy, and 45 Gy doses for the small intestine were 79.0%, 67.4%, 59.6%, 44.3%, 17.0%, 8.9%, and 6.0%, respectively in the prone group, which were lower than those in the supine group (P < 0.05). The mean radiation dose (Dmean) of the small intestine exposure in prone group was decreased (P < 0.001). Compared with the supine group, the prone group who suffered from acute radiation enteritis were much less. The probability of indigestion, nausea, vomiting, diarrhea, and abdominal pain in the prone position were 35.29%, 29.41%, 17.65%, 38.24%, and 5.88%, respectively. The differences in indigestion, nausea, and diarrhea between the two groups were statistically significant (P = 0.012, P = 0.029, and P = 0.041). Multivariate logistic regression analysis was shown that prone position was found to be protective against indigestion (P = 0.002), nausea (P = 0.013), vomiting (P = 0.035), and abdominal pain (P = 0.021). Conclusion: Prone position in IMRT for gynecological cancers could significantly reduce radiation dose to the small bowel and colon, which would decrease the occurrence and severity of acute intestinal side effects possibly. [ABSTRACT FROM AUTHOR]

Objective: Approximately fifteen million women in the United States live > 50 miles from a gynecologic oncologist. Telemedical technology allows patients’ local physicians to consult with subspecialist gynecologic oncologists without burdening patients with unnecessary in-person visits. Although critical to adoption of this technology, physicians’ input into implementation of clinician-to-clinician consultation has not been sought. We therefore gathered feedback about experiences with referrals, communication, and openness to telemedical consultation from gynecologic oncologists, gynecologists, and medical oncologists. Methods: We recruited gynecologic oncologists, gynecologists, and medical oncologists from practices serving rural patients to participate in semi-structured interviews. The Consolidated Framework for Implementation Research and the Theoretical Domains Framework guided the interviews. Questions focused on factors influencing adoption and implementation of clinician-to-clinician telemedicine. Interviews were conducted via WebEx, recorded, and transcribed. Two investigators coded interviews using the combined frameworks and identified salient themes. Results: We conducted 11 interviews (6 gynecologic oncologists, 3 gynecologists, 2 medical oncologists) and identified themes encompassing communication burnout, barriers to sharing patient information, need for further logistical information, and potential benefits to patients. Conclusions: Clinician-to-clinician telemedicine may improve access to gynecologic cancer care by decreasing barriers to subspecialty expertise while simultaneously benefiting referring and consultant clinicians through improved identification and workup of patients who may need in-person consultation. To optimize desired outcomes, telemedical consultation must allow for communication of relevant patient information and records and easy integration into clinical workflow. Importantly, clinicians must perceive the consultation as improving patients’ access to specialty care.

Over the past decade, there have been significant developments in treatment for ovarian cancer, yet the lack of targeted therapy with few side effects still represents a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the tumorigenesis process and metabolism of drugs and has a negative impact on therapy outcomes. Gaining more insight into CYP expression is crucial to understanding the pathophysiology of ovarian cancer since many isoforms are essential to the metabolism of xenobiotics and steroid hormones, which drive the disease's development. To the best of our knowledge, no review articles have documented the intratumoral expression of CYPs and their implications in ovarian cancer. Therefore, the purpose of this review is to provide a clear understanding of differential CYP expression in ovarian cancer and its implications for the prognosis of ovarian cancer patients, together with the effects of CYP polymorphisms on chemotherapy metabolism. Finally, we discuss opportunities to exploit metabolic CYP expression for the development of novel therapeutic methods to treat ovarian cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: The impact of stroke on patients with cancer is of significant concern, as gynecologic oncologists occasionally face medical challenges in managing patients who experience stroke during cancer treatment. However, the relationship between stroke and gynecological cancers has not been sufficiently explored. Here, we evaluated the risk factors for stroke in patients with three major types of gynecological cancers and their effects on cancer prognosis. Out of the 644 patients, 54 (8.4%) experienced a stroke, which is notably higher than the 2% of stroke occurrence rate in the general population. Stroke is significantly associated with age and hypertension. Contrary to our initial concerns, stroke was not found to be an independent prognostic factor for progression-free or overall survival. These findings suggest the importance of an appropriate management plan that considers the age, medical history, and tumor characteristics of the patient, rather than an excessive concern about stroke itself. Increased life expectancy and cancer prevalence rates expose patients to a higher risk of developing other comorbidities such as stroke. This study aimed to evaluate the risk factors for and prognosis of stroke in patients with gynecological cancers. A single-center retrospective cohort study was conducted on patients with cervical, endometrial, and epithelial ovarian cancers. Patients were classified into three groups based on the period of stroke onset: at least one year before cancer diagnosis, within one year before cancer diagnosis to six months after the last treatment date, and six months after the last treatment date. Among the 644 patients, stroke occurred in 54 (8.4%). In univariate analysis, stroke was significantly associated with overall survival. In contrast, in multivariate analysis, stroke was significantly associated with age and hypertension, but not with overall survival. Age, pulmonary thromboembolism/deep vein thrombosis, histological grade, and tumor stage were significantly associated with overall survival. Therefore, it is important to establish an appropriate examination and treatment plan for patients with gynecologic cancers using a multidisciplinary approach that incorporates the patient's age, medical condition, and tumor characteristics rather than excessively considering the adverse effects of stroke on cancer prognosis. [ABSTRACT FROM AUTHOR]

