Genetic Mechanisms Driving Uterine Leiomyoma Pathobiology, Epidemiology, and Treatment.

Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly understood. Several mechanisms of pathogenesis have been suggested, implicating various genes, growth factors, cytokines, chemokines, and microRNA aberrations. The purpose of this study is to summarize the current research on the relationship of genetics with UL. Specifically, we performed a literature review of published studies to identify how genetic aberrations drive pathophysiology, epidemiology, and therapeutic approaches of UL. With regards to pathophysiology, research has identified MED12 mutations, HMGA2 overexpression, fumarate hydratase deficiency, and cytogenetic abnormalities as contributors to the development of UL. Additionally, epigenetic modifications, such as histone acetylation and DNA methylation, have been identified as contributing to UL tumorigenesis. Specifically, UL stem cells have been found to contain a unique DNA methylation pattern compared to more differentiated UL cells, suggesting that DNA methylation has a role in tumorigenesis. On a population level, genome-wide association studies (GWASs) and epidemiologic analyses have identified 23 genetic loci associated with younger age at menarche and UL growth. Additionally, various GWASs have investigated genetic loci as potential drivers of racial disparities in UL incidence. For example, decreased expression of Cytohesin 4 in African Americans has been associated with increased UL risk. Recent studies have investigated various therapeutic options, including ten-eleven translocation proteins mediating DNA methylation, adenovirus vectors for drug delivery, and "suicide gene therapy" to induce apoptosis. Overall, improved understanding of the genetic and epigenetic drivers of UL on an individual and population level can propel the discovery of novel therapeutic options.

Uterine Fibroids.

This JAMA Insights in the Women's Health series discusses the incidence, diagnosis, and treatment of uterine fibroids.

Long-Term Risk of Reintervention After Surgical Leiomyoma Treatment in an Integrated Health Care System.

OBJECTIVE: To compare long-term risk of reintervention across four uterus-preserving surgical treatments for leiomyomas and to assess effect modification by sociodemographic factors in a prospective cohort study in an integrated health care delivery system. METHODS: We studied a cohort of 10,324 patients aged 18-50 (19.9% Asian, 21.2% Black, 21.3% Hispanic, 32.5% White, 5.2% additional races and ethnicities) who had a first uterus-preserving procedure (abdominal, laparoscopic, or vaginal myomectomy [referred to as myomectomy]; hysteroscopic myomectomy; endometrial ablation; uterine artery embolization) after leiomyoma diagnosis in the 2009-2021 electronic health records of Kaiser Permanente Northern California. We followed up patients until reintervention (second uterus-preserving procedure or hysterectomy) or censoring. We used a Kaplan-Meier estimator to calculate the cumulative incidence of reintervention and Cox regression models to estimate hazard ratios and 95% CIs comparing rates of reintervention across procedures, adjusting for age, parity, race and ethnicity, body mass index (BMI), Neighborhood Deprivation Index, and year. We also assessed effect modification by demographic characteristics. RESULTS: Median follow-up was 3.8 years (interquartile range 1.8-7.4 years). Index procedures were 18.0% (1,857) hysteroscopic myomectomies, 16.2% (1,669) uterine artery embolizations, 21.4% (2,211) endometrial ablations, and 44.4% (4,587) myomectomies. Accounting for censoring, the 7-year reintervention risk was 20.6% for myomectomy, 26.0% for uterine artery embolization, 35.5% for endometrial ablation, and 37.0% for hysteroscopic myomectomy; 63.2% of reinterventions were hysterectomies. Within each procedure type, reintervention rates did not vary by BMI, race and ethnicity, or Neighborhood Deprivation Index. However, rates of reintervention after uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy decreased with age, and reintervention rates for hysteroscopic myomectomy were higher for parous than nulliparous patients. CONCLUSION: Long-term reintervention risks for uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy are greater than for myomectomy, with potential variation by patient age and parity but not BMI, race and ethnicity, or Neighborhood Deprivation Index.

