Treatment options in the advanced and recurrent setting for endometrial cancer: an update.

INTRODUCTION: Uterine cancer is the most common gynecologic malignancy in women and is projected to surpass ovarian cancer as the deadliest gynecologic malignancy in the United States in 2024. Additionally, rates of advanced and high-risk uterine cancer have been on the rise in the United States, demonstrating a need for innovation in treatment options. There have been multiple recent trials investigating the incorporation of novel agents in the treatment of advanced and recurrent endometrial cancer. AREAS COVERED: This article will discuss the current landscape of the treatment of advanced and recurrent endometrial cancer, focusing on recent phase III trials published or presented on with the incorporation of immunotherapy and other novel therapeutics while also reviewing promising phase I and II trials in the field. Clinical trials were identified via clinicaltrials.gov and a PubMed literature search was performed (initially February 2024, updated May 2024). EXPERT OPINION: The treatment field is promising for patients as many of these trials appear to offer progression free and overall survival benefits in a disease with a historically poor prognosis. Molecular profiling of endometrial cancer will be the backbone of treatment paradigms in the future.

Percutaneous interstitial brachytherapy ablation for targeting oligometastatic gynecologic cancers.

INTRODUCTION: Treatment of recurrent oligometastatic gynecologic malignancy may involve targeted surgery, thermal ablation, or CT-guided high-dose-rate interstitial brachytherapy ablation (CT-HDR-IBTA). The purpose of this study was to describe the safety and efficacy of CT-HDR-IBTA for oligometastatic gynecologic malignancies. METHODS: With institutional review board approval (IRB) approval and compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliance, we searched our database to assemble a single-arm study cohort of all patients with oligometastatic gynecologic cancers who underwent CT-HDR-IBTA from 2012-2022 with follow-up. The electronic record was reviewed to determine relevant clinicopathological variables including patient demographics, prior treatments, clinical course, local control, and local and distant recurrence with follow-up imaging. RESULTS: The study cohort comprised 37 lesions in 34 patients treated with CT-HDR-IBTA for recurrent oligometastatic uterine (n = 17), cervix (n = 1), or ovarian cancer (n = 16) with an average lesion size of 2.5 cm with an average patient age of 61.4 years. Each lesion was treated with an average radiation dose of 23.8 Gy in 1.8 fractions and a median follow-up time of 24.0 months. The primary efficacy of CT HDR ITBA was 73% with a median progression-free survival of 8.0 months (95% CI 3.6-12.8 months) and with 58% of patients still alive at 43 months with median overall survival not reached. The rate of Grade 1 adverse events was 22% without any Grade 2, 3 or 4 events. CONCLUSIONS: CT HDR IBTA was safe and effective for treating oligometastatic gynecologic cancers in a heavily pretreated cohort.

The Role of Preprocedure Genetic Counseling in Pregnancies Interrupted for Fetal Abnormalities.