Women are experiencing growing rates of incarceration at twice the pace of that for men. Additionally, one-third will be older than 55 years of age by the end of the decade. Women who are incarcerated experience a higher prevalence of gynecologic malignancies and present with higher stage disease, which may be contributing to the greater mortality from cancer than the age-adjusted US population. Limited access to guideline-recommended screening and prevention and resource limitations across correctional facilities may result in gynecologic cancer disparities. Reasons for delayed gynecologic cancer care in prisons remain underexplored. Therefore, we sought to identify contributors to delayed gynecologic cancer care among women experiencing incarceration. Women at a single tertiary center in the Southeastern U.S. who were incarcerated and were diagnosed with a gynecologic cancer during 2014–2021 were identified in the electronic medical record. Note text was extracted and contributors to delay were identified and categorized using the RADaR method. Descriptive statistics were used to assess quantitative data. 14 patients were identified with a total of 14,879 text excerpts. Data reduction was performed to identify excerpts that were relevant to the central research question resulting in 175 relevant note excerpts. Delays prior to the tertiary care visit included patient and institutional contributors. Delays during transition from the tertiary center to prison included discharge planning and loss to follow-up during/after incarceration. Transportation, authorization, and restraints were concrete contributors. Abstract contributors included communication, and the patient's emotional experience. We identify myriad contributors to delayed or fractured gynecologic cancer care in women experiencing incarceration. The impact of these issues warrants further study and intervention to improve care. • During incarceration, patient and institutional factors delayed the initial gynecologic oncology visit • Discharge planning and loss to follow-up during and after incarceration introduced delays in the hospital-prison transition • Transportation, authorization, and the use of restraints were concrete delays • Abstract delays included communication and the patient's emotional experience [ABSTRACT FROM AUTHOR]

We investigated the association between methylenetetrahydrofolate reductase (gene MTHFR 677C>T, rs1801133), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR 2756A>G, rs1805087), and methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (gene MTHFD1 1958G>A, rs2236225)—well-studied functional variants involved in one-carbon metabolism—and gynecologic cancer risk, and the interaction between these polymorphisms and depression. A total of 200 gynecologic cancer cases and 240 healthy controls were recruited to participate in this study. Three single-nucleotide variants (SNVs) (rs1801133, rs1805087, rs2236225) were genotyped using the PCR-restriction fragment length polymorphism method. Depression was assessed in all patients using the Hamilton Depression Scale. Depression was statistically significantly more frequent in women with gynecologic cancers (69.5% vs. 34.2% in controls, p < 0.001). MTHFD1 rs2236225 was associated with an increased risk of gynecologic cancers (in dominant OR = 1.53, p = 0.033, and in log-additive models OR = 1.37, p = 0.024). Moreover, an association was found between depression risk and MTHFR rs1801133 genotypes in the controls but not in women with gynecologic cancers (in codominant model CC vs. TT: OR = 3.39, 95%: 1.49–7.74, p = 0.011). Cancers of the female reproductive system are associated with the occurrence of depression, and ovarian cancer may be associated with the rs2236225 variant of the MTHFD1 gene. In addition, in healthy aging women in the Polish population, the rs1801133 variant of the MTHFR gene is associated with depression. [ABSTRACT FROM AUTHOR]