Guideline No. 447: Diagnosis and Management of Endometrial Polyps.

OBJECTIVE: The primary objective of this clinical practice guideline is to provide gynaecologists with an algorithm and evidence to guide the diagnosis and management of endometrial polyps. TARGET POPULATION: All patients with symptomatic or asymptomatic endometrial polyps. OPTIONS: Options for management of endometrial polyps include expectant, medical, and surgical management. These will depend on symptoms, risks for malignancy, and patient choice. OUTCOMES: Outcomes include resolution of symptoms, histopathological diagnosis, and complete removal of the polyp. BENEFITS, HARMS, AND COSTS: The implementation of this guideline aims to benefit patients with symptomatic or asymptomatic endometrial polyps and provide physicians with an evidence-based approach toward diagnosis and management (including expectant, medical, and surgical management) of polyps. EVIDENCE: The following search terms were entered into PubMed/Medline and Cochrane: endometrial polyps, polyps, endometrial thickening, abnormal uterine bleeding, postmenopausal bleeding, endometrial hyperplasia, endometrial cancer, hormonal therapy, female infertility. All articles were included in the literature search up to 2021 and the following study types were included: randomized controlled trials, meta-analyses, systematic reviews, observational studies, and case reports. Additional publications were identified from the bibliographies of these articles. Only English-language articles were reviewed. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: Gynaecologists, family physicians, registered nurses, nurse practitioners, medical students, and residents and fellows. TWEETABLE ABSTRACT: Uterine polyps are common and can cause abnormal bleeding, infertility, or bleeding after menopause. If patients don't experience symptoms, treatment is often not necessary. Polyps can be treated with medication but often a surgery will be necessary. SUMMARY STATEMENTS: RECOMMENDATIONS.

Management of Uterine Fibroids and Sarcomas: The Palermo Position Paper.

BACKGROUND: Uterine fibroids are benign monoclonal tumors originating from the smooth muscle cells of the myometrium, constituting the most prevalent pathology within the female genital tract. Uterine sarcomas, although rare, still represent a diagnostic challenge and should be managed in centers with adequate expertise in gynecological oncology. OBJECTIVES: This article is aimed to summarize and discuss cutting-edge elements about the diagnosis and management of uterine fibroids and sarcomas. METHODS: This paper is a report of the lectures presented in an expert meeting about uterine fibroids and sarcomas held in Palermo in February 2023. OUTCOME: Overall, the combination of novel molecular pathways may help combine biomarkers and expert ultrasound for the differential diagnosis of uterine fibroids and sarcomas. On the one hand, molecular and cellular maps of uterine fibroids and matched myometrium may enhance our understanding of tumor development compared to histologic analysis and whole tissue transcriptomics, and support the development of minimally invasive treatment strategies; on the other hand, ultrasound imaging allows in most of the cases a proper mapping the fibroids and to differentiate between benign and malignant lesions, which need appropriate management. CONCLUSIONS AND OUTLOOK: The choice of uterine fibroid management, including pharmacological approaches, surgical treatment, or other strategies, such as high-intensity focused ultrasound (HIFU), should be carefully considered, taking into account the characteristics of the patient and reproductive prognosis.

Pregnancy Outcomes After Laparoscopic Radiofrequency Ablation of Uterine Leiomyomas Compared With Myomectomy.