OBJECTIVE: Congenital birth defects affect 3 to 5% of pregnancies. Genetic counseling can help patients navigate the testing process and understand results. The study objective was to identify predictors and utility of genetic counseling at the time of pregnancy termination. Additionally, we aimed to see what proportion of patients would benefit from additional testing based on the results of the genetic testing. STUDY DESIGN: This was a retrospective cohort review of all terminations performed for fetal anomalies by an academic center from July 2016 to May 2020. Indications were stratified by abnormal serum screening or types of abnormal ultrasound findings. Data were abstracted regarding uptake of genetic counseling and testing results. Abnormal results that warranted additional testing regarding recurrence risks were noted. Multivariable logistic regression was performed to identify predictors of receipt of genetic counseling and testing. RESULTS: Of 387 patients, 57% (n = 220) received preprocedure genetic counseling and 43% (n = 167) did not. Among patients who received diagnostic testing, 62% (n = 194) had genetic counseling compared with 38% (n = 121) without counseling (adjusted odds ratio 2.46, 95% confidence interval [1.41-4.29], p < 0.001). Among the entire cohort, 38% (n = 148) had suspected aneuploidy based on serum screening. Of these, 89% (n = 132/148) had definitive testing, 92% (n = 122/132) confirming the aneuploidy. Among the other 68% (n = 239) with structural anomalies, 76% (n = 183) had diagnostic testing with 29% (n = 53) yielding an abnormal result. Among those fetuses with structural anomalies, 36% (n = 19/53) of genetic diagnoses warranted additional parental testing because of risk of recurrence compared with only 2% (n = 2/122) of patients with abnormal serum screening results alone. CONCLUSION: Genetic counseling was associated with increased uptake of diagnostic testing, which yielded useful information and prompted additional testing. This is important for determining etiology and recurrence risk and should be offered to patients presenting for termination for fetal indications, as well as providing diagnostic closure for patients. KEY POINTS: · Genetic counseling increases the uptake of diagnostic testing in patients with fetal anomalies.. · Patients with ultrasound anomalies received less diagnostic testing despite actionable results 36% of the time.. · Genetic testing is invaluable for recurrence risk counseling even if patients chose to terminate..

Recurrent High-Grade Squamous Intraepithelial Lesion After Loop Excision Procedure Versus Loop Procedure With Top Hat.

OBJECTIVE: To evaluate single-pass loop electrosurgical excision procedure (LEEP-SP) versus LEEP with top hat (LEEP-TH) in terms of treatment failure defined as high-grade squamous intraepithelial lesion (HSIL) cytology within 2 years' follow-up. METHODS: This single-institution cohort study used a prospectively collected cervical dysplasia database including all patients who underwent LEEP-SP or LEEP-TH for biopsy-proven cervical intraepithelial neoplasia between 2005 and 2019. RESULTS: Of 340 patients included, 178 underwent LEEP-SP and 162 LEEP-TH. The LEEP-TH patients were more likely to be older (mean age, 40.4 vs 36.5 years; p < .001) and have a positive preprocedure endocervical sampling (68.5% vs 11.8%; p < .001). Positive margins were found in 23 LEEP-SP (12.9%) and in 25 LEEP-TH (15.4%; p = .507). There was no significant difference in depth of excision between LEEP-SP (13.21 ± 23.19 mm) and LEEP-TH (17.37 ± 28.26 mm; p = .138). At 2 years, there was no difference in the rates of HSIL cytology (5.2% vs 6.3%; p = .698), any positive human papillomavirus test, or HSIL cytology (25% vs 15%; p = .284). The 57 patients undergoing repeat excision were more likely to be older (mean age, 40.95 vs 37.52 years; p = .023), have had a LEEP-TH (26.3% vs 73.7%; p < .001), and have initial cytologic HSIL (64.9% vs 35.0%; p < .001). CONCLUSIONS: In this single-institution study, there is no difference in the rate of recurrent HSIL in patients undergoing LEEP-SP versus LEEP-TH. A LEEP-TH may have limited additional benefit over a LEEP-SP in the treatment of cervical HSIL.

The increasing incidence of stage IV cervical cancer in the USA: what factors are related?