The retrotransposon known as long interspersed nuclear element-1 (LINE-1), which is currently the sole autonomously mobile transposon in the human genome, can result in insertional mutations, chromosomal rearrangements, and genomic instability. In recent years, numerous studies have shown that LINE-1 is involved in the development of various diseases and also plays an important role in the immune regulation of the organism. The expression of LINE-1 in gynecologic tumors suggests that it is expected to be an independent indicator for early diagnosis and prognosis, and also, as a therapeutic target, LINE-1 is closely associated with gynecologic tumor prognosis. This article discusses the function of LINE-1 in the diagnosis, treatment, and prognosis of ovarian, cervical, and endometrial malignancies, as well as other gynecologic malignancies. It offers fresh perspectives on the early detection of tumors and the creation of novel anti-tumor medications. [ABSTRACT FROM AUTHOR]

Chemotherapy resistance remains a major challenge in the treatment of gynecologic malignancies. Increasing evidence suggests that circular RNAs (circRNAs) play a significant role in conferring chemoresistance in these cancers. In this review, we summarize the current understanding of the mechanisms by which circRNAs regulate chemotherapy sensitivity and resistance in gynecologic malignancies. We also discuss the potential clinical implications of these findings and highlight areas for future research. CircRNAs are a novel class of RNA molecules that are characterized by their unique circular structure, which confers increased stability and resistance to degradation by exonucleases. Recent studies have shown that circRNAs can act as miRNA sponges, sequestering miRNAs and preventing them from binding to their target mRNAs. This can lead to upregulation of genes involved in drug resistance pathways, ultimately resulting in decreased sensitivity to chemotherapy. We discuss several specific examples of circRNAs that have been implicated in chemoresistance in gynecologic cancers, including cervical cancer, ovarian cancer, and endometrial cancer. We also highlight the potential clinical applications of circRNA-based biomarkers for predicting chemotherapy response and guiding treatment decisions. Overall, this review provides a comprehensive overview of the current state of knowledge regarding the role of circRNAs in chemotherapy resistance in gynecologic malignancies. By elucidating the underlying mechanisms by which circRNAs regulate drug sensitivity, this work has important implications for improving patient outcomes and developing more effective therapeutic strategies for these challenging cancers. [ABSTRACT FROM AUTHOR]

Abstract The three most common gynaecologic cancers that seriously threaten female lives and health are ovarian cancer, cervical cancer, and endometrial cancer. Glycolysis plays a vital role in gynaecologic cancers. Several long noncoding RNAs (lncRNAs) are known to function as oncogenic molecules. LncRNAs impact downstream target genes by acting as ceRNAs, guides, scaffolds, decoys, or signalling molecules. However, the role of glycolysis-related lncRNAs in regulating gynaecologic cancers remains poorly understood. In this review, we emphasize the functional roles of many lncRNAs that have been found to promote glycolysis in gynaecologic cancers and discuss reasonable strategies for future research.

Objective: Although skilled goals of care (GOC) conversations are known to reduce aggressive futile end-of-life care, they have not been widely implemented nor standardized in the care of gynecologic malignancies. Clinicians express concern regarding patient readiness and willingness to participate in these conversations, which may be a barrier to GOC discussions. Methods: This is a qualitative study, conducted at an academic institution in the United States, of patients with gynecologic malignancies at high risk of death within six months and who had recently completed a GOC discussion with their oncology clinician during an ambulatory visit. Within 10 days of this conversation, patients were approached for potential participation in an hour-long semistructured interview. Patients enrolled in hospice or who were non-English speaking were excluded. Participants were enrolled until thematic saturation was reached. Interviews were transcribed and coded using the five-stage thematic approach. Results: Ten women were consented and participated in semistructured interviews, which occurred a median of 4 (range 1?18) days after the index GOC discussion. The median age was 64 (range 37?78), and the most common diagnosis (50%) was recurrent platinum-resistant ovarian cancer. Four themes were identified: (1) delivery of the GOC conversation, (2) importance of prioritizing individual values, (3) involving family in decision making, and (4) openness to discussing discontinuation of anticancer treatment and hospice. Patients generally felt these GOC conversations were useful, providing a space to express their values and did not compromise the patient?clinician relationship. Conclusions: Patients seemed willing to engage in GOC conversations and were appreciative of their clinicians' communication skills. Often, they used this conversation as an opportunity to convey personal values affecting their care.