OBJECTIVE: To compare pregnancy outcomes after laparoscopic radiofrequency ablation and myomectomy. METHODS: The ULTRA (Uterine Leiomyoma Treatment With Radiofrequency Ablation) study is an ongoing multicenter prospective cohort study with longitudinal follow-up up to 5 years comparing outcomes of radiofrequency ablation with myomectomy in premenopausal women older than age 21 years with symptomatic uterine leiomyomas. Participants were queried every 6 months after surgery to assess the incidence of pregnancy and pregnancy outcomes. RESULTS: Among 539 women enrolled in ULTRA, a total of 37 participants (mean age at first pregnancy 35.0±4.7 years) conceived 43 times as of March 2023 (22 radiofrequency ablation, 21 myomectomy). The average length of follow-up time after all procedures was 2.5±1.0 years. The baseline miscarriage rate in the study population was 33.3%. In participants who underwent radiofrequency ablation, 9 of 22 pregnancies (40.9%, 95% CI, 20.3-61.5%) ended in first-trimester miscarriage, 11 resulted in live births (50.0%, 95% CI, 29.1-70.9%), one resulted fetal death at 30 weeks of gestation, and one resulted in uterine rupture during miscarriage treatment with misoprostol 10 weeks after radiofrequency ablation. Among the live births in the radiofrequency ablation group, 45.5% were by vaginal delivery. In the myomectomy group, 9 of 21 pregnancies (42.9%, 95% CI, 21.7-64.0%) ended in first-trimester miscarriage and 12 resulted in live births (57.1%, 95% CI, 36.0-78.3%). There were no significant differences in the likelihood of live birth or miscarriage between the study groups. CONCLUSION: Full-term pregnancy and vaginal delivery are achievable after radiofrequency ablation of leiomyomas. However, in this interim analysis, the miscarriage rate in both radiofrequency ablation and myomectomy groups was higher than expected for women in this age group. Long-term data collection in the ongoing ULTRA study aims to further understand pregnancy outcomes after radiofrequency ablation compared with myomectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT0210094.

Evaluating the Effects of Water Balloons on High-Intensity Focused Ultrasound for Treating Uterine Fibroids.

OBJECTIVE: In the treatment of uterine fibroids with ultrasound-guided high-intensity focused ultrasound (HIFU), water balloons are considered to be a valuable aid for improving safety and efficiency. However, the water balloons worsen the pathway for acoustic transmission, causing degraded performance both in ultrasound therapy and in ultrasound imaging. This study was aimed at establishing a protocol to evaluate the effects of the water balloon. METHODS: Simulations and experiments were carefully conducted to quantitatively investigate the effects of water ballons on the efficiency of HIFU energy delivery and on the quality of ultrasound guiding images. More specifically, HIFU-induced temperature increases in the focal region, together with spatial resolution, contrast and signal-to-noise ratio in the ultrasound guiding images, were compared under the conditions with and without the water balloon. RESULTS: Experiment results revealed that the use of water balloons led to decreases in temperature up to 10ºC within the focal region in some specific situations, but the quality of the guiding images was relatively less affected. CONCLUSION: The study provided knowledge on what influence the water balloon could have in ultrasound-guided HIFU treatment; it also established a practical and standardized evaluation scheme for further optimizing the water balloon, for example, its material and internal liquid compositions. This study can potentially help improve the efficiency and safety of treating uterine fibroids with ultrasound-guided HIFU systems.

The impact of fibroid treatments on quality of life and mental health: a systematic review.

Fibroids significantly impact the quality of life (QOL) and mental health of affected women. However, there are limited comparative data on QOL measures after medical, surgical, and radiologic interventions in women with fibroids. This study aimed to assess the current literature evaluating the impact of fibroids on QOL measures using several validated questionnaires for radiologic, medical, or surgical interventions or a combination of interventions before and after treatment. PubMed, PsycINFO, ClinicalTrials.gov, Embase, and Cochrane Library were searched from January 1990 to October 2023 to evaluate the available evidence, and the risk of bias was assessed using Cochrane RoB 2.0 or the Newcastle-Ottawa Scale. The review criteria included randomized controlled trials (RCTs) and observational cohort studies that included premenopausal women with symptomatic uterine fibroids, confirmed by imaging, who underwent an intervention to target fibroid disease. Only reports using validated questionnaires with a numerical baseline (pretreatment) and posttreatment scores were included. The exclusion criteria included perimenopausal or postmenopausal patients, conditions in addition to uterine fibroids that share similar symptoms, or studies that did not focus on QOL assessment. Abstracts were screened, and full texts were reviewed to determine whether studies met the inclusion criteria. A total of 67 studies were included after final review: 18 RCTs and 49 observational studies. All interventions were associated with a significant improvement in uterine fibroid-specific QOL measures, mental health metrics, and a reduction in symptom severity scores after treatment. These data reveal a substantial impact of uterine fibroids on the QOL and mental health of women with fibroids and indicate the metrics that can be used to compare the effectiveness of fibroid treatment options.