OBJECTIVE: Cervical cancer (International Federation of Gynecology and Obstetrics (FIGO)) stage IVA-B (distant stage) is a rare diagnosis with an approximate 5 year survival rate of 17% and with limited treatment options. The objective of this study was to determine the trends in distant stage cervical cancer in the USA and identify possible factors related to these trends. METHODS: Data were obtained from the United States Cancer Statistics program from 2001 to 2018. Rates of cervical cancer screening and vaccination were evaluated using the Behavioral Risk Factor Surveillance System and TeenVaxView. SEER*Stat 8.3.8.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate incidence trends. RESULTS: Over the last 18 years, 29 715 women were diagnosed with distant stage cervical carcinoma. Black women have disproportionately higher rates at 1.55/100 000 versus 0.92/100 000 in White women (p<0.001). When examining the trends over time, there has been an annual increase in distant stage cervical cancer at a rate of 1.3% per year (p<0.001). The largest increase is seen in cervical adenocarcinoma with an average annual percent change of 2.9% (p<0.001). When performing an intersection analysis of race, region and age, White women in the South aged 40-44 have the highest rise in distant cervical cancer at a rate of 4.5% annually (p<0.001). Using the Behavioral Risk Factor Surveillance System and TeenVax data, compared with Black women, we found that White women have a nearly two-fold higher rate of missed or lack of guideline screening, 26.6% vs 13.8%. White teenagers (13-17 years) have the lowest human papillomavirus vaccination rate at 66.1% compared with others at 75.3%. CONCLUSIONS: Black women have a higher incidence of distant stage disease compared with White women. However, White women have a greater annual increase, particularly in adenocarcinomas. Compared with Black women, White women also have lower rates of guideline screening and vaccination.

Trends in Human Papillomavirus-Associated Cancers, Demographic Characteristics, and Vaccinations in the US, 2001-2017.

Importance: Nearly 45 000 human papillomavirus (HPV)-associated cancers are diagnosed annually in the US. The HPV vaccine has been approved since 2006, but information on the association between vaccination and the incidence of HPV-attributable cancers is unclear. Objective: To evaluate the potential association of screening and vaccination on the trends of HPV-associated cancers. Design, Setting, and Participants: A retrospective, population-based cross-sectional study was conducted using data on HPV-associated (oropharyngeal squamous cell carcinoma [SCC], anal/rectal SCC, vulvar SCC, vaginal SCC, cervical carcinoma, and penile SCC) cancers from the US Cancer Statistics Public Use Database, representing 99% of the US population, between January 1, 2001, and December 31, 2017; HPV vaccination and screening data from the Behavioral Risk Factor Surveillance between January 1, 2001, and December 31, 2016; and TeenVaxView between January 1, 2008, and December 31, 2018. National Cancer Database and Behavioral Risk Factor Surveillance were used to correct for hysterectomy. Data analysis was performed from April 1, 2020, to June 30, 2021. Exposures: Patient demographic characteristics, including age, race and ethnicity, sex, region, and vaccination status. Main Outcomes and Measures: The main outcomes examined in this study were diagnoses of any HPV-associated cancer and HPV vaccination status. Results: A total of 657 317 HPV-associated cancers (exact ages not collected by the United States Cancer Statistics); of these, 264 019 (40.2%) developed in men and 393 298 (59.8%) in women; 14 520 individuals (2.2%) were non-Hispanic Asian/Pacific Islander, 74 641 (11.4%) were non-Hispanic Black, 59 841 (9.1%) were Hispanic, and 499 899 were non-Hispanic White (76.1%). More than half (206 075 [52.4%]) of cancers in women were cervical, whereas most (211 421 [80.1%]) cancers in men were oropharyngeal. In female adolescents (aged 13-17 years), the vaccination rate increased from 37.2% to 69.9% from 2008 to 2018 (annual percent change: 6.57% [95% CI, 5.83%-7.32%]). Before vaccination approval, cervical cancer rates in the 20- to 24-year age group were decreasing at 2.29% annually (P = .045); after vaccine approval, this rate has been decreasing at 9.50% (P = .003). In men, annual increases were noted in oropharyngeal (2.71%) and anal/rectal (1.83%) cancers (P < .001); in women, the incidence of oropharyngeal remained stable but anal/rectal cancer increased at 2.83% every year (P < .001). Conclusions and Relevance: In the US, cervical cancer rates have decreased at a population level, especially in younger women. The findings of this study suggest this decrease may be associated with vaccination. Given the increase in oropharyngeal and anal/rectal cancers, particularly in men, it may be important to highlight vaccination uptake in both sexes.