The F-Box and WD Repeat Domain Containing 7 (FBXW7) protein has been shown to regulate cellular growth and act as a tumor suppressor. This protein, also known as FBW7, hCDC4, SEL10 or hAGO, is encoded by the gene FBXW7. It is a crucial component of the Skp1-Cullin1-F-box (SCF) complex, which is a ubiquitin ligase. This complex aids in the degradation of many oncoproteins, such as cyclin E, c-JUN, c-MYC, NOTCH, and MCL1, via the ubiquitin-proteasome system (UPS). The FBXW7 gene is commonly mutated or deleted in numerous types of cancer, including gynecologic cancers (GCs). Such FBXW7 mutations are linked to a poor prognosis due to increased treatment resistance. Hence, detection of the FBXW7 mutation may possibly be an appropriate diagnostic and prognostic biomarker that plays a central role in determining suitable individualized management. Recent studies also suggest that, under specific circumstances, FBXW7 may act as an oncogene. There is mounting evidence indicating that the aberrant expression of FBXW7 is involved in the development of GCs. The aim of this review is to give an update on the role of FBXW7 as a potential biomarker and also as a therapeutic target for novel treatments, particularly in the management of GCs. [ABSTRACT FROM AUTHOR]

• Implementation science is the systematic study of factors leading to sustained use of evidence-based interventions. • Implementation science frameworks can lend methodological rigor to studies of access to gynecologic cancer care. • The CFIR framework considers aspects of Innovation, Inner Setting, Outer Setting, Individuals, and Implementation Process. • We recommend moving past associational studies in favor of systematic assessment and correction of specific barriers to care. Barriers to access to cancer care are profoundly threatening to patients with gynecologic malignancies. Implementation science focuses on empirical investigation of factors influencing delivery of clinical best practices, as well as interventions designed to improve delivery of evidence-based care. We outline one prominent framework for conducting implementation research and discuss its application to improving access to gynecologic cancer care. Literature on the use of the Consolidated Framework for Implementation Research (CFIR) was reviewed. Delivery of cytoreductive surgery for advanced ovarian carcinoma was selected as an illustrative case of an evidence-based intervention (EBI) in gynecologic oncology. CFIR domains were applied to the context of cytoreductive surgical care, highlighting examples of empirically-assessable determinants of care delivery. CFIR domains include Innovation, Inner Setting, Outer Setting, Individuals, and Implementation Process. "Innovation" relates to characteristics of the surgical intervention itself; "Inner Setting" relates to the environment in which surgery is delivered. "Outer Setting" refers to the broader care environment influencing the Inner Setting. "Individuals" highlights attributes of persons directly involved in care delivery, and "Implementation Process" focuses on integration of the Innovation within the Inner Setting. Prioritization of implementation science methods in the study of access to gynecologic cancer care will help ensure that patients are able to utilize interventions with the greatest prospect of benefiting them. [ABSTRACT FROM AUTHOR]

Background/Aim: Patients with gynecologic cancers selected for external-beam radiotherapy or brachytherapy may experience emotional distress. We aimed to identify patients who may benefit from early psychooncological intervention. Patients and Methods: We investigated 10 potential risk factors of emotional distress in a retrospective series of 122 patients planned for radiotherapy of gynecologic cancers. Factors included COVID-19 pandemic, number of physical problems, age, performance status, tumor site/stage, surgery, chemotherapy, brachytherapy, and history of another tumor. p-Values <0.005 indicated significance, and p-values <0.06 trends. Results: Frequencies of worry, fear, sadness, depression, nervousness, and loss of interest were 41%, 57%, 39%, 16%, 38%, and 20%, respectively. Significant associations with at least one of these symptoms were found for =5 physical problems and no upfront surgery. Trends were observed for chemoradiotherapy, history of another tumor, worse performance status, and younger age. Conclusion: The prevalence of pre-radiotherapy emotional distress was remarkable in patients with gynecologic cancers. Patients with risk factors may benefit from immediate psychooncological assistance. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the associations between social determinants of health (SDOH) and psychoneurologic symptom (PNS) clusters in women with gynecologic cancers during cancer treatment. SAMPLE & SETTING: 67 women with gynecologic cancers who received radiation therapy were assessed at baseline, six to eight weeks after treatment, and six months after treatment at oncology clinics in Georgia. METHODS & VARIABLES: Fatigue, pain, sleep disturbances, cognitive impairment, and depressive symptoms were measured to determine a PNS cluster score. Associations between SDOH and PNS cluster scores were assessed using mixed-effect models. RESULTS: Larger mean PNS cluster scores were reported in individuals with less education, lower income, and unemployment, as well as in those living in more disadvantaged neighborhoods. IMPLICATIONS FOR NURSING: Individual- and community-level SDOH and their interactions were associated with more PNS clusters. Studying SDOH at multiple levels depicts how various social disadvantages can exacerbate poor health outcomes. [ABSTRACT FROM AUTHOR]