Comparing magnetic resonance imaging and ultrasound in the clinical evaluation of fibroids prior to uterine artery embolization.

PURPOSE: Uterine artery embolization has become established as a frontline treatment for uterine leiomyomata. In planning embolization, preprocedural imaging can further characterize pathology and anatomy, but it may also reveal coexisting diagnoses that have the potential to change clinical management. The purpose of this study is to compare the diagnostic outcomes of ultrasound and MRI performed for patients prior to undergoing embolization. METHODS: The study cohort consisted of 199 patients who underwent uterine artery embolization at a single academic institution between 2013 and 2018. Prior to embolization, all patients had an MRI confirming a leiomyomata diagnosis. Additionally, 118 patients underwent transvaginal ultrasound within five years prior to MRI. MRI findings were analyzed and, when applicable, compared to prior ultrasound impressions to assess for the incidence of new findings. The diagnoses of interest were adenomyosis, hydrosalpinx, predominantly infarcted leiomyomata, and large intracavitary leiomyomata. Data were collected from retrospective chart review and included demographics, symptomology, and imaging reports. RESULTS: 199 patients ultimately underwent embolization for treatment of MRI-confirmed leiomyomata. Of 118 patients who also had an ultrasound within five years prior to their MRI, 26 (22.0%) received a second gynecologic diagnosis based on MRI findings that was not previously seen on ultrasound. Of 81 patients who only had an MRI before embolization, 19 (23.5%) received a second gynecologic diagnosis not previously documented. The most common coexisting pathology was adenomyosis, presenting in 34 (17.1%) patients with leiomyomata, followed by large intracavitary leiomyomata (8, 4.0%), infarcted leiomyomata (7, 3.5%), and hydrosalpinx (6, 3.0%),. CONCLUSIONS: When considering uterine artery embolization for the treatment of symptomatic leiomyomata, preprocedural MRI is superior to ultrasound in detecting coexisting pathologies, including adenomyosis and hydrosalpinx. It can also better characterize leiomyomata, including identifying lesions as intracavitary or infarcted. These findings have the potential to alter clinical management or contraindicate embolization entirely.

Patient Characteristics Associated With Embolization Versus Hysterectomy for Uterine Fibroids: A Systematic Review and Meta-Analysis.

INTRODUCTION: Black and underinsured women in the United States are more likely than their counterparts to develop uterine fibroids (UFs) and experience more severe symptoms. Uterine artery embolization (UAE), a uterine-sparing therapeutic procedure, is less invasive than the common alternative, open hysterectomy. To determine whether demographic disparities persist in UF treatment utilization, we reviewed patient characteristics associated with UAE versus hysterectomy for UF among studies of US clinical practices. METHODS: A systematic literature review was conducted via PubMed, Embase, and CINAHL (PROSPERO CRD42023455051), yielding 1,350 articles (January 1, 1995, to July 15, 2023) that outlined demographic characteristics of UAE compared with hysterectomy. Two readers screened for inclusion criteria, yielding 13 full-text US-based comparative studies specifying at least one common demographic characteristic. Random effects meta-analysis was performed on the data (STATA v18.0). Egger's regression test was used to quantify publication bias. RESULTS: Nine (138,960 patients), four (183,643 patients), and seven (312,270 patients) studies were analyzed for race, insurance status, and age as predictors of treatment modality, respectively. Black race (odds ratio = 3.35, P < .01) and young age (P < .05) were associated with UAE, whereas private insurance (relative to Medicare and/or Medicaid) was not (odds ratio = 1.06, P = .52). Between-study heterogeneity (I2 > 50%) was detected in all three meta-analyses. Small-study bias was detected for age but not race or insurance. CONCLUSIONS AND IMPLICATIONS: Knowledge of demographic characteristics of patients with UFs receiving UAE versus hysterectomy is sparse (n = 13 studies). Among these studies, which seem to be racially well distributed, Black and younger women are more likely to receive UAE than their counterparts.