Favorable Simplified Bishop Score after cervical ripening associated with decreased cesarean birth rate.

BACKGROUND: A favorable Simplified Bishop Score (>5) before the induction of labor is associated with successful vaginal birth. Patients with an unfavorable Simplified Bishop Score (≤5) undergo cervical ripening before the administration of oxytocin. However, data are limited regarding the utility of the Simplified Bishop Score after cervical ripening. OBJECTIVE: The objective of this study was to determine if the Simplified Bishop Score before oxytocin induction but after cervical ripening is associated with cesarean delivery. STUDY DESIGN: We conducted a retrospective cohort study on patients undergoing induction of labor from the Consortium on Safe Labor. The patients with a singleton term pregnancy who initially underwent cervical ripening were included. Those with a history of cesarean delivery were excluded. The outcomes of patients with a favorable Simplified Bishop Score after cervical ripening were compared with those with an unfavorable Simplified Bishop Score. The primary outcome was the mode of birth. A log-binomial regression was performed to calculate the relative risk and control for confounders such as admission Simplified Bishop Score and parity. RESULTS: A total of 5807 patients met the criteria to be included in the study. 4235 (73%) patients had a favorable cervix, and 1572 (27%) patients had an unfavorable cervix after cervical ripening. The favorable group had a decreased rate of cesarean delivery than the unfavorable group (risk ratio, 0.35; 95% confidence interval, 0.30-0.40). Both the groups had low rates of maternal chorioamnionitis, though the patients with an unfavorable cervix were at a higher risk. There was no significant difference in the rates of postpartum hemorrhage or neonatal intensive care unit admission. Lower rates of cesarean delivery among the favorable group persisted when stratifying by parity (nulliparous: risk ratio, 0.37; 95% confidence interval, 0.31-0.43; multiparous: risk ratio, 0.22; 95% confidence interval, 0.14-0.36). After controlling for maternal age, prepregnancy body mass index, parity, gestational age, and Simplified Bishop Score at admission, a favorable cervix remained significantly associated with fewer cesarean births (risk ratio, 0.55; 95% confidence interval, 0.46-0.66). CONCLUSION: In women undergoing labor induction, a favorable Simplified Bishop Score after cervical ripening and before the start of oxytocin is associated with a decreased rate of cesarean delivery, even after adjusting for parity and Simplified Bishop Score at admission. Moreover, the Simplified Bishop Score assigned after cervical ripening could be used to inform the timing of oxytocin initiation. However, further research is necessary to determine the ideal endpoint of cervical ripening.

Burrowing behavior in mud and sand of morphologically divergent polychaete species (Annelida: Orbiniidae).

Muddy and sandy sediments have different physical properties. Muds are cohesive elastic solids, whereas granular beach sands are non-cohesive porous media. Infaunal organisms such as worms that burrow through sediments therefore face different mechanical challenges that potentially lead to a variety of burrowing strategies and morphologies. In this study we compared three morphologically distinct polychaete species representing different clades in the family Orbiniidae and related differences in their burrowing behaviors and morphologies to their natural environments (mud or sand). Worms burrowed in transparent analogs for muds and sands, and kinematic analysis showed differences both among species and between materials. Leitoscoloplos pugettensis lives in mud and burrows by fracture, using its pointed head to concentrate stress at the tip of the burrow. Naineris dendritica lives in sand and uses its broader head that fluctuates in width over a burrowing cycle to decrease backward slipping in sand, potentially preventing burrow collapse. Orbinia johnsoni lives in sand and uses internal body expansions to pack sand grains, another mechanism to prevent burrow collapse. By combining data from species and materials to obtain a broad range of burrowing velocities, we show that burrowing worms control their velocity by increasing or decreasing their burrowing frequency rather than by altering cycle distance as shown previously for crawling earthworms. This study demonstrates how fairly small evolutionary divergences in morphologies and behaviors facilitate locomotion in environments with different physical constraints.