Elizabeth A. Stewart

Fibroids and Health Equity: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel

While known health care disparities among patients with fibroids exist, there is a lack of research on health equity in this specific population and how it affects patients seeking care and the treatment options offered or ultimately the selection they make. Subject matter experts from interventional radiology, obstetrics and gynecology, epidemiology, public health, and patient advocacy participated in a Society of Interventional Radiology Foundation Research Consensus Panel to discuss and to prioritize critical research topics focusing on health equity in patients with uterine fibroids. After topic presentations and discussion of research ideas, the panelists prioritized the following topics: (a) a prospective study evaluating whether the introduction of a standard educational program to patients with low health literacy regarding fibroids improves their scores on standardized patient-reported outcome measures; (b) evaluation of whether a digital-based technology can be effectively used to improve health education and awareness of fibroids; and (c) performance of surveys of patients to understand their barriers to accessing fibroid care and their motivations for selecting different fibroid treatments.

Evaluation of the In Vivo Efficacy of the JAK Inhibitor AZD1480 in Uterine Leiomyomas Using a Patient-derived Xenograft Murine Model

Uterine leiomyomas are common noncancerous hormonally-dependent neoplasms comprised of uterine smooth-muscle cells and fibroblasts. Despite their significant impact on morbidity, effective non-hormonal medical treatments are lacking. In vitro studies have identified the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway as a promising target in leiomyoma cells. Our objective was to evaluate the efficacy of AZD1480, a JAK 1/2 inhibitor, in treating uterine leiomyomas using a patient-derived xenograft murine model. Ovariectomized immunodeficient mice received an estrogen and progesterone pellet and were subsequently implanted with human leiomyoma tissue surgically resected from premenopausal women not on hormonal medication. Mice were divided into treatment (n = 6) and vehicle control (n = 6) groups receiving either 50 mg/kg of AZD1480 or vehicle via oral gavage for 5 days/week for 28 days. Our results demonstrate a significant AZD1480-mediated reduction in both xenograft volume (59.5% vs. 0.3%; treated vs. control, p < .0001) and weight (56.0% vs. 31.2%; p = 0.03) compared to controls. Moreover, xenografts from the treated group exhibited a significant decrease in cell density(p = 0.01). Levels of pSTAT3-positive cells (4.1% vs. 10.3%), Ki67-positive cells (4.1% vs. 6.5%), and fibrillar collagen (19.8% vs. 29.5%) declined but did not reach statistical significance, whereas AZD1480 treatment significantly reduced blood vessel formation in the xenografts (20.1 vs 45.6 per FOV; p = 0.01). These findings suggest JAK inhibition as a potential treatment for uterine leiomyomas by targeting angiogenesis. However, further studies are warranted to explore alternative JAK inhibitors, examine downstream effects, optimize dosing, and establish clinical efficacy and safety.