High-Grade Endometrial Cancer: Molecular Subtypes, Current Challenges, and Treatment Options.

Although many recent advancements have been made in women's health, perhaps one of the most neglected areas of research is the diagnosis and treatment of high-grade endometrial cancer (EnCa). The molecular classification of EnCa in concert with histology was a major step forward. The integration of profiling for mismatch repair deficiency and Human Epidermal Growth Factor 2 (HER2) overexpression, can further inform treatment options, especially for drug resistant recurrent disease. Recent early phase trials suggest that regardless of subtype, combination therapy with agents that have distinct mechanisms of action is a fruitful approach to the treatment of high-grade EnCa. Unfortunately, although the importance of diagnosis and treatment of high-grade EnCa is well recognized, it is understudied compared to other gynecologic and breast cancers. There remains a tremendous need to couple molecular profiling and biomarker development with promising treatment options to inform new treatment strategies with higher efficacy and safety for all who suffer from high-grade recurrent EnCa.

Patterns of spread and genetic alterations of primary endometrioid carcinomas of the ovary.

OBJECTIVE: The primary objective was to characterize the rate of lymph node involvement in a cohort of patients with primary ovarian endometrioid adenocarcinoma. Additionally, we sought to quantify the recurrence rate, genetic alterations, and impact of lymphadenectomy on survival in this group of patients. METHODS: Patients diagnosed with primary endometrioid adenocarcinoma of the ovary without synchronous carcinomas of the female genital tract between 2012 and 2021 were identified. Demographic and disease-related data were collected from pathology reports and clinical records. Kaplan-Meier survival analysis using log rank test and Cox regression was performed. RESULTS: Sixty-three patients met inclusion criteria. Median age was 60 (range 22-90) years. Histologic grade was 1 in 20 (32%), 2 in 27 (43%), and 3 in 16 (25%) tumors. International Federation of Gynecology and Obstetrics (FIGO) stage after surgery included IA/B (n=20, 32%), IC (n=23, 37%), II (n=16, 25%), and III (n=4, 6%). Forty-one (65%) patients had pelvic and 33 (52%) had both pelvic and para-aortic lymphadenectomy. All assessed lymph nodes were negative for metastatic carcinoma. No patients with clinically pelvis-confined disease had tumors upstaged by either lymphadenectomy or omentectomy. Twenty-eight patients (44%) had germline mutational status documented; two had a germline BRCA mutation, confirmed to be pathogenic by molecular studies. Complete staging did not significantly impact progression free or overall survival, after adjusting for age and histologic grade in a Cox proportional hazards model. The recurrence rate was 15% for patients with grade 1 endometrioid carcinoma, 7% for grade 2, and 31% for grade 3, respectively. CONCLUSION: There were no lymph node metastases in patients with comprehensively staged primary endometrioid ovarian carcinoma. Staging did not impact survival and may be omitted, regardless of grade. Germline BRCA mutations are rare in ovarian endometrioid carcinoma compared with reported rates in high-grade serous carcinomas.

The evolving role of DNA damage response in overcoming therapeutic resistance in ovarian cancer.

Epithelial ovarian cancer (EOC) is treated in the first-line setting with combined platinum and taxane chemotherapy, often followed by a maintenance poly (ADP-ribose) polymerase inhibitor (PARPi). Responses to first-line treatment are frequent. For many patients, however, responses are suboptimal or short-lived. Over the last several years, multiple new classes of agents targeting DNA damage response (DDR) mechanisms have advanced through clinical development. In this review, we explore the preclinical rationale for the use of ATR inhibitors, CHK1 inhibitors, and WEE1 inhibitors, emphasizing their application to chemotherapy-resistant and PARPi-resistant ovarian cancer. We also present an overview of the clinical development of the leading drugs in each of these classes, emphasizing the rationale for monotherapy and combination therapy approaches.

Association of hospital-level factors with utilization of sentinel lymph node biopsy in patients with early-stage vulvar cancer.