True Costs of Uterine Artery Embolization: Time-Driven Activity-Based Costing in Interventional Radiology Over a 3-Year Period.

PURPOSE: The aim of this study is to uncover potential areas for cost savings in uterine artery embolization (UAE) using time-driven activity-based costing, the most accurate costing methodology for direct health care system costs. METHODS: One hundred twenty-three patients who underwent outpatient UAE for fibroids or adenomyosis between January 2020 and December 2022 were retrospectively reviewed. Utilization times were captured from electronic health record time stamps and staff interviews using validated techniques. Capacity cost rates were estimated using institutional data and manufacturer proxy prices. Costs were calculated using time-driven activity-based costing for personnel, equipment, and consumables. Differences in time utilization and costs between procedures by an interventional radiology attending physician only versus an interventional radiology attending physician and trainee were additionally performed. RESULTS: The mean total cost of UAE was $4,267 ± $1,770, the greatest contributor being consumables (51%; $2,162 ± $811), followed by personnel (33%; $1,388 ± $340) and equipment (7%; $309 ± $96). Embolic agents accounted for the greatest proportion of consumable costs, accounting for 51% ($1,273 ± $789), followed by vascular devices (15%; $630 ± $143). The cost of embolic agents was highly variable, driven mainly by the number of vials (range 1-19) of tris-acryl gelatin particles used. Interventional radiology attending physician only cases had significantly lower personnel costs ($1,091 versus $1,425, P = .007) and equipment costs ($268 versus $317, P = .007) compared with interventional radiology attending physician and trainee cases, although there was no significant difference in mean overall costs ($3,640 versus $4,386; P = .061). CONCLUSIONS: Consumables accounted for the majority of total cost of UAE, driven by the cost of embolic agents and vascular devices.

Efficacy of intra-arterial lidocaine administration on pain and inflammatory response after uterine artery embolization for symptomatic fibroids.

BACKGROUND: There have been conflicting outcomes regarding the use of lidocaine to reduce pain after uterine artery embolization (UAE). PURPOSE: To investigate the efficacy of intra-arterial lidocaine injection for pain and inflammatory response control within 24 h of UAE for symptomatic uterine fibroids. MATERIAL AND METHODS: Of 1530 patients who underwent UAE for uterine fibroids in 2007-2021, 5 mL of 1% lidocaine was injected into each uterine artery immediately after UAE in 23 patients. A disease-matched control group (n = 23) who did not receive intra-arterial lidocaine was generated from the same registry. The pain score, white blood cell (WBC) count, C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), and fentanyl consumption were compared before and after UAE. Complete infarction of the dominant fibroid was assessed using magnetic resonance imaging. RESULTS: Significantly lower WBC count, CRP level, and NLR were noted 24 h after UAE in the lidocaine group. No statistically significant difference was noted in the pain score between groups at 0-24 h. The cumulative fentanyl dose administered during the first 24 h after UAE was not significantly different. After embolization, fibroid-related symptoms resolved in all patients. No significant difference was observed in the rate of complete infarction of the dominant fibroid. CONCLUSION: Lidocaine administration immediately after UAE resulted in a significant reduction in the inflammatory response. However, such a difference in the inflammatory reaction did not contribute to significant reductions in pain scores or fentanyl consumption.

Treatment of adenomyosis, abdominal wall endometriosis and uterine leiomyoma with interventional radiology: A review of current evidences.