Racial health disparities within gynecologic cancers persist. We aim to explore the impact of epigenetics on these disparities and how social determinants of health fuel this effect. We queried PubMed with terms associated with social determinants of health and epigenetics in the scope of 3 gynecologic cancers: ovarian, endometrial, and cervical. Using the publications found, we highlight various socioeconomic and environmental factors that may influence epigenetic mechanisms and further disparities in cancer incidence, mortality, and treatment. This narrative review exposes existing gaps in evidence and provides recommendations of future preventive efforts that can target the mitigation of gynecologic cancer disparities. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel types of regulated cell death and is widely studied in cancers and many other diseases in recent years. It is characterized by iron accumulation and intense lipid peroxidation that ultimately inducing oxidative damage. So far, signaling pathways related to ferroptosis are involved in all aspects of determining cell fate, including oxidative phosphorylation, metal-ion transport, energy metabolism and cholesterol synthesis progress, et al. Recently, accumulated studies have demonstrated that ferroptosis is associated with gynecological oncology related to steroid hormone signaling. This review trends to summarize the mechanisms and applications of ferroptosis in cancers related to estrogen and progesterone, which is expected to provide a theoretical basis for the prevention and treatment of gynecologic cancers.

The current study aimed to explore attitudes toward genetic germline testing and intentions to test in Latinas from Southern California. We hypothesized that patients' acculturation and education levels, as well as comfort with health care providers, are positively associated with attitudes and intentions toward genetic testing. A survey was offered concurrently to Latinx female patients at a gynecologic oncology practice and to unaffiliated Latinx community members. The survey assessed demographics, structural, psychosocial, and acculturation factors and genetic testing attitudes and intentions via validated scales. Of 148 surveys collected, 66% of responders had low levels of acculturation. 50% of women had government-subsidized insurance; 22% had no schooling in the US. 67% of participants did not carry a diagnosis of cancer. Women with higher acculturation levels were more likely to consider genetic testing (r s = 0.54, p =.001). Higher acculturated women and less acculturated women under 50 were more likely to consider testing if it had been recommended by a female, trusted, or Hispanic/Latinx provider (r s = 0.22, p =.01, r s = 0.27, p =.003 and r s = 0.19, p =.003, respectively) or if there was a recent cancer diagnosis (self or family, r s = 0.19, p =.03). Overall, education correlated with intention to test. The more education outside of the US, the less negative was the attitude toward being tested (r s = −0.41, p =.002). Direct experiences with cancer, more schooling and higher acculturation coupled with provider characteristics determined if Latinas were more open to testing. Provider characteristics mattered: having a female, Latinx, Spanish speaking provider was important for genetic testing decision-making. These findings are particularly pertinent in areas with high Latinx populations. • Latinx women with higher acculturation are more likely to consider genetic testing. • Latinx women more likely to consider testing if recommended by trusted provider. • Education levels positively correlated with intention to undergo genetic testing. [ABSTRACT FROM AUTHOR]