OBJECTIVE: To evaluate utilization of sentinel lymph node biopsy (SLNB) for early-stage vulvar cancer at minority-serving hospitals and low-volume facilities. METHODS: Between 2012-2018, individuals with T1b vulvar squamous cell carcinoma were identified using the National Cancer Database. Patient, facility, and disease characteristics were compared between patients undergoing SLNB or inguinofemoral lymph node dissection (IFLD). Multivariable logistic regression, adjusted for patient, facility, and disease characteristics, was used to evaluate factors associated with SLNB. Kaplan-Meier survival analysis using log rank test and Cox regression was performed. RESULTS: Of the 3,532 patients, 2,406 (68.1%) underwent lymph node evaluation, with 1,704 (48.2%) undergoing IFLD and 702 (19.8%) SLNB. In a multivariable analysis, treatment at minority-serving hospitals (OR 0.39, 95% CI 0.19-0.78) and low-volume hospitals (OR 0.44, 95% CI 0.28-0.70) were associated with significantly lower odds of undergoing SLNB compared to receiving care at non-minority-serving and high-volume hospitals, respectively. While SLNB utilization increased over time for the entire cohort and stratified subgroups, use of the procedure did not increase at minority-serving hospitals. After controlling for patient and tumor characteristics, SLNB was not associated with worse OS compared to IFLD in patients with positive (HR 1.02, 95% CI 0.63-1.66) or negative (HR 0.92, 95% CI 0.70-1.21) nodal pathology. CONCLUSIONS: For patients with early-stage vulvar cancer, treatment at minority-serving or low-volume hospitals was associated with significantly decreased odds of undergoing SLNB. Future efforts should be concentrated toward ensuring that all patients have access to advanced surgical techniques regardless of where they receive their care.

Guideline-Discordant Care in Early-Stage Vulvar Cancer.

OBJECTIVE: To describe the use of National Comprehensive Cancer Network guideline-concordant inguinofemoral lymph node (LN) evaluation in individuals with early-stage vulvar cancer. METHODS: This retrospective cohort study identified patients with T1b and T2 vulvar squamous cell carcinoma diagnosed between 2012 and 2018 using the National Cancer Database. Factors associated with LN evaluation were examined using logistic regression analyses, adjusting for patient, disease, and facility-level characteristics. Kaplan-Meier survival analysis using log rank test and Cox regression was performed for the entire cohort and a subgroup of older patients , defined as individuals aged 80 years or older. RESULTS: Of the 5,685 patients with vulvar cancer, 3,756 (66.1%) underwent guideline-concordant LN evaluation. In our adjusted model, age 80 years or older (odds ratio [OR], 0.30; 95% CI 0.22-0.42) and Black race (OR 0.72; 95% CI 0.54-0.95) were associated with lower odds of LN evaluation. High-volume hospitals were associated with increased odds of LN evaluation compared with low-volume hospitals (OR 1.62; 95% CI 1.28-2.05). Older individuals who did not undergo LN evaluation had significantly worse overall survival than those with pathologically negative LNs (hazard ratio [HR] 0.45; 95% CI 0.37-0.55) and similar overall survival as those with pathologically positive LNs (HR 1.05; 95% CI 0.77-1.43). CONCLUSION: Guideline-concordant LN evaluation for early-stage vulvar squamous cell carcinoma is low. Lower utilization is associated with older age, Black race, and care at a low-volume hospital.

Psychometric properties of the Perceived Benefits of Thinness Scale in college-aged women.

Thin ideal internalization is a risk factor for disordered eating behaviors, poor body image, and eating disorders (EDs). This paper evaluated the psychometric properties of a novel measure, the Perceived Benefits of Thinness Scale (PBTS), which assesses how individuals feel being thinner would affect various aspects of their lives. Three separate studies with unique samples of college-aged women over 18 years were conducted to assess reliability and validity. In Study 1, exploratory and confirmatory factor analyses suggested all PBTS items loaded onto one factor that was distinct from a measure of weight and shape concerns. A large correlation between changes in PTBS scores and changes in ED psychopathology scores over 8 months (r = .57, p < .01) suggested sensitivity to change. Greater severity in ED pathology was also associated with higher scores on the PBTS. In Study 2, the PBTS showed good test-retest reliability (r = .84, p < .001) and, in Study 3, expected correlations with existing measures of thin ideal internalization (rs = .38-.60, ps < .001). Overall, the PBTS displayed good factor structure, reliability, concurrent validity, and sensitivity to change. By emphasizing social, emotional, and quality of life benefits, the PBTS may serve clinicians, researchers, and patients in understanding thin ideal internalization and associated ED risk.