Interventional radiology shows promises in the field of women's health, particularly in pelvic interventions. This review article discusses the latest advancements in interventional radiology techniques for pelvic conditions affecting women including adenomyosis, abdominal wall endometriosis and uterine leiomyoma. Extraperitoneal endometriosis involving the abdominal wall may be treated by percutaneous thermal ablation, such as cryoablation, whereas uterine leiomyoma and adenomyosis can be managed either using percutaneous thermal ablation or using uterine artery embolization. Continued research and development in interventional radiology will further enhance the minimally-invasive interventions available for women's health, improving outcomes and quality of life for this large patient population of women.

Immunosuppressive tumor microenvironment and uterine fibroids: Role in collagen synthesis.

Uterine fibroids (UF), also called uterine leiomyoma, is one of the most prevalent uterine tumors. UF represents a serious women's health global problem with a significant physical, emotional, and socioeconomic impact. Risk factors for UF include racial disparities, age, race, hormonal factors, obesity, and lifestyle (diet, physical activity, and stress. There are several biological contributors to UF pathogenesis such as cellular proliferation, angiogenesis, and extracellular matrix (ECM) accumulation. This review addresses tumor immune microenvironment as a novel mediator of ECM deposition. Polarization of immune microenvironment towards the immunosuppressive phenotype has been associated with ECM deposition. Immunosuppressive cells include M2 macrophage, myeloid-derived suppressor cells (MDSCs), and Th17 cells, and their secretomes include interleukin 4 (IL-4), IL-10, IL-13, IL-17, IL-22, arginase 1, and transforming growth factor-beta (TGF-ß1). The change in the immune microenvironment not only increase tumor growth but also aids in collagen synthesis and ECM disposition, which is one of the main hallmarks of UF pathogenesis. This review invites further investigations on the change in the UF immune microenvironment as well as a novel targeting approach instead of the traditional UF hormonal and supportive treatment.

Efficacy of uterine artery embolization (UAE) for uterine fibroids according to FIGO classification: a single-center experience.

OBJECTIVE: This study aims to retrospectively evaluate the outcomes of uterine artery embolization (UAE) for uterine fibroids (UFs), specifically submucosal UFs, according to the International Federation of Gynecology and Obstetrics (FIGO) classification of UFs. MATERIALS AND METHODS: Forty-two patients with symptomatic UFs underwent UAE with Embosphere® between July 2016 and November 2021. MRI was performed before, at 3 and 6 months after the UAE. At each examination, the volume of UF was measured, and the percentage volume reduction rate (VRR) was calculated. The technical success rate (TSR), symptom improvement rate (SIR), regrowth rate (RR) after 6 months, and adverse events (AEs) were examined; VRR was compared between patients with submucosal UFs (FIGO types 0-2, group A), those with submucosal contacts (FIGO type 3, group B), and those without submucosal UFs (FIGO types 4-7, group C). Statistical analysis was performed on the difference in VRR between groups A, B, and C at 3 and 6 months after UAE. The relationship with hormone levels before UAE and VRR was evaluated. RESULTS: Thirty-seven of the 42 patients were evaluated. Overall, VRR was 37.0% at 3 months and 52.1% at 6 months; TSR, SIR, and RR were 100%, 95.2%, and 5.4%, respectively; VRR at 6 months was 80.7% for group A (n = 7), 57.8% for group B (n = 13), and 37.1% for group C (n = 17). Significant differences were found between A and C (p < 0.001) and B and C (p = 0.023). Hormone levels before UAE had no effect on VRR. There was no significant AEs other than grade 3 pulmonary embolism in one patient. CONCLUSION: UAE was effective for submucosal FIGO types 0-3. UAE was especially useful as an option for FIGO type 3 with a low protrusion rate that is difficult to treat with transcervical resection.