The three most common gynaecologic cancers that seriously threaten female lives and health are ovarian cancer, cervical cancer, and endometrial cancer. Glycolysis plays a vital role in gynaecologic cancers. Several long noncoding RNAs (lncRNAs) are known to function as oncogenic molecules. LncRNAs impact downstream target genes by acting as ceRNAs, guides, scaffolds, decoys, or signalling molecules. However, the role of glycolysis-related lncRNAs in regulating gynaecologic cancers remains poorly understood. In this review, we emphasize the functional roles of many lncRNAs that have been found to promote glycolysis in gynaecologic cancers and discuss reasonable strategies for future research. [ABSTRACT FROM AUTHOR]

Gynecologic cancers are reproductive disorders characterized by pelvic pain and infertility. The identification of new predictive markers and therapeutic targets for the treatment of gynecologic cancers is urgently necessary. One of the recent successes in gynecologic cancers research is identifying the role of signaling pathways in the pathogenesis of the disease. Recent experiments showed long noncoding RNAs (lncRNA) can be novel therapeutic approaches for the diagnosis and treatment of gynecologic cancers. LncRNA are transcribed RNA molecules that play pivotal roles in multiple biological processes by regulating the different steps of gene expression. Metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) is a well-known lncRNA that plays functional roles in gene expression, RNA processing, and epigenetic regulation. High expression of MALAT1 is closely related to numerous human diseases. It is generally believed that MALAT1 expression is associated with cancer cell growth, autophagy, invasion, and metastasis. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) could contribute to the pathogenesis of gynecologic cancers. In this review, we will summarize functional roles of MALAT1 in the most common gynecologic cancers, including endometrium, breast, ovary, and cervix. [ABSTRACT FROM AUTHOR]

There are limited patient-reported outcome (PRO) data tracking changes in toxicity in patients actively undergoing radiotherapy. Between 2015–2019, acute toxicity was prospectively measured in 698 patients undergoing a 5-week course of pelvic radiotherapy for gynecologic cancers using a weekly PRO questionnaire. Our questionnaire was able detect a pattern of onset and resolution of acute gastrointestinal (GI) and genitourinary (GU) toxicity in 27 out of 32 questions. Logistic regression analysis showed that increasing GI and GU toxicity at week 2 could predict for severe toxicity at week 5. However, due to a low number of severe events, univariate results could not be productively added to a multivariate model. We observed a >70% response rate for all sections of the questionnaire, except for questions on sexual and vaginal health, which had a 13% average response rate. By demonstrating that PRO data can be used to track acute toxicity during radiotherapy, there is a need to further examine how this tool may be implemented in the clinic to provide complex, adaptive care, such as early side effect management, and modifying radiation delivery in real-time.

• VISTA is an inhibitory immune checkpoint that acts as a ligand or receptor to exert immunosuppressive effects. • Abnormal overexpression of VISTA in gynecological tumors promotes tumor progression. Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but has shown limited efficacy in gynecologic cancers. VISTA (V-domain Ig suppressor of T-cell activation), a member of the B7 family, is emerging as another checkpoint that regulates the anti-tumor immune responses within the tumor microenvironment. This paper reviews the structure, expression, and mechanism of action of VISTA. Furthermore, it highlights recent advances in VISTA-blocking therapies and their potential in improving outcomes for patients with gynecologic cancers. By understanding the role of VISTA in mediating the immune evasion of gynecologic tumors, we can develop more effective combinatory treatment strategies that could overcome resistance to current ICB therapies. [ABSTRACT FROM AUTHOR]

Over the past decade, there have been significant developments in treatment for ovarian cancer, yet the lack of targeted therapy with few side effects still represents a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the tumorigenesis process and metabolism of drugs and has a negative impact on therapy outcomes. Gaining more insight into CYP expression is crucial to understanding the pathophysiology of ovarian cancer since many isoforms are essential to the metabolism of xenobiotics and steroid hormones, which drive the disease’s development. To the best of our knowledge, no review articles have documented the intratumoral expression of CYPs and their implications in ovarian cancer. Therefore, the purpose of this review is to provide a clear understanding of differential CYP expression in ovarian cancer and its implications for the prognosis of ovarian cancer patients, together with the effects of CYP polymorphisms on chemotherapy metabolism. Finally, we discuss opportunities to exploit metabolic CYP expression for the development of novel therapeutic methods to treat ovarian cancer.

IntroductionCC-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.MethodsPatients 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.ResultsThere 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.ConclusionThe 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.

