Uterine Sarcoma

This study is to evaluate the efficacy and safety of elacestrant, in participants with advanced estrogen receptor (ER)-positive uterine sarcomas. The name of the study drug involved in this research study is: -Elacestrant (a type of selective estrogen receptor degrader)

In our previous study, based on the multi-center clinical big data collected from January 2012 to January 2025, we have completed the construction of a multimodal early warning model for the malignant transformation of uterine fibroids. The model was mainly based on T2WI and DWI sequences, and was trained and optimized by support vector machine (SVM) algorithm. In the retrospective study and internal validation, the model shows high sensitivity and specificity, which preliminarily proves that it has good application potential in identifying high-risk groups and predicting the risk of malignant transformation of uterine fibroids. However, there are still some limitations in retrospective studies and internal validation results, and its application value, universality and stability in real clinical environment have not been fully verified. Therefore, we plan to conduct a prospective validation study in consecutive patients enrolled after January 2025 to evaluate the clinical performance and generalization of the model in predicting the malignant tendency or risk of malignant transformation of uterine fibroids through practical application in the real population, and further analyze the operability in the actual diagnosis and treatment process and the potential value for patient management. This study will provide reliable evidence for early screening, follow-up management and individualized treatment of high-risk population, and has important clinical and public health significance for improving the early diagnosis rate, reducing the risk of malignant transformation and improving the prognosis of patients with uterine fibroids.

Multicenter ambispective observational study (prospective/retrospective)

Uterine sarcomas are rare and aggressive tumors originating from the muscular wall of the uterus. They have a high risk of recurrence and death, regardless of the stage of the disease at diagnosis. The therapy is surgical and involves hysterectomy preferably via laparotomy in consideration of the high risk of neoplastic dissemination through the rupture and fragmentation of the neoplasm as occurs through removal by other surgical routes which involve core drilling of the mass (laparoscopic, vaginal , hysteroscopic). Uterine myoma represents a very frequent benign pathology in women, with an incidence of approximately 70%-80%. Asymptomatic cases do not require treatment, while symptomatic cases can be treated through the administration of generally antiestrogenic drugs to block growth and symptoms. Only a small part is removed surgically. Currently the diagnosis of uterine sarcoma is almost always defined in the post-operative setting with the definitive histological examination, due to the lack of typical sonographic and radiological characteristics of certainty capable of differentiating benign neoplastic forms (myoma) from malignant ones of the uterus (sarcoma). Magnetic resonance imaging is currently the most reliable imaging modality for characterizing such uterine masses. Unfortunately, although it offers useful information, it is not able to discriminate with good precision a benign uterine lesion from a malignant one. CT is a method widely used in the staging of oncological diseases and therefore also in sarcomas. It is usually prescribed when there is an ultrasound doubt of a sarcoma before proceeding with surgery. However, although it is important in the definition of secondaries, it has very low sensitivity (60%) and specificity in the differential diagnosis between sarcoma and myoma. Radiomics is a novel approach that translates medical images into data by extracting a large number of quantitative features describing tissue characteristics, shape and texture, combining quantitative data analysis with biological and clinical endpoint. Capturing information from imaging that goes beyond the different biomedical imaging formats themselves is the great promise of this growing field. The application of radiomics analysis to CT with the aim of preoperatively discriminating between sarcoma (malignant) and myoma (benign) could be a valid support in the preoperative evaluation and therapeutic decision-making process in order to personalize the most appropriate therapeutic approach .

Rare gynecological cancers including uterine sarcomas, vulvar and non-epithelial ovarian cancers, are under-studied diseases and the absence of standardized diagnostic and therapeutic approaches or tailored clinical guidelines led to low survival rates and/or poor quality of life outcomes. The ROAR project aims at increasing the molecular understanding of these diseases in a multidisciplinary, interinstitutional setting including gynecologic oncologists, medical oncologists, phase I researchers, pathologists, molecular pathologist, research nurses, genetists, bioinformatics, psychologists and patients' advocacy groups. The project will pursue this aim through the following activities: 1. Harmonizing procedures and enabling safe and easy data sharing across all involved institutions; this will be achieved by reviewing the available clinical and molecular data (WP1), establishing an interinstitutional second-opinion board (WP2/Task1), developing a dedicated electronic customized research form (WP2/Task2) and deploying a genomics platform (WP2/Task3). 2. Performing comprehensive somatic and transcriptional profiling as well as immunological landscape assessments on high quality annotated samples stored in a biobank dedicated to rare gynecological cancers; this will require systematic and standardized clinical data and biological samples collection (WP3/WP4), standardization of pre-analytical and sequencing procedures (WP5/6). The board will tailor indications and modalities for genomics and liquid biopsy assessments based on clinical features. 3. Evaluating the clinical impact of the board on rare gynecological cancers management and, through the evidence gathered, implementing diagnostic and therapeutic strategies; this will include analyzing the activities of the board (WP7/Task 1.1), integrating -omics data in the board report (WP7/Task 1.2), evaluating liquid biopsy role in identifying minimal residual disease post-surgery, disease monitoring over time, capability of capturing tumor heterogeneity at baseline and identifying hot spot actionable molecular alterations. Finally, the evidence gathered from the ROAR project, will allow update of clinical guidelines or provide new recommendations for each rare gynecological cancer included. The results of ROAR will also be disseminated through direct access to the integrated platform developed.