[Diagnosis of uterine sarcomas and rare uterine mesenchymal tumours with malignant potential. Guidelines of the French Sarcoma Group and Rare Gynaecological Tumours]. / Diagnostic des sarcomes utérins et tumeurs mésenchymateuses utérines rares à potentiel de malignité. Référentiels du Groupe Sarcome Français et des Tumeurs Rares Gynécologiques.

The landscape of uterine sarcomas is becoming more complex with the description of new entities associated with recurrent driver molecular alterations. Uterine sarcomas, in analogy with soft tissue sarcomas, are distinguished into complex genomic and simple genomic sarcomas. Leiomyosarcomas and undifferentiated uterine sarcomas belong to complex genomic sarcomas group. Low-grade and high-grade endometrial stromal sarcomas, other rare tumors associated with fusion transcripts (such as NTRK, PDGFB, ALK, RET ROS1) and SMARCA4-deficient uterine sarcoma are considered simple genomic sarcomas. The most common uterine sarcoma are first leiomyosarcoma and secondly endometrial stromal sarcomas. Three different histological subtypes of leiomyosarcoma (fusiform, myxoid, epithelioid) are identified, myxoid and epithelioid leiomyosarcoma being more aggressive than fusiform leiomyosarcoma. The distinction between low-grade and high-grade endometrial stromal sarcoma is primarily morphological and immunohistochemical and the detection of fusion transcripts can help the diagnosis. Uterine PEComa is a rare tumor, which is distinguished into borderline and malignant, according to a risk assessment algorithm. Embryonal rhabdomyosarcoma of the uterine cervix is more common in children but can also occur in adult women. Embryonal rhabdomyosarcoma of the uterine cervix is almost always DICER1 mutated, unlike that of the vagina which is wild-type DICER1, and adenosarcoma which can be DICER1 mutated but with less frequency. Among the emerging entities, sarcomas associated with fusion transcripts involving the NTRK, ALK, PDGFB genes benefit from targeted therapy. The integration of molecular data with histology and clinical data allows better identification of uterine sarcomas in order to better treat them.

Underrepresentation of racial and ethnic minority groups in gynecologic oncology: An analysis of over 250 trials.

OBJECTIVE: To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Association between adherence to posttreatment National Comprehensive Cancer Network (NCCN) surveillance guidelines and detection of recurrent uterine cancer.

OBJECTIVE: To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer. METHODS: Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded. RESULTS: Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence. CONCLUSION: Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence.

Outcome prediction for symptomatic patients with fibroids who underwent uterine artery embolization.

PURPOSE: To predict the clinical outcome of symptomatic patients with uterine leiomyomas who underwent uterine artery embolization (UAE), based on clinical and radiological features. METHODS: Patients with symptomatic uterine leiomyomas who underwent UAE from March 2010 to September 2019 were consecutively included in this retrospective study. Patients with persistent or recurrent symptoms and those who needed repeated UAE, myomectomy, or hysterectomy following the initial treatment were considered to have a poor outcome after UAE. The total and enhancing volume of the dominant leiomyoma in each location and uterine volume were obtained before and after UAE. Univariate and multivariate Cox proportional hazard analyses were used to evaluate the parameters that could predict poor outcome. RESULTS: A total of 116 patients (mean age, 45 ± 5 years) were included. Forty-six patients (46/116, 39.7%) showed poor outcome. Cox regression analysis showed higher hazard of poor outcome for younger patients vs. older patients (HR: 0.92, p-value: 0.01), patients with adenomyosis vs. patients without adenomyosis (HR: 2.47, p-value < 0.01), patients with adenomyosis thickness > 2.5 cm before UAE vs. patients without adenomyosis (HR: 4.2, p-value < 0.01) and for patients with intramural fibroid enhancement volume > 440 cm3 compared to patients with no intramural fibroids (p-value: 0.06). Multivariate Cox regression analysis including age, the thickness of adenomyosis, and intramural leiomyoma volume of enhancement before UAE was chosen as the best model to predict the outcome. CONCLUSIONS: Pretreatment clinical and MRI features could identify patients with a higher risk for poor outcome after UAE.