Introductionchemotherapy-related cognitive dysfunction (CRCD) is a growing problem due to rising cancer rates and increasing numbers of cancer survivors. upwards of 70% of ovarian cancer patients report cognitive-changes following treatment for their cancer.Areas coveredthe underlying mechanisms of CRCD are a subject of active research and debate. the initial insult may start with the diagnosis of cancer itself, both in the number of peripheral cytokines it produces but also in the psychological changes caused by stress and anxiety associated with the diagnosis. chemotherapy, in its ability to alter dna in the replication cycle, has been shown to damage neurons and their stem cell precursors.Expert commentarybased on proposed mechanisms and advancements in other neuropsychological diseases, various pharmacologic and behavioral interventions have been demonstrated to show improvements in patient's quality of life and in their perceived cognitive abilities and memory. further research is necessary to be able to determine when and how these cognitive changes occur, and if their multiple potential biological underpinnings can synergize toward deleterious cognitive effects. future therapies will include prevention strategies to avert CRCD's effects on patients.

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.

Interstitial brachytherapy (ISBT) is an effective option for delivering conformal high dose radiation to the target volume with better organ-at risk sparing but is thought to be more invasive and painful than other methods. This study investigated pain levels and opioid consumption in patients who received spinal anesthesia (SA) or general anesthesia (GA) for their ISBT. Patients that underwent ISBT from April 2014 to September 2018 were analyzed from a prospective institutional database. The most prevalent malignancies were cervical (45%), recurrent endometrial (27%) and vaginal (20%) cancers. Baseline patient characteristics, radiation treatment details, anesthesia records, and inpatient charts were obtained. Opioid consumption was quantified as oral morphine equivalent per day (OMEq/day) from implantation until removal. Pain score levels were collected by using an 11-point scoring system. Ninety nine patients received GA and 40 patients received SA as their anesthesia for ISBT. During their first admission, 76 patients (55%) required intravenous opioids. Patients receiving SA had significantly lower mean pain scores on the morning of their procedure 6 (Interquartile range [IQR] 2–8) vs. 0 (IQR: 0–1); p < 0.001]. Pain did not significantly differ between cohorts at any other time. During the first admission, SA patients had a lower median opioid usage of 23 (IQR: 9–47) mg/day compared to GA patients at 38 (IQR: 21–71) mg/day (p = 0.011). No difference in opioid consumption was seen during subsequent admissions. In patients undergoing ISBT, SA provides better immediate pain control post insertion compared to GA. Patients who received SA used lower amounts of opioids during their first ISBT insertion. [ABSTRACT FROM AUTHOR]

Mounting evidence has demonstrated that a myriad of developmental signaling pathways, such as the Wnt, Notch, Hedgehog and Hippo, are frequently deregulated and play a critical role in regulating cancer stem cell (CSC) activity in human cancers, including gynecologic malignancies. In this review article, we describe an overview of various signaling pathways in human cancers. We further discuss the developmental roles how these pathways regulate CSCs from experimental evidences in gynecologic cancers. Moreover, we mention several compounds targeting CSCs in gynecologic cancers to enhance the treatment outcomes. Therefore, these signaling pathways might be the potential targets for developing targeted therapy in gynecologic cancers. [ABSTRACT FROM AUTHOR]

Introduction: Due to scant literature and the absence of high-level evidence, the treatment of vulvar cancer is even more challenging in countries facing limited resources, where direct application of international guidelines is difficult. Recommendations from a panel of experts convened to address some of these challenges were developed. Methods: The panel met in Rio de Janeiro in September 2019 during the International Gynecological Cancer Society congress and was composed of specialists from countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East. The panel addressed 62 questions and provided recommendations for the management of early, locally advanced, recurrent, and/or metastatic vulvar cancer. Consensus was defined as at least 75% of the voting members selecting a particular recommendation, whereas a majority vote was considered when one option garnered between 50.0% and 74.9% of votes. Resource limitation was defined as any issues limiting access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or funding for the provision of contemporary medical care. Results: Consensus was reached for nine of 62 (14.5%) questions presented to the panel, whereas a majority vote was reached for 29 (46.7%) additional questions. For the remaining questions, there was considerable heterogeneity in the recommendations. Conclusion: The development of guidelines focusing on areas of the world facing more severe resource limitations may improve medical practice and patient care. [ABSTRACT FROM AUTHOR]