Surveillance patterns of cervical cancer patients treated with conization alone.

OBJECTIVES: To determine surveillance patterns of stage I cervical cancer after cervical conization. METHODS: A 25-question electronic survey was sent to members of the Society of Gynecologic Oncology. Provider demographics, surveillance during year 1, years 1-3, and >3 years after cervical conization, use of pelvic examination, cytology, Human papillomavirus testing, colposcopy, and endocervical curettage were queried. Data were analyzed. RESULTS: 239/1175 (20.1%) responses were collected over a 5-week study period. All providers identified as gynecologic oncologists. During year 1, 66.7% of providers perform pelvic examination and 37.1% perform cytology every 3 months. During years 1-3, 61.6% perform pelvic examination and 46% perform cytology every 6 months. At >3 years, 54.4% perform pelvic examination every 6 months and 43% perform annual pelvic examination. 66.7% of respondents perform cytology annually, and 51.9% perform annual Human papilloma virus testing. 85% of providers do not offer routine colposcopy and 60% do not offer endocervical curettage at any point during 5-year follow-up. 76.3% of respondents screen patients for Human papilloma virus vaccination. CONCLUSIONS: To date, there are no specific surveillance guidelines for patients with stage I cervical cancer treated with cervical conization. The most common surveillance practice reported is pelvic examination with or without cytology every 3 months in year 1 and every 6 months thereafter. However, wide variation exists in visit frequency, cytology, and Human papillomavirus testing, and there is a clear trend away from using colposcopy and endocervical curettage. These disparate surveillance practices indicate a need for well-defined, uniform surveillance guidelines.

Heterotopic atypical trophoblasts mimicking ectopic choriocarcinoma coexistent with a viable intrauterine pregnancy: A diagnostic dilemma.

•Ectopic choriocarcinoma coexistent with viable IUP is rare but has been reported.•Atypical and proliferative trophoblasts are normal in an early conceptus.•Evaluation including MRI and CXR did not reveal metastatic choriocarcinoma.•IHC analysis for p57, molecular genotyping of DNA microsatellites was performed.•ß-hCGs appropriately rose then plateaued; remainder of pregnancy was unremarkable.

Epigenetics of autism-related impairment: copy number variation and maternal infection.

OBJECTIVE: Epidemiological data have suggested maternal infection and fever to be associated with increased risk of autism spectrum disorder (ASD). Animal studies show that gestational infections perturb fetal brain development and result in offspring with the core features of autism and have demonstrated that behavioral effects of maternal immune activation are dependent on genetic susceptibility. The goal of this study was to explore the impact of ASD-associated copy number variants (CNVs) and prenatal maternal infection on clinical severity of ASD within a dataset of prenatal history and complete genetic and phenotypic findings. METHODS: We analyzed data from the Simons Simplex Collection sample including 1971 children with a diagnosis of ASD aged 4 to 18 years who underwent array comparative genomic hybridization screening. Information on infection and febrile episodes during pregnancy was collected through parent interview. ASD severity was clinically measured through parent-reported interview and questionnaires. RESULTS: We found significant interactive effects between the presence of CNVs and maternal infection during pregnancy on autistic symptomatology, such that individuals with CNVs and history of maternal infection demonstrated increased rates of social communicative impairments and repetitive/restricted behaviors. In contrast, no significant interactions were found between presence of CNVs and prenatal infections on cognitive and adaptive functioning of individuals with ASD. CONCLUSIONS: Our findings support a gene-environment interaction model of autism impairment, in that individuals with ASD-associated CNVs are more susceptible to the effects of maternal infection and febrile episodes in pregnancy on behavioral outcomes and suggest that these effects are specific to ASD rather than to global neurodevelopment.

Validation of a six-item male body image concerns scale (MBICS).

Elevated body image concerns may be a risk factor for eating disorders among males and contribute to a range of other mental health problems. This study tested a 6-item measure of general male body image concerns in two studies with adolescent males ages 14-18 (total N = 122). The measure showed strong convergent validity, scale score reliability, and test-retest reliability, and was significantly correlated with the number of episodes of binge eating in the past month. A short scale will relieve participant burden and provide a useful research tool for studies with males at risk for or with eating disorders.